bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of JAK1/2 inhibition on bone marrow stromal cells of myeloproliferative neoplasm (MPN) patients and healthy individuals
Authors: Zacharaki Dimitra , Ghazanfari Roshanak , Li Hongzhe , Lim Hooi Ching , Scheding Stefan
Published: April 2018

Objective

Philadelphia‐negative myeloproliferative neoplasms (MPNs) commonly share hyperactive JAK‐STAT signaling affecting hematopoietic stem cells (HSC) and their progeny. The JAK1/2 inhibitor Ruxolitinib has remarkable clinical efficacy, including spleen reduction, improvement of constitutional symptoms, and bone marrow (BM) fibrosis reversal. Whether this is due to inhibition of JAK2‐mutated HSC only, or whether Ruxolitinib also affects BM stroma is not known.

Methods

This study investigated potential effects of Ruxolitinib on BM mesenchymal stromal cells (MSC), which are not only major regulators of hematopoiesis but also contribute to fibrosis, from 10 healthy donors and 7 JAK2V617F‐positive MPN patients.

Results

Ruxolitinib moderately inhibited the growth of healthy donor MSC (HD‐MSC) and MSC from JAK2V617F+ MPN patients (P‐MSC) in short‐ and long‐term assays. The clonogenic potential of HD‐MSC was not affected by Ruxolitinib. JAK‐STAT signaling, however, was markedly inhibited in both HD‐MSC and P‐MSC, the latter of which showed higher expression of fibrosis‐associated and hematopoiesis‐maintenance genes. Moreover, Ruxolitinib reduced MSC secretion of MCP‐1 and IL‐6.

Conclusion

Ruxolitinib affected JAK2 signaling in MSC at clinically relevant doses, which is likely to contribute to the normalization of the inflammatory milieu in MPNs. Thus, combined HSC and stroma‐directed interventions have the potential to improve constitutional symptoms and reduce stromal proliferation in MPNs.
Lifespan and age, but not residual reproductive value or condition, are related to behaviour in wild field crickets
Authors: Fisher David N. , David Morgan , Rodríguez‐Muñoz Rolando , Tregenza Tom
Published: April 2018

Individuals frequently show long‐term consistency in behaviour over their lifetimes, referred to as “personality.” Various models, revolving around the use of resources and how they are valued by individuals, attempt to explain the maintenance of these different behavioural types within a population, and evaluating them is the key for understanding the evolution of behavioural variation. The pace‐of‐life syndrome hypothesis suggests that differences in personalities result from divergent life‐history strategies, with more active/risk‐taking individuals reproducing rapidly but dying young. However, studies of wild animals provide only limited support for key elements of this and related hypotheses, such as a negative relationship between residual reproductive value and activity. Furthermore, alternative models make divergent predictions regarding the relationship between risk‐taking behaviours and variables consistent in the short‐term, such as condition. To test these predictions, we regularly measured willingness to leave a shelter and the activity level of wild adult field crickets (Gryllus campestris) at both short and long intervals over their entire adult lives. We found some support for a pace‐of‐life syndrome influencing personality, as lifespan was negatively related to willingness to leave the shelter and activity. Crickets did not appear to protect their “assets” however, as estimates of residual reproductive value were not related to behaviour. Although there was considerable variance attributed to the short‐term consistency, neither trait was affected by phenotypic condition, failing to support either of the models we tested. Our study confirms that behaviours may covary with some life‐history traits and highlights the scales of temporal consistency that are more difficult to explain.
Embryonic and larval defensive responses of agile frog (Rana dalmatina) to alien crayfish
Authors: Gazzola Andrea , Russo Giorgio , Balestrieri Alessandro
Published: April 2018

Red swamp crayfish Procambarus clarkii, a widespread invasive alien crayfish, represents a serious threat for several freshwater species, including amphibians, which are declining at a global scale. As a shared coevolutionary history is the main factor determining the emergence of antipredator responses, Anuran tadpoles may not be able to cope effectively with this introduced predator. We performed two experiments to assess agile frog's (Rana dalmatina) defensive responses to both P. clarkii and native dragonfly larvae (Anax imperator). First, we conditioned embryos (collected from two ponds 30 km away from each other) with predators’ chemical cues to explore possible variation in hatching time caused by predation risk. In the second experiment, to evaluate how predators’ diet affects tadpole behavior, we conditioned tadpoles for a 5‐week period with cues from tadpole‐fed and gammarid‐fed predators and recorded behavioral and morphological responses. Embryos did not alter hatching time in the presence of any predator cue, while tadpoles from both populations strongly reduced activity and visibility when raised in the presence of tadpole‐fed dragonfly larvae. Morphological changes were less straightforward and were induced only in one population, for which broader tails and a slight increase in body size of tadpoles exposed to tadpole‐fed predators were observed. The lack of defensive responses in crayfish‐exposed tadpoles suggests that the spreading of this invasive species in agricultural lowlands of northern Italy may represent a further threat to their conservation.
Intersexual conflict in androdioecious clam shrimp: Do androdioecious hermaphrodites evolve to avoid mating with males?
Authors: Ford Rebecah E. , Weeks Stephen C.
Published: April 2018

