bluuebunny/crossref_metadata_2025 huggingface dataset:
Site‐directed Mutagenesis of Key Residues Unveiled a Novel Allosteric Site on Human Adenosine Kinase for Pyrrolobenzoxa(thia)zepinone Non‐Nucleoside Inhibitors
Authors: Savi Lida , Brindisi Margherita , Alfano Gloria , Butini Stefania , La Pietra Valeria , Novellino Ettore , Marinelli Luciana , Lossani Andrea , Focher Federico , Cavella Caterina , Campiani Giuseppe , Gemma Sandra
Published: August 2015

Most nucleoside kinases, besides the catalytic domain, feature an allosteric domain which modulates their activity. Generally, non‐substrate analogs, interacting with allosteric sites, represent a major opportunity for developing more selective and safer therapeutics. We recently developed a series of non‐nucleoside non‐competitive inhibitors of human adenosine kinase (hAK), based on a pyrrolobenzoxa(thia)zepinone scaffold. Based on computational analysis, we hypothesized the existence of a novel allosteric site on hAK, topographically distinct from the catalytic site. In this study, we have adopted a multidisciplinary approach including molecular modeling, biochemical studies, and site‐directed mutagenesis to validate our hypothesis. Based on a three‐dimensional model of interaction between hAK and our molecules, we designed, cloned, and expressed specific, single and double point mutants of hAK (Q74A, Q78A, H107A, K341A, F338A, and Q74A‐F338A). Kinetic characterization of recombinant enzymes indicated that these mutations did not affect enzyme functioning; conversely, mutated enzymes are endowed of reduced susceptibility to our non‐nucleoside inhibitors, while maintaining comparable affinity for nucleoside inhibitors to the wild‐type enzyme. This study represents the first characterization and validation of a novel allosteric site in hAK and may pave the way to the development of novel selective and potent non‐nucleoside inhibitors of hAK endowed with therapeutic potential.
Identification of educational needs in the management of overweight and obesity: results of an international survey of attitudes and practice
Authors: Leiter L. A. , Astrup A. , Andrews R. C. , Cuevas A. , Horn D. B. , Kunešová M. , Wittert G. , Finer N.
Published: August 2015

Despite the availability of a growing range of interventions to assist control of body weight for people with excess weight or obesity, only a small proportion of people achieve their weight loss goals and are able to maintain body weight reductions in the long term. Negative attitudes and beliefs are often found among physicians and others involved in treating obesity and may adversely impact the effectiveness of management. In this international study, healthcare professionals were invited to complete an online survey of their attitudes and practice in the management of excess body weight. A total of 335 clinicians completed the survey of whom approximately half were based in Europe. A key finding from the survey is that, while participants are generally confident in their ability to manage overweight and obesity effectively, they also report that most of their patients are not successful in achieving their weight loss goals. At the same time, participants tended to overestimate the effectiveness of current medical management in maintaining reductions in body weight. Educational initiatives addressing the real‐life effectiveness of different weight control interventions may help to close the gap between clinicians' perceptions and reality in the management of excess body weight.
Profiling unauthorized natural resource users for better targeting of conservation interventions
Authors: Harrison Mariel , Baker Julia , Twinamatsiko Medard , Milner‐Gulland E.J.
Published: August 2015

Unauthorized use of natural resources is a key threat to many protected areas. Approaches to reducing this threat include law enforcement and integrated conservation and development (ICD) projects, but for such ICDs to be targeted effectively, it is important to understand who is illegally using which natural resources and why. The nature of unauthorized behavior makes it difficult to ascertain this information through direct questioning. Bwindi Impenetrable National Park, Uganda, has many ICD projects, including authorizing some local people to use certain nontimber forest resources from the park. However, despite over 25 years of ICD, unauthorized resource use continues. We used household surveys, indirect questioning (unmatched count technique), and focus group discussions to generate profiles of authorized and unauthorized resource users and to explore motivations for unauthorized activity. Overall, unauthorized resource use was most common among people from poor households who lived closest to the park boundary and farthest from roads and trading centers. Other motivations for unauthorized resource use included crop raiding by wild animals, inequity of revenue sharing, and lack of employment, factors that created resentment among the poorest communities. In some communities, benefits obtained from ICD were reported to be the greatest deterrents against unauthorized activity, although law enforcement ranked highest overall. Despite the sensitive nature of exploring unauthorized resource use, management‐relevant insights into the profiles and motivations of unauthorized resource users can be gained from a combination of survey techniques, as adopted here. To reduce unauthorized activity at Bwindi, we suggest ICD benefit the poorest people living in remote areas and near the park boundary by providing affordable alternative sources of forest products and addressing crop raiding. To prevent resentment from driving further unauthorized activity, ICDs should be managed transparently and equitably.
Regulatory Considerations in the Design and Manufacturing of Implantable 3D‐Printed Medical Devices
Authors: Morrison Robert J. , Kashlan Khaled N. , Flanangan Colleen L. , Wright Jeanne K. , Green Glenn E. , Hollister Scott J. , Weatherwax Kevin J.
Published: August 2015

