bluuebunny/crossref_metadata_2025 huggingface dataset:
Isolation and characterization of a prokaryotic cell organelle from the anammox bacterium Kuenenia stuttgartiensis
Authors: Neumann Sarah , Wessels Hans J. C. T. , Rijpstra W. Irene C. , Sinninghe Damsté Jaap S. , Kartal Boran , Jetten Mike S. M. , van Niftrik Laura
Published: October 2014

Anaerobic ammonium oxidizing (anammox) bacteria oxidize ammonium with nitrite to nitrogen gas in the absence of oxygen. These microorganisms form a significant sink for fixed nitrogen in the oceans and the anammox process is applied as a cost‐effective and environment‐friendly nitrogen removal system from wastewater. Anammox bacteria have a compartmentalized cell plan that consists of three separate compartments. Here we report the fractionation of the anammox bacterium Kuenenia stuttgartiensis in order to isolate and analyze the innermost cell compartment called the anammoxosome. The subcellular fractions were microscopically characterized and all membranes in the anammox cell were shown to contain ladderane lipids which are unique for anammox bacteria. Proteome analyses and activity assays with the isolated anammoxosomes showed that these organelles harbor the energy metabolism in anammox cells. Together the experimental data provide the first thorough characterization of a respiratory cell organelle from a bacterium and demonstrate the essential role of the anammoxosome in the production of a major portion of the nitrogen gas in our atmosphere.
Mycobacterium smegmatis BioQ defines a new regulatory network for biotin metabolism
Authors: Tang Qing , Li Xinfeng , Zou Tingting , Zhang Huimin , Wang Yingying , Gao Rongsui , Li Zhencui , He Jin , Feng Youjun
Published: October 2014

Biotin (vitamin H), the sulfur‐containing enzyme cofactor, is an essential micronutrient for three domains of life. Given the fact that biotin is an energetically expensive molecule whose de novo biosynthesis demands 20 ATP equivalents each, it is reasonable that bacteria have evolved diversified mechanisms in various microorganisms to tightly control biotin metabolism. Unlike the Escherichia coli BirA, the prototypical bi‐functional version of biotin protein ligase (BPL) in that it acts as a repressor for biotin biosynthesis pathway, the BirA protein of Mycobacterium smegmatis (M. smegmatis), a closely relative of the tuberculosis‐causing pathogen, Mycobacterium tuberculosis, lacked the DNA‐binding activity. It raised a possibility that an alternative new regulator might be present to compensate the loss of regulatory function. Here we report that this is the case. Genomic context analyses of M. smegmatis detected a newly identified BioQ homolog classified into the TetR family of transcription factor and its recognizable palindromes. The M. smegmatis BioQ protein was overexpressed and purified to homogeneity. Size‐exclusion chromatography combined with chemical cross‐linking studies demonstrated that the BioQ protein had a propensity to dimerize. The promoters of bioFD and bioQ/B were mapped using 5′‐RACE. Electrophoretic mobility shift assays revealed that BioQ binds specifically to the promoter regions of bioFD and bioQ/B. Further DNase I foot‐printing elucidated the BioQ‐binding palindromes. Site‐directed mutagenesis suggested the important residues critical for BioQ/DNA binding. The isogenic mutant of bioQ (ΔbioQ) was generated using the approach of homologous recombination. The in vivo data from the real‐time qPCR combined with the lacZ transcriptional fusion experiments proved that removal of bioQ gave significant increment with expression of bio operons. Also, expression of bio operons were repressed by exogenous addition of biotin, and this repression seemed to depend on the presence of BioQ protein. Thereby, we believed that M. smegmatis BioQ is not only a negative auto‐regulator but also a repressor for bioFD and bioB operons involved in the biotin biosynthesis pathway. Collectively, this finding defined the two‐protein paradigm of BirA and BioQ, representing a new mechanism for bacterial biotin metabolism.
An Ecological View of Whole‐Class Discussions in a Second Language Literature Classroom: Teacher Reformulations as Affordances for Learning
Authors: Thoms Joshua J.
Published: October 2014

This article analyzes whole‐class discussions between a teacher and her students in a Latin American Colonial literature course at the college level. The study is theoretical–exploratory in nature in that it (a) articulates theoretical assumptions inherent in an ecological perspective on second language learning and teaching and (b) attempts to operationalize the affordance construct (van Lier, 2000, 2004) in the context of a second language (L2) literature classroom. The study's findings underscore the importance of teacher reformulations in whole‐class discussions as well as students' engagement with and awareness of the unfolding talk. Furthermore, how the teacher dynamically interacts with one student and his/her contribution potentially affects other students' understanding of the ongoing discussion which, in turn, can influence their comprehension of the literary texts under analysis. Teacher reformulations during whole‐class discussions therefore can serve as affordances for learning. Theoretical implications of the affordance construct, in addition to implications for L2 language and literature teaching, are delineated.
The Effects of Practice Modality on Pragmatic Development in L2 Chinese
Authors: Li Shuai , Taguchi Naoko
Published: October 2014

