bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost‐effectiveness of USAID's Regional Program for Family Planning in West Africa
Authors: Shepard Donald S. , Bail Richard N. , Merritt C. Gary
Published: April 2004

Between 1994 and 1996, the United States Agency for International Development (USAID) closed 23 country missions worldwide, of which eight were in West and Central Africa. To preserve United States support for family planning and reproductive health in four countries in that region, USAID created a subregional program through a consortium of US‐based groups that hired mainly African managers and African organizations. This study assesses cost‐effectiveness of the program through an interrupted time‐series design spanning the 1990s and compares cost‐effectiveness in four similar countries in which mission‐based programs continued. Key indicators include costs, contraceptive prevalence rates, and imputed “women‐years of protection.” The study found that, taking into account all external financing for population and family planning, the USAID West Africa regional approach generated women‐years of protection at one‐third the cost of the mission‐based programs. This regional approach delivered family planning assistance in West Africa cost‐effectively, and the findings suggest that regional models may work well for many health and population services in small countries.
Trends and Determinants of Contraceptive Method Choice in Kenya
Authors: Magadi Monica A. , Curtis Siân L.
Published: April 2004

This study uses data from the 1989, 1993, and 1998 Kenya Demographic and Health Surveys to examine trends and determinants of contraceptive method choice in Kenya. The analysis, based on two‐level multinomial regression models, shows that, over time, the use of modern contraceptive methods, especially long‐term methods, is higher in urban than in rural areas, whereas the pattern is reversed for traditional methods. Use of barrier methods among unmarried women is steadily rising, but the levels remain disappointingly low, particularly in view of the HIV/AIDS epidemic in Kenya. One striking result from this analysis is the dramatic rise in the use of injectables. Of particular program relevance is the notably higher levels of use of injectables among rural women, women whose partners disapprove of family planning, uneducated women, and those less frequently exposed to family planning media messages, compared with their counterparts who have better access to services and greater exposure to family planning information.
Abortion Service Provision in South Africa Three Years After Liberalization of the Law
Authors: Dickson Kim Eva , Jewkes Rachel K. , Brown Heather , Levin Jonathan , Rees Helen , Mavuya Luyanda
Published: April 2004

In 1996, South Africa introduced legislation that liberalized women's access to termination of pregnancy. This study presents the findings of a survey undertaken to describe the availability and accessibility of abortion services in 1999, three years after the law was passed. All facilities that had been officially designated to perform these services were contacted by telephone to determine whether they were providing the services, their capacity, whether they were performing second‐trimester as well as first‐trimester terminations, and how long women had to wait for these services. Nationally, 292 facilities had been designated, but in 1999 only 32 percent were functioning. Of the functioning facilities, 27 percent were in the private sector. Mapping of available services indicated that substantial parts of the country were entirely without such services. Half of the country's induced abortions were being performed in Gauteng province, although only 19 percent of women of reproductive age were living there. This finding indicates that service provision in other provinces was inadequate or lacking. Although in the first years following the new legislation efforts were made to establish abortion services, this study reveals gross inequality in service availability. Strategies for improving coverage are suggested.
Building Communities of Learning in Family Business Programs
Authors: Jaffe Dennis T.
Published: April 2004

Community-based family business networks face significant challenges if they are to thrive and develop. They can increase their effectiveness by incorporating the principles and practices of a learning community into their programs. This paper presents a learning community approach to family business education where participants explore their assumptions about family and business, challenge their preconceptions, learn from each other, and discover new ways to take action. Also presented here are models for internal and cross-family learning, for professional development of family business participants, and for learning among the professional service sponsors.
How Australia's Dennis Family Corp. Professionalized Its Family Business
Authors: Craig Justin , Moores Ken
Published: April 2004

This paper examines a second-generation family business that recently introduced professional corporate governance structures to its organization. The paper includes an outline of the company and an in-depth interview with the second-generation family member who was responsible for the process. Advice to those who are considering corporate governance changes to their family business appears throughout the interview.
Industrial Family Businesses in Germany—Situation and Future
Authors: Kayser Gunter , Wallau Frank
Published: April 2004

Family businesses play an outstanding role in the German economy. Even in the manufacturing sector—seemingly dominated by large, multinational companies—90,431 out of 107,094 companies are family owned and led by a member of the owner family. In 2001, the authors, in a study conducted on behalf of the Federation of German Industry (BDI e.V.), and Ernst & Young carried out an in-depth survey of the structural qualities, strategic activities, and competitive strengths and weaknesses of family businesses in the manufacturing sector. The data of the survey were generated by a postal survey and cover approximately 1,000 respondents. The major findings are as follows: Although family members make the decisions in family enterprises, a wide range of experts from within or without the enterprise are consulted in the run up to crucial decisions. Between 1998 and 2000, turnover and employment were extremely favorable in family-owned manufacturing companies. Although manufacturing family businesses have a rather small number of products and customers due to their high degree of specialization, they export their products worldwide. Increasingly, the enterprises are intensifying their service orientation and entering into cooperative relations with other enterprises, even in sensitive strategic areas like R&D. This leads to the conclusion that despite the continuing high ranking of values such as independence and keeping the enterprise under the influence of the family, enterprises are open for cooperative activities within and without the firm.
Developing Consumer-Driven Services in University-Based Family Business Programs
Authors: DeMoss Michelle
Published: April 2004

