bluuebunny/crossref_metadata_2025 huggingface dataset:
Contested value and an ethics of resources: Water, mining and indigenous people in the Atacama Desert, Chile
Authors: Babidge Sally
Published: May 2015

The question of value is fundamental to contexts of resource scarcity given that contest over use and distribution of scarce resources centres on judgments about rights, interests and access. In mining processes, the use and extraction of water in great volumes commodifies and threatens supplies of what others understand to be a substance essential to all forms of life. In the Atacama, while industrial extraction and commodification by the mining industry are the basis for indigenous people's contestations over water resources, an analysis of everyday water practice and performance (as ‘ordinary ethics’) demonstrates that an indigenous ethics of resources includes commodity values under certain conditions. This paper examines a field of competing actors engaging in extraction and use of scarce waters in order to make an argument for the importance of considering the complexities and dynamics of ethical practice and water value.
The role of point‐of‐care tests in antibiotic stewardship for urinary tract infections in a resource‐limited setting on the Thailand–Myanmar border
Authors: Chalmers Lauren , Cross Jessica , Chu Cindy S. , Phyo Aung Pyae , Trip Margreet , Ling Clare , Carrara Verena , Watthanaworawit Wanitda , Keereecharoen Lily , Hanboonkunupakarn Borimas , Nosten François , McGready Rose
Published: May 2015

Objective

Published literature from resource‐limited settings is infrequent, although urinary tract infections (UTI) are a common cause of outpatient presentation and antibiotic use. Point‐of‐care test (POCT) interpretation relates to antibiotic use and antibiotic resistance. We aimed to assess the diagnostic accuracy of POCT and their role in UTI antibiotic stewardship.

Methods

One‐year retrospective analysis in three clinics on the Thailand–Myanmar border of non‐pregnant adults presenting with urinary symptoms. POCT (urine dipstick and microscopy) were compared to culture with significant growth classified as pure growth of a single organism >105 CFU/ml.

Results

In 247 patients, 82.6% female, the most common symptoms were dysuria (81.2%), suprapubic pain (67.8%) and urinary frequency (53.7%). After excluding contaminated samples, UTI was diagnosed in 52.4% (97/185); 71.1% (69/97) had a significant growth on culture, and >80% of these were Escherichia coli (20.9% produced extended‐spectrum β‐lactamase (ESBL)). Positive urine dipstick (leucocyte esterase ≥1 and/or nitrate positive) compared against positive microscopy (white blood cell >10/HPF, bacteria ≥1/HPF, epithelial cells <5/HPF) had a higher sensitivity (99% vs. 57%) but a lower specificity (47% vs. 89%), respectively. Combined POCT resulted in the best sensitivity (98%) and specificity (81%). Nearly one in ten patients received an antimicrobial to which the organism was not fully sensitive.

Conclusion

One rapid, cost‐effective POCT was too inaccurate to be used alone by healthcare workers, impeding antibiotic stewardship in a high ESBL setting. Appropriate prescribing is improved with concurrent use and concordant results of urine dipstick and microscopy.
Canine cutaneous melanocytic tumours: significance of β‐catenin and survivin immunohistochemical expression
Authors: Bongiovanni Laura , D'Andrea Alessandra , Porcellato Ilaria , Ciccarelli Andrea , Malatesta Daniela , Romanucci Mariarita , Della Salda Leonardo , Mechelli Luca , Brachelente Chiara
Published: May 2015

Background

Recent investigations have highlighted the controversial role of Wnt/β‐catenin pathway activation in human cutaneous melanoma. Survivin has been proposed as a valid prognostic marker for invasive and metastatic melanomas and lymph node melanoma metastasis in human cutaneous melanoma and is a promising therapeutic target.

Hypothesis/Objectives

Our aim was to investigate the immunohistochemical expression of survivin and β‐catenin in canine cutaneous melanocytic tumours, in order to understand their prognostic significance.

Methods

Twenty‐one melanocytic tumours (10 melanocytomas and 11 melanomas) were investigated by immunohistochemistry using specific anti‐survivin and anti‐β‐catenin antibodies. A semi‐quantitative method was used to analyse the results; β‐catenin immunolabelling in neoplastic cells was evaluated as cytoplasmic, membranous or nuclear. The number of survivin‐positive cells was counted within ~1000 neoplastic cells. Results were related to histopathological features, evaluated in haematoxylin‐ and eosin‐stained slides, and to the clinical data obtained through a telephone survey with referring veterinarians.

Results

Despite a low level of expression in the majority of cases, β‐catenin was found to be correlated strongly with malignant behaviour (P < 0.01). An overexpression of nuclear survivin was statistically related to histological features of malignancy, presence of metastasis and death related to melanoma spread (P < 0.01).

Conclusions and clinical importance

The low nuclear β‐catenin expression, mainly found in metastatic cases, would indicate that β‐catenin activation may have only limited importance in the development or progression of canine cutaneous melanoma. The correlation of nuclear survivin expression with malignancy would indicate that survivin is possibly a useful prognostic marker and therapeutic target in canine melanoma patients.
Nematode dermatitis due to Angiostrongylus vasorum infection in a dog
Authors: Cavana Paola , Bensignor Emmanuel , Blot Stéphane , Carlus Marine , Chermette René , Crosaz Odile , Grimm Felix , Hurion Murielle , Jeandel Aurélien , Polack Bruno
Published: May 2015

Background

Angiostrongylus vasorum is a nematode that primarily infects Canidae. The adult parasites are found in the pulmonary arterial circulation and the right side of the heart. The most common clinical sign is respiratory dysfunction. Bleeding, neurological, ocular, cardiovascular and gastrointestinal disorders are also reported. Skin lesions are very unusual.

