bluuebunny/crossref_metadata_2025 huggingface dataset:
Cryptic genetic variation uncovers evolution of environmentally sensitive parameters in Caenorhabditis vulval development
Authors: Grimbert Stéphanie , Braendle Christian
Published: August 2014

Understanding the robustness of developmental systems requires insights into the sensitivity of underlying molecular and cellular parameters to perturbations, and how such sensitivity evolves. We address these issues using vulval cell fate determination—a reproducible and robust patterning process regulated by a cross‐talk of EGF‐Ras‐MAPK and Delta‐Notch pathways. Although the final vulval cell fate pattern is identical in all Caenorhabditis species, the patterning process underlies extensive cryptic genetic variation between and within species. Here, we tested whether this cryptic genetic variation translates into variation in developmental sensitivity to environmental perturbations. We disrupted vulval patterning using thermal perturbations to quantify and compare environmental sensitivity of different system parameters between distinct genotypes of C. elegans and C. briggsae. Thermal perturbations globally debuffered vulval development, triggering diverse pattering variants, whose frequency and spectra were strongly species‐ and genotype‐dependent. This condition‐dependent variation indicates that environmental sensitivity of different system properties, such as vulval competence or vulval induction, is subject to evolutionary change. High temperature induced a genotype‐specific decrease of secondary fate induction and corresponding Notch pathway activity in the C. elegans N2 strain; in contrast, hypoinduction of the primary cell fate was never observed. Vulval precursor cells therefore differ in temperature sensitivity and such cell‐specific sensitivity shows evolutionary variation. We further compared spectra of temperature‐induced vulval variants to the ones induced by mutation accumulation in the same genotypes. In response to either perturbation, we observed similar genotype‐dependence of variant production, allowing identification of distinct system features most sensitive to both mutation and environment. Taken together, we show how sensitivity of system parameters regulating Caenorhabditis vulval development depends on subtle interactions between perturbations and genetic background. Our results imply that cryptic genetic variation may reflect evolutionary variation in developmental robustness, therefore potentially contributing to the maintenance of phenotypic precision when facing perturbations.
Variation in timing of ossification affects inferred heterochrony of cranial bones in Lissamphibia
Authors: Sheil Christopher A. , Jorgensen Michael , Tulenko Frank , Harrington Sean
Published: August 2014

The evolutionary origin of Lissamphibia likely involved heterochrony, as demonstrated by the biphasic lifestyles of most extant orders, differences between Anura (with tadpole‐to‐froglet metamorphosis) and Urodela (which lack strongly defined metamorphosis), and the appearance of direct development among separate lineages of frogs. Patterns in the timing of appearance of skeletal elements (i.e., ossification sequence data) represent a possible source of information for understanding the origin of Lissamphibia, and with the advent of analytical methods to directly optimize these data onto known phylogenies, there has been a renewed interest in assessing the role of changes in these developmental events. However, little attention has been given to the potential impact of variation in ossification sequence data—this is particularly surprising given that different criteria for collecting these data have been employed. Herein, new and previously published ossification data are compiled and all pairs of data for same‐species comparisons are selected. Analyses are run to assess the impact of using data that were collected by different methodologies: (1) wild‐ versus lab‐raised animals; (2) different criteria for recognizing timing of ossification; and (3) randomly selecting ossification sequences for species from which multiple studies have been published, but for which the data were collected by different criteria. Parsimov‐based genetic inference is utilized to map ossification sequence data onto an existing phylogeny to reconstruct ancestral sequences of ossification and infer instances of heterochrony. All analyses succeeded in optimizing sequence data on internal nodes and instances of heterochrony were identified. However, among all analyses little congruence was found in reconstructed ancestral sequences or among inferred instances of heterochrony. These results indicate a high degree of variation in timing of ossification, and suggest a cautionary note about use of these data, particularly given that in most instances issues associated with the original sources of data (e.g., wild‐ vs. lab‐raised animals; or criteria for identification of earliest ossification) are not addressed. Potential sources of variation in the original data are discussed and may explain the incongruence observed here.
Highly sensitive protein detection by combination of atomic force microscopy fishing with charge generation and mass spectrometry analysis
Authors: Ivanov Yuri D. , Pleshakova Tatyana , Malsagova Krystina , Kozlov Andrey , Kaysheva Anna , Kopylov Arthur , Izotov Alexander , Andreeva Elena , Kanashenko Sergey , Usanov Sergey , Archakov Alexander
Published: August 2014

An approach combining atomic force microscopy (AFM) fishing and mass spectrometry (MS) analysis to detect proteins at ultra‐low concentrations is proposed. Fishing out protein molecules onto a highly oriented pyrolytic graphite surface coated with polytetrafluoroethylene film was carried out with and without application of an external electric field. After that they were visualized by AFM and identified by MS. It was found that injection of solution leads to charge generation in the solution, and an electric potential within the measuring cell is induced. It was demonstrated that without an external electric field in the rapid injection input of diluted protein solution the fishing is efficient, as opposed to slow fluid input. The high sensitivity of this method was demonstrated by detection of human serum albumin and human cytochrome b5 in 10−17–10−18 m water solutions. It was shown that an external negative voltage applied to highly oriented pyrolytic graphite hinders the protein fishing. The efficiency of fishing with an external positive voltage was similar to that obtained without applying any voltage.
Mineral soil carbon pool responses to forest clearing in Northeastern hardwood forests
Authors: Petrenko Chelsea L. , Friedland Andrew J.
Published: August 2014

