bluuebunny/crossref_metadata_2025 huggingface dataset:
Migrants, Servants, and Slaves: Unfree Labor in Colonial British America. By Russell R. Menard. Aldershot, U.K.: Ashgate/Variorum, 2001. Pp. xiv, 302. $105.95.
Authors: Murray John E.
Published: February 2008

Quantitative economic history has enjoyed substantial successes in the field of early American history. A distinguishing characteristic of scholars of the early American economy has been their ability to reach a broad readership. Their work speaks to both mainstream and economic historians, which is no small achievement.
From Settler to Citizen: New Mexican Economic Development and the Creation of Vecino Society, 1750–1820. By Ross Frank. Berkeley: University of California Press, 2000. Pp. xxiv, 329. $45.00.
Authors: Salvucci Richard J.
Published: February 2008

The first Spanish expedition into New Mexico took place in 1598 under Juan de Oñate. Less than a century later, Spanish settlers were expelled from Santa Fe during the Pueblo revolt of 1680 and the Crown was unable to reestablish control until 1692. New Mexico thereafter remained little more than an insecure settlement on the northern edge of Spain's American empire. Like that of the other frontier marches, New Mexico's status changed dramatically after 1750, when Spain, impelled by growing foreign pressure, sought to strengthen the defensive margins of its possessions. New Mexico, Cuba, and the Argentine colony, for example, all received renewed attention in Madrid. Their subsequent development was dramatically altered by the metropolitan response to the Seven Years War (1756–1763), measures known collectively as the Bourbon reforms.
The Color of Work: The Struggle for Civil Rights in the Southern Paper Industry, 1945–1980. By Timothy J. Minchin. Chapel Hill: University of North Carolina Press, 2001. Pp. x, 277. $24.95, paper.
Authors: Boyd William
Published: February 2008

This book documents efforts to integrate the southern paper industry during the post–World War II period. It makes an important contribution not only to the vast and growing literature on the civil-rights movement but also to economic and legal history. In contrast to the traditional focus of civil-rights historians on voting rights, school desegregation, and public accommodations, Timothy Minchin takes up the issue of fair employment and access to jobs as components of the broader civil-rights struggle. Building on his earlier research on the textile industry (Hiring the Black Worker: The Racial Integration of the Southern Textile Industry, 1960–1980. Chapel Hill: University of North Carolina Press, 1999), Minchin focuses specifically on the role of black activists and civil-rights advocates in utilizing the legal machinery put in place by the Civil Rights Act of 1964 (specifically, Title VII) as a vehicle for litigation against companies and unions seeking to deny black workers equal employment opportunities. Drawing on the vast record generated by Title VII litigation and oral interviews with key actors, Minchin provides considerable insight into the lived experiences and strategic thinking of those struggling to integrate the industry. The overall story provides powerful support for the efficacy of federal civil-rights legislation in opening up new opportunities for black workers.
Urban Inequality: Evidence from Four Cities. Edited by Alice O'Connor, Chris Tilly, and Lawrence D. Bobo. New York: Russell Sage Foundation, 2001. Pp. xii, 549. $45.00.
Authors: Ziliak Stephen T.
Published: February 2008

In some inquiries, racism is a given, a fundamental assumption and fact that is known to shape economic and social and spatial inequalities. In such inquiries, from the empirical studies of W. E. B. Du Bois to the social thought of Patricia Williams, the world is believed to be racialized “always already”: the task of the researcher, then, is to probe the roots of racism in particular cases, and to liberate (or compensate) the people who are oppressed by its institutional manifestations. Other inquiries—guided by a methodology of rational choice—do not assume racism to be a given. For example, in mainstream economics after Gary Becker, race is a possible “factor,” one vector of a matrix, whose strength and direction of force on earnings or housing differences is to be examined in a regression equation once all other factors have been held constant. Indeed, some economists after Becker argue that racism cannot explain differences in earnings or in opportunities because if the marginal product of labor (or the bid on a house) of a person of color exceeds that of the white competition, the argument goes, then no profit-maximizing employer or seller would deny the offer of the person of color. And since all employers and households are assumed to be profit-maximizers, the color of one's skin will have no economic significance at all.
Rhetoric as Currency: Hoover, Roosevelt, and the Great Depression. By Davis W. Houck. College Station: Texas A&M University Press, 2001. Pp. 226. $39.95.
Authors: Green George D.
Published: February 2008

In this study of the economic rhetoric of Herbert Hoover and Franklin Roosevelt, 1929–1933, Davis Houck tries boldly to link the fields of rhetoric, history, and economics. He claims to “have established the crucial relationship between rhetoric and economics. Specifically, economic recovery is premised, in part, on collective confidence, which, in turn, is influenced by both presidential speech and cooperative legislative action” (p. 199).
Big Government and Affirmative Action: The Scandalous History of the Small Business Administration. By Jonathan L. Bean. Lexington: University of Kentucky Press, 2001. Pp. xii, 224. $29.95.
Authors: Wallsten Scott
Published: February 2008

