bluuebunny/crossref_metadata_2025 huggingface dataset:
Resourcefulness, positive cognitions, relocation controllability and relocation adjustment among older people: a cross‐sectional study of cultural differences
Authors: Bekhet Abir K. , Zauszniewski Jaclene A.
Published: July 2012

Background.  The population of older people in both the United States and Egypt is expected to double by the year 2030. With ageing, chronic illnesses increase and many older people need to relocate to retirement communities. Research has shown that positive cognitions and resourcefulness are positively correlated with adaptive functioning and better adjustment.

Aims and objectives.  The purpose of this study was to examine and compare relocation controllability, positive cognitions, resourcefulness and relocation adjustment between American and Egyptian older people living in retirement communities. The purpose of this cultural comparison is to gain insight into influencing factors in each culture that might lead to interventions to help relocated older adults in both cultures adjust to their new surroundings.

Design and method.  A cross‐sectional, descriptive design was used to compare relocation controllability, positive cognitions, resourcefulness and relocation adjustment of a convenience sample of American older people (n = 104) and a convenience sample of Egyptian older people (n = 94). The study was a secondary analysis of two studies of older people residing in six retirement communities in Northeast Ohio and in five retirement communities in Alexandria, Egypt.

Results.  Examination of mean scores and standard deviations on the measure of positive cognitions using independent sample t‐tests indicated that on average, the American older people reported more positive cognitions (t (131·16) = 11·29, P < 0·001), more relocation controllability (t (196) = −6·78, P < 0·001) and more relocation adjustment (t (196) = 9·42, P < 0·001) than the Egyptian older people. However, there was no significant difference between Egyptians and Americans in resourcefulness (t (174·16) = −0·97, P > 0·05).

Conclusion: The results provide direction for the development of positive cognition interventions and engaging older people in the decision‐making process to help them to adjust to relocation.

Implications for practice.  Positive thinking and resourcefulness training interventions can be used by nurses to help relocated older people to adjust to the stress of relocation to retirement communities. These interventions can be used on primary, secondary, and tertiary levels. Primary interventions can help to prevent the stress of relocation before happening by helping older people to use their positive thinking and their resources and work with them before relocating to retirement communities. Secondary prevention can be used by nurses to help older people who have already relocated to retirement communities and have already experienced stress of relocation to help them out by decreasing the stress that they are suffering. Tertiary prevention can be used to prevent further stress and deterioration for those who have suffered physical and psychological symptoms as a result of relocation.
Interacting epidemics? Sleep curtailment, insulin resistance, and obesity
Authors: Lucassen Eliane A. , Rother Kristina I. , Cizza Giovanni
Published: July 2012

In the last 50 years, the average self‐reported sleep duration in the United States has decreased by 1.5–2 hours in parallel with an increasing prevalence of obesity and diabetes. Epidemiological studies and meta‐analyses report a strong relationship between short or disturbed sleep, obesity, and abnormalities in glucose metabolism. This relationship is likely to be bidirectional and causal in nature, but many aspects remain to be elucidated. Sleep and the internal circadian clock influence a host of endocrine parameters. Sleep curtailment in humans alters multiple metabolic pathways, leading to more insulin resistance, possibly decreased energy expenditure, increased appetite, and immunological changes. On the other hand, psychological, endocrine, and anatomical abnormalities in individuals with obesity and/or diabetes can interfere with sleep duration and quality, thus creating a vicious cycle. In this review, we address mechanisms linking sleep with metabolism, highlight the need for studies conducted in real‐life settings, and explore therapeutic interventions to improve sleep, with a potential beneficial effect on obesity and its comorbidities.
Azide Quenching of Singlet Oxygen in Suspensions of Microenvironments of Neutral and Surface Charged Liposomes and Micelles
Authors: Musbat Lihi , Weitman Hana , Ehrenberg Benjamin
Published: July 2012

The azide anion is often used as a physical quencher of singlet oxygen, the important active intermediate in photosensitized oxidation. An observed effect of azide on the rate of a reaction is considered an indication to the involvement of singlet oxygen. In most biological photosensitizations, the light‐absorbing sensitizer is located in a membrane or in an intracellular organelle, whereas azide is water soluble. The quenching it causes relies on a physical encounter with singlet oxygen during the latter's short lifetime. This can happen either if azide penetrates into the membrane's lipid phase or if singlet oxygen is intercepted when diffusing in the aqueous phase. We demonstrate in this article the difference, in liposomes’ suspension, between the effect of azide when using a water‐soluble and membrane‐bound chemical targets of singlet oxygen, whereas this difference does not exist when micelles are used. We explain the difference on the population of sensitizer and target in the liposome vs micelle. We also show the effect that exists on azide quenching of singlet oxygen by electrically charged lipids in liposomes. This is a result of the accumulation or dilution of azide in the debye layer near the membranes’ surface, due to the surface Gouy–Chapman potential.
The genetic basis of cadmium resistance of Burkholderia cenocepacia
Authors: Schwager Stephan , Lumjiaktase Putthapoom , Stöckli Martina , Weisskopf Laure , Eberl Leo
Published: July 2012