Three‐dimensional (3D) printing, or additive manufacturing, technology has rapidly penetrated the medical device industry over the past several years, and innovative groups have harnessed it to create devices with unique composition, structure, and customizability. These distinctive capabilities afforded by 3D printing have introduced new regulatory challenges. The customizability of 3D‐printed devices introduces new complexities when drafting a design control model for FDA consideration of market approval. The customizability and unique build processes of 3D‐printed medical devices pose unique challenges in meeting regulatory standards related to the manufacturing quality assurance. Consistent material powder properties and optimal printing parameters such as build orientation and laser power must be addressed and communicated to the FDA to ensure a quality build. Postprinting considerations unique to 3D‐printed devices, such as cleaning, finishing and sterilization are also discussed. In this manuscript we illustrate how such regulatory hurdles can be navigated by discussing our experience with our group's 3D‐printed bioresorbable implantable device.
Diagnostic utility of 5‐hydroxymethylcytosine immunohistochemistry in melanocytic proliferations
Authors: Rodić Nemanja , Zampella John , Sharma Reema , Burns Kathleen H. , Taube Janis M.
Published: August 2015

Decreased hydroxymethylated cytosine (5‐hydroxymethycytosine, 5‐hmC) is reported to correlate with melanocyte dysplasia. The purpose of this study was to assess the diagnostic utility of this observation. 5‐hmC immunohistochemistry was performed on tissue microarrays containing 171‐melanocytic lesions from two different institutions. An immunohistochemical staining score representing the percentage and intensity of nuclear staining was assigned. The performance characteristics of 5‐hmC immunohistochemistry for discriminating between a nevus and melanoma were determined. Additional cases of melanoma arising in a nevus (n = 8), nodal nevi (n = 5) and melanoma micrometastases to a lymph node (n = 6) were also assessed. Pronounced 5‐hmC loss was observed in melanomas when compared with nevi (mean ± standard deviation = 6.71 ± 11.78 and 55.19 ± 23.66, respectively, p < 0.0001). While the mean immunohistochemical staining score values for melanocytic nevi and melanoma were distinct, there was considerable variability in immunohistochemical staining score within a single diagnostic category. The sensitivity and specificity of this assay for nevus vs. melanoma is 92.74 and 97.78%, respectively. Distinct biphasic staining patterns were observed in cases of melanoma arising in association with a nevus. Relative changes of 5‐hmC expression within a single lesion may be more informative than absolute values when using 5‐hmC as a diagnostic adjunct.
Eye examination as part of the equine prepurchase examination
Authors: Matthews A. G.
Published: August 2015

Prepurchase examination (PPE) is the most common reason for eye examination in first opinion equine practice. This paper describes a standard protocol for competent eye examination in the PPE, and reviews the interpretation of the more common clinical findings, particularly in relation to their expected influence on functional vision and their progression. The content is based on the limited existing literature, the personal opinions and experience of the author, and from discussions held with colleagues over the past 30 years.
Montane forest ecotones moved downslope in northeastern USA in spite of warming between 1984 and 2011
Authors: Foster Jane R. , D'Amato Anthony W.
Published: August 2015

Ecotones are transition zones that form, in forests, where distinct forest types meet across a climatic gradient. In mountains, ecotones are compressed and act as potential harbingers of species shifts that accompany climate change. As the climate warms in New England, USA, high‐elevation boreal forests are expected to recede upslope, with northern hardwood species moving up behind. Yet recent empirical studies present conflicting findings on this dynamic, reporting both rapid upward ecotonal shifts and concurrent increases in boreal species within the region. These discrepancies may result from the limited spatial extent of observations. We developed a method to model and map the montane forest ecotone using Landsat imagery to observe change at scales not possible for plot‐based studies, covering mountain peaks over 39 000 km2. Our results show that ecotones shifted downward or stayed stable on most mountains between 1991 and 2010, but also shifted upward in some cases (13–15% slopes). On average, upper ecotone boundaries moved down −1.5 m yr−1 in the Green Mountains, VT, and −1.3 m yr−1 in the White Mountains, NH. These changes agree with remeasured forest inventory data from Hubbard Brook Experimental Forest, NH, and suggest that processes of boreal forest recovery from prior red spruce decline, or human land use and disturbance, may swamp out any signal of climate‐mediated migration in this ecosystem. This approach represents a powerful framework for evaluating similar ecotonal dynamics in other mountainous regions of the globe.
Eight decades of sampling reveal a contemporary novel fish assemblage in coastal nursery habitats
Authors: Barceló Caren , Ciannelli Lorenzo , Olsen Esben M. , Johannessen Tore , Knutsen Halvor
Published: August 2015

In order to adequately monitor biodiversity trends through time and their responses to natural or anthropogenic impacts, researchers require long time series that are often unavailable. This general lack of datasets that are several decades or longer makes establishing a background or baseline of diversity metrics difficult – especially when attempting to understand species composition changes against a backdrop of climate and ecological variability. Here, we present an analysis of a community of juvenile nearshore fishes based on nearly 8 decades of highly standardized Norwegian survey records. Using multivariate statistical techniques, we: (i) characterize the change in taxonomic community composition through time, (ii) determine whether there has been an increase in warm‐water affinity species relative to their cold water affinity counterparts, and (iii) characterize the temporal change in the species’ functional trait assemblage. Our results strongly indicate a shift toward a novel fish assemblage between the late 1990s and 2000s. The context of changes within the most recent two decades is in stark contrast to those during the 1960s and 1970s, but similar to those during the previous warm period during the 1930s and 1940s. This novel assemblage is tightly linked to the warming temperatures in the region portrayed by the increased presence of warm‐water species and a higher incidence of pelagic, planktivorous species. The results indicate a clear influence of ocean temperature on the region's juvenile fish community that points to climate‐mediated effects on the species assemblages of an important fish nursery area.
Modelling the Lost City hydrothermal field: influence of topography and permeability structure
Authors: Titarenko S. S. , McCaig A. M.
Published: August 2015

