bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relationship Between Safety Climate and Recent Accidents: Behavioral Learning and Cognitive Attributions
Authors: Desai Vinit M. , Roberts Karlene H. , Ciavarelli Anthony P.
Published: December 2006

Objective: The association between accidents and subsequent work unit safety perceptions was assessed to address cognitive and behavioral changes following accidents. Background: Many studies attempt to predict accident rates using measures of work unit safety, but effects vary considerably. Conversely, this study examined whether recent accidents may be positively associated with work unit safety perceptions, as suggested by behavioral learning mechanisms (increases in safety investments following accidents) or cognitive mechanisms (defensive attributions regarding accident causality). Method: Lagged squadron-level accident experience was correlated with work unit safety perceptions obtained through a 61-question safety climate survey administered to 6,361 individuals in U.S. Navy flight squadrons. Results: Positive associations between minor or intermediately severe accidents and future safety climate scores were found, although no effect was found for major accidents. Conclusion: We suggest that accident history should be considered when examining work unit safety perceptions because recent accidents may be associated with higher safety climate scores. We did not find that this varies systematically with accident severity, and longitudinal research on additional samples is needed to further test this possibility. Application: This research may be used to refine measurement of work unit safety and to examine impacts of accidents or safety violations on workers' cognitive processes and group behavioral changes.
The Impact of Distraction Mitigation Strategies on Driving Performance
Authors: Donmez Birsen , Boyle Linda Ng , Lee John D.
Published: December 2006

Objectives: An experiment was conducted to assess the effects of distraction mitigation strategies on drivers? performance and productivity while engaged in an in-vehicle information system task. Background: Previous studies show that in-vehicle tasks undermine driver safety and there is a need to mitigate driver distraction. Method: An advising strategy that alerts drivers to potential dangers and a locking strategy that prevents the driver from continuing the distracting task were presented to 16 middle-aged and 12 older drivers in a driving simulator in two modes (auditory, visual) and two road conditions (curves, braking events). Results: Distraction was a problem for both age groups. Visual distractions were more detrimental than auditory ones for curve negotiation, as depicted by more erratic steering, F(6, 155) = 26.76, p < .05. Drivers did brake more abruptly under auditory distractions, but this effect was mitigated by both the advising, t(155) = 8.37, p < .05, and locking strategies, t(155) = 8.49, p < .05. The locking strategy also resulted in longer minimum time to collision for middle-aged drivers engaged in visual distractions, F(6, 138) = 2.43, p < .05. Conclusions: Adaptive interfaces can reduce abrupt braking on curve entries resulting from auditory distractions and can also improve the braking response for distracted drivers. Application: These strategies can be incorporated into existing in-vehicle systems, thus mitigating the effects of distraction and improving driver performance.
Detecting Transient Changes in Dynamic Displays: The More You Look, the Less You See
Authors: Boot Walter R. , Kramer Arthur F. , Becic Ensar , Wiegmann Douglas A. , Kubose Tate
Published: December 2006

Objective: Two experiments examined the detectability of transient changes in cluttered and dynamic displays and optimal scan strategies for performance. Background: Research has demonstrated that onset changes are prioritized by the attention system and onsets are often used to signal important display changes. However, research has mostly used uncluttered, static displays and has largely ignored the role of scan strategy. Method: W e had participants monitor a cluttered and dynamic display and respond when an object changed color or onset abruptly. Scan strategies were also evaluated. In another experiment participants were instructed to use particular strategies to detect changes. Results: Consistent with previous results, onset events were detected better than were color change events. Scan strategy accounted for a large proportion of variance in detection performance. Participants who made few eye movements performed best. Participants who actively scanned the display performed worst. When poor performers were instructed to make few eye movements, their performance matched that of the best performers. Conclusion: Onset alerts can be an effective means of signaling important events in complex displays. Additionally, scan strategy plays an important role in the detection of transient events. Application: These results have important implications for training operators to search for transient changes within dynamic and cluttered displays.
Community college missions: A theoretical and historical perspective
Authors: Dougherty Kevin J. , Townsend Barbara K.
Published: December 2006

This chapter analyzes various ways of conceptualizing the missions of the community college, describes how those missions have varied over time and across geographical regions, and examines how missions complement and conflict with one another.
Prioritizing service to the academically talented: The honors college
Authors: Floyd Deborah L. , Holloway Alexandria
Published: December 2006

This chapter describes community college honors programs and courses, emphasizing in particular the Honors College at Miami Dade College in Florida. The chapter discusses pros and cons of honors programs and courses in the context of their appropriateness to the community college mission of open access and egalitarianism.
Emerging institutional support for developmental education
Authors: Kozeracki Carol A. , Brooks J. Bryan
Published: December 2006

With large numbers of underprepared students enrolling at community colleges, faculty are beginning to recognize that developmental education is a collegewide responsibility that needs to be fully integrated with the college's broader curriculum and varied missions.
Competing missions: Balancing entrepreneurialism with community responsiveness in community college continuing education divisions
Authors: Downey John A. , Pusser Brian , Turner J. Kirsten
Published: December 2006

Continuing education divisions in community colleges tend to be among the most entrepreneurial and innovative programs in higher education. This chapter presents data from a national survey of continuing education programs and suggests that shifting economic and institutional factors influence the manner in which community colleges offer those programs.
Prioritizing community college missions: A directional effort
Authors: McPhail Christine Johnson , McPhail Irving Pressley
Published: December 2006