This paper presents the results of a study that assessed the demand of university-based family business centers' student market. The study examines and discusses students' demand for family business courses as a way to plan, implement, and control the internal and external programming component of a family business center effectively. College students were surveyed about whether their families own a business, their related career goals, and their needs and wants in a university-based family business center. Of the 260 students, over 36% came from a family business. The paper examines relationships between students from a family business and either their likelihood of pursuing a family business career or enrolling in family business courses or pursuing a minor in family business through a college of business. The paper also presents the implications of these findings for university-based family business centers.
Corporate America's Search for the “Right” Direction: Outlook and Opportunities for Family Firms
Authors: Adams A. Frank , True Sheb L. , Winsor Robert D.
Published: April 2004

The recent accounting scandals and corporate misdeeds of several high-profile Fortune 500 companies have left the investing public reeling. This paper highlights the attributes and characteristics of family firms that confer operational and financial performance advantages on them vis-à-vis nonfamily, or publicly controlled, firms. As a result, family firms have a unique opportunity to model the way regarding corporate reform.
Analysis of Haptoglobin and Hemoglobin-Haptoglobin Interactions with theNeisseria meningitidisTonB-Dependent Receptor HpuAB by Flow Cytometry
Authors: Rohde Kyle H. , Dyer David W.
Published: April 2004

Neisseria meningitidisexpresses a two-component TonB-dependent receptor, HpuAB, which mediates heme-iron (Hm-Fe) acquisition from hemoglobin and hemoglobin-haptoglobin complexes. Due to genetic polymorphisms in the human haptoglobin gene, haptoglobin (and hemoglobin-haptoglobin) exists as three structurally distinct phenotypes. In this study, we examined the influence of the haptoglobin phenotype on the interactions of HpuAB with apo-haptoglobin and hemoglobin-haptoglobin. Growth assays confirmed that HpuAB utilizes hemoglobin-haptoglobin more efficiently than hemoglobin as an Fe source and revealed a preference for human-specific, polymeric 2-2 or 2-1 hemoglobin-haptoglobin complexes. We developed a flow cytometry-based assay to measure the binding kinetics of fluorescein-labeled ligands to HpuAB on live, intact meningococci. The binding affinity of HpuAB for hemoglobin-haptoglobin phenotypes correlated well with the ability of each ligand to supportNeisseria meningitidisgrowth, with higher affinities exhibited for types 2-2 and 2-1 hemoglobin-haptoglobin. Saturable binding of Hb and apo-haptoglobin suggested that HpuAB-mediated utilization of hemoglobin-haptoglobin involves specific interactions with both components. In contrast to previous studies, we detected binding of HpuB expressed alone to hemoglobin, apo-haptoglobin, and hemoglobon-haptoglobin of all three phenotypes. However, in the absence of HpuA, the binding capacity and/or affinity of the receptor was reduced and the dissociation of hemoglobin was impaired. We did not detect binding of HpuA alone to hemoglobin, apo-haptoglobin, or hemoglobin-haptoglobin; however, the lipoprotein is crucial for optimal recognition and use of ligands by the receptor. Finally, this study confirmed the integral role of TonB and the proton motive force in the binding and dissociation of Hb and hemoglobin-haptoglobin from HpuAB.
Inhibition of Monocytic Interleukin-12 Production byCandida albicansvia Selective Activation of ERK Mitogen-Activated Protein Kinase
Authors: Tang Ningfeng , Liu Liming , Kang Kefei , Mukherjee Pranab K. , Takahara Masakazu , Chen Guofen , McCormick Thomas S. , Cooper Kevin D. , Ghannoum Mahmoud
Published: April 2004

Our previous data demonstrated that liveCandida albicansinhibits interleukin-12 (IL-12) production by human monocytes. Here we explored whetherC. albicansinhibits IL-12 via a released factor and whether the inhibition is mediated via mitogen-activated protein kinase (MAPK) regulation. Supernatant fluids were obtained from culturedC. albicans(SC5314) as well as culturedSaccharomyces cerevisiaeafter 20 h of incubation. At 2 h postincubation of monocytes with heat-killedC. albicans(HKCA) (2:1) to stimulate IL-12, concentrated fungal supernatant fluids were added and incubated for an additional 20 h. The present data show that, unlike supernatant fluids obtained fromS. cerevisiae, theC. albicanssupernatant fluids significantly suppressed IL-12 production induced by HKCA. This suggested that the inhibition isCandidaspecific. A preliminary biochemical analysis revealed that this secretory IL-12 inhibitory factor is glycoprotein in nature. The inhibitory activity had no effect on the phagocytosis of yeasts. Supernatant fluids fromC. albicansmarkedly induced the phosphorylation of ERK44/42 MAPK, but not p38 and SAPK, 1 min after they were added to monocytes. To test if the induction of ERK44/42 MAPK was central to the IL-12 inhibition, we used gamma interferon (IFN-γ) (1 ng/ml) plus lipopolysaccharide (LPS) (100 ng/ml) to stimulate IL-12 production by monocytes. The inhibition of ERK MAPK by the specific inhibitor PD 98059 significantly reduced phospho-ERK44/42 MAPK levels induced byC. albicanssupernatant fluids in the IFN-γ-plus-LPS-driven monocytes. Concomitantly, PD 98059 reversed the IL-12 inhibitory activity of theC. albicanssupernatant (P< 0.01). These data indicate thatC. albicanscan inhibit IL-12 production by secreting an ERK44/42 MAPK-stimulating factor and thus can attenuate effective immune responses.
Regulation of Proinflammatory Cytokine Expression by Shiga Toxin 1 and/or Lipopolysaccharides in the Human Monocytic Cell Line THP-1
Authors: Harrison Lisa M. , van Haaften Wilhelmina C. E. , Tesh Vernon L.
Published: April 2004

