bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of Research Findings Regarding Alzheimer's Disease: Part II, Care of People with AD
Authors: Bower Fay L. , McCullough Cyndi S. , Pille Barbara L.
Published: April 2004

(1) The purpose of this review is to present knowledge about the treatment of Alzheimer's disease (AD). Synthesized research findings about the pharmacological and nonpharmacological interventions used with patients who have Alzheimer's disease are presented and are followed by a discussion regarding the actions nurses can initiate to enhance functioning and delay institutionalization. While there is a great deal of interest and study of AD treatment, the research is variable and often with small populations. Even so, the results of these studies are promising, as they provide information about the ways AD symptoms can be controlled by medication and other means.
Evidence‐Based Development of a Hospital‐Based Heart Failure Center
Authors: Crowther Maryanne , Maroulis Ann , Shafer‐Winter Nancy , Hader Richard
Published: April 2004

In 2001, the Honor Society of Nursing, Sigma Theta Tau International and Nursing Spectrum sponsored an “Innovations in Clinical Excellence” contest to recognize examplars of evidence‐based nursing practice. This clinical column is one of the winning entries.
Systematic searches for molecular synapomorphies in model metazoan genomes give some support for Ecdysozoa after accounting for the idiosyncrasies of Caenorhabditis elegans
Authors: Copley Richard R. , Aloy Patrick , Russell Robert B. , Telford Maximilian J.
Published: April 2004

Summary There has been broad acceptance among evolutionary biologists of the Ecdysozoa hypothesis that, based principally on molecular phylogenetic studies of small and large subunit ribosomal RNA sequences, postulates a close relationship between molting taxa such as arthropods and nematodes. On the other hand, recent studies of as many as 100 additional genes do not support the Ecdysozoa hypothesis and instead favor the older Coelomata hypothesis that groups the coelomate arthropods with the coelomate vertebrates to the exclusion of the nematodes. Here, exploiting completely sequenced genomes, we examined this question using cladistic analyses of the phylogenetic distribution of 1712 orthologous genes and 2906 protein domain combinations; we found stronger support for the Coelomata hypothesis than for the Ecdysozoa hypothesis. However, although arrived at by considering very large data sets, we show that this conclusion is unreliable, biased toward grouping arthropods with chordates by systematic high rate of character loss in the nematode. When we addressed this problem, we found slightly more support for Ecdysozoa than for Coelomata. Our identification of this systematic bias even when using entire genomes has important implications for future phylogenetic studies. We conclude that the results from the intensively sampled ribosomal RNA genes supporting the Ecdysozoa hypothesis provide the most credible current estimates of metazoan phylogeny.
Developmental regulation of skull morphology. I. Ontogenetic dynamics of variance
Authors: Zelditch Miriam Leah , Lundrigan Barbara L. , Garland Theodore
Published: April 2004

SummaryIn the absence of processes regulating morphogenesis and growth, phenotypic variance of a population experiencing no selective mortality should increase throughout ontogeny. To determine whether it does, we measure variance of skull shape using geometric morphometrics and examine its ontogenetic dynamics in the precocial cotton rat (Sigmodon fulviventer) and the altricial house mouse (Mus musculus domesticus). In both species, variance of shape halves between the two youngest samples measured (between 1 and 10 days postnatal and 10 and 15 days postnatal, respectively) and thereafter is nearly constant. The reduction in variance did not appear to result from a general regulation of skull size or developmental timing, although skull size may also be regulated and developmental timing is an important component of the variation in skull shape of young house mice. The ontogenetic dynamics of variance suggest two possible scenarios. First, variation generated during fetal or early postnatal growth is not immediately compensated and therefore accumulates, whereas later in growth, variation is continually generated and rapidly compensated. Second, variation generated during fetal and early postnatal growth is rapidly compensated, after which no new variance is produced. Based on a general model for bone growth, we hypothesize that variance is generated when bone grows under the direction of disorganized muscular movements and decreases with increasing neuromuscular control. Additionally, increasing coherence of signals transmitted by the growing brain and sensory organs, which exert tensile forces on bone, may also canalize skull shape.
Anxious Moments: Openings in Negotiation
Authors: Wheeler Michael
Published: April 2004

Even experienced negotiators often feel anxiety about beginning a new negotiation. Subjects in this study described these opening moments with vivid imagery and metaphors, among them: lurking wolves, alligators, tightropes, and rushing trains. People's deep‐seated worries can be triggered by several factors: doubts about personal competence, fear about the attitudes and behavior of other parties, and the inevitable uncertainty about what path negotiation will take. The author compares openings in other contexts, notably in the arts, to illustrate how the impact of anxiety need not be entirely negative. These feelings can also spark creativity and support constructive relationships.
Improvisation and Negotiation: Making It Up as You Go Along
Authors: Harding Chet
Published: April 2004

The author explores the art and the science of acting in improvisational theater and how it relates to the unscripted critical moments in negotiation. Without any preparation, actors negotiate a scene through a series of offers and beats that builds to a comic crescendo and ends with a slapstick solution that delivers laughs, solidifies relationships, and keeps them coming back for more. The actor/author shows how, by actively listening, reading the cues of the performers, offering a clear point of view with a positive ‘yes, and’ perspective, and working together, the scene can evolve into an event that exceeds expectations and makes the most of each critical moment.
Surprise Moves in Negotiation
Authors: Stuart Harborne W.
Published: April 2004