A recent sexual conflict model posits that a form of intersexual conflict may explain the persistence of males in androdioecious (males + hermaphrodites) populations of animals that are being selected to transition from dioecious (gonochoristic) mating to self‐compatible hermaphroditism. During the evolutionary spread of a self‐compatible hermaphrodite to replace females, the selective pressures on males to outcross are in conflict with the selective pressures on hermaphrodites to self. According to this model, the unresolved conflict interferes with the evolutionary trajectory from dioecy to hermaphroditism, slowing or halting that transition and strengthening the otherwise “transitory” breeding system of androdioecy into a potentially stable breeding strategy. Herein, we assess this model using two dioecious and two androdioecious clam shrimp (freshwater crustaceans) to ask two questions: (1) Have hermaphrodites evolved so that males cannot effectively recognize them?; and (2) Do androdioecious hermaphrodites avoid males? Androdioecious males made more mistakes than dioecious males when guarding potential mates suggesting that androdioecious males were less effective at finding hermaphrodites than dioecious males were at finding females. Similarly, in a three‐chambered experiment, focal hermaphrodites chose to aggregate with their same sex, whereas focal dioecious males chose to aggregate with the alternate sex. Together, these two experiments support the sexual conflict model of the maintenance of androdioecy and suggest that hermaphrodites are indeed evolving to avoid and evade males.
Relationship between effective and demographic population size in continuously distributed populations
Authors: Pierson Jennifer C. , Graves Tabitha A. , Banks Sam C. , Kendall Katherine C. , Lindenmayer David B.
Published: April 2018

Genetic monitoring of wild populations can offer insights into demographic and genetic information simultaneously. However, widespread application of genetic monitoring is hindered by large uncertainty in the estimation and interpretation of target metrics such as contemporary effective population size, Ne. We used four long‐term genetic and demographic studies (≥9 years) to evaluate the temporal stability of the relationship between Ne and demographic population size (Nc). These case studies focused on mammals that are continuously distributed, yet dispersal‐limited within the spatial scale of the study. We estimated local, contemporary Ne with single‐sample methods (LDNE, Heterozygosity Excess, and Molecular Ancestry) and demographic abundance with either mark–recapture estimates or catch‐per‐unit effort indices. Estimates of Ne varied widely within each case study suggesting interpretation of estimates is challenging. We found inconsistent correlations and trends both among estimates of Ne and between Ne and Nc suggesting the value of Ne as an indicator of Nc is limited in some cases. In the two case studies with consistent trends between Ne and Nc, FIS was more stable over time and lower, suggesting FIS may be a good indicator that the population was sampled at a spatial scale at which genetic structure is not biasing estimates of Ne. These results suggest that more empirical work on the estimation of Ne in continuous populations is needed to understand the appropriate context to use LDNe as a useful metric in a monitoring programme to detect temporal trends in either Ne or Nc.
TMEM55B contributes to lysosomal homeostasis and amino acid–induced mTORC1 activation
Authors: Hashimoto Yutaka , Shirane Michiko , Nakayama Keiichi I.
Published: April 2018

Mammalian/mechanistic target of rapamycin complex 1 (mTORC1) responds to growth factors and nutrient availability. Amino acids induce the recruitment of mTORC1 to the lysosomal membrane and its consequent activation, but the molecular mechanism of such activation has remained unclear. We have now examined the role of TMEM55B, a lysosomal protein of unknown molecular function, in this process on the basis of the results of proteomics and immunofluorescence analyses showing that TMEM55B interacts with many proteins that participate in mTORC1 activation including components of the vacuolar‐type proton ATPase (V‐ATPase) and Ragulator complexes at the lysosomal membrane. The amino acid–induced phosphorylation of the mTORC1 substrates S6K and 4E‐BP was attenuated in TMEM55B‐depleted cells compared with control cells. Depletion of TMEM55B was also found to evoke lysosomal stress as showed by translocation of the transcription factor TFEB to the nucleus. Furthermore, recruitment of the V1 domain subcomplex of V‐ATPase to lipid rafts was abrogated in TMEM55B‐depleted cells. Collectively, our results suggest that TMEM55B contributes to assembly of the V‐ATPase complex in lipid rafts of the lysosomal membrane and to subsequent activation of mTORC1.
Effect of curing conditions on physical and chemical properties of MTA+
Authors: Zarra T. , Lambrianidis T. , Vasiliadis L. , Gogos C.
Published: April 2018

Aim

To evaluate setting time, pH, solubility and surface roughness of MTA+ and ProRoot MTA and characterize their hydration under several curing conditions.

Methodology

Specimens were prepared to evaluate setting time (n = 6 for each group, specimen dimensions 10 × 8 × 5 mm), solubility (n = 6 for each group, specimen dimension 20 mm in diameter and 1.5 mm thick) after 1 and 28 days, pH (n = 10 for each group, specimen dimensions 10 mm in diameter and 1 mm thick) after 1, 7, 14, 21 and 28 days and surface roughness (n = 10 for each group, specimen dimensions 4 mm in diameter and 3 mm high) after 28 days when cements were cured at 95% humidity or immersed in saline or HBSS at 37 °C. The powder and liquid were mechanically mixed by an amalgamator. The set materials were characterized using X‐ray diffraction analysis, scanning electron microscopy and X‐ray energy‐dispersive analysis. Statistical comparisons were employed using one‐way anova. The level of significance was set at P = 0.05.

Results

Setting time was significantly shorter when cements were cured at 95% humidity compared to those in saline (P < 0.001) and HBSS (P < 0.001). Setting time of MTA+ was significantly shorter than that of ProRoot MTA (P < 0.001), which had a significantly higher pH than MTA+ (P < 0.05) for all periods and immersion liquids. After immersion in saline, MTA+ was significantly less soluble than ProRoot MTA (P < 0.001); when immersed in HBSS, no significant difference was found (P = 1.00). The surface roughness of both cements was affected when exposed to HBSS (P < 0.001 for both cements) and saline (P < 0.001 for both cements). Storage in HBSS created a homogenous surface; incubation in saline or humidity created a biphasic surface. The main crystalline phases in both cements were tricalcium silicate, bismuth oxide and calcium hydroxide.