Infection with Shiga toxin (Stx)-producing bacteria and the subsequent release of Stxs and endotoxins into the bloodstream may damage blood vessels in the colon, kidneys, and central nervous system, leading to bloody diarrhea, acute renal failure, and neurological complications. The proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) may contribute to the pathogenesis of Stx-induced vascular lesions by up-regulating toxin receptor expression on endothelial cells. We previously showed that macrophages treated with purified Shiga toxin 1 (Stx1) or lipopolysaccharides (LPS) secrete TNF-α and IL-1β. Northern blot analysis revealed that treatment of the human monocytic cell line THP-1 with LPS induced a rapid and transient increase in steady-state TNF-α and IL-1β transcripts. In contrast, Stx1 induced slower but prolonged elevations in cytokine transcripts. The presence of both stimulants resulted in optimal cytokine mRNA induction in terms of kinetics and prolonged expression. Compared to LPS, Stx1 was a poor inducer of IL-1β protein expression, although levels of soluble IL-1β induced by all treatments continually increased over 72 h. IL-1β transcripts were not induced by Stx1 B-subunits. Using the transcriptional inhibitor actinomycin D, we determined that treatment with Stx1 or Stx1 plus LPS induced cytokine transcripts with increased stability compared to transcripts induced by LPS alone. For all treatments, IL-1β mRNA decay was slower than TNF-α. Collectively, our data suggest that Stxs affect cytokine expression, in part, at the posttranscriptional level by stabilizing mRNAs. Optimal TNF-α expression occurs when both Stxs and LPS are present.
Human Leukocyte Antigen Class II Alleles Influence Levels of Antibodies to thePlasmodium falciparumAsexual-Stage Apical Membrane Antigen 1 but Not to Merozoite Surface Antigen 2 and Merozoite Surface Protein 1
Authors: Johnson Armead H. , Leke Rose G. F. , Mendell Nancy R. , Shon Dewon , Suh Young Ju , Bomba-Nkolo Dennis , Tchinda Viviane , Kouontchou Samuel , Thuita Lucy W. , van der Wel Anne Marie , Thomas Alan , Stowers Anthony , Saul Allan , Zhou Ainong , Taylor Diane W. , Quakyi Isabella A.
Published: April 2004

The apical membrane antigen 1 (AMA1), merozoite surface antigen 2 (MSA2), and merozoite surface protein 1 (MSP1) are asexual-stage proteins currently being evaluated for inclusion in a vaccine forPlasmodium falciparum. Accordingly, it is important to understand factors that control antibody responses to these antigens. Antibody levels in plasma from residents of Etoa, Cameroon, between the ages of 5 and 70 years, were determined using recombinant AMA1, MSA2, and the N-terminal region of MSP1 (MSP1-190L). In addition, antibody responses to four variants of the C-terminal region of MSP1 (MSP119) were assessed. Results showed that all individuals produced antibodies to AMA1, MSA2, and MSP1-190L; however, a proportion of individuals never produced antibodies to the MSP119variants, although the percentage of nonresponders decreased with age. The influence of age and human leukocyte antigen (HLA)-DRB1/DQB1 alleles on antibody levels was evaluated using two-way analysis of variance. Age was correlated with levels of antibodies to AMA1 and MSP119but not with levels of antibodies to MSA2 and MSP1-190L. No association was found between a single HLA allele and levels of antibodies to MSA2, MSP1-190L, or any of the MSP119variants. However, individuals positive for DRB1*1201 had higher levels of antibodies to the variant of recombinant AMA1 tested than did individuals of all other HLA types. Since the effect was seen across all age groups, HLA influenced the level but not the rate of antibody acquisition. This association for AMA1, combined with the previously reported association between HLA class II alleles and levels of antibodies to rhoptry-associated protein 1 (RAP1) and RAP2, indicates that HLA influences the levels of antibodies to three of the five vaccine candidate antigens that we have evaluated.
Clostridium difficileToxin A Carboxyl-Terminus Peptide Lacking ADP-Ribosyltransferase Activity Acts as a Mucosal Adjuvant
Authors: Castagliuolo Ignazio , Sardina Marina , Brun Paola , DeRos Chiara , Mastrotto Cristina , Lovato Laura , Palù Giorgio
Published: April 2004