Hypothesis/Objectives

This report describes a nematode dermatitis due to A. vasorum infection. To the best of the authors' knowledge, this is the first case of a dog infected with this parasite that initially presented with skin lesions only.

Animal

A 3‐year‐old female Weimaraner dog presented with a crusted papular dermatitis on the bridge of the nose and on the pinnae, and an erythematous pododermatitis with erosions and perionyxis of one digit of 1 week's duration. Two weeks later the dog developed respiratory distress.

Methods and results

Skin scrapings and fungal culture were negative for parasites and dermatophytes. Histopathological examination showed dermal granulomas and pyogranulomas with eosinophils centred around parasitic elements compatible with nematode larvae. Angiostrongylus vasorum DNA was demonstrated in skin biopsies. Chest radiographs were compatible with verminous pneumonia and a Baermann test revealed A. vasorum larvae. The dog was treated orally with fenbendazole, with rapid improvement and complete cure after 3 months.

Conclusions and clinical importance

Angiostrongylus vasorum should be considered in dogs presented with skin lesions and respiratory signs. Skin biopsy, chest radiographs and Baermann test should be included in the diagnostic investigation.
Barcroft's bold assertion: All dwellers at high altitudes are persons of impaired physical and mental powers
Authors: West John B.
Published: May 2015

Barcroft's bold assertion that everyone at high altitude has physical and mental impairment compared with sea level was very provocative. It was a result of the expedition that he led to Cerro de Pasco in Peru, altitude 4300 m. Although it is clear that newcomers to high altitude have reduced physical powers, some people believe that this does not apply to permanent residents who have been at high altitude for generations. The best evidence supports Barcroft's contention, although permanent residents often perform better than acclimatized lowlanders. Turning to neuropsychological function, newcomers to high altitude certainly have some impairment, and there is evidence that the same applies to highlanders. However the notion that permanent residents are impaired is anathema to many people. For example the eminent Peruvian physician Carlos Monge took great exception to Barcroft's remark and even attributed it to the fact that Barcroft was suffering from acute mountain sickness when he made it! Monge referred to ‘climatic aggression’, by which he meant the negative consequences of the inevitable hypoxia of high altitude. Recent technological advances such as oxygen enrichment of room air can overcome this ‘aggression’. This might be useful in some settings at high altitude such as a nursery where newborn babies are cared for, and possibly operating rooms where the surgeon's dexterity may be enhanced. Other situations might be dormitories, conference rooms, and perhaps some school rooms. These constitute possible ways by which the effects of Barcroft's assertion might be countered.
Mixed-Mode Interactions Between Graphene and Substrates by Blister Tests
Authors: Cao Zhiyi , Tao Li , Akinwande Deji , Huang Rui , Liechti Kenneth M.
Published: May 2015

Many of the attractive properties of graphene will only be realized when it can be mass produced. One bottleneck is the efficient transfer of graphene between various substrates in nanomanufacturing processes such as roll-to-roll and transfer printing. In such processes, it is important to understand how the ratio of shear-to-tension at the interface between graphene and substrates affects the adhesion energy. With this in mind, this paper examines the mixed-mode adhesive interactions between chemical vapor deposition (CVD) grown graphene that had been transferred to copper or silicon substrates. The approach that was taken was to use blister tests with a range of graphene backing layer materials and thicknesses in order to provide a wide range of the shear-to-tension ratio or fracture mode-mix at the interface. Raman spectroscopy was used to ensure that graphene had indeed been delaminated from each substrate. Measurements of pressure, top surface deflection, and blister diameter were coupled with fracture mechanics analyses to obtain the delamination resistance curves and steady state adhesion energy of each interface. The results showed that the adhesive interactions between graphene and both substrates (Cu and Si) had a strong dependence on the fracture mode-mix. In the absence of plasticity effects, the most likely explanation of this effect is asperity locking from the inherent surface roughness of the substrates.
Customized Encryption of Computer Aided Design Models for Collaboration in Cloud Manufacturing Environment
Authors: Cai Xiantao , Li Weidong , He Fazhi , Li Xiaoxia
Published: May 2015

Computer aided design (CAD) models reflect design goals, intentions, and functions so that they are the key intellectual properties of companies. In a Cloud manufacturing environment, how to effectively protect the sensitive feature information for a model owner while enabling the owner to flexibly share the rest of the CAD model with collaborators is an important yet challenging research issue. In this paper, an innovative partial encryption approach, which is able to represent a CAD model into the granularity of sharing information in order to address various collaboration scenarios and customized requirements from the model owner and collaborators, is presented. The approach is composed of a customized encryption algorithm for a CAD model, a key based customized authorization algorithm for collaborators to decrypt shared features in the model, and a customized geometric transformation method to support the effective protection model-based visualization of the model for collaboration. With this approach, a CAD model can be flexibly encrypted to realize partial sharing of features and safe protection of the rest of the model according to collaboration requirements. Meanwhile, during encryption and decryption, the CAD model is always manifold no matter which feature is encrypted or decrypted to ensure user friendliness, model validity, and robustness of the approach. A case study is used to verify and illustrate the effectiveness of the approach. This research is a new attempt to design a content-based and customized encryption approach applicable to CAD model-based collaboration in a Cloud manufacturing environment.
Antiwindup Design for Zero-Phase Repetitive Controllers
Authors: Flores J. V. , Gomes da Silva, J. M. , Sbarbaro D. , Turner M. C. , Salton A. T.
Published: May 2015

