bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of generalized granuloma annulare – a systematic review
Authors: Lukács J. , Schliemann S. , Elsner P.
Published: February 2015

Granuloma annulare (GA) is a benign inflammatory skin disease. Localized GA is likely to resolve spontaneously, while generalized GA (GGA) is rare and may persist for decades. GGA usually is resistant to a variety of therapeutic modalities and takes a chronic course. The objective of this study was to summarize all reported treatments of generalized granuloma annulare. This is a systematic review based on MEDLINE, Embase and Cochrane Central Register search of articles in English and German and a manual search, between 1980 and 2013, to summarize the treatment of generalized granuloma annulare. Most medical literature on treatment of GGA is limited to individual case reports and small series of patients treated without a control group. Randomized controlled clinical studies are missing. Multiple treatment modalities for GGA were reported including topical and systemic steroids, PUVA, isotretinoin, dapsone, pentoxifylline, hydroxychloroquine, cyclosporine, IFN‐γ, potassium iodide, nicotinamide, niacinamide, salicylic acid, dipyridamole, PDT, fumaric acid ester, etanercept, infliximab, adalimumab. While there are numerous case reports of successful treatments in the literature including surgical, medical and phototherapy options, well‐designed, randomized, controlled clinical trials are required for an evidence‐based treatment of GGA.
Varieties of clinical reasoning
Authors: Bolton Jonathan W.
Published: February 2015

Rationale, aims and objectives

Clinical reasoning comprises a variety of different modes of inference. The modes that are practiced will be influenced by the sociological characteristics of the clinical settings and the tasks to be performed by the clinician.

Methods

This article presents C.S. Peirce's typology of modes of inference: deduction, induction and abduction. It describes their differences and their roles as stages in scientific argument. The article applies the typology to reasoning in clinical settings.

Results

The article describes their differences, and their roles as stages in scientific argument. It then applies the typology to reasoning in typical clinical settings.

Conclusions

Abduction is less commonly taught or discussed than induction and deduction. However, it is a common mode of inference in clinical settings, especially when the clinician must try to make sense of a surprising phenomenon. Whether abduction is followed up with deductive and inductive verification is strongly influenced by situational constraints and the cognitive and psychological stamina of the clinician. Recognizing the inevitability of abduction in clinical practice and its value to discovery is important to an accurate understanding of clinical reasoning.
Clinical thinking in psychiatry
Authors: Wells Lloyd A.
Published: February 2015

I discuss the lack of precision in the term ‘clinical reasoning’ and its relationship to evidence‐based medicine and critical thinking. I examine critical thinking skills, their underemphasis in medical education and successful attempts to remediate them. Evidence‐based medicine (and evidence‐based psychiatry) offer much but are hampered by the ubiquity and flaws of meta‐analysis. I explore views of evidence‐based medicine among psychiatry residents, as well as capacity for critical thinking in residents before and after a course in philosophy. I discuss decision making by experienced doctors and suggest possible futures of this issue.
Molecular mechanisms of non‐transferrin‐bound and transferring‐bound iron uptake in primary hippocampal neurons
Authors: Ji Changyi , Kosman Daniel J.
Published: February 2015