Jonathan Bean's book chronicles the growth and development of the Small Business Administration (SBA) from its inception in 1953 through the present. In addition to placing the SBA's actions in the context of changing political environments, the book focuses on three separate issues, though it is not organized this way. The first two are different types of affirmative action: preferences and subsidies for “small” firms, and preferences for people who have been “economically disadvantaged.” Finally, it chronicles the history of scandal and corruption that has plagued the SBA.
GENERAL AND MISCELLANEOUS Sexual Chemistry: A History of the Contraceptive Pill. By Lara V. Marks. London: Yale University Press, 2001. Pp. xi, 372. $29.95.
Authors: Jones Stacey
Published: February 2008

The contraceptive pill is widely assumed to have had a revolutionary effect on society, but its origins and the changes it is said to have brought about have not been fully explored. A recent history of the pill by Elizabeth Watkins did much to fill that gap (On the Pill: A Social History of Oral Contraceptives, 1950–1970. Baltimore: Johns Hopkins University Press, 1998). Sexual Chemistry adds both an international perspective and a rich level of detail to the story.
A Thousand Years of Nonlinear History. By Manuel De Landa. New York: Zone Books, 1997. Pp. 333. $16.00.
Authors: Coelho Philip R. P.
Published: February 2008

The title of this book is an outline of De Landa's agenda. He wants to convey his philosophical approach to history using examples chosen from the last 1,000 years of human history. “Nonlinear” refers to feedbacks and interactions that prevent movement toward a unique equilibrium. The author interprets history through a series of extended metaphors that link biology, geology, and linguistics to human history. The book is divided into sections corresponding to these classifications. The first, “Lavas and Magmas,” makes connections between history and geology; the second, “Flesh and Genes,” connects history and biology; and the third, “Memes and Norms,” connects history with linguistics. Within each section De Landa illustrates his approach with examples from the (approximately) last “thousand years of nonlinear history.”
THE SUPPLY PRICE OF LABOR DURING THE GREAT DEPRESSION
Authors: Simon Curtis J.
Published: February 2008

This article presents somewhat-more-direct evidence than has been available on the supply price of labor during the Depression. The new data comprise wages asked from situations-wanted ads for female clerical workers. Between 1929 and 1933 annual average clerical wages asked fell nominally by nearly 58 percent, markedly lower than wages of new or existing employees. Neither changes in labor quality nor self-selection explains the decline. Clerical wages asked fell by roughly the same percentage as did wages paid in agriculture. The data are strongly inconsistent with the market-clearing view of Depression-era labor markets.
The Measure of Man and Older Age Mortality: Evidence from the Gould Sample
Authors: COSTA DORA L.
Published: February 2008

This article documents differences in body size between white, black, and Indian mid-nineteenth-century American men and investigates the socioeconomic and demographic determinants of frame size using a unique data set of Civil War soldiers. It finds that over time men have grown taller and heavier and have relatively less abdominal fat, implying that “modern” chronic diseases such as ischemic heart disease were common in the past. Changes in frame size explain almost half of the mortality decline among white men between 1914 and 1988 and predict even sharper declines in older age mortality between 1988 and 2022.
Skill Intensity and Rising Wage Dispersion in Nineteenth-Century American Manufacturing
Authors: ATACK JEREMY , BATEMAN FRED , MARGO ROBERT A.
Published: February 2008

We study the correlates of the monthly establishment wage—the average monthly wage at the establishment level—and changes in wage dispersion between plants using a model of manufacturing developed by Goldin and Katz and data from manuscript censuses of manufacturing. We find that wages were decreasing in establishment size, but increasing in capital intensity and use of steam power. We also find an increase in inequality in the establishment wage between 1850 and 1880. Most of the increase occurred below the median wage and can be attributed, in part, to the growing concentration of employment in large establishments.
The U.S. Sugar Program and the Cuban Revolution
Authors: DYE ALAN , SICOTTE RICHARD
Published: February 2008

This article argues that one contributing factor to the Cuban Revolution of 1959 was the 1956 revision of U.S. sugar quotas. Its significance has been overlooked because its real economic impact was programmed to occur after 1959. Combining a statistical simulation and an event study of sugar companies' rates of return on equity, we show that the revision had adverse long-run consequences for sugar exports, and that forward-looking investors anticipated them and incorporated them into their valuation of sugar-company stocks after 1953. Further evidence shows that the Batista regime and prominent insurgents understood the vital nature of Cuba's sugar import quota.
Financial Intermediation in the Early Roman Empire
Authors: TEMIN PETER
Published: February 2008

I evaluate the effectiveness of financial markets in the early Roman Empire in this article. I review the theory of financial intermediation to describe a hierarchy of financial sources and survey briefly the history of financial intermediation in eighteenth-century Western Europe to provide a standard against which to evaluate the Roman evidence. I then describe the nature of financial arrangements in the early Roman Empire in terms of this hierarchy. This exercise reveals the extent to which the Roman economy resembled more recent societies and sheds light on the prospects for economic growth in the Roman Empire.
Comment on “The German Twin Crisis of 1931”
Authors: FERGUSON THOMAS , TEMIN PETER
Published: February 2008

It is lovely to see attention to this critical episode in the Great Depression. Isabel Schnabel repeats the familiar argument that bank behavior was a primary cause of the German crisis. We have argued elsewhere that the German crisis clearly began as a currency crisis, not a banking crisis. The purpose of this comment is to examine the data that Schnabel's article brings to bear on this question and evaluate the evidence it presents in support of its hypotheses.
Reply to Thomas Ferguson and Peter Temin's “Comment on ‘The German Twin Crisis of 1931”’
Authors: SCHNABEL ISABEL
Published: February 2008