Harvesting forests introduces substantial changes to the ecosystem, including physical and chemical alterations to the soil. In the Northeastern United States, soils account for at least 50% of total ecosystem C storage, with mineral soils comprising the majority of that storage. However, mineral soils are sometimes omitted from whole‐system C accounting models due to variability, lack of data, and sample collection challenges. This study aimed to provide a better understanding of how forest harvest affects mineral soil C pools over the century following disturbance. We hypothesized that mineral soil C pools would be lower in forests that had been harvested in the last one hundred years vs. forests that were >100 years old. We collected mineral soil cores (to 60 cm depth) from 20 forest stands across the Northeastern United States, representing seven geographic areas and a range of times since last harvest. We compared recently harvested forests to >100‐year‐old forests and used an information theoretic approach to model C pool dynamics over time after disturbance. We found no significant differences between soil C pools in >100‐year‐old and harvested forests. However, we found a significant negative relationship between time since forest harvest and the size of mineral soil C pools, which suggested a gradual decline in C pools across the region after harvesting. We found a positive trend between C : N ratio and % SOM in harvested forests, but in >100‐year‐old forests a weak negative trend was found. Our study suggests that forest harvest does cause biogeochemical changes in mineral soil, but that a small change in a C pool may be difficult to detect when comparing large, variable C pools. Our results are consistent with previous studies that found that soil C pools have a gradual and slow response to disturbance, which may last for several decades following harvest.
Knee flexion contracture in haemophilia: treatment with circular external fixator
Authors: Balci H. I. , Kocaoglu M. , Eralp L. , Bilen F. E.
Published: August 2014

Haemophilia, a bleeding disorder, causes recurrent intra‐articular bleeding of the joints result‐ing in chronic haemophilic arthropathy with fixed knee flexion deformity. Mid‐long‐term results (between 2002 and 2006) of deformity correction in haemophilic patients with Ilizarov type circular external fixators were retrospectively evaluated. There were six patients (five haemophilia A and one haemophilia B). The mean age was 14.7 years (range, 8–22 years) at the time of initial surgery. The mean knee flexion contracture was 45 degrees (range, 30–75 degrees). The mean arc of motion was 58.3 degrees (range, 40–100) before the surgery. The mean duration of follow‐up was 8 years (range, 5.5–10 years). The mean duration of external fixation was 4.4 months (range, 2.5–10.5 months). Full extension of the knee joint was obtained in all patients in the early postoperative period. No bleeding, neurological or vascular complications were encountered. The mean amount of recurrence in knee flexion contracture was 10 degrees (range, 0–15 degrees). The amount of the correction was significant (P = 0.0012) and the mean arc of motion was 51.6 degrees (range, 25–90 degrees) that show a decrease of 6.7 degrees (P = 0.04) at the end of follow‐up. The circular external fixator is an important, safe and less invasive alternative surgical treatment modality with low recurrence rate. Using the external hinges and distraction during the correction has a protective effect on the joint. It requires a team‐work consisting of a haematologist, an orthopaedic surgeon and a physical therapist.
Community periodontal treatment needs in South Korea
Authors: Lee M‐Y , Chang S‐J , Kim C‐B , Chung W‐G , Choi E‐M , Kim N‐H
Published: August 2014

Objectives

This study aimed to assess the relationship between socio‐economic factors and community periodontal treatment needs in Korea.

Methods

Data were obtained from the year 2009 Korean National Health and Nutrition Examination Survey. Our analysis included 7510 survey participants over the age of 19 years. To assess the relationship between socio‐economic factors and the need for periodontal scaling, we performed multivariate logistic regression analyses for data with a complex sampling structure. PASW statistics 19.0 (SPSS Inc., Chicago, IL, USA) was used to perform the statistical analyses, and the results were expressed as odds ratios (OR) with corresponding 95% confidence intervals (CIs).

Results

A very high percentage of Korean adults required periodontal scaling (71.5%). After adjusting for sex, age, and socio‐economic factors, the need for periodontal scaling was associated with low levels of education (OR: 1.41, 95% CI: 1.03–1.93), low incomes (OR: 1.27, 95% CI: 1.01–1.60), employment as a service and sales worker (OR: 1.39, 95% CI: 1.10–1.77), and employment as a manual worker (OR: 1.31, 95% CI: 1.02–1.69).