The receptor binding domains of the most potent mucosal adjuvants, bacterial toxins and plant lectins, are organized in repeat units to recognize specific sugar residues. The lectin-like structure of the C-terminal region ofClostridium difficiletoxin A prompted us to investigate the mucosal adjuvant properties of a nontoxigenic peptide corresponding to amino acids 2394 to 2706 (TxAC314). We compared TxAC314adjuvant activity to those of cholera toxin (CT) andEscherichia coliheat-labile enterotoxin subunit B (EtxB) coadministered orally or nasotracheally with poor peptide antigens (keyhole limpet hemocyanin [KLH] and hen egg lysozyme [HEL]). Levels of anti-KLH-specific serum immunoglobulin G (IgG) and IgA as well as that of mucosal IgA were significantly higher in animals immunized orally with TxAC314plus KLH than with KLH alone, CT plus KLH, or EtxB plus KLH. Following intranasal immunization with TxAC314plus HEL, levels of serum- and mucosa-specific antibodies were comparable to those induced by coadministering HEL with CT or EtxB. The TxAC314adjuvant effect following oral, but not intranasal, immunization was dose dependent. The analysis of the subclasses of anti-KLH-specific IgG isotypes and the cytokines released from splenocytes of immunized mice challenged in vitro with KLH indicates the induction of a mixed Th1/Th2-type immune response, with prevalence of the Th1 branch. We conclude that TxAC314enhances immune responses against mucosa-coadministered foreign antigens and represents a promising mucosal adjuvant, especially because its ability to stimulate mixed Th1/Th2 responses with a strong a Th1 component is extremely worthwhile against intracellular pathogens.
Bacterial and Host Factors Involved in the Major Histocompatibility Complex Class Ib-Restricted Presentation ofSalmonellaHsp 60: Novel Pathway
Authors: Lo Wei-Feng , Dunn Cory D. , Ong Helena , Metcalf Eleanor S. , Soloski Mark J.
Published: April 2004

Previously, a peptide epitope derived from the Hsp 60 molecule ofSalmonellathat is presented by the major histocompatibility complex (MHC) class Ib molecule Qa-1 to CD8+cytotoxic T cells (CTLs) was described. In the present study we investigated theSalmonella-induced processing and presentation pathway for generating this Qa-1-restricted epitope. Live bacteria and, to a lesser extent, opsonized heat-killed bacteria are able to sensitize target cells for lysis bySalmonella-specific CTL. In contrast, heat-killed bacteria cannot sensitize target cells. Presentation of the Hsp 60 epitope appears independent of bacterial internalization, because cytochalasin D does not affect presentation. Moreover,Salmonellastrains defective in the InvA or InvE operon, two critical components of the type III secretion pathway, are as efficient as wild-typeSalmonella entericaserovar Typhimurium in sensitizing infected targets to lysis. Collectively, these results suggest the existence of a novel antigen-processing pathway in which exogenous antigens gain access to the cytosolic MHC class I processing machinery. Considering the abundant nature of bacterial Hsp 60 and the upregulation of this protein afterSalmonellainfection of eukaryotic cells, this mode of antigen presentation may be particularly relevant to understanding the host defense mechanisms against gram-negative bacteria.
Mycobacteria Inhibit Nitric Oxide Synthase Recruitment to Phagosomes during Macrophage Infection
Authors: Miller Barbara H. , Fratti Rutilio A. , Poschet Jens F. , Timmins Graham S. , Master Sharon S. , Burgos Marcos , Marletta Michael A. , Deretic Vojo
Published: April 2004

Inducible nitric oxide synthase (iNOS) is a cytoplasmic protein responsible for the generation of nitric oxide (NO · ) in macrophages. In this work, we hypothesized that the intracellular localization of iNOS is significant for effective delivery of NO ·  to phagosomes containing ingested microorganisms. Using immunofluorescence microscopy and Western blot analysis, iNOS was shown to localize in the vicinity of phagosomes containing latex beads in stimulated macrophages. iNOS also localized to phagosomes containingEscherichia coli. The colocalization of iNOS with ingested latex beads was an actin-dependent process, since treatment with the actin microfilament disrupter cytochalasin D prevented iNOS recruitment to latex bead phagosomes. In contrast toE. coliand inert particle phagosomes, mycobacterial phagosomes did not colocalize with iNOS. This study demonstrates that (i) iNOS can be recruited to phagosomes; (ii) this recruitment is dependent on a functional actin cytoskeleton; (iii) certain microorganisms have the ability to prevent or reduce colocalization with iNOS; and (iv) spatial exclusion of iNOS may play a role inMycobacterium tuberculosispathogenesis.
Erythrocyte Invasion by
Babesia bovis
Merozoites Is Inhibited by Polyclonal Antisera Directed against Peptides Derived from a Homologue of
Plasmodium falciparum
Apical Membrane Antigen 1
Authors: Gaffar Fasila R. , Yatsuda Ana P. , Franssen Frits F. J. , de Vries Erik
Published: April 2004

Apical membrane antigen 1 (AMA-1) is a micronemal protein secreted to the surface of merozoites of
Plasmodium
species and
Toxoplasma gondii
tachyzoites in order to fulfill an essential but noncharacterized function in host cell invasion. Here we describe cloning and characterization of a
Babesia bovis
AMA-1 homologue designated BbAMA-1. The overall level of similarity of BbAMA-1 to
P. falciparum
AMA-1 was low (18%), but characteristic features like a transmembrane domain near the C terminus, a predicted short cytoplasmic C-terminal sequence with conserved sequence properties, and an extracellular domain containing 14 conserved cysteine residues putatively involved in disulfide bridge formation are typical of AMA-1. Rabbit polyclonal antisera were raised against three synthetic peptides derived from the N-terminal region and domains II and III of the putative extracellular domain and were shown to recognize specifically recombinant BbAMA-1 expressed in
Escherichia coli
. Immunofluorescence microscopy showed that there was labeling of the apical half of merozoites with these antisera. Preincubation of free merozoites with all three antisera reduced the efficiency of invasion of erythrocytes by a maximum of 65%. Antisera raised against the N-terminal peptide detected a 82-kDa protein on Western blots and a 69-kDa protein in the supernatant that was harvested after in vitro invasion, suggesting that proteolytic processing and secretion take place during or shortly after invasion. A combination of two-dimensional Western blotting and metabolic labeling allowing direct identification of spots reacting with the BbAMA-1 peptide antisera together with the very low silver staining intensity of these spots indicated that very low levels of BbAMA-1 are present in
Babesia
merozoites.
Role of Macrophages in Host Resistance to Group A Streptococci
Authors: Goldmann Oliver , Rohde Manfred , Chhatwal Gursharan Singh , Medina Eva
Published: April 2004