Ferguson and Temin criticize my article for only paying lip service to the notion of a twin crisis while providing a story of apurebanking crisis. In fact, I have never claimed that the crisis was a pure banking crisis. The question is whether and to what extent banks contributed to the crisis. Ferguson and Temin take the position that the crisis was apurecurrency crisis. I argue that weaknesses in the banking sector existed, which interacted with the currency problems in numerous ways. The focus of my article on banks reflects the nature of the question, rather than any view that currency problems were unimportant.
Relative U.K./U.S. Output Reconsidered: A Reply to Professor Broadberry
Authors: WARD MARIANNE , DEVEREUX JOHN
Published: February 2008

In the September 2003 issue of this JOURNAL, we provided benchmark comparisons of U.K./U.S. income from 1870 to 1990. In contrast to long-span projections from Angus Maddison and others, our estimates show the United States leading from 1870 in terms of income per capita and output per worker. In a 12-page comment that accompanies our article, Professor Stephen Broadberry criticizes our work on three grounds. First, he charges our estimates are inconsistent with his U.K./U.S. sectoral productivity comparisons. Second, he chastises us on the grounds that our price benchmarks conflict with standard U.S. and U.K. price indices. Finally, he queries our nominal GDP estimates.
The “Tuberculous Cattle Trust”: Disease Contagion in an Era of Regulatory Uncertainty
Authors: OLMSTEAD ALAN L. , RHODE PAUL W.
Published: February 2008

In 1900 bovine tuberculosis was a serious and growing threat to animal and human health. Early private and state initiatives in the United States often increased the incentives for the interstate trade of diseased stock. One unscrupulous dealer exposed thousands of dairy herds and families to the disease. Our study helps explain the expanding federal role in regulating food safety. In this case regulations arose from genuine health concerns. Before the development of strict regulations, diagnostic innovations that could have helped prevent the spread of the disease actually made the operation of markets worse by aggravating asymmetric information problems.
When the State is Untrustworthy: Public Finance and Private Banking in Porfirian Mexico
Authors: MAURER NOEL , GOMBERG ANDREI
Published: February 2008

All sovereign governments face a commitment problem: how can they promise to honor their own agreements? The standard solutions involve reputation or political institutions capable of tying the government's hands. Mexico's government in the 1880s used neither solution. It compensated its creditors by enabling them to extract rents from the rest of the economy. These rents came through special privileges over banking services and the right to administer federal taxes. Returns were extremely high: as long as the government refrained from confiscating all their assets (let alone repaying their debts) less than twice a decade, they would break even.
The Free Silver Movement in America: A Reinterpretation
Authors: GRAMM MARSHALL , GRAMM PHIL
Published: February 2008

Monetary historians have contended that Free Silver advocates were inflationists seeking debt reduction. We offer an alternative interpretation using a theory of money demand with differential returns on nominal units and a nonoptimum nominal money stock. Our explanation is more logically appealing and more consistent with contemporary evidence. The restrictive coinage laws of the period produced chronic shortages, and our empirical analysis provides clear evidence of these shortages. A shortage of coins valued at a half-day's wage and less, raised transactions costs, produced hardship and spawned protest.
The beginning and the end of the Šahrestānīhā ī Ērānšahr
Authors: De Jong Albert
Published: February 2008

Different readings of the first and the last phrase of the short Middle Persian text Šahrestānīhā ī Ērānšahr are suggested; these show that its beginning and end are not as strange or exceptional as is suggested in its latest edition. In particular, it is argued here that a Middle Persian translation of the title of the ‘Abbāsid caliph al-Manṣūr can be found in the text.
Popular visual language as global communication: the remediation of United Airlines Flight 93
Authors: WEBER CYNTHIA
Published: February 2008

This article argues that while the linguistic turn in mainstream IR is important in broadening how IR approaches global communications, the linguistic turn has its limitations because mainstream IR tends to, in Mattelart’s terms, ‘ex-communicate’ the visual from the linguistic. This is highly problematic, considering, firstly, that popular visual language is increasingly the language that amateurs and experts rely upon in order to claim contemporary literacy and, secondly, that much politics is conducted through popular visual language. If the challenge of this Special Issue is to think about how to bring the discipline of IR to meaningful, political life, then a very good place to start is by asking mainstream IR (again) to take popular visual language seriously as an important aspect of contemporary global communication. This article makes this demand of the discipline of IR. It does so by presenting a case-study – the official US remediation of United Airlines Flight 93 – as an illustration of how contemporary global communications move from the textual to the visual and of what is lost in not taking this move seriously. In particular, it claims that by failing to analyse popular visual language as integral to global communications, mainstream IR risks misunderstanding contemporary subjectivity, spatiality, and temporality.
Transversal communication, diaspora, and the Euro-Kurds
Authors: SOGUK NEVZAT
Published: February 2008