This paper addresses the antiwindup problem for linear systems equipped with the zero-phase repetitive controller (ZPRC). The antiwindup compensator is designed using a coprime factorization technique and conditions to characterize the sets of admissible references and disturbances are proposed. A numerical example illustrates the application and potentialities of the proposed methodology.
Coupled Lateral and Torsional Nonlinear Transient Rotor–Bearing System Analysis With Applications
Authors: Cao Jianming , Allaire Paul , Dimond Timothy
Published: May 2015

This paper provides a time transient method for solving coupled lateral and torsional analysis of a flexible rotor–bearing system including gyroscopic effects, nonlinear short journal bearings, nonlinear short squeeze film dampers (SFDs), and external nonlinear forces/torques. The rotor is modeled as linear, and the supporting components, including bearings and dampers, are modeled as nonlinear. An implicit Runge–Kutta method is developed to solve the nonlinear equations of motion with nonconstant operating speed since the unbalance force and the gyroscopic effect are related to both the rotational speed and the acceleration. The developed method is compared with a previous torsional analysis first to verify the nonlinear transient solver. Then the coupled lateral and torsional analysis of an example flexible three-disk rotor, perhaps representing a compressor, with nonlinear bearings and nonlinear dampers driven by a synchronous motor is approached. The acceleration effects on lateral and torsional amplitudes of vibration are presented in the analysis. The developed method can be used to study the rotor motion with nonconstant rotational speed such as during startup, shutdown, going through critical speeds, blade loss force, or other sudden loading.
Experimental Investigation of the Role of Large Scale Cavitating Vortical Structures in Performance Breakdown of an Axial Waterjet Pump
Authors: Tan David , Li Yuanchao , Wilkes Ian , Vagnoni Elena , Miorini Rinaldo L. , Katz Joseph
Published: May 2015

Flow phenomena and mechanisms involved in cavitation breakdown, namely, a severe degradation of pump performance caused by cavitation, have been a longstanding puzzle. In this paper, results of high-speed imaging as well as pressure and performance measurements are used to elucidate the specific mechanism involved with cavitation breakdown within an axial waterjet pump. The experiments have been performed using geometrically identical aluminum and transparent acrylic rotors, the latter allowing uninhibited visual access to the cavitation phenomena within the blade passage. The observations demonstrate that interaction between the tip leakage vortex (TLV) and trailing edge of the attached cavitation near the rotor blade tip that covers the suction side (SS) of the blade plays a key role in processes leading to breakdown. In particular, the vortical cloud cavitation developing at the trailing edge of the sheet cavity near the blade tip is entrained and re-oriented by the TLV in a direction that is nearly perpendicular to the blade SS surface, and then convected downstream through the blade passage. Well above breakdown cavitation indices, these “perpendicular cavitating vortices” or PCVs occur in the region where blades do not overlap, and they only affect the local flow complexity with minimal impact on the global pump performance. With decreasing pressure and growing sheet cavitation coverage of the blade surface, this interaction occurs in the region where two adjacent rotor blades overlap, and the PCV extends from the SS surface of the originating blade to the pressure side (PS) of the neighboring blade. Cavitation breakdown begins when the PCV extends between blades, effectively blocking the tip region of the rotor passage. With further decrease in pressure, the PCVs grow in size and strength, and extend deeper into the passage, causing rapid degradation in performance. Accordingly, the casing pressure measurements confirm that attachment of the PCV to the PS of the blade causes rapid decrease in the pressure difference across this blade, i.e., a rapid decrease in blade loading near the tip. Similar large perpendicular vortical structures have been observed in the heavily loaded cavitating rocket inducers (Acosta, 1958, “An Experimental Study of Cavitating Inducers,” Proceedings of the Second Symposium on Naval Hydrodynamics, ONR/ACR-38, pp. 537–557 and Tsujimoto, 2007, “Tip Leakage and Backflow Vortex Cavitation,” Fluid Dynamics of Cavitation and Cavitating Turbopumps, L. d'Agostino and M. Salvetti, eds., Springer, Vienna, Austria, pp. 231–251), where they extend far upstream of the rotor and cause global flow instabilities.
Single-Crystalline, Nanoporous Gallium Nitride Films With Fine Tuning of Pore Size for Stem Cell Engineering
Authors: Han Lin , Zhou Jing , Schimert Kristin I. , Sun Yubing , Zhang Yu , Han Jung , Fu Jianping , Fan Rong
Published: May 2015

Single-crystalline nanoporous gallium nitride (GaN) thin films were fabricated with the pore size readily tunable in 20–100 nm. Uniform adhesion and spreading of human mesenchymal stem cells (hMSCs) seeded on these thin films peak on the surface with pore size of 30 nm. Substantial cell elongation emerges as pore size increases to ∼80 nm. The osteogenic differentiation of hMSCs occurs preferentially on the films with 30 nm sized nanopores, which is correlated with the optimum condition for cell spreading, which suggests that adhesion, spreading, and stem cell differentiation are interlinked and might be coregulated by nanotopography.
Lanthanum quantification for optimization of advanced high-k/metal gate stacks using low energy electron x-ray emission spectrometry
Authors: Martinez Eugénie , Bertin François , Trouiller C. , Caubet P. , Moret M. P. , Robbes A.-S. , Bui-T Meura K.-A. , Dulac O. , Morel N.
Published: May 2015

