bluuebunny/crossref_metadata_2025 huggingface dataset:
Saxagliptin reduces renal tubulointerstitial inflammation, hypertrophy and fibrosis in diabetes
Authors: Gangadharan Komala Muralikrishna , Gross Simon , Zaky Amgad , Pollock Carol , Panchapakesan Usha
Published: September 2015

Aim

In addition to lowering blood glucose in patients with type 2 diabetes mellitus, dipeptidyl peptidase 4 (DPP4) inhibitors have been shown to be antifibrotic and anti‐inflammatory. We have previously shown that DPP4 inhibition in human kidney proximal tubular cells exposed to high glucose reduced fibrotic and inflammatory markers. Hence, we wanted to demonstrate renoprotection in an in vivo model.

Methods

We used a type 1 diabetic animal model to explore the renoprotective potential of saxagliptin independent of glucose lowering. We induced diabetes in enos −/− mice using streptozotocin and matched glucose levels using insulin. Diabetic mice were treated with saxagliptin and outcomes compared with untreated diabetic mice.

Results

We provide novel data that saxagliptin limits renal hypertrophy, transforming growth factor beta‐related fibrosis and NF‐κBp65‐mediated macrophage infiltration. Overall, there was a reduction in histological markers of tubulointerstitial fibrosis. There was no reduction in albuminuria or glomerulosclerosis.

Conclusion

Our findings highlight the potential of DPP4 inhibition as additional therapy in addressing the multiple pathways to achieve renoprotection in diabetic nephropathy.
Surviving metabolic arrest: photosynthesis during desiccation and rehydration in resurrection plants
Authors: Challabathula Dinakar , Puthur Jos T. , Bartels Dorothea
Published: September 2015

Photosynthesis is the key process that is affected by dehydration in plants. Desiccation‐tolerant resurrection plants can survive conditions of very low relative water content. During desiccation, photosynthesis is not operational, but is recovered within a short period after rehydration. While homoiochlorophyllous resurrection plants retain their photosynthetic apparatus during desiccation, poikilochlorophyllous resurrection species dismantle chloroplasts and degrade chlorophyll but resynthesize them again during rehydration. Dismantling the chloroplasts avoids the photooxidative stress in poikilochlorophyllous resurrection plants, whereas it is minimized in homoiochlorophyllous plants through the synthesis of antioxidant enzymes and protective proteins or metabolites. Although the cellular protection mechanisms in both of these species vary, these mechanisms protect cells from desiccation‐induced damage and restore photosynthesis upon rehydration. Several of the proteins synthesized during dehydration are localized in chloroplasts and are believed to play major roles in the protection of photosynthetic structures and in recovery in resurrection species. This review focuses on the strategies of resurrection plants in terms of how they protect their photosynthetic apparatus from oxidative stress during desiccation without membrane damage and with full recovery during rehydration. We review the role of the dehydration‐induced protection mechanisms in chloroplasts and how photosynthesis is restored during rehydration.
Calcium signaling as a mediator of cell energy demand and a trigger to cell death
Authors: Bhosale Gauri , Sharpe Jenny A. , Sundier Stephanie Y. , Duchen Michael R.
Published: September 2015

Calcium signaling is pivotal to a host of physiological pathways. A rise in calcium concentration almost invariably signals an increased cellular energy demand. Consistent with this, calcium signals mediate a number of pathways that together serve to balance energy supply and demand. In pathological states, calcium signals can precipitate mitochondrial injury and cell death, especially when coupled to energy depletion and oxidative or nitrosative stress. This review explores the mechanisms that couple cell signaling pathways to metabolic regulation or to cell death. The significance of these pathways is exemplified by pathological case studies, such as those showing loss of mitochondrial calcium uptake 1 in patients and ischemia/reperfusion injury.
Basiliximab treatment for autoimmune bowel disease in a pediatric heart transplant patient
Authors: Puri K. , Kocoshis S. , Risma K. , Perez L. , Hart C. , Chin C. , Ryan T. D. , Jefferies J. L. , Schumacher K. R. , Castleberry C.
Published: September 2015

Autoimmune‐mediated bowel disease has been reported after pediatric heart transplantation. Recognition and treatment of these patients has been difficult. We describe a patient who responded to steroids and basiliximab therapy after an inflammatory process secondary to abnormal T‐cell activation. Our patient is a 28‐month‐old female who received a heart transplant at five wk of age. At 24 months post‐transplant, she developed fever and bloody stools. Initial investigations were significant for an elevated ESR (>120) and CRP (15.2). Symptoms persisted despite bowel rest and mycophenolate discontinuation. Endoscopic evaluation revealed discontinuous ulcerative disease involving esophagus, terminal ileum, right and left colon, necessitating extensive bowel resection. She had additional airway inflammation leading to a TEF at the site of esophageal ulceration, requiring tracheostomy. Immune evaluation revealed autoimmune dysregulation that responded to parenteral methylprednisolone. Chronic basiliximab therapy allowed for successful weaning of steroids with sustained remission. She has been transitioned to sirolimus and tacrolimus maintenance immunosuppression with plans to discontinue basiliximab once off steroids. In conclusion, bowel disease in the setting of pediatric heart transplantation can be severe and refractory to traditional treatment methods. Tailoring immune therapy to activated T cells can result in remission. Basiliximab therapy was used in our patient to maintain steroid‐induced remission, but long‐term complications of this disease process are unknown.
Comparison of Cramer–Rao lower bounds of variances for at least equal protection of respondents
Authors: Lee Cheon‐Sig , Su Shu‐Ching , Mondragon Katrina , Salinas Veronica I. , Zamora Monique L. , Sedory Stephen Andrew , Singh Sarjinder
Published: September 2015

