bluuebunny/crossref_metadata_2025 huggingface dataset:
Patterns of delivery of dietetic care in private practice for patients referred under Medicare Chronic Disease Management: results of a national survey
Authors: Cant Robyn P.
Published: May 2010

A national survey was used to examine patterns of delivery of dietetic care for patients referred to private practitioners under Medicare Chronic Disease Management (CDM). This asked dietitians about referrals from general practitioners, patient management, fees charged and patient billing. There were 356 (47%) Australian private practice dietitians who responded to the questionnaire; 330 (94%) were Medicare providers. They described a counselling-type service and inability to complete initial patient education within funded consultation time. Many provided a longer consultation than was reported as being funded by Medicare. Fees for initial appointments were generally higher than the scheduled Medical Benefit Scheme fee of AU$56.25 (median $80), requiring patients to pay a fee gap. For review appointments, two of every five dietitians bulk-billed or charged an identical fee ($47.85). Providers communicated by written reports (as required under Medicare policy). There was little evidence of team-based chronic care management. The dietetics Medicare CDM process should mirror other counselling-type Medicare services which provide for both longer and more frequent consultations and higher payment. System integration between dietitians and general practitioners is required to achieve true collaboration and team care of chronic disease patients.
What is known about the topic?Medicare ‘Chronic Disease Management’ program allows eligible patients with chronic or complex medical conditions subsidized consultations with accredited dietitians in private clinics. We know little about how this program is delivered by GPs and dietitians.
What does this paper add?This paper reports data on a first evaluation. Surveyed dietitians viewed chronic cases as complex and described barriers to their practice imposed by Medicare policy.
What are the implications for practitioners?Changes in Medicare CDM policy and dietetic practices are required to achieve true collaboration and team care of dietetic patients with chronic diseases.
Cost effectiveness of a general practice chronic disease management plan for coronary heart disease in Australia
Authors: Chew Derek P. , Carter Robert , Rankin Bree , Boyden Andrew , Egan Helen
Published: May 2010

Background.The cost effectiveness of a general practice-based program for managing coronary heart disease (CHD) patients in Australia remains uncertain. We have explored this through an economic model. Methods.A secondary prevention program based on initial clinical assessment and 3 monthly review, optimising of pharmacotherapies and lifestyle modification, supported by a disease registry and financial incentives for quality of care and outcomes achieved was assessed in terms of incremental cost effectiveness ratio (ICER), in Australian dollars per disability adjusted life year (DALY) prevented. Results.Based on 2006 estimates, 263 487 DALYs were attributable to CHD in Australia. The proposed program would add $115 650 000 to the annual national heath expenditure. Using an estimated 15% reduction in death and disability and a 40% estimated program uptake, the program’s ICER is $8081 per DALY prevented. With more conservative estimates of effectiveness and uptake, estimates of up to $38 316 per DALY are observed in sensitivity analysis. Conclusions.Although innovation in CHD management promises improved future patient outcomes, many therapies and strategies proven to reduce morbidity and mortality are available today. A general practice-based program for the optimal application of current therapies is likely to be cost-effective and provide substantial and sustainable benefits to the Australian community. What is known about this topic?Chronic disease management programs are known to provide gains with respect to reductions in death and disability among patients with coronary heart disease. The cost effectiveness of such programs in the Australian context is not known. What does this paper add?This paper suggests that implementing a coronary heart disease program in Australia is highly cost-effective across a broad range of assumptions of uptake and effectiveness. What are the implications for practitioners? These data provide the economic rationale for the implementation of a chronic disease management program with a disease registry and regular review in Australia.
Medicare and chronic disease management: integrated care as an exceptional circumstance?
Authors: Taylor Michael J. , Swerissen Hal
Published: May 2010

Chronic disease represents a significant challenge to the design and reform of the Australian healthcare system. The Medicare Benefits Schedule (MBS) provides a framework of numerous chronic disease management programs; however, their use at the patient level is complex. This analysis of the MBS chronic disease framework uses a hypothetical case study of a diabetic patient (with disease-related complications and a complex psychosocial background) to illustrate the difficulties in delivering appropriate multidisciplinary chronic disease care under the MBS. The complexities at each step – from care planning, service provision, and monitoring and review – are described, as are the intricacies involved in providing patient care under different MBS programs as well as those in the broader health and community care system. As demonstrated by this case study, under certain circumstances the provision of truly integrated care to this hypothetical patient would constitute an ‘exceptional circumstance’ under the MBS. Although quality improvement efforts can improve functioning within the limitations of the current system, system-wide reforms are necessary to overcome complexity and fragmentation. What is known about the topic?Chronic disease management requires optimal health system design to provide appropriate patient care. In Australia, the Medicare Benefits Schedule (MBS) provides chronic disease-focussed programs, but the multitude of available programs and items are administratively complex, overlapping and subject to claiming incompatibilities. What does this paper add? This paper illustrates the complexity of the various MBS programs for chronic disease management using a case study of the potential service response to a single diabetic patient with disease-related complications and a complex psychosocial background. This analysis illustrates the manifold problematic interactions and incompatibilities that may arise in relation to this hypothetical patient. What are the implications for practitioners?Under the current MBS framework, providing patients with optimum chronic disease management requires both clinical and administrative skill on the part of GPs. Time spent on administrative requirements is time away from clinical care. Although quality improvement efforts may improve functioning within the existing system to a certain extent, broader system reforms are necessary to support optimal chronic disease management in Australia.
Interprofessional education in clinical practice: not a single vaccine
Authors: Henderson Amanda J. , O'Keefe Maree F. , Alexander Heather G.
Published: May 2010