The International Relations discipline (IR) has been uniquely resistant to practices and knowledges aimed at broadening the horizons of IR’s subjects. The discipline has worked to incarcerate its subjects in a location of analysis – spatially Cartesian and politically state-oriented – conditioned to ignore the transnational and transversal formations that have become central to politics. However, this disciplining has also engendered counter-movements pressuring the well-rehearsed disciplinary horizons. This article explores such movements through the Kurdish diaspora in Europe. It regards Kurdish diasporic formations as transversal practices that communicate against the disciplinary boundaries imposed upon the political imagination through traditional IR.
Never mind the bollocks: the punk rock politics of global communication
Authors: DUNN KEVIN C.
Published: February 2008

Largely ignored by scholars of world politics, the global punk rock scene provides a fruitful basis for exploring the multiple circuits of exchange and circulation of goods, people, and messages that moves beyond the limitations of IR. Punk can also offer new ways of thinking about international relations and communication from the lived experiences of people’s daily lives. At its core, this essay has two arguments. First, punk offers the possibility for counter-hegemonic expression within systems of global communication. Punk has simultaneously worked within and against the hegemony of capitalist telecommunication networks, navigating an increasingly interconnected and mediated world. Second, punk is a subversive message in its own right. Focusing on punk’s Do-It-Yourself (DIY) ethos and the resource it offers for resisting the multiple forms of alienation in modern society, the story I construct here is one of agency and empowerment often overlooked by traditional IR.
Propagation and hindered settling of laboratory ash flows
Authors: Girolami L. , Druitt T. H. , Roche O. , Khrabrykh Z.
Published: February 2008

The fluidal behavior of pyroclastic flows is commonly attributed to high gas pore pressures and associated fluidization effects. We carried out experiments on flows of fluidized volcanic ash at 170°C, which is hot enough to reduce cohesive effects of moisture. The flows were generated in a 3‐m‐long, horizontal lock‐exchange flume. The ash was fluidized and expanded uniformly in the flume reservoir by up to 43% above loose packing and was then released. Each flow defluidized progressively down the flume until motion ceased. Initial expansion E and initial height h0 were varied independently of one another. The flows traveled in a laminar manner. Flow fronts exhibited three main phases of transport: (1) a brief initial phase of gravitational slumping, (2) a dominant, approximately constant velocity phase, and (3) a brief stopping phase. Phase 2 frontal velocities scaled with , like other types of dam‐break flow. Deposition from initially expanded flows took place by progressive sediment aggradation at a rate that was independent of distance and varied only with E. Despite rates of shear up to 80 s−1, aggradation rates were identical to those determined independently, at the same value of E, in quasi‐static collapse tests. Sedimentation caused the flows to thin progressively during transit until they ran out of volume. The dynamics were governed to a first order by two dimensionless parameters: (1) the initial aspect ratio h0/x0 in the lock reservoir and (2) the ratio tsett/tgrav of two timescales: a particle settling time tsett and a gravitational acceleration time tgrav.
Decadal variability in the northeast Pacific in a physical‐ecosystem model: Role of mixed layer depth and trophic interactions
Authors: Alexander Michael , Capotondi Antonietta , Miller Arthur , Chai Fei , Brodeur Richard , Deser Clara
Published: February 2008

A basin‐wide interdecadal change in both the physical state and the ecology of the North Pacific occurred near the end of 1976. Here we use a physical‐ecosystem model to examine whether changes in the physical environment associated with the 1976–1977 transition influenced the lower trophic levels of the food web and if so by what means. The physical component is an ocean general circulation model, while the biological component contains 10 compartments: two phytoplankton, two zooplankton, two detritus pools, nitrate, ammonium, silicate, and carbon dioxide. The model is forced with observed atmospheric fields during 1960–1999. During spring, there is a ∼40% reduction in plankton biomass in all four plankton groups during 1977–1988 relative to 1970–1976 in the central Gulf of Alaska (GOA). The epoch difference in plankton appears to be controlled by the mixed layer depth. Enhanced Ekman pumping after 1976 caused the halocline to shoal, and thus the mixed layer depth, which extends to the top of the halocline in late winter, did not penetrate as deep in the central GOA. As a result, more phytoplankton remained in the euphotic zone, and phytoplankton biomass began to increase earlier in the year after the 1976 transition. Zooplankton biomass also increased, but then grazing pressure led to a strong decrease in phytoplankton by April followed by a drop in zooplankton by May: Essentially, the mean seasonal cycle of plankton biomass was shifted earlier in the year. As the seasonal cycle progressed, the difference in plankton concentrations between epochs reversed sign again, leading to slightly greater zooplankton biomass during summer in the later epoch.
Increase of cloud droplet size with aerosol optical depth: An observation and modeling study
Authors: Yuan Tianle , Li Zhanqing , Zhang Renyi , Fan Jiwen
Published: February 2008

