bluuebunny/crossref_metadata_2025 huggingface dataset:
Type‐II NADH:quinone oxidoreductase from Staphylococcus aureus has two distinct binding sites and is rate limited by quinone reduction
Authors: Sena Filipa V. , Batista Ana P. , Catarino Teresa , Brito José A. , Archer Margarida , Viertler Martin , Madl Tobias , Cabrita Eurico J. , Pereira Manuela M.
Published: July 2015

A prerequisite for any rational drug design strategy is understanding the mode of protein–ligand interaction. This motivated us to explore protein–substrate interaction in Type‐II NADH:quinone oxidoreductase (NDH‐2) from Staphylococcus aureus, a worldwide problem in clinical medicine due to its multiple drug resistant forms. NDHs‐2 are involved in respiratory chains and recognized as suitable targets for novel antimicrobial therapies, as these are the only enzymes with NADH:quinone oxidoreductase activity expressed in many pathogenic organisms.

We obtained crystal and solution structures of NDH‐2 from S. aureus, showing that it is a dimer in solution. We report fast kinetic analyses of the protein and detected a charge‐transfer complex formed between NAD+ and the reduced flavin, which is dissociated by the quinone. We observed that the quinone reduction is the rate limiting step and also the only half‐reaction affected by the presence of HQNO, an inhibitor. We analyzed protein–substrate interactions by fluorescence and STD‐NMR spectroscopies, which indicate that NADH and the quinone bind to different sites.

In summary, our combined results show the presence of distinct binding sites for the two substrates, identified quinone reduction as the rate limiting step and indicate the establishment of a NAD+‐protein complex, which is released by the quinone.
The Clostridium difficile cell wall protein CwpV confers phase‐variable phage resistance
Authors: Sekulovic Ognjen , Ospina Bedoya Maicol , Fivian‐Hughes Amanda S. , Fairweather Neil F. , Fortier Louis‐Charles
Published: July 2015

Bacteriophages are present in virtually all ecosystems, and bacteria have developed multiple antiphage strategies to counter their attacks. Clostridium difficile is an important pathogen causing severe intestinal infections in humans and animals. Here we show that the conserved cell‐surface protein CwpV provides antiphage protection in C. difficile. This protein, for which the expression is phase‐variable, is classified into five types, each differing in their repeat‐containing C‐terminal domain. When expressed constitutively from a plasmid or the chromosome of locked ‘ON’ cells of C. difficile R20291, CwpV conferred antiphage protection. Differences in the level of phage protection were observed depending on the phage morphological group, siphophages being the most sensitive with efficiency of plaquing (EOP) values of < 5 × 10−7 for phages ϕCD38‐2, ϕCD111 and ϕCD146. Protection against the myophages ϕMMP01 and ϕCD52 was weaker, with EOP values between 9.0 × 10−3 and 1.1 × 10−1. The C‐terminal domain of CwpV carries the antiphage activity and its deletion, or part of it, significantly reduced the antiphage protection. CwpV does not affect phage adsorption, but phage DNA replication is prevented, suggesting a mechanism reminiscent of superinfection exclusion systems normally encoded on prophages. CwpV thus represents a novel ubiquitous host‐encoded and phase‐variable antiphage system in C. difficile.
Kranke Frauen
Authors: Potter Edward T.
Published: July 2015

Hypochondria in literature serves as a metaphoric means of negotiating norms relating to gender roles and marriage. Mid‐eighteenth‐century physicians understood hypochondria as a physical disease with emotional and mental components with a broad spectrum of possible causes. At the same time, comedic dramatists such as Luise Adelgunde Victoria Gottsched (1713–1762) and Christian Fürchtegott Gellert (1715–1769) thematized the ailment in their comedies, most particularly inDie ungleiche Heirath(1743) andDas Testament(1745) by Gottsched and inDas Loos in der Lotterie(1747) andDie kranke Frau(1747) by Gellert. These mid‐eighteenth‐century literary constructions of hypochondria invest the disease with potent metaphorical meaning, and they provide a valuable perspective on the topic of hypochondria as it relates to women and marriage, in that three of these texts depict married women as hypochondriacs and one of them depicts a widow using disease in order to bring about her own second marriage. Although hypochondria is ridiculed in these comedies, it functions as a strategy for negotiating and resisting the patriarchal power structures of marriage, for the hypochondria of these middle‐class and aristocratic female characters empowers them by serving as a means of acquiring and maintaining control and authority within the confines of marriage.
Transcription factor Rex in regulation of pathophysiology in oral pathogens
Authors: Bitoun J.P. , Wen Z.T.
Published: July 2015