The authors report about accurate monitoring of ultralow La doses inserted in advanced high-k/metal gate stacks for threshold voltage tuning purposes. Three characterization techniques are implemented for precise and reproducible lanthanum quantification. Low energy electron x-ray emission spectrometry capabilities are highlighted in terms of sensitivity and accuracy, thanks to a comparison with reference results obtained by Rutherford Backscattering Spectrometry. The capabilities of state-of-the-art Auger nanoprobes for depth profiling in the subnanometer range are also illustrated.
Association of Longitudinal Changes of Physical Activity on Smoking Cessation Among Young Daily Smokers
Authors: Loprinzi Paul D. , Walker Jerome F.
Published: May 2015

Objective:

To our knowledge, no longitudinal epidemiological study among daily smokers has examined the effects of physical activity change/trajectory on smoking cessation. The purpose of this study was to examine the longitudinal effects of changes in physical activity on smoking cessation among a national sample of young (16–24 y) daily smokers.

Methods:

Data from the 2003–2005 National Youth Smoking Cessation Survey were used (N = 1178). Using hierarchical agglomerative cluster analysis, 5 distinct self-reported physical activity trajectories over 3 time periods (baseline, 12-month, and 24-month follow-up) were observed, including stable low physical activity, decreasing physical activity, curvilinear physical activity, stable high physical activity, and increasing physical activity. Nicotine dependence (Heaviness of Smoking Index) and demographic parameters were assessed via survey.

Results:

With stable low physical activity (16.2% quit smoking) serving as the referent group, those in the stable high physical activity (24.8% quit smoking) group had 1.8 greater odds of not smoking at the 24-month follow-up period (odds ratio = 1.81; 95% confidence interval, 1.12–2.91) after adjusting for nicotine dependence, age, gender, race-ethnicity, and education.

Conclusions:

Maintenance of regular physical activity among young daily smokers may help to facilitate smoking cessation.
Phosphorylation of GATA-6 is required for vascular smooth muscle cell differentiation after mTORC1 inhibition
Authors: Xie Yi , Jin Yu , Merenick Bethany L. , Ding Min , Fetalvero Kristina M. , Wagner Robert J. , Mai Alice , Gleim Scott , Tucker David F. , Birnbaum Morris J. , Ballif Bryan A. , Luciano Amelia K. , Sessa William C. , Rzucidlo Eva M. , Powell Richard J. , Hou Lin , Zhao Hongyu , Hwa John , Yu Jun , Martin Kathleen A.
Published: May 2015

Increasing the activity of the transcription factor GATA-6 prevents excessive proliferation of vascular smooth muscle cells in injured blood vessels.
How inhibition of TORC1 stimulates gene expression
Authors: VanHook Annalisa M.
Published: May 2015

The transcription factors REPTOR and REPTOR-BP stimulate the expression of nutrient stress genes in response to reduced TORC1 signaling.
Staphylococcus aureus Metabolic Adaptations during the Transition from a Daptomycin Susceptibility Phenotype to a Daptomycin Nonsusceptibility Phenotype
Authors: Gaupp Rosmarie , Lei Shulei , Reed Joseph M. , Peisker Henrik , Boyle-Vavra Susan , Bayer Arnold S. , Bischoff Markus , Herrmann Mathias , Daum Robert S. , Powers Robert , Somerville Greg A.
Published: May 2015

Staphylococcus aureus
is a major cause of nosocomial and community-acquired infections. The success of
S. aureus
as a pathogen is due in part to its many virulence determinants and resistance to antimicrobials. In particular, methicillin-resistant
S. aureus
has emerged as a major cause of infections and led to increased use of the antibiotics vancomycin and daptomycin, which has increased the isolation of vancomycin-intermediate
S. aureus
and daptomycin-nonsusceptible
S. aureus
strains. The most common mechanism by which
S. aureus
acquires intermediate resistance to antibiotics is by adapting its physiology and metabolism to permit growth in the presence of these antibiotics, a process known as adaptive resistance. To better understand the physiological and metabolic changes associated with adaptive resistance, six daptomycin-susceptible and -nonsusceptible isogenic strain pairs were examined for changes in growth, competitive fitness, and metabolic alterations. Interestingly, daptomycin nonsusceptibility coincides with a slightly delayed transition to the postexponential growth phase and alterations in metabolism. Specifically, daptomycin-nonsusceptible strains have decreased tricarboxylic acid cycle activity, which correlates with increased synthesis of pyrimidines and purines and increased carbon flow to pathways associated with wall teichoic acid and peptidoglycan biosynthesis. Importantly, these data provided an opportunity to alter the daptomycin nonsusceptibility phenotype by manipulating bacterial metabolism, a first step in developing compounds that target metabolic pathways that can be used in combination with daptomycin to reduce treatment failures.
Population Pharmacokinetics, Tolerability, and Safety of Dihydroartemisinin-Piperaquine and Sulfadoxine-Pyrimethamine-Piperaquine in Pregnant and Nonpregnant Papua New Guinean Women
Authors: Benjamin John M. , Moore Brioni R. , Salman Sam , Page-Sharp Madhu , Tawat Somoyang , Yadi Gumal , Lorry Lina , Siba Peter M. , Batty Kevin T. , Robinson Leanne J. , Mueller Ivo , Davis Timothy M. E.
Published: May 2015