This chapter delineates the essential elements of a framework for establishing mission priorities for community colleges.
Submissive voices dominate in depression: Assimilation analysis of a helpful session
Authors: Osatuke Katerine , Mosher James K. , Goldsmith Jacob Z. , Stiles William B. , Shapiro David A. , Hardy Gillian E. , Barkham Michael
Published: December 2006

Using the assimilation model, we describe a theoretical paradox in which interpersonally assertive parts of the depressed person's personality are dominated and suppressed by parts that are interpersonally submissive and passive. We examine the relevance of this paradox to therapeutic work, focusing on a particularly helpful session (according to the therapist) from the case of Joan, a woman seen for depression in cognitive‐behavioral therapy. We consider how the therapist intervened to enhance communication between the interpersonally submissive and dominant parts of Joan and discuss the implications of this process for therapy with such clients. © 2007 Wiley Periodicals, Inc. J Clin Psychol: In Session 63: 153–164, 2007.
Multiplicity of selves and others: Cognitive analytic therapy
Authors: Ryle Anthony , Fawkes Liz
Published: December 2006

In cognitive analytic therapy (CAT), multiplicity is understood in terms of a range of self‐other patterns (reciprocal role relationships) originating in childhood. These alternate in determining experience and action according to the situation (contextual multiplicity). They may be restricted by adverse childhood experiences (diminished multiplicity), and severe deprivation or abuse may result in a structural dissociation of self‐processes ( pathological multiplicity). Therapeutic interventions, to be effective, must be based on an understanding of the structure of the individual patient's self‐processes. In CAT practice, descriptions of dysfunctional relationship patterns and of transitions between them are worked out by therapist and patient at the start of therapy and are used by both throughout its course. This approach is illustrated by an account of the treatment of a depressed and anxious 70‐year‐old man who alternated between two main patterns. © 2007 Wiley Periodicals, Inc. J Clin Psychol: In Session 63: 165–174, 2007.
The multistory self: Why the self is more than the sum of its autoparts
Authors: Power M. J.
Published: December 2006

A summary is presented of both the theoretical and clinical points made by the contributors to this issue of Journal of Clinical Psychology: In Session on the multiplicity of self. It is argued that there are many theoretical and clinical commonalities in the diverse range of psychotherapies that have been developed and that have been used in work with problems in the self‐concept. Core problems encountered in clinical practice include an apparent self‐integration that is attained through the exclusion of important parts of the self. The key to opening up clients who present such problems is through the use of experienced emotions and the therapeutic relationship. More extreme problems in the self‐concept can be seen in the personality and psychotic disorders, in which the self may be chaotic or disintegrated. Such clients may need help with the development of a reflective self that can integrate and regulate the separate parts of the self‐concept. © 2007 Wiley Periodicals, Inc. J Clin Psychol: In Session 63: 187–198, 2007.
The circular chromatic numbers of planar digraphs
Authors: Soh Chin‐Ann
Published: December 2006

The circular chromatic number is a refinement of the chromatic number of a graph. It has been established in [3,6,7] that there exists planar graphs with circular chromatic number r if and only if r is a rational in the set {1} ∪ [2,4]. Recently, Mohar, in [1,2] has extended the concept of the circular chromatic number to digraphs and it is interesting to ask what the corresponding result is for digraphs. In this article, we shall prove the new result that there exist planar digraphs with circular chromatic number r if and only if r is a rational in the interval [1,4]. © 2006 Wiley Periodicals, Inc. J Graph Theory 55: 14–26, 2007
Contractible subgraphs in k‐connected graphs
Authors: Jin Zemin , Yu Xingxing , Zhang Xiaoyan
Published: December 2006

For a graph G we define a graph T(G) whose vertices are the triangles in G and two vertices of T(G) are adjacent if their corresponding triangles in G share an edge. Kawarabayashi showed that if G is a k‐connected graph and T(G) contains no edge, then G admits a k‐contractible clique of size at most 3, generalizing an earlier result of Thomassen. In this paper, we further generalize Kawarabayashi's result by showing that if G is k‐connected and the maximum degree of T(G) is at most 1, then G admits a k‐contractible clique of size at most 3 or there exist independent edges e and f of G such that e and f are contained in triangles sharing an edge and G/e/f is k‐connected. © 2006 Wiley Periodicals, Inc. J Graph Theory 55: 121–136, 2007
Gas transport properties of asymmetric polyimide membranes prepared by ion‐beam irradiation
Authors: Sannomiya A. , Fukui K. , Nagaoka S. , Suzuki Y. , Iwaki M. , Kawakami H.
Published: December 2006

Ion beam irradiation has been widely used to modify the structure and properties of membrane surface layers. In this study, the gas permeability and selectivity of an asymmetric polyimide membrane modified by He ion irradiation were investigated using a high vacuum apparatus equipped with a Baratron absolute pressure gauge at 76 cmHg and 35 °C. Specifically, we estimated the effects of the gas diffusion and solubility on the gas permeation properties of the asymmetric membranes with the carbonized skin layer prepared by ion irradiation. The asymmetric polyimide membranes were prepared by a dry–wet phase inversion process, and the surface skin layer on the membrane was irradiated by He ions at fluences of 1 × 1015 to 5 × 1015 ions/cm2 at 50 keV. The increase in the gas permeability of the He+‐irradiated asymmetric polyimide membrane is entirely due to an increase in the gas diffusion, and the gas selectivity increases of the membranes were responsible for the high gas diffusion selectivities. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 262–269, 2007.
The student affairs portfolio in small colleges
Authors: Heida Debbie E.
Published: December 2006