Burkholderia species are highly resistant to heavy metals (HMs), yet their resistance mechanisms are largely unknown. In this study we screened 5000 mini‐Tn5 transposon insertion mutants of Burkholderia cenocepacia H111 for loss of cadmium tolerance. Of the four genes identified three affected outer membrane biogenesis and integrity or DNA repair. The fourth gene, BCAE0587, encoded a P1‐type ATPase belonging to the CadA family of HM exporters. CadA‐deficient strains lost the ability to grow in the presence of cadmium, zinc and lead, whereas resistance to nickel, copper and cobalt was not affected. Expression studies using a transcriptional fusion of the cadA promoter to gfp confirmed this specificity, as induction was only observed in presence of cadmium, zinc and lead. The promoter activity was found to be highest at neutral pH with an activation threshold of 30 nM cadmium. Inoculation of the HM‐hyperaccumulating plant Arabidopsis halleri with a RFP‐marked derivative of B. cenocepacia H111 containing the PcadA–gfp fusion demonstrated the applicability of this biosensor for monitoring cadmium at the single cell level in a natural environment.
Attitudes of primary care physicians towards patients with mental illness in Hong Kong
Authors: Lam Tai Pong , Lam Kwok Fai , Lam Edmund Wing Wo , Ku Yin Shuen
Published: July 2012

Introduction

This study aims to describe the attitudes of primary care physicians towards mental health patients in Hong Kong, especially to examine the doctors’ views on schizophrenia and depression, and the influence of their demographic variables.

Methods

A questionnaire developed by the research team was sent to members of Hong Kong College of Family Physicians. Potential respondents were allocated on equal basis to one of the two sets of questionnaire, set 1 for clinical vignette of schizophrenia and set 2 for depression.

Results

A response rate of 37% (500 of 1,360) was achieved. There were 255 and 245 returned questionnaires for set 1 and set 2, respectively. Comparing the two clinical vignettes, there were large differences in their willingness to have the patient on practice list for mental issues (40.0% for schizophrenia versus 71.5% for depression) and to deal with the patient's needs (37.0% versus 60.9%). Multiple ordinal logistic regression analysis showed that doctors with the following demographic factors tended to have more worries or stigma on mental health patients: “having longer years of practice,” “being female,” “working in hospital,” “employed in public sector,” and “not having a relative/friend with mental health problems.”

Discussion

Our study shows that two‐thirds of primary care doctors are prepared to look after patients with depression, which is substantially higher than that for schizophrenia. In contrast with the Australian findings, the experienced doctors in Hong Kong have more negative attitudes towards mental health patients than the younger ones.
Thoracoscopic pericardiotomy for management of purulent pneumococcal pericarditis in a child
Authors: Agrawal V , Saxena A , Sethi A , Acharya H , Sharma D
Published: July 2012

Purulent pericarditis is an extremely rare complication of pneumococcal pneumonia in children that may result in to cardiac tamponade. While image‐guided pericardiocentesis is the treatment of choice for such a condition, it may fail in the presence of thick pus; loculations and thoracoscopic pericardiotomy are useful procedures for such situations. Herein, we report such a case involving a 6‐year‐old boy who presented with purulent pneumococcal pericarditis that was managed with thoracoscopic pericardiotomy and who recovered well. Thoracoscopic pericardiotomy is a safe procedure that allows effective drainage under vision, pericardial biopsy for diagnosis, and a simultaneous opportunity to perform thoracoscopic pleural drainage.
A new approach for posterior mediastinal tumors: Thoracoscopic resection in the prone position
Authors: Daiko H , Fujita T , Matsumura Y , Nishimura M
Published: July 2012

Video‐assisted thoracoscopic surgery in the lateral position has been the standard surgical approach for posterior mediastinal tumors. Herein, we report the successful thoracoscopic resection of a posterior mediastinal tumor with the patient in the prone position. The patient was a 62‐year‐old man with a posterior mediastinal mass. We were able to completely extirpate the posterior mediastinal tumor by means of thoracoscopic resection, with the patient in the prone position, much in the manner of solo surgery. The prone position has the potential to become the standard thoracoscopic surgical approach for posterior mediastinal tumors because it provides excellent exposure of the posterior mediastinum.
Reversed intestinal malrotation with concurrent cecal carcinoma
Authors: Morimoto M , Horie H , Kumano H , Lefor A , Utano K , Yasuda Y
Published: July 2012

A 57‐year‐old man was admitted with a type 2 (ulcerated with clear margin) cancer in the cecum. Contrast‐enhanced CT showed that the superior mesenteric vein was anterior to the superior mesenteric artery, and the patient was suspected of having intestinal malrotation. A laparoscopic‐assisted ileocecal resection was performed. At operation, the cecum and the transverse colon passed through the root of the mesentery behind the superior mesenteric artery with the duodenum. Therefore, this was thought to be a reversed‐type intestinal malrotation. After the operation, 3D‐CT colonography with duodenography images were reconstructed to retrospectively confirm the diagnosis of a reversed malrotation. These images clearly demonstrated the abnormal anatomy and overall orientation of the intestine. Patients with a reversed intestinal malrotation and concurrent cecal cancer are extremely rare. Herein, we present a patient who underwent a laparoscopic‐assisted ileocecal resection for cecal cancer that presented concurrently with a reversed intestinal malrotation.
Utilization of prescription drugs with warnings of suicidal thoughts and behaviours in the USA and the US Department of Veterans Affairs, 2009
Authors: Lavigne Jill E. , Au Anthony , Jiang Rong , Wang Yu , Good Chester P. , Glassman Peter , Cunningham Frances
Published: July 2012

Objectives

To develop a list of prescription medications labelled with warnings for adverse effects of suicidal ideation or behaviour and to describe utilization in the USA and in the Department of Veterans Affairs (VA) in 2009.