The tolerability, safety, and disposition of dihydroartemisinin (DHA) and piperaquine (PQ) were assessed in 32 pregnant (second/third trimester) and 33 nonpregnant Papua New Guinean women randomized to adult treatment courses of DHA-PQ (three daily doses) or sulfadoxine-pyrimethamine (SP)-PQ (three daily PQ doses, single dose of SP). All dose adminstrations were observed, and subjects fasted for 2 h postdose. Plasma PQ was assayed by using high-performance liquid chromatography, and DHA was assessed by using liquid chromatography-mass spectrometry. Compartmental pharmacokinetic models were developed using a population-based approach. Both regimens were well tolerated. There was an expected increase in the rate-corrected electrocardiographic QT interval which was independent of pregnancy and treatment. Two pregnant and two nonpregnant women had
Plasmodium falciparum
parasitemia which cleared within 48 h, and no other subject became slide positive for malaria during 42 days of follow-up. Of 30 pregnant women followed to delivery, 27 (90%) delivered healthy babies and 3 (10%) had stillbirths; these obstetric outcomes are consistent with those in the general population. The area under the plasma PQ concentration-time curve (AUC
0–∞
) was lower in the pregnant patients (median [interquartile range], 23,721 μg · h/liter [21,481 to 27,951 μg · h/liter] versus 35,644 μg · h/liter [29,546 to 39,541 μg · h/liter];
P
< 0.001) in association with a greater clearance relative to bioavailability (73.5 liters/h [69.4 to 78.4] versus 53.8 liters/h [49.7 to 58.2];
P
< 0.001), but pregnancy did not influence the pharmacokinetics of DHA. The apparent pharmacokinetic differences between the present study and results from other studies of women with uncomplicated malaria that showed no effect of pregnancy on the AUC
0–∞
of PQ and greater bioavailability may reflect differences in postdose fat intake, proportions of women with malaria, and/or racial differences in drug disposition.
Pharmacokinetics of Piperaquine Transfer into the Breast Milk of Melanesian Mothers
Authors: Moore Brioni R. , Salman Sam , Benjamin John , Page-Sharp Madhu , Yadi Gumal , Batty Kevin T. , Siba Peter M. , Mueller Ivo , Davis Timothy M. E.
Published: May 2015

Transfer of piperaquine (PQ) into breast milk was examined in 27 Papua New Guinean women given a 3-day course of dihydroartemisinin-PQ or sulfadoxine-pyrimethamine-PQ during the second/third trimester. Breast milk was sampled on days 1, 2, 3 to 5, 7 to 11, and 14 to 17 postdelivery, a median of 70 days postdose (range, 6 to 145 days). A blood sample was taken at delivery, and additional serial samples were available from 9 women who delivered within 42 days of dosing. Milk and plasma PQ were assayed by high-performance liquid chromatography. A population-based approach was used to model the log
e
(plasma) and milk concentration-time data. A sigmoid
E
max
model best described PQ breast milk transfer. The population average milk:plasma PQ ratio was 0.58, with a peak of 2.5 at delivery. The model-derived maximum milk intake (148 ml/kg of body weight/day) was similar to the accepted value of 150 ml/kg/day. The median estimated absolute and relative cumulative infant PQ doses were 22 μg and 0.07%, respectively, corresponding to absolute and relative daily doses of 0.41 μg/kg and 0.004%. Model-based simulations for PQ treatment regimens given at birth, 1 week postdelivery, and 6 weeks postdelivery showed that the highest median estimated relative total infant dose (0.36%; median absolute total dose of 101 μg/kg) was seen after maternal PQ treatment 6 weeks postpartum. The maximum simulated relative total and daily doses from any scenario were 4.3% and 2.5%, respectively, which were lower than the recommended 10% upper limit. Piperaquine is transferred into breast milk after maternal treatment doses, but PQ exposure for suckling infants appears safe.
Identification of OprF as a Complement Component C3 Binding Acceptor Molecule on the Surface of Pseudomonas aeruginosa
Authors: Mishra Meenu , Ressler Adam , Schlesinger Larry S. , Wozniak Daniel J.
Published: May 2015

Pseudomonas aeruginosa
is a versatile opportunistic pathogen that can cause devastating persistent infections. Complement is a highly conserved pathway of the innate immune system, and its role in the first line of defense against pathogens is widely appreciated. One of the earliest events in the complement cascade is the conversion of C3 to C3a and C3b, the latter typically binds to one or more acceptor molecules on the pathogen surface. We previously demonstrated that complement C3b binding acceptors exist on the
P. aeruginosa
surface. In the current study, we utilized either C3 polyclonal or C3b monoclonal antibodies in a far-Western technique followed by mass spectroscopy to identify the C3b acceptor molecule(s) on the
P. aeruginosa
surface. Our data provide evidence that OprF (an outer membrane porin, highly conserved in the
Pseudomonadaceae
) binds C3b. An
oprF
-deficient
P. aeruginosa
strain exhibits reduced C3 deposition compared to the wild type. We observed reduced internalization of
oprF
-deficient bacteria by neutrophils after opsonization compared with wild-type
P. aeruginosa
. Heterologous expression of OprF significantly enhanced C3b binding and increased serum-mediated bactericidal effects in complement-susceptible
Escherichia coli
. Furthermore, the predicted secondary structure of the C-terminal, surface-exposed region of OprF has high structural identity to the OmpA domain of several other Gram-negative bacteria, one of which is known to bind C3b. Therefore, these findings provide new insights into the biology of complement interactions with
P. aeruginosa
and other Gram-negative bacteria.
Allergic Lung Inflammation Reduces Tissue Invasion and Enhances Survival from Pulmonary Pneumococcal Infection in Mice, Which Correlates with Increased Expression of Transforming Growth Factor β1 and SiglecF
low
Alveolar Macrophages
Authors: Sanfilippo Alan M. , Furuya Yoichi , Roberts Sean , Salmon Sharon L. , Metzger Dennis W.
Published: May 2015