Conclusions

MTA+ had a shorter setting time than ProRoot MTA, promoted lower pH and had lower solubility in saline. Curing conditions affected the surface roughness and microstructure of the cements.
Effect of pressure and temperature on viscosity of a borosilicate glass
Authors: Ding Linfeng , Thieme Manuel , Demouchy Sylvie , Kunisch Clemens , Kaus Boris J. P.
Published: April 2018

During industrial glass production processes, the actual distribution of stress components in the glass during scribing remains, to date, poorly quantified, and thus continues to be challenging to model numerically. In this work, we experimentally quantified the effect of pressure and temperature on the viscosity of SCHOTT N‐BK7® glass, by performing in situ deformation experiments at temperatures between 550 and 595°C and confining pressures between 100 and 300 MPa. Experiments were performed at constant displacement rates to produce almost constant strain rates between 9.70 × 10−6 and 4.98 × 10−5 s−1. The resulting net axial stresses range from 81 to 802 MPa, and the finite strains range from 1.4% to 8.9%. The mechanical results show that the SCHOTT N‐BK7® glass is viscoelastic near the glass transition temperature at 300 MPa of confining pressure. To elucidate the data, we incorporated both 1‐element and 2‐element generalized Maxwell viscoelastic models in an inversion approach, for which we provide MATLAB scrips. Results show that the 2‐element Maxwell model fits the experimental data well. The stress decreases with increasing temperature at 300 MPa and the temperature dependence yields a similar activation energy (601 ± 10 kJ mol−1 or ∆H/R = 7.2 × 104 K) to a previously reported value at 1‐atm (615 kJ mol−1 or ∆H/R = 7.4 × 104 K). The SCHOTT N‐BK7® glass shows a limited linear increase in viscosity with increasing pressure of ~0.1 log10 (Pa·s)/100 MPa, which is in agreement with the most recent 2‐internal‐parameter relaxation model (based on experiments).
Diets of reef‐dwelling labrids (Choerodon species) vary with body size, season and habitat: influence of foraging ability, specialization and opportunism
Authors: Lek E. , Platell M. E. , Fairclough D. V. , Hall N. G. , Potter I. C.
Published: April 2018

Contemporary multivariate statistics were used to test the hypotheses that the dietary compositions of three populations of labrids on the west Australian coast are related to body size and undergo seasonal changes and to elucidate the relative extents and basis for any dietary differences within and between those populations. Gut content analyses determined the dietary compositions of Choerodon rubescens in marine waters of the outer reefs in the World Heritage Area of Shark Bay (26° S; 114° E) and of Choerodon schoenleinii in inner protected reefs of that large embayment. The dietary compositions of C. rubescens and C. schoenleinii differed significantly among length classes, progressed serially with increasing body size, both overall and almost invariably in each season and were more closely related to body size than season, whose effect was at best minimal. The size‐related dietary change in C. rubescens involved, in particular, a shift from crustaceans and non‐mytilid bivalves to mytilid bivalves and echinoid echinoderms. Although the diet of C. schoenleinii followed similar size‐related changes, it contained a greater volume of gastropods when the fish were small and mytilids when large and only a small volume of echinoids. The dietary composition of C. rubescens in the Abrolhos Islands, 300 km to the south of Shark Bay, was related both to length class and season and differed from that of this labrid in Shark Bay with the ingestion of lesser volumes of mytilids and greater volumes of echinoids. The size‐related changes in diet imply that these species shift from foraging over soft substrata to over reefs as their very well‐developed jaws become sufficiently strong to remove attached and larger prey. The dietary compositions of C. rubescens and C. schoenleinii in Shark Bay and of C. rubescens at the Abrolhos Islands were related far more to habitat–locational differences than to length class and season. The above intraspecific and interspecific differences in diet are consistent with qualitative accounts of the relative abundances of the main prey in their respective environments, supporting the view that, despite specializations in their feeding apparatus, these labrids can feed opportunistically to a certain extent and could thus potentially respond to moderate changes in the composition of their prey caused by climate change and other anthropogenic effects.
Comparison of clinical outcome of hepatic arterial infusion chemotherapy and sorafenib for advanced hepatocellular carcinoma according to macrovascular invasion and transcatheter arterial chemoembolization refractory status
Authors: Kodama Kenichiro , Kawaoka Tomokazu , Aikata Hiroshi , Uchikawa Shinsuke , Inagaki Yuki , Hatooka Masahiro , Morio Kei , Nakahara Takashi , Murakami Eisuke , Tsuge Masataka , Hiramatsu Akira , Imamura Michio , Kawakami Yoshiiku , Masaki Keiichi , Honda Yoji , Mori Nami , Takaki Shintaro , Tsuji Keiji , Kohno Hirotaka , Kohno Hiroshi , Moriya Takashi , Nonaka Michihiro , Hyogo Hideyuki , Aisaka Yasuyuki , Chayama Kazuaki
Published: April 2018

Background and Aim

Sorafenib is the standard treatment for patients with advanced hepatocellular carcinoma (HCC) with distant metastasis, unresectable HCC, and HCC refractory to transcatheter arterial chemoembolization (TACE) or with macroscopic vascular invasion (MVI). Also, hepatic arterial infusion chemotherapy (HAIC) has been used for advanced HCC in Southeast and East Asian countries. However, clearer information is needed for choosing appropriately between these therapies.

Methods

The subjects were 391 HAIC and 431 sorafenibs administered at our hospital and related hospitals. In this case, cases that satisfy the following three conditions were targeted: (i) no extrahepatic metastasis, (ii) Child‐Pugh A, and (ii) not having received treatment of both HAIC and sorafenib during the course. As a result, 150 cases of HAIC and 134 cases of sorafenib were analyzed this time.