This study investigated the effects of input‐based and output‐based practice on the development of accuracy and speed in recognizing and producing request‐making forms in L2 Chinese. Fifty American learners of Chinese with intermediate level proficiency were randomly assigned to an input‐based training group, an output‐based training group, or a control group. The input and output groups practiced the target forms over four consecutive days. The control group did not practice the forms. The effects of practice were measured by a Listening Judgment Test (LJT) and an Oral Discourse Completion Test (ODCT). The results showed that the effects of input‐based and output‐based practice were shared across task modalities on measures of performance accuracy (i.e., accuracy in the LJT and ODCT) but not on measures of performance speed (i.e., LJT response times, ODCT planning times, and speech rates).
Investigation of minor species Candida africana, Candida stellatoidea and Candida dubliniensis in the Candida albicans complex among Yaoundé (Cameroon) HIV‐infected patients
Authors: Ngouana Thierry K. , Krasteva Donika , Drakulovski Pascal , Toghueo Rufin K. , Kouanfack Charles , Ambe Akaba , Reynes Jacques , Delaporte Eric , Boyom Fabrice F. , Mallié Michèle , Bertout Sébastien
Published: October 2014

Minor species of the Candida albicans complex may cause overestimation of the epidemiology of C. albicans, and misidentifications could mask their implication in human pathology. Authors determined the occurrence of minor species of the C. albicans complex (C. africana, C. dubliniensis and C. stellatoidea) among Yaoundé HIV‐infected patients, Cameroon. Stool, vaginal discharge, urine and oropharyngeal samples were analysed by mycological diagnosis. Isolates were identified by conventional methods and mass spectrometry (MS; carried out by the matrix‐assisted laser desorption–ionisation time‐of‐flight MS protocol). Candida albicans isolates were thereafter submitted to the PCR amplification of the Hwp1 gene. The susceptibility of isolates to antifungal drugs was tested using the Clinical and Laboratory Standards Institute M27‐A3 protocol. From 115 C. albicans obtained isolates, neither C. dubliniensis nor C. stellatoidea was observed; two strains of C. africana (422PV and 448PV) were identified by PCR electrophoretic profiles at 700 bp. These two C. africana strains were vaginal isolates. The isolate 448PV was resistant to ketoconazole at the minimal inhibitory concentration of 2 μg ml−1, and showed reduced susceptibility to amphotericin B at 1 μg ml−1. This first report on C. africana occurrence in Cameroon brings clues for the understanding of the global epidemiology of this yeast as well as that of minor species of the C. albicans complex.
Paired box gene 8 (PAX8) expression is associated with sonic hedgehog (SHH)/wingless int (WNT) subtypes, desmoplastic histology and patient survival in human medulloblastomas
Authors: Harter Patrick N. , Baumgarten Peter , Zinke Jenny , Schilling Karl , Baader Stefan , Hartmetz Ann‐Kathrin , Schittenhelm Jens , Beschorner Rudi , Liebner Stefan , Schulte Dorothea , Plate Karl‐Heinz , Gutwein Paul , Korshunov Andrey , Pfister Stefan M. , Jones David T. W. , Doberstein Kai , Mittelbronn Michel
Published: October 2014

Aims

The paired box gene 8 (PAX8) plays crucial roles in organ patterning and cellular differentiation during development and tumorigenesis. Although its function is partly understood in vertebrate development, there is poor data concerning human central nervous system (CNS) development and brain tumours.

Methods

We investigated developing human (n = 19) and mouse (n = 3) brains as well as medulloblastomas (MBs) (n = 113) for PAX8 expression by immunohistochemistry. Human MB cell lines were assessed for PAX8 expression using polymerase chain reaction and immunoblotting and analysed for growth and migration following PAX8 knock‐down by small interfering ribonucleic acid (siRNA).

Results

PAX8 protein expression was associated with germinal layers in human and murine forebrain and hindbrain development. PAX8 expression significantly decreased over time in the external granule cell layer but increased in the internal granule cell layer. In MB subtypes, we observed an association of PAX8 expression with sonic hedgehog (SHH) and wingless int subtypes but not with group 3 and 4 MBs. Beyond that, we detected high PAX8 levels in desmoplastic MB subtypes. Univariate analyses revealed high PAX8 levels as a prognostic factor associated with a significantly better patient prognosis in human MB (overall survival: Log‐Rank P = 0.0404, Wilcoxon P = 0.0280; progression‐free survival: Log‐Rank P = 0.0225; Wilcoxon P = 0.0136). In vitro assays revealed increased proliferation and migration of MB cell lines after PAX8 siRNA knock‐down.

Conclusion

In summary, high PAX8 expression is linked to better prognosis in MBs potentially by suppressing both proliferative and migratory properties of MB cells. The distinct spatio‐temporal expression pattern of PAX8 during brain development might contribute to the understanding of distinct MB subtype histogenesis.
Case of subacute cerebellar ataxia with anti‐glutamic acid decarboxylase antibodies in cerebrospinal fluid, but not in serum
Authors: Takino Toru , Fukushima Takao , Yanagimura Fumihiro , Makino Kunihiko
Published: October 2014

A 67‐year‐old woman presented with dysarthria and trunk and limb ataxia, which progressed in a subacute manner. Anti‐glutamic acid decarboxylase antibodies were negative in the serum, but were detected in the cerebrospinal fluid. Steroid pulse therapy was administered on the suspicion that the presence of anti‐glutamic acid decarboxylase antibodies in the cerebrospinal fluid might be associated with cerebellar ataxia. Treatment resulted in a marked improvement in clinical symptoms, leading to a diagnosis of anti‐glutamic acid decarboxylase antibody‐positive cerebellar ataxia. The outcome showed that measuring anti‐glutamic acid decarboxylase antibodies levels in the cerebrospinal fluid is important, even when levels are negative in the serum.
Is Bigger Better? Activity and Success in Negotiations in the United Nations General Assembly
Authors: Panke Diana
Published: October 2014

Theorists often claim that being bigger than one's counterparts offers advantages in multilateral negotiations. In this article, I examine that argument using data from negotiations in the United Nations General Assembly (UNGA). The article analyzes and compares the activity levels of smaller and larger states in international negotiations, and sheds light on the conditions under which the latter “punch below their weight.”