Conclusions

In South Korea, the need for periodontal scaling was associated with socio‐economic factors, such as low levels of education, low incomes, employment as a service and sales worker and employment as a manual worker. Consequently, clinical and community dental hygienists should consider adults with these risk factors as belonging to high‐priority subgroups to whom they should respond first.
Cooperation in the repeated prisoner's dilemma game with local interaction and local communication
Authors: Cho Myeonghwan
Published: August 2014

This paper considers a repeated prisoner's dilemma game in a network in which each agent interacts with his neighbors and cannot observe the actions of other agents who are not directly connected to him. If there is global information processing through public randomization and global communication, it is not difficult to construct a sequential equilibrium which supports cooperation and satisfies a property, called stability, which requires that cooperation resumes after any history. In this paper, we allow agents to locally communicate with their neighbors and show that it is possible to construct such an equilibrium without global information processing. Here, the role of local communication is to resolve the discrepancy of agents’ expectations about their neighbor's future actions.
Addition of intrarectal local analgesia to periprostatic nerve block improves pain control for transrectal ultrasonography‐guided prostate biopsy: A systematic review and meta‐analysis
Authors: Wang Jue , Wang Lei , Du Yiqing , He Dalin , Chen Xingfa , Li Lei , Nan Xunyi , Fan Jinhai
Published: August 2014

Objectives

To evaluate the efficacy and safety of combined intrarectal local analgesia and periprostatic nerve block versus periprostatic nerve block alone for pain control during transrectal ultrasound‐guided prostate biopsy.

Methods

We comprehensively searched PubMed, Embase and the Cochrane Library trials. Studies comparing the two techniques were identified and pooled for cumulative analysis. The outcome measurements included visual pain scales of three consecutive procedures of transrectal ultrasound‐guided prostate biopsy, as well as short‐term postoperative complication rates.

Results

There were 18 studies that were finally eligible for the quantitative analysis involving 2076 participants. Combined modalities significantly reduced the pain associated with probe manipulation (weighted mean difference −2.06, 95% confidence interval −2.77 to −1.35, P < 0.001), anesthesia infiltration (weighted mean difference −1.45, 95% confidence interval −2.20 to −0.70, P < 0.001) and needle biopsy (weighted mean difference −0.55, 95% confidence interval −0.76 to −0.34, P < 0.001). Subgroup analyses assessing different local analgesics showed that local anesthetics are generally more effective than myorelaxant and non‐steroidal anti‐inflammatory drugs. Lidocaine‐prilocaine cream proved the most effective in pain control regardless of the origin of pain. No significant difference of short‐term postoperative complications (fever, dysuria, acute urinary retention, hematuria, hematospermia and rectal bleeding) was found between the two techniques. The only side‐effect associated with local analgesics was headache reported in studies using glyceryl trinitrate ointment.

Conclusions

Combined modalities show better analgesic efficacy than periprostatic nerve block alone for transrectal ultrasound‐guided prostate biopsy without increased morbidities. Among the various local analgesics, lidocaine‐prilocaine cream seems to offer the best overall efficacy.
Understanding the relationships between interest in online math games and academic performance
Authors: Zhang M.
Published: August 2014

Although the Internet is widely used by students in both formal and informal environments, little is known about how and where youth spend their time online. Using Internet search and Web analytics data, this study discovered a large‐scale phenomenon associated with the poor performance of elementary school students in the USA that has been overlooked by educational researchers. This study found that approximately 10 million Internet users in the USA, many of whom are presumably youth, spend about 89 million hours in a year on a popular math game site that targets children. The number of game site users is equivalent to half of the K‐5 Internet population in the USA. However, there is little evidence that the math games on the website meet the criteria for effective instruction as described in the literature. This study found a significant negative correlation between search volumes for the game site in the 50 states in the USA and 4th grade students' performance in mathematics and reading. Moreover, Internet users in the states with greater numbers of low‐income families and fewer college graduates were more likely to search for the game site. The implications of these findings are discussed.
Characterization of squamous cell carcinomas of the head and neck using methods of spatial statistics
Authors: MATTFELDT T. , FLEISCHER F.
Published: August 2014

In the present study, 53 cases of squamous cell carcinomas of the head and neck were characterized by a quantitative histological texture analysis based on principles of spatial statistics. A planar tessellation of the epithelial tumour component was generated by a skeletonization algorithm. The size distribution of the virtual cells of this planar tessellation, and the size distribution of the profiles of the tumour cell nuclei were estimated in terms of area and boundary length. The intensity, the reduced second moment function (K‐function) and the pair correlation function of the point process of the centroids of the profiles of the tumour cell nuclei were also estimated. For both purposes, it is necessary to correct for edge effects, which we consider in this paper in some detail. Specifically, the point patterns of the tumour cell nuclei were considered as realizations of a point process, where the points exist only in the epithelial tumour component (the permitted phase) and not in the stroma (the forbidden phase). The methods allow to characterize each individual tumour by a series of summary statistics. The total set of cases was then partitioned into two groups: 19 cases without lymph node metastases (pN0), and 34 nodal positive cases (pN1 or pN2). Statistical analysis showed no significant differences between the intensities, the mean K‐functions and the mean pair correlation functions of the tumour cell nucleus profiles of the two groups. However, there were some significant differences between the sizes of the virtual cells and of the nucleus profiles of the nodal negative cases as compared to the nodal positive cases. In a logistic regression analysis, one of the quantitative nuclear size variables (mean nuclear area) was found to be a significant predictor of lymph node metastasis, in addition to tumour stage. The study shows the potential of methods of spatial statistics for objective quantitative grading of squamous cell carcinomas of the head and neck, and provides an example for modelling histological point patterns as realizations of planar point processes occupying a reference phase which is only a partial component of the total tissue.
Heterogeneity of shale documented by micro‐FTIR and image analysis
Authors: CHEN YANYAN , MASTALERZ MARIA , SCHIMMELMANN ARNDT
Published: August 2014