Methods

A systematic search of US Food and Drug Administration and other references using ‘suicide’, ‘suicidal’ and ‘suicidality’ was used to identify prescription drugs labelled for risk of suicidal ideation or behaviour. Prescription medications sold in the USA by sales volume are reported alongside VA utilization as determined from national electronic pharmacy records.

Key findings

One hundred and twenty-five prescription drugs were labelled for potential adverse effects of suicidal ideation or behaviour. Forty-five of these drugs were among the top 200 prescription medications sold in the USA in 2009 with a total sales volume of 540.8 million prescriptions. Rank-ordered utilization was similar in the VA. VA total fill volume was 5.99 million prescriptions.

Conclusions

The majority of prescriptions with adverse effect warnings of suicidal ideation or behaviour were generic. Relatively high volumes of drugs with warnings for suicidal ideation or behaviour are filled in the USA and in the VA.
Cardiac Troponin I in Racing Standardbreds
Authors: Slack J. , Boston R.C. , Soma L. , Reef V.B.
Published: July 2012

Background

Upper reference limits for cTnI have not been established for healthy Standardbred racehorses.

Objectives

To establish cTnI upper reference limits for Standardbred racehorses and determine if increases in plasma cTnI concentration can be detected in 1–2 hours after a race.

Animals

Samples were obtained from 586 apparently healthy Standardbreds aged 2–14 years before racing and from the winners of 144 races 1–2 hours after the end of the race.

Methods

Prospective, observational study; convenience sampling; assay validation; and reference limits determinations were performed according to ASCVP guidelines. Plasma cardiac troponin I concentrations before racing were determined, potential outliers identified, and the 95th and 99th percentile upper reference limits calculated using nonparametric methods. The correlation between cTnI concentration and age, differences in median cTnI concentrations by subgroups and differences between cTnI concentrations before and after racing in winning horses were determined.

Results

The 95th and 99th percentile upper reference limits for all horses excluding outliers were < 0.04ng/mL and 0.06 ng/mL. There were no significant differences in cTnI concentrations based on age (P = .06), sex (P = .35), gait (P = .55), or race classification (P = .65) and a weak correlation of cTnI with age (ρ = 0.09, P = .03). There were no significant differences between cTnI concentrations before and after racing in winning horses (P = .70).

Conclusions and Clinical Importance

Because of lack of standardization across cTnI assays, the reference limits apply only to the Stratus CS immunoassay. Future studies looking at the effects of high intensity, short duration exercise on cTnI should consider sampling more than 2 hours after racing or using an ultrasensitive assay.
Endothelial impairment and bone marrow‐derived CD34+/133+ cells in diabetic patients with erectile dysfunction
Authors: Murata Miho , Tamemoto Hiroyuki , Otani Taeko , Jinbo Sachimi , Ikeda Nahoko , Kawakami Masanobu , Ishikawa San‐e
Published: July 2012

Aims/Introduction

The present study was undertaken to determine vascular endothelial impairment and endothelial progenitor cells (EPCs) in patients with type 2 diabetes mellitus and erectile dysfunction (ED).

Materials and Methods

A total of 100 type 2 diabetic men were enrolled. Flow‐mediated dilatation (FMD) and anaerobic threshold (AT) were measured. Also, EPCs in the peripheral blood were determined by flow cytometry.

Results

In the 42 ED diabetic patients, FMD and AT were significantly less than those in the 58 patients with normal erectile function (FMD 2.84 vs 3.82%, P = 0.038, and AT 11.2 vs 12.7 mL/kg/min, P = 0.022). Exercise tolerance significantly increased the number of EPCs in the patients with and without ED (49–60 cells/100 μL, P = 0.015, and 72–99 cells/100 μL, P = 0.003). In the diabetic patients without autonomic neuropathy, FMD was significantly reduced in the patients with ED than those without ED (P = 0.015). In response to exercise tolerance, the number of EPCs increased in both the diabetic patients with ED (P = 0.003) and without ED (P = 0.007). In contrast, in the diabetic patients with autonomic neuropathy, there was no difference in FMD between the patients with and without ED. The exercise tolerance increased the number of EPCs in the patients without ED (P = 0.023), but it disappeared in those with ED.

Conclusions

ED diabetic patients have endothelial impairment during the early period of diabetic complications, whose deranged endothelial function is concomitantly repaired by promoting bone marrow‐derived EPCs.
Projecting species’ range expansion dynamics: sources of systematic biases when scaling up patterns and processes
Authors: Bocedi Greta , Pe’er Guy , Heikkinen Risto K. , Matsinos Yiannis , Travis Justin M. J.
Published: July 2012

1. Dynamic simulation models are a promising tool for assessing how species respond to habitat fragmentation and climate change. However, sensitivity of their outputs to impacts of spatial resolution is insufficiently known.

2. Using an individual‐based dynamic model for species’ range expansion, we demonstrate an inherent risk of substantial biases resulting from choices relating to the resolution at which key patterns and processes are modelled.

3. Increasing cell size leads to overestimating dispersal distances, the extent of the range shift and population size. Overestimation accelerates with cell size for species with short dispersal capacity and is particularly severe in highly fragmented landscapes.

4. The overestimation results from three main interacting sources: homogenisation of spatial information, alteration of dispersal kernels and stabilisation/aggregation of population dynamics.

