bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexual Development in
Cryptococcus neoformans
Requires
CLP1
, a Target of the Homeodomain Transcription Factors Sxi1α and Sxi2
a
Authors: Ekena Joanne L. , Stanton Brynne C. , Schiebe-Owens Jessica A. , Hull Christina M.
Published: November 2007

Sexual development in the human fungal pathogen
Cryptococcus neoformans
is a multistep process that results in the formation of spores, the likely infectious particles. A critical step in this developmental process is the transition from bud-form growth to filamentous growth. This transition is controlled by the homeodomain transcription factors Sxi1α and Sxi2
a
, whose targets are largely unknown. Here we describe the discovery of a gene,
CLP1
, that is regulated by Sxi1α and Sxi2
a
and is essential for sexual development. In vitro binding studies also show that the
CLP1
promoter is bound directly by Sxi1α and Sxi2
a
. The deletion of
CLP1
leads to a block in sexual development after cell fusion but before filament formation, and cells without
CLP1
are unable to grow vegetatively after cell fusion. Our findings lead to a model in which
CLP1
is a downstream target of the Sxi proteins that functions to promote growth after mating and to establish the filamentous state, a critical step in the production of spores.
Campylobacter jejuniBiofilms Up-Regulated in the Absence of the Stringent Response Utilize a Calcofluor White-Reactive Polysaccharide
Authors: McLennan Meghan K. , Ringoir Danielle D. , Frirdich Emilisa , Svensson Sarah L. , Wells Derek H. , Jarrell Harold , Szymanski Christine M. , Gaynor Erin C.
Published: November 2007

The enteric pathogenCampylobacter jejuniis a highly prevalent yet fastidious bacterium. Biofilms and surface polysaccharides participate in stress survival, transmission, and virulence inC. jejuni; thus, the identification and characterization of novel genes involved in each process have important implications for pathogenesis. We found thatC. jejunireacts with calcofluor white (CFW), indicating the presence of surface polysaccharides harboring β1-3 and/or β1-4 linkages. CFW reactivity increased with extended growth, under 42°C anaerobic conditions, and in a ΔspoTmutant defective for the stringent response (SR). Conversely, two newly isolateddimmutants exhibited diminished CFW reactivity as well as growth and serum sensitivity differences from the wild type. Genetic, biochemical, and nuclear magnetic resonance analyses suggested that differences in CFW reactivity between wild-type and ΔspoTanddimmutant strains were independent of well-characterized lipooligosaccharides, capsular polysaccharides, andN-linked polysaccharides. Targeted deletion ofcarBdownstream of thedim13mutation also resulted in CFW hyporeactivity, implicating a possible role for carbamoylphosphate synthase in the biosynthesis of this polysaccharide. Correlations between biofilm formation and production of the CFW-reactive polymer were demonstrated by crystal violet staining, scanning electron microscopy, and confocal microscopy, with theC. jejuniΔspoTmutant being the first SR mutant in any bacterial species identified as up-regulating biofilms. Together, these results provide new insight into genes and processes important for biofilm formation and polysaccharide production inC. jejuni.
Fur Regulates Expression of theSalmonellaPathogenicity Island 1 Type III Secretion System through HilD
Authors: Ellermeier Jeremy R. , Slauch James M.
Published: November 2007

The invasion of intestinal epithelial cells bySalmonella entericaserovar Typhimurium is mediated by a type III secretion system (T3SS) encoded onSalmonellapathogenicity island 1 (SPI1). Expression of the SPI1 T3SS is tightly regulated by the combined action of HilC, HilD, and RtsA, three AraC family members that can independently activatehilA, which encodes the direct regulator of the SPI1 structural genes. Expression ofhilC,hilD, andrtsAis controlled by a number of regulators that respond to a variety of environmental signals. In this work, we show that one such signal is iron mediated by Fur (ferric uptake regulator). Fur activateshilAtranscription in a HilD-dependent manner. Fur regulation of HilD does not appear to be simply at the transcriptional or translational level but rather requires the presence of the HilD protein. Fur activation of SPI1 is not mediated through the Fur-regulated small RNAs RfrA and RfrB, which are theSalmonellaortholog and paralog of RyhB that control expression ofsodB. Fur regulation of HilD is also not mediated through the known SPI1 repressor HilE or the CsrABC system. Although understanding the direct mechanism of Fur action on HilD requires further analysis, this work is an important step toward elucidating how various global regulatory systems control SPI1.
Roles of SigB and SigF in theMycobacterium tuberculosisSigma Factor Network
Authors: Lee Jong-Hee , Karakousis Petros C. , Bishai William R.
Published: November 2007