The NAD+ and NADH‐sensing transcriptional regulator Rex is widely conserved across gram‐positive bacteria. Rex monitors cellular redox poise and controls the expression of genes/operons involved in diverse pathways including alternative fermentation, oxidative stress responses, and biofilm formation. The oral cavity undergoes frequent and drastic fluctuations in nutrient availability, pH, temperature, oxygen tension, saliva, and shear forces. The oral streptococci are major colonizers of oral mucosa and tooth surfaces and include commensals as well as opportunistic pathogens, including the primary etiological agent of dental caries, Streptococcus mutans. Current understanding of the Rex regulon in oral bacteria is mostly based on studies in S. mutans and endodontic pathogen Enterococcus faecalis. Indeed, other oral bacteria encode homologs of the Rex protein and much is to be gleaned from more in‐depth studies. Our current understanding has Rex positioned at the interface of oxygen and energy metabolism. In biofilms, heterogeneous oxygen tension influences the ratio of intracellular NADH and NAD+, which is finely tuned through glycolysis and fermentation. In S. mutans, Rex regulates the expression of glycolytic enzyme NAD+‐dependent glyceraldehyde 3‐phosphate dehydrogenase, and NADH‐dependent fermentation enzymes/complexes lactate dehydrogenase, pyruvate dehydrogenase, alcohol‐acetaldehyde dehydrogenase, and fumarate reductase. In addition, Rex controls the expression of NADH oxidase, a major enzyme used to eliminate oxidative stress and regenerate NAD+. Here, we summarize recent studies carried out on the Rex regulators in S. mutans and E. faecalis. This research has important implications for understanding how Rex monitors redox balance and optimizes fermentation pathways for survival and subsequent pathogenicity.
The relationship between the season of birth and early‐onset food allergies in children
Authors: Tanaka Kajiyo , Matsui Teruaki , Sato Arisa , Sasaki Kemal , Nakata Joon , Nakagawa Tomoko , Sugiura Shiro , Kando Naoyuki , Nishiyama Takeshi , Kojima Seiji , Ito Komei
Published: July 2015

Background

This study examined the relationship between the season of birth (SoB) and other factors with the development of FA.

Methods

A multicenter, cross‐sectional pilot study recruited 1197 patients with FA. The main study recruited 440 incident cases (FA group) definitively diagnosed as FA at 0–1 year of age. In both studies, the frequency of autumn–winter births (AWBs) in FA patients was compared to the regional control population. In the main study, we analyzed the differences in the SoB and other factors between patients in the FA group and those in the non‐FA group (n = 332) in allergy clinics.

Results

The pilot study showed that the frequency of AWB (57.6%) in the FA patients was significantly higher than that of the regional control population (50.4%, OR, 1.34; p < 0.001). The main study also showed the dominance of AWB (62.7%) in the FA group in comparison with that in the regional control population (50.2%, OR, 1.70; p < 0.001). Preterm birth (OR, 0.43; p = 0.027) and the presence of two or more elder siblings (OR, 0.27; p = 0.012) were significantly associated with a lower frequency of FA than those of non‐FA. AWB (RR, 1.21; p = 0.020) and preterm birth (RR, 0.55; p = 0.017) were significantly associated with a number of trigger foods. The SoB effect was observed in FA patients irrespective of the presence of infantile eczema.

Conclusions

AWB was predominant in the patients with newly diagnosed food allergies.
Attachment‐informed therapy for adults: Towards a unifying perspective on practice
Authors: Berry Katherine , Danquah Adam
Published: July 2015

Purpose

We aimed to provide an integrated overview of the key goals and strategies of an attachment‐informed psychotherapy by summarizing the literature describing the clinical implications of attachment theory for psychological therapy for adults.

Method

We carried out a narrative thematic review of 58 texts from a diverse range of therapeutic schools, until we agreed that we had reached a saturation of themes.

Results

We identified six key themes: Changing internal working models; the therapeutic relationship and creating a secure base; formulating and processing relationship experiences; countertransference; separation, termination and boundary issues; and working with different attachment styles or patterns. We discuss empirical evidence in relation to each theme and highlight areas for research.

Conclusions

Attachment theory provides a useful framework to inform psychological therapy with adults, but there is a pressing need for further research to empirically demonstrate the ‘added value’ of an attachment perspective.

Practitioner points

Attachment theory should be used to inform individual psychological therapy in adulthood.

From the outset of their careers, therapists should receive training and supervision to enhance their awareness of their own and their clients' attachment experiences and how these play out during therapy.

There is a need for greater empirical research to investigate whether the degree to which therapists formulate and meet clients' attachment needs influences outcomes.
Melanins and melanogenesis: from pigment cells to human health and technological applications
Authors: d'Ischia Marco , Wakamatsu Kazumasa , Cicoira Fabio , Di Mauro Eduardo , Garcia‐Borron Josè Carlos , Commo Stephane , Galván Ismael , Ghanem Ghanem , Kenzo Koike , Meredith Paul , Pezzella Alessandro , Santato Clara , Sarna Tadeusz , Simon John D. , Zecca Luigi , Zucca Fabio A. , Napolitano Alessandra , Ito Shosuke
Published: July 2015

During the past decade, melanins and melanogenesis have attracted growing interest for a broad range of biomedical and technological applications. The burst of polydopamine‐based multifunctional coatings in materials science is just one example, and the list may be expanded to include melanin thin films for organic electronics and bioelectronics, drug delivery systems, functional nanoparticles and biointerfaces, sunscreens, environmental remediation devices. Despite considerable advances, applied research on melanins and melanogenesis is still far from being mature. A closer intersectoral interaction between research centers is essential to raise the interests and increase the awareness of the biomedical, biomaterials science and hi‐tech sectors of the manifold opportunities offered by pigment cells and related metabolic pathways. Starting from a survey of biological roles and functions, the present review aims at providing an interdisciplinary perspective of melanin pigments and related pathway with a view to showing how it is possible to translate current knowledge about physical and chemical properties and control mechanisms into new bioinspired solutions for biomedical, dermocosmetic, and technological applications.
Proton magnetic resonance spectroscopy revealed differences in the glutamate + glutamine/creatine ratio of the anterior cingulate cortex between healthy and pediatric post‐traumatic stress disorder patients diagnosed after 2008 Wenchuan earthquake
Authors: Yang Zhi‐Yong , Quan Hong , Peng Zu‐Lai , Zhong Yang , Tan Zhi‐Jie , Gong Qi‐Yong
Published: July 2015

Aims

Earthquakes always leave many surviving teenagers suffering from various mental problems, such as post‐traumatic stress disorder (PTSD). We studied the metabolites in current and remitted pediatric PTSD patients and healthy controls after an earthquake, aiming to find the neurochemistry differences in these teenagers.