In this study, four New Albany Shale Devonian and Mississippian samples, with vitrinite reflectance [Ro] values ranging from 0.55% to 1.41%, were analyzed by micro‐FTIR mapping of chemical and mineralogical properties. One additional postmature shale sample from the Haynesville Shale (Kimmeridgian, Ro = 3.0%) was included to test the limitation of the method for more mature substrates. Relative abundances of organic matter and mineral groups (carbonates, quartz and clays) were mapped across selected microscale regions based on characteristic infrared peaks and demonstrated to be consistent with corresponding bulk compositional percentages. Mapped distributions of organic matter provide information on the organic matter abundance and the connectivity of organic matter within the overall shale matrix. The pervasive distribution of organic matter mapped in the New Albany Shale sample MM4 is in agreement with this shale's high total organic carbon abundance relative to other samples. Mapped interconnectivity of organic matter domains in New Albany Shale samples is excellent in two early mature shale samples having Ro values from 0.55% to 0.65%, then dramatically decreases in a late mature sample having an intermediate Ro of 1.15% and finally increases again in the postmature sample, which has a Ro of 1.41%. Swanson permeabilities, derived from independent mercury intrusion capillary pressure porosimetry measurements, follow the same trend among the four New Albany Shale samples, suggesting that micro‐FTIR, in combination with complementary porosimetric techniques, strengthens our understanding of porosity networks. In addition, image processing and analysis software (e.g. ImageJ) have the capability to quantify organic matter and total organic carbon – valuable parameters for highly mature rocks, because they cannot be analyzed by micro‐FTIR owing to the weakness of the aliphatic carbon–hydrogen signal.
Non‐surgical periodontal therapy with systemic antibiotics in patients with untreated chronic periodontitis: a systematic review and meta‐analysis
Authors: Keestra J. A. J. , Grosjean I. , Coucke W. , Quirynen M. , Teughels W.
Published: August 2014

Objective

The purpose of this meta‐analysis is to evaluate the effectiveness of different systemic antibiotics in combination with scaling and root planing (SRP) when compared to SRP alone in patients with untreated chronic periodontitis.

Background

Although chronic periodontitis is mostly treated without adjunctive systemic antibiotics, some recent meta‐analyses have shown clinical benefit for some systemic antibiotics when used as an adjunct to SRP. However, there is a wide variety of systemic antibiotic regimens used today. It remains unclear if the selected type of systemic antibiotic influences the magnitude of clinical benefit.

Material and Methods

The MEDLINE‐PubMed database was searched from their earliest records through May 16, 2013. Several journals were hand searched and some authors were contacted for additional information. Outcome measures analysed were mean bleeding on probing change, mean clinical attachment level gain and mean probing pocket depth reduction. Extracted data were pooled using a random effect model. Weighted mean differences were calculated and heterogeneity was assessed.

Results

The search yielded 281 abstracts. Ultimately, 95 studies were selected, describing 43 studies meeting the eligibility criteria. Systemic antibiotics showed a significant (p < 0.05) additional pocket depth reduction for moderate (at 3 mo 0.27 mm ± 0.09, at 6 mo 0.23 mm ± 0.10 and at 12 mo 0.25 mm ± 0.27) and deep pockets (at 3 mo 0.62 mm ± 0.17, at 6 mo 0.58 mm ± 0.16 and at 12 mo 0.74 mm ± 0.30). Statistically, no specific type of antibiotic was superior over another. However, when analysing the clinical data for initially moderate pockets or deep pockets, some trends became apparent.

Conclusion

Systemic antibiotics combined with SRP offer additional clinical improvements compared to SRP alone. Although there were no statistically significant differences, there was a trend that for initially moderate and deep pockets, metronidazole or metronidazole combined with amoxicillin, resulted in clinical improvements that were more pronounced over doxycycline or azithromycin. Additionally, there was a trend that the magnitude of the clinical benefit became smaller over time (1 year).
Effect of Calamondin Fiber on Rheological, Antioxidative and Sensory Properties of Dough and Steamed Bread
Authors: Fu Jhong‐Tai , Shiau Sy‐Yu , Chang Rei‐Chu
Published: August 2014

Calamondin fiber (CF) was extracted and incorporated into dough and steamed bread. Results showed that the substitution of wheat flour by CF resulted in a stiffer and less extensible dough. Both Peleg–Normand and Wiechert models fitted well to the stress relaxation data of steamed bread. Hardness of steamed bread increased with the increase of CF substitution, but the cohesiveness, specific volume and elasticity decreased with the fiber substitution. As CF substitution was increased from 0 to 9%, total phenolic content and 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical‐scavenging capacity of the steamed bread were improved by about 23 and 34, 52 and 53, as well as 77 and 74%, respectively. In sensory evaluation, steamed breads with 0–6% CF had similar flavor, texture and overall scores. These results suggest that the addition of 3 or 6% CF can produce healthy and acceptable fiber‐enriched steamed bread with higher phytochemicals and antioxidant capacity.