To characterize the roles of SigB and SigF in sigma factor regulation inMycobacterium tuberculosis, we used chemically inducible recombinant strains to conditionally overexpresssigBandsigF.Using whole genomic microarray analysis and quantitative reverse transcription-PCR, we investigated the resulting global transcriptional changes aftersigBinduction, and we specifically tested the relative expression of other sigma factor genes after knock-in expression ofsigBandsigF. Overexpression ofsigBresulted in significant upregulation of genes encoding several early culture filtrate antigens (ESAT-6-like proteins), ribosomal proteins, PE-PGRS proteins, the keto-acyl synthase, KasA, and the regulatory proteins WhiB2 and IdeR. Of note, the induction ofsigBdid not alter the expression of other sigma factor genes, indicating that SigB is likely to serve as an end regulator for at least one branch of theM. tuberculosissigma factor regulatory cascade. Analysis of the 5′-untranslated region (UTR) of SigB-dependent transcripts revealed a putative consensus sequence of NGTGG-N14-18-NNGNNG. This sequence appeared upstream of bothsigB(Rv2710) and the gene following it,ideR(Rv2711), and in vitro transcription analysis with recombinant SigB-reconstituted RNA polymerase confirmed SigB-dependent transcription from each of these promoters. Knock-in expression ofsigFrevealed that only thesigCgene was significantly upregulated 6 and 12 h aftersigFinduction. The previously identified SigF promoter consensus sequence AGTTTG-N15-GGGTTT was identified in the 5′ UTR of thesigCgene, and SigF-dependent in vitro transcription of the promoter upstream ofsigCwas confirmed by using recombinant SigF-reconstituted RNA polymerase. These two knock-in recombinant strains were tested in a macrophage model of infection which showed that overexpression ofsigBandsigFresulted in reduced rates ofM. tuberculosisintracellular growth. These results define the SigB promoter consensus recognition sequence and members of the SigB regulon. Moreover, the data suggest that, in addition to serving as an end regulator in a sigma factor cascade, SigB may auto-amplify its own expression under certain conditions.
A Multiprotein Bicarbonate Dehydration Complex Essential to Carboxysome Function in Cyanobacteria
Authors: Cot Swan S.-W. , So Anthony K.-C. , Espie George S.
Published: November 2007

Carboxysomes are proteinaceous biochemical compartments that constitute the enzymatic “back end” of the cyanobacterial CO
2
-concentrating mechanism. These protein-bound organelles catalyze HCO
3
−
dehydration and photosynthetic CO
2
fixation. In
Synechocystis
sp. strain PCC6803 these reactions involve the β-class carbonic anhydrase (CA), CcaA, and Form 1B ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). The surrounding shell is thought to be composed of proteins encoded by the
ccmKLMN
operon, although little is known about how structural and catalytic proteins integrate to form a functional carboxysome. Using biochemical activity assays and molecular approaches we have identified a catalytic, multiprotein HCO
3
−
dehydration complex (BDC) associated with the protein shell of
Synechocystis
carboxysomes. The complex was minimally composed of a CcmM73 trimer, CcaA dimer, and CcmN. Larger native complexes also contained RbcL, RbcS, and two or three immunologically identified smaller forms of CcmM (62, 52, and 36 kDa). Yeast two-hybrid analyses indicated that the BDC was associated with the carboxysome shell through CcmM73-specific protein interactions with CcmK and CcmL. Protein interactions between CcmM73 and CcaA, CcmM73 and CcmN, or CcmM73 and itself required the N-terminal γ-CA-like domain of CcmM73. The specificity of the CcmM73-CcaA interaction provided both a mechanism to integrate CcaA into the fabric of the carboxysome shell and a means to recruit this enzyme to the BDC during carboxysome biogenesis. Functionally, CcaA was the catalytic core of the BDC. CcmM73 bound H
14
CO
3
−
but was unable to catalyze HCO
3
−
dehydration, suggesting that it may potentially regulate BDC activity.
Transcriptome Profiling and Functional Analysis ofAgrobacterium tumefaciensReveals a General Conserved Response to Acidic Conditions (pH 5.5) and a Complex Acid-Mediated Signaling Involved inAgrobacterium-Plant Interactions
Authors: Yuan Ze-Chun , Liu Pu , Saenkham Panatda , Kerr Kathleen , Nester Eugene W.
Published: November 2007

Agrobacterium tumefacienstransferred DNA (T-DNA) transfer requires that the virulence genes (virregulon) on the tumor-inducing (Ti) plasmid be induced by plant phenolic signals in an acidic environment. Using transcriptome analysis, we found that these acidic conditions elicit two distinct responses: (i) a general and conserved response through whichAgrobacteriummodulates gene expression patterns to adapt to environmental acidification and (ii) a highly specialized acid-mediated signaling response involved inAgrobacterium-plant interactions. Overall, 78 genes were induced and 74 genes were repressed significantly under acidic conditions (pH 5.5) compared to neutral conditions (pH 7.0). Microarray analysis not only confirmed previously identified acid-inducible genes but also uncovered many new acid-induced genes which may be directly involved inAgrobacterium-plant interactions. These genes includevirE0,virE1,virH1, andvirH2. Further, thechvG-chvItwo-component system, previously shown to be critical for virulence, was also induced under acid conditions. Interestingly, acidic conditions induced a type VI secretion system and a putative nonheme catalase. We provide evidence suggesting that acid-induced gene expression was independent of the VirA-VirG two-component system. Our results, together with previous data, support the hypothesis that there is three-step sequential activation of thevirregulon. This process involves a cascade regulation and hierarchical signaling pathway featuring initial direct activation of the VirA-VirG system by the acid-activated ChvG-ChvI system. Our data strengthen the notion thatAgrobacteriumhas evolved a mechanism to perceive and subvert the acidic conditions of the rhizosphere to an important signal that initiates and directs the early virulence program, culminating in T-DNA transfer.
Multiple Phospholipid
N
-Methyltransferases with Distinct Substrate Specificities Are Encoded in
Bradyrhizobium japonicum
Authors: Hacker Stephanie , Sohlenkamp Christian , Aktas Meriyem , Geiger Otto , Narberhaus Franz
Published: November 2007