Cloud droplet effective radius (DER) is generally negatively correlated with aerosol optical depth (AOD) as a proxy of cloud condensation nuclei. In this study, cases of positive correlation were found over certain portions of the world by analyzing the Moderate Resolution Imaging Spectroradiometer (MODIS) satellite products, together with a general finding that DER may increase or decrease with aerosol loading depending on environmental conditions. The slope of the correlation between DER and AOD is driven primarily by water vapor amount, which explains 70% of the variance in our study. Various potential artifacts that may cause the positive relation are investigated including the effects of aerosol swelling, partially cloudy, atmospheric dynamics, cloud three‐dimensional (3‐D) and surface influence effects. None seems to be the primary cause for the observed phenomenon, although a certain degree of influence exists for some of the factors. Analyses are conducted over seven regions around the world representing different types of aerosols and clouds. Only two regions show positive dependence of DER on AOD, near coasts of the Gulf of Mexico and South China Sea, which implies physical processes may at work. Using a 2‐D Goddard Cumulus Ensemble model (GCE) with spectral‐bin microphysics which incorporated a reformulation of the Köhler theory, two possible physical mechanisms are hypothesized. They are related to the effects of slightly soluble organics (SSO) particles and giant cloud condensation nuclei (CCN). Model simulations show a positive correlation between DER and AOD, due to a decrease in activated aerosols with an increasing SSO content. Addition of a few giant CCNs also increases the DER. Further investigations are needed to fully understand and clarify the observed phenomenon.
Geomorphic evidence for former lobate debris aprons at low latitudes on Mars: Indicators of the Martian paleoclimate
Authors: Hauber E. , van Gasselt S. , Chapman M. G. , Neukum G.
Published: February 2008

Circumferential depressions enclosing mesas and plateaus in the northern Kasei Valles and in the Tartarus Colles regions of Mars are interpreted as indicators of the former extent of lobate debris aprons, thought to be mixtures of ice and clastic particles. These former lobate debris aprons existed about 1 Ga ago and were embayed by lavas or other flow deposits. After the lobate debris aprons had been removed by sublimation and deflation, topographic depressions with a depth of 50 m and a width of several kilometers were left behind between the mesa or plateau scarp and the solidified flow materials. These depressions or moats are located equatorward of ±30° at significantly lower latitudes than generally observed for occurrences of modern, intact lobate debris aprons. This observation provides evidence that the paleoclimate at that time was different than today, probably due to a higher averaged obliquity of the planet's rotational axis.
Biophysical and Physiological Effects of Solar Radiation on Human Skin
Authors:   European Society Photobiology
Published: February 2008

In an era of global warming knowledge of the effects of solar radiation on humans is of great importance and the latest discoveries in environmental photobiology are presented in this book. The Editor has brought together a wide range of world class contributors to provide the reader with information on the clinical effects of solar radiation, such as inflammation, pigmentation, immune-suppression, cancer and aging, with emphasis on the ethnic or genetic background. The book also offers updates on the biochemical mechanisms involved in the generation of damage to DNA, lipids and proteins and on their removal. Each chapter has been written to provide a "historical" description of the phenomenology followed by the description of the state of the art. In this way, non-specialized and specialised readers alike can be updated in the essential aspects of the field. Key topics include: - Damages from acute versus chronic sun exposure - Skin Color, Melanin, Race/Ethnicity and UV-Induced DNA Damage - The effects of solar radiation on the immune response in humans - Genetic background and UV-induced skin cancer - The photochemistry of indirect damages: Lipid and Protein Damage provoked by UV radiation - DNA repair therapy This title will become an indispensable resource for students and professional at all levels working in fields relating to photochemistry, environmental science, biochemistry and biotechnology.
The impact of specific oxidized amino acids on protein turnover in J774 cells
Authors: Dunlop Rachael A. , Dean Roger T. , Rodgers Kenneth J.
Published: February 2008

Oxidized protein deposition and accumulation have been implicated in the aetiology of a wide variety of age-related pathologies. Protein oxidation in vivo commonly results in the in situ modification of amino acid side chains, generating new oxidized amino acid residues in proteins. We have demonstrated previously that certain oxidized amino acids can be (mis)incorporated into cell proteins in vitro via protein synthesis. In the present study, we show that incorporation of o- and m-tyrosine resulted in increased protein catabolism, whereas dopa incorporation generated proteins that were inefficiently degraded by cells. Incorporation of higher levels of L-dopa into proteins resulted in an increase in the activity of lysosomal cathepsins, increased autofluorescence and the generation of high-molecular-mass SDS-stable complexes, indicative of protein aggregation. These effects were due to proteins containing incorporated L-dopa, since they were not seen with the stereoisomer D-dopa, which enters the cell and generates the same reactive species as L-dopa, but cannot be incorporated into proteins. The present study highlights how the nature of the oxidative modification to the protein can determine the efficiency of its removal from the cell by proteolysis. Protection against the generation of dopa and other species that promote resistance to proteolysis might prove to be critical in preventing toxicity from oxidative stress in pathologies associated with protein deposition, such as atherosclerosis, Alzheimer's disease and Parkinson's disease.
Extracellular point mutations in FGFR2 result in elevated ERK1/2 activation and perturbation of neuronal differentiation
Authors: Schüller Annika C. , Ahmed Zamal , Ladbury John E.
Published: February 2008