My analysis indicates that size directly affects participation, but not success rates. Bigger states can better formulate national positions on a broad range of issues, enabling their diplomats to more actively participate in negotiations, while smaller states are absent more often. Activity is conducive to success, which helps bigger states. But not every negotiation strategy is equally effective. In the UNGA's one‐state, one‐vote context, bigger states are not able to systematically exert disproportionate influence despite their often superior financial resources and bargaining strategies.
Creativity in Court‐Connected Mediation: Myth or Reality?
Authors: Adrian Lin , Mykland Solfrid
Published: October 2014

In this study, we examined creativity in court‐connected mediation. We analyzed 129 mediated agreements from civil cases in Norway and Denmark and compared the outcomes with the parties' original claims to determine whether the agreement addressed only the disputants' demands or contained other elements. If the mediated agreements contained elements in addition to the original claims, we considered them to be “creative.” We devised a creativity scale and found that approximately two thirds of the cases contained creative elements and one quarter of them contained more than five creative elements.

We then sought to determine which aspects of the mediation promoted creativity by looking at a variety of mediation characteristics (length of mediation, characteristics of the parties, etc.). We found that lengthier mediations tended to feature more creativity as did cases that involved two private individuals rather than businesses. Cases whose issues involved inheritance as well as the division of property following divorce seemed to foster the highest levels of creativity. Finally, we found that the amount of money at issue also seemed to be relevant: the highest levels of creativity were found in cases in which more money was at stake. In this article, we also discuss the implications of our findings for future research, practice, and training.
Questioning the association between bisphosphonates and atypical femoral fractures
Authors: Pazianas Michael , Kim Se‐min , Yuen Tony , Sun Li , Epstein Sol , Zaidi Mone
Published: October 2014

Bisphosphonates are the first‐line treatment for osteoporosis. Structurally, they are stable analogues of pyrophosphate and therefore exhibit a high affinity for bone mineral. They reduce bone loss by attenuating the ability of the osteoclast to resorb bone, decreasing activation frequency, and the rate of remodeling. Large prospective randomized placebo‐control trials provide unequivocal evidence for a reduction in the incidence of fractures. Impressively, 40 years since their first use in patients, the safety profile of bisphosphonates has been equally reassuring. Questions have arisen lately as to whether bisphosphonates could cause atypical fractures, a rare type of atraumatic or minimal trauma femur fracture occurring below the great trochanter. This question has prompted calls for a broader examination of the long‐term effects of bisphosphonate use. An attempt by the Food and Drug Administration to garner consensus and provide definitive views was not successful. This has led to continued anxiety among treating physicians and patients alike, resulting in an overall reduction in prescriptions for bisphosphonates and for osteoporosis therapies in general. Here, we provide an overview of the current data on atypical fractures and bisphosphonate use.
Calcium concentration in hypoxic–ischemic encephalopathy during hypothermia
Authors: Yamamoto Yutaka , Ibara Satoshi , Tokuhisa Takuya , Hirakawa Eiji , Yoneda Satoshi , Kobayashi Kosuke , Kato Eiji , Maruyama Yuko , Maede Yoshinobu , Kuwabara Takako
Published: October 2014

Background

The aim of this study was to investigate the relationship between prognosis and the changes in serum‐ionized calcium concentration in neonates with hypoxic–ischemic encephalopathy (HIE) before and during brain hypothermia (BHT).

Methods

Serum samples were obtained from 16 HIE neonates who underwent BHT. All patients underwent developmental testing at 18 months of age.

Results

Mean serum‐ionized calcium concentration in the poor outcome group (developmental quotient [DQ], <80; nine infants) was significantly lower than in the good outcome group (DQ >80; seven infants), both immediately before and after 6 h of BHT. Mean serum‐ionized calcium concentration significantly decreased in both groups for 6 h, and the lowest adjusted serum‐ionized calcium during 6 h of BHT was <1.05 mmol/L, known as the cut‐off value for poor outcome, in 57.1% of the good outcome group.

Conclusion

The influx of calcium into cells continues regardless of neurological prognosis during the early phase of BHT, but BHT might protect some high‐risk patients against neurological damage at low adjusted serum‐ionized calcium concentration.
Reproducing under a warming climate: long winter flowering and extended flower longevity in the only Mediterranean and maritime Primula
Authors: Aronne G. , Buonanno M. , De Micco V.
Published: October 2014

Under the pressure of global warming, general expectations of species migration and evolution of adaptive traits should always be confirmed with species‐specific studies. Within this framework, some species can be used as study systems to predict possible consequences of global warming also on other relatives. Unlike its mountain congeneric, Primula palinuri Petagn. has endured all the climatic fluctuations since the Pleistocene, while surviving on Mediterranean coastal cliffs. The aim of this work was to investigate the possible evolution of reproductive biological and ecological traits in P. palinuri adaptation to a warmer environment. Data showed that flowering starts in mid‐winter; single flowers remain open for over a month, changing from pendulous to erect. The number of insects visiting flowers of P. palinuri increases during the flowering season, and pollination reduces flower longevity. Overall, the best pollen performances, in terms of viability and germinability, occur at winter temperatures, while pollinator activity prolongs flowering until spring. Moreover, extended longevity of single flowers optimises reproductive success. Both phenotypic plasticity and selective processes might have occurred in P. palinuri. However, we found that reproductive traits of the only Mediterranean Primula remain more associated with cold mountain habitats than warm coastal cliffs. Given the rapid trend of climate warming, migration and new adaptive processes in P. palinuri are unlikely. Response to past climate warming of P. palinuri provides useful indications for future scenarios in other Primula species.
Proteomic analysis of residual proteins in blades and petioles of fallen leaves of Brassica napus
Authors: Desclos‐Théveniau M. , Coquet L. , Jouenne T. , Etienne P.
Published: October 2014

