bluuebunny/crossref_metadata_2025 huggingface dataset:
Accumulation of STIM1 is associated with the degenerative muscle fibre phenotype in ALS and other neurogenic atrophies
Authors: Goswami Anand , Jesse Christofer Marvin , Chandrasekar Akila , Bushuven Eva , Vollrath Jan Tilmann , Dreser Alice , Katona Istvan , Beyer Cordian , Johann Sonja , Feller A. C. , Grond M. , Wagner S. , Nikolin Stefan , Troost Dirk , Weis Joachim
Published: June 2014

Aim

Upon denervation, skeletal muscle fibres initiate complex changes in gene expression. Many of these genes are involved in muscle fibre remodelling and atrophy. Amyotrophic lateral sclerosis (ALS) leads to progressive neurodegeneration and neurogenic muscular atrophy (NMA). Disturbed calcium homeostasis and misfolded protein aggregation both in motor neurones and muscle fibres are key elements of ALS pathogenesis that are mutually interdependent. Therefore, we hypothesized that the calcium sensor STIM1 might be abnormally modified and involved in muscle fibre degeneration in ALS and other types of NMA.

Methods

We examined ALS and NMA patient biopsy and autopsy tissue and tissue from G93A SOD1 mice by immunohistochemistry and immunoblotting.

Results

In normal human and mouse muscle STIM1 was found to be differentially expressed in muscle fibres of different types and to concentrate at neuromuscular junctions, compatible with its known role in calcium sensing. Denervated muscle fibres of sALS and NMA cases and SOD1 mice showed diffusely increased STIM1 immunoreactivity along with ubiquitinated material. In addition, distinct focal accumulations of STIM1 were observed in target structures within denervated fibres of sALS and other NMA as well as SOD1 mouse muscles. Large STIM1‐immunoreactive structures were found in ALS‐8 patient muscle harbouring the P56S mutation in the ER protein VAPB.

Conclusion

These findings suggest that STIM1 is involved in several ways in the reaction of muscle fibres to denervation, probably reflecting alterations in calcium homeostasis in denervated muscle fibres.
Shaping the future of nursing: developing an appraisal framework for public engagement with nursing policy reports
Authors: Bradshaw Ann
Published: June 2014

It is accepted that research should be systematically examined to judge its trustworthiness and value in a particular context. No such appraisal is required of reports published by organizations that have possibly even greater influence on policy that affects the public. This paper explores a philosophical framework for appraising reports. It gives the reasons why informed engagement is important, drawing on Popper's concept of the open society, and it suggests a method for appraisal. Gadamer's concept of the two horizons and Jauss's reception theory offer a methodological framework to enable the individual citizen, whether professional or lay, to engage in debate about policy that affects him or her. By way of a worked example, the framework is applied to two international reports on nursing. Conclusions suggest that nursing policy should be subjected to robust interrogatory appraisal by both profession and public for a democratic debate and creative discourse. Although this analysis is related to international nursing policy, it has a wider relevance and application beyond nursing.
Evaluation of salivary function in patients with burning mouth syndrome
Authors: Lee YC , Hong IK , Na SY , Eun YG
Published: June 2014

Objectives

To investigate salivary function in patients with primary burning mouth syndrome (BMS) compared with control and to evaluate salivary hypofunction using salivary gland scintigraphy (SGS).

Methods

A total of 33 patients with primary BMS and 30 control subjects were enrolled in our study. The severity of the pain and the burning sensation on a 10‐cm visual analog scale (VAS) and the Oral Health Impact Profile‐14 (OHIP‐14) were assessed. Unstimulated and stimulated salivary flow rates (SFRs) were measured. 99mTc pertechnetate SGS was used to evaluate salivary gland function.

Results

Unstimulated SFR in patients with BMS was significantly lower than that in the control group (0.11 ± 0.15 vs 0.21 ± 0.16 ml min−1, P = 0.014). There was no significant difference in stimulated SFR between the two groups. The VAS scores for oral pain and burning sensation, the total OHIP‐14 score, and salivary gland function by salivary scintigraphy were not significantly different between BMS patients with normal flow rate and hyposalivation.

Conclusions

Patients with primary BMS exhibited a significant decrease in unstimulated SFR compared with control group. In addition, we could not find any difference in salivary gland function between BMS patients with or without hyposalivation.
Asthma with allergic comorbidities in adolescence is associated with bronchial responsiveness and airways inflammation
Authors: Hovland Vegard , Riiser Amund , Mowinckel Petter , Carlsen Kai‐Håkon , Carlsen Karin C. Lødrup
Published: June 2014

Background

Childhood asthma frequently has allergic comorbidities. However, there is limited knowledge of the longitudinal development of asthma comorbidites and their association to bronchial hyper‐responsiveness (BHR) and airway inflammation markers. We therefore aimed to assess the association between childhood asthma with allergic comorbidities and BHR and fractional exhaled nitric oxide (FENO) and the impact of gender on these associations.

Methods

Based on data from 550 adolescents in the prospective birth cohort ‘Environment and Childhood Asthma’ study, asthma was defined for the three time periods 0–2, 2–10 and 10–16 years of age, using recurrent bronchial obstruction (rBO) 0–2 years of age as a proxy for early asthma. Asthma comorbidities included atopic dermatitis (AD) and allergic rhinitis (AR) from 10 to 16 years. At age 16 years BHR, assessed by metacholine bronchial challenge, and airway inflammation, assessed by FENO, were compared between the groups of asthma with or without the two comorbidities, to a reference group with no never asthma, and subsequently stratified by gender.

Results

Boys with asthma and AR, regardless of AD had significantly more severe BHR and higher FENO than the other asthma phenotypes. Almost half of the children remained in the asthma and AR category from 10 to 16 years, the entire difference being determined by new incident cases from 10 to 16 years.