Macrophages provide the first line of defense against invading pathogens. The aim of this study was to determine the role of macrophages during infection with group A streptococci (Streptococcus pyogenes) in mice. Here, we report that resident macrophages can efficiently take up and killS. pyogenesduring in vivo infection, as demonstrated by immunofluorescence and electron microscopy, as well as colony counts. To evaluate the contribution of macrophages to the resolution of experimental infection withS. pyogenes, we compared the susceptibility of BALB/c mice rendered macrophage deficient by treatment with carrageenan with that of intact mice. The results show that depletion of macrophages enhanced the susceptibility of BALB/c mice toS. pyogenesinfection, as evidenced by 100% mortality of macrophage-depleted mice compared to 90% survival of nondepleted control animals. The in vivo depletion of macrophages strongly enhanced bacterial loads in the blood and systemic organs. Resistance toS. pyogenescan be restored in macrophage-depleted mice by adoptive transfer of purified macrophages. The in vivo blocking of the macrophage phagocytic function by treatment with gadolinium III chloride also resulted in enhanced susceptibility toS. pyogenes.Interestingly, depletion of macrophages prior to or during the first 24 h of infection decreased survival dramatically; in contrast, no mortality was observed in infected nondepleted animals or mice depleted after 48 h of infection. These results emphasize the important contribution of macrophages to the early control ofS. pyogenesinfection.
Tick Saliva Reduces Adherence and Area of Human Neutrophils
Authors: Montgomery Ruth R. , Lusitani Denise , de Boisfleury Chevance Anne , Malawista Stephen E.
Published: April 2004

During natural infection with the agent of Lyme disease,Borrelia burgdorferi, spirochetes are delivered with vector saliva, which contains anti-inflammatory and antihemostatic activities. We show here that the saliva of ixodid ticks reduces polymorphonuclear leukocyte (PMN) adhesion via downregulation of β2-integrins and decreases the efficiency of PMN in the uptake and killing of spirochetes. Inhibition of integrin adhesion and signaling reduces anti-inflammatory functions of PMN. These effects may favor the initial survival of spirochetes in vivo.
Vaccination with anOstertagia ostertagiPolyprotein Allergen Protects Calves against Homologous Challenge Infection
Authors: Vercauteren Isabel , Geldhof Peter , Vercruysse Jozef , Peelaers Iris , Van Den Broeck Wim , Gevaert Kris , Claerebout Edwin
Published: April 2004

As an alternative to antihelminthic drugs, we are exploiting vaccination to control infections with the abomasal nematodeOstertagia ostertagiin cattle. Our focus for vaccine targets is excretory-secretory (ES) products of this parasite. One of the most abundant antigens in larval and adultOstertagiaES products is a protein homologous to nematode polyprotein allergens. We found that theOstertagiapolyprotein allergen (OPA) is encoded by a single-copy gene. OPA comprises three or more repeated units, and only the 15-kDa subunits are found in ES products. The native antigen is localized in the intestinal cells of third-stage larvae and in the hypodermis and cuticle of fourth-stage larvae and adult parasites. Vaccination of cattle with native OPA (nOPA) in combination with QuilA resulted in protection againstOstertagiachallenge infections. The geometric mean cumulative fecal egg counts in the nOPA-vaccinated animals were reduced by 60% compared to the counts in the control group during the 2-month course of the experiment. Both male and female adult worms in nOPA-vaccinated animals were significantly shorter than the worms in the control animals. In the abomasal mucus of vaccinated animals the nOPA-specific immunoglobulin G1 (IgG1) and IgG2 levels were significantly elevated compared to the levels in the control animals. Reductions in theOstertagiaegg output and the length of the adult parasites were significantly correlated with IgG1 levels. IgG2 titers were only negatively associated with adult worm length. Protected animals showed no accumulation of effector cells (mast cells, globular leukocytes, and eosinophils) in the mucosa. In contrast to the native antigen, recombinant OPA expressed inEscherichia colidid not stimulate any protection.
The Extra Cytoplasmic Function Sigma Factor σ
E
Is Essential for
Mycobacterium tuberculosis
Virulence in Mice
Authors: Manganelli Riccardo , Fattorini Lanfranco , Tan Dejiang , Iona Elisabetta , Orefici Graziella , Altavilla Giuseppe , Cusatelli Paola , Smith Issar
Published: April 2004

The virulence of a
Mycobacterium tuberculosis
H37Rv
sigE
mutant was studied in immunodeficient and immunocompetent mice. The mutant was strongly attenuated in both animal models and induced formation of granulomas with different characteristics than those induced by the wild-type strain.
Presence of Pili on the Surface of
Francisella tularensis
Authors: Gil Horacio , Benach Jorge L. , Thanassi David G.
Published: April 2004