Brassica napus L. is an important crop plant, characterised by high nitrogen (N) levels in fallen leaves, leading to a significant restitution of this element to the soil, with important consequences at the economic and environmental levels. It is now well established that the N in fallen leaves is due to weak N remobilisation that is especially related to incomplete degradation of foliar proteins during leaf senescence. Identification of residual proteins in a fallen leaf (i.e. incompletely degraded in the last step of the N remobilisation process) constitutes important information for improving nutrient use efficiency. Proteome analysis of the vascular system (petioles) and blades from fallen leaves of Brassica napus was performed, and the 30 most abundant residual proteins in each tissue were identified. Among them, several proteins involved in N recycling remain in the leaf after abscission. Moreover, this study reveals that some residual proteins are associated with energy metabolism, protection against oxidative stress, and more surprisingly, photosynthesis. Finally, comparison of blade and petiole proteomes show that, despite their different physiological roles in the non‐senescing leaf, both organs redirect their metabolism in order to ensure catabolic reactions. Taken together, the results suggest that a better degradation of these leaf proteins during the senescence process could enable improvements in the N use efficiency of Brassica napus.
Are tyrosine residues involved in the photoconversion of the water‐soluble chlorophyll‐binding protein ofChenopodium album?
Authors: Takahashi S. , Seki Y. , Uchida A. , Nakayama K. , Satoh H.
Published: October 2014

Non‐photosynthetic and hydrophilic chlorophyll (Chl) proteins, called water‐solubleChl‐binding proteins (WSCPs), are distributed in various species ofChenopodiaceae,Amaranthaceae,Polygonaceae andBrassicaceae. Based on their photoconvertibility,WSCPs are categorised into two classes: Class I (photoconvertible) and Class II (non‐photoconvertible).Chenopodium albumWSCP(CaWSCP; Class I) is able to convert the chlorin skeleton ofChlainto a bacteriochlorin‐like skeleton under light in the presence of molecular oxygen. Potassium iodide (KI) is a strong inhibitor of the photoconversion. BecauseKIattacks tyrosine residues in proteins, tyrosine residues inCaWSCPare considered to be important amino acid residues for the photoconversion. Recently, we identified the gene encodingCaWSCPand found that the mature region ofCaWSCPcontained four tyrosine residues:Tyr13,Tyr14,Tyr87 andTyr134. To gain insight into the effect of the tyrosine residues on the photoconversion, we constructed 15 mutant proteins (Y13A, Y14A, Y87A, Y134A, Y13‐14A, Y13‐87A, Y13‐134A, Y14‐87A, Y14‐134A, Y87‐134A, Y13‐14‐87A, Y13‐14‐134A, Y13‐87‐134A, Y14‐87‐134A and Y13‐14‐87‐134A) using site‐directed mutagenesis. Amazingly, all the mutant proteins retained not only chlorophyll‐binding activity, but also photoconvertibility. Furthermore, we found thatKIstrongly inhibited the photoconversion of Y13‐14‐87‐134A. These findings indicated that the four tyrosine residues are not essential for the photoconversion.
Clinical characteristics of pulmonary arteriovenous malformations in Koreans
Authors: Kim Hyun‐Jung , Lee Jae‐Seung , Oh Yeon‐Mok , Shim Tae‐Sun , Lim Chae‐Man , Koh Youn‐Suck , Kim Woo‐Sung , Lee Sang‐Do
Published: October 2014

Background and objective

Although pulmonary arteriovenous malformations (PAVMs) are rare, they are important in clinical practice because they are associated with life‐threatening complications such as brain abscess, stroke and lung haemorrhage. The aims of the present study were to characterize PAVMs in a Korean population and to examine the incidence and factors associated with cerebral complications, which are a major cause of mortality.

Methods

The medical records of patients with PAVMs between 2000 and 2013 were retrospectively reviewed. PAVMs were confirmed by enhanced chest computed tomography or by pulmonary angiography.

Results

Ninety patients (median age, 47.5 years; 81.8% female) with PAVMs were included. Twelve patients (13.3%) were clinically diagnosed with hereditary haemorrhagic telangiectasia (HHT) according to the Curacao criteria. Sixty‐three patients underwent transcatheter embolization with no severe adverse events. Three patients required retreatment during a mean follow‐up period of 3.3 years. Six and 14 patients suffered brain abscess or stroke, respectively, as a complication of PAVMs. These complications were not associated with the diameter of the arteries feeding the PAVMs (odds ratio, 1.106; 95% confidence interval, 0.895–1.366; P = 0.352)