In a game‐theoretic model of a negotiation, a surprise move always has the potential to create uncertainty. This uncertainty can be beneficial to just the player making the move, or it can be beneficial to all the players involved. Moreover, there are situations in which a surprise move can change the very nature of the interactions. In particular, if the interactions follow specified procedures, the surprise move can reduce the effect of the procedures on the outcome. By showing that these results hold in the precisely defined world of game theory, it is argued that they are applicable in the more ambiguous world of real negotiations. At a broader level, the game‐theoretic results imply that there is a sense in which the context can never be known for sure. The results also imply that the uncertainty created by surprise moves can be strategically useful.
Staying in the Game or Changing It: An Analysis of Moves and Turns in Negotiation
Authors: Kolb Deborah M.
Published: April 2004

As parties bargain over the terms of an agreement, they are concurrently negotiating their relationship. In this parallel negotiation, parties seek to position themselves to advantage by using a variety of strategic moves. In so doing the other party can be put into a defensive position making it difficult to advocate effectively. Turns, such as interrupting, correcting, questioning, naming, and diverting, challenge these moves. Turns can be used restoratively to move out of a defensive position or participatively, to engage the other in collaboration. Anticipating strategic moves and having turns in mind is part of preparing to negotiate.
The Present Moment as a Critical Moment
Authors: Stern Daniel N.
Published: April 2004

Like a musical interlude, the present moment hovers between becoming the past and progressing into the future. Critical moments, for the author, are moments in which the parties are fully in the present or the “now,” caught in a pivotal space where any action, or even inaction, will change the destiny of the situation and the actors themselves. It is a transformative journey, taken together, that starts with moment of suspense, and traverses a landscape of emotion and intention where a world of change becomes possible.
Gender‐role Attitudes among Egyptian Adolescents
Authors: Mensch Barbara S. , Ibrahim Barbara L. , Lee Susan M. , El‐Gibaly Omaima
Published: April 2004

Using nationally representative survey data, this study explores gender‐role attitudes among unmarried adolescents aged 16–19 in Egypt, a society characterized by distinct and often segregated roles for men and women. Adolescents' views about desirable qualities in a spouse as well as more direct indicators of gender‐role attitudes are examined, including opinions about whether wives should defer to their husbands, share in household decision making, and have the responsibility for performing domestic tasks. The findings regarding spousal characteristics reflect strong gender differentiation. Girls and boys provide divergent profiles of an ideal spouse, profiles that reflect traditional gender roles. Girls are significantly less likely than boys to favor educational inequality between spouses, however. Neither boys nor girls have egalitarian gender‐role attitudes, although girls are significantly more likely to express less traditional attitudes. Multivariate analyses indicate that girls' and boys' attitudes do not vary consistently and significantly by socioeconomic background; in particular, increased schooling does not always promote egalitarian attitudes. The implications of these findings are discussed.
Inconsistent Reporting of Female Genital Cutting Status in Northern Ghana: Explanatory Factors and Analytical Consequences
Authors: Jackson Elizabeth F. , Akweongo Patricia , Sakeah Evelyn , Hodgson Abraham , Asuru Rofina , Phillips James F.
Published: April 2004

Although many cross‐sectional social surveys have included questions about female genital cutting status and correlated personal characteristics, no longitudinal studies have been launched that permit investigation of response biases associated with such surveys. This study draws upon the findings of a longitudinal study of women aged 15 to 49 in rural northern Ghana. The self‐reported circumcision status of women interviewed in 1995 was compared with the status they reported when they were interviewed again in 2000 after the government began enforcing a law banning the practice and public information campaigns against it were launched. In all, 13 percent of respondents who reported in 1995 that they had been circumcised stated that they had not been circumcised in the 2000 reinterview; this inconsistency reached 50 percent for the youngest age group. Analysis shows that women who said they had not been circumcised are significantly younger, more likely to be educated, and less likely to practice traditional religion than are women who reported that they were circumcised. Factors that may explain these correlates of denial are discussed, and implications for research are reviewed.
The Quality of Family Planning Programs: Concepts, Measurements, Interventions, and Effects
Authors: RamaRao Saumya , Mohanam Raji
Published: April 2004

This study reviews the major research and interventions concerning readiness and quality of care in family planning programs. It has three aims: to identify and describe the principal methodological research including conceptual frameworks, perspectives, and tools for measuring and improving quality; to describe the results from various intervention studies; and to assess what is known about the effect of such interventions. The review suggests that interventions that improve client‐provider interactions show the greatest promise. Good quality of care results in such positive outcomes as clients’ satisfaction, increased knowledge, and more effective and longer use of contraceptives. Rigorously documented evidence of the effects of interventions is sorely needed. The review indicates areas requiring additional research.
A Four Factor Model: A Guide to Planning Next Generation Involvement in the Family Firm
Authors: Stavrou Eleni T.
Published: April 2004

The involvement of and the reasons for the involvement of offspring in their parents' firms can significantly affect the firm's future. In this paper, a conceptual model is presented that explains the decision process through which the most suitable level of involvement for the next generation in the firm may be assessed. The decision process involves four factors: family, business, personal, and market. These factors set the context for managing intergenerational transitions in family firms.
Interview with Massimo Ferragamo
Authors: Karofsky Paul I.
Published: April 2004