In increasingly complex health service environments, the quality of teamwork and co-operation between doctors, nurses and allied health professionals, is ‘under the microscope’. Interprofessional education (IPE), a process whereby health professionals learn ‘from, with and about each other’, is advocated as a response to widespread calls for improved communication and collaboration between healthcare professionals.
Although there is much that is commendable in IPE, the authors caution that the benefits may be overstated if too much is attributed to, or expected of, IPE activities. The authors propose that clarity is required around what can realistically be achieved. Furthermore, engagement with clinicians in the clinical practice setting who are instrumental in assisting students make sense of their knowledge through practice, is imperative for sustainable outcomes.
Ventral lateral and DN1 clock neurons mediate distinct properties of male sex drive rhythm in
Drosophila
Authors: Fujii Shinsuke , Amrein Hubert
Published: May 2010

Male sex drive rhythm (MSDR) in
Drosophila
is a circadian behavior only observed in the social context of male-female pairs. In the presence of a female, males exhibit long periods of courtship activity with a pronounced rest phase at dusk, although isolated males exhibit an activity peak at dusk. The molecular mechanisms regulating the switch between these activity patterns are unknown. Here, we genetically manipulate the molecular clock in different subsets of neurons and find that proper oscillation of the molecular clock in ventral lateral neurons is essential for MSDR. These neurons express pigment-dispersing factor, the lack of which disrupts MSDR. Furthermore, we show that a cluster of dorsal neurons (DN1s) requires the molecular clock to synchronize the trough phase at dusk in MSDR and to establish the evening peak in single fly locomotor rhythm (SLR). Finally, we provide evidence that DN1s exert their roles in MSDR and SLR via distinct signaling pathways.
G protein-coupled receptors function as logic gates for nanoparticle binding and cell uptake
Authors: Hild Wolfgang , Pollinger Klaus , Caporale Andrea , Cabrele Chiara , Keller Max , Pluym Nicola , Buschauer Armin , Rachel Reinhard , Tessmar Joerg , Breunig Miriam , Goepferich Achim
Published: May 2010

More selective interactions of nanoparticles with cells would substantially increase their potential for diagnostic and therapeutic applications. Thus, it would not only be highly desirable that nanoparticles can be addressed to any cell with high target specificity and affinity, but that we could unequivocally define whether they rest immobilized on the cell surface as a diagnostic tag, or if they are internalized to serve as a delivery vehicle for drugs. To date no class of targets is known that would allow direction of nanoparticle interactions with cells alternatively into one of these mutually exclusive events. Using MCF-7 breast cancer cells expressing the human Y
1
-receptor, we demonstrate that G protein-coupled receptors provide us with this option. We show that quantum dots carrying a surface-immobilized antagonist remain with nanomolar affinity on the cell surface, and particles carrying an agonist are internalized upon receptor binding. The receptor functions like a logic “and-gate” that grants cell access only to those particles that carry a receptor ligand “and” where the ligand is an agonist. We found that agonist- and antagonist-modified nanoparticles bind to several receptor molecules at a time. This multiligand binding leads to five orders of magnitude increased-receptor affinities, compared with free ligand, in displacement studies. More than 800 G protein-coupled receptors in humans provide us with the paramount advantage that targeting of a plethora of cells is possible, and that switching from cell recognition to cell uptake is simply a matter of nanoparticle surface modification with the appropriate choice of ligand type.
Conserved role for autophagy in Rho1-mediated cortical remodeling and blood cell recruitment
Authors: Kadandale Pavan , Stender Joshua D. , Glass Christopher K. , Kiger Amy A.
Published: May 2010

Dynamic regulation of cell shape underlies many developmental and immune functions. Cortical remodeling is achieved under the central control of Rho GTPase pathways that modulate an exquisite balance in the dynamic assembly and disassembly of the cytoskeleton and focal adhesions. Macroautophagy (autophagy), associated with bulk cytoplasmic remodeling through lysosomal degradation, has clearly defined roles in cell survival and death. Moreover, it is becoming apparent that proteins, organelles, and pathogens can be targeted for autophagic clearance by selective mechanisms, although the extent and roles of such degradation are unclear. Here we report a conserved role for autophagy specifically in the cortical remodeling of
Drosophila
blood cells (hemocytes) and mouse macrophages. Continuous autophagy was required for integrin-mediated hemocyte spreading and Rho1-induced cell protrusions. Consequently, hemocytes disrupted for autophagy were impaired in their recruitment to epidermal wounds. Cell spreading required
ref(2)P
, the
Drosophila
p62 multiadaptor, implicating selective autophagy as a novel mechanism for modulating cortical dynamics. These results illuminate a specific and conserved role for autophagy as a regulatory mechanism for cortical remodeling, with implications for immune cell function.
Gold nanorod delivery of an ssRNA immune activator inhibits pandemic H1N1 influenza viral replication
Authors: Chakravarthy Krishnan V. , Bonoiu Adela C. , Davis William G. , Ranjan Priya , Ding Hong , Hu Rui , Bowzard J. Bradford , Bergey Earl J. , Katz Jacqueline M. , Knight Paul R. , Sambhara Suryaprakash , Prasad Paras N.
Published: May 2010