Results

Univariate and multivariate analyses were performed for the HAIC and sorafenib groups. TACE refractory status and MVI were factors contributing to overall survival (OS). Therefore, this study divided all cases according to those variables. The median survival time of MVI‐positive and non‐TACE refractory cases was significantly better with HAIC (13 months) versus sorafenib (6 months). However, in MVI‐negative and TACE refractory cases, the median survival time of HAIC (8 months) was significantly poorer than for sorafenib (20 months).

Conclusion

Transcatheter arterial chemoembolization refractory status with HAIC and MVI with sorafenib were factors for poor prognosis. In particular, HAIC was significantly better than sorafenib as primary treatment in MVI and non‐TACE refractory cases. It is necessary to consider these factors in treatment selection.
Costs and outcomes of Lynch syndrome screening in the Australian colorectal cancer population
Authors: Cenin Dayna R , Naber Steffie K , Lansdorp‐Vogelaar Iris , Jenkins Mark A , Buchanan Daniel D , Preen David B , Ee Hooi C , O'Leary Peter
Published: April 2018

Background and Aim

Individuals with Lynch syndrome (LS) are at increased risk of LS‐related cancers including colorectal cancer (CRC). CRC tumor screening for mismatch repair (MMR) deficiency is recommended in Australia to identify LS, although its cost‐effectiveness has not been assessed. We aim to determine the cost‐effectiveness of screening individuals with CRC for LS at different age‐at‐diagnosis thresholds.

Methods

We developed a decision analysis model to estimate yield and costs of LS screening. Age‐specific probabilities of LS diagnosis were based on Australian data. Two CRC tumor screening pathways were assessed (MMR immunohistochemistry followed by MLH1 methylation (MLH1‐Pathway) or BRAF V600E testing (BRAF‐Pathway) if MLH1 expression was lost) for four age‐at‐diagnosis thresholds—screening < 50, screening < 60, screening < 70, and universal screening.

Results

Per 1000 CRC cases, screening < 50 identified 5.2 LS cases and cost $A7041 per case detected in the MLH1‐Pathway. Screening < 60 increased detection by 1.5 cases for an incremental cost of $A25 177 per additional case detected. Screening < 70 detected 1.6 additional cases at an incremental cost of $A40 278 per additional case detected. Compared with screening < 70, universal screening detected no additional LS cases but cost $A158 724 extra. The BRAF‐Pathway identified the same number of LS cases for higher costs.

Conclusions

The MLH1‐Pathway is more cost‐effective than BRAF‐Pathway for all age‐at‐diagnosis thresholds. MMR immunohistochemistry tumor screening in individuals diagnosed with CRC aged < 70 years resulted in higher LS case detection at a reasonable cost. Further research into the yield of LS screening in CRC patients ≥ 70 years is needed to determine if universal screening is justified.
Petrogenesis of kyanite‐ and corundum‐bearing mafic granulite in a meta‐ophiolite, SE Turkey
Authors: Awalt Mitchell B. , Whitney Donna L.
Published: April 2018

Although ophiolitic rocks are abundant in Anatolia (Turkey), only in rare cases have they experienced high‐grade metamorphism. Even more uncommon, in Anatolia and elsewhere are high‐grade meta‐ophiolites that retain an oceanic lithosphere stratigraphy from upper crustal mafic volcanic rocks through lower crustal gabbro to mantle peridotite. The Berit meta‐ophiolite of SE Turkey exhibits both features: from structurally higher to lower levels, it consists of garnet amphibolite (metabasalt), granulite facies metagabbro (as lenses in amphibolite inferred to be retrogressed granulite) and metaperidotite (locally with metapyroxenite layers). Whole‐rock major and trace‐element data indicate a tholeiitic protolith that formed in a suprasubduction setting. This paper presents new results for the metamorphic P–T conditions and path of oceanic lower crustal rocks in the Berit meta‐ophiolite, and an evaluation of the tectonic processes that may drive granulite facies metamorphism of ophiolite gabbro. In the Doğanşehir (Malatya, Turkey) region, granulite facies gabbroic rocks contain garnet (Grt)+clinopyroxene (Cpx)+plagioclase (Pl)+corundum (Crn)±orthopyroxene (Opx)±kyanite (Ky)±sapphirine (Spr)±rutile. Some exhibit symplectites consisting of Crn+Cpx, Ky+Cpx and/or coronas of garnet (outer shell) around a polygonal aggregate of clinopyroxene that in some cases surrounds a polygonal aggregate of orthopyroxene. Coronitic and non‐coronitic textures occur in proximity in mm‐ to cm‐scale layers; corona structures typically occur in plagioclase‐rich layers. Their formation is therefore related primarily to protolith type (troctolite v. gabbro) rather than P–T path. Phase diagrams calculated for a kyanite‐rich granulite, a plagioclase‐rich non‐coronitic granulite, and a plagioclase‐rich coronitic granulite (taking into account changes in effective bulk composition during texture development) predict peak conditions of ~800°C, 1.1–1.5 GPa; these conditions do not require invoking an unusually high geothermal gradient. In the coronitic metagabbro, reaction textures formed along the prograde path: Crn–Cpx symplectites grew at the expense of garnet, sapphirine and plagioclase. Peak conditions were followed by isobaric cooling of ~150°C. Hornblende–plagioclase thermometry results for host amphibolite (Hbl+Pl±Crn±Grt±relict Cpx) indicate retrograde conditions of 620–675°C and 0.5–0.8 GPa accompanied by infiltration of H2O‐rich fluid. This anticlockwise P–T path differs from an isothermal decompression path previously proposed for these rocks based on the presence of symplectite. Metamorphism of the ophiolitic rocks was driven by closing of the southern Neotethys Ocean, as oceanic lithosphere was obducted (most SE Anatolian ophiolites) or underthrust (Berit meta‐ophiolite). This was followed by subduction of a continental margin, driving cooling of the Berit granulite after the thermal peak at depths of ~40 km.
Cell and molecular mechanisms behind diet‐induced hypothalamic inflammation and obesity
Authors: Ávalos Y. , Kerr B. , Maliqueo M. , Dorfman M.
Published: April 2018