Massimo Ferragamo is the youngest of six children of Wanda and the late Salvatore Ferragamo. Massimo, with his siblings and mother, has built Salvatore Ferragamo, SpA, into one of the world's most highly recognized prestige brands of apparel and fashion ac- cessories. On May 14, 1997, Paul Karofsky met with Massimo Ferragamo in New York City. During the interview Karofsky asked Ferragamo to expand on and update several significant issues explored in the 1993 Harvard Business School case study of Salvatore Ferragamo, SpA.
Leadership, Legacy, and Emotional Process in Family Business
Authors: Baker Katharine G. , Wiseman Kathleen K.
Published: April 2004

This article presents a model for the practice of consulting to family business that is grounded in Bowen Systems Theory. Concepts from the theory, such as differentiation of self, the emotional system, the multigenerational transmission process, triangles, and the projection process are defined and discussed. Translation of the theory into consultation is described through the presentation of a case. Emphasis throughout the article is on the consultant's calm management of self in the presence of anxious clients who are dealing with difficult family business dilemmas.
Handling Transitions from Mother to Son in the Family Business: The Knotty Issues
Authors: Kaslow Florence W.
Published: April 2004

Most of the literature in the field of family business and the majority of cases discussed deals with succession as occurring within the male lineage. Although in the past decade more attention has been given to the role of women in family businesses and their contention for senior level positions, little has been written about women as originators and CEOs of family businesses. This article addresses such situations and the unique difficulties powerful women encounter when designating an only son as their successor. Two cases are discussed to illustrate the kinds of interactions and dynamics that may unfold between motherqsonqdaughter-in-law, and some of the consultative strategies utilized.
Happy Landings: The Opportunity to Fly Again
Authors: Kaye Kenneth
Published: April 2004

The success of a business for its owners is measurable in terms of the opportunities it creates for their beneficiaries. Perpetuating that business is only one of many possible opportunities for them.
Strategic Questions for University-Based Family Business Programs
Authors: Frishkoff Patricia A.
Published: April 2004

Family business programs are popular at universities and will continue to emerge and develop. But sustaining a program is not easy. This article poses strategic questions that are important to leaders of both new and long-standing programs. The article begins with a core question—Why should this university have a family business program] Topics that follow challenge, ask further questions, and provide advice.
Succession in Women-Owned Family Businesses: A Case Study
Authors: Cadieux Louise , Lorrain Jean , Hugron Pierre
Published: April 2004

Succession is one of the most studied aspects of family businesses. However, although it is estimated that women own more than 33% of such organizations, to our knowledge, few studies focus on succession in them. Our objective is to explore and understand the process of succession in family-owned businesses run by women. This paper presents the results of a case study of four women who own and run family businesses in the manufacturing sector and who have shared the management of their organizations with their successors for at least three years.
The Evolution of Family Institution and Its Impact on Society and Business
Authors: Belardinelli Sergio
Published: April 2004

If the family can be a great financial enterprise (and there should be no doubt about that), then the spirit and the virtues essential for building a financial enterprise are not produced automatically— they need to be cultivated.
What to Do When Talking Fails: Strategies for Minority Owners to Turn Stock Certificates into Money
Authors: Krasnow Henry C.
Published: April 2004

Conflicts often arise over issues of liquidity and minority owners' power. This article explores minority owners' options after talking has failed to resolve that conflict. It discusses legal strategies that can facilitate reaching an agreement on those issues. It also addresses types of agreements between family shareholders designed to avoid this conflict.
The Shareholder Role in the Family Business: Conflict of Interests and Objectives Between Nonemployed Shareholders and Top Management Team
Authors: Vilaseca Alvaro
Published: April 2004

This article focuses on the role of the family business shareholder. Based on Agency Theory, it examines the elements that influence the conflict of interests and objectives between nonemployed shareholders and the top management team and its impact on commitment to the family firm. Data were empirically obtained from a field study of 156 shareholders and executives of 10 Spanish family firms. Combining quantitative and qualitative data, investigation results show that the degree of commitment to the family business is negatively correlated with the number of family members on the board of directors. Nevertheless, the most robust and statistically significant correlation (positive) was found between the number of external board members and the commitment level of the nonemployed shareholders. Regarding the mechanisms and processes implemented, results depended on the attention that the family business paid to the institutional overlap of the three subsystems: ownership, family, and business.
Freeing the Shackles of Family Business Ownership
Authors: Thomas Jill
Published: April 2004

Ownership and management succession are recognized as defining processes for family businesses worldwide. Through the generations, as the family tree spreads, shareholdings become more dispersed, with no guarantee that all family shareholders will have the same degree of commitment to, and interest in, the family business. This paper discusses factors influencing the outcome of external and internal challenges to ownership of two interrelated Australian family businesses— one in its fifth generation, the other in its third. It concludes with guidelines to allow for effective and timely ownership transfer for those wishing to realize capital or retain control of their inherited investment.
Genetic Evidence that
Legionella pneumophila
RpoS Modulates Expression of the Transmission Phenotype in Both the Exponential Phase and the Stationary Phase
Authors: Bachman Michael A. , Swanson Michele S.
Published: April 2004