In this paper, a new randomized response model is proposed, which is shown to have a Cramer–Rao lower bound of variance that is lower than the Cramer–Rao lower bound of variance suggested by Singh and Sedory at equal protection or greater protection of respondents. A new measure of protection of respondents in the setup of the efficient use of two decks of cards, because of Odumade and Singh, is also suggested. The developed Cramer–Rao lower bounds of variances are compared under different situations through exact numerical illustrations. Survey data to estimate the proportion of students who have sometimes driven a vehicle after drinking alcohol and feeling over the legal limit are collected by using the proposed randomization device and then analyzed. The proposed randomized response technique is also compared with a black box technique within the same survey. A method to determine minimum sample size in randomized response sampling based on a small pilot survey is also given.
Probing soil physical and biological resilience data from a broad sampling of arable farms in Scotland
Authors: Griffiths B. S. , Hallett P. D. , Daniell T. J. , Hawes C. , Squire G. S. , Mitchell S. M. , Caul S. , Valentine T. A. , Binnie K. , Adeloye A. J. , Rustum R. , Nevison I.
Published: September 2015

Physical and biological soil stabilities (i.e. resistance and resilience) were measured on a range of arable farms across eastern Scotland under a range of management practices, with the objective of using a geographically restricted set of soils under similar land use to detect any underlying associations between soil stability, management factors and soil properties. Data were analysed using a combination of a stepwise fixed effects model selection within a linear mixed‐model framework (LMM) and neural network analysis using a Kohonen self‐organising map (KSOM). In general, physical and biological measures of stability were associated with both physical and biological soil properties, particularly bulk density, water retention characteristics, soil carbon and bacterial community structure. A strength of KSOM is its ability to fit more flexible models than the linear relationships of LMM. However, a weakness is that it does not have the ability of LMM to model the sampling design, which is likely to lead to overstating statistical significance. Consequently, KSOM identified more significant associations between soil properties and stability than LMM, while the latter identified significant associations at the between‐farm level. The high‐level land management decisions of farm type (conventional, organic, integrated), crop type or underlying soil type were not associated with stability at this regional scale, thus indicating that the effects of different management practices between farms were overridden by the soil properties on each farm. Management decisions on improving soil stability therefore need to be taken at the individual field scale.
Antibody‐reactive class I epitopes defined by pairs of mismatched eplets and self‐eplets
Authors: Resse M. , Paolillo R. , Minucci B. P. , Moccia G. , Napoli C.
Published: September 2015

The identification of human leukocyte antigen (HLA) antibodies in the sera of candidates awaiting organ transplantation has evolved over time. This has been possible because of the introduction of more sensitive techniques and to the increasing focus on the structural aspects of the HLA epitopes. The use of the HLAMatchmaker algorithm in the analysis of positive sera and the verification of HLA ABC epitopes in the HLA Epitope Registry website provide new stimuli on the interpretation of antibody reactivity. The epitopes defined by eplet pairs often involve a nonself‐eplet and a self‐eplet (nonself–self paradigm), suggesting that the antibody response to an HLA mismatch must have an auto‐reactive component. Here, we report an application of the nonself–self paradigm that provides a basis for better knowledge and interpretation of HLA‐antibody reactivity in Luminex assays with single alleles.
Use of antibiotics by urban and rural residents in Heilongjiang Province, China: cross‐sectional study
Authors: Gu Jiarui , Zhao Jizi , Huang Ying , Yang Weidong , Ren Zheng , Li Wenjing , Fan Yuzhuo , Zhang Qiao , Zhang Fengmin , Fu Yingmei
Published: September 2015

Objective

To identify and compare the factors affecting the knowledge of, attitude towards and use of antibiotics between urban and rural residents in China.

Methods

A total of 3631 urban and rural residents in Heilongjiang Province, China, were selected using random sampling. Questionnaires recorded demographic characteristics and participant knowledge of, attitude towards and use of antibiotics. The responses of rural and urban residents were compared, and logistic regression analysis was applied to identify the factors that may contribute to the knowledge of, attitude towards and use of antibiotics.

Results

The majority of the participants (>60%) were aware that antibiotics could be used to treat bacterial infections and that bacteria could be resistant to antibiotics. However, only roughly half (40–60%) of the participants were aware that bacterial resistance to antibiotics had become a problem in China. Urban participants reported a more adequate knowledge of, attitude towards and use of antibiotics than rural participants. Logistic regression analysis indicated that urban residency, female gender and level of education were associated with knowledge of, attitude towards and use of antibiotics.