Asthma is generally thought to confer an increased risk for invasive pneumococcal disease (IPD) in humans. However, recent reports suggest that mortality rates from IPD are unaffected in patients with asthma and that chronic obstructive pulmonary disease (COPD), a condition similar to asthma, protects against the development of complicated pneumonia. To clarify the effects of asthma on the subsequent susceptibility to pneumococcal infection, ovalbumin (OVA)-induced allergic lung inflammation (ALI) was induced in mice followed by intranasal infection with A66.1 serotype 3
Streptococcus pneumoniae
. Surprisingly, mice with ALI were significantly more resistant to lethal infection than non-ALI mice. The heightened resistance observed following ALI correlated with enhanced early clearance of pneumococci from the lung, decreased bacterial invasion from the airway into the lung tissue, a blunted inflammatory cytokine and neutrophil response to infection, and enhanced expression of transforming growth factor β1 (TGF-β1). Neutrophil depletion prior to infection had no effect on enhanced early bacterial clearance or resistance to IPD in mice with ALI. Although eosinophils recruited into the lung during ALI appeared to be capable of phagocytizing bacteria, neutralization of interleukin-5 (IL-5) to inhibit eosinophil recruitment likewise had no effect on early clearance or survival following infection. However, enhanced resistance was associated with an increase in levels of clodronate-sensitive, phagocytic SiglecF
low
alveolar macrophages within the airways following ALI. These findings suggest that, while the risk of developing IPD may actually be decreased in patients with acute asthma, additional clinical data are needed to better understand the risk of IPD in patients with different asthma phenotypes.
Vitamin A-Deficient Hosts Become Nonsymptomatic Reservoirs of Escherichia coli-Like Enteric Infections
Authors: McDaniel Kaitlin L. , Restori Katherine H. , Dodds Jeffery W. , Kennett Mary J. , Ross A. Catharine , Cantorna Margherita T.
Published: May 2015

Vitamin A deficiency (A−) remains a public health concern in developing countries and is associated with increased susceptibility to infection.Citrobacter rodentiumwas used to model humanEscherichia coliinfections. A−mice developed a severe and lethal (40%) infection. Vitamin A-sufficient (A+) mice survived and cleared the infection by day 25. Retinoic acid treatment of A−mice at the peak of the infection eliminatedC. rodentiumwithin 16 days. Inflammation levels were not different between A+and A−mouse colons, although the A−mice were still infected at day 37. Increased mortality of A−mice was not due to systemic cytokine production, an inability to clear systemicC. rodentium, or increased pathogenicity. Instead, A−mice developed a severe gut infection with most of the A−mice surviving and resolving inflammation but not eliminating the infection. Improvements in vitamin A status might decrease susceptibility to enteric pathogens and prevent potential carriers from spreading infection to susceptible populations.
The Human Antimicrobial Protein Calgranulin C Participates in Control of Helicobacter pylori Growth and Regulation of Virulence
Authors: Haley Kathryn P. , Delgado Alberto G. , Piazuelo M. Blanca , Mortensen Brittany L. , Correa Pelayo , Damo Steven M. , Chazin Walter J. , Skaar Eric P. , Gaddy Jennifer A.
Published: May 2015

During infectious processes, antimicrobial proteins are produced by both epithelial cells and innate immune cells. Some of these antimicrobial molecules function by targeting transition metals and sequestering these metals in a process referred to as “nutritional immunity.” This chelation strategy ultimately starves invading pathogens, limiting their growth within the vertebrate host. Recent evidence suggests that these metal-binding antimicrobial molecules have the capacity to affect bacterial virulence, including toxin secretion systems. Our previous work showed that the S100A8/S100A9 heterodimer (calprotectin, or calgranulin A/B) binds zinc and represses the elaboration of the
H. pylori
cag
type IV secretion system (T4SS). However, there are several other S100 proteins that are produced in response to infection. We hypothesized that the zinc-binding protein S100A12 (calgranulin C) is induced in response to
H. pylori
infection and also plays a role in controlling
H. pylori
growth and virulence. To test this, we analyzed gastric biopsy specimens from
H. pylori
-positive and -negative patients for S100A12 expression. These assays showed that S100A12 is induced in response to
H. pylori
infection and inhibits bacterial growth and viability
in vitro
by binding nutrient zinc. Furthermore, the data establish that the zinc-binding activity of the S100A12 protein represses the activity of the
cag
T4SS, as evidenced by the gastric cell “hummingbird” phenotype, interleukin 8 (IL-8) secretion, and CagA translocation assays. In addition, high-resolution field emission gun scanning electron microscopy (FEG-SEM) was used to demonstrate that S100A12 represses biogenesis of the
cag
T4SS. Together with our previous work, these data reveal that multiple S100 proteins can repress the elaboration of an oncogenic bacterial surface organelle.
Immunogold Localization of Key Metabolic Enzymes in the Anammoxosome and on the Tubule-Like Structures of Kuenenia stuttgartiensis
Authors: de Almeida Naomi M. , Neumann Sarah , Mesman Rob J. , Ferousi Christina , Keltjens Jan T. , Jetten Mike S. M. , Kartal Boran , van Niftrik Laura
Published: May 2015