The Lost City hydrothermal field (LCHF) is hosted in serpentinite at the crest of the Atlantis Massif, an oceanic core complex close to the mid‐Atlantic Ridge. It is remarkable for its longevity and for venting low‐temperature (40–91°C) alkaline fluids rich in hydrogen and methane. IODP Hole U1309D, 5 km north of the LCHF, penetrated 1415 m of gabbroic rocks and contains a near‐conductive thermal gradient close to 100°C km−1. This is remarkable so close to an active hydrothermal field. We present hydrothermal modelling using a topographic profile through the vent field and IODP site U1309. Long‐lived circulation with vent temperatures similar to the LCHF can be sustained at moderate permeabilities of 10−14 to 10−15 m2 with a basal heatflow of 0.22 W m−2. Seafloor topography is an important control, with vents tending to form and remain in higher topography. Models with a uniform permeability throughout the Massif cannot simultaneously maintain circulation at the LCHF and the near‐conductive gradient in the borehole, where permeabilities <10−16 m2 are required. A steeply dipping permeability discontinuity between the LCHF and the drill hole is required to stabilize venting at the summit of the massif by creating a lateral conductive boundary layer. The discontinuity needs to be close to the vent site, supporting previous inferences that high permeability is most likely produced by faulting related to the transform fault. Rapid increases in modelled fluid temperatures with depth beneath the vent agree with previous estimates of reaction temperature based on geochemical modelling.
The enigma of the clandestine association between chloroquine and HIV‐1 infection
Authors: Chauhan A , Tikoo A
Published: August 2015

Objectives

The antimalarial drug chloroquine (CQ) dampens the immune system and is used in the treatment of autoimmune disorders. CQ also shows antiviral activity against nonenveloped and enveloped viruses, including HIV‐1. Persistent immune activation in chronic HIV‐1infection leads to CD4 T‐cell depletion. CQ is envisioned to attenuate immune activation and virus activity in HIV‐1‐infected patients. The role of CQ in immune activation and virus activity is discussed here.

Methods

To elucidate the effect of CQ on immune activation, a retrospective review of published clinical trials, in vivo experimental studies in animals, and the most relevant in vitro observations in HIV‐1‐infected cells, together with observations from our own laboratory studies, was carried out and the findings discussed.

Results

In a few clinical studies and animal experiments, CQ was ineffective in decreasing immune activation and HIV‐1 infection. In vitro, CQ markedly increased HIV‐1 infection in astrocytes and other non‐CD4 cells.

Conclusions

The use of CQ in HIV‐1‐infected patients is questionable. The evidence for a dampening of immune activation by CQ is inconclusive.
Outcome of neuropsychiatric symptoms related to an antiretroviral drug following its substitution by nevirapine: the RELAX study
Authors: Pedrol E , Llibre JM , Tasias M , Currán A , Guardiola JM , Deig E , Guelar A , Martínez‐Madrid O , Tikhomirova L , Ramírez R ,   RELAX Study Group
Published: August 2015

Objectives

The primary objective was to evaluate the improvement in neuropsychiatric symptoms attributed to an antiretroviral drug after that drug was substituted with nevirapine. The secondary objective was to evaluate the impact on patient adherence and quality of life.

Methods

A prospective, observational study was carried out that included patients with HIV‐1 plasma suppression for whom an antiretroviral drug was substituted with nevirapine because of central nervous system (CNS) side effects, a Pittsburgh Sleep Quality Index (PSQI) score > 5 or a Hospital Anxiety and Depression Scale (HADS) score ≥ 10, and who had not initiated psychoactive drug treatment during the prior 6 weeks. Evaluations were carried out at baseline and 1 and 3 months after the switch using the PSQI, HADS, Epworth Sleepiness Scale, Medical Outcomes Study‐Short Form 30 items (MOS‐SF‐30) and Simplified Medication Adherence Questionnaire (SMAQ).

Results

A total of 129 patients were included in the study. The drug substituted was mainly efavirenz (89.9%), and reasons for the switch included sleep disturbances (75.2%), anxiety (65.1%), depression (38.7%), attention disturbances (31%), and other reasons (31%), with a mean of 2.4 neuropsychiatric disturbances per patient. A statistically significant improvement was observed in all the tests evaluating neuropsychiatric symptoms and adherence at 1 and 3 months. The CD4 lymphocyte count remained stable (P = 0.096). Three (2.3%) patients had a detectable plasma HIV‐1 RNA at the end of the study. Nine patients (6.9%) withdrew because of nevirapine‐related toxicity (rash in seven patients and hypertransaminasaemia in two patients, none of which were > grade 2).

Conclusions

The switch to nevirapine from a drug causing neuropsychiatric disturbances (primarily efavirenz) in subjects with virological suppression was effective in resolving those disturbances, with an improvement in all the parameters studied. This led to better adherence to treatment and quality of life, with no detrimental effect on their immunological and virological control.
Impact of smoking on the age at diagnosis of upper tract urothelial carcinoma: Subanalysis of the Japanese Urological Association multi‐institutional national database
Authors: Miyazaki Jun , Nishiyama Hiroyuki , Fujimoto Hiroyuki , Ohyama Chikara , Koie Takuya , Hinotsu Shiro , Kikuchi Eiji , Sakura Mizuaki , Inokuchi Junichi , Hara Tomohiko ,   the Cancer Registration Committee of the Japanese Urological Association
Published: August 2015

Objectives

To examine the influence of smoking history on the diagnosis and other tumor characteristics of upper tract urothelial carcinoma in Japan.