Practical Applications

Consumption of dietary fiber offers health benefits including lower risk for many chronic diseases. The increased consumption of steamed bread enriched with calamondin fiber is proposed for health reasons. Calamondin is one of citrus fruits, and its pomace contains some phytochemicals, such as fiber, phenolics and flavonoids. The calamondin fiber was extracted and could be supplied as a potential source of dietary fiber. The study demonstrated that fiber‐enriched steamed bread with good sensory and nutritional quality could be produced by the partial substitution of wheat flour by calamondin fiber.
Effects of Maropitant Citrate or Acepromazine on the Incidence of Adverse Events Associated with Hydromorphone Premedication in Dogs
Authors: Claude A.K. , Dedeaux A. , Chiavaccini L. , Hinz S.
Published: August 2014

Background

Vomiting is a common complication associated with the use of hydromorphine for pre‐emptive analgesia in dogs. The ideal anti‐emetic protocol for prevention of this complication has not been established.

Hypothesis

Maropitant administered concurrently or before hydromorphone would reduce the incidence of vomiting, signs of nausea, ptyalism, and increased panting compared to administration of acepromazine or a 0.9% saline control.

Animals

Sixty mixed‐breed female dogs scheduled for ovariohysterectomy.

Methods

Randomized, blinded, placebo‐controlled experimental study. Dogs were assigned to 4 experimental groups with 15 dogs per group. All groups received 0.2 mg/kg of hydromorphone IM. Group “Control” received 0.1 mL/kg saline SC 30–45 minutes before hydromorphone, group “Marop1” received 1 mg/kg maropitant SC 30–45 minutes before hydromorphone, group “Ace” received 0.02 mg/kg IM acepromazine 30–45 minutes before hydromorphone, and group “Marop2” received 1 mg/kg SC maropitant concurrently with hydromorphone. A trained and blinded observer documented adverse events from the time hydromorphone was administered until the time dogs were induced for surgery.

Results

Marop1 had significantly less vomiting (0%) compared to Control (87%; P < .01) and Ace (53%; P < .01). Marop2 had significantly less vomiting (27%) compared to Control (P < .01). Marop1 had significantly greater incidence of ptyalism (73%) compared to Ace (P < .01; 20%). Ace showed significantly less panting (33%) compared to Marop2 (93%; P < .01).

Conclusions and Clinical Importance

In healthy dogs, maropitant citrate administered before hydromorphone significantly decreases the incidence of vomiting in dogs but does not improve signs of nausea, ptyalism, or increased panting.
Antitrust Law and Distributive Politics in the American States
Authors: Provost Colin
Published: August 2014

State enforcement by state attorneys general (AGs) has become a major component of American antitrust law. Much has been written about state antitrust enforcement, but existing accounts of AG incentives and behavior are incomplete. As elected officials in forty‐three states, AGs must represent their constituents and, therefore, will be drawn to cases that maximize the level of settlement reward—cases with large, wealthy defendants. I hypothesize and find that state AGs represent their constituents along ideological lines, but this relationship is conditioned by case characteristics that involve the potential settlement reward. Moreover, incentives to participate are likely to be higher when there are clear violations of the law, as in price‐fixing cases, rather than in merger cases, where no wrongdoing has necessarily been established. The study adds to our understanding of antitrust law but also has implications for how distributive politics shapes political responsiveness to the electorate.
The Meteoritical Bulletin, No. 100, 2014 June
Authors: Ruzicka Alex , Grossman Jeffrey N. , Garvie Laurence
Published: August 2014

Meteoritical Bulletin 100 contains 1943 meteorites including 8 falls (Boumdeid [2011], Huaxi, Košice, Silistra, Sołtmany, Sutter's Mill, Thika, Tissint), with 1575 ordinary chondrites, 139 carbonaceous chondrites, 96 HED achondrites, 25 ureilites, 18 primitive achondrites, 17 iron meteorites, 15 enstatite chondrites, 11 lunar meteorites, 10 mesosiderites, 10 ungrouped achondrites, 8 pallasites, 8 Martian meteorites, 6 Rumuruti chondrites, 3 enstatite achondrites, and 2 angrites, and with 937 from Antarctica, 592 from Africa, 230 from Asia, 95 from South America, 44 from North America, 36 from Oceania, 6 from Europe, and 1 from an unknown location. This will be the last Bulletin published in the current format. Information about approved meteorites can be obtained from the Meteoritical Bulletin Database (MBD) available online at http://www.lpi.usra.edu/meteor/
Early and late response of Nematostella vectensis transcriptome to heavy metals
Authors: Elran Ron , Raam Maayan , Kraus Roey , Brekhman Vera , Sher Noa , Plaschkes Inbar , Chalifa‐Caspi Vered , Lotan Tamar
Published: August 2014