Conclusions

Within our sample in Heilongjiang Province, the knowledge of, attitude towards and use of antibiotics were suboptimal in roughly half of all urban and rural residents, but better in urban than in rural residents. Targeted interventions to educate rural residents in particular may reduce the misuse of antibiotics.
Boom‐and‐bust Cycles, External Imbalances and the Real Exchange Rate
Authors: Müller‐Plantenberg Nikolas A.
Published: September 2015

When the current account balance and net capital outflows do not exactly offset each other, international payment flows arise. Payment flows into a country push the real exchange rate up, payment outflows push it down. This article uses a model of optimal consumption and portfolio choice to determine the factors that drive international payment flows during boom‐and‐bust cycles. It shows that during such episodes, capital inflows first exceed the deficit on current account, strengthening the currency. Later on, when the return on domestic capital reverts to its normal level, the current account recovers, yet the overall decline of the net foreign asset position provokes a fall of the real exchange rate even below its initial level. Case studies of countries experiencing rapid economic expansions followed by economic and financial meltdowns confirm the article's theoretical predictions.
Expression of Concern: Tumour necrosis factor‐alpha‐induced protein 8 (TNFAIP8) expression associated with cell survival and death in cancer cell lines infected with canine distemper virus
Authors: Garcia J. A. , Ferreira H. L. , Vieira F. V. , Gameiro R. , Andrade A. L. , Eugênio F. R. , Flores E. F. , Cardoso T. C.
Published: September 2015

Oncolytic virotherapy is a novel strategy for treatment of cancer in humans and companion animals as well. Canine distemper virus (CDV), a paramyxovirus, has proven to be oncolytic through induction of apoptosis in canine‐derived tumour cells, yet the mechanism behind this inhibitory action is poorly understood. In this study, three human mammary tumour cell lines and one canine‐derived adenofibrosarcoma cell line were tested regarding to their susceptibility to CDV infection, cell proliferation, apoptosis, mitochondrial membrane potential and expression of tumour necrosis factor‐alpha‐induced protein 8 (TNFAIP8). CDV replication‐induced cytopathic effect, decrease of cell proliferation rates, and >45% of infected cells were considered death and/or under late apoptosis/necrosis. TNFAIP8 and CDVM gene expression were positively correlated in all cell lines. In addition, mitochondrial membrane depolarization was associated with increase in virus titres (p < 0.005). Thus, these results strongly suggest that both human and canine mammary tumour cells are potential candidates for studies concerning CDV‐induced cancer therapy.
Increased susceptibility of skin from HERDA (Hereditary Equine Regional Dermal Asthenia)‐affected horses to bacterial collagenase degradation: a potential contributing factor to the clinical signs of HERDA
Authors: Rashmir‐Raven Ann , Lavagnino Michael , Sedlak Aleksa , Gardner Keri , Arnoczky Steven
Published: September 2015

Background

Hereditary equine regional dermal asthenia (HERDA) is a genetic disorder of collagen resulting in fragile, hyper‐extensible skin and ulcerative lesions. The predominance of skin lesions have been shown to occur on the dorsum of HERDA‐affected horses. While this has been postulated to be due to increased exposure to sunlight of these areas, the precise pathological mechanism which causes this to occur is unclear.

Hypothesis/objectives

We hypothesized that an increase in collagenase activity, that has been associated with the exposure of dermal fibroblasts to sunlight, will significantly degrade the material properties of skin from HERDA‐affected horses when compared to unaffected controls.

Animals

Six unaffected and seven HERDA‐affected horses, all euthanized for other reasons.

Methods

Full‐thickness skin samples from similar locations on each horse were collected and cut into uniform strips and their material properties (tensile modulus) determined by mechanical testing before (n = 12 samples/horse) or after (n = 12 samples/horse) incubation in bacterial collagenase at 37°C for 6 h. The change in modulus following treatment was then compared between HERDA‐affected and unaffected horses using a Student's t‐test.

Results

The modulus of skin from HERDA‐affected horses decreased significantly more than that from unaffected horses following collagenase treatment (54 ± 7% versus 30 ± 16%, P = 0.004).

Conclusions and clinical importance

The significant decrease in the modulus of skin from HERDA‐affected horses following collagenase exposure suggests that their altered collagen microarchitecture is more susceptible to enzymatic degradation and may explain the localization of skin lesions in HERDA‐affected horses to those areas of the body most exposed to sunlight. These findings appear to support the previously reported benefits of sunlight restriction in HERDA‐affected horses.
Influence of contractile force on the architecture and morphology of the quadriceps femoris
Authors: Massey Garry , Evangelidis Pavlos , Folland Jonathan
Published: September 2015

New Findings

What is the central question of this study?

Does contraction influence the fascicle length, pennation angle and effective physiological cross‐sectional area (effPCSA) of the quadriceps femoris muscle? Is there a stronger relationship between effPCSA and maximal strength if effPCSA is measured during maximal contraction rather than at rest?

What is the main finding and its importance?

Fascicle length decreased, pennation angle increased and effPCSA increased in a non‐linear manner with isometric torque. The effPCSA during maximal contraction and rest were correlated in a similar manner to maximal strength. The effPCSA at rest is sufficient to characterize the muscle size–strength relationship.