Methods

Proton magnetic resonance spectroscopy (1H‐MRS) was performed in the anterior cingulate cortex (ACC) of 21 healthy, 10 PTSD and 23 remitted subjects.

Results

Significantly lower glutamate + glutamine/creatine (Glx/Cr) levels in the ACC (1.15 ± 0.14 vs 1.37 ± 0.08, P = 0.047) were found in PTSD subjects relative to remitted subjects; and significantly lower Glx/Cr levels in the ACC (1.37 ± 0.08 vs 1.59 ± 0.10, P = 0.045) were found in remitted subjects relative to healthy controls.

Conclusions

Our findings imply that the Glx/Cr ratio in the ACC can be used to differentiate not only between healthy and pediatric PTSD patients, but also between the current and remitted phases of pediatric PTSD. The changes in the Glx/Cr ratio may be caused by brain dysfunction in the current phase and recovery in the remitted phase.
Effects of rater bias and assessment method on disease severity estimation with regard to hypothesis testing
Authors: Chiang K. S. , Bock C. H. , El Jarroudi M. , Delfosse P. , Lee I. H. , Liu H. I.
Published: July 2015

The effects of bias (over‐ and underestimates) in estimates of disease severity on hypothesis testing using different assessment methods was explored. Nearest percentage estimates (NPE), the Horsfall–Barratt (H‐B) scale, and two linear category scales (10% increments, with and without additional grades at low severity) were compared using simulation modelling to assess effects of bias. Type I and type II error rates were used to compare two treatment differences. The power of the H‐B scale and the 10% scale were least for correctly testing a hypothesis compared with the other methods, and the effects of rater bias on type II errors were greater over specific severity ranges. Apart from NPEs, the amended 10% category scale was most often superior to other methods at all severities tested for reducing the risk of type II errors. It should thus be a preferred method for raters who must use a category scale for disease assessments. Rater bias and assessment method had little effect on type I error rates. The power of the hypothesis test using unbiased estimates was most often greater compared with biased estimates, regardless of assessment method. An unanticipated observation was the greater impact of rater bias compared with assessment method on type II errors. Knowledge of the effects of rater bias and scale type on hypothesis testing can be used to improve accuracy and reliability of disease severity estimates, and can provide a logical framework for improving aids to estimate severity visually, including standard area diagrams and rater training software.
History of Maternal Fetal Loss and Childhood Leukaemia Risk in Subsequent Offspring: Differentials by Miscarriage or Stillbirth History and Disease Subtype
Authors: Karalexi M. A. , Skalkidou A. , Thomopoulos T. P. , Belechri M. , Biniaris‐Georgallis S.‐I. , Bouka E. , Baka M. , Hatzipantelis E. , Kourti M. , Polychronopoulou S. , Sidi V. , Stiakaki E. , Moschovi M. , Dessypris N. , Petridou E. Th.
Published: July 2015

Background

Despite the putative intrauterine origins of childhood (0–14 years) leukaemia, it is complex to assess the impact of perinatal factors on disease onset. Results on the association of maternal history of fetal loss (miscarriage/stillbirth) with specific disease subtypes in the subsequent offspring are in conflict. We sought to investigate whether miscarriage and stillbirth may have different impacts on the risk of acute lymphoblastic leukaemia (ALL) and of its main immunophenotypes (B‐cell and T‐cell ALL), as contrasted to acute myeloid leukaemia (AML).

Methods

One thousand ninety‐nine ALL incidents (957 B‐ALL) and 131 AML cases along with 1:1 age and gender‐matched controls derived from the Nationwide Registry for Childhood Hematological Malignancies and Brain Tumors (1996–2013) were studied. Multivariable regression models were used to assess the roles of previous miscarriage(s) and stillbirth(s) on ALL (overall, B‐, T‐ALL) and AML, controlling for potential confounders.

Results

Statistically significant exposure and disease subtype‐specific associations of previous miscarriage(s) exclusively with AML [odds ratio (OR) 1.67, 95% confidence interval (CI) 1.00, 2.81] and stillbirth(s) with ALL [OR 4.82, 95% CI 1.63, 14.24] and B‐ALL particularly, emerged.

Conclusion

Differential pathophysiological pathways pertaining to genetic polymorphisms or cytogenetic aberrations are likely to create hostile environments leading either to fetal loss or the development of specific leukaemia subtypes in subsequent offspring, notably distinct associations of maternal miscarriage history confined to AML and stillbirth history confined to ALL (specifically B‐ALL). If confirmed and further supported by studies revealing underlying mechanisms, these results may shed light on the divergent leukemogenesis processes.
An Empirical Study of the Volkswagen Crisis in China: Customers’ Information Processing and Behavioral Intentions
Authors: Wei Jiuchang , Zhao Ming , Wang Fei , Cheng Peng , Zhao Dingtao
Published: July 2015