Conclusions

PAVMs are less associated with HHT in Koreans than in Western populations. Transcatheter embolization of PAVMs is safe and effective, and physicians need to consider treating the small arteries feeding PAVMs to prevent cerebral complications.
Effects of short flexible seagrass Zostera noltei on flow, erosion and deposition processes determined using flume experiments
Authors: Ganthy Florian , Soissons Laura , Sauriau Pierre‐Guy , Verney Romaric , Sottolichio Aldo
Published: October 2014

Innovative flume experiments were conducted in a recirculating straight flume. Zostera noltei meadows were sampled in their natural bed sediments in the field at contrasting stages of their seasonal growth. The aims of this study were: (i) to quantify the combined effects of leaf flexibility and development characteristics of Zostera noltei canopies on their interaction with hydrodynamics; and (ii) to quantify the role of Zostera noltei meadows in suspended sediment trapping and bed sediment resuspension related with changes in hydrodynamic forcing caused by the seasonal development of seagrasses. Velocity within the canopy was significantly damped. The attenuation in velocity ranged from 34 to 87% compared with bare sediments and was associated with a density threshold resulting from the flow‐induced canopy reconfiguration. The reduction in flow was higher in dense canopies at higher velocities than in less dense canopies, in which the reduction in flow was greater at low velocities. These contrasted results can be explained by competition between a rough‐wall boundary layer caused by the bed and a shear layer caused by the canopy. The velocity attenuation was associated with a two to three‐fold increase in bottom shear stress compared with unvegetated sediment. Despite the increase in near‐bed turbulence, protection of the sediment against erosion increased under a fully developed meadow, while sediment properties were found to be the main factor controlling erosion in a less developed meadow. Deposition fluxes were higher on the vegetated bed than on bare sediments, and these fluxes increased with leaf density. Fewer freshly deposited sediments were resuspended in vegetated beds, resulting in an increase in net sediment deposition with meadow growth. However, in the case of a very high leaf area index, sediment was mostly deposited on leaves, which facilitated subsequent resuspension and resulted in less efficient sediment trapping than in the less developed meadow.
On False Discovery and Non‐discovery Proportions of the Dynamic Adaptive Procedure
Authors: Xin‐Bing Kong , Qin‐Feng Xu
Published: October 2014

This paper studies the asymptotic behaviour of the false discovery and non‐discovery proportions of the dynamic adaptive procedure under some dependence structure. A Bahadur‐type representation of the cut point in simultaneously performing a large scale of tests is presented. The asymptotic bias decompositions of the false discovery and non‐discovery proportions are given under some dependence structure. In addition to existing literatures, we find that the randomness due to the dynamic selection of the tuning parameter in estimating the true null rate serves as a source of the approximation error in the Bahadur representation and enters into the asymptotic bias term of the false discovery proportion and those of the false non‐discovery proportion. The theory explains to some extent why some seemingly attractive dynamic adaptive procedures do not outperform the competing fixed adaptive procedures substantially in some situations. Simulations justify our theory and findings.
Management by Knowledge in Practice – Implementation of National Healthcare Guidelines in Sweden
Authors: Kalkan Almina , Sandberg Johanna , Garpenby Peter
Published: October 2014

In the last ten years, the concept of management by knowledge has gained growing attention in Swedish healthcare, as well as internationally. In Sweden, the most prominent example of management by knowledge is the National Guidelines, aimed at influencing both clinical and political decision‐making in the health sector. The objective of this article is to explore the response among four Swedish county councils to the National Guidelines for Cardiac Care (NGCC). Empirical material was collected through 155 expert interviews with the target groups of the NGCC, politicians, administrators and clinical managers. Analysis of the responses to this multifaceted policy instrument was addressed by drawing on implementation theory (Matland 1995) and institutional theory (Oliver 1991). The NGCC are primarily based on the voluntary diffusion of norms. The county councils are a long way from having adapted all the means suggested by the National Board of Health and Welfare (NBHW): explicit prioritization, healthcare programmes and dialogue between the various actor groups. The high degree of ambiguity in the content of the NGCC, the inherent conflict and the multiplicity and uncertainty in the context of the county councils, have often resulted in avoidance and compromise. The strategic responses we observe can be viewed as an attempt to balance multiple constituents and achieve the various internal organizational goals. The ambiguity and conflict inherent in the policy of the NGCC influence the strategic responses made by the organization. The question remains how far management by knowledge can be applied in a political context.
Does Baumol's Cost Disease Account for Nonfederal Public‐Sector Cost Growth in the United States? A New Test of an Old Idea*
Authors: Bates Laurie J. , Santerre Rexford E.
Published: October 2014

Objectives

To examine if Baumol's cost disease of the service sector offers an explanation for the growth of state and local government costs in the United States.

Methods

The study tests whether state‐wide increases in wage rates relative to productivity influence the growth of state and local government spending using a relatively new econometric test along with a panel data set of the 50 states over the period from 1980 to 2009.

Results

Findings are robust to various multiple regression specifications and show that Baumol's cost disease does account for some of the growth of state and local government costs over time.