The primary purpose of this study was to document the influence of muscle contraction on quadriceps femoris (QF) muscle architecture [fascicle length (Lf) and pennation angle (θp)] and effective physiological cross‐sectional area (effPCSA). Secondarily, we aimed to determine whether effPCSA measured during maximal voluntary contraction (MVC) had a stronger relationship to maximal strength than effPCSA at rest. Fifteen young men performed a series of voluntary knee‐extension isometric ramp contractions. Isometric maximal voluntary torque (MVT) was recorded during separate MVCs. Measurements of architecture and effPCSA of each constituent muscle of the QF and, subsequently, the whole QF were made at rest, during 20% increments of maximal voluntary torque and during an MVC. The QF muscle architecture and morphology changed in a curvilinear manner with relative torque (%MVT), with significant differences being observed between incremental torque levels for Lf, θp and effPCSA. Specifically, from rest to MVC, QF Lf decreased (–23.5 ± 3.3%), whereas θp increased (+39.7 ± 6.6%). The QF effPCSA was +26.5 ± 5.7% greater during MVC than at rest. Similar moderate correlations existed for MVT and effPCSA at rest (r = 0.519, P = 0.047) and for MVT and effPCSA during MVC (r = 0.530, P = 0.042). Substantial changes in QF architecture (Lf, θp) and effPCSA occur in a curvilinear manner with relative torque production. The effPCSA during MVC was no more strongly associated with MVT than effPCSA measured at rest, which implies that resting measurements of muscle size are suitable for characterizing the muscle size–strength relationship.
Mild dehydration modifies the cerebrovascular response to the cold pressor test
Authors: Perry Blake G. , Bear Tracey L. K. , Lucas Samuel J. E. , Mündel Toby
Published: September 2015

New Findings

What is the central question of this study?

The cold pressor test (CPT) is commonly used to investigate cerebrovascular regulation. Despite blood viscosity per se being able to modulate cerebral blood flow, it is unknown whether hydration status alters this response, nor is it commonly reported. We investigated the effects of mild dehydration on the cerebrovascular response to the CPT.

What is the main finding and its importance?

The main finding from this study is that when compared with euhydration, mild dehydration reduced cerebral blood flow via a decrease in the partial pressure of end‐tidal CO2. This demonstrates that hydration status is an important modulator of the cerebrovascular response to the CPT and should be reported and controlled for.

The cold pressor test (CPT) is widely used in clinical practice and physiological research. It is characterized by a robust autonomic response, with associated increases in heart rate (HR), mean arterial pressure (MAP) and mean middle cerebral artery blood flow velocity (MCAvmean). Hydration status is not commonly reported when conducting this test, yet blood viscosity alone can modulate MCAvmean, potentially modifying the MCAvmean response to the CPT. We investigated the effect of mild dehydration on the physiological response to the CPT in 10 healthy men (mean ± SD: age 28 ± 5 years; body mass 83 ± 5 kg). All participants completed two CPTs, cold water (0°C) immersion of both feet for 90 s, with the order of the euhydration and dehydration trials counterbalanced. Beat‐to‐beat MCAv, MAP, HR and breath‐by‐breath partial pressure of end‐tidal CO2 () were measured continuously. Participants’ pain perception was measured 1 min into the CPT using a visual analog scale (no pain = 0; maximal pain = 10). Dehydration significantly elevated plasma osmolality and urine specific gravity and reduced body mass (all P < 0.01). The MAP and HR responses were not different between treatments (both P > 0.05). After 90 s of immersion, the change in MCAvmean from baseline was less in the dehydration compared with the euhydration trial (change 0 ± 5 versus 7 ± 7 cm s−1, P = 0.01), as was (change −3 ± 2 versus 0 ± 3 mmHg, P = 0.02). Dehydration was associated with greater relative pain sensation during the CPT (7.0 ± 1.3 vs 5.8 ± 1.8, P = 0.02). Our results demonstrate that mild dehydration can modify the cerebrovascular response to the CPT, with dehydration increasing perceived pain, lowering and, ultimately, blunting the MCAvmean response.
Numerical Analysis to Investigate the Effects of Thermal-Hydraulic Instabilities on Deterioration Heat Transfer and Wall Temperature in the CANDU Supercritical Water Reactor
Authors: Dutta Goutam , Zhang Chao , Jiang Jin
Published: September 2015

The present work analyzes the thermal-hydraulic behavior of the CANDU supercritical water reactor (SCWR) using a 1-D numerical model. The possibility of a static instability, the Ledinegg excursion, is investigated, which reveals it can occur only in a hypothetical condition, far from the proposed operating regime of the CANDU SCWR. The investigation demonstrates the possibility of density wave oscillations (DWOs), a dynamic instability, in the operating regime of the CANDU SCWR and its marginal stability boundary (MSB) is obtained. The phenomenon of the deterioration in heat transfer is observed, and the related investigation shows that the strong buoyancy effect is responsible for its appearance inside the heating section of the channel of the CANDU SCWR core. The MSB is found to be inadequate in determining the safe operating zone of the reactor because the wall temperature can exceed the allowable limit from metallurgical consideration. The investigations also determine the safe as well as stable zone where the CANDU SCWR should operate in order to avoid the maximum temperature limit and DWOs.
Optimal Determination of Respiratory Airflow Patterns for a General Multicompartment Lung Mechanics System With Nonlinear Resistance and Compliance Parameters
Authors: Paul Hou Saing , Meskin Nader , Haddad Wassim M.
Published: September 2015