Diet‐induced obesity (DIO) is associated with chronic, low‐grade inflammation in the hypothalamus, a key regulator of energy homeostasis. Current studies have revealed the involvement of different cell types, as well as cell and molecular mechanisms, that contribute to diet‐induced hypothalamic inflammation (DIHI) and DIO. Subsequent to the discovery that high‐fat diet and saturated fatty acids increase the expression of hypothalamic cytokines prior to weight gain, research has focused on understanding the cellular and molecular mechanisms underlying these changes, in addition to the role of inflammation in the pathogenesis of obesity. Recent studies have proposed that the inhibition of pro‐inflammatory pathways in microglia and astrocytes is sufficient to protect against DIHI and prevent obesity. In addition, impairment of intracellular and epigenetic mechanisms, such as hypothalamic autophagy and changes in the methylation pattern of certain genes, have been implicated in susceptibility to DIHI and DIO. Interestingly, a sexual dimorphism has been found during DIO in hypothalamic inflammation, glial activation and metabolic diseases, and recent data support an important role of sex steroids in DIHI. These new exciting findings uncover novel obesity pathogenic mechanisms and provide targets to develop therapeutic approaches.
A Systematic Review and Integration of Concept Analyses of Self‐Care and Related Concepts
Authors: Matarese Maria , Lommi Marzia , De Marinis Maria Grazia , Riegel Barbara
Published: April 2018

Purpose

This systematic review identified, synthesized, and integrated concept analyses on self‐care and related concepts.

Design

The guidelines for systematic literature reviews of the Joanna Briggs Institute were followed.

Methods

The Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed, PsycINFO, and EMBASE databases were searched for concept analyses published in the past 20 years.

Findings

A total of 26 concept analyses were identified that had been published on self‐care, self‐care agency, self‐monitoring, self‐management, self‐management support, symptom management, and self‐efficacy. Differences and commonalities in the examined literature were identified, and a model was delineated, explaining the relations among the various concepts from the nursing perspective.

Conclusions

The healthcare literature has broadly described self‐care and related concepts; however, consensus on the definitions remains beyond our reach and should not be expected, due to the different perspectives and paradigms from which the concepts are interpreted. From a nursing perspective, self‐care can be considered a broad concept encompassing the other concepts, which describe more specific individual levels of activities and processes.

Clinical Relevance

Nurses are actively involved in disease management and self‐management support as well as in promoting self‐care in healthy and sick people. Referring to a model on self‐care and related concepts could avoid misinterpretations in nursing practice, research, and policy.
Feasibility of recruiting publicly insured children with special health care needs for a population‐based clinical study
Authors: Yoo Michael , Chi Donald L.
Published: April 2018

Objective

Assess the feasibility of recruiting children with special health care needs (CSHCN) into a clinical study using Medicaid data.

Methods

We used the 3M Clinical Risk Grouping software to identify and classify Medicaid‐enrolled CSHCN ages 7‐17 years in Washington into one of three chronic condition severity groups: episodic, life‐long, or malignancy/catastrophic. We compared contact, recruitment, enrollment, and data completion proportions across severity groups using the Pearson chi‐square or Fisher's exact test.

Results

Of the 2,666 CSHSN in the Medicaid files, we contacted 922 and recruited 211 CSHCN (22.8 percent). One‐hundred‐thirteen made their study visit (53.6 percent) and 98 had complete data (86.7 percent). We contacted and recruited significantly larger proportions of CSHCN with malignancies/catastrophic conditions (P < 0.01). Across severity groups, there were no differences in enrollment (P = 0.27), but a smaller proportion of CSHCN with life‐long conditions had complete data (P = 0.03).

Conclusion

It is feasible to recruit CSHCN from Medicaid files for clinical studies.
Evolution of a xenobiotic degradation pathway: formation and capture of the labile phthaloyl‐CoA intermediate during anaerobic phthalate degradation
Authors: Mergelsberg Mario , Egle Valentin , Boll Matthias
Published: April 2018

Xenobiotic phthalates are industrially produced on the annual million ton scale. The oxygen‐independent enzymatic reactions involved in anaerobic phthalate degradation have only recently been elucidated. In vitro assays suggested that phthalate is first activated to phthaloyl‐CoA followed by decarboxylation to benzoyl‐CoA. Here, we report the heterologous production and characterization of the enzyme initiating anaerobic phthalate degradation from ‘Aromatoleum aromaticum’: a highly specific succinyl‐CoA:phthalate CoA transferase (SPT, class III CoA transferase). Phthaloyl‐CoA formed by SPT accumulated only to sub‐micromolar concentrations due to the extreme lability of the product towards intramolecular substitution with a half‐life of around 7 min. Upon addition of excess phthaloyl‐CoA decarboxylase (PCD), the combined activity of both enzymes was drastically shifted towards physiologically relevant benzoyl‐CoA formation. In conclusion, a massive overproduction of PCD in phthalate‐grown cells to concentrations >140 μM was observed that allowed for efficient phthaloyl‐CoA conversion at concentrations 250‐fold below the apparent Km‐value of PCD. The results obtained provide insights into an only recently evolved xenobiotic degradation pathway where a massive cellular overproduction of PCD compensates for the formation of the probably most unstable CoA ester intermediate in biology.
The distinct PhoPR mediated responses to phosphate limitation in Bacillus subtilis subspecies subtilis and spizizenii stem from differences in wall teichoic acid composition and metabolism
Authors: Prunty Michael P. , Noone David , Devine Kevin M.
Published: April 2018