Conclusion

Unless the delivery of public services takes on a more capital‐intensive process or is absorbed by the private sector, the implication is that consumer‐voters should become better accustomed to the government sector comprising an increasingly larger proportion of their state and local economies over time.
Character state‐based taxa erected to accommodate fossil and extant needle stoneflies (Leuctridae – Leuctrida tax.n.) and close relatives
Authors: BÉTHOUX OLIVIER , KONDRATIEFF BORIS , GRÍMSSON FRIÐGEIR , ÓLAFSSON ERLING , WAPPLER TORSTEN
Published: October 2014

In order to accommodate a newly discovered fossil specimen related to a subset of extant needle stoneflies (Leuctridae sensu Zwick, 2000), we provide a comparative analysis of the wing venation of these insects, and of their close relatives, primarily based on extant material. A number of character states potentially supporting monophyletic taxa are identified, and are used to erect taxon names under the cladotypic nomenclatural procedure. We introduce a new standard definition in which the mention of the antonym of the defining character state is applied. The proposed taxa, and taxa inclusiveness, are as follows: Nemouromorpha > Capniida/Leuctrida/‘Nemouridae s.l.’, and Leuctrida > Exeleuctrida > Mioleuctrida & Eleuctrida > Collaleuctrida. This scheme allowed us to tentatively accommodate several fossil species described earlier and the new specimen, left undetermined at the genus and species levels, but assigned to Collaleuctrida. To optimize retrieval of hierarchical information, we introduce the use of ‘nec’ (Latin for ‘but not’) into the taxonomic address to indicate exclusion from a taxon. For example, Mioleuctrida nec Collaleuctrida †yehae indicates that †yehae can be assigned to Mioleuctrida but can also be conclusively excluded from Collaleuctrida. Based on the investigated case, it is finally argued that the cladotypic nomenclatural procedure is optimal regarding name use and numbers, and allows adequate treatment of homoplasy.
When to consider transfusion therapy for patients with non‐transfusion‐dependent thalassaemia
Authors: Taher A. T. , Radwan A. , Viprakasit V.
Published: October 2014

Non‐transfusion‐dependent thalassaemia (NTDT) refers to all thalassaemia disease phenotypes that do not require regular blood transfusions for survival. Thalassaemia disorders were traditionally concentrated along the tropical belt stretching from sub‐Saharan Africa through the Mediterranean region and the Middle East to South and South‐East Asia, but global migration has led to increased incidence in North America and Northern Europe. Transfusionists may be familiar with β‐thalassaemia major because of the lifelong transfusions needed by these patients. Although patients with NTDT do not require regular transfusions for survival, they may require transfusions in some instances such as pregnancy, infection or growth failure. The complications associated with NTDT can be severe if not properly managed, and many are directly related to chronic anaemia. Awareness of NTDT is important, and this review will outline the factors that should be taken into consideration when deciding whether to initiate and properly plan for transfusion therapy in these patients in terms of transfusion interval and duration of treatment.
On families of 7- and 11-congruent elliptic curves
Authors: Fisher Tom
Published: October 2014

We use an invariant-theoretic method to compute certain twists of the modular curves $\def \xmlpi #1{}\def \mathsfbi #1{\boldsymbol {\mathsf {#1}}}\let \le =\leqslant \let \leq =\leqslant \let \ge =\geqslant \let \geq =\geqslant \def \Pr {\mathit {Pr}}\def \Fr {\mathit {Fr}}\def \Rey {\mathit {Re}}X(n)$ for $n=7,11$. Searching for rational points on these twists enables us to find non-trivial pairs of $n$-congruent elliptic curves over ${\mathbb{Q}}$, that is, pairs of non-isogenous elliptic curves over ${\mathbb{Q}}$ whose $n$-torsion subgroups are isomorphic as Galois modules. We also find a non-trivial pair of 11-congruent elliptic curves over ${\mathbb{Q}}(T)$, and hence give an explicit infinite family of non-trivial pairs of 11-congruent elliptic curves  over ${\mathbb{Q}}$.

Supplementary materials are available with this article.
Peripheral pain is enhanced by insulin-like growth factor 1 through a G protein–mediated stimulation of T-type calcium channels
Authors: Zhang Yuan , Qin Wenjuan , Qian Zhiyuan , Liu Xingjun , Wang Hua , Gong Shan , Sun Yan-Gang , Snutch Terrance P. , Jiang Xinghong , Tao Jin
Published: October 2014

Blocking insulin-like growth factor–induced stimulation of a calcium channel in sensory neurons may be a therapeutic target in pain disorders.
Tyrosine phosphorylation of NEDD4 activates its ubiquitin ligase activity
Authors: Persaud Avinash , Alberts Philipp , Mari Sara , Tong Jiefei , Murchie Ryan , Maspero Elena , Safi Frozan , Moran Michael F. , Polo Simona , Rotin Daniela
Published: October 2014

The receptor tyrosine kinases FGFR1 and EGFR promote phosphorylation of the ubiquitin ligase NEDD4, leading to activation of its catalytic activity.
Excess Signaling Is Bad for the Aging Brain
Authors: Ray L. Bryan
Published: October 2014

Excess signaling by type I interferon contributes to cognitive decline in aged mice.
Mapping Human Drug Targets in the Cell
Authors: Vinson Valda
Published: October 2014

Monitoring drug effects on the thermal profile of a cell’s proteins identifies drug targets and off-targets.
Swim Away from the Light
Authors: Berndt Jason D.
Published: October 2014

Melatonin signaling controls circadian swimming behaviors in zooplankton.
Rifampin Induces Hydroxyl Radical Formation in Mycobacterium tuberculosis
Authors: Piccaro Giovanni , Pietraforte Donatella , Giannoni Federico , Mustazzolu Alessandro , Fattorini Lanfranco
Published: October 2014