Environmental contamination from heavy metals poses a global concern for the marine environment, as heavy metals are passed up the food chain and persist in the environment long after the pollution source is contained. Cnidarians play an important role in shaping marine ecosystems, but environmental pollution profoundly affects their vitality. Among the cnidarians, the sea anemone Nematostella vectensis is an advantageous model for addressing questions in molecular ecology and toxicology as it tolerates extreme environments and its genome has been published. Here, we employed a transcriptome‐wide RNA‐Seq approach to analyse N. vectensis molecular defence mechanisms against four heavy metals: Hg, Cu, Cd and Zn. Altogether, more than 4800 transcripts showed significant changes in gene expression. Hg had the greatest impact on up‐regulating transcripts, followed by Cu, Zn and Cd. We identified, for the first time in Cnidaria, co‐up‐regulation of immediate‐early transcription factors such as Egr1, AP1 and NF‐κB. Time‐course analysis of these genes revealed their early expression as rapidly as one hour after exposure to heavy metals, suggesting that they may complement or substitute for the roles of the metal‐mediating Mtf1 transcription factor. We further characterized the regulation of a large array of stress‐response gene families, including Hsp, ABC, CYP members and phytochelatin synthase, that may regulate synthesis of the metal‐binding phytochelatins instead of the metallothioneins that are absent from Cnidaria genome. This study provides mechanistic insight into heavy metal toxicity in N. vectensis and sheds light on ancestral stress adaptations.
Plasticity in ploidy underlies plant fitness compensation to herbivore damage
Authors: Scholes Daniel R. , Paige Ken N.
Published: August 2014

How plants mitigate damage by animal herbivores is a fundamental ecological and evolutionary question of plant–animal interactions. Some plants can increase their fitness when damaged in a phenomenon termed ‘overcompensation’. Despite overcompensation being observed in a variety of plant species, its mechanistic basis remains elusive. Recent research has shown that the Arabidopsis thaliana genotype Columbia‐4 employs endoreduplication, the replication of the genome without mitosis, following damage and that it overcompensates for seed yield. The related genotype Landsberg erecta, in contrast, does not increase its endoreduplication following damage and suffers reduced seed yield. While these results suggest that a plant's ability to plastically increase its ploidy during regrowth may promote its mitigation of damage, no studies have explicitly linked the endoreduplication genetic pathway to the regrowth and fitness of damaged plants. By comparing fitness and ploidy between undamaged and damaged plants of Columbia‐4, Landsberg erecta and their offspring, we provide evidence that endoreduplication is directly involved in compensatory performance. We then overexpressed an endoreduplication regulator and compared this mutant's endoreduplication and compensation with its background genotype Columbia‐0, an undercompensator. Enhancing Columbia‐0's ability to endoreduplicate during regrowth led to the complete mitigation of the otherwise detrimental effects of damage on its fitness. These results suggest that the ability of these plants to increase their ploidy via endoreduplication directly impacts their abilities to compensate for damage, providing a novel mechanism by which some plants can mitigate or even benefit from apical damage with potential across the wide range of plant taxa that endoreduplicate.
Rotigotine transdermal system: developing continuous dopaminergic delivery to treat Parkinson's disease and restless legs syndrome
Authors: Benitez Arturo , Edens Heather , Fishman Jesse , Moran Kimberly , Asgharnejad Mahnaz
Published: August 2014

Rotigotine is a nonergoline dopamine receptor agonist with structural similarity to dopamine. Rotigotine binds to the D1 through D5 dopamine receptors, having several times more affinity than dopamine does to the D2 and D3 receptors. Although rotigotine was demonstrated to restore locomotor activity in animal models of Parkinson's disease (PD), the rapid metabolism of rotigotine limited the development of an orally administered formulation. Rotigotine's high lipid solubility and extended duration of action when applied to the skin in experimental models of PD suggested that rotigotine was a candidate for transdermal application. The constant transdermal delivery of rotigotine over 24 h is hypothesized to approximate continuous agonist–receptor stimulation, which conceptually more closely mimics physiologic striatal dopamine receptor function. Randomized clinical studies have demonstrated rotigotine's efficacy, safety, and tolerability in patients with early‐ and advanced‐stage PD, including improvements in motor symptoms and off‐time. Although the etiology is unknown, restless legs syndrome (RLS) is thought to involve dopaminergic dysregulation. Randomized clinical studies also have demonstrated the efficacy of rotigotine in improving the symptoms of moderate‐to‐severe primary RLS. This review examines rotigotine's developmental history for transdermal administration leading to its approval for the treatment of early‐ and advanced‐stage PD and moderate‐to‐severe primary RLS.
Regulation of competence and gene expression in Streptococcus mutans by the RcrR transcriptional regulator
Authors: Seaton K. , Ahn S.‐J. , Burne R.A.
Published: August 2014

An intimate linkage between the regulation of biofilm formation, stress tolerance and genetic competence exists in the dental caries pathogen Streptococcus mutans. The rcrRPQ genes encode ABC exporters (RcrPQ) and a MarR‐family transcriptional repressor of the rcr operon (RcrR) that play a dominant role in the regulation of the development of genetic competence and connect competence with stress tolerance and (p)ppGpp production in S. mutans. Here we identify the target for efficient RcrR binding in the rcr promoter region using purified recombinant RcrR (rRcrR) protein in electrophoretic mobility shift assays and show that DNA fragments carrying mutations in the binding region were not bound as efficiently by rRcrR in vitro. Mutations in the RcrR binding site impacted expression from the rcrR promoter in vivo and elicited changes in transformation efficiency, competence gene expression, and growth inhibition by competence‐stimulating peptide; even when the changes in rcrRPQ transcription were minor. An additional mechanistic linkage of RcrR with competence and (p)ppGpp metabolism was identified by showing that the rRcrR protein could bind to the promoter regions of comX, comYA and relP, although the binding was not as efficient as to the rcrRPQ promoter under the conditions tested. Hence, tightly controlled autogenous regulation of the rcrRPQ operon by RcrR binding to specific target sites is essential for cellular homeostasis, and RcrR contributes to the integration of genetic competence, (p)ppGpp metabolism, and acid and oxidative stress tolerance in S. mutans through both direct and indirect mechanisms.
Ligand binding and homology modelling of insect odorant‐binding proteins
Authors: Venthur Herbert , Mutis Ana , Zhou Jing‐Jiang , Quiroz Andrés
Published: August 2014