The opportunistic pathogen
Legionella pneumophila
alternates between two states: replication within phagocytes and transmission between host amoebae or macrophages. In broth cultures that model this life cycle, during the replication period, CsrA inhibits expression of transmission traits. When nutrients become limiting, the alarmone (p)ppGpp accumulates and the sigma factors RpoS and FliA and the positive activators LetA/S and LetE promote differentiation to the transmissible form. Here we show that when cells enter the postexponential growth phase, RpoS increases expression of the transmission genes
fliA
,
flaA
, and
mip
, factors
L. pneumophila
needs to establish a new replication niche. In contrast, in exponential (E)-phase cells whose (p)ppGpp levels are low,
rpoS
inhibits expression of transmission traits, on the basis of three separate observations. First,
rpoS
RNA levels peak in the E phase, suggestive of a role for RpoS during replication. Second, in multiple copies,
rpoS
decreases the amounts of
csrA
,
letE
,
fliA
, and
flaA
transcripts and inhibits the transmission traits of motility, infectivity, and cytotoxicity. Third,
rpoS
blocks expression of cytotoxicity and motility by E-phase bacteria that have been induced to express the LetA activator ectopically. The data are discussed in the context of a model in which the alarmone (p)ppGpp enables RpoS to outcompete other sigma factors for binding to RNA polymerase to promote transcription of transmission genes, while LetA/S acts in parallel to relieve CsrA posttranscriptional repression of the transmission regulon. By coupling transcriptional and posttranscriptional control pathways, intracellular
L. pneumophila
could respond to stress by rapidly differentiating to a transmissible form.
Involvement of Lipoprotein NlpI in the Virulence of Adherent Invasive
Escherichia coli
Strain LF82 Isolated from a Patient with Crohn's Disease
Authors: Barnich Nicolas , Bringer Marie-Agnès , Claret Laurent , Darfeuille-Michaud Arlette
Published: April 2004

Escherichia coli
strain LF82 recovered from a chronic lesion of a patient with Crohn's disease (CD) is able to adhere to and invade cultured intestinal epithelial cells and to replicate within macrophages. One mutant selected for its impaired ability to invade epithelial cells had an insertion of a Tn
phoA
transposon within the
nlpI
gene encoding the lipoprotein NlpI. A NlpI-negative isogenic mutant showed a 35-fold decrease in its ability to adhere to and a 45-fold decrease in its ability to invade Intestine-407 cells, but its ability to survive and to replicate within macrophages was similar to that of wild-type strain LF82. In addition, this mutant did not express flagella and synthesized very small amounts of type 1 pili. Downregulation of type 1 pili in the NlpI-negative mutant resulted from a preferential switch toward the OFF position of the invertible DNA element located upstream of the
fim
operon. The FimB and FimE recombinases act in concert to control the switch, and a large decrease in
fimB
and
fimE
mRNA levels was observed. The absence of flagellar structures correlated with a drastic 19-fold decrease in the
fliC
mRNA level, regardless of the FlhD
2
C
2
transcriptional regulator and of the σ
28
transcription factor. The key role of NlpI in virulence is independent of type 1 pili and motility, since induced type 1 pilus expression and/or forced contact between bacteria and intestinal epithelial cells did not restore the ability of the NlpI mutant to adhere to and to invade intestinal epithelial cells.
Caspase-8 Activation Precedes Alterations of Mitochondrial Membrane Potential during Monocyte Apoptosis Induced by Phagocytosis and Killing of
Staphylococcus aureus
Authors: Weęglarczyk Kazimierz , Baran Jarosław , Zembala Marek , Pryjma Juliusz
Published: April 2004

Human peripheral blood monocytes become apoptotic following phagocytosis and killing of
Staphylococcus aureus
. Although this type of monocyte apoptosis is known to be initiated by Fas-Fas ligand (FasL) interactions, the downstream signaling pathway has not been determined. In this work the involvement of mitochondria and the kinetics of caspase-8 and caspase-3 activation after phagocytosis of
S. aureus
were studied. Caspase-8 activity was measured in cell lysates by using the fluorogenic substrate Ac-IETD-AFC. Active caspase-3 levels and mitochondrial membrane potential (Δψ
m
) were measured in whole cells by flow cytometry using monoclonal antibodies reacting with activated caspase-3 and chloromethyl-X-rosamine, respectively. The results show that caspase-8 was activated shortly after phagocytosis of bacteria. Caspase-8 activation was followed by progressive disruption of Δψ
m
, which is associated with the production of reactive oxygen intermediates. The irreversible caspase-8 inhibitor zIETD-FMK prevented the disruption of Δψ
m
and the release of cytochrome
c
from
S. aureus
-exposed monocytes. Caspase-3 activation occurred following disruption of Δψ
m
. These results strongly suggest that apoptosis of monocytes that have phagocytosed and killed
S. aureus
is driven by the Fas-FasL-initiated pathway, which is typical for type II cells.
Impairment of Tetanus-Specific Cellular and Humoral Responses following Tetanus Vaccination in Human Lymphatic Filariasis
Authors: Nookala Suba , Srinivasan Sundaram , Kaliraj Perumal , Narayanan Rangarajan Badri , Nutman Thomas B.
Published: April 2004