This chapter provides an overview of functional areas included in the portfolio of the small college dean. Four examples of organizational charts are offered, as well as factors that will influence the small college student affairs portfolio in the future.
Computer‐Assisted Operative Planning in Adult Living Donor Liver Transplantation: A New Way to Resolve the Dilemma of the Middle Hepatic Vein
Authors: Radtke A. , Nadalin S. , Sotiropoulos G. C. , Molmenti E. P. , Schroeder T. , Valentin‐Gamazo C. , Lang H. , Bockhorn M. , Peitgen H.O. , Broelsch C. E. , Malagó M.
Published: December 2006

An adequate venous outflow is essential for securing viability of both graft and remnant in adult living donor liver transplantation (ALDLT). Seventy‐five potential live liver donors were evaluated for LDLT by means of an “all‐in‐one” CT, which defined the biliary tree, portal vein, hepatic artery, and hepatic vein anatomy. The acquired data sets were further analysed by means of the software HepaVision (MeVis, Germany). Only a minority (29%) of potential donors were found to have a vascular and biliary anatomy consistent with the classically described “normal” patterns. The vast majority (71%) had “anatomical variations”. Thirty‐nine (52%) donors underwent ALDLT hepatectomy. The right hepatic vein was dominant in 64 cases, representing 48 ± 6% of the total liver volume (TLV). The middle hepatic vein was dominant in 11 cases, making up 40 ± 8% of the TLV. The left hepatic vein was never dominant. The volume contribution of the middle hepatic vein (MHV) was 114–782 ml for the right and 87–419 ml for the left hemiliver. Computer‐assisted planning allows for the 3D reconstruction of the vascular and biliary anatomy, automatic calculation of the total and territorial liver volumes, and risk analysis of hepatic vein dominance relationships. This comprehensive data acquisition supports preoperative evaluation and provides a high degree of safety for donors and improved outcomes for recipients.
Impact of Patient‐ and Disease‐Specific Factors on SLNB in Breast Cancer Patients. Are Current Guidelines Justified?
Authors: Bembenek A. , Fischer J. , Albrecht H. , Kemnitz E. , Gretschel S. , Schneider U. , Dresel S. , Schlag P. M.
Published: December 2006

Background

The evidence on which to base guidelines for sentinel lymph node biopsy (SLNB) in breast cancer is still limited. In order to facilitate the further implementation of renewed guidelines, we evaluated patient‐ and disease‐specific factors for their impact on the results of SLNB.

Materials and methods

Prospective data acquisition from patients undergoing surgery for primary invasive breast cancer was performed. All patients underwent SLNB using the radiocolloid or the combined technique. The association of patient‐ and disease‐specific factors to detection rate and false‐negative rate was calculated using univariate and multivariate analyses (P < 0.05 considered as significant). Calculation of the false‐negative rate was based on patients who underwent a backup axillary dissection.

Results

Among 455 consecutively enrolled patients, a significant inverse association to the detection rate was found for extracapsular extension of non‐SLN metastases, body mass index (BMI), number of involved lymph nodes, pT category, tumor size, and age. A significant association to the false‐negative rate to identify macrometastases was found for pT category, tumor size, and grading. Other factors, such as prior surgery, multicentric tumor growth, or vascular invasion, showed no influence. A cut‐point analysis revealed that a tumor size of 2 cm separated the collective of patients with the highest significance in regard to the false‐negative rate (9% vs. 25%).

Conclusion

Our results indicate that SLNB can be safely used in elderly and obese patients with multicentric tumors and those having undergone prior surgery for benign breast disease. However, the method should be applied with caution in patients with tumors larger than 2 cm.
Breast Cancer Local Recurrence: Risk Factors and Prognostic Relevance of Early Time to Recurrence
Authors: Neri A. , Marrelli D. , Rossi S. , De Stefano A. , Mariani F. , De Marco G. , Caruso S. , Corso G. , Cioppa T. , Pinto E. , Roviello F.
Published: December 2006

Background

Local recurrence occurs in 10%–20% of patients treated with breast‐conserving surgery for stage I–II breast cancer. The aim of the present study was to investigate breast cancer local recurrence, potential risk factors, and prognostic impact.

Methods

A total of 503 patients treated with breast‐conserving surgery were included in the study. All patients underwent axillary dissection and postoperative radiotherapy, and all patients had negative margins at pathological examination. Median follow‐up was 82 months. Local recurrence was classified as early when it occurred within 2 years from surgery. The risk factors for local recurrence and overall survival were estimated by univariate and multivariate analyses.