Product‐harm crises usually lead to product recalls, which may cause consumers concern about the product quality and safety. This study systematically examines customers’ immediate responses to the Volkswagen product recall crisis in China. Particular attention was given to customers’ responses to the risk information influencing their behavioral intentions. By combining the protective action decision model and the heuristic‐systematic model, we constructed a hypothetical model to explore this issue. A questionnaire survey was conducted to collect data involving 467 participants drawn from the customers of Volkswagen. We used structural equation modeling to explore the model. The results show that customers’ product knowledge plays an important role in their responses to the crisis. Having more knowledge would make them perceive a lower risk, but they might need even more information, making them more likely to seek and process information, and subsequently increasing their positive behavioral intentions toward the firm (that is pro‐firm behavioral intentions). Risk perception increased customers’ information needs, information seeking, and information processing but decreased their pro‐firm behavioral intentions. In addition to promoting information seeking, information needed to also facilitate customers’ systematic processing and thus increase their behavioral intentions to take corrective action. Customers’ behavioral intentions were also spurred by systematic processing, but failed to be predicted by information seeking. In summary, theoretical and practical implications and suggestions for further research are also discussed.
On new variance approximations for linear models with inequality constraints
Authors: Knottnerus Paul
Published: July 2015

In this paper, we examine the estimation of linear models subject to inequality constraints with a special focus on new variance approximations for the estimated parameters. For models with one inequality restriction, the proposed variance formulas are exact. The variance approximations proposed in this paper can be used in regression analysis, Kalman filtering, and balancing national accounts, when inequality constraints are to be incorporated in the estimation procedure.
Magico‐spiritual power, female sexuality and ritual sex in Muslim Java: Unveiling the kesekten of magical women
Authors: Smith Bianca J. , Woodward Mark
Published: July 2015

This article argues that in practice, concepts of magico‐spiritual power (Javanese: kesekten; Indonesian: kesaktian) are linked with sexuality, particularly female sexuality, in some segments of contemporary Central and East Javanese Muslim society. Few scholars have turned attention to the interconnectedness of these seemingly contradictory topics. Feminist studies tend to focus on the ways in which women locate themselves within and critique Sharia‐based discursive and social orders, without considering the roles that magico‐spiritual power and associated practices play in these Islamic systems or in Islam in a more general sense. Similarly, male scholarship that considers the cultural relevance of Islam and magic rarely refers to gendered and sexual dimensions as praxis from a feminist perspective. By drawing on examples of ‘magical women’ including the Javanese spirit queen of the southern ocean Gusti Kanjeng Ratu Kidul, the historical Hindu figure Ken Dedes, and contemporary ritual sex practices at a Muslim saint's grave, we show how women, female spiritual beings and female sexuality, and sexuality in general, can be considered sources of magico‐spiritual power in Muslim Java. Our arguments conclude that in Javanese Islam, transgression of Sharia sexual norms can be both a sign and a source of magico‐spiritual power.
Lessons learnt from the management of a case of Lassa fever and follow‐up of nosocomial primary contacts in Nigeria during Ebola virus disease outbreak in West Africa
Authors: Iroezindu Michael O. , Unigwe Uche S. , Okwara Celestine C. , Ozoh Gladys A. , Ndu Anne C. , Ohanu Martin E. , Nwoko Ugochukwu O. , Okoroafor Uwadiegwu W. , Ejimudo Esinulo , Tobin Ekaete A. , Asogun Danny A.
Published: July 2015

Objective

To describe our experiences in the management of a case of Lassa fever (LF) and follow‐up of nosocomial primary contacts during the 2014 Ebola outbreak in West Africa.

Methods

Clinical management of the index case and infection control/surveillance activities for primary contacts are described. Laboratory confirmation was by Lassa virus‐specific reverse‐transcriptase PCR.

Results

A 28‐year‐old man with a 10‐day history of febrile illness was referred to a major tertiary hospital in south‐east Nigeria from a city that previously experienced a LF outbreak and was recently affected by Ebola. On observation of haemorrhagic features, clinicians were at a crossroads. Diagnosis of LF was confirmed at a National Reference Centre. The patient died despite initiation of ribavirin therapy. Response activities identified 121 primary contacts comprising 78 (64.5%) hospital staff/interns, 19 (15.7%) medical students, 18 (14.9%) inpatients and 6 (5.0%) relatives. Their mean age was 32.8 ± 6.6 years, and 65.3% were women. Twenty (16.5%) had high‐risk exposure and were offered ribavirin as post‐exposure prophylaxis. No secondary case of LF occurred. Fatigue (43.8%) and dizziness (31.3%) were the commonest side effects of ribavirin.

Conclusions

Response activities contained nosocomial spread of LF, but challenges were experienced including lack of a purpose‐built isolation facility, absence of local Lassa virus laboratory capacity, failure to use appropriate protective equipment and stigmatisation of contacts. A key lesson is that the weak health systems of Africa should be comprehensively strengthened; otherwise, we might win the Ebola battle but lose the one against less virulent infections for which effective treatment exists.
Diagnostic and treatment delays of multidrug‐resistant tuberculosis before initiating treatment: a cross‐sectional study
Authors: Zhang Xiulei , Yin Jia , Li Haitao , Li Shuguang , Walley John , Zou Guanyang , Zhang Zhitong , Wei Xiaolin
Published: July 2015

Objective

Shandong Province has implemented the standardised treatment of multidrug‐resistant tuberculosis (MDR‐TB) supported by the Global Fund. The study aimed to understand the managements and delays of patients with MDR‐TB before initiating their treatments.

Methods

All patients with MDR‐TB who had completed intensive phase treatment from January 2010 to May 2012 were interviewed using a structured questionnaire. Delays and treatments were analysed. Diagnosis delay is defined as the period between having sputum smear results and drug susceptibility test (DST) results. Treatment delay was defined as starting MDR‐TB treatment more than 2 days after receiving the diagnosis of MDR‐TB. Total delay is the sum of diagnosis delay and treatment delay.