In this paper, we develop a framework for determining optimal respiratory airflow patterns for a multicompartment lung mechanics system with nonlinear resistance and compliance parameters. First, a nonlinear multicompartment lung mechanics model that accounts for nonlinearities in both the airway resistances and the lung compliances is developed. In particular, we assume that the resistive losses are characterized by a Rohrer-type model with resistive losses defined as the sum of linear and quadratic terms of the airflow. The proposed model is more realistic than those presented in the literature, since it takes into account the heterogeneity of lung anatomy and function as well as the nonlinearity of lung resistance and compliance parameters. This model can be used to provide a better understanding of pulmonary function as well as the process of mechanical ventilation. Next, using the proposed nonlinear multicompartment lung model, we develop a framework for determining optimal respiratory airflow patterns. Specifically, an optimization criterion that involves the minimization of the oxygen consumption of the lung muscles and lung volume acceleration for the inspiratory phase, and the minimization of the elastic potential energy and rapid airflow rate changes for the expiratory phase is formulated and solved. The solution to the formulated optimization problem is derived using classical calculus of variation techniques. Finally, several illustrative numerical examples are presented to illustrate the efficacy of the proposed nonlinear multicompartment lung model and the corresponding optimal airflow patterns. Comparison with experimental data shows that our nonlinear resistance model predicts the airflow patterns more accurately than linear resistance models. Moreover, the optimization criterion used in this paper also provides a more accurate prediction of the optimal airflow patterns.
Three-Dimensional Blade-Stacking Strategies and Understanding of Flow Physics in Low-Pressure Steam Turbines—Part I: Three-Dimensional Stacking Mechanisms
Authors: Havakechian Said , Denton John
Published: September 2015

Optimization of blade stacking in the last stage of low-pressure (LP) steam turbines constitutes one of the most delicate and time-consuming parts of the design process. This is the first of two papers focusing on the stacking strategies applied to the last stage guide vane (G0). Following a comprehensive review of the main features that characterize the LP last stage aerodynamics, the three-dimensional (3D) computational fluid dynamics (CFD) code used for the investigation and options related to the modeling of wet steam are described. Aerodynamic problems related to the LP last stage and the principles of 3D stacking are reviewed in detail. In this first paper, the results of a systematic study on an isolated LP stator row are used to elucidate the effects of stacking schemes, such as lean, twist, sweep, and hub profiling. These results show that stator twist not only has the most powerful influence on the reaction variation but it also produces undesirable spanwise variations in angular momentum at stator exit. These may be compensated by introducing a positive stagnation pressure gradient at entry to the last stage.
NOx Emissions Modeling and Uncertainty From Exhaust-Gas-Diluted Flames
Authors: Lipardi Antonio C. A. , Bergthorson Jeffrey M. , Bourque Gilles
Published: September 2015

Oxides of nitrogen (NOx) are pollutants emitted by combustion processes during power generation and transportation that are subject to increasingly stringent regulations due to their impact on human health and the environment. One NOx reduction technology being investigated for gas-turbine engines is exhaust-gas recirculation (EGR), either through external exhaust-gas recycling or staged combustion. In this study, the effects of different percentages of EGR on NOx production will be investigated for methane–air and propane–air flames at a selected adiabatic flame temperature of 1800 K. The variability and uncertainty of the results obtained by the gri-mech 3.0 (GRI), San-Diego 2005 (SD), and the CSE thermochemical mechanisms are assessed. It was found that key parameters associated with postflame NO emissions can vary up to 192% for peak CH values, 35% for thermal NO production rate, and 81% for flame speed, depending on the mechanism used for the simulation. A linear uncertainty analysis, including both kinetic and thermodynamic parameters, demonstrates that simulated postflame nitric oxide levels have uncertainties on the order of ±50–60%. The high variability of model predictions, and their relatively high associated uncertainties, motivates future experiments of NOx formation in exhaust-gas-diluted flames under engine-relevant conditions to improve and validate combustion and NOx design tools.
Fluorophore-based sensor for oxygen radicals in processing plasmas
Authors: Choudhury Faraz A. , Sabat Grzegorz , Sussman Michael R. , Nishi Yoshio , Shohet J. Leon
Published: September 2015

A high concentration of radicals is present in many processing plasmas, which affects the processing conditions and the properties of materials exposed to the plasma. Determining the types and concentrations of free radicals present in the plasma is critical in order to determine their effects on the materials being processed. Current methods for detecting free radicals in a plasma require multiple expensive and bulky instruments, complex setups, and often, modifications to the plasma reactor. This work presents a simple technique that detects reactive-oxygen radicals incident on a surface from a plasma. The measurements are made using a fluorophore dye that is commonly used in biological and cellular systems for assay labeling in liquids. Using fluorometric analysis, it was found that the fluorophore reacts with oxygen radicals incident from the plasma, which is indicated by degradation of its fluorescence. As plasma power was increased, the quenching of the fluorescence significantly increased. Both immobilized and nonimmobilized fluorophore dyes were used and the results indicate that both states function effectively under vacuum conditions. The reaction mechanism is very similar to that of the liquid dye.
Induced magnetic moment in stainless steel components of orthodontic appliances in 1.5 T MRI scanners
Authors: Wang Zhiyue J. , Rollins Nancy K. , Liang Hui , Park Yong Jong
Published: September 2015

Purpose:

Most orthodontic appliances are made of stainless steel materials and induce severe magnetic susceptibility artifacts in brain MRI. In an effort for correcting these artifacts, it is important to know the value of induced magnetic moments in all parts of orthodontic appliances. In this study, the induced magnetic moment of stainless steel orthodontic brackets, molar bands, and arch‐wires from several vendors is measured.