To investigate the consequences of the impaired parasite-specific immune response in lymphatic filariasis, the effect of concurrentWuchereria bancroftiinfection on the immune response to tetanus toxoid (TT) following tetanus vaccination was studied in 20 asymptomatic microfilaremic (MF) patients, 20 patients with chronic lymphatic obstruction/elephantiasis (chronic pathology [CP]), and 10 endemic normal (EN) control individuals at baseline and at 3 and 6 months after TT vaccination. Peripheral blood mononuclear cell (PBMC) proliferative responses to TT before vaccination were not significantly different between the EN control and CP groups, but the MF group showed significantly lower baseline proliferative responses to TT compared with either the EN or CP group. Six months following vaccination, the change in proliferative response to TT was significantly greater in the EN and CP groups than in the MF group. This difference in proliferative response was reiterated in the gamma interferon (IFN-γ) response in the EN group, in that they increased IFN-γ production by 400% at 6 months, in contrast to that seen in the filaria-infected groups. In contrast to the IFN-γ responses, PBMCs from the MF group produced significantly increased levels of TT-specific IL-10 compared with PBMCs from the EN group. Although there was significantly greater TT-specific immunoglobulin G (IgG) production at baseline between the EN and MF groups, postvaccination IgG (and IgG1 isotype) responses did not differ among the groups, whereas TT-specific IgG2, IgG3, and IgG4 were all increased in the EN group compared with the filaria-infected groups. These studies indicate that concurrent infection withW. bancroftican diminish the immune response to an unrelated antigen by a mechanism that is likely to involve IL-10.
Intranasal Immunization with a Colloid-Formulated Bacterial Extract Induces an Acute Inflammatory Response in the Lungs and Elicits Specific Immune Responses
Authors: Rial A. , Lens D. , Betancor L. , Benkiel H. , Silva J. S. , Chabalgoity J. A.
Published: April 2004

Nonspecific stimulation of lung defenses by repeated oral administration of immunomodulators, such as bacterial extracts, has shown potential for the prevention of respiratory tract infections. Here, we show that intranasal (i.n.) immunization with a bacterial extract formulated as a colloid induces an acute inflammatory response in the lungs characterized by increased production of CCL and CXCL chemokines and a major influx of dendritic cells (DCs) and neutrophils, with a higher proportion of DCs showing an activated phenotype (high CD80/CD86 expression). Cytokine levels measured in bronchoalveolar-lavage samples showed a small increase in the production of tumor necrosis factor alpha and similar levels of the other cytokines measured (interleukin 10 [IL-10], IL-12, and gamma interferon [IFN-γ]) in immunized mice compared with control mice. However, the recall response of primed animals after antigenic challenge induced increased expression of IL-12 and IFN-γ mRNAs in lung homogenates. Overall, all these effects were not due to the lipopolysaccharide content in the bacterial extract. Furthermore, we found that three i.n. doses administered 2 to 3 weeks apart were enough to elicit long-lasting specific serum immunoglobulin G (IgG) and secretory IgA antibody responses. Assessment of IgG subclasses showed a balanced pattern of IgG1-IgG2a responses. The serum total IgE concentrations were also elevated in immunized mice 2 weeks after the third dose, but they significantly decreased soon afterwards. Our results suggest that simple formulations of bacterial extracts administered i.n. are highly immunogenic, eliciting local and systemic immune responses, and may serve as the basis for cost-effective immunotherapies for the prevention and treatment of respiratory infections.
Dialysis Unmasks the Fungicidal Properties of Glandular Salivary Secretions
Authors: Helmerhorst Eva J. , Flora Bianca , Troxler Robert F. , Oppenheim Frank G.
Published: April 2004

Several salivary proteins exhibit fungicidal activity against the opportunistic oral pathogen
Candida albicans
when they are tested as pure proteins in vitro. However, salivary secretions that are examined by the same assays either lack or exhibit very low candidacidal activity. Since ionic strength is known to have an inhibitory effect on the fungicidal activities of some proteins, parotid secretion was subjected to dialysis with membranes having molecular weight cutoffs (MWCOs) of 500, 1,000, 10,000, and 25,000. Dialysis with membranes with MWCOs of ≥1,000 promoted fungicidal activity of parotid secretion, and this activity was dose dependent. The addition of sodium chloride to dialyzed, fungicidal parotid secretion abolished this activity, indicating that the fungicidal component was salt sensitive. Similar results were obtained with submandibular and sublingual secretions. Polyacrylamide gel electrophoresis under native and denaturing conditions was used to analyze the composition of the dialysate. Unexpectedly, proteins with MWs much lower than the nominal MWCOs of the membranes were not lost during dialysis. Among the retained proteins, the two fractions with MWs of approximately 17,000 and 4,000 exhibited fungicidal activity. These results are consistent with the presence of lysozyme and histatins, respectively, which may represent the major candidacidal capacity of dialyzed parotid secretion.
Enhanced Mucosal Delivery of Antigen with Cell Wall Mutants of Lactic Acid Bacteria
Authors: Grangette Corinne , Müller-Alouf Heide , Hols Pascal , Goudercourt Denise , Delcour Jean , Turneer Mireille , Mercenier Annick
Published: April 2004