Results

In total, 110 patients with MDR‐TB participated in the study. Median delay for diagnosis was 102 days. Over 80% of patients had a diagnosis delay longer than 90 days. MDR‐TB treatments commenced after a median of 9 days after DST results, and over 37% of the patients with MDR‐TB experienced treatment delays. Chronic cases or patients with indifferent attitude had significantly longer treatment delay than other groups (P = 0.03 and 0.03, respectively). During their delays, of 44 patients with retreatment failures, 12 (27.3%) were treated through adding single second line drugs (SLDs) to first‐line regimens, and 25 (56.8%) were treated with first‐line drugs. A high proportion of initial treatment failure/relapsed/returned cases (37%) and new cases (43%) were administered with SLDs.

Conclusions

Most of the patients with MDR‐TB experienced prolonged diagnosis delay, which was the most important factor contributing to the total delay. Misuse of SLDs during the days was common, so necessary training should be given to prevent irrational prescription of medications.
Evaluation of small noncoding RNAs in ex vivo stored human mature red blood cells: changes in noncoding RNA levels correlate with storage lesion events
Authors: Sarachana Tewarit , Kulkarni Sandhya , Atreya Chintamani D.
Published: July 2015

BACKGROUND

While biomarkers of storage lesions (SLs) for red blood cells (RBCs) abound, the physiologic consequences of SLs and associated important events are poorly understood. Previously we have identified differentially expressed regulatory small noncoding RNAs (ncRNAs) in stored RBCs, suggesting their role in the RBC SL process and their potential as quality biomarkers of stored RBCs.

STUDY DESIGN AND METHODS

Comprehensive ncRNA expression analysis of RBCs stored for up to 56 days was performed on RNAs collected from enriched mature RBCs on Days 0, 7, 14, 28, 42, and 56. Three known RBC SL processes, that is, mature RBCs’ suicidal death (eryptosis), ATP loss, and changes in RBC indices, were correlated with differentially expressed ncRNAs to gain knowledge on the SL molecular processes.

RESULTS

The analysis identified four ncRNAs whose changes in the expression levels were correlated with the selected three SL processes. Differential expression on Days 14 and 28 of the four selected ncRNAs was confirmed by TaqMan quantitative reverse transcription–polymerase chain reaction analysis. Bioinformatics analysis identified potential targets and biologic functions of these ncRNAs. Overexpression of one such ncRNA, hsa‐miR‐196a, in a human erythroblast cell line confirmed its protective effects against the cell death and ATP loss.

CONCLUSION

Overall, this study demonstrates that changes in the levels of small ncRNAs of stored RBCs correlate with some of the SL events and thus they have the potential to serve as the storage quality markers.
Ecophysiological characteristics of five weeds and a wheat crop in the Indo‐Gangetic Plains, India
Authors: Singh Vartika , Gupta Sweta , Singh Hema , Raghubanshi Akhilesh Singh
Published: July 2015

The objective of this research was to compare selected ecophysiological parameters for a wheat crop found in the Indo‐Gangetic Plains of India and its five dominant weeds. The dominant and regionally ubiquitous weeds in the wheat field that was selected for the study were Anagallis arvensis, Chenopodium album, Melilotus albus, Phalaris minor and Rumex dentatus. Taller weeds, such as C. album and P. minor, constituted one group along with the crop, with a low photosynthetic rate, specific leaf area, leaf nitrogen mass basis, chlorophyll content, photosynthetic nitrogen‐use efficiency and leaf area ratio, in comparison to shorter weeds, such as A. arvensis, M. albus and R. dentatus, which formed another group with a high photosynthetic rate, specific leaf area, leaf nitrogen mass basis, chlorophyll content, photosynthetic nitrogen‐use efficiency and leaf area ratio. Interspecific variations in the photosynthetic rate were driven mainly by variability in the specific leaf area and leaf nitrogen content. The taller weeds and the crop had a low specific leaf area later in the season, whereas the smaller weeds had a relatively high specific leaf area, which might be an adaptation to the shaded environment below the canopy. The result indicates that any weed management in the wheat fields of the Indo‐Gangetic Plains will need two different approaches because of the different strategies followed by the two weed groups that were identified in the present study.
Human thrombomodulin regulates complement activation as well as the coagulation cascade in xeno‐immune response
Authors: Kim Hwajung , Hawthorne Wayne J. , Kang Hee Jung , Lee Yoo Jin , Hwang Jong‐Ik , Hurh Sunghoon , Ro Han , Jeong Jong Cheol , Cho Bumrae , Yang Jaeseok , Ahn Curie
Published: July 2015

Background

With the introduction of the α1, 3‐galactosyltransferase gene‐knockout (GT‐KO) pig and its pivotal role in preventing hyperacute rejection (HAR), coagulation remains a considerable obstacle yet to be overcome in order to provide long‐term xenograft survival. Thrombomodulin (TBM) plays a critical anticoagulant and anti‐inflammatory role in its part of the protein C pathway. Many studies have demonstrated the strong anticoagulant effects of TBM in xenotransplantation, but its complement regulatory effects have not been appropriately examined. Here, we investigate whether TBM can regulate complement activation as well as coagulation in response to xenogeneic stimuli.

Methods

We transfected porcine endothelial cells (MPN‐3) with adenovirus vectors containing the human TBM gene (ad‐hTBM), or a control gene containing GFP (ad‐GFP). The expression level of ad‐hTBM was measured by flow cytometry. To confirm the anticoagulant effect of TBM, coagulation time was measured after treatment with recalcified human plasma in ad‐hTBM‐transfected MPN‐3, and a thrombin activity assay was performed after treatment with 50% human serum in ad‐hTBM‐infected MPN‐3.