Phosphatidylcholine (PC) is the major phospholipid in eukaryotic membranes. In contrast, it is found in only a few prokaryotes including members of the family
Rhizobiaceae
. In these bacteria, PC is required for pathogenic and symbiotic plant-microbe interactions, as shown for
Agrobacterium tumefaciens
and
Bradyrhizobium japonicum
. At least two different phospholipid
N
-methyltransferases (PmtA and PmtX) have been postulated to convert phosphatidylethanolamine (PE) to PC in
B. japonicum
by three consecutive methylation reactions. However, apart from the known PmtA enzyme, we identified and characterized three additional
pmt
genes (
pmtX1
,
pmtX3
, and
pmtX4
), which can be functionally expressed in
Escherichia coli
, showing different substrate specificities.
B. japonicum
expressed only two of these
pmt
genes (
pmtA
and
pmtX1
) under all conditions tested. PmtA predominantly converts PE to monomethyl PE, whereas PmtX1 carries out both subsequent methylation steps.
B. japonicum
is the first bacterium known to use two functionally different Pmts. It also expresses a PC synthase, which produces PC via condensation of CDP-diacylglycerol and choline. Our study shows that PC biosynthesis in bacteria can be much more complex than previously anticipated.
Identification of the
bchP
Gene, Encoding Geranylgeranyl Reductase in
Chlorobaculum tepidum
Authors: Gomez Maqueo Chew Aline , Frigaard Niels-Ulrik , Bryant Donald A.
Published: November 2007

The
Chlorobaculum tepidum
genome contains two paralogous genes, CT2256 and CT1232, whose products are members of the FixC dehydrogenase superfamily and have sequence similarity to geranylgeranyl reductases. Each gene was insertionally inactivated, and the resulting mutants were characterized. CT2256 encodes geranylgeranyl reductase (BchP); CT1232 is not involved in bacteriochlorophyll or chlorophyll biosynthesis.
Influence of Quorum Sensing and Iron on Twitching Motility and Biofilm Formation in
Pseudomonas aeruginosa
Authors: Patriquin Glenn M. , Banin Ehud , Gilmour Christie , Tuchman Rivka , Greenberg E. Peter , Poole Keith
Published: November 2007

Reducing iron (Fe) levels in a defined minimal medium reduced the growth yields of planktonic and biofilm
Pseudomonas aeruginosa
, though biofilm biomass was affected to the greatest extent and at FeCl
3
concentrations where planktonic cell growth was not compromised. Highlighting this apparently greater need for Fe, biofilm growth yields were markedly reduced in a mutant unable to produce pyoverdine (and, so, deficient in pyoverdine-mediated Fe acquisition) at concentrations of FeCl
3
that did not adversely affect biofilm yields of a pyoverdine-producing wild-type strain. Concomitant with the reduced biofilm yields at low Fe concentrations,
P. aeruginosa
showed enhanced twitching motility in Fe-deficient versus Fe-replete minimal media. A mutant deficient in low-Fe-stimulated twitching motility but normal as regards twitching motility on Fe-rich medium was isolated and shown to be disrupted in
rhlI
, whose product is responsible for synthesis of the
N
-butanoyl homoserine lactone (C4-HSL) quorum-sensing signal. In contrast to wild-type cells, which formed thin, flat, undeveloped biofilms in Fe-limited medium, the
rhlI
mutant formed substantially developed though not fully mature biofilms under Fe limitation. C4-HSL production increased markedly in Fe-limited versus Fe-rich
P. aeruginosa
cultures, and cell-free low-Fe culture supernatants restored the twitching motility of the
rhlI
mutant on Fe-limited minimal medium and stimulated the twitching motility of
rhlI
and wild-type
P. aeruginosa
on Fe-rich minimal medium. Still, addition of exogenous C4-HSL did not stimulate the twitching motility of either strain on Fe-replete medium, indicating that some Fe-regulated and RhlI/C4-HSL-dependent extracellular product(s) was responsible for the enhanced twitching motility (and reduced biofilm formation) seen in response to Fe limitation.
SipA Is Required for Pilus Formation in
Streptococcus pyogenes
Serotype M3
Authors: Zähner Dorothea , Scott June R.
Published: November 2007

Pili are a major surface feature of the human pathogen
Streptococcus pyogenes
(group A streptococcus [GAS]). The T3 pilus is composed of a covalently linked polymer of protein T3 (formerly Orf100 or Fct3) with an ancillary protein, Cpa, attached. A putative signal peptidase, SipA (also called LepA), has been identified in several pilus gene clusters of GAS. We demonstrate that the SipA2 allele of a GAS serotype M3 strain is required for synthesis of T3 pili. Heterologous expression in
Escherichia coli
showed that SipA2, along with the pilus backbone protein T3 and the sortase SrtC2, is required for polymerization of the T3 protein. In addition, we found that SipA2 is also required for linkage of the ancillary pilin protein Cpa to polymerized T3. Despite partial conservation of motifs of the type I signal peptidase family proteins, SipA lacks the highly conserved and catalytically important serine and lysine residues of these enzymes. Substitution of alanine for either of the two serine residues closest to the expected location of an active site serine demonstrated that these serine residues are both dispensable for T3 polymerization. Therefore, it seems unlikely that SipA functions as a signal peptidase. However, a T3 protein mutated at the P-1 position of the signal peptide cleavage site (alanine to arginine) was unstable in the presence of SipA2, suggesting that there is an interaction between SipA and T3. A possible chaperone-like function of SipA2 in T3 pilus formation is discussed.
Localization of phosphorylated αB-crystallin to heart mitochondria during ischemia-reperfusion
Authors: Jin J.-K. , Whittaker R. , Glassy M. S. , Barlow S. B. , Gottlieb R. A. , Glembotski C. C.
Published: November 2007