Methods:

Individual stainless steel brackets, molar bands, and short segments of arch‐wire were positioned in the center of spherical flask filled with water through a thin plastic rod. The induced magnetic moment at 1.5 T was determined by fitting the B0 map to the z‐component of the magnetic dipole field using a computer routine.

Results:

The induced magnetic moment at 1.5 T was dominated by the longitudinal component mz, with a small contribution from the transverse components. The mz was insensitive to the orientation of the metal parts. The orthodontic brackets collectively dominated the magnetic dipole moment in orthodontic appliances. In brackets from six vendors, the total induced mz from 20 brackets for nonmolar teeth ranged from 0.108 to 0.158 (median 0.122) A ⋅ m2. The mz in eight molar bands with bracket attachment from two vendors ranged from 0.0004 to 0.0166 (median 0.0035) A ⋅ m2. Several full length arch wires had induced magnetic moment in the range of 0.006–0.025 (median 0.015) A ⋅ m2.

Conclusions:

Orthodontic brackets collectively contributed most to the total magnetic moment. Different types of brackets, molar bands, and arch wires all exhibit substantial variability in the induced magnetic moment.
The Effect of Postexercise Milk Protein Intake on Rehydration of Children
Authors: Volterman Kimberly , Moore Daniel , Obeid Joyce , Offord Elizabeth A. , Timmons Brian W.
Published: September 2015

Purpose:

In adults, rehydration after exercise in the heat can be enhanced with a protein-containing beverage; however, whether this applies to children remains unknown. This study examined the effect of milk protein intake on postexercise rehydration in children.

Method:

Fifteen children (10–12 years) performed three exercise trials in the heat (34.4 ± 0.2 °C, 47.9 ± 1.1% relative humidity). In a randomized, counterbalanced crossover design, participants consumed iso-caloric and electrolyte-matched beverages containing 0 g (CONT), 0.76 g (Lo-PRO) or 1.5 g (Hi-PRO) of milk protein/100 mL in a volume equal to 150% of their body mass (BM) loss during exercise. BM was then assessed over 4 h of recovery.

Results:

Fluid balance demonstrated a significant condition × time interaction (p = .012) throughout recovery; Hi-PRO was less negative than CONT at 2 hr (p = .01) and tended to be less negative at 3 h (p = .07). Compared with CONT, beverage retention was enhanced by Hi-PRO at 2 h (p < .05).

Conclusion:

A postexercise beverage containing milk protein can favorably affect fluid retention in children. Further research is needed to determine the optimal volume and composition of a rehydration beverage for complete restoration of fluid balance.
Parkinson’s disease: From human genetics to clinical trials
Authors: van der Brug Marcel P. , Singleton Andrew , Gasser Thomas , Lewis Patrick A.
Published: September 2015

In this Perspective, van der Brug and colleagues discuss the road from elucidating the genetics of Parkinson's disease through drug discovery to clinical trials, mapping the challenges along the way.
Durable sequence stability and bone marrow tropism in a macaque model of human pegivirus infection
Authors: Bailey Adam L. , Lauck Michael , Mohns Mariel , Peterson Eric J. , Beheler Kerry , Brunner Kevin G. , Crosno Kristin , Mejia Andres , Mutschler James , Gehrke Matthew , Greene Justin , Ericsen Adam J. , Weiler Andrea , Lehrer-Brey Gabrielle , Friedrich Thomas C. , Sibley Samuel D. , Kallas Esper G. , Capuano Saverio , Rogers Jeffrey , Goldberg Tony L. , Simmons Heather A. , O’Connor David H.
Published: September 2015

A monkey model of human pegivirus infection provides new insights into the biology of this virus.
Effects of caffeine on the human circadian clock in vivo and in vitro
Authors: Burke Tina M. , Markwald Rachel R. , McHill Andrew W. , Chinoy Evan D. , Snider Jesse A. , Bessman Sara C. , Jung Christopher M. , O’Neill John S. , Wright Kenneth P.
Published: September 2015

Caffeine delays the human circadian clock and affects cellular timekeeping through an adenosine receptor–dependent mechanism.
Targeting the glucocorticoid receptor in breast and prostate cancers
Authors: Kach Jacob , Conzen Suzanne D. , Szmulewitz Russell Z.
Published: September 2015

The glucocorticoid receptor has a context-dependent role in breast and prostate cancers and may serve as a therapeutic target.
No longer aware of what cannot be remembered
Authors: Statland Jeffrey
Published: September 2015

Loss of awareness of a cognitive decline occurs before the onset of dementia and is associated with post mortem dementia pathology.
Basket trials: Making sense of context
Authors: Thomas Anish
Published: September 2015

“Basket” clinical trials help identify drug activity in multiple tumor types and allow for the influence of tumor lineage on drug sensitivity.
Effect of Serotype on Pneumococcal Competition in a Mouse Colonization Model
Authors: Trzciński Krzysztof , Li Yuan , Weinberger Daniel M. , Thompson Claudette M. , Cordy Derrick , Bessolo Andrew , Malley Richard , Lipsitch Marc
Published: September 2015