The molecular mechanisms of iron trafficking in neurons have not been elucidated. In this study, we characterized the expression and localization of ferrous iron transporters Zip8, Zip14 and divalent metal transporter 1 (DMT1), and ferrireductases Steap2 and stromal cell‐derived receptor 2 in primary rat hippocampal neurons. Steap2 and Zip8 partially co‐localize, indicating these two proteins may function in Fe3+ reduction prior to Fe2+ permeation. Zip8, DMT1, and Steap2 co‐localize with the transferrin receptor/transferrin complex, suggesting they may be involved in transferrin receptor/transferrin‐mediated iron assimilation. In brain interstitial fluid, transferring‐bound iron (TBI) and non‐transferrin‐bound iron (NTBI) exist as potential iron sources. Primary hippocampal neurons exhibit significant iron uptake from TBI (Transferrin‐59Fe3+) and NTBI, whether presented as 59Fe2+‐citrate or 59Fe3+‐citrate; reductase‐independent 59Fe2+ uptake was the most efficient uptake pathway of the three. Kinetic analysis of Zn2+ inhibition of Fe2+ uptake indicated that DMT1 plays only a minor role in the uptake of NTBI. In contrast, localization and knockdown data indicate that Zip8 makes a major contribution. Data suggest also that cell accumulation of 59Fe from TBI relies at least in part on an endocytosis‐independent pathway. These data suggest that Zip8 and Steap2 play a major role in iron accumulation from NTBI and TBI by hippocampal neurons.

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Analysis of the expression and localization of known iron uptake transporters demonstrated that Zip8 makes a major contribution to iron accumulation in primary cultures of rat embryonic hippocampal neurons. These cells exhibit uptake pathways for ferrous and ferric iron (non‐transferrin‐bound iron, NTBI in figure) and for transferrin‐bound iron; the ferrireductases Steap2 and SDR2 support the uptake of ferric iron substrates. Zip8 and Steap2 are strongly expressed in the plasma membrane of both soma and processes, implying a crucial role in iron accumulation from NTBI and transferrin‐bound iron (TBI) by hippocampal neurons.
Positive allosteric modulation of alpha‐7 nicotinic receptors promotes cell death by inducing Ca2+ release from the endoplasmic reticulum
Authors: Guerra‐Álvarez María , Moreno‐Ortega Ana J. , Navarro Elisa , Fernández‐Morales José Carlos , Egea Javier , López Manuela G. , Cano‐Abad María F.
Published: February 2015

Positive allosteric modulation of α7 isoform of nicotinic acetylcholine receptors (α7‐nAChRs) is emerging as a promising therapeutic approach for central nervous system disorders such as schizophrenia or Alzheimer's disease. However, its effect on Ca2+ signaling and cell viability remains controversial. This study focuses on how the type II positive allosteric modulator (PAM II) PNU120596 affects intracellular Ca2+ signaling and cell viability. We used human SH‐SY5Y neuroblastoma cells overexpressing α7‐nAChRs (α7‐SH) and their control (C‐SH). We monitored cytoplasmic and endoplasmic reticulum (ER) Ca2+ with Fura‐2 and the genetically encoded cameleon targeting the ER, respectively. Nicotinic inward currents were measured using patch‐clamp techniques. Viability was assessed using methylthiazolyl blue tetrazolium bromide or propidium iodide staining. We observed that in the presence of a nicotinic agonist, PNU120596 (i) reduced viability of α7‐SH but not of C‐SH cells; (ii) significantly increased inward nicotinic currents and cytosolic Ca2+ concentration; (iii) released Ca2+ from the ER by a Ca2+‐induced Ca2+ release mechanism only in α7‐SH cells; (iv) was cytotoxic in rat organotypic hippocampal slice cultures; and, lastly, all these effects were prevented by selective blockade of α7‐nAChRs, ryanodine receptors, or IP3 receptors. In conclusion, positive allosteric modulation of α7‐nAChRs with the PAM II PNU120596 can lead to dysregulation of ER Ca2+, overloading of intracellular Ca2+, and neuronal cell death.