The cytosolic small heat shock protein αB-crystallin (αBC) is a molecular chaperone expressed in large quantities in the heart, where it protects from stresses such as ischemia-reperfusion (I/R). Upon I/R, p38 MAP kinase activation leads to phosphorylation of αBC on Ser59(P-αBC-S59), which increases its protective ability. αBC confers protection, in part, by interacting with and affecting the functions of key components in stressed cells. We investigated the hypothesis that protection from I/R damage in the heart by P-αBC-S59 can be mediated by localization to mitochondria. We found that P-αBC-S59 localized to mitochondria isolated from untreated mouse hearts and that this localization increased more than threefold when the hearts were subjected to ex vivo I/R. Mitochondrial P-αBC-S59 decreased when hearts were treated with the p38 inhibitor SB-202190. Moreover, SB-202190-treated hearts exhibited more tissue damage and less functional recovery upon reperfusion than controls. I/R activates mitochondrial permeability transition (MPT) pore opening, which increases cell damage. We found that mitochondria incubated with a recombinant mutant form of αBC that mimics P-αBC-S59 exhibited decreased calcium-induced MPT pore opening. These results indicate that mitochondria may be among the key components in stressed cells with which P-αBC-S59 interacts and that this localization may protect the myocardium, in part, by modulating MPT pore opening and, thus, reducing I/R injury.
Selective quantification of the cardiac sympathetic and parasympathetic nervous systems by multisignal analysis of cardiorespiratory variability
Authors: Chen Xiaoxiao , Mukkamala Ramakrishna
Published: November 2007

Heart rate (HR) power spectral indexes are limited as measures of the cardiac autonomic nervous systems (CANS) in that they neither offer an effective marker of the β-sympathetic nervous system (SNS) due to its overlap with the parasympathetic nervous system (PNS) in the low-frequency (LF) band nor afford specific measures of the CANS due to input contributions to HR [e.g., arterial blood pressure (ABP) and instantaneous lung volume (ILV)]. We derived new PNS and SNS indexes by multisignal analysis of cardiorespiratory variability. The basic idea was to identify the autonomically mediated transfer functions relating fluctuations in ILV to HR (ILV→HR) and fluctuations in ABP to HR (ABP→HR) so as to eliminate the input contributions to HR and then separate each estimated transfer function in the time domain into PNS and SNS indexes using physiological knowledge. We evaluated these indexes with respect to selective pharmacological autonomic nervous blockade in 14 humans. Our results showed that the PNS index derived from the ABP→HR transfer function was correctly decreased after vagal and double (vagal + β-sympathetic) blockade ( P < 0.01) and did not change after β-sympathetic blockade, whereas the SNS index derived from the same transfer function was correctly reduced after β-sympathetic blockade in the standing posture and double blockade ( P < 0.05) and remained the same after vagal blockade. However, this SNS index did not significantly decrease after β-sympathetic blockade in the supine posture. Overall, these predictions were better than those provided by the traditional high-frequency (HF) power, LF-to-HF ratio, and normalized LF power of HR variability.
The small heat shock-related protein, HSP20, is a cAMP-dependent protein kinase substrate that is involved in airway smooth muscle relaxation
Authors: Komalavilas Padmini , Penn Raymond B. , Flynn Charles R. , Thresher Jeffrey , Lopes Luciana B. , Furnish Elizabeth J. , Guo Manhong , Pallero Manuel A. , Murphy-Ullrich Joanne E. , Brophy Colleen M.
Published: November 2007

Activation of the cAMP/cAMP-dependent PKA pathway leads to relaxation of airway smooth muscle (ASM). The purpose of this study was to examine the role of the small heat shock-related protein HSP20 in mediating PKA-dependent ASM relaxation. Human ASM cells were engineered to constitutively express a green fluorescent protein-PKA inhibitory fusion protein (PKI-GFP) or GFP alone. Activation of the cAMP-dependent signaling pathways by isoproterenol (ISO) or forskolin led to increases in the phosphorylation of HSP20 in GFP but not PKI-GFP cells. Forskolin treatment in GFP but not PKI-GFP cells led to a loss of central actin stress fibers and decreases in the number of focal adhesion complexes. This loss of stress fibers was associated with dephosphorylation of the actin-depolymerizing protein cofilin in GFP but not PKI-GFP cells. To confirm that phosphorylated HSP20 plays a role in PKA-induced ASM relaxation, intact strips of bovine ASM were precontracted with serotonin followed by ISO. Activation of the PKA pathway led to relaxation of bovine ASM, which was associated with phosphorylation of HSP20 and dephosphorylation of cofilin. Finally, treatment with phosphopeptide mimetics of HSP20 possessing a protein transduction domain partially relaxed precontracted bovine ASM strips. In summary, ISO-induced phosphorylation of HSP20 or synthetic phosphopeptide analogs of HSP20 decreases phosphorylation of cofilin and disrupts actin in ASM, suggesting that one possible mechanism by which HSP20 mediates ASM relaxation is via regulation of actin filament dynamics.
Expression of the dystrophin-glycoprotein complex is a marker for human airway smooth muscle phenotype maturation
Authors: Sharma Pawan , Tran Thai , Stelmack Gerald L. , McNeill Karol , Gosens Reinoud , Mutawe Mark M. , Unruh Helmut , Gerthoffer William T. , Halayko Andrew J.
Published: November 2007