Methods

A total of 1509 patients with upper tract urothelial carcinoma who were diagnosed in 2005 from 348 Japanese institutions were registered using the multi‐institutional national database of the Japanese Urological Association and included in this analysis. Clinical data of the patients were collected in 2011. The associations between the patients’ self‐reported smoking history and their age at the diagnosis of upper tract urothelial carcinoma, sex, pathological T stage and tumor grade were analyzed.

Results

The mean age at the diagnosis of upper tract urothelial carcinoma was approximately 5 years earlier for the 238 current smokers than for the 618 current non‐smokers (P < 0.0001). Similar associations between smoking and the early diagnosis of upper tract urothelial carcinoma were shown in the sex subgroups and in subgroups stratified by pathological T stages. Among the current smokers, the age at diagnosis for the smoking ≥ 20 cigarettes per day group was 6.5 years lower than that of the < 20 cigarettes per day group, which was significantly different (P < 0.0001).

Conclusion

Current smoking is a significant risk factor for the earlier diagnosis of upper tract urothelial carcinoma. The finding is important from the perspective of both healthcare and medical economies.
Geographical pattern of isolation and diversification in karst habitat islands: a case study in the Primulina eburnea complex
Authors: Gao Yong , Ai Bin , Kong Hanghui , Kang Ming , Huang Hongwen
Published: August 2015

Aim

This study aimed to clarify species boundaries as well as phylogenetic relationships among species of the Primulina eburnea complex, a rapidly diversifying group of edaphic specialists confined to karst habitat islands in southern China. We investigated patterns of genetic isolation and diversification in this complex.

Location

Limestone karsts in southern China.

Methods

We analysed data from three chloroplast DNA (cpDNA) regions and eight nuclear microsatellite loci, representing five closely related species in the P. eburnea complex sampled from 62 populations across its entire distributional range. We conducted a Bayesian phylogenetic analysis, constructed maximum parsimony haplotype networks and assessed population genetic diversity, population differentiation and geographical structure within and between species.

Results

Of the 60 identified haplotypes, eight were shared between populations and only one was shared between species. Both cpDNA and the nuclear markers revealed a high level of population genetic differentiation and a strong phylogeographical structure. Four main genetic clusters were identified according to their geographical proximity, although geographical structuring differed slightly between the cpDNA and the nuclear loci. The pattern of genetic structure of both the cpDNA and microsatellite genomes can be explained by patterns of isolation by distance (IBD), across both the distribution of the complex and the populations of individual species.

Main conclusions

This is the first study to investigate geographical isolation and speciation in a clade associated with karst habitat islands in southern China. Geographically structured population differentiation of the P. eburnea complex suggests that divergence is mainly driven by genetic drift, with little evidence of gene flow. Allopatric speciation is the main mode of diversification in the group. These results highlight the importance of geographical isolation in promoting population differentiation in karst habitat islands.
Exaggerated Exercise Blood Pressure Response and Future Cardiovascular Disease
Authors: Tzemos Nikolaos , Lim Pitt O. , Mackenzie Isla S. , MacDonald Thomas M.
Published: August 2015

Exaggerated blood pressure (BP) response to exercise predicts future hypertension. However, there is considerable lack of understanding regarding the mechanism of how this abnormal response is generated, and how it relates to the future establishment of cardiovascular disease. The authors studied 82 healthy male volunteers without cardiovascular risk factors. The participants were categorized into two age‐matched groups depending on their exercise systolic BP (ExSBP) rise after 3 minutes of exercise using a submaximal step test: exaggerated ExSBP group (hyper‐responders [peak SBP ≥180 mm Hg]) and low ExSBP responder group (hypo‐responders [peak SBP <180 mm Hg]). Forearm venous occlusion plethysmography and intra‐arterial infusions of acetylcholine (ACh), NG‐monomethyl‐L‐arginine (L‐NMMA), sodium nitroprusside (SNP), and norepinephrine (NE) were used to assess vascular reactivity. Proximal aortic compliance was assessed with ultrasound, and neurohormonal blood sampling was performed at rest and during peak exercise. The hyper‐responder group exhibited a significantly lower increase in forearm blood flow (FBF) with ACh compared with the hypo‐responder group (ΔFBF 215% [14] vs 332.3% [28], mean [standard error of the mean]; P<.001), as well as decreased proximal aortic compliance. The vasoconstrictive response to L‐NMMA was significantly impaired in the hyper‐responder group in comparison to the hypo‐responder group (ΔFBF −40.2% [1.6] vs −50.2% [2.6]; P<.05). In contrast, the vascular response to SNP and NE were comparable in both groups. Peak exercise plasma angiotensin II levels were significantly higher in the hyper‐responder group (31 [1] vs 23 [2] pg/mL, P=.01). An exaggerated BP response to exercise is related to endothelial dysfunction, decreased proximal aortic compliance, and increased exercise‐related neurohormonal activation, the constellation of which may explain future cardiovascular disease.
Correlation of 24‐Hour Blood Pressure and Heart Rate Variability to Renal Function Parameters in Hypertensive Patients. The Effect of Smoking
Authors: Liakos Charalampos I. , Karpanou Eva A. , Markou Maria I. , Grassos Charalampos A. , Vyssoulis Gregory P.
Published: August 2015