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This study focuses on how the type II positive allosteric modulator PNU120596 (PAM II PNU12) affects intracellular Ca2+ signaling and cell viability. Using SH‐SY5Y neuroblastoma cells overexpressing α7‐nAChRs (α7‐SH) and their control (C‐SH), we find that PAM of α7‐nAChRs with PNU120596: (i) increases inward calcium current (ICa) and cytosolic Ca2+ concentration ([Ca2+]cyt); (ii) releases Ca2+ from the ER ([Ca2+]ER) by a Ca2+‐induced Ca2+ release mechanism; and (iv) reduces cell viability. These findings were corroborated in rat hippocampal organotypic cultures. [Ca2+]cyt, cytosolic Ca2+ concentration; [Ca2+]ER, endoplasmic reticulum Ca2+ concentration; α7 nAChR, α7 isoform of nicotinic acetylcholine receptors; α7‐SH, SH‐SY5Y stably overexpressing α7 nAChRs cells; C‐SH, control SH‐SY5Y cells; Nic, nicotine; PNU12, PNU120596.
Increased expression of receptor for activated C kinase 1 in temporal lobe epilepsy
Authors: Xu Xin , Yang Xiaoyan , Xiong Yan , Gu Juan , He Changlong , Hu Yida , Xiao Fei , Chen Guojun , Wang Xuefeng
Published: February 2015

Mesial temporal lobe epilepsy (MTLE) is characterized by spontaneous recurrent complex partial seizures. Increased neurogenesis and neuronal plasticity have been reported in animal models of MTLE, but not in detail in human MTLE cases. Here, we showed that receptor for activated C kinase 1 (RACK1) was expressed in the hippocampus and temporal cortex of the MTLE human brain. Interestingly, most of the cells expressing RACK1 in the epileptic temporal cortices co‐expressed both polysialylated neural cell adhesion molecules, the migrating neuroblast marker, and the beta‐tubulin isotype III, an early neuronal marker, suggesting that these cells may be post‐mitotic neurons in the early phase of neuronal development. A subpopulation of RACK1‐positive cells also co‐express neuronal nuclei, a mature neuronal marker, suggesting that epilepsy may promote the generation of new neurons. Moreover, in the epileptic temporal cortices, the co‐expression of both axonal and dendritic markers in the majority of RACK1‐positive cells hints at enhanced neuronal plasticity. The expression of β‐tubulin II (TUBB2B) associated with neuronal migration and positioning, was decreased. This study is the first to successfully identify a single population of cells expressing RACK1 in the human temporal cortex and the brain of the animal model, which can be up‐regulated in epilepsy. Therefore, it is possible that these cells are functionally relevant to the pathophysiology of epilepsy.

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Mesial temporal lobe epilepsy is associated with increased neurogenesis and neuronal plasticity. We demonstrate expression of receptor for activated C kinase 1 (RACK1) and other markers associated with neuronal migration, synaptic plasticity and neurogenesis in the epileptic human and animal brains. The expression of tubulin, beta 2B class IIb (TUBB2B), associated with neuronal migration was decreased. Our findings raise the possibility that RACK1 is functionally relevant in epilepsy pathophysiology.
New forms of old drugs: improving without changing
Authors: Domingos Sofia , André Vânia , Quaresma Sílvia , Martins Inês C B , Minas da Piedade M Fátima , Duarte Maria Teresa
Published: February 2015

Objectives

In a short approach, we want to present the improvements that have recently been done in the world of new solid forms of known active pharmaceutical ingredients (APIs). The different strategies will be addressed, and successful examples will be given.

Key findings

This overview presents a possible step to overcome the 10–15 years of hard work involved in launching a new drug in the market: the use of new forms of well-known APIs, and improve their efficiency by enhancing their bioavailability and pharmacokinetics. It discusses some of the latest progresses.

We want to present, in a brief overview, what recently has been done to improve the discovery of innovative methods of using well-known APIs, and improve their efficiency. Multicomponent crystal forms have shown to be the most promising achievements to accomplish these aims, by altering API physico-chemical properties, such as solubility, thermal stability, shelf life, dissolution rate and compressibility. API-ionic liquids (ILs) and their advantages will be briefly referred. An outline of what has recently been achieved in metal drug coordination and in drug storage and delivery using bio-inspired metal-organic frameworks (BioMOFs) will also be addressed.
Bacterial spot of tomato and pepper: diverse Xanthomonas species with a wide variety of virulence factors posing a worldwide challenge
Authors: Potnis Neha , Timilsina Sujan , Strayer Amanda , Shantharaj Deepak , Barak Jeri D. , Paret Mathews L. , Vallad Gary E. , Jones Jeffrey B.
Published: February 2015