Results

Forty‐six cases (9.1%) of local recurrence were observed, 11 of which occurred within 24 months of surgery; the other 35, sometime later. Statistically significant risk factors for local recurrence were premenopausal status, peritumoral vascular invasion, multifocality, and absence of estrogen receptors. Independent negative prognostic factors for overall survival at 5 and 10 years were N stage, absence of estrogen receptors, and early time to recurrence. Overall survival at 10 years was 10.0% for patients with early recurrence, 87.5% for patients with late recurrence, and 87.9% for patients without recurrence.

Conclusions

None of the studied clinicopathological characteristics alone is a determinant for the choice of surgical treatment. Younger patients treated with breast‐conserving surgery should receive aggressive postsurgical treatment and should be followed with an intensive follow‐up program when metastatic axillary lymph nodes, negative estrogen receptors, or peritumoral vascular invasion are present.
Iatrogenic Vascular Injuries in Varicose Vein Surgery: a Systematic Review
Authors: Rudström Håkan , Björck Martin , Bergqvist David
Published: December 2006

Background

Iatrogenic vascular injuries during varicose vein surgery are serious. The aim of this study was to investigate their nature and consequences.

Method

A systematic literature research was performed.

Results

The incidence is low (0.0017%–0.3%). We found 81 patients suffering from 87 vascular injuries—44 arterial and 43 deep vein injuries.

Conclusion

Vascular injuries during varicose surgery are rare but serious. They are avoidable, and when they occur, early recognition is crucial.

Bleeding is a common symptom, especially in deep venous injury. In our study, we reviewed the literature on 81 patients with 87 vascular injuries. Laceration or division of the femoral vein dominated venous injuries (28/43). Partial stripping of the femoral vein was not common (4/43) and occurred when the strip probe passed into the deep veins through a perforator. Arterial stripping predominated in arterial injuries (17/44) and happened when stripping distally during a primary operation, as reported by experienced surgeons, in nonobese women. Major arterial complications resulted in ischemia, often with diagnostic delay and poor reconstruction results. Only 30% (13/44) of arterial injuries were detected peroperatively. The amputation rate was 34% (15/44), but rose to 100% if combined with intra‐arterial sclerotherapy (5/5 cases). When stripping an artery below the femoral artery, the amputation rate was high (42%; 5/12) and morbidity severe (85%; 11/12). All fatal injuries (5 cases) were venous. Anatomic knowledge and awareness of the possibility of vascular complications should be preventive. Early detection by routine checking of arterial circulation is important.
Effect of mid‐late mouse fetus' microenvironment on the growth of tumor cells after intrauterine transplantation
Authors: Ma Fang , Zhou Lan , Fang Liao‐Qiong , Bai Jin , Zhao Jie , Wang Yuan , Wang Zhi‐Biao
Published: December 2006

Successful intrauterine transplantation (IUT) of stem cells for treatment of fetal defects in some animal models of human diseases has prompted us to study the mechanisms of transplantation, immunological tolerance and embryonic environment. The objective of this study was to determine whether intrauterine transplantation of tumor cells would affect the survival and growth of the tumor cells themselves as well as fetus development. A total of 2 × 106 H22 cells or S180 cells were transplanted into the amniotic or abdominal cavity of NIH mice on D9–D12 or D13–D18 of gestation. The adult and newborn NIH mice which were inoculated with the same number of H22 cells and S180 cells by intraperitoneal injection were used as positive controls for the cancer bearing control group while undisrupted fetuses of the same gestation were used as negative controls (i.e. for the normal development) group. The development of fetuses transplanted with tumor cells in utero was monitored by several developmental indices, and the tumor growth of them were observed by some distinctive bearing cancer index. The H22 transplanted group was further assessed for minimal cancer bearing by detection of alpha‐fetoprotein (AFP) using radioimmunoassay (RIA) and reverse transcription‐polymerase chain reaction (RT‐PCR). In addition, tumor burden and the development of the F1 generation of the mice by IUT were also investigated. Protein kinase C (PKC) and proliferating cell nuclear antigen (PCNA) of GFP‐expressing H22 cells transplanted in the uterus were analyzed under laser confocal microscopy. There was no significant difference in the developmental indices between the experimental and control groups. HE staining of the major organs, including liver, kidney, and lung, showed that these organs properly developed. No tumor ascites were found in those delivered mice after intrauterine transplantation with H22 cells and S180 cells. Furthermore, as minimal bearing cancer index for H22 cells, AFP expression analyzed by RIA and RT‐PCR indicated that no tumor cells were detected in the experimental groups. The F1 progenies developed normally without any signs of tumor development. Fluorescence analysis revealed that expression of PKC and PCNA was markedly reduced in the H22 cells after injection for 24, 48, and 72 h. Our study showed that the tumor cells did not grow in the mice by intrauterine transplantation, whereas transplantation of the same number of tumor cells resulted in obvious ascites tumor in the adult and newborn mice. Furthermore, the differentiation and proliferation of H22 cells changed dramatically after injection. Our results suggest that, while the embryonic transplantation of tumor cells does not affect fetal development, the survival and growth of implanted tumor cells may be significantly inhibited in the embryonic microenvironment.
B
2
1
(
Σ
u
+
1
)
excited state decay dynamics in CS2
Authors: Townsend Dave , Satzger Helmut , Ejdrup Tine , Lee Anthony M. D. , Stapelfeldt Henrik , Stolow Albert
Published: December 2006