This review describes the main characteristics of odorant‐binding proteins (OBPs) for homology modelling and presents a summary of structure prediction studies on insect OBPs, along with the steps involved and some limitations and improvements. The technique involves a computing approach to model protein structures and is based on a comparison between a target (unknown structure) and one or more templates (experimentally determined structures). As targets for structure prediction, OBPs are considered to play a functional role for recognition, desorption, scavenging, protection and transportation of hydrophobic molecules (odourants) across an aqueous environment (lymph) to olfactory receptor neurones (ORNs) located in sensilla, the main olfactory units of insect antennae. Lepidopteran pheromone‐binding proteins, a subgroup of OBPs, are characterized by remarkable structural features, in which high sequence identities (approximately 30%) among these OBPs and a large number of available templates can facilitate the prediction of precise homology models. Approximately 30 studies have been performed on insect OBPs using homology modelling as a tool to predict their structures. Although some of the studies have assessed ligand‐binding affinity using structural information and biochemical measurements, few have performed docking and molecular dynamic (MD) simulations as a virtual method to predict best ligands. Docking and MD simulations are discussed in the context of discovery of novel semiochemicals (super‐ligands) using homology modelling to conceive further strategies in insect management.
Temperature and photoperiod affect stress resistance traits in Drosophila melanogaster
Authors: Bauerfeind Stephanie S. , Kellermann Vanessa , Moghadam Neda N. , Loeschcke Volker , Fischer Klaus
Published: August 2014

The long‐term survival of species and populations depends on their ability to adjust phenotypic values to environmental conditions. In particular, the capability of dealing with environmental stress to buffer detrimental effects on fitness is considered to be of pivotal importance. Resistance traits are readily modulated by a wide range of environmental factors. In the present study, Drosophila melanogaster Meigen is used to investigate plastic responses to temperature and photoperiod in stress resistance traits. The results reveal that stress resistance traits (cold, heat, starvation and desiccation resistance) are affected by the factors temperature and sex predominantly. Cooler temperatures compared with warmer temperatures increase cold tolerance, desiccation and starvation resistance, whereas they reduce heat tolerance. Except for heat resistance, females are more stress‐resistant than males. Stress resistance traits are also affected by photoperiod. Shorter photoperiods decrease cold tolerance, whereas longer photoperiods enhance desiccation resistance. Overall, thermal effects are pervasive throughout all measured resistance traits, whereas photoperiodic effects are of limited importance in the directly developing (i.e. nondiapausing) flies used here, suggesting that pronounced photoperiodic effects on stress resistance traits may be largely limited to, and triggered by, diapause‐inducing effects.
Gastric carcinoma with an invasive micropapillary carcinoma component showing HER2 gene amplification and CD10 expression: A case report and review of the literature
Authors: Tajima Shogo , Kodama Hiroki , Kamiya Tadahiro , Terasaki Masaki
Published: August 2014

An 81‐year‐old man was referred to our hospital because gastric cancer was detected on screening esophagogastroduodenoscopy. Surgical resection of the tumor was performed. It was 25 × 20 mm in size and swollen lymph nodes were present nearby. Lymphadenectomy was also performed. Histopathologically, the tumor reached the proper muscle layer via venous invasion. There were three components that constituted the tumor, that is, 40% of mass was invasive micropapillary carcinoma (IMPC), 40% was papillary adenocarcinoma and 20% tubular adenocarcinoma. Vascular invasion was prominent. Immunohistochemistry revealed that the tumor showed an entirely intestinal mucin phenotype, being positive only for CD10 and negative for MUC2, MUC5AC, and MUC6. HER2 staining score ranged from 2+ to 3+, depending on the components described above. HER2 gene amplification was present in all the components according to dual‐color in situ hybridization. The metastatic lymph nodes were similar to the primary site in morphology and immunohistochemistry, but HER2 amplification was higher in the lymph nodes. The IMPC component with HER2 amplification is rarely seen and its positivity for CD10 is an unexpected finding for gastric IMPC. Hence, this is a highly unusual case judging by the literature; further studies are needed to clarify the nature of gastric IMPC.
Nested and microcystic variants of urothelial carcinoma displaying immunohistochemical features of basal‐like urothelial cells: An immunohistochemical and histopathogenetic study
Authors: Mai Kien T. , Hakim Shaheed W. , Ball Christopher G. , Flood Trevor A. , Belanger Eric C.
Published: August 2014