The PhoPR‐mediated response to phosphate limitation (PHO response) in Bacillus subtilis subsp subtilis is amplified and maintained by reducing the level of Lipid VG composed of poly(glycerol phosphate), a wall teichoic acid (WTA) biosynthetic intermediate that inhibits PhoR autokinase activity. However, the reduction in Lipid VG level is effected by activated PhoP∼P, raising the question of how the PHO response is first initiated. Furthermore, that WTA is composed of poly(ribitol phosphate) in Bacillus subtilis subsp spizizenii prompted an investigation of how the PHO response is regulated in that bacterium. We report that the PHO responses of B. subtilis subsp subtilis and subsp spizizenii are distinct. The PhoR kinases of the two B. subtilis subspecies are functionally equivalent and are activated either by the TagA/TarA or TagB/TarB enzyme product. However, they are inhibited by Lipid VG composed of poly(glycerol phosphate) but not by Lipid VR composed of poly(ribitol phosphate). Therefore, the distinctive PHO responses of these B. subtilis subspecies stem from the differential sensitivity of PhoR kinases to the polyol composition of Lipid V and from the genomic organization of WTA biosynthetic genes and the regulation of their expression.
MLCK‐mediated intestinal permeability promotes immune activation and visceral hypersensitivity in PI‐IBS mice
Authors: Long Y. , Du L. , Kim J. J. , Chen B. , Zhu Y. , Zhang Y. , Yao S. , He H. , Zheng X. , Huang Z. , Dai N.
Published: April 2018

Background

Alterations in intestinal permeability regulated by tight junctions (TJs) are associated with immune activation and visceral hypersensitivity in irritable bowel syndrome (IBS). Myosin light chain kinase (MLCK) is an important mediator of epithelial TJ. The aim of this study is to investigate the role of MLCK in the pathogenesis of IBS using a post infectious IBS (PI‐IBS) mouse model.

Methods

Trichinella spiralis‐infected PI‐IBS mouse model was used. Urine lactulose/mannitol ratio was measured to assess intestinal epithelial permeability. Western blotting was used to evaluate intestinal TJ protein (zonula occludens‐1) and MLCK‐associated protein expressions. Immune profile was assessed by measuring Th (T helper) 1/Th2 cytokine expression. Visceral sensitivity was determined by abdominal withdrawal reflex in response to colorectal distension.

Results

Eight weeks after inoculation with T. spiralis, PI‐IBS mice developed decreased pain and volume thresholds during colorectal distention, increased urine lactulose/mannitol ratio, elevated colonic Th1/Th2 cytokine ratio, and decreased zonula occludens‐1 expression compared to the control mice. MLCK expression was dramatically elevated in the colonic mucosa of PI‐IBS mice compared to the control mice, alongside increased pMLC/MLC and decreased MLCP expression. Administration of MLCK inhibitor and TJ blocker both reversed the increased intestinal permeability, visceral hypersensitivity, and Th1‐dominant immune profile in PI‐IBS mice.

Conclusion

MLCK is a pivotal step in inducing increased intestinal permeability promoting low‐grade intestinal immune activation and visceral hypersensitivity in PI‐IBS mice. MLCK inhibitor may provide a potential therapeutic option in the treatment of IBS.
Colchicine may be of therapeutic benefit in prurigo pigmentosa
Authors: An Isa , Ucmak Derya , Ibiloglu Ibrahim , Demir Vasfiye , Akdeniz Sedat
Published: April 2018

Prurigo pigmentosa (PP) is a rare inflammatory skin disease. Neutrophil‐mediated inflammation is considered to be responsible for the etiopathogenesis of PP. We consider that colchicine may be an effective agent in the treatment of PP since it exerts an antiinflammatory effect by inhibiting neutrophil chemotaxis. Further studies are required to verify whether colchicine is an effective treatment option for PP.
Zircon U–Pb and Wolframite Sm–Nd Dating of the Bayinsukhtu Tungsten Deposit in Southern Mongolia and its Geological Significance
Authors: Guo Zhihua , Zhang Baolin , Guo Bowei , Dang Yongqi , Hou Jinliang
Published: April 2018

The Bayinsukhtu tungsten deposit is a newly discovered quartz‐vein tungsten deposit in the Xing'an–Mongolia Orogenic Belt (XMOB) in southern Mongolia, hosted by the Bayinsukhtu granite porphyry. The granite porphyry is located mainly south of the study area, over 3 km2. The rock consists of quartz and feldspar phenocrysts in a fine‐grained matrix, also mainly composed of feldspar and quartz. The granite porphyry samples demonstrate high SiO2 and high alkalinity. All samples also straddle the high‐potassium calc‐alkaline series. In a plot of the molar ratios of A/NK versus A/CNK, the granites are metaluminous. The chondrite‐normalized REE patterns are characterized by large negative Eu anomalies and fractionated LREEs. The U–Pb age of zircons from the granite porphyry is 298.8 ± 1.8 Ma, and the Sm–Nd age of the five wolframite samples from the tungsten deposit is 303 ± 19 Ma. The cooling age of the granite porphyry and tungsten mineralization is within the error of measurement and is of the Late Carboniferous age. Geological and geochronological evidence shows that the tungsten mineralization and the granite porphyry at Bayinsukhtu are genetically closely related and that they are results of Carboniferous magmatism. Their tectonic setting is related to the accretion of the Central Asian Orogenic Belt during the late Paleozoic era.
The Discursive Construction of National Identity in Speeches of Wen Jiabao in Response to the 2008─2011 Global Financial-Economic Recessions
Authors: Ar Mustafa
Published: April 2018