The authors report time resolved photoelectron spectra of the B21(Σu+1) state of CS2 at pump wavelengths in the region of 200nm. In contrast to previous studies, the authors find that the predissociation dynamics is not well described by a single exponential decay. Biexponential modeling of the authors’ data reveals a rapid decay pathway (τ<50fs), in addition to a longer lived channel (τ∼350–650fs) that displays a marked change in apparent lifetime when the polarization of the pump laser is rotated with respect to that of the probe. Since the initially populated B21(Σu+1) state may decay to form either S(D1) or S(P3) products (the latter produced via a spin-orbit induced crossing from a singlet to a triplet electronic surface), this lifetime observation may be rationalized in terms of changes in the relative ionization cross section of these singlet and triplet states of CS2 as a function of laser polarization geometry. The experimentally observed lifetime of the longer lived channel is therefore a superposition of these two pathways, both of which decay on very similar time scales.
Topological dynamics of holins in programmed bacterial lysis
Authors: Park Taehyun , Struck Douglas K. , Deaton John F. , Young Ry
Published: December 2006

The fate of phage-infected bacteria is determined by the holin, a small membrane protein that triggers to disrupt the membrane at a programmed time, allowing a lysozyme to attack the cell wall. S
21
68, the holin of phage 21, has two transmembrane domains (TMDs) with a predicted N-in, C-in topology. Surprisingly, TMD1 of S
21
68 was found to be dispensable for function, to behave as a SAR (“signal-anchor-release”) domain in exiting the membrane to the periplasm, and to engage in homotypic interactions in the soluble phase. The departure of TMD1 from the bilayer coincides with the lethal triggering of the holin and is accelerated by membrane depolarization. Basic residues added at the N terminus of S
21
68 prevent the escape of TMD1 to the periplasm and block hole formation by TMD2. Lysis thus depends on dynamic topology, in that removal of the inhibitory TMD1 from the bilayer frees TMD2 for programmed formation of lethal membrane lesions.
Processive enzyme mimic: Kinetics and thermodynamics of the threading and sliding process
Authors: Coumans Ruud G. E. , Elemans Johannes A. A. W. , Nolte Roeland J. M. , Rowan Alan E.
Published: December 2006

The kinetics and thermodynamics of the treading and dethreading process of polymers through the cavity of a synthetic toroidal host is investigated by studying its complexation with a series of end-functionalized polymers of different lengths containing an end group that is selectively recognized by the host. The system is designed in such a way that complexation is only observed if the host has traveled all of the way across the complete polymer. Detailed kinetic investigations using fluorescence spectroscopy have revealed that the barrier for this process is length dependent and most likely related to the stretching of the polymer. Moreover, the results indicate that our previously reported processive enzyme mimic most likely operates by randomly sliding along its macromolecular substrate.
Filamentation byEscherichia colisubverts innate defenses during urinary tract infection
Authors: Justice Sheryl S. , Hunstad David A. , Seed Patrick C. , Hultgren Scott J.
Published: December 2006

To establish disease, an infecting organism must overcome a vast array of host defenses. During cystitis, uropathogenicEscherichia coli(UPEC) subvert innate defenses by invading superficial umbrella cells and rapidly increasing in numbers to form intracellular bacterial communities (IBCs). In the late stages of the IBC pathway, filamentous and bacillary UPEC detach from the biofilm-like IBC, fluxing out of this safe haven to colonize the surrounding epithelium and initiate subsequent generations of IBCs, and eventually they establish a quiescent intracellular reservoir. Filamentous UPEC are not observed during acute infection in mice lacking functional Toll-like receptor 4 (TLR4), suggesting that the filamentous phenotype arises in response to host innate immunity. We investigated SulA, a cell division inhibitor associated with the SOS response, to gain insight into the role of filamentous UPEC in pathogenesis. A transcriptional reporter from PsulArevealed spatial and temporal differences in expression within IBCs, and it was active in the majority of filamentous UPEC. Although UTI89 and UTI89 ΔsulAboth formed first-generation IBCs equally well, UTI89 ΔsulAwas sharply attenuated in formation of second-generation IBCs and establishment of the quiescent intracellular reservoir. The virulence of UTI89 ΔsulAwas restored in TLR4-deficient mice, suggesting that filamentation facilitates the transition to additional rounds of IBC formation by subverting innate immune responses. These findings demonstrate that transient SulA-mediated inhibition of cell division is essential for UPEC virulence in the murine model of cystitis.
Selection for
Staphylococcus aureus
small-colony variants due to growth in the presence of
Pseudomonas aeruginosa
Authors: Hoffman Lucas R. , Déziel Eric , D'Argenio David A. , Lépine François , Emerson Julia , McNamara Sharon , Gibson Ronald L. , Ramsey Bonnie W. , Miller Samuel I.
Published: December 2006