Conclusions

Asthma phenotypes characterized by allergic comorbidities and AR in particular appears closely associated with BHR and FENO, especially among boys.
Parental hay fever reinforces IgE to pollen as pre‐clinical biomarker of hay fever in childhood
Authors: Hatzler Laura , Panetta Valentina , Illi Sabina , Hofmaier Stephanie , Rohrbach Alexander , Hakimeh Dani , Bauer Carl P. , Hoffman Ute , Forster Johannes , Zepp Fred , Schuster Antje , Stock Philippe , Wahn Ulrich , Keil Thomas , Lau Susanne , Matricardi Paolo M.
Published: June 2014

Background

An early IgE response to grass or birch pollen can anticipate seasonal allergic rhinitis to pollen later in life or remain clinically silent.

Objective

To identify risk factors early in life that allow discriminating pathogenic from non‐pathogenic IgE responses and contribute to the development of seasonal allergic rhinitis to grass pollen.

Methods

The German Multicentre Allergy Study examined a birth cohort born in 1990. A questionnaire was yearly administered and blood samples collected at age 1,2,3,5,6,7,10,13 yr. The definition of the primary outcome grass‐ and birch‐pollen‐related seasonal allergic rhinitis (SARg, SARb) was based on nasal symptoms in June/July and April, respectively. Serum IgE antibodies to Phleum pratense and Betula verrucosae extracts were monitored with immune‐enzymatic singleplex assays.

Results

Of the 820 examined children, 177 and 148 developed SARg and SARb, respectively. Among healthy children aged 3 or more years, IgE to grass pollen was the strongest risk factor of SARg (OR 10.39, 95%CI 6.1–17.6, p < 0.001), while parental hay fever was the only risk factor in early childhood independently associated with future SARg (1 parent: OR 2.56, 95%CI 1.4–4.5, p < 0.001; 2 parents: OR 4.17, 95%CI 1.7–10.1) and SARb (1 parent OR: 5.21, 95%CI 2.20–12.4, p < 0.001; 2 parents: OR 8.02, 95%CI 2.0–32.9, p < 0.001). Parental hay fever was associated with an increase of the concentration of pollen‐specific IgE in seropositive subjects, after the age of 6 and was also a hallmark of molecularly more complex specific IgE responses to grass or birch pollen at age 6 or older.

Conclusions

Parental hay fever and specific IgE to grass and/or birch pollen are strong pre‐clinical determinants and potentially good predictors of seasonal allergic rhinitis.
Pediatric video laryngoscope versus direct laryngoscope: a meta‐analysis of randomized controlled trials
Authors: Sun Yu , Lu Yi , Huang Yan , Jiang Hong
Published: June 2014

Background

We reviewed the updated literature and performed a meta‐analysis based on randomized controlled trials in children to compare the clinical efficacy between video laryngoscopes (VLs) and direct laryngoscopes (DLs).

Methods

We searched articles published in English matching the key words ‘video laryngoscope (including Airtraq, GlideScope, Storz, TruView, AWS, Bullard, McGrath)’ AND ‘direct laryngoscope’ AND ‘children (including pediatric, infant, neonate)’ in PubMed, Ovid, Google Scholar, and the Cochrane Library databases. Only prospective randomized controlled trials (RCTs), which compared the use of VLs and DLs in children, were included. The relative risk (RR), weighted mean difference (WMD), and their corresponding 95% confidence interval (95% CI) were calculated using the quality effects model of the metaxl 1.3 software for outcome data.

Results

Fourteen studies were included in this meta‐analysis. Although VLs improved the glottis visualization in most children either with normal airways or with potentially difficult intubations, the time to intubation (TTI) was prolonged in comparison to DLs (WMD: 4.9 s; 95% CI: 2.6–7.1). Subgroup analysis showed the GlideScope (WMD: 5.2 s; 95% CI: 2.0–8.5), TruView (WMD: 5.1 s; 95% CI: 0.7–9.5), Storz (WMD: 6.4 s; 95% CI: 4.8–8.1), and Bullard (WMD: 37.5 s; 95% CI: 21.0–54.0) rather than Airtraq (WMD: 0.6 s; 95% CI: −7.7–8.9) prolonged TTI. Although the success rate of the first attempt (RR: 0.96; 95% CI: 0.92–1.00) and associated complications (RR: 1.11; 95% CI: 0.39–3.16) were similar in both groups, VLs were associated with a higher incidence of failure (RR: 6.70; 95% CI: 1.53–29.39).

Conclusion

This meta‐analysis demonstrates that although VLs improved glottis visualization in pediatric patients, this was at the expense of prolonged TTI and increased failures. However, further studies are needed to clarify the efficacy and safety of VLs in hands of nonexperts and in children with airway problems.
Comparison of performance and efficacy of air‐Q intubating laryngeal airway and flexible laryngeal mask airway in anesthetized and paralyzed infants and children
Authors: Darlong Vanlal , Biyani Ghansham , Pandey Ravindra , Baidya Dalim K. , Chandralekha   , Punj Jyotsna
Published: June 2014

Background

Flexible laryngeal mask airway is a commonly used supraglotic airway device (SAD) during ophthalmic surgeries. Air‐Q intubating laryngeal airway (ILA) is a newer SAD used as primary airway device and as a conduit for intubation as well. Available literature shows that air‐Q performs equal or better than other SADs in children and adults. However, limited data is available using air‐Q in infants and small children <10 kg. So, our aim was ‘To compare the performance and efficacy of these two devices in infants and small children’. Our hypothesis is that air‐Q due to its improved cuff design will yield better airway seal pressures and improved laryngeal alignment as compared to flexible laryngeal mask airway.