5. We urge for caution in selecting the spatial resolution used in dynamic simulations and other predictive models and highlight the urgent need to develop upscaling methods that maintain important patterns and processes at fine scales.
Fractures of the tibial malleoli
Authors: Smith M. R. W.
Published: July 2012

Fractures of the tibial malleoli are relatively uncommon injuries, and most frequently affect the lateral malleolus. They most commonly occur following falls. The tibial malleoli have extensive collateral ligament attachments, and this is likely to contribute to fracture pathogenesis. Although most fractures are best managed by surgical removal, large fractures should be repaired as removal may result in tarsal instability. Arthroscopic removal has recently become the standard of care for most fractures, and good results can be expected following surgery.
Product standardisation as a tool to control prescribing costs – a case study of alginate liquid preparations
Authors: Alahdab Ola G , Crealey Grainne , Scott Michael G , Mairs Jill , McElnay James C
Published: July 2012

Introduction

Product standardisation involves promoting the prescribing of pre-selected products within a particular category across a healthcare region and is designed to improve patient safety by promoting continuity of medicine use across the primary/secondary care interface, in addition to cost containment without compromising clinical care (i.e. maintaining safety and efficacy).

Objectives

To examine the impact of product standardisation on the prescribing of compound alginate preparations within primary care in Northern Ireland.

Methods

Data were obtained on alginate prescribing from the Northern Ireland Central Services Agency (Prescription Pricing Branch), covering a period of 43 months. Two standardisation promotion interventions were carried out at months 18 and 33. In addition to conventional statistical analyses, a simple interrupted time series analysis approach, using graphical interpretation, was used to facilitate interpretation of the data.

Results

There was a significant increase in the prescribed share of the preferred alginate product in each of the four health boards in Northern Ireland and a decrease in the cost per Defined Daily Dose for alginate liquid preparations overall. Compliance with the standardisation policy was, however, incomplete and was influenced to a marked degree by the activities of the pharmaceutical industry. The overall economic impact of the prescribing changes during the study was small (3.1%).

Conclusion

The findings suggested that product standardisation significantly influenced the prescribing pattern for compound alginate liquid preparations within primary care across Northern Ireland.
Endocannabinoid‐dependent plasticity at spinal nociceptor synapses
Authors: Kato Ako , Punnakkal Pradeep , Pernía‐Andrade Alejandro Javier , von Schoultz Carolin , Sharopov Salim , Nyilas Rita , Katona István , Zeilhofer Hanns Ulrich
Published: July 2012

Key points

Synaptic plasticity between primary nociceptors and second order dorsal horn neurons serves key roles in pain and analgesia

A contribution of NMDA receptors to long‐term potentiation and long‐term depression at these synapses has been demonstrated before, but much less is known about a possible role of endocannabinoids and cannabinoid (CB)1 receptors.

Here we show that CB1 receptors residing on the spinal terminals of primary nociceptors critically contribute to an NMDA receptor‐independent form of long‐term depression at these synapses, which requires simultaneous pre‐ and postsynaptic activity.

A similar long‐lasting depression of nociceptive signal transmission can also be obtained with application of CB1 receptor agonists in the presence of presynaptic stimulation alone.

These findings identify a previously unknown form of long‐term depression at spinal nociceptor synapses, which may be important for our understanding of pain‐related neural plasticity and analgesic actions of CB1 receptor agonists.

Abstract  Neuroplastic changes at the spinal synapses between primary nociceptors and second order dorsal horn neurons play key roles in pain and analgesia. NMDA receptor‐dependent forms of long‐term plasticity have been studied extensively at these synapses, but little is known about possible contributions of the endocannabinoid system. Here, we addressed the role of cannabinoid (CB)1 receptors in activity‐dependent plasticity at these synapses. We report that conditional low‐frequency stimulation of high‐threshold primary sensory nerve fibres paired with depolarisation of the postsynaptic neuron evoked robust long‐term depression (LTD) of excitatory synaptic transmission by about 40% in the vast majority (90%) of recordings made in wild‐type mice. When recordings were made from global or nociceptor‐specific CB1 receptor‐deficient mice (CB1−/− mice and sns‐CB1−/− mice), the portion of neurons exhibiting LTD was strongly reduced to about 25%. Accordingly, LTD was prevented to a similar extent by the CB1 receptor antagonist AM 251 and mimicked by pharmacological activation of CB1 receptors. In a subset of neurons with EPSCs of particularly high stimulation thresholds, we furthermore found that the absence of CB1 receptors in CB1−/− and sns‐CB1−/− mice converted the response to the paired conditioning stimulation protocol from LTD to long‐term potentiation (LTP). Our results identify CB1 receptor‐dependent LTD as a form of synaptic plasticity previously unknown in spinal nociceptors. They furthermore suggest that prevention of LTP may be a second hitherto unknown function of CB1 receptors in primary nociceptors. Both findings may have important implications for our understanding of endogenous pain control mechanisms and of analgesia evoked by cannabinoid receptor agonists.
The human Nav1.5 F1486 deletion associated with long QT syndrome leads to impaired sodium channel inactivation and reduced lidocaine sensitivity
Authors: Song Weihua , Xiao Yucheng , Chen Hanying , Ashpole Nicole M. , Piekarz Andrew D. , Ma Peilin , Hudmon Andy , Cummins Theodore R. , Shou Weinian
Published: July 2012

Key points

We investigated how the F1486 deletion LQT3 mutation impairs the functional properties of the human cardiac voltage‐gated sodium channel (hNav1.5) and alters action potential firing.