Although the relationship between discourse and identity has generally been explored in academic literature, critical research on the constitutive role of discourse in constructing national identity in the domain of the contemporary global economy has received scant attention. The main objective of this article is to identify and describe the linguistic resources used to construct national identity in the political economic speeches during the 2008–2011 global financial-economic recessions. The study is also an attempt to explain the opaque relationship between the discursive and economic elements in the formation of national identity. The sources of data are derived from three political economic speeches of the former Premier Wen Jiabao of China. Drawing upon critical discourse analysis and cultural political economy, the article reveals that at the micro level the first person plural ‘we’, nominal groups, and adverbs of place make up linguistic elements deployed to construct China’s national identity. At the macro level, constructive strategies are employed to inculcate national identity. With respect to political economy, the speeches entrench the neoliberal economic policy while obfuscating national interests of China as being a country with a form of state-led market economy.
Heartbeat type classification with optimized feature vectors
Authors: Yildirim Özal , Baloglu Ulas Baran
Published: April 2018

In this study, a feature vector optimization based method has been proposed for classification of the heartbeat types. Electrocardiogram (ECG) signals of five different heartbeat type were used for this aim. Firstly, wavelet transform (WT) method were applied on these ECG signals to generate all feature vectors. Optimizing these feature vectors is provided by performing particle swarm optimization (PSO), genetic search, best first, greedy stepwise and multi objective evoluationary algorithms on these vectors. These optimized feature vectors are later applied to the classifier inputs for performance evaluation. A comprehensive assessment was presented for the determination of optimized feature vectors for ECG signals and best-performing classifier for these optimized feature vectors was determined.
Alpha Centauri's siren call has frustrated planet hunters
Authors: Clery Daniel
Published: April 2018

The nearest sunlike stars have failed to yield exoplanets so far, but searches for Earth-like ones are ramping up.
A blueprint for demonstrating quantum supremacy with superconducting qubits
Authors: Neill C. , Roushan P. , Kechedzhi K. , Boixo S. , Isakov S. V. , Smelyanskiy V. , Megrant A. , Chiaro B. , Dunsworth A. , Arya K. , Barends R. , Burkett B. , Chen Y. , Chen Z. , Fowler A. , Foxen B. , Giustina M. , Graff R. , Jeffrey E. , Huang T. , Kelly J. , Klimov P. , Lucero E. , Mutus J. , Neeley M. , Quintana C. , Sank D. , Vainsencher A. , Wenner J. , White T. C. , Neven H. , Martinis J. M.
Published: April 2018

Scaling up to supremacy

Quantum information scientists are getting closer to building a quantum computer that can perform calculations that a classical computer cannot. It has been estimated that such a computer would need around 50 qubits, but scaling up existing architectures to this number is tricky. Neill
et al.
explore how increasing the number of qubits from five to nine affects the quality of the output of their superconducting qubit device. If, as the number of qubits grows further, the error continues to increase at the same rate, a quantum computer with about 60 qubits and reasonable fidelity might be achievable with current technologies.

Science
, this issue p.
195
Building one molecule from a reservoir of two atoms
Authors: Liu L. R. , Hood J. D. , Yu Y. , Zhang J. T. , Hutzler N. R. , Rosenband T. , Ni K.-K.
Published: April 2018

Lighting the way to molecules, one by one

When chemists run reactions, what they are really doing is mixing up an enormous number of reacting partners and then hoping that they collide productively. It is possible to manipulate atoms more deliberately with a scanning tunneling microscope tip, but the process is then confined to a surface. Liu
et al.
directly manipulated individual atoms with light to form single molecules in isolation (see the Perspective by Narevicius). They used optical tweezers of two different colors to selectively steer ultracold sodium (Na) and cesium (Cs) atoms together. A subsequent optical excitation formed NaCs.

Science
, this issue p.
900
; see also p.
855
High-resolution cryo-EM analysis of the yeast ATP synthase in a lipid membrane
Authors: Srivastava Anurag P. , Luo Min , Zhou Wenchang , Symersky Jindrich , Bai Dongyang , Chambers Melissa G. , Faraldo-Gómez José D. , Liao Maofu , Mueller David M.
Published: April 2018

Protons find a path

Adenosine triphosphate (ATP) synthases are dynamos that interconvert rotational and chemical energy. Capturing the complete structure of these multisubunit membrane-bound complexes has been hindered by their inherent ability to adopt multiple conformations. Srivastava
et al.
used protein engineering to freeze mitochondrial ATP synthase from yeast in a single conformation and obtained a structure with the inhibitor oligomycin, which binds to the rotating c-ring within the membrane. Hahn
et al.
show that chloroplast ATP synthase contains a built-in inhibitor triggered by oxidizing conditions in the dark chloroplast. The mechanisms by which these machines are powered are remarkably similar: Protons are shuttled through a channel to the membrane-embedded c-ring, where they drive nearly a full rotation of the rotor before exiting through another channel on the opposite side of the membrane (see the Perspective by Kane).