Methods

ASA I–II infants and children weighing <10 kg, undergoing cataract or glaucoma surgery, were randomly divided into two groups of 25 each. After induction of anesthesia and muscle relaxation, we measured oropharyngeal leak pressure (OLP), fibre‐optic (FO) view of glottis, first insertion success rate, time to insert, and any other complications.

Results

There was no difference between the groups in demographic data, first insertion success rate, time to insert, and postoperative complications. Air‐Q provided significantly more OLP [21.1 ± 6.4 cmH2O vs 17.4 ± 4.1 cmH2O, P = 0.02] and better FO view of glottis (good view 84% vs 48%, P = 0.0016) as compared to flexible laryngeal mask airway.

Conclusion

We conclude that air‐Q is superior to flexible laryngeal mask airway in providing higher airway sealing pressures and better FO grade of laryngeal view in infants and children.
The role of strigolactones in photomorphogenesis of pea is limited to adventitious rooting
Authors: Urquhart Shelley , Foo Eloise , Reid James B.
Published: June 2014

The recently discovered group of plant hormones, the strigolactones, have been implicated in regulating photomorphogenesis. We examined this extensively in our strigolactone synthesis and response mutants and could find no evidence to support a major role for strigolactone signaling in classic seedling photomorphogenesis (e.g. elongation and leaf expansion) in pea (Pisum sativum), consistent with two recent independent reports in Arabidopsis. However, we did find a novel effect of strigolactones on adventitious rooting in darkness. Strigolactone‐deficient mutants, Psccd8 and Psccd7, produced significantly fewer adventitious roots than comparable wild‐type seedlings when grown in the dark, but not when grown in the light. This observation in dark‐grown plants did not appear to be due to indirect effects of other factors (e.g. humidity) as the constitutively de‐etiolated mutant, lip1, also displayed reduced rooting in the dark. This role for strigolactones did not involve the MAX2 F‐Box strigolactone response pathway as Psmax2 f‐box mutants did not show a reduction in adventitious rooting in the dark compared with wild‐type plants. The auxin‐deficient mutant bushy also reduced adventitious rooting in the dark, as did decapitation of wild‐type plants. Rooting was restored by the application of indole‐3‐acetic acid (IAA) to decapitated plants, suggesting a role for auxin in the rooting response. However, auxin measurements showed no accumulation of IAA in the epicotyls of wild‐type plants compared with the strigolactone synthesis mutant Psccd8, suggesting that changes in the gross auxin level in the epicotyl are not mediating this response to strigolactone deficiency.
Evaluation of periodontal disease and oral inflammatory load in adults with special needs using oral neutrophil quantification
Authors: Moosani Anita , Sigal Michael J. , Glogauer Michael , Lawrence Herenia P. , Goldberg Michael , Tenenbaum Howard C.
Published: June 2014

The purpose of this study was to validate and assess the feasibility of using an assay of oral neutrophils to measure periodontal inflammation in uncooperative adults with special needs. Conventional periodontal measurements and neutrophil counts obtained from oral swabs were performed on patients having dental care under general anesthesia (GA) and at subsequent recall. Forty‐nine patients were assessed under GA and 30 (61%) returned for follow‐up. A high prevalence of gingival inflammation was found at baseline and oral neutrophil levels positively correlated with traditional periodontal parameters (p < 0.05). Neutrophils were acquired using swabs for 100% of patients examined at recall and a significant reduction in oral inflammatory load was noted after a single treatment session (p < 0.05), despite the persistence of poor oral hygiene and prolonged recall intervals. This study demonstrates that oral neutrophil quantification may serve as a novel and standardized method for clinical assessment of periodontal diseases in people with special needs.
HLA‐A*02:01:79, a novel allele, which has arisen by silent mutation in codon 230
Authors: Zou H.‐Y. , Jin S.‐Z. , Li Z.
Published: June 2014

A*02:01:79 is identical to A*02:01:01:01, except for one nucleotide change at nt 762 in exon 4 from C to T.
Role of the gibberellin receptors GID1 during fruit‐set in Arabidopsis
Authors: Gallego‐Giraldo Carolina , Hu Jianhong , Urbez Cristina , Gomez Maria Dolores , Sun Tai‐ping , Perez‐Amador Miguel A.
Published: June 2014

Gibberellins (GAs) play a critical role in fruit‐set and fruit growth. Gibberellin is perceived by its nuclear receptors GA INSENSITIVE DWARF1s (GID1s), which then trigger degradation of downstream repressors DELLAs. To understand the role of the three GA receptor genes (GID1A, GID1B and GID1C) in Arabidopsis during fruit initiation, we have examined their temporal and spatial localization, in combination with analysis of mutant phenotypes. Distinct expression patterns are revealed for each GID1: GID1A is expressed throughout the whole pistil, while GID1B is expressed in ovules, and GID1C is expressed in valves. Functional study of gid1 mutant combinations confirms that GID1A plays a major role during fruit‐set and growth, whereas GID1B and GID1C have specific roles in seed development and pod elongation, respectively. Therefore, in ovules, GA perception is mediated by GID1A and GID1B, while GID1A and GID1C are involved in GA perception in valves. To identify tissue‐specific interactions between GID1s and DELLAs, we analyzed spatial expression patterns of four DELLA genes that have a role in fruit initiation (GAI, RGA, RGL1 and RGL2). Our data suggest that GID1A can interact with RGA and GAI in all tissues, whereas GID1C–RGL1 and GID1B–RGL2 interactions only occur in valves and ovules, respectively. These results uncover specific functions of each GID1–DELLA in the different GA‐dependent processes that occur upon fruit‐set. In addition, the distribution of GA receptors in valves along with lack of expression of GA biosynthesis genes in this tissue, strongly suggests transport of GAs from the developing seeds to promote fruit growth.
A plasma membrane‐tethered transcription factor, NAC062/ANAC062/NTL6, mediates the unfolded protein response in Arabidopsis
Authors: Yang Zheng‐Ting , Lu Sun‐Jie , Wang Mei‐Jing , Bi Dong‐Ling , Sun Ling , Zhou Shun‐Fan , Song Ze‐Ting , Liu Jian‐Xiang
Published: June 2014