Voltage‐clamp recordings from HEK 293 cells and cardiomyocytes expressing recombinant channels demonstrated that the F1486del mutation reduces peak current density but also impairs inactivation and increases late current density.

Current‐clamp recordings from cardiomyocytes indicated that the increase in late current density would result in prolonged action potential duration and this was confirmed using computer simulations.

The deletion of F1486 abolished the ability of lidocaine to stabilize the inactivated state and eliminated the high‐affinity binding of lidocaine to inactivated channels.

Our data show that the hNav1.5‐F1486del mutation has complex functional consequences and indicate that knowledge of the specific molecular defect is critical when developing potential treatments for individuals with prolonged QT intervals.

Abstract  The deletion of phenylalanine 1486 (F1486del) in the human cardiac voltage‐gated sodium channel (hNav1.5) is associated with fatal long QT (LQT) syndrome. In this study we determined how F1486del impairs the functional properties of hNav1.5 and alters action potential firing in heterologous expression systems (human embryonic kidney (HEK) 293 cells) and their native cardiomyocyte background. Cells expressing hNav1.5‐F1486del exhibited a loss‐of‐function alteration, reflected by an 80% reduction of peak current density, and several gain‐of‐function alterations, including reduced channel inactivation, enlarged window current, substantial augmentation of persistent late sodium current and an increase in ramp current. We also observed substantial action potential duration (APD) prolongation and prominent early afterdepolarizations (EADs) in neonatal cardiomyocytes expressing the F1486del channels, as well as in computer simulations of myocyte activity. In addition, lidocaine sensitivity was dramatically reduced, which probably contributed to the poor therapeutic outcome observed in the patient carrying the hNav1.5‐F1486del mutation. Therefore, despite the significant reduction in peak current density, the F1486del mutation also leads to substantial gain‐of‐function alterations that are sufficient to cause APD prolongation and EADs, the predominant characteristic of LQTs. These data demonstrate that hNav1.5 mutations can have complex functional consequences and highlight the importance of identifying the specific molecular defect when evaluating potential treatments for individuals with prolonged QT intervals.
Engineering Design at Harvey Mudd College: Innovation Institutionalized, Lessons Learned
Authors: Dym Clive L. , Gilkeson M. Mack , Phillips J. Richard
Published: July 2012

This paper outlines the development of Harvey Mudd College’s Engineering program, describes its resulting form, and articulates how some truly innovative ideas in engineering design education, now widely accepted as “best practices,” were developed and implemented. The paper also describes the lessons learned from Harvey Mudd College’s Engineering curriculum, as well as some of the efforts made to disseminate these lessons.
Considering Landowner Participation in Wind Farm Layout Optimization
Authors: Chen Le , MacDonald Erin
Published: July 2012

Current wind farm layout optimization research assumes a continuous piece of land is readily available and focuses on advancing optimization methods. In reality, projects rely on landowners’ permission for success. When a viable site is identified, local residents are approached for permission to build turbines on their land, typically in exchange for monetary compensation. Landowners play a crucial role in the development process, and some land parcels are more important to the success of project than others. This paper relaxes the assumption that a continuous piece of land is available, developing a novel approach that includes a model of landowner participation rates. A genetic algorithm (GA) is adopted to solve the nonlinear constrained optimization problem, minimizing cost and maximizing power output. The optimization results show that, given a projected participation rate, we can identify the most crucial plots prior to the negotiation process with landowners. This will ultimately increase the efficiency of wind farm development.
Optimal Cellular Core Topologies for One-Dimensional Morphing Aircraft Structures
Authors: Olympio K. Raymond , Gandhi Farhan
Published: July 2012

Unlike a conventional aircraft’s wing, a morphing aircraft’s wing could undergo large deformations in order to fly efficiently. This requires a wing’s skin meeting conflicting requirements such as large deformation capability to allow morphing of the underlying structure and high flexural stiffness to maintain the airfoil shape. In this paper, the design of composite skins with a cellular core is considered for the particular case of one-dimensional morphing. Cellular core topologies are calculated using a multi-objective genetic algorithm coupled with a local search optimizer. Morphological filtering is used to remove small features in the topology. As a multi-objective problem, no single solution emerges as the clear best solution because of conflicting objectives. However, the solutions found help guide the design of cellular-based morphing skins. A design is selected from the set of solutions obtained, and a cellular core under combined in-plane morphing and out-of-plane loading is examined with respect to the local stresses, the energy of deformation and the core’s out-of-plane deformation to validate the approach used.
Analytical Study of a Pin-Loaded Hole in Unidirectional Laminated Composites With Triangular and Circular Fibers
Authors: Robati Hossein , Mahdi Attar Mohammad
Published: July 2012

The problem of stress concentrations in the vicinity of pin-loaded holes is of particular importance in the design of multilayered composite structures made of triangular or circular glass fibers. It is assumed that all of the fibers in the laminate lie in one direction while loaded by a force p0 at infinity, parallel to the direction of the fibers. According to the shear lag model, equilibrium equations are derived for both types of fibers. A rectangular arrangement is postulated in either case. Upon the proper use of boundary and bondness conditions, stress fields are derived within the laminate, along with the surrounding pinhole. The analytical results are compared to those of the finite element values. A very good agreement is observed between the two methods. According to the results, composite structures made of triangular glass fibers result in lower values of stress concentrations around the pin, as opposed to those of circular glass fibers.
Notch and the Survival of Regulatory T Cells: Location Is Everything!
Authors: Minter Lisa M. , Osborne Barbara A.
Published: July 2012