Opportunistic infections are often polymicrobial. Two of the most important bacterial opportunistic pathogens of humans,
Pseudomonas aeruginosa
and
Staphylococcus aureus
, frequently are coisolated from infections of catheters, endotracheal tubes, skin, eyes, and the respiratory tract, including the airways of people with cystic fibrosis (CF). Here, we show that suppression of
S. aureus
respiration by a
P. aeruginosa
exoproduct, 4-hydroxy-2-heptylquinoline-
N
-oxide (HQNO), protects
S. aureus
during coculture from killing by commonly used aminoglycoside antibiotics such as tobramycin. Furthermore, prolonged growth of
S. aureus
with either
P. aeruginosa
or with physiological concentrations of pure HQNO selects for typical
S. aureus
small-colony variants (SCVs), well known for stable aminoglycoside resistance and persistence in chronic infections, including those found in CF. We detected HQNO in the sputum of CF patients infected with
P. aeruginosa
, but not in uninfected patients, suggesting that this HQNO-mediated interspecies interaction occurs in CF airways. Thus, in all coinfections with
P. aeruginosa
,
S. aureus
may be underappreciated as a pathogen because of the formation of antibiotic-resistant and difficult to detect small-colony variants. Interspecies microbial interactions, analogous to those mediated by HQNO, commonly may alter not only the course of disease and the response to therapy, but also the population structure of bacterial communities that promote the health of host animals, plants, and ecosystems.
Phosphoinositide 3-kinase γ/δ inhibition limits infarct size after myocardial ischemia/reperfusion injury
Authors: Doukas John , Wrasidlo Wolfgang , Noronha Glenn , Dneprovskaia Elena , Fine Richard , Weis Sara , Hood John , DeMaria Anthony , Soll Richard , Cheresh David
Published: December 2006

Although phosphoinositide 3-kinases (PI3Ks) play beneficial pro-cell survival roles during tissue ischemia, some isoforms (γ and δ) paradoxically contribute to the inflammation that damages these same tissues upon reperfusion. We therefore considered the possibility that selectively inhibiting proinflammatory PI3K isoforms during the reperfusion phase could ultimately limit overall tissue damage seen in ischemia/reperfusion injuries such as myocardial infarction. Panreactive and isoform-restricted PI3K inhibitors were identified by screening a novel chemical family; molecular modeling studies attributed isoform specificity based on rotational freedom of substituent groups. One compound (TG100-115) identified as a selective PI3K γ/δ inhibitor potently inhibited edema and inflammation in response to multiple mediators known to participate in myocardial infarction, including vascular endothelial growth factor and platelet-activating factor; by contrast, endothelial cell mitogenesis, a repair process important to tissue survival after ischemic damage, was not disrupted. In rigorous animal MI models, TG100-115 provided potent cardioprotection, reducing infarct development and preserving myocardial function. Importantly, this was achieved when dosing well after myocardial reperfusion (up to 3 h after), the same time period when patients are most accessible for therapeutic intervention. In conclusion, by targeting pathologic events occurring relatively late in myocardial damage, we have identified a potential means of addressing an elusive clinical goal: meaningful cardioprotection in the postreperfusion time period.
The first armadillo repeat is involved in the recognition and regulation of β-catenin phosphorylation by protein kinase CK1
Authors: Bustos Victor H. , Ferrarese Anna , Venerando Andrea , Marin Oriano , Allende Jorge E. , Pinna Lorenzo A.
Published: December 2006

Multiple phosphorylation of β-catenin by glycogen synthase kinase 3 (GSK3) in the Wnt pathway is primed by CK1 through phosphorylation of Ser-45, which lacks a typical CK1 canonical sequence. Synthetic peptides encompassing amino acids 38–64 of β-catenin are phosphorylated by CK1 on Ser-45 with low affinity (
K
m
≈1 mM), whereas intact β-catenin is phosphorylated at Ser-45 with very high affinity (
K
m
≈200 nM). Peptides extended to include a putative CK1 docking motif (FXXXF) at 70–74 positions or a F74AA mutation in full-length β-catenin had no significant effect on CK1 phosphorylation efficiency. β-Catenin C-terminal deletion mutants up to residue 181 maintained their high affinity, whereas removal of the 131–181 fragment, corresponding to the first armadillo repeat, was deleterious, resulting in a 50-fold increase in
K
m
value. Implication of the first armadillo repeat in β-catenin targeting by CK1 is supported in that the Y142E mutation, which mimics phosphorylation of Tyr-142 by tyrosine kinases and promotes dissociation of β-catenin from α-catenin, further improves CK1 phosphorylation efficiency, lowering the
K
m
value to <50 nM, approximating the physiological concentration of β-catenin. In contrast, α-catenin, which interacts with the N
-
terminal region of β-catenin, prevents Ser-45 phosphorylation of CK1 in a dose-dependent manner. Our data show that the integrity of the N-terminal region and the first armadillo repeat are necessary and sufficient for high-affinity phosphorylation by CK1 of Ser-45. They also suggest that β-catenin association with α-catenin and β-catenin phosphorylation by CK1 at Ser-45 are mutually exclusive.
Identification of long-range regulatory elements in the protocadherin-α gene cluster
Authors: Ribich Scott , Tasic Bosiljka , Maniatis Tom
Published: December 2006