The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) triggers a well conserved pathway called the unfolded protein response (UPR) in eukaryotic cells to mitigate ER stress. Two signaling pathways, S2P‐bZIP28 and IRE1‐bZIP60, play important roles in transmitting ER stress signals from the ER to the nucleus in Arabidopsis (Arabidopsis thaliana). It is not known whether other components in the secretory pathway also contribute to the alleviation of ER stress. Here we report the identification of a plasma membrane‐associated transcription factor, NAC062 (also known as ANAC062/NTL6), as another important UPR mediator in Arabidopsis plants. NAC062 relocates from the plasma membrane to the nucleus and regulates the expression of ER stress responsive genes in Arabidopsis. Knock‐down of NAC062 in the wild‐type background confers ER stress sensitivity, while inducible expression of a nucleus‐localized form of NAC062, NAC062D, in the bZIP28 and bZIP60 double mutant (zip28zip60) background increases ER stress tolerance. Knock‐down of NAC062 impairs ER‐stress‐induced expression of UPR downstream genes while over‐expression of NAC062D‐MYC induces the expression of UPR downstream genes under normal growth condition. CHIP‐qPCR reveals that NAC062D‐MYC is enriched at the promoter regions of several UPR downstream genes such as BiP2. Furthermore, NAC062 itself is also up‐regulated by ER stress, which is dependent on bZIP60 but not on bZIP28. Thus, our results have uncovered an alternative UPR pathway in plants in which the membrane‐associated transcription factor NAC062 relays ER stress signaling from the plasma membrane to the nucleus and plays important roles in regulating UPR downstream gene expression.
Diagnostic and prognostic values of ADAMTS13 activity measured during daily plasma exchange therapy in patients with acquired thrombotic thrombocytopenic purpura
Authors: Wu Nan , Liu Jia , Yang Shangbin , Kellett Eric T. , Cataland Spero R. , Li Hong , Wu Haifeng M.
Published: June 2014

Background

Thrombotic thrombocytopenic purpura (TTP) requires immediate treatment with plasma exchange (PE) to prevent disease mortality and/or morbidity. Frequently, PE is initiated before blood sample is collected to confirm ADAMTS13 deficiency. However, the effect of PE treatments on the evaluation of ADAMTS13 is uncertain. Moreover, the pertinence of ADAMTS13 activity during PE therapy to prediction of treatment outcomes is unclear. Thus, clarification of the diagnostic and prognostic values of ADAMTS13 activity obtained during PE treatment is an unmet clinical need.

Study Design and Methods

A total of 212 sequential samples were obtained during the course of daily PE treatment from 19 patients with acquired TTP. ADAMTS13 activity levels were determined in these longitudinal samples for analysis.

Results

After the initial three daily PE procedures, the sensitivities of ADAMTS13 activity in diagnosis of TTP (<10%) were 89, 83, and 78%, respectively. To determine prognostic value, patients with (n = 7) and without (n = 12) a recovery of ADAMTS13 activity to more than 10% within seven sessions of daily PE treatment were compared. Recovery of ADAMTS13 activity to more than 10% within 7 days is significantly associated with a timely achievement of clinical response (p < 0.01). In contrast, the patients without more than 10% ADAMTS13 within 1 week appear at risk for worse treatment outcomes manifested as TTP exacerbation, treatment refractoriness, or death.

Conclusion

The data suggest that ADAMTS13 activities measured during the initial period of PE therapy offer both diagnostic and prognostic values in acquired TTP.
Propagation of Gravity Waves Past Multiple Bottom-Standing Barriers
Authors: Karmakar D. , Guedes Soares C.
Published: June 2014

The interaction of oblique surface gravity waves with multiple bottom-standing flexible porous breakwaters is analyzed based on the linearized theory of water waves. Using the method of eigenfunction expansion and the least square approximation, the wave propagation in the presence of single bottom-standing barriers is analyzed considering the upper edge to be: (i) free and (ii) moored, whereas the lower edge is considered to be clamped at the bottom. The wide-spacing approximation is used to analyze the wave interaction with multiple porous bottom-standing flexible barriers to understand the effect of the submerged flexible barriers as an effective breakwater. A brief comparison of both the upper edge conditions is carried out to analyze the effect of wave dissipation due to the presence of multiple barriers. The numerical results for the reflection and transmission coefficients along with the free surface vertical deflection are obtained for the case of two and three multiple bottom-standing barriers. The attenuation in the wave height due to the presence of porosity, change in barrier depth, and distance between the barriers are analyzed. The present study will be helpful in the analysis of proper functioning of porous bottom-standing barrier as an effective breakwater for the protection of offshore structures.
Transient Characterization of Hybrid Microfluidic-Thermoelectric Cooling Scheme for Dynamic Thermal Management of Microprocessor
Authors: Sahu Vivek , Fedorov Andrei G. , Joshi Yogendra K.
Published: June 2014