The antituberculosis (anti-TB) drug rifampin (RIF) binds to the beta subunit of the RNA polymerase (RpoB) of
Mycobacterium tuberculosis
, but the bactericidal responses triggered after target interaction are not known. To evaluate whether RIF induced an oxidative burst, lysates of RIF-treated
M. tuberculosis
were tested for determination of reactive oxygen species (ROS) by the electron paramagnetic resonance (EPR) technique using 1-hydroxy-3-carboxy-pyrrolidine (CPH) and 5,5-dimethyl-1-pyrrolidine-
N
-oxide (DMPO) as spin traps.
M. tuberculosis
killing by RIF stimulated an increase in the rate of formation of the CPH radical (CP·). Lysate pretreatment with the O
2
·
−
and ·OH scavengers superoxide dismutase (SOD) and thiourea (THIO), respectively, or with the metal chelator diethylene triamine pentaacetic acid (DTPA) inhibited CP· formation, arguing in favor of a metal-catalyzed ROS response. Formation of CP· did not increase following treatment of RIF-resistant strains with RIF, indicating that the ROS were induced after RpoB binding. To identify the ROS formed, lysates of RIF-treated bacilli were incubated with DMPO, a spin trap specific for ·OH and O
2
·
−
, with or without pretreatment with SOD, catalase, THIO, or DTPA. Superoxide dismutase, catalase, and THIO decreased formation of the DMPO-OH adduct, and SOD plus DTPA completely suppressed it, suggesting that RIF activated metal-dependent O
2
·
−
-mediated mechanisms producing ·OH inside tubercle bacilli. The finding that the metal chelator DTPA reduced the bactericidal activity of RIF supported the possibility that ·OH was generated through these mechanisms and that it participated at least in part in
M. tuberculosis
killing by the drug.
Heterogeneity of
mprF
Sequences in Methicillin-Resistant Staphylococcus aureus Clinical Isolates: Role in Cross-Resistance between Daptomycin and Host Defense Antimicrobial Peptides
Authors: Bayer Arnold S. , Mishra Nagendra N. , Sakoulas George , Nonejuie Poochit , Nast Cynthia C. , Pogliano Joseph , Chen Kuan-Tsen , Ellison Steven N. , Yeaman Michael R. , Yang Soo-Jin
Published: October 2014

Over the past several years, single-nucleotide polymorphisms (SNPs) within the
mprF
open reading frame (ORF) have been proposed to be associated with a gain-of-function phenotype in terms of daptomycin (DAP) nonsusceptibility (referred to as daptomycin resistance [DAP-R] herein for ease of presentation) in
Staphylococcus aureus
. We investigated the frequencies of SNPs within the
mprF
ORF and the relationships of such SNPs to cross-resistance between DAP and cationic host defense peptides (HDPs). Thirty-five well-characterized, unique DAP-susceptible (DAP-S) and DAP-R methicillin-resistant
S. aureus
(MRSA) isolates of the clonal complex 5 genotype were used. In addition to
mprF
SNPs and DAP-HDP cross-resistance, several other key genotypic and phenotypic metrics often associated with DAP-R were delineated, as follows: (i)
mprF
expression, (ii) membrane phospholipid content, (iii) positive surface charge, (iv) DAP binding, and (v) cell wall thickness profiles. A number of DAP-S strains (MICs of ≤1 μg/ml) exhibited
mprF
SNPs, occasionally with high-level
mprF
sequence variation from the genotype reference strain. However, none of these SNPs were localized to well-chronicled
mprF
hot spot locations associated with DAP-R in
S. aureus
. In contrast, all 8 DAP-R isolates demonstrated SNPs within such known
mprF
hot spots. Moreover, only the DAP-R strains showed MprF gain-of-function phenotypes, enhanced
mprF
expression, higher survival against two prototypical HDPs, and reduced DAP binding. Although a heterogenous array of
mprF
SNPs were often found in DAP-S strains, only selected hot spot SNPs, combined with concurrent
mprF
dysregulation, were associated with the DAP-R phenotype.
Triazole-Based Compound as a Candidate To Develop Novel Medicines To Treat Toxoplasmosis
Authors: Dzitko Katarzyna , Paneth Agata , Plech Tomasz , Pawełczyk Jakub , Węglińska Lidia , Paneth Piotr
Published: October 2014

This article reports anti-
Toxoplasma gondii
activity of 3-(thiophen-2-yl)-1,2,4-triazole-5-thione. The compound displayed significant and reproducible antiparasitic effects at nontoxic concentrations for the host cells, with an experimentally determined 50% inhibitory concentration (IC
50
) at least 30 times better than that of the known chemotherapeutic agent sulfadiazine. Purine nucleoside phosphorylase was defined as the probable target for anti-
Toxoplasma
activity of the tested compound. These results provide the foundation for future work to develop a new class of medicines to better treat toxoplasmosis.
Antibacterial Properties of Magnesium
In Vitro
and in an
In Vivo
Model of Implant-Associated Methicillin-Resistant Staphylococcus aureus Infection
Authors: Li Yang , Liu Guangwang , Zhai Zanjing , Liu Lina , Li Haowei , Yang Ke , Tan Lili , Wan Peng , Liu Xuqiang , Ouyang Zhengxiao , Yu Zhifeng , Tang Tingting , Zhu Zhenan , Qu Xinhua , Dai Kerong
Published: October 2014