Airway smooth muscle (ASM) cells may contribute to asthma pathogenesis through their capacity to switch between a synthetic/proliferative and a contractile phenotype. The multimeric dystrophin-glycoprotein complex (DGC) spans the sarcolemma, linking the actin cytoskeleton and extracellular matrix. The DGC is expressed in smooth muscle tissue, but its functional role is not fully established. We tested whether contractile phenotype maturation of human ASM is associated with accumulation of DGC proteins. We compared subconfluent, serum-fed cultures and confluent cultures subjected to serum deprivation, which express a contractile phenotype. Western blotting confirmed that β-dystroglycan, β-, δ-, and ε-sarcoglycan, and dystrophin abundance increased six- to eightfold in association with smooth muscle myosin heavy chain (smMHC) and calponin accumulation during 4-day serum deprivation. Immunocytochemistry showed that the accumulation of DGC subunits was specifically localized to a subset of cells that exhibit robust staining for smMHC. Laminin competing peptide (YIGSR, 1 μM) and phosphatidylinositol 3-kinase (PI3K) inhibitors (20 μM LY-294002 or 100 nM wortmannin) abrogated the accumulation of smMHC, calponin, and DGC proteins. These studies demonstrate that the accumulation of DGC is an integral feature for phenotype maturation of human ASM cells. This provides a strong rationale for future studies investigating the role of the DGC in ASM smooth muscle physiology in health and disease.
Black Canadian Historical Writing 1970-2006
Authors: Este David C.
Published: November 2007

Since 1970, there have been numerous contributions to the discipline of Black Canadian history. This article assesses the work of a number of historians and other social scientists in the literature. Each of the authors clearly acknowledges that Black Canadians have experienced racism and discrimination since their arrival in Canada and discusses how members of the community responded to these practices. Collectively, the work of these authors clearly fills a void in the writing of Canadian history in which people of African descent are typically excluded.
A Retrospective on the Strengths of African Nova Scotian Communities
Authors: Sehatzadeh Adrienne Lucas
Published: November 2007

Nova Scotia is home to Canada's largest indigenous Black population, whose roots reach back to 1750. From early settlers followed by Black Loyalists, slaves, Maroons, and Black Refugees, life for Black people was marked by abject poverty, marginalization, and systemic and systematic racism. Yet African Nova Scotians refused to be beaten. Some communities remain, some were destroyed by forced removal of their residents, and others suffered from dispersal of their residents over time in search of better opportunities. Such was the case of a small, African Nova Scotian community with no official name and no local institutions, unofficially known as “The Avenue.” This commentary underscores the complexities that work historically to deny a people full and equitable citizenship. It is a story that reinforces the strength of community beyond geographical boundaries.
HARAMBEC! Quebec Black Women Pulling Together
Authors: Small Shirley , Thornhill Esmeralda M. A.
Published: November 2007

North of the Canada—U.S. border, conditions, attitudes, and behaviors toward Blacks practiced during the time of slavery have continued sometimes in crude displays of racism, sometimes in more subtle forms. No Black is exempt—male or female, adult or child. Advocacy is unavoidable; proactive interventions are necessary. This exposé deals with the little-known story of Black women challenging the Canadian system in an ongoing bid for quality life for themselves and their families. This valiant, ongoing encounter can only result in some modifications favorable to an improved quality of life for Canadian Blacks. In essence, Harambec opens a window on Black women organizing in Quebec under the aegis of the Congress of Black Women of Canada—a vibrant national organization intent on changing behaviors, perceptions, policies, and practice across the Canadian social, political, and economic landscape.
Perceptions of Domestic Violence and Mock Jurors' Sentencing Decisions
Authors: Kern Rosalie , Libkuman Terry M. , Temple Stacey L.
Published: November 2007

The purpose of the investigation was to examine the influence of the victim's provocation and hopefulness on the sentencing of a husband convicted of domestic violence. It was hypothesized that mock jurors would assign less-severe sentencing if the victim was provoking and hopeful. Mock jurors read one of four factorial court case combinations of provocation and hopefulness and rendered an individual predeliberation sentence and a group postdeliberation sentence. Analyses revealed a significant effect of provocation, indicating that participants reduced the sentencing for the defendant when the wife was provoking relative to when she was not provoking. The analyses also revealed an effect of gender on predeliberation sentencing, with women delivering more-severe sentences than men. The effect of gender was not present in the postdeliberation sentencing, indicating that deliberation produced a sentencing compromise between women and men. The implications of these findings are discussed.
Juvenile Delinquency and Victimization
Authors: Cuevas Carlos A. , Finkelhor David , Turner Heather A. , Ormrod Richard K.
Published: November 2007