Power dissipated by modern microprocessors is a function of time and continuously changes with the workload, giving rise to temporal hotspots of local areas with very high power dissipation. A hybrid cooling scheme has been proposed, which combines solid-state cooling to remove the dynamically changing hotspots in real time while addressing the steady-state background power dissipation using liquid cooling in embedded microchannels. In this paper, we have investigated the transient behavior of the hybrid scheme through experiments as well as computational modeling. Infrared microscopy, equipped with transient detector, was used to study the transient cooling behavior when a power spike is produced by a microfabricated heater, emulating a hot spot. The results indicate that solid-state superlattice cooling (SLC) offers an extremely fast transient response, having time constant of the order of few tens of microseconds which matches with dynamics of microprocessor power dissipation. The effect of various geometric and operating conditions on the transient behavior of the hybrid scheme has been assessed to provide an insight and guidelines for optimal design and operation of the proposed hybrid cooling scheme.
Multi-objective Design Optimization of Branching, Multifloor, Counterflow Microheat Exchangers
Authors: Abdoli Abas , Dulikravich George S.
Published: June 2014

Heat removal capacity, coolant pumping power requirement, and surface temperature nonuniformity are three major challenges facing single-phase flow microchannel compact heat exchangers. In this paper multi-objective optimization has been performed to increase heat removal capacity, and decrease pumping power and temperature nonuniformity in complex networks of microchannels. Three-dimensional (3D) four-floor configurations of counterflow branching networks of microchannels were optimized to increase heat removal capacity from surrounding silicon substrate (15 × 15 × 2 mm). Each floor has four different branching subnetworks with opposite flow direction with respect to the next one. Each branching subnetwork has four inlets and one outlet. Branching patterns of each of these subnetworks could be different from the others. Quasi-3D conjugate heat transfer analysis has been performed by developing a software package which uses quasi-1D thermofluid analysis and a 3D steady heat conduction analysis. These two solvers were coupled through their common boundaries representing surfaces of the cooling microchannels. Using quasi-3D conjugate analysis was found to require one order of magnitude less computing time than a fully 3D conjugate heat transfer analysis while offering comparable accuracy for these types of application. The analysis package is capable of generating 3D branching networks with random topologies. Multi-objective optimization using modeFRONTIER software was performed using response surface approximation and genetic algorithm. Diameters and branching pattern of each subnetwork and coolant flow direction on each floor were design variables of multi-objective optimization. Maximizing heat removal capacity, while minimizing coolant pumping power requirement and temperature nonuniformity on the hot surface, were three simultaneous objectives of the optimization. Pareto-optimal solutions demonstrate that thermal loads of up to 500 W/cm2 can be managed with four-floor microchannel cooling networks. A fully 3D thermofluid analysis was performed for one of the optimal designs to confirm the accuracy of results obtained by the quasi-3D simulation package used in this paper.
The rattleback revisited
Authors: Case William , Jalal Sahar
Published: June 2014

A rattleback is a canoe-shaped body that, when spun on a smooth surface, rotates stably in one direction only; when spun in the reverse direction it oscillates violently (i.e., it “rattles”) and reverses its direction of spin. This behavior can be traced to the misalignment of the principal axes of the body with respect to the symmetry axis of its bottom surface. Although analyses of the phenomenon exist in the literature, there is not a clear, direct presentation of the basic mechanism responsible for the reversal of direction. The goal of this paper is to present, as clearly as possible, a treatment of the phenomenon by focusing on the geometry of the usual rattleback. Two initial conditions are considered: rotation about the vertical axis with no oscillation, and oscillation about a horizontal axis with no rotation. For the first initial state, oscillatory motion about the two horizontal axes is analyzed using a combination of linearization and reasonable assumptions. The reversal is then analyzed using energy considerations. The analysis for the second initial state is more direct and elementary. In combination, these analyses explain the transitions from rotation to oscillation to rotation in the opposite direction. The non-reversal for the rotation opposite initial rotation is also accounted for. We also comment on how the rattleback might be modified allowing it to reverse in both directions and thus to repeatedly reverse its direction of rotation.
The Effects of Two Different Doses of Calcium Lactate on Blood pH, Bicarbonate, and Repeated High-Intensity Exercise Performance
Authors: Painelli Vitor de Salles , da Silva Rafael Pires , de Oliveira Odilon Marques , de Oliveira Luana Farias , Benatti Fabiana Braga , Rabelo Tobias , Guilherme João Paulo Limongi França , Junior Antonio Herbert Lancha , Artioli Guilherme Giannini
Published: June 2014

We investigated the effects of low- and high-dose calcium lactate supplementation on blood pH and bicarbonate (Study A) and on repeated high-intensity performance (Study B). In Study A, 10 young, physically active men (age: 24 ± 2.5 years; weight: 79.2 ± 9.45 kg; height: 1.79 ± 0.06 m) were assigned to acutely receive three different treatments, in a crossover fashion: high-dose calcium lactate (HD: 300 mg·kg−1 body mass), low-dose calcium lactate (LD: 150 mg·kg−1 body mass) and placebo (PL). During each visit, participants received one of these treatments and were assessed for blood pH and bicarbonate 0, 60, 90, 120, 150, 180, and 240 min following ingestion. In Study B, 12 young male participants (age: 26 ± 4.5 years; weight: 82.0 ± 11.0 kg; height: 1.81 ± 0.07 m) received the same treatments of Study A. Ninety minutes after ingestion, participants underwent 3 bouts of the upper-body Wingate test and were assessed for blood pH and bicarbonate 0 and 90 min following ingestion and immediately after exercise. In Study A, both HD and LD promoted slight but significant increases in blood bicarbonate (31.47 ± 1.57 and 31.69 ± 1.04 mmol·L−1, respectively) and pH levels (7.36 ± 0.02 and 7.36 ± 0.01, respectively), with no effect of PL. In Study B, total work done, peak power, mean power output were not affected by treatments. In conclusion, low- and high-dose calcium lactate supplementation induced similar, yet very discrete, increases in blood pH and bicarbonate, which were not sufficiently large to improve repeated high-intensity performance.
Gastrointestinal Bleeding After High Intake of Omega-3 Fatty Acids, Cortisone and Antibiotic Therapy: A Case Study
Authors: Detopoulou Paraskevi , Papamikos Vasilios
Published: June 2014