Competitive interactions between
Streptococcus pneumoniae
strains during host colonization could influence the serotype distribution in nasopharyngeal carriage and pneumococcal disease. We evaluated the competitive fitness of strains of serotypes 6B, 14, 19A, 19F, 23F, and 35B in a mouse model of multiserotype carriage. Isogenic variants were constructed using clinical strains as the capsule gene donors. Animals were intranasally inoculated with a mixture of up to six pneumococcal strains of different serotypes, with separate experiments involving either clinical isolates or isogenic capsule-switch variants of clinical strain TIGR4. Upper-respiratory-tract samples were repeatedly collected from animals in order to monitor changes in the serotype ratios using quantitative PCR. A reproducible hierarchy of capsular types developed in the airways of mice inoculated with multiple strains. Serotype ranks in this hierarchy were similar among pneumococcal strains of different genetic backgrounds in different strains of mice and were not altered when tested under a range of host conditions. This rank correlated with the measure of the metabolic cost of capsule synthesis and
in vitro
measure of pneumococcal cell surface charge, both parameters considered to be predictors of serotype-specific fitness in carriage. This study demonstrates the presence of a robust competitive hierarchy of pneumococcal serotypes
in vivo
that is driven mainly, but not exclusively, by the capsule itself.

IMPORTANCE
Streptococcus pneumoniae
(pneumococcus) is the leading cause of death due to respiratory bacterial infections but also a commensal frequently carried in upper airways. Available vaccines induce immune responses against polysaccharides coating pneumococcal cells, but with over 90 different capsular types (serotypes) identified, they can only target strains of the selected few serotypes most prevalent in disease. Vaccines not only protect vaccinated individuals against disease but also protect by reducing carriage of vaccine-targeted strains to induce herd effects across whole populations. Unfortunately, reduction in the circulation of vaccine-type strains is offset by increase in carriage and disease from nonvaccine strains, indicating the importance of competitive interactions between pneumococci in shaping the population structure of this pathogen. Here, we showed that the competitive ability of pneumococcal strains to colonize the host strongly depends on the type of capsular polysaccharide expressed by pneumococci and only to a lesser degree on strain or host genetic backgrounds or on variation in host immune responses.
Insights into Substrate Specificity of NlpC/P60 Cell Wall Hydrolases Containing Bacterial SH3 Domains
Authors: Xu Qingping , Mengin-Lecreulx Dominique , Liu Xueqian W. , Patin Delphine , Farr Carol L. , Grant Joanna C. , Chiu Hsiu-Ju , Jaroszewski Lukasz , Knuth Mark W. , Godzik Adam , Lesley Scott A. , Elsliger Marc-André , Deacon Ashley M. , Wilson Ian A.
Published: September 2015

Bacterial SH3 (SH3b) domains are commonly fused with papain-like Nlp/P60 cell wall hydrolase domains. To understand how the modular architecture of SH3b and NlpC/P60 affects the activity of the catalytic domain, three putative NlpC/P60 cell wall hydrolases were biochemically and structurally characterized. These enzymes all have γ-
d
-Glu-A
2
pm (A
2
pm is diaminopimelic acid) cysteine amidase (or
dl
-endopeptidase) activities but with different substrate specificities. One enzyme is a cell wall lysin that cleaves peptidoglycan (PG), while the other two are cell wall recycling enzymes that only cleave stem peptides with an N-terminal
l
-Ala. Their crystal structures revealed a highly conserved structure consisting of two SH3b domains and a C-terminal NlpC/P60 catalytic domain, despite very low sequence identity. Interestingly, loops from the first SH3b domain dock into the ends of the active site groove of the catalytic domain, remodel the substrate binding site, and modulate substrate specificity. Two amino acid differences at the domain interface alter the substrate binding specificity in favor of stem peptides in recycling enzymes, whereas the SH3b domain may extend the peptidoglycan binding surface in the cell wall lysins. Remarkably, the cell wall lysin can be converted into a recycling enzyme with a single mutation.

IMPORTANCE
Peptidoglycan is a meshlike polymer that envelops the bacterial plasma membrane and bestows structural integrity. Cell wall lysins and recycling enzymes are part of a set of lytic enzymes that target covalent bonds connecting the amino acid and amino sugar building blocks of the PG network. These hydrolases are involved in processes such as cell growth and division, autolysis, invasion, and PG turnover and recycling. To avoid cleavage of unintended substrates, these enzymes have very selective substrate specificities. Our biochemical and structural analysis of three modular NlpC/P60 hydrolases, one lysin, and two recycling enzymes, show that they may have evolved from a common molecular architecture, where the substrate preference is modulated by local changes. These results also suggest that new pathways for recycling PG turnover products, such as tracheal cytotoxin, may have evolved in bacteria in the human gut microbiome that involve NlpC/P60 cell wall hydrolases.
From past sailors’ eras to the present day: scurvy as a surprising manifestation of an uncommon gastrointestinal disease
Authors: Branquinho Diogo Ferreira , Pinto-Gouveia Miguel , Mendes Sofia , Sofia Carlos
Published: September 2015