The emergence of the pandemic 2009 H1N1 influenza virus has become a world-wide health concern. As drug resistance appears, a new generation of therapeutic strategies will be required. Here, we introduce a nanotechnology approach for the therapy of pan-demic and seasonal influenza virus infections. This approach uses gold nanorods (GNRs) to deliver an innate immune activator, pro-ducing a localized therapeutic response. We demonstrated the utility of a biocompatible gold nanorod, GNR-5′PPP-ssRNA nanoplex, as an antiviral strategy against type A influenza virus. In human respiratory bronchial epithelial cells, this nanoplex activated the retinoic acid-inducible gene I (RIG-I) pathogen recognition pathway, resulting in increased expression of IFN-β and other IFN-stimulated genes (ISGs) (e.g.,
PKR, MDA5, IRF1, IRF7,
and
MX1
). This increase in type I IFN and ISGs resulted in a decrease in the replication of H1N1 influenza viruses. These findings suggest that further evaluation of biocompatible nanoplexes as unique antivirals for treatment of seasonal and pandemic influenza viruses is warranted.
In vivo expansion of naive and activated CD4
+
CD25
+
FOXP3
+
regulatory T cell populations in interleukin-2–treated HIV patients
Authors: Weiss Laurence , Letimier Fabrice A. , Carriere Matthieu , Maiella Sylvie , Donkova-Petrini Vladimira , Targat Brice , Benecke Arndt , Rogge Lars , Levy Yves
Published: May 2010

HIV-1 infection is characterized by a progressive decline in CD4
+
T cells leading to a state of profound immunodeficiency. IL-2 therapy has been shown to improve CD4
+
counts beyond that observed with antiretroviral therapy. Recent phase III trials revealed that despite a sustained increase in CD4
+
counts, IL-2-treated patients did not experience a better clinical outcome [Abrams D, et al. (2009)
N Engl J Med
361(16):1548–1559]. To explain these disappointing results, we have studied phenotypic, functional, and molecular characteristics of CD4
+
T cell populations in IL-2-treated patients. We found that the principal effect of long-term IL-2 therapy was the expansion of two distinct CD4
+
CD25
+
T cell populations (CD4
+
CD25
lo
CD127
lo
FOXP3
+
and CD4
+
CD25
hi
CD127
lo
FOXP3
hi
) that shared phenotypic markers of Treg but could be distinguished by the levels of CD25 and FOXP3 expression. IL-2-expanded CD4
+
CD25
+
T cells suppressed proliferation of effector cells in vitro and had gene expression profiles similar to those of natural regulatory CD4
+
CD25
hi
FOXP3
+
T cells (Treg) from healthy donors, an immunosuppressive T cell subset critically important for the maintenance of self-tolerance. We propose that the sustained increase of the peripheral Treg pool in IL-2-treated HIV patients may account for the unexpected clinical observation that patients with the greatest expansion of CD4
+
T cells had a higher relative risk of clinical progression to AIDS.
Functional analyses of variants reveal a significant role for dominant negative and common alleles in oligogenic Bardet–Biedl syndrome
Authors: Zaghloul Norann A. , Liu Yangjian , Gerdes Jantje M. , Gascue Cecilia , Oh Edwin C. , Leitch Carmen C. , Bromberg Yana , Binkley Jonathan , Leibel Rudolph L. , Sidow Arend , Badano Jose L. , Katsanis Nicholas
Published: May 2010

Technological advances hold the promise of rapidly catalyzing the discovery of pathogenic variants for genetic disease. However, this possibility is tempered by limitations in interpreting the functional consequences of genetic variation at candidate loci. Here, we present a systematic approach, grounded on physiologically relevant assays, to evaluate the mutational content (125 alleles) of the 14 genes associated with Bardet–Biedl syndrome (BBS). A combination of in vivo assays with subsequent in vitro validation suggests that a significant fraction of BBS-associated mutations have a dominant-negative mode of action. Moreover, we find that a subset of common alleles, previously considered to be benign, are, in fact, detrimental to protein function and can interact with strong rare alleles to modulate disease presentation. These data represent a comprehensive evaluation of genetic load in a multilocus disease. Importantly, superimposition of these results to human genetics data suggests a previously underappreciated complexity in disease architecture that might be shared among diverse clinical phenotypes.
The
Mohawk
homeobox gene is a critical regulator of tendon differentiation
Authors: Ito Yoshiaki , Toriuchi Naoya , Yoshitaka Teruhito , Ueno-Kudoh Hiroe , Sato Tempei , Yokoyama Shigetoshi , Nishida Keiichiro , Akimoto Takayuki , Takahashi Michiko , Miyaki Shigeru , Asahara Hiroshi
Published: May 2010

Mohawk
(
Mkx
) is a member of the Three Amino acid Loop Extension superclass of atypical homeobox genes that is expressed in developing tendons. To investigate the in vivo functions of Mkx, we generated
Mkx
−/−
mice. These mice had hypoplastic tendons throughout the body. Despite the reduction in tendon mass, the cell number in tail tendon fiber bundles was similar between wild-type and
Mkx
−/−
mice. We also observed small collagen fibril diameters and a down-regulation of type I collagen in
Mkx
−/−
tendons. These data indicate that Mkx plays a critical role in tendon differentiation by regulating type I collagen production in tendon cells.
Structural organization of a filamentous influenza A virus
Authors: Calder Lesley J. , Wasilewski Sebastian , Berriman John A. , Rosenthal Peter B.
Published: May 2010