Nested/microcystic (NV/MV) urothelial carcinoma (UC) variants are associated with mild cytologic atypia and commonly present at high‐stage disease. The histopathogenesis is investigated using urothelial basal cell markers. Archival 14 NV/MV and three inverted papilloma (IP) were immunostained for CD44, cytokeratin 5 (CK5), CK34bE12 and p63. Twenty consecutive cases of invasive high‐grade UC including 14 superficial and 6 muscle‐invasive UC cases were used as control. Immunostaining was scored as high for staining of full or more than 50% thickness of the epithelial nest or epithelium and low for lesser immunoreactivity and negative reactivity. All 14 NV/MV, 3 IP and 6 control cases showed a high score of immunoreactivity for CK5, CD44, CK34bE12 and focally for p63. The remaining control cases showed a high score of immunoreactivity for CK34bE12, while negative or low for CK5, CD44 and p63. In conclusion, immunoreactivity CK5 and CD44 commonly immunostained NV/MV and some invasive high grade UC. Other basal cell markers (CK34bE12 and p63) appear to be non specific or non sensitive. NV and MV and some UC likely represent a subset of UC displaying immunohistochemical features of urothelial basal cells. They had tendency of endophytic growth and early invasion despite the innocuous cytologic appearance.
A GIS Toolbox for Measuring and Mapping Person‐Based Space‐Time Accessibility
Authors: Charleux Laure
Published: August 2014

This article presents a toolbox to compute and map person‐based accessibility indicators, based on classical time geography concepts. The intent is to provide GIS and urban planning practitioners with a user‐friendly and easily customizable tool. While it relies on well‐known concepts, the toolbox implements a major innovation in person‐based accessibility assessment by taking into account opening hours when measuring the accessibility of urban facilities. The toolbox can be downloaded from http://bit.ly/1h6yg5Z.
Two Arabidopsis proteins synthesize acetylated xylan in vitro
Authors: Urbanowicz Breeanna R. , Peña Maria J. , Moniz Heather A. , Moremen Kelley W. , York William S.
Published: August 2014

Xylan is the third most abundant glycopolymer on earth after cellulose and chitin. As a major component of wood, grain and forage, this natural biopolymer has far‐reaching impacts on human life. This highly acetylated cell wall polysaccharide is a vital component of the plant cell wall, which functions as a molecular scaffold, providing plants with mechanical strength and flexibility. Mutations that impair synthesis of the xylan backbone give rise to plants that fail to grow normally because of collapsed xylem cells in the vascular system. Phenotypic analysis of these mutants has implicated many proteins in xylan biosynthesis; however, the enzymes directly responsible for elongation and acetylation of the xylan backbone have not been unambiguously identified. Here we provide direct biochemical evidence that two Arabidopsis thaliana proteins, IRREGULAR XYLEM 10–L (IRX10‐L) and ESKIMO1/TRICOME BIREFRINGENCE 29 (ESK1/TBL29), catalyze these respective processes in vitro. By identifying the elusive xylan synthase and establishing ESK1/TBL29 as the archetypal plant polysaccharide O‐acetyltransferase, we have resolved two long‐standing questions in plant cell wall biochemistry. These findings shed light on integral steps in the molecular pathways used by plants to synthesize a major component of the world's biomass and expand our toolkit for producing glycopolymers with valuable properties.
UBC13, an E2 enzyme for Lys63‐linked ubiquitination, functions in root development by affecting auxin signaling and Aux/IAA protein stability
Authors: Wen Rui , Wang Sheng , Xiang Daoquan , Venglat Prakash , Shi Xianzong , Zang Yuepeng , Datla Raju , Xiao Wei , Wang Hong
Published: August 2014

Unlike conventional lysine (K) 48–linked polyubiquitination, K63‐linked polyubiquitination plays signaling roles in yeast and animals. Thus far, UBC13 is the only known ubiquitin‐conjugating enzyme (E2) specialized in K63‐linked polyubiquitination. Previous identification of Arabidopsis genes encoding UBC13 as well as its interacting partner UEV1 indicates that the UBC13‐mediated ubiquitination pathway is conserved in plants; however, little is known about functions and signaling mediated through K63‐linked polyubiquitination in plants. To address the functions of UBC13‐mediated ubiquitination in plants, we created Arabidopsis ubc13 null mutant lines in which the two UBC13 genes were disrupted. The double mutant displayed altered root development, including shorter primary root, fewer lateral roots and only a few short root hairs in comparison with the wild type and single mutant plants, indicating that UBC13 activity is critical for all major aspects of root development. The double mutant plants were insensitive to auxin treatments, suggesting that the strong root phenotypes do not simply result from a reduced level of auxin. Instead, the ubc13 mutant had a reduced auxin response, as indicated by the expression of an auxin‐responsive DR5 promoter‐GFP. Furthermore, both the enzymatic activity and protein level of an AXR3/IAA17‐GUS reporter were greatly increased in the ubc13 mutant, whereas the induction of many auxin‐responsive genes was suppressed. Collectively, these results suggest that Aux/IAA proteins accumulate in the ubc13 mutant, resulting in a reduced auxin response and defective root development. Hence, this study provides possible mechanistic links between UBC13‐mediated protein ubiquitination, root development and auxin signaling.