The clustered protocadherins (Pcdh) are encoded by three closely linked gene clusters (
Pcdh
-α, -β, and -γ) that span nearly 1 million base pairs of DNA. The
Pcdh
-α gene cluster encodes a family of 14 distinct cadherin-like cell surface proteins that are expressed in neurons and are present at synaptic junctions. Individual
Pcdh
-α mRNAs are assembled from one of 14 “variable” (V) exons and three “constant” exons in a process that involves both differential promoter activation and alternative pre-mRNA splicing. In individual neurons, only one (and rarely two) of the
Pcdh
α1–12 promoters is independently and randomly activated on each chromosome. Thus, in most cells, this unusual form of monoallelic expression leads to the expression of two different
Pcdh
-α 1–12 V exons, one from each chromosome. The two remaining V exons in the cluster (
Pcdh
-αC1 and αC2) are expressed biallelically in every neuron. The mechanisms that underlie promoter choice and monoallelic expression in the
Pcdh
-α gene cluster are not understood. Here we report the identification of two long-range cis-regulatory elements in the
Pcdh
-α gene cluster, HS5–1 and HS7. We show that HS5–1 is required for maximal levels of expression from the
Pcdh
α1–12 and αC1 promoters, but not the
Pcdh
-αC2 promoter. The nearly cluster-wide requirement of the HS5–1 element is consistent with the possibility that the monoallelic expression of
Pcdh
-α V exons is a consequence of competition between individual V exon promoters for the two regulatory elements.
Bidirectional signaling between calcium channels of skeletal muscle requires multiple direct and indirect interactions
Authors: Sheridan David C. , Takekura Hiroaki , Franzini-Armstrong Clara , Beam Kurt G. , Allen Paul D. , Perez Claudio F.
Published: December 2006

We have defined regions of the skeletal muscle ryanodine receptor (RyR1) essential for bidirectional signaling with dihydropyridine receptors (DHPRs) and for the organization of DHPR into tetrad arrays by expressing RyR1–RyR3 chimerae in dyspedic myotubes. RyR1–RyR3 constructs bearing RyR1 residues 1–1681 restored wild-type DHPR tetrad arrays and, in part, skeletal-type excitation–contraction (EC) coupling (orthograde signaling) but failed to enhance DHPR Ca
2+
currents (retrograde signaling) to WT RyR1 levels. Within this region, the D2 domain (amino acids 1272–1455), although ineffective on its own, dramatically enhanced the formation of tetrads and EC coupling rescue by constructs that otherwise are only partially effective. These findings suggest that the orthograde signal and DHPR tetrad formation require the contributions of numerous RyR regions. Surprisingly, we found that RyR3, although incapable of supporting EC coupling or tetrad formation, restored a significant level of Ca
2+
current, revealing a functional interaction with the skeletal muscle DHPR. Thus, our data support the hypotheses that (
i
) the structural/functional link between RyR1 and the skeletal muscle DHPR requires multiple interacting regions, (
ii
) the D2 domain of RyR1 plays a key role in stabilizing this interaction, and (
iii
) a form of retrograde signaling from RyR3 to the DHPR occurs in the absence of direct protein–protein interactions.
Modulation of Leydig cell function by cyclic nucleotide phosphodiesterase 8A
Authors: Vasta Valeria , Shimizu-Albergine Masami , Beavo Joseph A.
Published: December 2006

Leydig cells produce testosterone in the testes under the pulsatile control of pituitary luteinizing hormone (LH). cAMP is the intracellular messenger for LH action on steroidogenesis, and pharmacological evidence indicates that the response to LH can be modulated by cyclic nucleotide phosphodiesterases (PDEs). However the types and roles of the PDEs present in Leydig cells have not been fully defined. We report here that PDE8A is expressed in Leydig cells, and using PDE8A knockout mice we provide evidence that PDE8A is a key regulator of LH signaling and steroidogenesis. A 4-fold increase in the sensitivity to LH for testosterone production was detected in Leydig cells isolated from PDE8A knockout mice. In Leydig cells from wild-type mice, 3-isobutyl-1-methylxanthine, a compound that inhibits all cAMP PDEs except PDE8A, elicited only a small increase in the sensitivity of testosterone production to LH. However, in the PDE8-null mice, the effect of this inhibitor is much more pronounced. These observations indicate that PDE8A and at least one other PDE control the same or a complementary pool of cAMP that mediates LH-regulated steroidogenesis. Overall, these results suggest that pharmacological manipulation of PDE8A, alone or in combination with other PDEs present in Leydig cells, may be exploited to modulate testosterone synthesis and possibly to treat various conditions where the local levels of this androgen need to be altered.
Order from disorder: Self-organization in mammalian hair patterning
Authors: Wang Yanshu , Badea Tudor , Nathans Jeremy
Published: December 2006

Hairs, feathers, and scales normally exhibit precise orientations with respect to the body axes. In
Frizzled6
(
Fz6
)
−/−
mice, the global orientation of hair follicles is disrupted, leading to waves, whorls, and tufts, each comprising many hundreds of hairs. By analyzing the orientation of developing hair follicles, we observed that the nearly parallel arrangement of wild-type (WT) hairs arises from fields of imperfectly aligned follicles, and that the
Fz6
−/−
hair patterns arise from fields of grossly misoriented or randomly oriented follicles. Despite their large size, both mutant and WT hair follicles display a remarkable and unexpected plasticity, reorienting on a time scale of days in what seems to be a self-organized refinement process. The essential features of this process can be studied with a simple cellular automata model in which a local consensus “rule” acts iteratively to bias each hair's orientation in favor of the average orientation of its neighbors. These experiments define two systems for hair orientation: a global orienting system that acts early in development and is
Fz6
-dependent, and a local self-organizing system that acts later and is
Fz6
independent.
Structural transitions of complement component C3 and its activation products
Authors: Nishida Noritaka , Walz Thomas , Springer Timothy A.
Published: December 2006