Results

Thrombin generation was significantly decreased in a dose‐dependent manner in ad‐TBM group, and coagulation time was increased in the ad‐hTBM group when compared to the ad‐GFP group. Complement‐dependent serum toxicity assays were performed after treatment with 20% human serum or heat‐inactivated human serum by LDH assay. Complement‐dependent toxicity was significantly attenuated in the ad‐hTBM group, but complement‐independent toxicity was not attenuated in the ad‐hTBM group. These results suggest that human thrombomodulin (hTBM) has complement regulatory effects as well as anticoagulant effects. To further investigate the mechanisms of complement regulation by hTBM, we deleted the EGF5, 6 domains that are involved in thrombin generation or the lectin‐like domain involved in inflammation of TBM and functional tests were performed using these modified forms. We showed that the EGF5, 6 domain of TBM principally inhibits complement activation rather than the lectin domain.

Conclusion

The EGF5, 6 domains of TBM appear to be the major domains for down‐regulating the complement system rather than the lectin‐like domain during xenogenic stimuli. The role of EGF5, 6 domains of hTBM may be due to inhibition of thrombin as thrombin can cleave C3a and C5a directly and hTBM may also be involved in complement regulation. Clearly then human TBM has complement regulatory effects as well as anticoagulant effects in xeno‐immune response, and it is a promising target for attenuating xenograft rejection.
Systematic Selection and Siting of Vehicle Fueling Infrastructure to Synergistically Meet Future Demands for Alternative Fuels
Authors: Willette Peter J. , Shaffer Brendan , Scott Samuelsen G.
Published: July 2015

In order to meet the increasing demand for low carbon and renewable transportation fuels, a methodology for systematically establishing build-out scenarios is desirable. In an effort to minimize initial investment costs associated with the development of fueling infrastructure, the analytical hierarchy process (AHP) has been developed and applied, as an illustration, to the case of hydrogen fueling infrastructure deployment in the State of California. In this study, five parameters are selected in order to rank hydrogen transportation fuel generation locations within the State. In order to utilize meaningful weighting factors within the AHP, expert inputs were gathered and employed in the exercising of the models suite of weighting parameters. The analysis uses statewide geographic information and identifies both key energy infrastructure expansion locations and critical criteria that make the largest impact in the location of selected sites.
Tree-based control software for multilevel sequencing in thin film deposition applications
Authors: Piercy Brandon D. , Losego Mark D.
Published: July 2015

A simple, extensible control software scheme for sequential deposition applications including atomic layer deposition, molecular beam epitaxy, and layer-by-layer deposition is presented. While single-component loops are easily programmed, nested loop architectures needed for complex multilayer thin films or compositionally graded structures are cumbersome to implement with only “For-loop” coding. Software code based on a generic tree architecture is introduced to achieve multilevel or compound sequencing. This architecture makes it possible to write many different deposition sequences without modifying the underlying software. The tree can be easily traversed using recursive techniques, simplifying the programmer's task and opening up novel material combinations and sequences to thin film researchers. A labview software implementation consisting of a few simple functions is presented, as well as a sampling of the potential complex deposition schemes facilitated by this architecture.
Locating and characterizing a crack in concrete with diffuse ultrasound: A four-point bending test
Authors: Larose Eric , Obermann Anne , Digulescu Angela , Planès Thomas , Chaix Jean-Francois , Mazerolle Frédéric , Moreau Gautier
Published: July 2015

This paper describes an original imaging technique, named Locadiff, that benefits from the diffuse effect of ultrasound waves in concrete to detect and locate mechanical changes associated with the opening of pre-existing cracks, and/or to the development of diffuse damage at the tip of the crack. After giving a brief overview of the theoretical model to describe the decorrelation of diffuse waveforms induced by a local change, the article introduces the inversion procedure that produces the three dimensional maps of density of changes. These maps are interpreted in terms of mechanical changes, fracture opening, and damage development. In addition, each fracture is characterized by its effective scattering cross section.
Envelope analysis with a genetic algorithm-based adaptive filter bank for bearing fault detection
Authors: Kang Myeongsu , Kim Jaeyoung , Choi Byeong-Keun , Kim Jong-Myon
Published: July 2015

This paper proposes a fault detection methodology for bearings using envelope analysis with a genetic algorithm (GA)-based adaptive filter bank. Although a bandpass filter cooperates with envelope analysis for early identification of bearing defects, no general consensus has been reached as to which passband is optimal. This study explores the impact of various passbands specified by the GA in terms of a residual frequency components-to-defect frequency components ratio, which evaluates the degree of defectiveness in bearings and finally outputs an optimal passband for reliable bearing fault detection.
Guidelines to Classify Female Subject Groups in Sport-Science Research
Authors: Decroix Lieselot , De Pauw Kevin , Foster Carl , Meeusen Romain
Published: July 2015

Aim:

To review current cycling-related sport-science literature to formulate guidelines to classify female subject groups and to compare this classification system for female subject groups with the classification system for male subject groups.

Methods:

A database of 82 papers that described female subject groups containing information on preexperimental maximal cycle-protocol designs, terminology, biometrical and physiological parameters, and cycling experience was analyzed. Subject groups were divided into performance levels (PLs), according to the nomenclature. Body mass, body-mass index, maximal oxygen consumption (VO2max), peak power output (PPO), and training status were compared between PLs and between female and male PLs.