The potential of recombinant lactic acid bacteria (LAB) to deliver heterologous antigens to the immune system and to induce protective immunity has been best demonstrated by using the C subunit of tetanus toxin (TTFC) as a model antigen. Two types of LAB carriers have mainly been used,Lactobacillus plantarumandLactococcus lactis, which differ substantially in their abilities to resist passage through the stomach and to persist in the mouse gastrointestinal tract. Here we analyzed the effect of a deficiency in alanine racemase, an enzyme that participates in cell wall synthesis, in each of these bacterial carriers. Recombinant wild-type and mutant strains ofL. plantarumNCIMB8826 andL. lactisMG1363 producing TTFC intracellularly were constructed and used in mouse immunization experiments. Remarkably, we observed that the two cell wall mutant strains were far more immunogenic than their wild-type counterparts when the intragastric route was used. However, intestinal TTFC-specific immunoglobulin A was induced only after immunization with the recombinantL. plantarummutant strain. Moreover, the alanine racemase mutant of either LAB strain allowed induction of a much stronger serum TTFC-specific immune response after immunization via the vagina, which is a quite different ecosystem than the gastrointestinal tract. The design and use of these mutants thus resulted in a major improvement in the mucosal delivery of antigens exhibiting vaccine properties.
Bovine Leukocyte Antigen Major Histocompatibility Complex Class IIDRB3*2703andDRB3*1501Alleles Are Associated with Variation in Levels of Protection againstTheileria parvaChallenge following Immunization with the Sporozoite p67 Antigen
Authors: Ballingall Keith T. , Luyai Anthony , Rowlands G. John , Sales Jill , Musoke Anthony J. , Morzaria Subash P. , McKeever Declan J.
Published: April 2004

Initial laboratory trials of an experimental subunit vaccine againstTheileria parvabased on the 67-kDa major sporozoite surface antigen revealed a range of responses to challenge. We have analyzed convergence in seven sets of monozygotic twins which suggests that genetic factors may have an influence in determining the degree of protection provided by p67 immunization. In addition, we have examined whether allelic diversity at major histocompatibility complex class II loci influences protection. Analysis of bovine leukocyte antigenDRB3diversity in 201 animals identified significant associations with vaccine success (DRB3*2703;P= 0.027) and vaccine failure (DRB3*1501;P= 0.013). Furthermore,DRB3*2703was associated with the likelihood of immunized animals showing little to no clinical signs of disease following challenge. We discuss the acquired and innate immune mechanisms that may be behind the associations described here.
Mucosal and Cellular Immune Responses Elicited by RecombinantLactococcus lactisStrains Expressing Tetanus Toxin Fragment C
Authors: Robinson K. , Chamberlain L. M. , Lopez M. C. , Rush C. M. , Marcotte H. , Le Page R. W. F. , Wells J. M.
Published: April 2004

The mucosal and cellular responses of mice were studied, following mucosal-route administration of recombinantLactococcus lactisexpressing tetanus toxin fragment C (TTFC), which is a known immunogen protective against tetanus. A TTFC-specific T-cell response with a mixed profile of T-helper (Th) subset-associated cytokines was elicited in the intestine, with a Th2 bias characteristic of a mucosal response. These results correlated with the humoral response, where equivalent titers of anti-TTFC immunoglobulin G1 (IgG1) and IgG2a in serum were accompanied by an elevated IgA-specific response at more than one mucosal site. The route of vaccination had an important role in determining the immune response phenotype, as evidenced by the fact that an IgG1-biased subclass profile was obtained when lactococci were administered parenterally. Stimulation of splenic or mesenteric lymph node cells with lactococci resulted in their proliferation and the secretion of gamma interferon via antigen-specific and innate immune mechanisms. The data therefore provide further evidence of the potential of recombinant lactococcal vaccines for inducing systemic and mucosal immune responses.
Differential Regulation of β-Defensin Gene Expression duringCryptosporidium parvumInfection
Authors: Zaalouk Tarek K. , Bajaj-Elliott Mona , George John T. , McDonald Vincent
Published: April 2004

Invasion of enterocytes by pathogenic microbes evokes both innate and adaptive immune responses, and microbial pathogens have developed strategies to overcome the initial host immune defense. β-Defensins are potentially important endogenous antibiotic-like effectors of innate immunity expressed by intestinal epithelia. In this study, the interplay between the enteric protozoan parasiteCryptosporidium parvumand host epithelial β-defensin expression was investigated. Using human and murine models of infection, we demonstrated thatC. parvuminfection differentially regulates β-defensin gene expression. Downregulation of murine β-defensin-1 mRNA and protein was observed in both in vitro and in vivo models of infection. Infection of the human colonic HT29 cell line with the parasite resulted in differential effects on various members of the defensin gene family. Partial reduction in human β-defensin-1 (hBD-1), induction of hBD-2, and no effect on hBD-3 gene expression was observed. Recombinant hBD-1 and hBD-2 peptides exhibited significant antimicrobial activity againstC. parvumsporozoites in vitro. These findings demonstrate thatC. parvuminfection of enterocytes may affect the expression of various defensins in different ways and suggest that the overall outcome of the effect of antimicrobial peptides on early survival of the parasite may be complex.
Binding of Hematin by a New Class of Glutathione Transferase from the Blood-Feeding Parasitic NematodeHaemonchus contortus
Authors: van Rossum Arjan J. , Jefferies James R. , Rijsewijk Frans A. M. , LaCourse E. James , Teesdale-Spittle Paul , Barrett John , Tait Andrew , Brophy Peter M.
Published: April 2004