Cytosolic localization of Notch protects regulatory but not effector T cells from apoptosis caused by cytokine withdrawal.
Science Signaling
Podcast: 24 July 2012
Authors: Kirsch David G. , Lee Chang-Lung , VanHook Annalisa M.
Published: July 2012

A transcription factor protects the heart from radiation-induced damage.
Anti-Hepatitis C Virus Activity and Toxicity of Type III Phosphatidylinositol-4-Kinase Beta Inhibitors
Authors: LaMarche M. J. , Borawski J. , Bose A. , Capacci-Daniel C. , Colvin R. , Dennehy M. , Ding J. , Dobler M. , Drumm J. , Gaither L. A. , Gao J. , Jiang X. , Lin K. , McKeever U. , Puyang X. , Raman P. , Thohan S. , Tommasi R. , Wagner K. , Xiong X. , Zabawa T. , Zhu S. , Wiedmann B.
Published: July 2012

Type III phosphatidylinositol-4-kinase beta (PI4KIIIβ) was previously implicated in hepatitis C virus (HCV) replication by small interfering RNA (siRNA) depletion and was therefore proposed as a novel cellular target for the treatment of hepatitis C. Medicinal chemistry efforts identified highly selective PI4KIIIβ inhibitors that potently inhibited the replication of genotype 1a and 1b HCV replicons and genotype 2a virus
in vitro
. Replicon cells required more than 5 weeks to reach low levels of 3- to 5-fold resistance, suggesting a high resistance barrier to these cellular targets. Extensive
in vitro
profiling of the compounds revealed a role of PI4KIIIβ in lymphocyte proliferation. Previously proposed functions of PI4KIIIβ in insulin secretion and the regulation of several ion channels were not perturbed with these inhibitors. Moreover, PI4KIIIβ inhibitors were not generally cytotoxic as demonstrated across hundreds of cell lines and primary cells. However, an unexpected antiproliferative effect in lymphocytes precluded their further development for the treatment of hepatitis C.
Identification and Partial Characterization of Extracellular Aspartic Protease Genes from Metschnikowia pulcherrima IWBT Y1123 and Candida apicola IWBT Y1384
Authors: Reid Vernita J. , Theron Louwrens W. , du Toit Maret , Divol Benoit
Published: July 2012

The extracellular acid proteases of non-Saccharomyceswine yeasts may fulfill a number of roles in winemaking, which include increasing the available nitrogen sources for the growth of fermentative microbes, affecting the aroma profile of the wine, and potentially reducing protein haze formation. These proteases, however, remain poorly characterized, especially at genetic level. In this study, two extracellular aspartic protease-encoding genes were identified and sequenced, from two yeast species of enological origin: one gene fromMetschnikowia pulcherrimaIWBT Y1123, namedMpAPr1, and the other gene fromCandida apicolaIWBT Y1384, namedCaAPr1.In silicoanalysis of these two genes revealed a number of features peculiar to aspartic protease genes, and both the MpAPr1 and CaAPr1 putative proteins showed homology to proteases of yeast genera. Heterologous expression ofMpAPr1inSaccharomyces cerevisiaeYHUM272 confirmed that it encodes an aspartic protease. MpAPr1 production, which was shown to be constitutive, and secretion were confirmed in the presence of bovine serum albumin (BSA), casein, and grape juice proteins. TheMpAPr1gene was found to be present in 12 otherM. pulcherrimastrains; however, plate assays revealed that the intensity of protease activity was strain dependent and unrelated to the gene sequence.
Effects of Disinfection on Legionella spp., Eukarya, and Biofilms in a Hot Water System
Authors: Farhat Maha , Moletta-Denat Marina , Frï¿½re Jacques , Onillon Sï¿½verine , Trouilhï¿½ Marie-Cï¿½cile , Robine Enric
Published: July 2012

Legionella
species are frequently detected in hot water systems, attached to the surface as a biofilm. In this work, the dynamics of
Legionella
spp. and diverse bacteria and eukarya associated together in the biofilm, coming from a pilot scale 1 system simulating a real hot water system, were investigated throughout 6 months after two successive heat shock treatments followed by three successive chemical treatments. Community structure was assessed by a fingerprint technique, single-strand conformation polymorphism (SSCP). In addition, the diversity and dynamics of
Legionella
and eukarya were investigated by small-subunit (SSU) ribosomal cloning and sequencing. Our results showed that pathogenic
Legionella
species remained after the heat shock and chemical treatments (
Legionella pneumophila
and
Legionella anisa
, respectively). The biofilm was not removed, and the bacterial community structure was transitorily affected by the treatments. Moreover, several amoebae had been detected in the biofilm before treatments (
Thecamoebae
sp.,
Vannella
sp., and
Hartmanella vermiformis
) and after the first heat shock treatment, but only
H. vermiformis
remained. However, another protozoan affiliated with Alveolata, which is known as a host cell for
Legionella
, dominated the eukaryal species after the second heat shock and chemical treatment tests. Therefore, effective
Legionella
disinfection may be dependent on the elimination of these important microbial components. We suggest that eradicating
Legionella
in hot water networks requires better study of bacterial and eukaryal species associated with
Legionella
in biofilms.
Requirement of Signal Peptidase ComC and Thiol-Disulfide Oxidoreductase DsbA for Optimal Cell Surface Display of Pseudopilin ComGC in Staphylococcus aureus
Authors: van der Kooi-Pol Magdalena M. , Reilman Ewoud , Sibbald Mark J. J. B. , Veenstra-Kyuchukova Yanka K. , Kouwen Thijs R. H. M. , Buist Girbe , van Dijl Jan Maarten
Published: July 2012