Results:

Five female PLs were defined, representing untrained, active, trained, well-trained, and professional female subjects. VO2max and PPO significantly increased with PL, except for PL3 and PL4 (P < .01). For each PL, significant differences were observed in absolute and relative VO2max and PPO between male and female subject groups. Relative VO2max is the most cited parameter for female subject groups and is proposed as the principal parameter to classify the groups.

Conclusion:

This systematic review shows the large variety in the description of female subject groups in the existing literature. The authors propose a standardized preexperimental testing protocol and guidelines to classify female subject groups into 5 PLs based on relative VO2max, relative PPO, training status, absolute VO2max, and absolute PPO.
Cross-sectional and Longitudinal Associations Between Parents’ and Preschoolers’ Physical Activity and Television Viewing: The HAPPY Study
Authors: Abbott Gavin , Hnatiuk Jill , Timperio Anna , Salmon Jo , Best Keren , Hesketh Kylie D.
Published: July 2015

Background:

Parental modeling has been shown to be important for school-aged children’s physical activity (PA) and television (TV) viewing, yet little is known about its impact for younger children. This study examined cross-sectional and 3-year longitudinal associations between PA and TV viewing behaviors of parents and their preschool children.

Methods:

In 2008–2009 (T1), parents in the Healthy Active Preschool and Primary Years (HAPPY) cohort study (n = 450) in Melbourne, Australia, self-reported their weekly PA and TV viewing and proxy-reported their partner’s PA and TV viewing and their 3- to 5-year-old preschool child’s TV viewing. Children’s PA was assessed via accelerometers. Repeat data collection occurred in 2011–2012 (T2).

Results:

Mothers’ and fathers’ PAs were associated with PA among preschool girls at T1, but not boys. Parents’ TV viewing times were significant correlates of girls’ and boys’ TV viewing at T1. Longitudinally, mothers’ PA at baseline predicted boys’ PA at T2, whereas sex-specific associations were found for TV viewing, with mothers’ and fathers’ TV viewing at T1 associated with girls’ and boys’ TV viewing respectively at T2.

Conclusions:

The PA and TV viewing of both parents are significantly associated with these behaviors in preschool children. The influence of the sex-matched parent appears to be important longitudinally for children’s TV viewing.
The rise in computational systems biology approaches for understanding NF-κB signaling dynamics
Authors: Williams Richard A. , Timmis Jon , Qwarnstrom Eva E.
Published: July 2015

The combination of mathematical modeling with imaging experiments helps to interpret how NF-κB signaling is controlled.
Periodic dieting promotes health
Authors: VanHook Annalisa M.
Published: July 2015

Adherence to a periodic fast-mimicking diet improves health and promotes longevity.
Effects of Klebsiella pneumoniae Carbapenemase Subtypes, Extended-Spectrum β-Lactamases, and Porin Mutations on the
In Vitro
Activity of Ceftazidime-Avibactam against Carbapenem-Resistant K. pneumoniae
Authors: Shields Ryan K. , Clancy Cornelius J. , Hao Binghua , Chen Liang , Press Ellen G. , Iovine Nicole M. , Kreiswirth Barry N. , Nguyen M. Hong
Published: July 2015

Avibactam is a novel β-lactamase inhibitor with affinity for
Klebsiella pneumoniae
carbapenemases (KPCs). In combination with ceftazidime, the agent demonstrates activity against KPC-producing
K. pneumoniae
(KPC-Kp). KPC-Kp strains are genetically diverse and harbor multiple resistance determinants, including defects in outer membrane proteins and extended-spectrum β-lactamases (ESBLs). Mutations in porin gene
ompK36
confer high-level carbapenem resistance to KPC-Kp strains. Whether specific mechanisms of antimicrobial resistance also influence the activity of ceftazidime-avibactam is unknown. We defined the effects of ceftazidime-avibactam against 72 KPC-Kp strains with diverse mechanisms of resistance, including various combinations of KPC subtypes and ESBL and
ompK36
mutations. Ceftazidime MICs ranged from 64 to 4,096 μg/ml and were lowered by a median of 512-fold with the addition of avibactam. All strains exhibited ceftazidime-avibactam MICs at or below the CLSI breakpoint for ceftazidime (≤4 μg/ml; range, 0.25 to 4). However, the MICs were within two 2-fold dilutions of the CLSI breakpoint against 24% of the strains, and those strains would be classified as nonsusceptible to ceftazidime by EUCAST criteria (MIC > 1 μg/ml). Median ceftazidime-avibactam MICs were higher against KPC-3 than KPC-2 variants (
P
= 0.02). Among KPC-2-Kp strains, the presence of both ESBL and porin mutations was associated with higher drug MICs compared to those seen with either factor alone (
P
= 0.003 and
P
= 0.02, respectively). In conclusion, ceftazidime-avibactam displays activity against genetically diverse KPC-Kp strains. Strains with higher-level drug MICs provide a reason for caution. Judicious use of ceftazidime-avibactam alone or in combination with other agents will be important to prevent the emergence of resistance.
Influence of the
yjiL-mdtM
Gene Cluster on the Antibacterial Activity of Proline-Rich Antimicrobial Peptides Overcoming Escherichia coli Resistance Induced by the Missing SbmA Transporter System
Authors: Krizsan Andor , Knappe Daniel , Hoffmann Ralf
Published: July 2015