Complement sensitizes pathogens for phagocytosis and lysis. We use electron microscopy to examine the structural transitions in the activation of the pivotal protein in the complement pathway, C3. In the cleavage product C3b, the position of the thioester domain moves ≈100 Å, which becomes covalently coupled to antigenic surfaces. In the iC3b fragment, cleavage in an intervening domain creates a long flexible linker between the thioester domain and the macroglobulin domain ring of C3. Studies on two products of nucleophile addition to C3 reveal a structural intermediate in activation, and a final product, in which the anaphylatoxin domain has undergone a remarkable movement through the macroglobulin ring.
Site-directed alkylation and the alternating access model for LacY
Authors: Kaback H. Ronald , Dunten R. , Frillingos S. , Venkatesan P. , Kwaw I. , Zhang W. , Ermolova Natalia
Published: December 2006

In a functional lactose permease mutant from
Escherichia coli
(LacY) devoid of native Cys residues, almost every residue was replaced individually with Cys and tested for reactivity with the permeant alkylating agent
N
-ethylmaleimide in right-side-out membrane vesicles. Here we present the results in the context of the crystal structure of LacY. Engineered Cys replacements located near or within the inward-facing hydrophilic cavity or at other solvent-accessible positions in LacY react well with this alkylating agent. Cys residues facing the low dielectric of the membrane or located in tightly packed regions of the structure react poorly. Remarkably, in the presence of ligand, increased reactivity is observed with Cys replacements located predominantly on the periplasmic side of the sugar-binding site. In contrast, other Cys replacements largely on the cytoplasmic side of the binding site exhibit decreased reactivity. Furthermore, both sets of Cys replacements in the putative cavities are located at the periplasmic (increased reactivity) and cytoplasmic (decreased reactivity) ends of the same helices and distributed in a pseudosymmetrical manner. The results are consistent with a model in which the single sugar-binding site in the approximate middle of the molecule is alternately exposed to either side of the membrane due to opening and closing of cytoplasmic and periplasmic hydrophilic cavities.
On the height of cell aggregates formed with positive dielectrophoresis
Authors: Venkatesh A G , Markx Gerard H
Published: December 2006

The influence of a number of parameters on the height of cell aggregates formed by positive dielectrophoresis was systematically investigated. It was found that the aggregate height could be increased by following a number of simple rules. Interdigitated electrodes with oppositely placed castellations gave higher aggregate heights than interdigitated parallel electrodes. The optimal frequency was identified to be 1 MHz. To obtain the highest aggregates, the conductivity of the suspending medium should be kept to the lowest value obtainable, as should the fluid flow rate through the chamber. Aggregate height increased with increasing voltage, but the effect of increasing the voltage diminished as higher aggregate heights were reached. Optima were observed in the aggregate height as a function of the electrode characteristic size, which depended on the cell type and cell size. It was shown to be possible to create aggregate heights of over 150 µm for all the three cell types (bacteria, yeasts and mammalian cells) employed, using voltages of only 20 Vpk–pk.
The Rice Kinase Database. A Phylogenomic Database for the Rice Kinome
Authors: Dardick Christopher , Chen Johann , Richter Todd , Ouyang Shu , Ronald Pamela
Published: December 2006

The rice (Oryza sativa) genome contains 1,429 protein kinases, the vast majority of which have unknown functions. We created a phylogenomic database (http://rkd.ucdavis.edu) to facilitate functional analysis of this large gene family. Sequence and genomic data, including gene expression data and protein-protein interaction maps, can be displayed for each selected kinase in the context of a phylogenetic tree allowing for comparative analysis both within and between large kinase subfamilies. Interaction maps are easily accessed through links and displayed using Cytoscape, an open source software platform. Chromosomal distribution of all rice kinases can also be explored via an interactive interface.
Saponin Biosynthesis in Saponaria vaccaria. cDNAs Encoding β-Amyrin Synthase and a Triterpene Carboxylic Acid Glucosyltransferase
Authors: Meesapyodsuk Dauenpen , Balsevich John , Reed Darwin W. , Covello Patrick S.
Published: December 2006

Saponaria vaccaria (Caryophyllaceae), a soapwort, known in western Canada as cowcockle, contains bioactive oleanane-type saponins similar to those found in soapbark tree (Quillaja saponaria; Rosaceae). To improve our understanding of the biosynthesis of these saponins, a combined polymerase chain reaction and expressed sequence tag approach was taken to identify the genes involved. A cDNA encoding a β-amyrin synthase (SvBS) was isolated by reverse transcription-polymerase chain reaction and characterized by expression in yeast (Saccharomyces cerevisiae). The SvBS gene is predominantly expressed in leaves. A S. vaccaria developing seed expressed sequence tag collection was developed and used for the isolation of a full-length cDNA bearing sequence similarity to ester-forming glycosyltransferases. The gene product of the cDNA, classified as UGT74M1, was expressed in Escherichia coli, purified, and identified as a triterpene carboxylic acid glucosyltransferase. UGT74M1 is expressed in roots and leaves and appears to be involved in monodesmoside biosynthesis in S. vaccaria.