Staphylococcus aureus
is an important Gram-positive bacterial pathogen producing many secreted and cell surface-localized virulence factors. Here we report that the staphylococcal thiol-disulfide oxidoreductase DsbA is essential for stable biogenesis of the ComGC pseudopilin. The signal peptidase ComC is indispensable for ComGC maturation and optimal cell surface exposure.
Protein A-Specific Monoclonal Antibodies and Prevention of Staphylococcus aureus Disease in Mice
Authors: Kim Hwan Keun , Emolo Carla , DeDent Andrea C. , Falugi Fabiana , Missiakas Dominique M. , Schneewind Olaf
Published: July 2012

Staphylococcus aureusis a leading cause of human soft tissue infections and bacterial sepsis. The emergence of antibiotic-resistant strains (methicillin-resistantS. aureus[MRSA]) has prompted research into staphylococcal vaccines and preventive measures. The envelope ofS. aureusis decorated with staphylococcal protein A (SpA), which captures the Fcγ portion of immunoglobulins to prevent opsonophagocytosis and associates with the Fab portion of VH3-type B cell receptors to trigger B cell superantigen activity. Nontoxigenic protein A (SpAKKAA), when used as an immunogen in mice, stimulates humoral immune responses that neutralize the Fcγ and the VH3+Fab binding activities of SpA and provide protection from staphylococcal abscess formation in mice. Here, we isolated monoclonal antibodies (MAbs) against SpAKKAAthat, by binding to the triple-helical bundle fold of its immunoglobulin binding domains (IgBDs), neutralize the Fcγ and Fab binding activities of SpA. SpAKKAAMAbs promoted opsonophagocytic killing of MRSA in mouse and human blood, provided protection from abscess formation, and stimulated pathogen-specific immune responses in a mouse model of staphylococcal disease. Thus, SpAKKAAMAbs may be useful for the prevention and therapy of staphylococcal disease in humans.
Innate Immune Gene Polymorphisms in Tuberculosis
Authors: Azad Abul K. , Sadee Wolfgang , Schlesinger Larry S.
Published: July 2012

Tuberculosis (TB) is a leading cause worldwide of human mortality attributable to a single infectious agent. Recent studies targeting candidate genes and “case-control” association have revealed numerous polymorphisms implicated in host susceptibility to TB. Here, we review current progress in the understanding of causative polymorphisms in host innate immune genes associated with TB pathogenesis. We discuss genes encoding several types of proteins: macrophage receptors, such as the mannose receptor (MR, CD206), dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN, CD209), Dectin-1, Toll-like receptors (TLRs), complement receptor 3 (CR3, CD11b/CD18), nucleotide oligomerization domain 1 (NOD1) and NOD2, CD14, P2X7, and the vitamin D nuclear receptor (VDR); soluble C-type lectins, such as surfactant protein-A (SP-A), SP-D, and mannose-binding lectin (MBL); phagocyte cytokines, such as tumor necrosis factor (TNF), interleukin-1β (IL-1β), IL-6, IL-10, IL-12, and IL-18; chemokines, such as IL-8, monocyte chemoattractant protein 1 (MCP-1), RANTES, and CXCL10; and other important innate immune molecules, such as inducible nitric oxide synthase (iNOS) and solute carrier protein 11A1 (SLC11A1). Polymorphisms in these genes have been variably associated with susceptibility to TB among different populations. This apparent variability is probably accounted for by evolutionary selection pressure as a result of long-term host-pathogen interactions in certain regions or populations and, in part, by lack of proper study design and limited knowledge of molecular and functional effects of the implicated genetic variants. Finally, we discuss genomic technologies that hold promise for resolving questions regarding the evolutionary paths of the human genome, functional effects of polymorphisms, and corollary impacts of adaptation on human health, ultimately leading to novel approaches to controlling TB.
The Amino Acid Sequence of Neisseria lactamica PorB Surface-Exposed Loops Influences Toll-Like Receptor 2-Dependent Cell Activation
Authors: Toussi Deana N. , Carraway Margaretha , Wetzler Lee M. , Lewis Lisa A. , Liu Xiuping , Massari Paola
Published: July 2012