It is a widely voiced notion that juvenile delinquency and victimization co-occur extensively in the youth population, in particular because delinquent youth engage in risky activities. But theory from the bullying and traumatic stress literatures suggests that there may be additional pathways by which delinquency and victimization are connected. This analysis looks for possible subtypes of delinquents and victims consistent with such pathways. Using the Developmental Victimization Survey, a national sample of 1,000 youth aged 10 to 17 were interviewed over the phone. Support emerges for three distinct types of delinquent-victims, who are termed bully-victims, delinquent sex/maltreatment— victims, and property delinquent—victims. There is also evidence for substantial groups of youth who are primarily delinquent but not seriously victimized, as well as youth who are primarily victimized but not delinquent.
DNA methylation-independent loss of RARA gene expression in acute myeloid leukemia
Authors: Glasow Annegret , Barrett Angela , Petrie Kevin , Gupta Rajeev , Boix-Chornet Manuel , Zhou Da-Cheng , Grimwade David , Gallagher Robert , von Lindern Marieke , Waxman Samuel , Enver Tariq , Hildebrandt Guido , Zelent Arthur
Published: November 2007

The retinoic acid receptor (RAR) α gene (RARA) encodes 2 major isoforms and mediates positive effects of all-trans retinoic acid (ATRA) on myelomonocytic differentiation. Expression of the ATRA-inducible (RARα2) isoform increases with myelomonocytic differentiation and appears to be down-regulated in many acute myeloid leukemia (AML) cell lines. Here, we demonstrate that relative to normal myeloid stem/progenitor cells, RARα2 expression is dramatically reduced in primary AML blasts. Expression of the RARα1 isoform is also significantly reduced in primary AML cells, but not in AML cell lines. Although the promoters directing expression of RARα1 and RARα2 are respectively unmethylated and methylated in AML cell lines, these regulatory regions are unmethylated in all the AML patient cell samples analyzed. Moreover, in primary AML cells, histones associated with the RARα2 promoter possessed diminished levels of H3 acetylation and lysine 4 methylation. These results underscore the complexities of the mechanisms responsible for deregulation of gene expression in AML and support the notion that diminished RARA expression contributes to leukemogenesis.
Hydroxyurea nitrosylates and activates soluble guanylyl cyclase in human erythroid cells
Authors: Cokic Vladan P. , Andric Silvana A. , Stojilkovic Stanko S. , Noguchi Constance T. , Schechter Alan N.
Published: November 2007

Hydroxyurea, a drug widely used for treating myeloproliferative diseases, has also been approved for the treatment of sickle cell disease by raising fetal hemoglobin (HbF). We have shown that nitric oxide (NO) and the soluble guanylyl cyclase (sGC) pathways are involved in hydroxyurea induction of HbF levels in erythroid progenitor cells (EPCs). We demonstrate now that during erythroid differentiation, endothelial NO synthase mRNA and protein levels decline steadily, as does the production of NO derivatives and cyclic adenosine monophosphate (cAMP) levels, but guanosine 3′,5′-cyclic monophosphate (cGMP) levels are stable. Hydroxyurea increased intracellular cGMP levels and cAMP levels in EPCs. The NO donor, DEANONOate, induced much higher cGMP levels, but reduced cAMP levels. Hydroxyurea (1 mM) induced production of approximately 45 pM cGMP/minute/ng of purified sGC, similar to induction by 1 μM DEANONOate. We found that hydroxyurea and ProliNONOate produced iron-nitrosyl derivatives of sGC. Thus, we confirm that hydroxyurea can directly interact with the deoxy-heme of sGC, presumably by a free-radical nitroxide pathway, and activate cGMP production. These data add to an expanding appreciation of the role of hydroxyurea as an inducer of the NO/cGMP pathway in EPCs. These mechanisms may also be involved in the cytostatic effects of hydroxyurea, as well as the induction of HbF.
Melville's Celibatory Machines \-\- Bartleby, Pierre, and The Paradise of Bachelors
Authors: Arsić Branka
Published: November 2007

Branka Arsić's essay analyzes the complex relations among law, writing, and marriage described by Melville in Pierre, "The Paradise of Bachelors and the Tartarus of Maids," and Bartleby, the Scrivener. The major argument of the essay is that Melville conceives of both writing and marriage as "celibatory machines," cut in two by the power of the law, which explains the obsessive return to the question of the law in his writing. The celibatory machine functions to divide the same in two such that any future fusion of, or even encounter between, the parts becomes impossible. The law in Melville is also such a severing blade that hollows the subject within itself, making it, as it were, empty and so rendering it inoperative. That accounts for the overwhelming presence of "passive" characters in Melville's work. However, since the law also imposes its power upon itself, it is emptied of its own lawfulness and thus deactivated. Hence everything in Melville happens within the space of the law, yet nothing ever functions lawfully.
The Marriage Translation and the Contexts of Common Life: From the Pacs to Benjamin and Beyond
Authors: Bishop Will
Published: November 2007

"The Marriage Translation" argues that a Benjaminian account of translation can shed new light on the ways in which contemporary practices of queer alliance transform, and are transformed by, legal and political discourse. In a constellation of readings—of arguments for the French pacs, of Benjamin's essays on translation, and on Goethe's Elective Affinities, as well as of two photos of the illegal weddings celebrated in San Francisco and in Bègles, France—the article emphasizes the ways social contexts are sometimes reinvigorated and at other times ignored by the demand for certain forms of legal recognition.
Marital, Martial, Maritime Law: Toward Some Controversial Passages in Kant's Doctrine of Right
Authors: Fenves Peter D. (Peter David)
Published: November 2007