Periprosthetic infection remains a challenging clinical complication. We investigated the antibacterial properties of pure (99.9%) magnesium (Mg)
in vitro
and in an
in vivo
rat model of implant-related infection. Mg was highly effective against methicillin-resistant
Staphylococcus aureus
-induced osteomyelitis and improved new peri-implant bone formation. Bacterial
icaA
and
agr
RNAIII transcription levels were also assessed to characterize the mechanism underlying the antibacterial properties of the Mg implant.
Mycoplasma pneumoniae Modulates STAT3-STAT6/EGFR-FOXA2 Signaling To Induce Overexpression of Airway Mucins
Authors: Hao Yonghua , Kuang Zhizhou , Jing Jia , Miao Jinfeng , Mei Li Yu , Lee Ryan J. , Kim Susie , Choe Shawn , Krause Duncan C. , Lau Gee W.
Published: October 2014

Aberrant mucin secretion and accumulation in the airway lumen are clinical hallmarks associated with various lung diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis.
Mycoplasma pneumoniae
, long appreciated as one of the triggers of acute exacerbations of chronic pulmonary diseases, has recently been reported to promote excessive mucus secretion. However, the mechanism of mucin overproduction induced by
M. pneumoniae
remains unclear. This study aimed to determine the mechanism by which
M. pneumoniae
induces mucus hypersecretion by using
M. pneumoniae
infection of mouse lungs, human primary bronchial epithelial (NHBE) cells cultured at the air-liquid interface, and the conventionally cultured airway epithelial NCI-H292 cell line. We demonstrated that
M. pneumoniae
induced the expression of mucins MUC5AC and MUC5B by activating the STAT6-STAT3 and epidermal growth factor receptor (EGFR) signal pathways, which in turn downregulated FOXA2, a transcriptional repressor of mucin biosynthesis. The upstream stimuli of these pathways, including interleukin-4 (IL-4), IL-6, and IL-13, increased dramatically upon exposure to
M. pneumoniae
. Inhibition of the STAT6, STAT3, and EGFR signaling pathways significantly restored the expression of FOXA2 and attenuated the expression of airway mucins MUC5AC and MUC5B. Collectively, these studies demonstrated that
M. pneumoniae
induces airway mucus hypersecretion by modulating the STAT/EGFR-FOXA2 signaling pathways.
Contribution of the Interaction of Streptococcus mutans Serotype
k
Strains with Fibrinogen to the Pathogenicity of Infective Endocarditis
Authors: Nomura Ryota , Otsugu Masatoshi , Naka Shuhei , Teramoto Noboru , Kojima Ayuchi , Muranaka Yoshinori , Matsumoto-Nakano Michiyo , Ooshima Takashi , Nakano Kazuhiko
Published: October 2014

Streptococcus mutans
, a pathogen responsible for dental caries, is occasionally isolated from the blood of patients with bacteremia and infective endocarditis (IE). Our previous study demonstrated that serotype
k
-specific bacterial DNA is frequently detected in
S. mutans
-positive heart valve specimens extirpated from IE patients. However, the reason for this frequent detection remains unknown. In the present study, we analyzed the virulence of IE from
S. mutans
strains, focusing on the characterization of serotype
k
strains, most of which are positive for the 120-kDa cell surface collagen-binding protein Cbm and negative for the 190-kDa protein antigen (PA) known as SpaP, P1, antigen I/II, and other designations. Fibrinogen-binding assays were performed with 85 clinical strains classified by Cbm and PA expression levels. The Cbm
+
/PA
−
group strains had significantly higher fibrinogen-binding rates than the other groups. Analysis of platelet aggregation revealed that SA31, a Cbm
+
/PA
−
strain, induced an increased level of aggregation in the presence of fibrinogen, while negligible aggregation was induced by the Cbm-defective isogenic mutant SA31CBD. A rat IE model with an artificial impairment of the aortic valve created using a catheter showed that extirpated heart valves in the SA31 group displayed a prominent vegetation mass not seen in those in the SA31CBD group. These findings could explain why Cbm
+
/PA
−
strains are highly virulent and are related to the development of IE, and the findings could also explain the frequent detection of serotype
k
DNA in
S. mutans
-positive heart valve clinical specimens.
Anaplasma marginale Superinfection Attributable to Pathogen Strains with Distinct Genomic Backgrounds
Authors: Vallejo Esquerra Eduardo , Herndon David R. , Alpirez Mendoza Francisco , Mosqueda Juan , Palmer Guy H.
Published: October 2014

Strain superinfection occurs when a second pathogen strain infects a host already infected with a primary strain. The selective pressures that drive strain divergence, which underlies superinfection, and allow penetration of a new strain into a host population are critical knowledge gaps relevant to shifts in infectious disease epidemiology. In regions of endemicity with a high prevalence of infection, broad population immunity develops against
Anaplasma marginale
, a highly antigenically variant rickettsial pathogen, and creates strong selective pressure for emergence of and superinfection with strains that differ in their Msp2 variant repertoires. The strains may emerge either by
msp2
locus duplication and allelic divergence on an existing genomic background or by introduction of a strain with a different
msp2
allelic repertoire on a distinct genomic background. To answer this question, we developed a multilocus typing assay based on high-throughput sequencing of non-
msp2
target loci to distinguish among strains with different genomic backgrounds. The technical error level was statistically defined based on the percentage of perfect sequence matches of clones of each target locus and validated using experimental single strains and strain pairs. Testing of
A. marginale
-positive samples from tropical regions where
A. marginale
infection is endemic identified individual infections that contained unique alleles for all five targeted loci. The data revealed a highly significant difference in the number of strains per animal in the tropical regions compared to infections in temperate regions and strongly supported the hypothesis that transmission of genomically distinct
A. marginale
strains predominates in high-prevalence areas of endemicity.