Influenza is a lipid-enveloped, pleomorphic virus. We combine electron cryotomography and analysis of images of frozen-hydrated virions to determine the structural organization of filamentous influenza A virus. Influenza A/Udorn/72 virions are capsule-shaped or filamentous particles of highly uniform diameter. We show that the matrix layer adjacent to the membrane is an ordered helix of the M1 protein and its close interaction with the surrounding envelope determines virion morphology. The ribonucleoprotein particles (RNPs) that package the genome segments form a tapered assembly at one end of the virus interior. The neuraminidase, which is present in smaller numbers than the hemagglutinin, clusters in patches and are typically present at the end of the virion opposite to RNP attachment. Incubation of virus at low pH causes a loss of filamentous morphology, during which we observe a structural transition of the matrix layer from its helical, membrane-associated form to a multilayered coil structure inside the virus particle. The polar organization of the virus provides a model for assembly of the virion during budding at the host membrane. Images and tomograms of A/Aichi/68 X-31 virions show the generality of these conclusions to non-filamentous virions.
Control of bacterial iron homeostasis by manganese
Authors: Puri Sumant , Hohle Thomas H. , O'Brian Mark R.
Published: May 2010

Perception and response to nutritional iron availability by bacteria are essential to control cellular iron homeostasis. The Irr protein from
Bradyrhizobium japonicum
senses iron through the status of heme biosynthesis to globally regulate iron-dependent gene expression. Heme binds directly to Irr to trigger its degradation. Here, we show that severe manganese limitation created by growth of a Mn
2+
transport mutant in manganese-limited media resulted in a cellular iron deficiency. In wild-type cells, Irr levels were attenuated under manganese limitation, resulting in reduced promoter occupancy of target genes and altered iron-dependent gene expression. Irr levels were high regardless of manganese availability in a heme-deficient mutant, indicating that manganese normally affects heme-dependent degradation of Irr. Manganese altered the secondary structure of Irr in vitro and inhibited binding of heme to the protein. We propose that manganese limitation destabilizes Irr under low-iron conditions by lowering the threshold of heme that can trigger Irr degradation. The findings implicate a mechanism for the control of iron homeostasis by manganese in a bacterium.
Inhibition of lung tumor growth by complex pulmonary delivery of drugs with oligonucleotides as suppressors of cellular resistance
Authors: Garbuzenko Olga B. , Saad Maha , Pozharov Vitaly P. , Reuhl Kenneth R. , Mainelis Gediminas , Minko Tamara
Published: May 2010

Development of cancer cell resistance, low accumulation of therapeutic drug in the lungs, and severe adverse treatment side effects represent main obstacles to efficient chemotherapy of lung cancer. To overcome these difficulties, we propose inhalation local delivery of anticancer drugs in combination with suppressors of pump and nonpump cellular resistance. To test this approach, nanoscale-based delivery systems containing doxorubicin as a cell death inducer, antisense oligonucleotides targeted to MRP1 mRNA as a suppressor of pump resistance and to BCL2 mRNA as a suppressor of nonpump resistance, were developed and examined on an orthotopic murine model of human lung carcinoma. The experimental results show high antitumor activity and low adverse side effects of proposed complex inhalatory treatment that cannot be achieved by individual components applied separately. The present work potentially contributes to the treatment of lung cancer by describing a unique combinatorial local inhalation delivery of drugs and suppressors of pump and nonpump cellular resistance.
B-RafV600Eand thrombospondin-1 promote thyroid cancer progression
Authors: Nucera Carmelo , Porrello Alessandro , Antonello Zeus Andrea , Mekel Michal , Nehs Matthew A. , Giordano Thomas J. , Gerald Damien , Benjamin Laura E. , Priolo Carmen , Puxeddu Efisio , Finn Stephen , Jarzab Barbara , Hodin Richard A. , Pontecorvi Alfredo , Nose Vânia , Lawler Jack , Parangi Sareh
Published: May 2010

Although B-RafV600Eis the most common somatic mutation in papillary thyroid carcinoma (PTC), how it induces tumor aggressiveness is not fully understood. Using gene set enrichment analysis and in vitro and in vivo functional studies, we identified and validated a B-RafV600Egene set signature associated with tumor progression in PTCs. An independent cohort of B-RafV600E-positive PTCs showed significantly higher expression levels of many extracellular matrix genes compared with controls. We performed extensive in vitro and in vivo validations on thrombospondin-1 (TSP-1), because it has been previously shown to be important in the regulation of tumor angiogenesis and metastasis and is present in abundance in tumor stroma. Knockdown of B-RafV600Eresulted in TSP-1 down-regulation and a reduction of adhesion and migration/invasion of human thyroid cancer cells. Knockdown of TSP-1 resulted in a similar phenotype. B-RafV600Ecells in which either B-RafV600Eor TSP-1 were knocked down were implanted orthotopically into the thyroids of immunocompromised mice, resulting in significant reduction in tumor size and fewer pulmonary metastases from the primary carcinoma as compared with the control cells. Treatment of orthotopic thyroid tumors, initiated 1 week after tumor cell implantation with PLX4720, an orally available selective inhibitor of B-RafV600E, caused a significant tumor growth delay and decreased distant metastases, without evidence of toxicity. In conclusion, B-RafV600Eplays an important role in PTC progression through genes (i.e., TSP-1) important in tumor invasion and metastasis. Testing of a patient's thyroid cancer for B-RafV600Ewill yield important information about potential tumor aggressiveness and also allow for future use of targeted therapies with selective B-RafV600Einhibitors, such as PLX4720.
African apes as reservoirs of
Plasmodium falciparum
and the origin and diversification of the
Laverania
subgenus
Authors: Duval Linda , Fourment Mathieu , Nerrienet Eric , Rousset Dominique , Sadeuh Serge A. , Goodman Steven M. , Andriaholinirina Nicole V. , Randrianarivelojosia Milijaona , Paul Richard E. , Robert Vincent , Ayala Francisco J. , Ariey Frédéric
Published: May 2010