The phase II detoxification system glutathione transferase (GST) is associated with the establishment of parasitic nematode infections within the gastrointestinal environment of the mammalian host. We report the functional analysis of a GST from an important worldwide parasitic nematode of small ruminants,Haemonchus contortus. This GST shows limited activity with a range of classical GST substrates but effectively binds hematin. The high-affinity binding site for hematin was not present in the GST showing the most identity, CE07055 from the free-living nematodeCaenorhabditis elegans. This finding suggests that the high-affinity binding of hematin may represent a parasite adaptation to blood or tissue feeding from the host.
Functional Transfer of
Salmonella
Pathogenicity Island 2 to
Salmonella bongori
and
Escherichia coli
Authors: Hansen-Wester Imke , Chakravortty Dipshikha , Hensel Michael
Published: April 2004

The type III secretion system (T3SS) encoded by the
Salmonella
pathogenicity island 2 (SPI2) has a central role in systemic infections by
Salmonella enterica
and for the intracellular phenotype. Intracellular
S. enterica
uses the SPI2-encoded T3SS to translocate a set of effector proteins into the host cell, which modify host cell functions, enabling intracellular survival and replication of the bacteria. We sought to determine whether specific functions of the SPI2-encoded T3SS can be transferred to heterologous hosts
Salmonella bongori
and
Escherichia coli
Mutaflor, species that lack the SPI2 locus and loci encoding effector proteins. The SPI2 virulence locus was cloned and functionally expressed in
S. bongori
and
E. coli
. Here, we demonstrate that
S. bongori
harboring the SPI2 locus is capable of secretion of SPI2 substrate proteins under culture conditions, as well as of translocation of effector proteins under intracellular conditions. An SPI2-mediated cellular phenotype was induced by
S. bongori
harboring the SPI2 if the
sifA
locus was cotransferred. An interference with the host cell microtubule cytoskeleton, a novel SPI2-dependent phenotype, was observed in epithelial cells infected with
S. bongori
harboring SPI2 without additional effector genes.
S. bongori
harboring SPI2 showed increased intracellular persistence in a cell culture model, but SPI2 transfer was not sufficient to confer to
S. bongori
systemic pathogenicity in a murine model. Transfer of SPI2 to heterologous hosts offers a new tool for the study of SPI2 functions and the phenotypes of individual effectors.
Macrophages Release Tumor Necrosis Factor Alpha and Interleukin-12 in Response to Intracellular
Bacillus anthracis
Spores
Authors: Pickering Alison K. , Merkel Tod J.
Published: April 2004

Herein we report that infection of a murine macrophage cell line with
Bacillus anthracis
results in the production of tumor necrosis factor alpha and interleukin-12 (IL-12). When infected with
B. anthracis
spores in combination with lipopolysaccharide, macrophages release increased amounts of IL-12. We found no evidence of inhibition of cytokine responses in macrophages infected with
B. anthracis
spores.
Pneumococcal Surface Protein C Contributes to Sepsis Caused byStreptococcus pneumoniaein Mice
Authors: Iannelli Francesco , Chiavolini Damiana , Ricci Susanna , Oggioni Marco Rinaldo , Pozzi Gianni
Published: April 2004

The role of pneumococcal surface protein C (PspC; also called SpsA, CbpA, and Hic) in sepsis byStreptococcus pneumoniaewas investigated in a murine infection model. ThepspCgene was deleted in strains D39 (type 2) and A66 (type 3), and the mutants were tested by being injected intravenously into mice. The animals infected with the mutant strains showed a significant increase in survival, with the 50% lethal dose up to 250-fold higher than that for the wild type. Our findings indicate that PspC affords a decisive contribution to sepsis development.
LATE CENOZOIC INCREASE IN ACCUMULATION RATES OF TERRESTRIAL SEDIMENT: How Might Climate Change Have Affected Erosion Rates?
Authors: Molnar Peter
Published: April 2004

▪ Abstract  Accumulation rates of terrestrial sediment have increased in the past few million years both on and adjacent to continents, although not everywhere. Apparently, erosion has increased in elevated terrain regardless of when last tectonically active or what the present-day climate. In many regions, sediment coarsened abruptly in late Pliocene time. Sparser data suggest increased sedimentation rates at ∼15 Ma, approximately when oxygen isotopes in benthic foraminifera imply high-latitude cooling. If climate change effected accelerated erosion, understanding how it did so remains the challenge. Some obvious candidates, such as lowered sea level leading to erosion of continental shelves or increased glaciation, account for increased sedimentation in some, but not all, areas. Perhaps stable climates that varied slowly allowed geomorphic processes to maintain a state of equilibrium with little erosion until ∼3–4 Ma, when large oscillations in climate with periods of 20,000–40,000 years developed and denied the landscape the chance to reach equilibrium.
BEDROCK RIVERS AND THE GEOMORPHOLOGY OF ACTIVE OROGENS
Authors: Whipple Kelin X.
Published: April 2004