A 45-year-old man presented with follicular exanthema in his lower limbs, alternating bowel habits and significant weight loss. His medical history included seronegative arthritis, bipolar disease and an inconclusive diagnostic laparoscopy. Diagnostic work up revealed microcytic anaemia and multivitamin deficiency. Skin biopsy of the exanthema suggested scurvy. Owing to these signs of malabsorption, upper endoscopy with duodenal biopsies was performed, exhibiting villous atrophy and extensive periodic acid-Schiff-positive material in the lamina propria, therefore diagnosing Whipple's disease (WD). After starting treatment with ceftriaxone and co-trimoxazole, an impressive recovery was noted, as the wide spectrum of malabsorption signs quickly disappeared. After a year of antibiotics, articular and cutaneous manifestations improved, allowing the patient to stop taking corticosteroids and antidepressants. This truly unusual presentation reflects the multisystemic nature of WD, often leading to misdiagnosis of other entities. Scurvy is a rare finding in developed countries, but its presence should raise suspicion for small bowel disease.
Rare presentation of orbital plasmablastic lymphoma with oral cavity involvement in an HIV-negative patient
Authors: Podder Sidhertha , Khetan Prerna , Sivamurthy Shetra , Mandal Kaushik
Published: September 2015

Plasmablastic lymphoma is described as a subtype of non-Hodgkin's lymphoma under the category of diffuse large B-cell lymphoma. It is classified by WHO as HIV-associated lymphoma of the oral cavity. Several cases have been reported in non-HIV patients with extra-oral involvement. The characteristic immunohistochemical markers are generally positive for CD138, CD38 and MUM1/IRF4, and negative or weakly positive for pan B-cell markersCD20, CD79a, PAX-5 and BCL-6. We report a rare case of orbital plasmablastic lymphoma with oral and oropharyngeal involvement where the immunohistochemical markers were positive for CD138, CD43, CD45, CD79a and MUM1. A small subset of markers was weakly positive for CD20, CD30 and κ, and negative for CD10, BCL-6, CD4, CD56 and Epstein–Barr virus-encoded small RNA (EBER). Our case reinforces the fact that plasmablastic lymphoma is a different entity of non-Hodgkin's lymphoma that cannot simply be classified under diffuse large B-cell lymphoma. It demands modification of the WHO classification.
Sick and still at school: an empirical study of sickness presence among students in Norwegian secondary school
Authors: Johansen Vegard
Published: September 2015

Objectives

This paper investigates sickness presence (SP) among students. The research questions asked are: What is the distribution of SP among students in Norwegian secondary school? What characterises students with high SP in Norwegian secondary schools?

Design

A cross-sectional survey conducted in 10th grade in lower secondary school (LSS) and level 2 in upper secondary school (USS). The study was conducted using multivariate binomial logistic regression analysis.

Participants

The survey was administered to 66 schools, and 2 or 3 classes participated at each school. The response rate was 84% in LSS (n=1880) and 81% in USS (n=1160).

Primary and secondary outcome measures

The paper provides information about the distribution of SP in secondary schools. The paper also examines which factors influence high SP.

Results

75% of students in LSS and 80% of students in USS reported SP in the previous school year. 24% of students in LSS and 33% of students in USS reported high SP (4 episodes or more). Students with high absence from school were more likely to report high SP (ORLSS=1.7, ORUSS=2.0) than those with low/no absence. Girls were more likely to report high SP (ORLSS=1.5, ORUSS=1.5) than boys. In LSS, students with high school motivation reported high SP more often than students with low/medium motivation. In USS, students in vocational studies programmes reported high SP more often than students in general/academic studies programmes.

Conclusions

Some SP during a school year may be more common than no SP. Gender, absence, motivation and education programme were important factors for high SP in secondary school.
DNA methylation patterns in naïve CD4+ T cells identify epigenetic susceptibility loci for malar rash and discoid rash in systemic lupus erythematosus
Authors: Renauer Paul , Coit Patrick , Jeffries Matlock A , Merrill Joan T , McCune W Joseph , Maksimowicz-McKinnon Kathleen , Sawalha Amr H
Published: September 2015

Objective

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterised by heterogeneous clinical manifestations, autoantibody production and epigenetic dysregulation in T cells. We sought to investigate the epigenetic contribution to the development of cutaneous manifestations in SLE.

Methods

We performed genome-wide DNA methylation analyses in patients with SLE stratified by a history of malar rash, discoid rash or neither cutaneous manifestation, and age, sex and ethnicity matched healthy controls. We characterised differentially methylated regions (DMRs) in naïve CD4+ T cells unique to each disease subset, and assessed functional relationships between DMRs using bioinformatic approaches.

Results

We identified 36 and 37 unique DMRs that contribute to the epigenetic susceptibility to malar rash and discoid rash, respectively. These DMRs were primarily localised to genes mediating cell proliferation and apoptosis. Hypomethylation ofMIR886andTRIM69,and hypermethylation ofRNF39were specific to patients with SLE with a history of malar rash. Hypomethylation of the cytoskeleton-related geneRHOJwas specific to patients with SLE with a history of discoid rash. In addition, discoid rash-specific hypomethylated DMRs were found in genes involved in antigen-processing and presentation such asTAP1andPSMB8. Network analyses showed that DMRs in patients with SLE with but not without a history of cutaneous manifestations are associated with TAP-dependent processing and major histocompatibility-class I antigen cross-presentation (p=3.66×10−18in malar rash, and 3.67×10−13in discoid rash).

Conclusions

We characterised DNA methylation changes in naïve CD4+ T cells specific to malar rash and discoid rash in patients with SLE. These data suggest unique epigenetic susceptibility loci that predispose to or are associated with the development of cutaneous manifestations in SLE.