We investigated two mitochondrial genes (
cytb
and
cox1
), one plastid gene (
tufA
), and one nuclear gene (
ldh
) in blood samples from 12 chimpanzees and two gorillas from Cameroon and one lemur from Madagascar. One gorilla sample is related to
Plasmodium falciparum
, thus confirming the recently reported presence in gorillas of this parasite. The second gorilla sample is more similar to the recently defined
Plasmodium gaboni
than to the
P. falciparum–Plasmodium reichenowi
clade, but distinct from both. Two chimpanzee samples are
P. falciparum
. A third sample is
P. reichenowi
and two others are
P. gaboni
. The other chimpanzee samples are different from those in the ape clade: two are
Plasmodium ovale
, and one is
Plasmodium malariae
. That is, we have found three human
Plasmodium
parasites in chimpanzees. Four chimpanzee samples were mixed: one species was
P. reichenowi
; the other species was
P. gaboni
in three samples and
P. ovale
in the fourth sample. The lemur sample, provisionally named
Plasmodium malagasi
, is a sister lineage to the large cluster of primate parasites that does not include
P. falciparum
or ape parasites, suggesting that the
falciparum
+ ape parasite cluster (
Laverania
clade) may have evolved from a parasite present in hosts not ancestral to the primates. If malignant malaria were eradicated from human populations, chimpanzees, in addition to gorillas, might serve as a reservoir for
P. falciparum
.
LuxR homolog-independent gene regulation by acyl-homoserine lactones in
Pseudomonas aeruginosa
Authors: Chugani Sudha , Greenberg Everett Peter
Published: May 2010

Pseudomonas aeruginosa
quorum control of gene expression involves three LuxR-type signal receptors LasR, RhlR, and QscR that respond to the LasI- and RhlI-generated acyl-homoserine lactone (acyl-HSL) signals 3OC12-HSL and C4-HSL. We found that a LasR-RhlR-QscR triple mutant responds to acyl-HSLs by regulating at least 37 genes. LuxR homolog-independent activation of the representative genes
antA
and
catB
also occurs in the wild type. Expression of
antA
was influenced the most by C10-HSL and to a lesser extent by other acyl-HSLs, including the
P. aeruginosa
3OC12-HSL and C4-HSL signals. The
ant
and
cat
operons encode enzymes for the degradation of anthranilate to tricarboxylic acid cycle intermediates. Our results indicate that LuxR homolog-independent acyl-HSL control of the
ant
and
cat
operons occurs via regulation of
antR
, which codes for the transcriptional activator of the
ant
operon. Although
P. aeruginosa
has multiple pathways for anthranilate synthesis, one pathway—the kynurenine pathway for tryptophan degradation—is required for acyl-HSL activation of the
ant
operon. The kynurenine pathway is also the critical source of anthranilate for energy metabolism via the
antABC
gene products, as well as the source of anthranilate for synthesis of the
P. aeruginosa
quinolone signal. Our discovery of LuxR homolog-independent responses to acyl-HSLs provides insight into acyl-HSL signaling.
Non-Mendelian determinant [
ISP
+
] in yeast is a nuclear-residing prion form of the global transcriptional regulator Sfp1
Authors: Rogoza Tatyana , Goginashvili Alexander , Rodionova Sofia , Ivanov Maxim , Viktorovskaya Olga , Rubel Alexander , Volkov Kirill , Mironova Ludmila
Published: May 2010

Four protein-based genetic determinants or prions—[
SWI
+
], [
MCA
], [
OCT
+
], and [

MOT3
+

]—are recent additions to the list of well-known
Saccharomyces cerevisiae
prions, [
PSI
+
], [
URE3
], and [
PIN
+
]. A rapid expansion of this list may indicate that many yeast proteins can convert into heritable prion forms and underscores a problem of prion input into cellular physiology. Here, we prove that the global transcriptional regulator Sfp1 can become a prion corresponding to the prion-like determinant [
ISP
+
] described earlier. We show that
SFP1
deletion causes an irreversible [
ISP
+
] loss, whereas increased
SFP1
expression induces [
ISP
+
] appearance. Cells that display the [
ISP
+
] phenotype contain the aggregated form of Sfp1. Indeed, these aggregates demonstrate a nuclear location. We also show that the phenotypic manifestation of Sfp1 prionization differs from the manifestation of
SFP1
deletion. These properties and others distinguish [
ISP
+
] from yeast prions described to date.
Structure of the N terminus of cadherin 23 reveals a new adhesion mechanism for a subset of cadherin superfamily members
Authors: Elledge Heather M. , Kazmierczak Piotr , Clark Peter , Joseph Jeremiah S. , Kolatkar Anand , Kuhn Peter , Müller Ulrich
Published: May 2010

The cadherin superfamily encodes more than 100 receptors with diverse functions in tissue development and homeostasis. Classical cadherins mediate adhesion by binding interactions that depend on their N-terminal extracellular cadherin (EC) domains, which swap N-terminal β-strands. Sequence alignments suggest that the strand-swap binding mode is not commonly used by functionally divergent cadherins. Here, we have determined the structure of the EC1–EC2 domains of cadherin 23 (CDH23), which binds to protocadherin 15 (PCDH15) to form tip links of mechanosensory hair cells. Unlike classical cadherins, the CDH23 N terminus contains polar amino acids that bind Ca
2+
. The N terminus of PCDH15 also contains polar amino acids. Mutations in polar amino acids within EC1 of CDH23 and PCDH15 abolish interaction between the two cadherins. PCDH21 and PCDH24 contain similarly charged N termini, suggesting that a subset of cadherins share a common interaction mechanism that differs from the strand-swap binding mode of classical cadherins.
Nebulin regulates actin filament lengths by a stabilization mechanism
Authors: Pappas Christopher T. , Krieg Paul A. , Gregorio Carol C.
Published: May 2010