▪ Abstract  Bedrock rivers set much of the relief structure of active orogens and dictate rates and patterns of denudation. Quantitative understanding of the role of climate-driven denudation in the evolution of unglaciated orogens depends first and foremost on knowledge of fluvial erosion processes and the factors that control incision rate. The results of intense research in the past decade are reviewed here, with the aim of highlighting remaining unknowns and suggesting fruitful avenues for further research. This review considers in turn (a) the occurrence and morphology of bedrock channels and their relation to tectonic setting; (b) the physical processes of fluvial incision into rock; and (c) models of river incision, their implications, and the field and laboratory data needed to test, refine, and extend them.
SPHERULE LAYERS—RECORDS OF ANCIENT IMPACTS
Authors: Simonson Bruce M. , Glass Billy P.
Published: April 2004

▪ Abstract  A large extraterrestrial object striking Earth at cosmic velocity melts and vaporizes silicate materials, which can condense into highly spheroidal, sand-size particles that get deposited hundreds to thousands of kilometers from the point of impact. These particles, known as impact spherules, have been detected in great abundance in a relatively small number of thin, discrete layers ranging in age from less than a million years to 3.47 billion years. Unaltered impact spherules consist entirely of glass (microtektites) or a combination of glass and crystals grown in flight (microkrystites). Impact spherule layers form very rapidly and can be very extensive, even global in extent [e.g., the Cretaceous-Tertiary (K/T) boundary layer], so they form excellent time-stratigraphic markers. Because they are always found in a stratigraphic context, spherule layers are probably superior to terrestrial craters and related structures for assessing the environmental and biotic effects of large impacts. A record of impacts whose craters have since been obliterated, most notably those in pre-Mesozoic oceanic crust, could survive in the form of spherule layers. Secular changes in surface environments and/or the nature of the impactors striking Earth through its history could also be reflected in differences in spherules and spherule layers as a function of geologic age. In this paper, we briefly review what spherules and spherule layers are and the processes that create them, then speculate about what might be learned through wider identification of and more extensive study of impact spherule layers.
ROCK TO SEDIMENT—SLOPE TO SEA WITH 10BE—RATES OF LANDSCAPE CHANGE
Authors: Robert Bierman Paul , Nichols Kyle Keedy
Published: April 2004

▪ Abstract  Measurements of cosmogenic nuclides, predominately 10Be, allow new insights into the ways in which and the rates at which sediment is generated, transported, and deposited over timescales ranging from 103 to 106 years. Samples from rock exposures are used to estimate erosion rates at points on the landscape, whereas samples of fluvial sediment provide estimates of basin-scale rates of denudation integrated over <1 to >104 km2. Nuclide data show that hilltop, bare rock outcrops erode more slowly than basins as a whole, suggesting the potential for relief to increase over time as well-drained outcrops grow higher. More elaborate experiments and interpretive models provide insight into the distribution of hillslope processes, including the bedrock-to-soil conversion rate, which appears to increase under shallow soil cover and then decrease under deeper soils. Changes in average nuclide activity down slopes can be used to estimate grain speed over millennia, suggesting, for example, that sediment on desert piedmonts moves, on average, decimeters to meters per year. In other cases, changes in nuclide activity down river networks or along shorelines can be interpreted with mixing models to indicate sediment sources. Sediment deposition rates in otherwise undateable deposits can now be estimated by analyzing samples collected from depth profiles. Over the past decade, the analysis and interpretation of cosmogenic nuclides has given geomorphologists an unprecedented opportunity to measure rates and infer the distribution of geomorphic processes across Earth's varied landscapes. Long-standing models of landscape change can now be tested quantitatively.
COMPRESSIONAL STRUCTURES ON MARS
Authors: Mueller Karl , Golombek Matthew
Published: April 2004

▪ Abstract  Wrinkle ridges accommodate very low amounts of shortening strain around immense volcanic constructs and within impact basins on Mars. They originate from stresses distributed uniformly throughout the brittle lithosphere and are consistently located in stratified deposits, including lava flows and sediment. Most recent models interpret wrinkle ridges as the surface manifestation of folding above underlying blind thrusts that accommodate similarly low strain and likely penetrate tens of kilometers into the brittle crust. Alternative models suggest shortening accommodated by some wrinkle ridges is confined to only the upper few kilometers of the crust. The interpretation of the geometry of blind thrusts on Mars appears to be quite varied and remains controversial, although some models suggest they may ultimately flatten into the brittle-ductile transition in the middle to lower crust. Small-scale crenulations superposed on ridges are interpreted as produced by high-level back thrusts nucleating at a weak layer in the upper crust, or by flexural slip faults that facilitate bending of layered materials. Wrinkle ridges are related to their structural cousins, lobate scarps that accommodate shortening in older Noachian cratered highlands as surface fault ruptures. Wrinkle ridges thus form when displacement across upwardly propagating blind thrusts is consumed by folding of layered material near the surface. Conversely, lobate scarps are formed by blind thrusts that are not impeded by folding of overlying layered deposits. Broad, low-amplitude arches associated with ridges on the Tharsis rise also accommodate shortening, but their relationship to adjacent or superposed ridges remains enigmatic. The evenly spaced nature of wrinkle ridges that appears to vary systematically between the ridged plains and northern lowlands may be related to the depth of the brittle-ductile transition, which is respectively located in the middle crust and upper mantle in these regions.