Two independent gain-of-function point mutations (S252W and P253R) in the extracellular region of the FGFR2 (fibroblast growth factor receptor 2) increase the binding affinity for the growth factor. The effect of this enhanced growth factor binding by these mutants is expected to be an increase in activation of regular signalling pathways from FGFR2 as a result of more receptors being engaged by ligand at any given time. Using PC12 (pheochromocytoma) cells as a model cell system we investigated the effect of these mutations on protein phosphorylation including the receptor, the activation of downstream signalling pathways and cell differentiation. Our results show that the effects of both of these extracellular mutations have unexpected intracellular phenotypes and cellular responses. Receptor phosphorylation was altered in both the ligand-stimulated and unstimulated states. The mutants also resulted in differential phosphorylation of a number of intracellular proteins. Both mutations resulted in enhanced ERK1/2 (extracellular-signalregulated kinase1/2) activation. Although ERK1/2 activation is believed to transduce signals resulting in cell differentiation, this response was abrogated in the cells expressing the mutant receptors. The results of the present study demonstrate that single extracellular point mutations in the FGFR2 have a profound effect on intracellular signalling and ultimately on cell fate.
Curcumin inhibits FtsZ assembly: an attractive mechanism for its antibacterial activity
Authors: Rai Dipti , Singh Jay Kumar , Roy Nilanjan , Panda Dulal
Published: February 2008

The assembly and stability of FtsZ protofilaments have been shown to play critical roles in bacterial cytokinesis. Recent evidence suggests that FtsZ may be considered as an important antibacterial drug target. Curcumin, a dietary polyphenolic compound, has been shown to have a potent antibacterial activity against a number of pathogenic bacteria including Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus. We found that curcumin induced filamentation in the Bacillus subtilis 168, suggesting that it inhibits bacterial cytokinesis. Further, curcumin strongly inhibited the formation of the cytokinetic Z-ring in B. subtilis 168 without detectably affecting the segregation and organization of the nucleoids. Since the assembly dynamics of FtsZ protofilaments plays a major role in the formation and functioning of the Z-ring, we analysed the effects of curcumin on the assembly of FtsZ protofilaments. Curcumin inhibited the assembly of FtsZ protofilaments and also increased the GTPase activity of FtsZ. Electron microscopic analysis showed that curcumin reduced the bundling of FtsZ protofilaments in vitro. Further, curcumin was found to bind to FtsZ in vitro with a dissociation constant of 7.3±1.8 μM and the agent also perturbed the secondary structure of FtsZ. The results indicate that the perturbation of the GTPase activity of FtsZ assembly is lethal to bacteria and suggest that curcumin inhibits bacterial cell proliferation by inhibiting the assembly dynamics of FtsZ in the Z-ring.
Sp1 up-regulates cAMP-response-element-binding protein expression during retinoic acid-induced mucous differentiation of normal human bronchial epithelial cells
Authors: Hong Jeong Soo , Kim Seung-Wook , Koo Ja Seok
Published: February 2008

CREB [CRE (cAMP-response element)-binding protein] is an important transcription factor that is differentially regulated in cells of various types. We recently reported that RA (retinoic acid) rapidly activates CREB without using RARs (RA receptors) or RXRs (retinoid X receptors) in NHTBE cells (normal human tracheobronchial epithelial cells). However, little is known about the role of RA in the physiological regulation of CREB expression in the early mucous differentiation of NHTBE cells. In the present study, we report that RA up-regulates CREB gene expression and that, using 5′-serial deletion promoter analysis and mutagenesis analyses, two Sp1 (specificity protein 1)-binding sites located at nt −217 and −150, which flank the transcription initiation site, are essential for RA induction of CREB gene transcription. Furthermore, we found that CREs located at nt −119 and −98 contributed to basal promoter activity. Interestingly, RA also up-regulated Sp1 in a time- and dose-dependent manner. Knockdown of endogenous Sp1 using siRNA (small interfering RNA) decreased RA-induced CREB gene expression. However, the converse was not true: knockdown of CREB using CREB siRNA did not affect RA-induced Sp1 gene expression. We conclude that RA up-regulates CREB gene expression during the early stage of NHTBE cell differentiation and that RA-inducible Sp1 plays a major role in up-regulating human CREB gene expression. This result implies that co-operation of these two transcription factors plays a crucial role in mediating early events of normal mucous cell differentiation of bronchial epithelial cells.
Endosomes and lysosomes play distinct roles in sulfatide-induced neuroblastoma apoptosis: potential mechanisms contributing to abnormal sulfatide metabolism in related neuronal diseases
Authors: Zeng Youchun , Cheng Hua , Jiang Xuntian , Han Xianlin
Published: February 2008

Alterations in sulfatide metabolism, trafficking and homoeostasis are present at the earliest clinically recognizable stages of Alzheimer's disease and are associated with metachromatic leukodystrophy. However, the role of sulfatide in these disease states remains unknown. In the present study, we investigated the sequelae of NB (neuroblastoma) cells upon sulfatide supplementation and the biochemical mechanisms contributing to the sulfatide-induced changes. By using shotgun lipidomics, we showed dramatic accumulations of sulfatide, ceramide and sphingosine in NB cells in a time- and dose-dependent manner. Further studies utilizing subcellular fractionation and shotgun lipidomics analyses demonstrated that most of the increased ceramide content was generated in the endosomal compartment, whereas sulfatides predominantly accumulated in lysosomes. In addition, we determined that the sulfatide-mediated increase in endosomal ceramide content mainly resulted from β-galactosidase activity, which directly hydrolyses sulfatide to ceramide without a prior desulfation step. Substantial cell apoptosis occurred in parallel with the accumulation of sulfatides and ceramides, as revealed by mitochondrial membrane depolarization, by phosphatidylserine translocation and by the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) assay. These findings were also demonstrated with primary neuron cultures. Collectively, our results demonstrate that abnormal sulfatide metabolism can induce cell apoptosis due to endosome-mediated ceramide generation and the accumulation of cytotoxic levels of sulfatides in lysosomes.
Structure and mode of action of the antimicrobial peptide arenicin
Authors: Andrä Jörg , Jakovkin Igor , Grötzinger Joachim , Hecht Oliver , Krasnosdembskaya Anna D. , Goldmann Torsten , Gutsmann Thomas , Leippe Matthias
Published: February 2008