Anaerobic ammonium-oxidizing (anammox) bacteria oxidize ammonium with nitrite as the terminal electron acceptor to form dinitrogen gas in the absence of oxygen. Anammox bacteria have a compartmentalized cell plan with a central membrane-bound “prokaryotic organelle” called the anammoxosome. The anammoxosome occupies most of the cell volume, has a curved membrane, and contains conspicuous tubule-like structures of unknown identity and function. It was suggested previously that the catalytic reactions of the anammox pathway occur in the anammoxosome, and that proton motive force was established across its membrane. Here, we used antibodies raised against five key enzymes of the anammox catabolism to determine their cellular location. The antibodies were raised against purified native hydroxylamine oxidoreductase-like protein kustc0458 with its redox partner kustc0457, hydrazine dehydrogenase (HDH; kustc0694), hydroxylamine oxidase (HOX; kustc1061), nitrite oxidoreductase (NXR; kustd1700/03/04), and hydrazine synthase (HZS; kuste2859-61) of the anammox bacterium
Kuenenia stuttgartiensis
. We determined that all five protein complexes were exclusively located inside the anammoxosome matrix. Four of the protein complexes did not appear to form higher-order protein organizations. However, the present data indicated for the first time that NXR is part of the tubule-like structures, which may stretch the whole length of the anammoxosome. These findings support the anammoxosome as the locus of catabolic reactions of the anammox pathway.

IMPORTANCE
Anammox bacteria are environmentally relevant microorganisms that contribute significantly to the release of fixed nitrogen in nature. Furthermore, the anammox process is applied for nitrogen removal from wastewater as an environment-friendly and cost-effective technology. These microorganisms feature a unique cellular organelle, the anammoxosome, which was proposed to contain the energy metabolism of the cell and tubule-like structures with hitherto unknown function. Here, we purified five native enzymes catalyzing key reactions in the anammox metabolism and raised antibodies against these in order to localize them within the cell. We showed that all enzymes were located within the anammoxosome, and nitrite oxidoreductase was located exclusively at the tubule-like structures, providing the first insights into the function of these subcellular structures.
In Salmonella enterica, Ethanolamine Utilization Is Repressed by 1,2-Propanediol To Prevent Detrimental Mixing of Components of Two Different Bacterial Microcompartments
Authors: Sturms Ryan , Streauslin Nicholas A. , Cheng Shouqiang , Bobik Thomas A.
Published: May 2015

Bacterial microcompartments (MCPs) are a diverse family of protein-based organelles composed of metabolic enzymes encapsulated within a protein shell. The function of bacterial MCPs is to optimize metabolic pathways by confining toxic and/or volatile metabolic intermediates. About 20% of bacteria produce MCPs, and there are at least seven different types. Different MCPs vary in their encapsulated enzymes, but all have outer shells composed of highly conserved proteins containing bacterial microcompartment domains. Many organisms have genes encoding more than one type of MCP, but given the high homology among shell proteins, it is uncertain whether multiple MCPs can be functionally expressed in the same cell at the same time. In these studies, we examine the regulation of the 1,2-propanediol (1,2-PD) utilization (Pdu) and ethanolamine utilization (Eut) MCPs in
Salmonella
. Studies showed that 1,2-PD (shown to induce the Pdu MCP) represses transcription of the Eut MCP and that the PocR regulatory protein is required. The results indicate that repression of the Eut MCP by 1,2-PD is needed to prevent detrimental mixing of shell proteins from the Eut and Pdu MCPs. Coexpression of both MCPs impaired the function of the Pdu MCP and resulted in the formation of hybrid MCPs composed of Eut and Pdu MCP components. We also show that plasmid-based expression of individual shell proteins from the Eut MCP or the β-carboxysome impaired the function of Pdu MCP. Thus, the high conservation among bacterial microcompartment (BMC) domain shell proteins is problematic for coexpression of the Eut and Pdu MCPs and perhaps other MCPs as well.

IMPORTANCE
Bacterial MCPs are encoded by nearly 20% of bacterial genomes, and almost 40% of those genomes contain multiple MCP gene clusters. In this study, we examine how the regulation of two different MCP systems (Eut and Pdu) is integrated in
Salmonella
. Our findings indicate that 1,2-PD (shown to induce the Pdu MCP) represses the Eut MCP to prevent detrimental mixing of Eut and Pdu shell proteins. These findings suggest that numerous organisms which produce more than one type of MCP likely need some mechanism to prevent aberrant shell protein interactions.
Non-puerperal uterine inversion in a patient with intracranial sigmoid sinus thrombosis and facial palsy
Authors: Datta Mamta Rath , Nag Deb Sanjay , Kabiraj Manas
Published: May 2015

Non-puerperal uterine inversion and cranial nerve palsies in patients with sigmoid sinus thrombosis are both extremely rare. We report a case of a patient who presented with both simultaneously. The symptoms of sigmoid sinus thrombosis resolved with subcutaneous enoxaparin, and an abdominal dissection with removal of the uterus vaginally resulted in a successful outcome for the patient.
Wearable technology: using Google Glass as a teaching tool
Authors: Knight Hui Min , Gajendragadkar Parag Ravindra , Bokhari Awais
Published: May 2015