Efficient muscle contraction requires regulation of actin filament lengths. In one highly cited model, the giant protein nebulin has been proposed to function as a molecular ruler specifying filament lengths. We directly challenged this hypothesis by constructing a unique, small version of nebulin (mini-nebulin). When endogenous nebulin was replaced with mini-nebulin in skeletal myocytes, thin filaments extended beyond the end of mini-nebulin, an observation which is inconsistent with a strict ruler function. However, under conditions that promote actin filament depolymerization, filaments associated with mini-nebulin were remarkably maintained at lengths either matching or longer than mini-nebulin. This indicates that mini-nebulin is able to stabilize portions of the filament it has no contact with. Knockdown of nebulin also resulted in more dynamic populations of thin filament components, whereas expression of mini-nebulin decreased the dynamics at both filament ends (i.e., recovered loss of endogenous nebulin). Thus, nebulin regulates thin filament architecture by a mechanism that includes stabilizing the filaments and preventing actin depolymerization.
Pathological versus protective functions of IL-22 in airway inflammation are regulated by IL-17A
Authors: Sonnenberg Gregory F. , Nair Meera G. , Kirn Thomas J. , Zaph Colby , Fouser Lynette A. , Artis David
Published: May 2010

IL-22 has both proinflammatory and tissue-protective properties depending on the context in which it is expressed. However, the factors that influence the functional outcomes of IL-22 expression remain poorly defined. We demonstrate that after administration of a high dose of bleomycin that induces acute tissue damage and airway inflammation and is lethal to wild-type (WT) mice, Th17 cell–derived IL-22 and IL-17A are expressed in the lung. Bleomycin-induced disease was ameliorated in Il22−/− mice or after anti–IL-22 monoclonal antibody (mAb) treatment of WT mice, indicating a proinflammatory/pathological role for IL-22 in airway inflammation. However, despite increased bleomycin-induced IL-22 production, Il17a−/− mice were protected from airway inflammation, suggesting that IL-17A may regulate the expression and/or proinflammatory properties of IL-22. Consistent with this, IL-17A inhibited IL-22 production by Th17 cells, and exogenous administration of IL-22 could only promote airway inflammation in vivo by acting in synergy with IL-17A. Anti–IL-22 mAb was delivered to Il17a−/− mice and was found to exacerbate bleomycin-induced airway inflammation, indicating that IL-22 is tissue protective in the absence of IL-17A. Finally, in an in vitro culture system, IL-22 administration protected airway epithelial cells from bleomycin-induced apoptosis, and this protection was reversed after coadministration of IL-17A. These data identify that IL-17A can regulate the expression, proinflammatory properties, and tissue-protective functions of IL-22, and indicate that the presence or absence of IL-17A governs the proinflammatory versus tissue-protective properties of IL-22 in a model of airway damage and inflammation.
Hand Hygiene in Long-Term Care Facilities A Multicenter Study of Knowledge, Attitudes, Practices, and Barriers
Authors: Ashraf Muhammad Salman , Hussain Syed Wasif , Agarwal Nimit , Ashraf Sadaf , EL-Kass Gabriel , Hussain Roshan , Nemat Hashim , Haller Nairmeen , Pekmezaris Renee , Sison Cristina , Walia Rajni , Eichorn Ann , Cal Charles , Dlugacz Yosef , Edwards Barbara T. , Louis Betina , Alano Gloria , Wolf-Klein Gisele
Published: May 2010

An anonymous survey of 1143 employees in 17 nursing facilities assessed knowledge of, attitudes about, self-perceived compliance with, and barriers to implementing the 2002 Centers for Disease Control and Prevention hand hygiene guidelines. Overall, employees reported positive attitudes toward the guidelines but differed with regard to knowledge, compliance, and perceived barriers. These findings provide guidance for practice improvement programs in long-term care settings.
Involvement of Silicon Influx Transporter OsNIP2;1 in Selenite Uptake in Rice
Authors: Zhao Xue Qiang , Mitani Namiki , Yamaji Naoki , Shen Ren Fang , Ma Jian Feng
Published: May 2010

Rice (Oryza sativa) as a staple food, provides a major source of dietary selenium (Se) for humans, which essentially requires Se, however, the molecular mechanism for Se uptake is still poorly understood. Herein, we show evidence that the uptake of selenite, a main bioavailable form of Se in paddy soils, is mediated by a silicon (Si) influx transporter Lsi1 (OsNIP2;1) in rice. Defect of OsNIP2;1 resulted in a significant decrease in the Se concentration of the shoots and xylem sap when selenite was given. However, there was no difference in the Se concentration between the wild-type rice and mutant of OsNIP2;1 when selenate was supplied. A short-term uptake experiment showed that selenite uptake greatly increased with decreasing pH in the external solution. Si as silicic acid did not inhibit the Se uptake from selenite in both rice and yeast (Saccharomyces cerevisiae) at low pHs. Expression of OsNIP2;1 in yeast enhanced the selenite uptake at pH 3.5 and 5.5 but not at pH 7.5. On the other hand, defect of Si efflux transporter Lsi2 did not affect the uptake of Se either from selenite or selenate. Taken together, our results indicate that Si influx transporter OsNIP2;1 is permeable to selenite.
NFκB, cytokines, TLR 3 and 7 expression in human end‐stage HCV and alcoholic liver disease
Authors: Stärkel Peter , De Saeger Christine , Strain Alastair J. , Leclercq Isabelle , Horsmans Yves
Published: May 2010