Intrarenal hemodynamics depend on blood pressure (BP), heart rate (HR), and smoking. Although BP levels have been associated with kidney function, the effect of HR levels, BP, and HR variability on renal function are less well clarified. This cross‐sectional study sought to determine the association of 24‐hour BP and HR variability with kidney function in hypertensive patients, stratified by smoking. The study comprised 9600 nondiabetic, never‐treated hypertensive individuals without evident renal impairment examined from 1985 to 2014 (aged 53.3±13.4 years, 55.3% males). The 24‐hour systolic BP (SBP) and HR variability were estimated via their coefficient of variation (CV=standard deviation×100/mean value) derived from ambulatory recording. The CVSBP‐to‐CVHR ratio (CVR) was used as a marker of the interplay between 24‐hour SBP and HR variability. Renal function was estimated via 24‐hour urine creatinine clearance (CrCl), estimated glomerular filtration rate (eGFR), albumin‐to‐creatinine ratio (ACR), and 24‐hour urine α1‐microglobulin. After adjustment for age, sex, and smoking, CVSBP was found to be weakly correlated to eGFR (r=−0.017, P=.1) and somewhat more strongly to CrCl, ACR, and α1‐microglobulin (r=−0.032, 0.072, and 0.065; P=.002, <.001 and <.001, respectively). CVHR was much better related to renal function, with stronger adjusted correlations to CrCl, eGFR, ACR, and α1‐microglobulin (r=0.185, 0.134, −0.306, −0.247; all P<.001, respectively). CVR also showed equally good adjusted correlations (r=−0.175, −0.125, 0.336, 0.262; all P<.001, respectively). Most adjusted correlations for CVHR and CVR were even better in smokers (r=0.213, 0.158, −0.332, −0.272 and −0.183, −0.118, 0.351, 0.275, respectively; all P<.001). CVHR and CVR emerge as better related to kidney function than CVSBP, especially in smokers. The correlation of CVHR and CVSBP to renal function is inverse to each other. ACR and α1‐microglobulin are better related to variability indices than CrCl and eGFR. However, causal relations cannot be proved.
New tools (DNA barcoding), old hypothesis: the case of the taxonomic identity of the Argentine hakes (Actinopterygii: Merluccius)
Authors: Deli Antoni M. Y. , González‐Castro M. , Díaz de Astarloa J. M.
Published: August 2015

The present study evaluated the possible occurrence of cryptic species among Merluccidae from Argentina by examining sequences of cytochrome c oxidase subunit I (coI) mtDNA. This approach can discriminate Merluccius hubbsi and Merluccius australis; specimens with morphological diagnostic characters of Merluccius patagonicus formed a cohesive cluster with M. hubbsi specimens. BIN analysis confirmed the effectiveness of barcoding within a global context.
Application of X‐ray microcomputed tomography in the characterization of irradiated nuclear fuel and material specimens
Authors: SILVA C.M. , SNEAD L.L. , HUNN J.D. , SPECHT E.D. , TERRANI K.A. , KATOH Y.
Published: August 2015

X‐ray microcomputed tomography (μCT) was applied in characterizing the internal structures of a number of irradiated materials, including carbon‐carbon fibre composites, nuclear‐grade graphite and tristructural isotropic‐coated fuel particles. Local cracks in carbon‐carbon fibre composites associated with their synthesis process were observed with μCT without any destructive sample preparation. Pore analysis of graphite samples was performed quantitatively, and qualitative analysis of pore distribution was accomplished. It was also shown that high‐resolution μCT can be used to probe internal layer defects of tristructural isotropic‐coated fuel particles to elucidate the resulting high release of radioisotopes. Layer defects of sizes ranging from 1 to 5 μm and up could be isolated by tomography. As an added advantage, μCT could also be used to identify regions with high densities of radioisotopes to determine the proper plane and orientation of particle mounting for further analytical characterization, such as materialographic sectioning followed by optical and electron microscopy. In fully ceramic matrix fuel forms, despite the highly absorbing matrix, characterization of tristructural isotropic‐coated particles embedded in a silicon carbide matrix was accomplished using μCT and related advanced image analysis techniques.
Are GLP‐1 receptor agonists useful against traumatic brain injury?
Authors: Combs Colin K.
Published: August 2015

image

This Editorial highlights a study by Li et al. (2015) in the current issue of J. Neurochem. The image depicts the hypothesized neuroprotective pathway that is proposed by the authors. Using a combination of SH‐SY5Y and primary rat neuron cultures the GLP‐1R agonist, Liraglutide, was shown to increase SH‐SY5Y proliferation and CREB phosphorylation correlating with reduced toxicity, preservation of Bcl2 protein levels, and decreased caspase 3 activity following glutamate or H2O2 stimulations. These in vitro observations correlated with a Liraglutide‐dependent improvement in memory performance in mice subjected to a mild TBI. Bcl2, B‐cell lymphoma 2; CREB, cAMP‐response element binding protein; GLP‐1R, glucagon‐like peptide 1 receptor; TBI, traumatic brain injury; PKA, protein kinase A.
Impact of Spices and Wine‐Based Marinades on Tenderness, Fragmentation of Myofibrillar Proteins and Color Stability in Bovine Biceps Femoris Muscle
Authors: Istrati Daniela , Simion Ciuciu Ana‐Maria , Vizireanu Camelia , Ionescu Aurelia , Carballo Javier
Published: August 2015