Francisella tularensis
is a highly infectious gram-negative bacterium with potential for use as a bioweapon. Analysis of the
F. tularensis
live vaccine strain (LVS) ultrastructure by electron microscopy revealed the presence of long, thin fibers, similar in appearance to type 4 pili. The highly virulent
F. tularensis
Schu S4 strain was found to contain type 4 pilus genes, and we confirmed that these genes are present and expressed in the LVS.
Legionella pneumophila
Replication Vacuole Formation Involves Rapid Recruitment of Proteins of the Early Secretory System
Authors: Derré Isabelle , Isberg Ralph R.
Published: April 2004

Legionella pneumophila
vacuole biogenesis was analyzed by using a cell-free system. We show that calnexin, Sec22b, and Rab1 are recruited to the vacuole very shortly after bacterial uptake, and we have identified Rab1 as a potential host factor involved in the endoplasmic reticulum recruitment process.
Proinflammatory Cytokine Expression in the Early Phase ofTrypanosoma brucei rhodesienseInfection in Vervet Monkeys (Cercopithecus aethiops)
Authors: Maina Naomi , Ngotho Joseph Maina , Were Tom , Thuita John Kibuthu , Mwangangi David Mumo , Kagira John Maina , Ndung'u Joseph Mathu , Sternberg Jeremy
Published: April 2004

A vervet monkey model of trypanosomiasis was used to study inflammatory cytokine responses in serum and cerebrospinal fuid (CSF). Gamma interferon levels were transiently up-regulated in serum between days 6 and 8 of infection, followed by a sustained up-regulation of tumor necrosis factor alpha (TNF-α) and soluble TNF receptor 1. At no time were these cytokines detectable in the CSF.
GENES, DIVERSITY, AND GEOLOGIC PROCESS ON THE PACIFIC COAST
Authors: Jacobs David K. , Haney Todd A. , Louie Kristina D.
Published: April 2004

▪ Abstract  We examine the genetics of marine diversification along the West Coast of North America in relation to the Late Neogene geology and climate of the region. Trophically important components of the diverse West Coast fauna, including kelp, alcid birds (e.g., auks, puffins), salmon, rockfish, abalone, and Cancer crabs, appear to have radiated during peaks of upwelling primarily in the Late Miocene and in some cases secondarily in the Pleistocene. Phylogeographic barriers associated with Mio-Pliocene estuaries of the mid-California coast, the Pliocene opening of the Gulf of California, tectonic and eustatic evolution of the California Bight, as well as the influence of Pleistocene and Holocene climate change on genetic structure are assessed in a geologic context. Comparisons to East Coast and western freshwater systems, as well as upwelling systems around the globe, provide perspective for the survey.
YUCCA MOUNTAIN: Earth-Science Issues at a Geologic Repository for High-Level Nuclear Waste
Authors: Long Jane C.S. , Ewing Rodney C.
Published: April 2004

▪ Abstract  The nation has over 40,000 metric tonnes (MT) of nuclear waste destined for disposal in a geologic repository at Yucca Mountain. In this review, we highlight some of the important geoscience issues associated with the project and place them in the context of the process by which a final decision on Yucca Mountain will be made. The issues include understanding how water could infiltrate the repository, corrode the canisters, dissolve the waste, and transport it to the biosphere during a 10,000-year compliance period in a region, the Basin and Range province, that is known for seismic and volcanic activity. Although the site is considered to be “dry,” a considerable amount of water is present as pore waters and as structural water in zeolites. The geochemical environment is oxidizing, and the present repository design will maintain temperatures at greater than 100°C for thousands of years. Geoscientists in this project are challenged to make unprecedented predictions about coupled thermal, hydrologic, mechanical, and geochemical processes governing the future behavior of the repository and to conduct research in a regulatory and legal environment that requires a quantitative analysis of repository performance.
RIVER AVULSIONS AND THEIR DEPOSITS
Authors: Slingerland Rudy , Smith Norman D.
Published: April 2004

▪ Abstract  Avulsion is the natural process by which flow diverts out of an established river channel into a new permanent course on the adjacent floodplain. Avulsions are primarily features of aggrading floodplains. Their recurrence interval varies widely among the few modern rivers for which such data exist, ranging from as low as 28 years for the Kosi River (India) to up to 1400 years for the Mississippi. Avulsions cause loss of life, property damage, destabilization of shipping and irrigation channels, and even coastal erosion as sediment is temporarily sequestered on the floodplain. They are also the main process that builds alluvial stratigraphy. Their causes remain relatively unknown, but stability analyses of bifurcating channels suggest that thresholds in the relative energy slope and Shields parameter of the bifurcating channel system are key factors.
MULTISPECTRAL AND HYPERSPECTRAL REMOTE SENSING OF ALPINE SNOW PROPERTIES
Authors: Dozier Jeff , Painter Thomas H.
Published: April 2004