In view of increasing health threats from multiresistant pathogens, antimicrobial peptides (AMPs) and, specifically, proline-rich AMPs (PrAMPs) have been investigated in animal models. PrAMPs enter bacteria via the ABC transporter SbmA and inhibit intracellular targets. We used phage transduction (Tn
10
insertion) to screen by random mutagenesis for alternative uptake mechanisms for analogs of apidaecin 1b, a honeybee-derived PrAMP. All 24 apidaecin-resistant mutants had the Tn
10
insertion in the
sbmA
gene. These
sbmA
::Tn
10
insertion mutants and the
Escherichia coli
BW25113 Δ
sbmA
(JW0368) strain were still susceptible to the bactenecin PrAMP Bac7(1-35) and oncocin PrAMPs Onc18 and Onc112, as well as to Chex1-Arg20, despite significantly reduced internalizations. In a second round of random mutagenesis, the remaining susceptibility was linked to the
yjiL-mdtM
gene cluster.
E. coli
BW25113 and its Δ
yjiL
null mutant (JW5785) were equally susceptible to all PrAMPs tested, whereas the BW25113 Δ
mdtM
mutant was less susceptible to oncocins. The JW0368
yjiL
::Tn
10
transposon mutant (BS2) was resistant to all short PrAMPs and susceptible only to full-length Bac7 and A3-APO. Interestingly, PrAMPs appear to enter bacteria via MdtM, a multidrug resistance transporter (drug/H
+
antiporter) of the major facilitator superfamily (MFS) that can efflux antibiotics, biocides, and bile salts. In conclusion, PrAMPs enter bacteria via ABC and MFS transporters that efflux antibiotics and cytotoxic compounds from the cytoplasm to the periplasm.
Reversible Conformational Change in the Plasmodium falciparum Circumsporozoite Protein Masks Its Adhesion Domains
Authors: Herrera Raul , Anderson Charles , Kumar Krishan , Molina-Cruz Alvaro , Nguyen Vu , Burkhardt Martin , Reiter Karine , Shimp Richard , Howard Randall F. , Srinivasan Prakash , Nold Michael J. , Ragheb Daniel , Shi Lirong , DeCotiis Mark , Aebig Joan , Lambert Lynn , Rausch Kelly M. , Muratova Olga , Jin Albert , Reed Steven G. , Sinnis Photini , Barillas-Mury Carolina , Duffy Patrick E. , MacDonald Nicholas J. , Narum David L.
Published: July 2015

The extended rod-like
Plasmodium falciparum
circumsporozoite protein (CSP) is comprised of three primary domains: a charged N terminus that binds heparan sulfate proteoglycans, a central NANP repeat domain, and a C terminus containing a thrombospondin-like type I repeat (TSR) domain. Only the last two domains are incorporated in RTS,S, the leading malaria vaccine in phase 3 trials that, to date, protects about 50% of vaccinated children against clinical disease. A seroepidemiological study indicated that the N-terminal domain might improve the efficacy of a new CSP vaccine. Using a panel of CSP-specific monoclonal antibodies, well-characterized recombinant CSPs, label-free quantitative proteomics, and
in vitro
inhibition of sporozoite invasion, we show that native CSP is N-terminally processed in the mosquito host and undergoes a reversible conformational change to mask some epitopes in the N- and C-terminal domains until the sporozoite interacts with the liver hepatocyte. Our findings show the importance of understanding processing and the biophysical change in conformation, possibly due to a mechanical or molecular signal, and may aid in the development of a new CSP vaccine.
The Global Transcription Factor Lrp Controls Virulence Modulation in Xenorhabdus nematophila
Authors: Hussa Elizabeth A. , Casanova-Torres Ángel M. , Goodrich-Blair Heidi
Published: July 2015

The bacterium
Xenorhabdus nematophila
engages in phenotypic variation with respect to pathogenicity against insect larvae, yielding both virulent and attenuated subpopulations of cells from an isogenic culture. The global regulatory protein Lrp is necessary for
X. nematophila
virulence and immunosuppression in insects, as well as colonization of the mutualistic host nematode
Steinernema carpocapsae
, and mediates expression of numerous genes implicated in each of these phenotypes. Given the central role of Lrp in
X. nematophila
host associations, as well as its involvement in regulating phenotypic variation pathways in other bacteria, we assessed its function in virulence modulation. We discovered that expression of
lrp
varies within an isogenic population, in a manner that correlates with modulation of virulence. Unexpectedly, although Lrp is necessary for optimal virulence and immunosuppression, cells expressing high levels of
lrp
were attenuated in these processes relative to those with low to intermediate
lrp
expression. Furthermore, fixed expression of
lrp
at high and low levels resulted in attenuated and normal virulence and immunosuppression, respectively, and eliminated population variability of these phenotypes. These data suggest that fluctuating
lrp
expression levels are sufficient to drive phenotypic variation in
X. nematophila
.

IMPORTANCE
Many bacteria use cell-to-cell phenotypic variation, characterized by distinct phenotypic subpopulations within an isogenic population, to cope with environmental change. Pathogenic bacteria utilize this strategy to vary antigen or virulence factor expression. Our work establishes that the global transcription factor Lrp regulates phenotypic variation in the insect pathogen
Xenorhabdus nematophila
, leading to attenuation of virulence and immunosuppression in insect hosts. Unexpectedly, we found an inverse correlation between Lrp expression levels and virulence: high levels of expression of Lrp-dependent putative virulence genes are detrimental for virulence but may have an adaptive advantage in other aspects of the life cycle. Investigation of
X. nematophila
phenotypic variation facilitates dissection of this phenomenon in the context of a naturally occurring symbiosis.