The solution structure and the mode of action of arenicin isoform 1, an antimicrobial peptide with a unique 18-residue loop structure, from the lugworm Arenicola marina were elucidated here. Arenicin folds into a two-stranded antiparallel β-sheet. It exhibits high antibacterial activity at 37 and 4 °C against Gram-negative bacteria, including polymyxin B-resistant Proteus mirabilis. Bacterial killing occurs within minutes and is accompanied by membrane permeabilization, membrane detachment and release of cytoplasm. Interaction of arenicin with reconstituted membranes that mimic the lipopolysaccharide-containing outer membrane or the phospholipid-containing plasma membrane of Gram-negative bacteria exhibited no pronounced lipid specificity. Arenicin-induced current fluctuations in planar lipid bilayers correspond to the formation of short-lived heterogeneously structured lesions. Our results strongly suggest that membrane interaction plays a pivotal role in the antibacterial activity of arenicin.
Vimentin supports mitochondrial morphology and organization
Authors: Tang Ho Lam , Lung Hong Lok , Wu Ka Chun , Le Anh-Huy Phan , Tang Ho Man , Fung Ming Chiu
Published: February 2008

Vimentin is one of the intermediate filaments that functions in structural support, signal transduction and organelle positioning of a cell. In the present study, we report the contribution of vimentin in mitochondrial morphology and organization. Using subcellular fractionation, immunoprecipitation and fluorescence microscopy analyses, we found that vimentin was associated with mitochondria. Knockdown of vimentin resulted in mitochondrial fragmentation, swelling and disorganization. We further demonstrated that the vimentin cytoskeleton co-localized and interacted with mitochondria to a greater extent than other cytoskeletal components known to support mitochondria. Our results also suggest that vimentin could participate in the mitochondrial association of microtubules. As mitochondrial morphologies determine mitochondrial function, our findings revealed a potentially important relationship between the vimentin-based intermediate filaments and the regulation of mitochondria.
The interaction of liver fatty-acid-binding protein (FABP) with anionic phospholipid vesicles: is there extended phospholipid anchorage under these conditions?
Authors: Hagan Robert M. , Worner-Gibbs Jane , Wilton David C.
Published: February 2008

Liver FABP (fatty-acid-binding protein) binds a variety of non-polar anionic ligands including fatty acids, fatty acyl CoAs, lysophospholipids and bile acids. Liver FABP is also able to bind to anionic phospholipid vesicles under conditions of low ionic strength, and membrane binding results in the release of bound ligand. However, the molecular interactions involved in binding to the phospholipid interface and the mechanism of ligand release are not known. Ligand release could be due to a significant conformational change in the protein at the interface or interaction of a phospholipid molecule with the ligand-binding cavity of the protein resulting in ligand displacement. Two portal mutant proteins of liver FABP, L28W and M74W, have now been used to investigate the binding of liver FABP to anionic phospholipid vesicles, monitoring changes in fluorescence and also fluorescence quenching in the presence of brominated lipids. There is a large increase in fluorescence intensity when the L28W mutant protein binds to vesicles prepared from DOPG (dioleoyl-sn-phosphatidylglycerol), but a large decrease in fluorescence intensity when the M74W mutant binds to these vesicles. The Br4-phospholipid prepared by bromination of DOPG dramatically quenches both L28W and M74W, consistent with the close proximity of a fatty acyl chain to the tryptophan residues. The binding of liver FABP to DOPG vesicles is accompanied by only a minimal change in the CD spectrum. Overall, the results are consistent with a molecule of anionic phospholipid interacting with the central cavity of the liver FABP, possibly involving the phospholipid molecule in an extended conformation.
Crystallographic analysis shows substrate binding at the −3 to +1 active-site subsites and at the surface of glycoside hydrolase family 11 endo-1,4-β-xylanases
Authors: Vandermarliere Elien , Bourgois Tine M. , Rombouts Sigrid , van Campenhout Steven , Volckaert Guido , Strelkov Sergei V. , Delcour Jan A. , Rabijns Anja , Courtin Christophe M.
Published: February 2008

GH 11 (glycoside hydrolase family 11) xylanases are predominant enzymes in the hydrolysis of heteroxylan, an abundant structural polysaccharide in the plant cell wall. To gain more insight into the protein–ligand interactions of the glycone as well as the aglycone subsites of these enzymes, catalytically incompetent mutants of the Bacillus subtilis and Aspergillus niger xylanases were crystallized, soaked with xylo-oligosaccharides and subjected to X-ray analysis. For both xylanases, there was clear density for xylose residues in the −1 and −2 subsites. In addition, for the B. subtilis xylanase, there was also density for xylose residues in the −3 and +1 subsite showing the spanning of the −1/+1 subsites. These results, together with the observation that some residues in the aglycone subsites clearly adopt a different conformation upon substrate binding, allowed us to identify the residues important for substrate binding in the aglycone subsites. In addition to substrate binding in the active site of the enzymes, the existence of an unproductive second ligand-binding site located on the surface of both the B. subtilis and A. niger xylanases was observed. This extra binding site may have a function similar to the separate carbohydrate-binding modules of other glycoside hydrolase families.
Sec22b-dependent assembly of endoplasmic reticulum Q-SNARE proteins
Authors: Aoki Takehiro , Kojima Masaki , Tani Katsuko , Tagaya Mitsuo
Published: February 2008