Eur J Clin Invest 2010; 40 (7): 575–584

Background/aims Conflicting observations exist concerning the role of nuclear factor kappa B (NFκB) in alcoholic liver disease (ALD) in animal models. To date no studies have examined this aspect in human liver tissue. We here assessed cytokines and toll‐like receptors (TLRs) expressions in conjunction with NFκB activation in non‐active end‐stage human ALD compared with normal livers and hepatitis C virus (HCV) related end‐stage disease.

Methods mRNA and protein expression were examined by quantitative PCR and Western blotting, DNA‐binding by electrophoretic mobility shift assays and NFκB sub‐cellular localization by immunofluorescent staining of livers.

Results NFκB mRNA and protein expression as well as strong DNA‐binding were preserved in ALD but significantly down‐regulated in HCV compared with normal livers. P50 immunofluorescence was found in hepatocytes and bile ducts in ALD and normal livers, whereas a shift was observed in p65 staining from non‐parenchymal cells in normal livers to hepatocytes in ALD. NFκB responsive genes mRNA levels IkBα and interleukin 6 were significantly higher in ALD compared with HCV. Tumour necrosis factor alpha (TNFα), TLRs 3 and 7 mRNA were up‐regulated in ALD and HCV compared with normal liver with TNFα and TLR7 being the highest in HCV. Strong induction of interferon beta was found in HCV but not in ALD or normal liver tissue.

Conclusions Persistent NFκB activation together with high pro‐inflammatory cytokine expression and upregulation of TLR3 and TLR7 is associated with end‐stage ALD in humans and could contribute to disease progression even in absence of alcohol intake.
Facing up to ‘challenging behaviour’: a model for training in staff–client interaction
Authors: Farrell Gerald A. , Shafiei Touran , Salmon Peter
Published: May 2010

farrell g.a., shafiei t. & salmon p. (2010) Facing up to ‘challenging behaviour’: a model for training in staff–client interaction.Journal of Advanced Nursing 66(7), 1422–1434.

Title. Facing up to ‘challenging behaviour’: a model for training in staff‐client interaction

Aim. This paper draws on theory and evidence to develop a conceptual staff training model for the management of ‘challenging behaviour’.

Background. Staff working with clients who are experienced as challenging commonly report negative feelings such as anxiety, anger, guilt, fear, self‐blame and powerlessness, as well as dissatisfaction with their jobs. Current training programmes in challenging behaviour offer a ‘smorgasbord’ of content, without a clearly defined conceptual framework.

Data sources. Medline and PsychInfo were searched for papers in English from 1998 to 2008, linking ‘nurs*’ to ‘challenging behavio*’ and its related terms. Additional hand‐searching identified informative papers from disciplines outside nursing older than the search period.

Discussion. We developed an applied model for training educators in respect of challenging behaviours. The model directs educators to consider: the influence of the nurse, including their values, emotional processes and behavioural skills; features of the client; and features of the situation in which the behaviour occurs, including its culture and working practices and physical environment.

Implications for nursing. The most striking implication of the model is that it explicitly recognizes the importance of domains of learning other than skill. This enables educators to find educationally appropriate responses to resource limitations that inevitably constrain training.

Conclusion. Challenging behaviour should be considered as a product of several intertwined factors: the actors involved – nurses, clients and others – and the situation in which the behaviour occurs, including its culture and working practices and physical environment.
Protecting the Environment the Natural Way: Ethical Consumption and Commodity Fetishism
Authors: Carrier James G.
Published: May 2010

Abstract: One of the ways that conservation and capitalism intersect is in ethical consumption, the shaping of purchasing decisions by an evaluation of the moral attributes of objects on offer. It is increasingly important as a way that people think that they can affect the world around them, including protecting the natural environment. This paper describes commodity fetishism in ethical consumption, and the degree to which this fetishism makes it difficult for ethical consumers to be effective both in their evaluation of objects on offer and in influencing the world around them. It looks at three forms of fetishism in ethical consumption: fetishism of objects, fetishism of the purchase and consumption of objects, fetishism of nature.
Effects of Fisheries Closures and Gear Restrictions on Fishing Income in a Kenyan Coral Reef
Authors: McCLANAHAN TIMOTHY R.
Published: May 2010

Abstract:  The adoption of fisheries closures and gear restrictions in the conservation of coral reefs may be limited by poor understanding of the economic profitability of competing economic uses of marine resources. Over the past 12 years, I evaluated the effects of gear regulation and fisheries closures on per person and per area incomes from fishing in coral reefs of Kenya. In two of my study areas, the use of small‐meshed beach seines was stopped after 6 years; one of these areas was next to a fishery closure. In my third study area, fishing was unregulated. Fishing yields on per capita daily wet weight basis were 20% higher after seine‐net fishing was stopped. The per person daily fishing income adjacent to the closed areas was 14 and 22% higher than the fishing income at areas with only gear restrictions before and after the seine‐net restriction, respectively. Incomes differed because larger fish were captured next to the closed area and the price per weight (kilograms) increased as fish size increased and because catches adjacent to the closure contained fish species of higher market value. Per capita incomes were 41 and 135% higher for those who fished in gear‐restricted areas and near‐closed areas, respectively, compared with those who fished areas with no restrictions. On a per unit area basis (square kilometers), differences in fishing income among the three areas were not large because fishing effort increased as the number of restrictions decreased. Changes in catch were, however, larger and often in the opposite direction expected from changes in effort alone. For example, effort declined 21% but nominal profits per square kilometer (not accounting for inflation) increased 29% near the area with gear restrictions. Gear restrictions also reduced the cost of fishing and increased the proportion of self‐employed fishers.
Analgesic Effects of Ethanol Are Influenced by Family History of Alcoholism and Neuroticism
Authors: Ralevski Elizabeth , Perrino Albert , Acampora Gregory , Koretski Julia , Limoncelli Diana , Petrakis Ismene
Published: May 2010