Toll-like receptors (TLRs) play a major role in host mucosal and systemic defense mechanisms by recognizing a diverse array of conserved pathogen-associated molecular patterns (PAMPs). TLR2, with TLR1 and TLR6, recognizes structurally diverse bacterial products such as lipidated factors (lipoproteins and peptidoglycans) and nonlipidated proteins, i.e., bacterial porins. PorB is a pan-neisserial porin expressed regardless of organisms' pathogenicity. However, commensal
Neisseria lactamica
organisms and purified
N. lactamica
PorB (published elsewhere as Nlac PorB) induce TLR2-dependent proinflammatory responses of lower magnitude than
N. meningitidis
organisms and
N. meningitidis
PorB (published elsewhere as Nme PorB). Both PorB types bind to TLR2
in vitro
but with different apparent specificities. The structural and molecular details of PorB-TLR2 interaction are only beginning to be unraveled and may be due to electrostatic attraction. PorB molecules have significant strain-specific sequence variability within surface-exposed regions (loops) putatively involved in TLR2 interaction. By constructing chimeric recombinant PorB loop mutants in which surface-exposed loop residues have been switched between
N. lactamica
PorB and
N. meningitidis
PorB, we identified residues in loop 5 and loop 7 that influence TLR2-dependent cell activation using HEK cells and BEAS-2B cells. These loops are not uniquely responsible for PorB interaction with TLR2, but NF-κB and MAP kinases signaling downstream of TLR2 recognition are likely influenced by a hypothetical “TLR2-binding signature” within the sequence of PorB surface-exposed loops. Consistent with the effect of purified PorB
in vitro
, a chimeric
N. meningitidis
strain expressing
N. lactamica
PorB induces lower levels of interleukin 8 (IL-8) secretion than wild-type
N. meningitidis
, suggesting a role for PorB in induction of host cell activation by whole bacteria.
Evaluation of the Trimeric Autotransporter Ata as a Vaccine Candidate against Acinetobacter baumannii Infections
Authors: Bentancor Leticia V. , Routray Abhisek , Bozkurt-Guzel Cagla , Camacho-Peiro Ana , Pier Gerald B. , Maira-Litrán Tomás
Published: July 2012

Acinetobacter baumannii
is a multidrug-resistant (MDR) nosocomial pathogen for which immunotherapeutic alternatives are needed. We previously identified a surface autotransporter of
A. baumannii
, Ata, that bound to various extracellular matrix/basal membrane proteins and was required for full virulence, biofilm formation, and the adhesion of
A. baumannii
to collagen type IV. We show here that Ata binding to collagen type IV was inhibited by antibodies to Ata. In addition, in the presence of complement and polymorphonuclear cells (PMNs), antibodies to Ata were highly opsonic against
A. baumannii
ATCC 17978 and showed low to moderate killing activity against four heterologous
A. baumannii
strains, whereas in the absence of PMNs, antibody to Ata efficiently promoted complement-dependent bactericidal killing of all of the tested
A. baumannii
isolates. Using a pneumonia model of infection in both immunocompetent and immunocompromised mice, we found that, compared to normal rabbit sera, antisera to Ata significantly reduced the levels of
A. baumannii
ATCC 17978 and two MDR strains in the lungs of infected mice. The ability of Ata to engender anti-adhesive, bactericidal, opsonophagocytic, and protective antibodies validates its potential use as an antigenic target against MDR
A. baumannii
infections.
Basis for the Essentiality of H-NS Family Members in Pseudomonas aeruginosa
Authors: Castang Sandra , Dove Simon L.
Published: July 2012

Members of the histone-like nucleoid-structuring (H-NS) family of proteins have been shown to play important roles in silencing gene expression and in nucleoid compaction. InPseudomonas aeruginosa, the two H-NS family members MvaT and MvaU are thought to bind the same AT-rich regions of the chromosome and function coordinately to control a common set of genes. Here we present evidence that the loss of both MvaT and MvaU cannot be tolerated because it results in the production of Pf4 phage that superinfect and kill cells or inhibit their growth. Using a ClpXP-based protein depletion system in combination with transposon mutagenesis, we identify mutants ofP. aeruginosathat can tolerate the depletion of MvaT in an ΔmvaUmutant background. Many of these mutants contain insertions in genes encoding components, assembly factors, or regulators of type IV pili or contain insertions in genes of the prophage Pf4. We demonstrate that cells that no longer produce type IV pili or that no longer produce the replicative form of the Pf4 genome can tolerate the loss of both MvaT and MvaU. Furthermore, we show that the loss of both MvaT and MvaU results in an increase in expression of Pf4 genes and that cells that cannot produce type IV pili are resistant to infection by Pf4 phage. Our findings suggest that type IV pili are the receptors for Pf4 phage and that the essential activities of MvaT and MvaU are to repress the expression of Pf4 genes.
Identification and Characterization of the Functional Toxboxes in the Vibrio cholerae Cholera Toxin Promoter
Authors: Dittmer Jennifer B. , Withey Jeffrey H.
Published: July 2012

Following the consumption of contaminated food or water by a human host, the
Vibrio cholerae
bacterium produces virulence factors, including cholera toxin (CT), which directly causes voluminous diarrhea, producing cholera. A complex regulatory network controls virulence gene expression and responds to various environmental signals and transcription factors. Ultimately, ToxT, a member of the AraC/XylS transcription regulator family, is responsible for activating the transcription of the virulence genes. ToxT-regulated promoters all contain one or more copies of the toxbox, a 13-bp DNA sequence which ToxT recognizes. Nucleotides 2 through 7 of the toxbox sequence are well conserved and contain an invariant tract of four consecutive T nucleotides, whereas the remainder of the toxbox sequence is not highly conserved other than being A/T rich. The binding of ToxT to toxboxes is required to activate the transcription of virulence genes, and toxboxes in several virulence gene promoters have been characterized. However, the toxboxes required for the activation of transcription from the cholera toxin promoter P
ctxAB
have not been identified. P
ctxAB
contains a series of heptad repeats (GATTTTT), each of which matches the 5′ end of the toxbox consensus sequence and is a potential binding site for ToxT. Using site-directed mutagenesis and high-resolution copper-phenanthroline footprinting, we have identified the functional toxboxes required for the ToxT activation of P
ctxAB
. Our findings suggest that ToxT binds to only two toxboxes within P
ctxAB
, despite the presence of several other potential ToxT binding sites within the promoter. Both toxboxes are essential for DNA binding and the full activation of
ctxAB
transcription.