Beginning with an analysis of an early satire of Kant's doctrine of marital law, this essay draws on Walter Benjamin's condensed exposition of this doctrine in order to ask whether Kant's notoriously unsentimental representation of marriage is, in fact, from the perspective of his own idea of law, overly sentimental. Whereas Kant ridicules the idea of a "law of war" in his program for perpetual peace, he accepts the possibility of legally sanctioned intercourse, in which people use others and themselves. Between marital law and martial law lies maritime law, which concerns a surface that can be used but not mastered.
Literature and a Woman's Right to Choose \-\- Not to Marry
Authors: Miller J. Hillis (Joseph Hillis)
Published: November 2007

A woman's right to say no to a proposal of marriage, in defiance of her family and friends, was an essential feature of Victorian middle- and upper-class ideology, as it is represented in novels of the time. This right was based on the assumptions that falling in love is to some degree fortuitous, but that it is a permanent ontological change of selfhood. A good woman is justified in saying no even to an advantageous marriage proposal if she does not love her suitor. Anthony Trollope's novels offer varied dramatizations of these assumptions, while Henry James's novels recount their incipient breakdown.
Introduction: Literature and the Right to Marriage
Authors: Miller Steven , Guyer Sara Emilie
Published: November 2007

"Literature and the Right to Marriage," which bears the same title as the special issue that it introduces, takes up the challenge of the claim that marriage is a universal right. Framing the questions that traverse the five essays in the collection with a close reading of the sections on marriage from Hegel's Elements of the Philosophy of Right, the authors argue that if marriage can be considered a right, this right both guarantees access to and is founded upon each partner's vow to abide by his or her vows to the other. Hegel's text is important because it underscores the linguistic dimension of the marriage ceremony; and it thus helps to show that, if the right to marriage were universal, it must be understood as the right to an irreplaceable kind of ritual speech. Moreover, this text is remarkably modern in its emphasis upon love as the condition of rightful marriage. Hegel considered the exchange of marriage vows to be a political event at which love becomes ethical (distinct from seduction), and ethics becomes political (distinct from morality and inseparable from civil society and the state); and thus also the point at which the model for "ethical love" becomes the verbally solemnized love between a man and a woman rather than the priestly love of the neighbor. Marriage, for Hegel, is always a turning point, both in the lives of the couple and in the history of the state. But this means that the importance of any marriage cannot be measured in terms of a norm; it can only be measured in terms of the amorous situation that precedes the event of marriage. Hegel's analyses are indispensable for grasping the stakes of the essays collected in this special issue and for addressing contemporary questions about which couples have the right to marry and what marriage becomes when those who would marry already have shared long and complex lives together.
Global Politics in the 1580s: One Canal, Twenty Thousand Cannibals, and an Ottoman Plot to Rule the World
Authors: Casale Giancarlo
Published: November 2007

Yemen with a small war fl eet and headed for the Portuguese-controlled city-states of Africa's Swahili coast. Although ultimately unsuccessful, his expedition was conceived as only the fi rst step in an extended effort to create a centralized Ottoman imperial infrastructure throughout the Indian Ocean basin. And had it not been for the fortuitous intervention of several thousand "Zimba" warriors on the eve of the fi nal encounter between Ottoman and Portuguese forces at Mombasa in March 1589, the available evidence suggests that Mir Ali and his men might very well have carried the day.
Sati and the Task of the Historian
Authors: Fisch Jörg
Published: November 2007

The article's approach to sati and similar phenomena is functionally and morally neutral. A society that practices following in death is not, for that matter, considered inferior. Schneewind, however, pleads for a normative moral approach, ranking societies according to their ability to rid themselves of harmful customs. What in the article is shown as a mere functional difference between European (or Christian) and (some) non-Western societies thereby appears as an illegitimate Eurocentrism or ethnocentrism. Such a view should not be read into the text, as it will inhibit consideration of important questions.
The Concept of "Decisive Battles" in World History
Authors: Harari Yuval N
Published: November 2007

This article discusses the historiography of the concept of "decisive battles" and tries to explain both its popularity and its present eclipse, focusing in particular on the ideological and aesthetic foundations of the concept. The article further considers whether the concept might still be useful for the writing of world history. It concludes that there is some merit in the traditional view of decisive battles as events that change the course of history and bring a signifi cant element of chaos into it. There is, however, less merit in the view of decisive battles as symbols for long-term historical developments.
Reconsidering " Sati in Universal Context"
Authors: Schneewind Sarah
Published: November 2007

While world and comparative historians need not research each local instance in great depth, Jörg Fisch's recent article "Dying for the Dead: Sati in Universal Context" neglects most of the research on a case he stresses, China. Fisch's argument that only "outsiders" can end following in death practices overlooks how historical movements compromise such clear categorization and relies rhetorically on terms that foreclose the possibility of abolition by "insiders." His claim that only "outsiders" have historically ended such practices overlooks the complexities of the effects (and causes) of colonialism and the unanswerable question of what might have happened without it. His choice to set aside in his analysis the means of death confl icts with evidence he provides that suggests means might have fi gured in women's own calculations about how to demonstrate faithfulness to the dead, further foreclosing the possibility that insiders can change their own societies.
Socialist Paths in a Capitalist Conundrum: Reconsidering the German Catastrophe of 1933
Authors: Smaldone William
Published: November 2007