Omega-3 fatty acids exert a plethora of physiological actions including triglycerides lowering, reduction of inflammatory indices, immunomodulation, anti- thrombotic effects and possibly promotion of exercise performance. Their use is widespread and for commonly ingested doses their side- effects are minimal. We report a case of a 60y amateur athlete who consumed about 20 g omega-3 fatty acids daily from supplements and natural sources for a year. After the intake of cortisone and antibiotics he presented duodenum ulcer and bleeding although he had no previous history of gastrointestinal problems. Although several animal data support gastro-protective effects of omega-3 fatty acids in the present case they were not able to prevent ulcer generation. The present observation may be explained by (i) the high dose of omega-3 fatty acids and their effect on bleeding, (ii) the fact that cortisone increases their oxidation and may render them proinflammatory, (iii) other antithrombotic microconstituents included in the consumed cod-oil and/or the diet of the subject and (iv) the differences in the coagulation and fibrinolytic systems of well- trained subjects. Further studies are needed to substantiate any possible interaction of cortisone and omega-3 fatty acids in wide ranges of intake.
Impact of Maximum Speed on Sprint Performance During High-Level Youth Female Field Hockey Matches: Female Athletes in Motion (FAiM) Study
Authors: Vescovi Jason D.
Published: June 2014

The aim of this study was to examine the impact of maximum sprint speed on peak and mean sprint speed during youth female field hockey matches. Two high-level female field hockey teams (U-17, n = 24, and U-21, n = 20) were monitored during a 4-game international test series using global position system technology and tested for maximum sprint speed. Dependent variables were compared using a 3-factor ANOVA (age group, position, and speed classification); effect sizes (Cohen d) and confidence limits were also calculated. Maximum sprint speed was similar between age groups and positions, with faster players having greater speed than slower players (29.3 ± 0.4 vs 27.2 ± 1.1 km/h). Overall, peak match speed in youth female field hockey players reaches approximately 90% of maximum sprint speed. Absolute peak match speed and mean sprint speed during matches were similar among the age groups (except match 1) and positions (except match 2); however, peak match speed was greater for faster players in matches 3 and 4. No differences were observed in the relative proportion for mean sprint speeds for age groups or positions, but slower players consistently displayed similar relative mean sprint speeds by using a greater proportion of their maximum sprint speed.
Reliable Encoding of Stimulus Intensities Within Random Sequences of Intracellular Ca
2+
Spikes
Authors: Thurley Kevin , Tovey Stephen C. , Moenke Gregor , Prince Victoria L. , Meena Abha , Thomas Andrew P. , Skupin Alexander , Taylor Colin W. , Falcke Martin
Published: June 2014

Mathematical analysis of Ca
2+
signals in single cells reveals how cells can encode stimulus intensity in the frequency of Ca
2+
spikes.
Cell Fate Control—A Numbers Game
Authors: Ray L. Bryan
Published: June 2014

An analysis reveals how the very low terminal differentiation rates in adipocytes are maintained.
Yeast Metacaspase: Grim Reaper or Savior?
Authors: Hurtley Stella M.
Published: June 2014

An enzyme linked to cell death in animal cells protects yeast cells from misfolded protein aggregates.
Breathing Freely
Authors: Smith Orla M.
Published: June 2014

Locking the integrin αvβ8 in a specific conformation inhibits TGF-β activation and ameliorates symptoms of airway disease in mice.
Structural Insights into and Activity Analysis of the Antimicrobial Peptide Myxinidin
Authors: Cantisani Marco , Finamore Emiliana , Mignogna Eleonora , Falanga Annarita , Nicoletti Giovanni Francesco , Pedone Carlo , Morelli Giancarlo , Leone Marilisa , Galdiero Massimiliano , Galdiero Stefania
Published: June 2014

The marine environment has been poorly explored in terms of potential new molecules possessing antibacterial activity. Antimicrobial peptides (AMPs) offer a new potential class of pharmaceuticals; however, further optimization is needed if AMPs are to find broad use as antibiotics. We focused our studies on a peptide derived from the epidermal mucus of hagfish (
Myxine glutinosa
L.), which was previously characterized and showed high antimicrobial activity against human and fish pathogens. In the present work, the activities of myxinidin peptide analogues were analyzed with the aim of widening the original spectrum of action of myxinidin by suitable changes in the peptide primary structure. The analysis of key residues by alanine scanning allowed for the design of novel peptides with increased activity. We identified the amino acids that are of the utmost importance for the observed antimicrobial activities against a set of pathogens comprising both Gram-negative and Gram-positive bacteria. Overall, optimized bactericidal potency was achieved by adding a tryptophan residue at the N terminus and by the simultaneous substitution of residues present in positions 3, 4, and 11 with arginine. These results indicate that the myxinidin analogues emerge as an attractive alternative for treating drug-resistant infectious diseases and provide key insights into a rational design for novel agents against these pathogens.
Relationship between Glycopeptide Production and Resistance in the Actinomycete Nonomuraea sp. ATCC 39727
Authors: Marcone Giorgia Letizia , Binda Elisa , Carrano Lucia , Bibb Mervyn , Marinelli Flavia
Published: June 2014