Background:  Although personality factors and family history of substance abuse influence how individuals experience pain and respond to analgesics, the combined effects of those factors have not been extensively studied. The objective of this study was to consider the possible role of personality trait of neuroticism and family history of alcoholism on the experience of pain and their role in the analgesic response to an ethanol challenge.

Methods:  Forty‐eight healthy subjects participated in this study; thirty‐one had a positive family history of alcoholism (FHP), seventeen had a negative family history of alcoholism (FHN). They were also categorized based on their neuroticism (N) scores (low N = 28, and high N = 20). This was a double‐blind, placebo‐controlled, randomized, within‐subject design study of intravenous administration of three doses of ethanol. The testing consisted of 3 separate test days scheduled at least 3 days apart. Test days included a placebo day (saline solution), low‐exposure ethanol day (targeted breathalyzer = 0.040 g/dl), and high‐exposure ethanol day (targeted breathalyzer = 0.100 g/dl). Noxious electrical stimulation and pain assessments were performed prior to start of infusion and at the 60‐minute infusion mark.

Results:  The analgesic effect of ethanol was mediated by an interaction between the personality trait of neuroticism and family history. Individuals with family history of alcoholism and high N scores reported significantly more analgesia on low dose of ethanol than those with low N scores. There was no difference in the analgesic response to ethanol among FHNs with low and high N scores.

Conclusion:  These findings support the conclusion that neuroticism and family history of alcoholism both influence the analgesic response of alcohol. Individuals with high N scores and FHP have the strongest response to ethanol analgesia particularly on the low exposure to alcohol.
A Morphologically Simple Species of Acrasis (Heterolobosea, Excavata), Acrasis helenhemmesae n. sp.
Authors: BROWN MATTHEW W. , SILBERMAN JEFFREY D. , SPIEGEL FREDERICK W.
Published: May 2010

ABSTRACT. In the course of a large‐scale global survey of mycetozoans, amoeboid organisms that form fruiting bodies, a new species of Acrasis was discovered from several subtropical locales in Hawaii, Australia, Bermuda, and South Africa. We isolated four strains from dead, still attached, plant material, and one strain from attached bark of a tree. Each isolate forms simple uniseriate multicellular fruiting bodies typically consisting of two bottle‐shaped, basal stalk cells and a chain of <20 spores. The isolate from Bermuda often forms dichotomous simple branches, each consisting of <10 spores. Amoebae from these new isolates are limax with eruptive pseudopodial formation and display rapid locomotion—characters indicative of amoebae in the excavate taxon Heterolobosea. These isolates form simpler fruiting bodies than is typical of the well‐known Acrasis rosea. Although in the original description, A. rosea is known to form uniseriate fruiting bodies similar to our isolates, A. rosea isolates typically form more complex fruiting structures along side simple ones, but never strictly simple ones. Nuclear‐encoded 18S rRNA gene phylogenies demonstrate that our five isolates form a highly supported clade that is sister to A. rosea. Given the differences both in gene sequences and fruiting body morphology between our isolates and A. rosea, we propose the new species, Acrasis helenhemmesae n. sp.
Comparison of A2E Cytotoxicity and Phototoxicity with all‐trans‐Retinal in Human Retinal Pigment Epithelial Cells†
Authors: Wielgus Albert R. , Chignell Colin F. , Ceger Patricia , Roberts Joan E.
Published: May 2010

All‐trans‐retinal is the precursor of A2E, a fluorophore within lipofuscin, which accumulates in human retinal pigment epithelial (hRPE) cells and contributes to age‐related macular degeneration. Here we have compared the in vitro dark cytotoxicity and visible‐light‐mediated photoreactivity of all‐trans‐retinal and A2E in hRPE cells. All‐trans‐retinal caused distinct cytotoxicity in hRPE cells measured with cell metabolic activity (MTS) and lactate dehydrogenase release assays. Significant increases in intracellular oxidized glutathione (GSSG), extracellular GSH and GSSG levels and lipid hydroperoxide production were observed in cells incubated in the dark with 25 and 50 μm all‐trans‐retinal. Light modified all‐trans‐retinal’s harmful action and decreased extracellular glutathione and hydroperoxide levels. A2E (<25 μm) did not affect cell metabolism or cytoplasmic membrane integrity in the dark or when irradiated. 25 μm A2E raised the intracellular GSSG level in hRPE cells to a much smaller extent than 25 μm all‐trans‐retinal. A2E did not induce glutathione efflux or hydroperoxide generation in the dark or after irradiation. These studies support our previous conclusions that although A2E may be harmful at high concentrations or when oxidized, its phototoxic properties are insignificant compared to those of all‐trans‐retinal. The endogenous production of A2E may serve as a protective mechanism to prevent damage to the retina by free all‐trans‐retinal.