Fresh beef slices were marinated by immersion in marinades based on dry red wine, lime‐tree honey, salt, spices and seasoning plants such as thyme (Thymus vulgaris), marjoram (Majorana hortensis), garlic (Allium sativum) and horseradish (Armoracia rusticana). Once marinated, meat pieces were vacuum packed and stored at 4C for 12 days. Experimental data indicated that marination of bovine Biceps femoris muscle in wine‐based marinades with spices and seasoning plants addition significantly decreased (P < 0.05) cooking losses. A significant increase in tenderness (P < 0.05) was observed in the samples marinated compared with the control. The effect of marination on biceps femoris muscle was not significant (P > 0.05) on L*, a* and b* but significant on Mb (myoglobin), MMb (metmyoglobin) and MbO2 (oxymyoglobin) percentages. Electrophoretic pattern of muscle proteins showed reduction of molecular weight and relative density (%) of some protein fractions for marinated samples compared with the control.

Practical Applications

Meat quality can be defined as a combination of sensory characteristics and technological aspects, such as color, water‐holding capacity, cooking losses and texture. Marinades based on dry red wine, lime‐tree honey, salt, spices and seasoning plants might be used as a marinating agent for improving the tenderness of tough meat and decreasing cooking losses with no effect on meat color. It can be easily applied at household and industrial levels as an easy technique to improve meat tenderness. Improvement in tenderness will be of great value to both consumers and meat processors.
Price Effects of the Minimum Wage: A Survey Data Analysis for theGerman Construction Sector
Authors: Werner Thomas , Sell Friedrich L.
Published: August 2015

Utilizing the link between employment and price changes as a result of minimum wages, we use firm‐level data to evaluate the effect of minimum wage introduction in theGerman construction sector. In EastGermany we find significant positive price effects that exclude the possibility of rising employment. Rather, the results indicate the existence of a competitive sector‐specific labour market, and thus declining employment. In contrast, we cannot find any significant price reaction forWestGermany. This suggests that the implemented minimum wage inWestGermany is too low in comparison to the predominantly paid wages and is hence not binding.
ArsP: a methylarsenite efflux permease
Authors: Chen Jian , Madegowda Mahendra , Bhattacharjee Hiranmoy , Rosen Barry P.
Published: August 2015

Trivalent organoarsenic compounds are far more toxic than either pentavalent organoarsenicals or inorganic arsenite. Many microbes methylate inorganic arsenite (As(III)) to more toxic and carcinogenic methylarsenite (MAs(III)). Additionally, monosodium methylarsenate (MSMA or MAs(V)) has been used widely as an herbicide and is reduced by microbial communities to MAs(III). Roxarsone (3‐nitro‐4‐hydroxybenzenearsonic acid) is a pentavalent aromatic arsenical that is used as antimicrobial growth promoter for poultry and swine, and its active form is the trivalent species Rox(III). A bacterial permease, ArsP, from Campylobacter jejuni, was recently shown to confer resistance to roxarsone. In this study, C. jejuni arsP was expressed in Escherichia coli and shown to confer resistance to MAs(III) and Rox(III) but not to inorganic As(III) or pentavalent organoarsenicals. Cells of E. coli expressing arsP did not accumulate trivalent organoarsenicals. Everted membrane vesicles from those cells accumulated MAs(III) > Rox(III) with energy supplied by NADH oxidation, reflecting efflux from cells. The vesicles did not transport As(III), MAs(V) or pentavalent roxarsone. Mutation or modification of the two conserved cysteine residues resulted in loss of transport activity, suggesting that they play a role in ArsP function. Thus, ArsP is the first identified efflux system specific for trivalent organoarsenicals.
PspF‐binding domain PspA1–144 and the PspA·F complex: New insights into the coiled–coil‐dependent regulation of AAA+ proteins
Authors: Osadnik Hendrik , Schöpfel Michael , Heidrich Eyleen , Mehner Denise , Lilie Hauke , Parthier Christoph , Risselada H. Jelger , Grubmüller Helmut , Stubbs Milton T. , Brüser Thomas
Published: August 2015

Phage shock protein A (PspA) belongs to the highy conserved PspA/IM30 family and is a key component of the stress inducible Psp system in Escherichia coli. One of its central roles is the regulatory interaction with the transcriptional activator of this system, the σ54 enhancer‐binding protein PspF, a member of the AAA+ protein family. The PspA/F regulatory system has been intensively studied and serves as a paradigm for AAA+ enzyme regulation by trans‐acting factors. However, the molecular mechanism of how exactly PspA controls the activity of PspF and hence σ54‐dependent expression of the psp genes is still unclear. To approach this question, we identified the minimal PspF‐interacting domain of PspA, solved its structure, determined its affinity to PspF and the dissociation kinetics, identified residues that are potentially important for PspF regulation and analyzed effects of their mutation on PspF in vivo and in vitro. Our data indicate that several characteristics of AAA+ regulation in the PspA·F complex resemble those of the AAA+ unfoldase ClpB, with both proteins being regulated by a structurally highly conserved coiled‐coil domain. The convergent evolution of both regulatory domains points to a general mechanism to control AAA+ activity for divergent physiologic tasks via coiled‐coil domains.
Coevolution can explain defensive secondary metabolite diversity in plants
Authors: Speed Michael P. , Fenton Andy , Jones Meriel G. , Ruxton Graeme D. , Brockhurst Michael A.
Published: August 2015

Many plant species produce defensive compounds that are often highly diverse within and between populations. The genetic and cellular mechanisms by which metabolite diversity is produced are increasingly understood, but the evolutionary explanations for persistent diversification in plant secondary metabolites have received less attention. Here we consider the role of plant–herbivore coevolution in the maintenance and characteristics of diversity in plant secondary metabolites.