Science
, this issue p.
eaas9699
, p.
eaat4318
; see also p.
600
A Single Amino Acid in the Polymerase Acidic Protein Determines the Pathogenicity of Influenza B Viruses
Authors: Bae Joon-Yong , Lee Ilseob , Kim Jin Il , Park Sehee , Yoo Kirim , Park Miso , Kim Gayeong , Park Mee Sook , Lee Joo-Yeon , Kang Chun , Kim Kisoon , Park Man-Seong
Published: April 2018

Influenza B virus (IBV) is one of the human respiratory viruses and one of the targets of seasonal vaccination. However, the bifurcation of two antigenically distinct lineages of IBVs makes it difficult to arrange proper medical countermeasures. Moreover, compared with pathogenicity-related molecular markers known for influenza A virus, little has been known for IBVs. To understand pathogenicity caused by IBVs, we investigated the molecular determinants of IBV pathogenicity in animal models. After serial lung-to-lung passages of Victoria lineage B/Brisbane/60/2008 (Vc_BR60) and Yamagata lineage B/Wisconsin/01/2010 (Ym_WI01) viruses in BALB/c mice, we identified the mouse-adapted Vc_BR60 (maVc_BR60) and Ym_WI01 (maYm_WI01) viruses, respectively. To find a molecular clue(s) to the increased pathogenicity of maVc_BR60 and maYm_WI01, we determined their genetic sequences. Several amino acid mutations were identified in the PB2, PB1, PA, BM2, and/or NS1 protein-coding regions, and one concurrent lysine (K)-to-arginine (R) mutation in PA residue 338 (PA K338R) was found in both maVc_BR60 and maYm_WI01 viruses. When analyzed using viruses rescued through reverse genetics, it was shown that PA K338R alone could increase the pathogenicity of both IBVs in mice and viral replication in the respiratory tracts of ferrets. In a subsequent minireplicon assay, the effect of PA K338R was highlighted by the enhancement of viral polymerase complex activity of both Vc_BR60 and Ym_WI01 viruses. These results suggest that the PA K338R mutation may be a molecular determinant of IBV pathogenicity via modulating the viral polymerase function of IBVs.

IMPORTANCE
To investigate molecular pathogenic determinants of IBVs, which are one of the targets of seasonal influenza vaccines, we adapted both Victoria and Yamagata lineage IBVs independently in mice. The recovered mouse-adapted viruses exhibited increased virulence, and of the various mutations identified from both mouse-adapted viruses, a concurrent amino acid mutation was found in the PA protein-coding region. When analyzed using viruses rescued through reverse genetics, the PA mutation alone appeared to contribute to viral pathogenicity in mice within the compatible genetic constellation between the IBV lineages and to the replication of IBVs in ferrets. Regarding the potential mechanism of increased viral pathogenicity, it was shown that the PA mutation could upregulate the viral polymerase complex activity of both IBV lineages. These results indicate that the PA mutation could be a newly defined molecular pathogenic determinant of IBVs that substantiates our understanding of the viral pathogenicity and public health risks of IBVs.
Geology and vertebrate paleontology of Tule Springs Fossil Beds National Monument, Nevada, USA
Authors: Springer Kathleen B. , Pigati Jeffrey S. , Scott Eric
Published: April 2018

Tule Springs Fossil Beds National Monument (TUSK) preserves 22,650 acres of the upper Las Vegas Wash in the northern Las Vegas Valley, Nevada, USA. TUSK is home to extensive and stratigraphically complex groundwater discharge (GWD) deposits, called the Las Vegas Formation, which represent springs and desert wetlands that covered much of the valley during the late Quaternary. The GWD deposits record hydrologic changes that occurred here in a dynamic and temporally congruent response to abrupt climatic oscillations over the last ~300 ka (thousands of years). The deposits also entomb the Tule Springs Local Fauna (TSLF), one of the most significant late Pleistocene (Rancholabrean) vertebrate assemblages in the American Southwest. The TSLF is both prolific and diverse, and includes a large mammal assemblage dominated by Mammuthus columbiandCamelops hesternus.Two and possibly three distinct species ofEquus,two species ofBison, Panthera atrox, Smilodon fatalis, Canis dirus, Megalonyx jeffersonii,andNothrotheriops shastensis are also present, and newly recognized faunal components include micromammals, amphibians, snakes, and birds. Invertebrates, plant macrofossils, and pollen also occur in the deposits and provide important and complementary paleoenvironmental information. This field compendium highlights some of the classic stratigraphic sequences of the Las Vegas Formation within TUSK, emphasizes the significant hydrologic changes that occurred in the area during the recent geologic past, and examines the subsequent and repeated effect of rapid climate change on the local desert wetland ecosystem.
Actinomyces cavernous sinus infection: a case and systematic literature review
Authors: Lubomski Michal , Dalgliesh James , Lee Kenneth , Damodaran Omprakash , McKew Genevieve , Reddel Stephen
Published: April 2018

A 63-year-old man presented with a 2-month history of progressive right-sided exophthalmos, painful ophthalmoplegia and fevers. As more features developed, he was diagnosed with giant cell arteritis, then Tolosa-Hunt syndrome, and transiently responded to corticosteroids. A bland cerebrospinal fluid and highly metabolically active brain (18F)-fluoro-D-glucose-positron emission tomography suggested lymphoma. Biopsy of the mass showed sulphur granules with Gram-positive filamentous bacteria with Actinomyces-like colonies. Actinomyces cavernous sinus infections are rare and indolent. They often mimic non-infective causes including other inflammatory and infiltrative conditions, vascular and neoplastic causes, particularly lymphoma. Clinicians should consider infective cavernous sinus syndromes in people with a fluctuating painful ophthalmoplegia that responds poorly to corticosteroids. The term Tolosa-Hunt syndrome is problematic and should be retired or used only with reservation.