SNARE (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor) proteins involved in membrane fusion usually contain a conserved α-helix (SNARE motif) that is flanked by a C-terminal transmembrane domain. They can be classified into Q-SNARE and R-SNARE based on the structural property of their motifs. Assembly of four SNARE motifs (Qa, b, c and R) is supposed to trigger membrane fusion. We have previously shown that ER (endoplasmic reticulum)-localized syntaxin 18 (Qa) forms a complex with BNIP1 (Qb), p31/Use1 (Qc), Sec22b (R) and several peripheral membrane proteins. In the present study, we examined the interaction of syntaxin 18 with other SNAREs using pulldown assays and CD spectroscopy. We found that the association of syntaxin 18 with Sec22b induces an increase in α-helicity of their SNARE motifs, which results in the formation of high-affinity binding sites for BNIP1 and p31. This R-SNARE-dependent Q-SNARE assembly is quite different from the assembly mechanisms of SNAREs localized in organelles other than the ER. The implication of the mechanism of ER SNARE assembly is discussed in the context of the physiological roles of the syntaxin 18 complex.
The Effects of Curvature on the Grid Illusions
Authors: Levine Michael W , McAnany J Jason
Published: February 2008

Grid illusions, including the Hermann grid and scintillating grid (in which light disks are superimposed upon the grid intersections), are diminished by curving the alleys that limn the repeating pattern. Curvature might either disrupt the processes that induce the illusion, or simply make the illusory effects harder to see. To determine which mechanism might be invoked, we examined the effects of curving the alleys upon the vanishing-disk illusion, a phenomenon in which a single disk in a grid intersection is rendered less detectable. This illusion is of reduced visibility, rather than generating an illusory apparition as in the Hermann grid or scintillating grid. Thus, inhibition of illusory influence would enhance disk visibility, while a general reduction of visibility would render disks even harder to detect. We find that thresholds for both scintillation and the disk itself increase in a graded manner with increased curvature. Measuring the effect of curvature upon the vanishing disk with traditional forced-choice staircase methods demonstrates that the effect of curvature is upon detection, not subjective criterion. Furthermore, disks that are easy to detect within a rectilinear grid are more difficult to detect when the alleys are curved. Thus, curvature of the alleys induces a general tendency to inhibit the visibility of features, and is not specifically a repression of illusory effects.
Structure of a protein–DNA complex essential for DNA protection in spores of
Bacillus
species
Authors: Lee Ki Seog , Bumbaca Daniela , Kosman Jeffrey , Setlow Peter , Jedrzejas Mark J.
Published: February 2008

The DNA-binding α/β-type small acid-soluble proteins (SASPs) are a major factor in the resistance and long-term survival of spores of
Bacillus
species by protecting spore DNA against damage due to desiccation, heat, toxic chemicals, enzymes, and UV radiation. We now report the crystal structure at 2.1 Å resolution of an α/β-type SASP bound to a 10-bp DNA duplex. In the complex, the α/β-type SASP adopt a helix–turn–helix motif, interact with DNA through minor groove contacts, bind to ≈6 bp of DNA as a dimer, and the DNA is in an A-B type conformation. The structure of the complex provides important insights into the molecular details of both DNA and α/β-type SASP protection in the complex and thus also in spores.
Peptoids that mimic the structure, function, and mechanism of helical antimicrobial peptides
Authors: Chongsiriwatana Nathaniel P. , Patch James A. , Czyzewski Ann M. , Dohm Michelle T. , Ivankin Andrey , Gidalevitz David , Zuckermann Ronald N. , Barron Annelise E.
Published: February 2008

Antimicrobial peptides (AMPs) and their mimics are emerging as promising antibiotic agents. We present a library of “ampetoids” (antimicrobial peptoid oligomers) with helical structures and biomimetic sequences, several members of which have low-micromolar antimicrobial activities, similar to cationic AMPs like pexiganan. Broad-spectrum activity against six clinically relevant BSL2 pathogens is also shown. This comprehensive structure–activity relationship study, including circular dichroism spectroscopy, minimum inhibitory concentration assays, hemolysis and mammalian cell toxicity studies, and specular x-ray reflectivity measurements shows that the
in vitro
activities of ampetoids are strikingly similar to those of AMPs themselves, suggesting a strong mechanistic analogy. The ampetoids' antibacterial activity, coupled with their low cytotoxicity against mammalian cells, make them a promising class of antimicrobials for biomedical applications. Peptoids are biostable, with a protease-resistant
N
-substituted glycine backbone, and their sequences are highly tunable, because an extensive diversity of side chains can be incorporated via facile solid-phase synthesis. Our findings add to the growing evidence that nonnatural foldamers will emerge as an important class of therapeutics.