▪ Abstract  Models of processes in the alpine snow cover fundamentally depend on the spatial distribution of the surface energy balance over areas where topographic variability causes huge differences in the incoming solar radiation and in snow depth because of redistribution by wind. At a spatial scale commensurate with that of the terrain, we want to know which areas are covered by snow, and we want to estimate the snow's spectral albedo, along with other properties such as grain size, contaminants, temperature, liquid water content, and depth or water equivalent. From multispectral and hyperspectral remote sensing at wavelengths from 0.4–15 μm, the retrievable properties include snow-covered area, albedo, grain size, liquid water very near the surface, and temperature. Spectral mixture analysis allows the retrieval of the subpixel variability of snow-covered area, along with the snow's albedo. Remaining research challenges include the remote sensing of absorbing impurities; accounting for variability in the bidirectional-reflectance distribution function and the variability of grain size with depth; retrieving snow cover in forested regions; reconciling field measurements of emissivity with snow properties; and adapting the algorithms to frequent, large-scale processing.
SPACE WEATHERING OF ASTEROID SURFACES
Authors: Chapman Clark R.
Published: April 2004

▪ Abstract  Visible and near-infrared spectra of reflected sunlight from asteroid surfaces exhibit features that hold the promise for identifying surface mineralogy. However, the very surfaces that are observed by remote-sensing are also subject to impingement by micrometeoroids and solar wind particles, which are believed to play the dominant role in space weathering, which is the time-dependent modification of an asteroid's reflectance spectrum. Such space weathering has confused the interpretations of telescopic spectra of asteroids, especially concerning the possible association of common ordinary chondritic meteorites with so-called S-type asteroids. Recent spacecraft studies of asteroids (especially of Eros by NEAR-Shoemaker) have documented aspects of space weathering processes, but we still do not understand the physics of space weathering well enough to confidently assay mineralogy of diverse asteroids by remote-sensing. A review of the intellectual history of this topic reveals the complexity of interdisciplinary research on far-away astronomical bodies.
Active involvement of PKC for insulin-mediated rates of muscle protein synthesis in Zucker rats
Authors: Fluckey James D. , Cortright Ronald N. , Tapscott Edward , Koves Timothy , Smith Latasha , Pohnert Steven , Dohm G. Lynis
Published: April 2004

A recent report from our group demonstrated that insulin facilitates muscle protein synthesis in obese Zucker rats. The purpose of this study was to determine whether PKC, a probable modulator of insulin signal transduction and/or mRNA translation, has a role in this insulin-mediated anabolic response. In the first portion of the study, gastrocnemius muscles of lean and obese Zucker rats ( n = 5–7 for each phenotype) were bilaterally perfused with or without insulin to assess cytosolic and membrane PKC activity. Limbs perfused with insulin demonstrated greater PKC activity in both lean and obese Zucker rats ( P < 0.05) compared with no insulin, but overall activity was greater in obese animals (by ∼27% compared with lean, P < 0.05). To determine whether PKC plays a role in muscle protein synthesis, hindlimbs ( n = 6–8 for each phenotype) were bilaterally perfused with or without insulin and/or GF-109203X (GF; a PKC inhibitor). The presence of GF did not influence the rates of insulin-mediated protein synthesis in gastrocnemius muscle of lean Zucker rats. However, when obese rats were perfused with GF ( P < 0.05), the effect of insulin on elevating rates of protein synthesis was not observed. We also used phorbol 12-myristate 13-acetate (TPA, a PKC activator; n = 5–7 for each phenotype) with and without insulin to determine the effect of PKC activation on muscle protein synthesis. TPA alone did not elevate muscle protein synthesis in lean or obese rats. However, TPA plus insulin resulted in elevated rates of protein synthesis in both phenotypes that were similar to rates of insulin alone of obese rats. These results suggest that PKC is a modulator and is necessary, but not sufficient, for insulin-mediated protein anabolic responses in skeletal muscle.
Neuromedin U has a physiological role in the regulation of food intake and partially mediates the effects of leptin
Authors: Jethwa Preeti H. , Small Caroline J. , Smith Kirsty L. , Seth Asha , Darch Sarah J. , Abbott Caroline R. , Murphy Kevin G. , Todd Jeannie F. , Ghatei Mohammad A. , Bloom Stephen R.
Published: April 2004

Intracerebroventricular (ICV) administration of Neuromedin U (NMU), a hypothalamic neuropeptide, or leptin, an adipostat hormone released from adipose tissue, reduces food intake and increases energy expenditure. Leptin stimulates the release of NMU in vitro, and NMU expression is reduced in models of low or absent leptin. We investigated the role of NMU in mediating leptin-induced satiety. ICV administration of anti-NMU immunoglobulin G (IgG) (5 nmol) to satiated rats significantly increased food intake 4 h after injection, an effect seen for ≤8 h after injection. ICV administration of NMU (1 nmol) to fasted rats reduced food intake 1 h after injection compared with control, an effect attenuated by pretreatment with anti-NMU IgG. ICV administration of leptin (0.625 nmol) reduced 24-h food intake. This was partially attenuated by the administration of anti-NMU IgG [24 h after onset of dark phase: vehicle, 22.5 ± 2.0 g; leptin, 13.7 ± 2.3 g ( P < 0.005 vs. vehicle), leptin/NMU IgG, 19.4 ± 1.3 g ( P < 0.05 vs. leptin)]. Intraperitoneal administration of leptin (1.1 mg/kg body wt) reduced 24-h food intake. This was partially attenuated by ICV administration of anti-NMU IgG [24 h after onset of dark phase: vehicle, 31.4 ± 4.9 g; leptin, 20.8 ± 2.6 g ( P < 0.01 vs. vehicle); leptin/NMU IgG, 28.7 ± 1.1 g ( P < 0.01 vs. leptin)]. These results suggest that NMU plays a physiological role in the regulation of appetite and partially mediates the leptin-induced satiety.
Nonlinear Population Codes
Authors: Shamir Maoz , Sompolinsky Haim
Published: April 2004

Theoretical and experimental studies of distributed neuronal representations of sensory and behavioral variables usually assume that the tuning of the mean firing rates is the main source of information. However, recent theoretical studies have investigated the effect of cross-correlations in the trial-to-trial fluctuations of the neuronal responses on the accuracy of the representation. Assuming that only the first-order statistics of the neuronal responses are tuned to the stimulus, these studies have shown that n the presence of correlations, similar to those observed experimentally in cortical ensembles of neurons, the amount of information in the population is limited, yielding nonzero error levels even in the limit of infinitely large populations of neurons.