Wearable technology holds great promise in revolutionising healthcare delivery. The benefits can also be seen in medical education and delivering healthcare in remote places. We report the use of Google Glass technology as a teaching tool in broadcasting a procedure onto a mobile phone as a viewer, replacing expensive and often cumbersome existing equipment.
Successful treatment of a patient with severe atopic dermatitis and severe asthma by centrifugal therapeutic plasma exchange
Authors: Fuller Louise , Maru Benit , Isserlis Neil , Cerio Rino
Published: May 2015

This is a case of a 42-year-old atopic man with severe atopic dermatitis and asthma who despite long-term immunosuppression was not well controlled. He had a very high IgE at 7897 Iu/mL prior to treatment. He underwent two therapeutic plasma exchanges (TPEs) through two peripheral lines in our outpatient department, which led to an absolute decrease of 44.1% and 37% in his plasma IgE for each exchange, and immediate sustained improvement in shortness of breath, and atopic dermatitis, and hence led to a vast improvement in his quality of life. TPE offers a new exciting adjunctive treatment option for severe atopic individuals, where it may provide a novel role to reduce health burden and improve clinical symptoms. Further studies need to be performed to establish an optimal protocol and potential maintenance with recently available targeted anti-IgE biologics.
Pagetoid polyostotic fibrous dysplasia
Authors: Hosalkar Rashmi Maruti , Pathak Jigna , Swain Niharika , Mohanty Neeta
Published: May 2015

Fibrous dysplasia (FD) is a benign skeletal lesion occurring due to mutation of Gs α gene and involves one or multiple bones. We present a case of a 30-year-old female patient, with a 1-year history of swelling under her right eye that had gradually increased in size. Extraoral examination revealed a diffuse swelling extending anteroposteriorly from preauricular region to nasolabial fold, frontonasal region and superoinferiorly from zygoma to body of mandible, causing ipsilateral proptosis and contralateral deviation of nose. Intraoral examination showed obliteration of right upper and lower buccal vestibule. CT disclosed expansile lytic lesions involving multiple skull bones, jaws, sternum, rib and thoracic vertebrae. Histopathology displayed broad and interconnected trabeculae connected to the host bone exhibiting reversal lines resembling the mosaic pattern of Paget's disease. These features suggested pagetoid polyostotic FD. The patient underwent cosmetic recontouring and is under regular follow-up postoperatively.
Subarachnoid hemorrhage then thrombosis of posterior inferior cerebellar artery dissection: is early surgical exploration warranted?
Authors: Alexiades Nikita G , Ellis Jason A , Meyers Philip M , Connolly E Sander
Published: May 2015

The natural history of spontaneous cerebral artery dissection and thrombosis remains uncertain. Concurrent subarachnoid hemorrhage further complicates the therapeutic approach. Thus the best strategy for managing patients with acute vessel thrombosis in the setting of subarachnoid hemorrhage is unclear. Here we present a case of spontaneous posterior inferior cerebellar artery dissection presenting with subarachnoid hemorrhage and acute thrombosis. Although the patient was initially managed conservatively, angiographic follow-up demonstrated recanalization of the diseased vessel, necessitating definitive treatment. Thus we propose that angiographic follow-up is necessary in the management of patients with subarachnoid hemorrhage in association with apparent vessel thrombosis.
A large mesenteric paraganglioma with lymphovascular invasion
Authors: Mohd Slim Mohd Afiq , Yoong Susan , Wallace William , Gardiner Keith
Published: May 2015

Mesenteric paraganglioma is a rare tumour with only 17 known published case reports so far. This is the second case that demonstrates lymphovascular invasion of the tumour and the third that exhibits its malignant potential. We present a case of a 69-year-old woman with a large palpable abdominal mass that was thought to arise from the ovary following a staging CT scan. Intraoperatively, a large ovoid mass measuring 18 cm×15 cm×11.5 cm was found on the small bowel mesentery. Histological examination revealed the characteristic Zellbalen pattern with lymphovascular involvement. Mesenteric paraganglioma is rare and remains a diagnostic dilemma. Although the majority of paragangliomas are non-functional and do not show any malignant potential, individual case-based management is needed in view of their unpredictable nature. A multidisciplinary approach with genetic counselling and long-term follow-up are usually necessary to monitor for future disease recurrence.
Atrial myxoma: a rare but well-described cause of increased erythrocyte sedimentation rate and anaemia
Authors: Ekström Mattias , Svenarud Peter
Published: May 2015

A 56-year-old woman visited her general practitioner 12 months prior with eczema. Blood samples showed anaemia, a haemoglobin level of 105 g/L and a high erythrocyte sedimentation rate (ESR) of 80 mm. Her eczema was diagnosed as discoid lupus erythaematosus but there were no signs of systemic lupus erythaematosus. Extensive investigations were made including testing of serial blood samples, repeated examinations by specialists in dermatology, rheumatology and gynaecology, and several X-rays including CT of the chest and the abdomen, all without finding a reasonable underlying diagnosis. One year later, the patient presented with dyspnoea associated with effort and body position; she was sent for echocardiography, which showed an atrial myxoma filling almost the whole left atrium and affecting the mitral valve. She was treated with urgent surgical removal and now, 6 weeks postsurgery, has fully recovered. She no longer has dyspnoea, her haemoglobin level and ESR have normalised, and the eczema has almost disappeared.