Glycopeptides and β-lactams inhibit bacterial peptidoglycan synthesis in Gram-positive bacteria; resistance to these antibiotics is studied intensively in enterococci and staphylococci because of their relevance to infectious disease. Much less is known about antibiotic resistance in glycopeptide-producing actinomycetes that are likely to represent the evolutionary source of resistance determinants found in bacterial pathogens.Nonomuraeasp. ATCC 39727, the producer of A40926 (the precursor for the semisynthetic dalbavancin), does not harbor the canonicalvanHAXgenes. Consequently, we investigated the role of the β-lactam-sensitived,d-peptidase/d,d-carboxypeptidase encoded byvanYn, the onlyvan-like gene found in the A40926 biosynthetic gene cluster, in conferring immunity to the antibiotic inNonomuraeasp. ATCC 39727. Taking advantage of the tools developed recently to genetically manipulate this uncommon actinomycete, we variedvanYngene dosage and expressedvanHatAatXatfrom the teicoplanin producerActinoplanes teichomyceticusinNonomuraeasp. ATCC 39727. Knocking outvanYn, complementing avanYnmutant, or duplicatingvanYnhad no effect on growth but influenced antibiotic resistance and, in the cases of complementation and duplication, antibiotic production.Nonomuraeasp. ATCC 39727 was found to be resistant to penicillins, but its glycopeptide resistance was diminished in the presence of penicillin G, which inhibits VanYnactivity. The heterologous expression ofvanHatAatXatincreased A40926 resistance inNonomuraeasp. ATCC 39727 but did not increase antibiotic production, indicating that the level of antibiotic production is not directly determined by the level of resistance. ThevanYn-based self-resistance inNonomuraeasp. ATCC 39727 resembles the glycopeptide resistance mechanism described recently in mutants ofEnterococcus faeciumselectedin vitrofor high-level resistance to glycopeptides and penicillins.
Changes in Antigen-Specific Cytokine and Chemokine Responses to Plasmodium falciparum Antigens in a Highland Area of Kenya after a Prolonged Absence of Malaria Exposure
Authors: Ochola Lyticia A. , Ayieko Cyrus , Kisia Lily , Magak Ng'wena G. , Shabani Estela , Ouma Collins , John Chandy C.
Published: June 2014

Individuals naturally exposed toPlasmodium falciparumlose clinical immunity after a prolonged lack of exposure.P. falciparumantigen-specific cytokine responses have been associated with protection from clinical malaria, but the longevity ofP. falciparumantigen-specific cytokine responses in the absence of exposure is not well characterized. A highland area of Kenya with low and unstable malaria transmission provided an opportunity to study this question. The levels of antigen-specific cytokines and chemokines associated in previous studies with protection from clinical malaria (gamma interferon [IFN-γ], interleukin-10 [IL-10], and tumor necrosis factor alpha [TNF-α]), with increased risk of clinical malaria (IL-6), or with pathogenesis of severe disease in malaria (IL-5 and RANTES) were assessed by cytometric bead assay in April 2008, October 2008, and April 2009 in 100 children and adults. During the 1-year study period, none had an episode of clinicalP. falciparummalaria. Two patterns of cytokine responses emerged, with some variation by antigen: a decrease at 6 months (IFN-γ and IL-5) or at both 6 and 12 months (IL-10 and TNF-α) or no change over time (IL-6 and RANTES). These findings document thatP. falciparumantigen-specific cytokine responses associated in prior studies with protection from malaria (IFN-γ, TNF-α, and IL-10) decrease significantly in the absence ofP. falciparumexposure, whereas those associated with increased risk of malaria (IL-6) do not. The study findings provide a strong rationale for future studies of antigen-specific IFN-γ, TNF-α, and IL-10 responses as biomarkers of increased population-level susceptibility to malaria after prolonged lack ofP. falciparumexposure.
Antibodies to PhnD Inhibit Staphylococcal Biofilms
Authors: Lam Hubert , Kesselly Augustus , Stegalkina Svetlana , Kleanthous Harry , Yethon Jeremy A.
Published: June 2014

Biofilm formation on central lines or peripheral catheters is a serious threat to patient well-being. Contaminated vascular devices can act as a nidus for bloodstream infection and systemic pathogen dissemination. Staphylococcal biofilms are the most common cause of central-line-associated bloodstream infections, and antibiotic resistance makes them difficult to treat. As an alternative to antibiotic intervention, we sought to identify anti-staphylococcal biofilm targets for the development of a vaccine or antibody prophylactic. A screening strategy was devised using a microfluidic system to test antibody-mediated biofilm inhibition under biologically relevant conditions of shear flow. Affinity-purified polyclonal antibodies to target antigen PhnD inhibited both
Staphylococcus epidermidis
and
S. aureus
biofilms. PhnD-specific antibodies blocked biofilm development at the initial attachment and aggregation stages, and deletion of
phnD
inhibited normal biofilm formation. We further adapted our microfluidic biofilm system to monitor the interaction of human neutrophils with staphylococcal biofilms and demonstrated that PhnD-specific antibodies also serve as opsonins to enhance neutrophil binding, motility, and biofilm engulfment. These data support the identification of PhnD as a lead target for biofilm intervention strategies performed either by vaccination or through passive administration of antibodies.
Amino Acid Residues of RegA Important for Interactions with the CbbR-DNA Complex of Rhodobacter sphaeroides
Authors: Dangel Andrew W. , Luther Amanda , Tabita F. Robert
Published: June 2014