In this letter, we study correlated neuronal populations whose higher-order statistics, and in particular response variances, are also modulated by the stimulus. We ask two questions: Does the correlated noise limit the accuracy of the neuronal representation of the stimulus? and, How can a biological mechanism extract most of the information embedded in the higher-order statistics of the neuronal responses? Specifically, we address these questions in the context of a population of neurons coding an angular variable. We show that the information embedded in the variances grows linearly with the population size despite the presence of strong correlated noise. This information cannot be extracted by linear readout schemes, including the linear population vector. Instead, we propose a bilinear readout scheme that involves spatial decorrelation, quadratic nonlinearity, and population vector summation. We show that this nonlinear population vector scheme yields accurate estimates of stimulus parameters, with an efficiency that grows linearly with the population size. This code can be implemented using biologically plausible neurons.
Global Environmental Change and the Nation State
Authors: Biermann Frank , Dingwerth Klaus
Published: April 2004

This article outlines the theoretical problematique and some empirical knowledge regarding the impacts of global environmental change on the nation state; thereby it also introduces this special issue of Global Environmental Politics. We argue that global environmental change decreases the capacity of nation states to fulfill their definitional functions without the cooperation of other states. The added stress due to environmental change also increases the demand for adaptive capacities of nation states, which further diminishes their resources to fulfill other core functions. Based on an overview of the complex interplay between global environmental change and the nation state, we focus on the various ways in which the nation state may mitigate, or adapt to, the impacts of global environmental change, including horizontal diffusionism and vertical institutionalism. In summarizing the other contributions to this special issue, we further argue that a reconsideration of key theoretical concepts such as sovereignty, agency, and multilevel governance is required in order to improve our understanding of the complexities of global environmental governance.
The functional roles of passive electroreception in non-electric fishes
Authors: Collin Shaun , Whitehead Darryl
Published: April 2004

Passive electroreception is a complex and specialised sense found in a large range of aquatic vertebrates primarily designed for the detection of weak bioelectric fields. Particular attention has traditionally focused on cartilaginous fishes, but a range of teleost and non-teleost fishes from a diversity of habitats have also been examined. As more species are investigated, it has become apparent that the role of electroreception in fishes is not restricted to locating prey, but is utilised in other complex behaviours. This paper presents the various functional roles of passive electroreception in non-electric fishes, by reviewing much of the recent research on the detection of prey in the context of differences in species' habitat (shallow water, deep-sea, freshwater and saltwater). A special case study on the distribution and neural groupings of ampullary organs in the omnihaline bull shark, Carcharhinus leucas, is also presented and reveals that prey-capture, rather than navigation, may be an important determinant of pore distribution. The discrimination between potential predators and conspecifics and the role of bioelectric stimuli in social behaviour is discussed, as is the ability to migrate over short or long distances in order to locate environmentally favourable conditions. The various theories proposed regarding the importance and mediation of geomagnetic orientation by either an electroreceptive and/or a magnetite-based sensory system receives particular attention. The importance of electroreception to many species is emphasised by highlighting what still remains to be investigated, especially with respect to the physical, biochemical and neural properties of the ampullary organs and the signals that give rise to the large range of observed behaviours.
Major sex differences in the development of myelination are prominent in song system nucleus HVC but not lMAN
Authors: Nixdorf-Bergweiler Barbara , von Bohlen und Halbach Viola
Published: April 2004

Myelination of axonal processes is an important feature for setting up the connectivity in the neuronal network. Processes of myelination are also indicatives for changes in neuronal plasticity. The primary objective of this paper was to determine the time course of myelination—expressed in the number of myelinated profiles and the overall coverage of myelinated profiles per unit area of tissue—in two well-known song nuclei (HVC and lMAN) that have been implicated in song recognition in both male and female birds. While large sex differences have been described for many aspects of morphology in HVC, lMAN is much less dimorphic. Therefore, we wanted to know: 1) whether these differences in the extent of sexual dimorphism are also reflected in the extent of myelination; and 2) whether spatial and temporal features of myelin appearance differ in these two song nuclei in males. We analysed toluidine blue-stained Epon-embedded semithin sections with high resolution light microscopy using a computer-based morphometric system. Myelination in HVC increases substantially in males at 60 days of age, whereas, in lMAN, myelination starts early in development with an additional increase between 60 days and adulthood. In contrast to female HVC, where no changes in myelination can be observed throughout development, myelination in female lMAN increases. This increase, however, is of a different dynamic and of lesser extent in comparison to males. Henceforth, myelination in males lasts until adulthood, indicating long lasting plastic changes in both song nuclei, HVC and lMAN, whereas in females myelination is only prominent in lMAN.