We present a simple model in which plants can evolve to invest in a range of defensive toxins, and herbivores can evolve resistance to these toxins. We allow either single‐species evolution or reciprocal coevolution.

Our model shows that coevolution maintains toxin diversity within populations. Furthermore, there is a fundamental coevolutionary asymmetry between plants and their herbivores, because herbivores must resist all plant toxins, whereas plants need to challenge and nullify only one resistance trait. As a consequence, average plant fitness increases and insect fitness decreases as number of toxins increases. When costs apply, the model showed both arms race escalation and strong coevolutionary fluctuation in toxin concentrations across time.

We discuss the results in the context of other evolutionary explanations for secondary metabolite diversification.
A chemical genetic strategy identify the PHOSTIN, a synthetic molecule that triggers phosphate starvation responses in Arabidopsis thaliana
Authors: Bonnot Clémence , Pinson Benoît , Clément Mathilde , Bernillon Stéphane , Chiarenza Serge , Kanno Satomi , Kobayashi Natsuko , Delannoy Etienne , Nakanishi Tomoko M. , Nussaume Laurent , Desnos Thierry
Published: August 2015

Plants display numerous strategies to cope with phosphate (Pi)‐deficiency. Despite multiple genetic studies, the molecular mechanisms of low‐Pi‐signalling remain unknown. To validate the interest of chemical genetics to investigate this pathway we discovered and analysed the effects of PHOSTIN (PSN), a drug mimicking Pi‐starvation in Arabidopsis.

We assessed the effects of PSN and structural analogues on the induction of Pi‐deficiency responses in mutants and wild‐type and followed their accumulation in plants organs by high pressure liquid chromotography (HPLC) or mass‐spectrophotometry.

We show that PSN is cleaved in the growth medium, releasing its active motif (PSN11), which accumulates in plants roots. Despite the overaccumulation of Pi in the roots of treated plants, PSN11 elicits both local and systemic Pi‐starvation effects. Nevertheless, albeit that the transcriptional activation of low‐Pi genes by PSN11 is lost in the phr1;phl1 double mutant, neither PHO1 nor PHO2 are required for PSN11 effects.

The range of local and systemic responses to Pi‐starvation elicited, and their dependence on the PHR1/PHL1 function suggests that PSN11 affects an important and early step of Pi‐starvation signalling. Its independence from PHO1 and PHO2 suggest the existence of unknown pathway(s), showing the usefulness of PSN and chemical genetics to bring new elements to this field.
Middle finger length‐based tracheal intubation depth improves the rate of appropriate tube placement in children
Authors: Zhou Qing‐he , Xiao Wang‐pin , Zhou Hong‐mei
Published: August 2015

Background

It is challenging for anesthetists to determine the optimal tracheal intubation depth in children. We hypothesize that a measure three times the length of the middle finger can be used for predicting tracheal tube depth in children.

Methods

Eighty‐six children (4–14 years of age) were included in this study. After the children were anesthetized, a fiberoptic bronchoscope (FOB) was inserted into the trachea, the lengths from the upper incisor teeth to carina and vocal cords were measured, and a suitably sized cuffed tracheal tube was inserted into the trachea. Age‐based and middle finger length‐based formulas were used to determine the tracheal intubation depth.

Results

All 86 children enrolled were included in this study. Compared with the age‐based intubation, the rate of appropriate tube placement was higher for middle finger length‐based intubation (88.37% vs 66.28%, P = 0.001). The proximal intubation rate was lower in middle finger length‐based intubation (4.65% vs 32.56%, P < 0.001). There was only weak evidence for a difference in the distal intubation rate between the two methods (6.97% vs 1.16%, P = 0.054). The correlation coefficient between middle finger length and optimal tracheal tube depth was larger than that between age and optimal tracheal tube depth (0.883 vs 0.845).

Conclusions

Our data indicate that the appropriate tube placement rate can be improved by using three times the middle finger length as the tracheal intubation depth in children.
When flanker meets the n‐back: What EEG and pupil dilation data reveal about the interplay between the two central‐executive working memory functions inhibition and updating
Authors: Scharinger Christian , Soutschek Alexander , Schubert Torsten , Gerjets Peter
Published: August 2015