The collapse of the Weimar Republic in 1933 was a disaster of world-historical dimensions. While most historians focus on the Social Democratic role in that debacle primarily within its German and European contexts, this essay examines it within the broader framework of the global history of democratic socialism in the twentieth century. By comparing Social Democracy's defeat in 1933 with the experiences of the Popular Unity Party in Chile in 1973, the Sandinistas in Nicaragua in 1989, and the African National Congress in South Africa in 1994, the essay examines the Socialist failure in 1933 from a new perspective and raises questions about the dilemmas faced by democratic socialist movements in bringing about radical change.
Reconstructing World History in the People's Republic of China since the 1980s
Authors: Xu Luo
Published: November 2007

This article offers a critical review of the efforts made by Chinese historians since the 1980s to reconceptualize and reconstruct world history from a global perspective as well as the complex ideological, institutional, and sociopsychological issues that hindered their efforts. It argues that the success and failure of their work were in many ways related to the extent to which they were able (or unable) to overcome these barriers. The article discusses the new theoretical framework that Chinese historians developed, newly published world history texts, and reactions to recent Western scholarship. It concludes that, despite various problems, the Chinese historians' efforts signifi ed an important step in their long endeavor to envision a world history with Chinese characteristics.
Intellectual Property and Biotechnology: The European Debate
Authors: Brody Baruch A
Published: November 2007

The European patent system allows for the introduction of moral issues into decisions about the granting of patents. This feature has greatly impacted European debates about the patenting of biotechnology. This essay explores the European experience, in both the European Union and the European Patent Organization. It argues that there has been great confusion surrounding these issues primarily because the Europeans have not developed a general theory about when exclusion from patentability is the best social mechanism for dealing with morally offensive technologies.
Getting the Ethics Right Regarding Research in the Emergency Setting: Lessons from the PolyHeme Study
Authors: Dickert Neal , Sugarman Jeremy
Published: November 2007

Research in emergency settings (RES) has become a major public issue with urgent policy implications. Significant attention has focused recently on RES in response to the trial of PolyHeme, a synthetic blood substitute, in trauma victims in hemorrhagic shock. Unfortunately, the discussion of the PolyHeme trial in the popular and scholarly press leaves important questions unanswered. This paper articulates three important lessons from the PolyHeme trial that have significant policy implications. First, the RES regulations should be re-visited, particularly the requirement that existing treatments be unproven or unsatisfactory in order for research to be acceptable without consent. Second, further conceptual and empirical scholarship is needed to accomplish the goal of effectively involving communities. Third, a more subtle analysis is needed regarding how to balance the needs of maintaining public trust and protecting confidential trade information in the context of RES.
The Primacy of the Public: In Support of Bioethics Commissions as Deliberative Forums
Authors: Dzur Albert W , Levin Daniel Lessard
Published: November 2007

In a 2004 article, we argued that bioethics commissions should be assessed in terms of their usefulness as public forums. A 2006 article by Summer Johnson argued that our perspective was not supported by the existing literature on presidential commissions, which had not previously identified commissions as public forums and that we did not properly account for the political functions of commissions as instruments of presidential power. Johnson also argued that there was nothing sufficiently unique about bioethics commissions to make the public forum perspective particularly applicable. We respond by arguing that analysis of commissions' work as public forums fits well within the literature on commissions, especially on their agenda-setting functions, and that the political functions of commissions are often compatible with their functioning as public forums. We also demonstrate how the origins and concerns of bioethics make public forum analysis particularly applicable to bioethics commissions.
Corrupt Practices in Chinese Medical Care: The Root in Public Policies and a Call for Confucian-Market Approach
Authors: Fan Ruiping
Published: November 2007

This paper argues that three salient corrupt practices that mark contemporary Chinese health care, namely the over-prescription of indicated drugs, the prescription of more expensive forms of medication and more expensive diagnostic work-ups than needed, and illegal cash payments to physicians—i.e., red packages—result not from the introduction of the market to China, but from two clusters of circumstances. First, there has been a loss of the Confucian appreciation of the proper role of financial reward for good health care. Second, misguided governmental policies have distorted the behavior of physicians and hospitals. The distorting policies include (1) setting very low salaries for physicians, (2) providing bonuses to physicians and profits to hospitals from the excessive prescription of drugs and the use of more expensive drugs and unnecessary expensive diagnostic procedures, and (3) prohibiting payments by patients to physicians for higher quality care. The latter problem is complicated by policies that do not allow the use of governmental insurance and funds from medical savings accounts in private hospitals as well as other policies that fail to create a level playing field for both private and government hospitals. The corrupt practices currently characterizing Chinese health care will require not only abolishing the distorting governmental policies but also drawing on Confucian moral resources to establish a rightly directed appreciation of the proper place of financial reward in the practice of medicine.
Making Public Bioethics Sufficiently Public: The Legitimacy and Authority of Bioethics Commissions
Authors: Johnson Summer
Published: November 2007

Bioethics commissions have been critiqued on the basis that they are not sufficiently public or are too reliant upon expertise to have legitimacy or authority in regard to public policy debates. Adequately assessing the legitimacy and authority of commissions requires thinking clearly about the "publics" these commissions serve, the primary tasks of public bioethics, and how those tasks might be performed with a certain kind of ethical expertise and limited authority that makes them legitimate players in public policy debates concerning bioethics.