CbbR and RegA (PrrA) are transcriptional regulators of the Calvin-Benson-Bassham (CBB) CO
2
fixation pathway (

cbb
I

and

cbb
II

) operons of
Rhodobacter sphaeroides
. The CbbR and RegA proteins interact, but CbbR must be bound to the promoter DNA in order for RegA-CbbR protein-protein interactions to occur. RegA greatly enhances the ability of CbbR to bind the

cbb
I

promoter or greatly enhances the stability of the CbbR/promoter complex. The N-terminal receiver domain and the DNA binding domain of RegA were shown to interact with CbbR. Residues in α-helix 7 and α-helix 8 of the DNA binding domain (helix-turn-helix) of RegA directly interacted with CbbR, with α-helix 7 positioned immediately above the DNA and α-helix 8 located in the major groove of the DNA. A CbbR protein containing only the DNA binding motif and the linker helix was capable of binding to RegA. In contrast, a truncated CbbR containing only the linker helix and recognition domains I and II (required for effector binding) was not able to interact with RegA. The accumulated results strongly suggest that the DNA binding domains of both proteins interact to facilitate optimal transcriptional control over the
cbb
operons.
In vivo
analysis, using constitutively active mutant CbbR proteins, further indicated that CbbR must interact with phosphorylated RegA in order to accomplish transcriptional activation.
Pentaplex PCR Assay for Detection of Hemorrhagic Bacteria from Stool Samples
Authors: Al-Talib Hassanain , Latif Baha , Mohd-Zain Zaini
Published: June 2014

Diarrheal diseases cause illness and death among children younger than 10 years in developing countries. Conventional testing for the detection of hemorrhagic bacteria takes 2 to 5 days to yield complete information on the organism and its antibiotic sensitivity pattern. Hence, in the present study, we developed a molecular-based diagnostic assay that identifies common hemorrhagic bacteria in stool samples. A set of specific primers were designed for the detection of
Salmonella
spp.,
Shigella
spp., enterohemorrhagic
Escherichia coli
(EHEC), and
Campylobacter
spp., suitable for use in a one-tube PCR assay. The assay in the present study simultaneously detected five genes, namely,
ompC
for the
Salmonella
genus,
virA
for the
Shigella
genus,
eaeA
for EHEC, 16S rRNA for the
Campylobacter
genus, and
hemA
for an internal control. Specific primer pairs were successfully designed and simultaneously amplified the targeted genes. Validation with 20 Gram-negative and 17 Gram-positive strains yielded 100% specificity. The limit of detection of the multiplex PCR assay was 1 × 10
3
CFU at the bacterial cell level and 100 pg at the genomic DNA level. Further evaluation of the multiplex PCR with 223 bacterium-spiked stool specimens revealed 100% sensitivity and specificity. We conclude that the developed multiplex PCR assay was rapid, giving results within 4 h, which is essential for the identification of hemorrhagic bacteria, and it might be useful as an additional diagnostic tool whenever time is important in the diagnosis of hemorrhagic bacteria that cause diarrhea. In addition, the presence of an internal control in the multiplex PCR assay is important for excluding false-negative cases.
Diagnosis of Ureaplasma urealyticum Septic Polyarthritis by PCR Assay and Electrospray Ionization Mass Spectrometry in a Patient with Acute Lymphoblastic Leukemia
Authors: Balsat Marie , Galicier Lionel , Wargnier Alain , Pereyre Sabine , Itzykson Raphaël , Zouakh Myriem , Bébéar Cécile , Boissel Nicolas
Published: June 2014

We report a case of polyarthritis with axial involvement in a young female patient treated for acute lymphoblastic leukemia. Detection in the hip fluid of
Ureaplasma urealyticum
by broad-range PCR followed by electrospray ionization mass spectrometry allowed the diagnosis of septic arthritis and
ad integrum
recovery upon adapted antibiotic therapy.
Detection of Chronic Wasting Disease in the Lymph Nodes of Free-Ranging Cervids by Real-Time Quaking-Induced Conversion
Authors: Haley Nicholas J. , Carver Scott , Hoon-Hanks Laura L. , Henderson Davin M. , Davenport Kristen A. , Bunting Elizabeth , Gray Shawn , Trindle Bruce , Galeota Judith , LeVan Ivy , Dubovos Tracy , Shelton Paul , Hoover Edward A.
Published: June 2014

Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of deer, elk, and moose, is the only prion disease affecting free-ranging animals. Since the disease was first identified in northern Colorado and southern Wyoming in 1967, new epidemic foci of the disease have been identified in 20 additional states, as well as two Canadian provinces and the Republic of South Korea. Identification of CWD-affected animals currently requires postmortem analysis of brain or lymphoid tissues using immunohistochemistry (IHC) or an enzyme-linked immunosorbent assay (ELISA), with no practical way to evaluate potential strain types or to investigate the epidemiology of existing or novel foci of disease. Using a standardized real-time (RT)-quaking-induced conversion (QuIC) assay, a seeded amplification assay employing recombinant prion protein as a conversion substrate and thioflavin T (ThT) as an amyloid-binding fluorophore, we analyzed, in a blinded manner, 1,243 retropharyngeal lymph node samples from white-tailed deer, mule deer, and moose, collected in the field from areas with current or historic CWD endemicity. RT-QuIC results were then compared with those obtained by conventional IHC and ELISA, and amplification metrics using ThT and thioflavin S were examined in relation to the clinical history of the sampled deer. The results indicate that RT-QuIC is useful for both identifying CWD-infected animals and facilitating epidemiological studies in areas in which CWD is endemic or not endemic.
Encephalitis Caused by Chikungunya Virus in a Traveler from the Kingdom of Tonga
Authors: Nelson Joanna , Waggoner Jesse J. , Sahoo Malaya K. , Grant Philip M. , Pinsky Benjamin A.
Published: June 2014

Febrile travelers from countries with unique endemic pathogens pose a significant diagnostic challenge. In this report, we describe the case of a Tongan man presenting with fever, rash, and altered mental status. The diagnosis of Chikungunya encephalitis was made using a laboratory-developed real-time RT-PCR and serologic testing.