We investigated the interplay between inhibition and updating, two executive working memory (WM) functions. We applied a novel task paradigm consisting of flanker stimuli presented within an n‐back task and studied the interaction between inhibitory demands and load on WM updating using behavioral measures, EEG, and pupil dilation. In contrast to studies that examine the interaction between inhibitory demands and load on WM storage components, the current task paradigm allowed testing the interaction between the executive WM components updating and inhibition. We found a reduced flanker interference effect for the highest (2‐back) updating load condition compared to lower updating load conditions on most measures. We interpret these findings as indicating that inhibitory control and WM updating are closely intertwined executive functions. Increased load on updating seemed to result in an overall more activated attentional network thus enhancing inhibitory control, such that task performance is less susceptible to distracting information.
Effects of testing on subsequent re‐encoding and long‐term forgetting of action‐relevant materials: On the influence of recall type
Authors: Kubik Veit , Nilsson Lars‐Göran , Olofsson Jonas K. , Jönsson Fredrik U.
Published: August 2015

Testing one's memory of previously studied information reduces the rate of forgetting, compared to restudy. However, little is known about how thisdirect testing effectapplies to action phrases (e.g., “wash the car”) – a learning material relevant to everyday memory. As action phrases consist of two different components, a verb (e.g., “wash”) and a noun (e.g., “car”), testing can either be implemented as noun‐cued recall of verbs or verb‐cued recall of nouns, which may differently affect later memory performance. In the present study, we investigated the effect of testing for these two recall types, using verbally encoded action phrases as learning materials. Results showed that repeated study–test practice, compared to repeated study–restudy practice, decreased the forgetting rate across 1 week to a similar degree for both noun‐cued and verb‐cued recall types. However, noun‐cued recall of verbs initiated more new subsequent learning during the first restudy, compared to verb‐cued recall of nouns. The study provides evidence that testing has benefits on both subsequent restudy and long‐term retention of action‐relevant materials, but that these benefits are differently expressed with testing via noun‐cued versus verb‐cued recall.
FE, a phloem‐specific Myb‐related protein, promotes flowering through transcriptional activation of FLOWERING LOCUS T and FLOWERING LOCUS T INTERACTING PROTEIN 1
Authors: Abe Mitsutomo , Kaya Hidetaka , Watanabe‐Taneda Ayako , Shibuta Mio , Yamaguchi Ayako , Sakamoto Tomoaki , Kurata Tetsuya , Ausín Israel , Araki Takashi , Alonso‐Blanco Carlos
Published: August 2015

In many flowering plants, the transition to flowering is primarily affected by seasonal changes in day length (photoperiod). An inductive photoperiod promotes flowering via synthesis of a floral stimulus, called florigen. In Arabidopsis thaliana, the FLOWERING LOCUS T (FT) protein is an essential component of florigen, which is synthesized in leaf phloem companion cells and is transported through phloem tissue to the shoot apical meristem where floral morphogenesis is initiated. However, the molecular mechanism involved in the long‐distance transport of FT protein remains elusive. In this study, we characterized the classic Arabidopsis mutant fe, which is involved in the photoperiodic induction of flowering, and showed that FE encodes a phloem‐specific Myb‐related protein that was previously reported as ALTERED PHLOEM DEVELOPMENT. Phenotypic analyses of the fe mutant showed that FT expression is reduced in leaf phloem companion cells. In addition, the transport of FT protein from leaves to the shoot apex is impaired in the fe mutant. Expression analyses further demonstrated that FE is also required for transcriptional activation of FLOWERING LOCUS T INTERACTING PROTEIN 1 (FTIP1), an essential regulator for selective trafficking of the FT protein from companion cells to sieve elements. These findings indicate that FE plays a dual role in the photoperiodic induction of flowering: as a transcriptional activator of FT on the one hand, and its transport machinery component, FTIP1, on the other hand. Thus, FE is likely to play a role in regulating FT by coordinating FT synthesis and FT transport in phloem companion cells.
Loss of function mutations in the rice chromomethylase OsCMT3a cause a burst of transposition
Authors: Cheng Chaoyang , Tarutani Yoshiaki , Miyao Akio , Ito Tasuku , Yamazaki Muneo , Sakai Hiroaki , Fukai Eigo , Hirochika Hirohiko
Published: August 2015

Methylation patterns of plants are unique as, in addition to the methylation at CG dinucleotides that occurs in mammals, methylation also occurs at non‐CG sites. Genes are methylated at CG sites, but transposable elements (TEs) are methylated at both CG and non‐CG sites. The role of non‐CG methylation in transcriptional silencing of TEs is being extensively studied at this time, but only very rare transpositions have been reported when non‐CG methylation machineries have been compromised. To understand the role of non‐CG methylation in TE suppression and in plant development, we characterized rice mutants with changes in the chromomethylase gene, OsCMT3a. oscmt3a mutants exhibited a dramatic decrease in CHG methylation, changes in the expression of some genes and TEs, and pleiotropic developmental abnormalities. Genome resequencing identified eight TE families mobilized in oscmt3a during normal propagation. These TEs included tissue culture‐activated copia retrotransposons Tos17 and Tos19 (Lullaby), a pericentromeric clustered high‐copy‐number non‐autonomous gypsy retrotransposon Dasheng, two copia retrotransposons Osr4 and Osr13, a hAT‐tip100 transposon DaiZ, a MITE transposon mPing, and a LINE element LINE1‐6_OS. We confirmed the transposition of these TEs by polymerase chain reaction (PCR) and/or Southern blot analysis, and showed that transposition was dependent on the oscmt3a mutation. These results demonstrated that OsCMT3a‐mediated non‐CG DNA methylation plays a critical role in development and in the suppression of a wide spectrum of TEs. These in planta mobile TEs are important for studying the interaction between TEs and the host genome, and for rice functional genomics.