Taxonomic status

Bacteria; Phylum Proteobacteria; Class Gammaproteobacteria; Order Xanthomonadales; Family Xanthomonadaceae; Genus Xanthomonas; Species Xanthomonas euvesicatoria, Xanthomonas vesicatoria, Xanthomonas perforans and Xanthomonas gardneri.

Microbiological properties

Gram‐negative, rod‐shaped bacterium, aerobic, motile, single polar flagellum.

Host range

Causes bacterial spot disease on plants belonging to the Solanaceae family, primarily tomato (Solanum lycopersicum), pepper (Capsicum annuum) and chilli peppers (Capsicum frutescens).

Disease symptoms

Necrotic lesions on all above‐ground plant parts.

Distribution

Worldwide distribution of X. euvesicatoria and X. vesicatoria on tomato and pepper; X. perforans and X. gardneri increasingly being isolated from the USA, Canada, South America, Africa and Europe.

A wide diversity within the bacterial spot disease complex, with an ability to cause disease at different temperatures, makes this pathogen group a worldwide threat to tomato and pepper production. Recent advances in genome analyses have revealed the evolution of the pathogen with a plethora of novel virulence factors. Current management strategies rely on the use of various chemical control strategies and sanitary measures to minimize pathogen spread through contaminated seed. Chemical control strategies have been a challenge because of resistance by the pathogen. Breeding programmes have been successful in developing commercial lines with hypersensitive and quantitative resistance. However, durability of resistance has been elusive. Recently, a transgenic approach has resulted in the development of tomato genotypes with significant levels of resistance and improved yield that hold promise. In this article, we discuss the current taxonomic status, distribution of the four species, knowledge of virulence factors, detection methods and strategies for disease control with possible directions for future research.
Strong altitudinal partitioning in the distributions of ectomycorrhizal fungi along a short (300 m) elevation gradient
Authors: Jarvis Susan G. , Woodward Steve , Taylor Andy F. S.
Published: February 2015

Changes in species richness and distributions of ectomycorrhizal (ECM) fungal communities along altitudinal gradients have been attributed to changes in both host distributions and abiotic variables. However, few studies have considered altitudinal relationships of ECM fungi associated with a single host to identify the role of abiotic drivers. To address this, ECM fungal communities associated with one host were assessed along five altitudinal transects in Scotland.

Roots of Scots pine (Pinus sylvestris) were collected from sites between 300 and 550–600 m altitude, and ECM fungal communities were identified by 454 pyrosequencing of the fungal internal transcribed spacer (ITS) region. Soil moisture, temperature, pH, carbon : nitrogen (C : N) ratio and organic matter content were measured as potential predictors of fungal species richness and community composition.

Altitude did not affect species richness of ECM fungal communities, but strongly influenced fungal community composition. Shifts in community composition along the altitudinal gradient were most clearly related to changes in soil moisture and temperature.

Our results show that a 300 m altitudinal gradient produced distinct shifts in ECM fungal communities associated with a single host, and that this pattern was strongly related to climatic variables. This finding suggests significant climatic niche partitioning among ECM fungal species.
The potential use of cell‐based therapies in the treatment of oral diseases
Authors: Kagami H
Published: February 2015

A recent and exciting development in medicine is the use of living cells for patient treatment. The utility of living cells to treat diseases was first proved in hematopoietic stem cell transplantation for leukemia patients. This approach has been expanded for other diseases such as islet transplantation for diabetic patients. In those cases, the cells were isolated from donors or the patient and used without complex manipulation. Since the 1980s, cells have been expanded outside of the body for the treatment of burn patients’ skin. This novel treatment strategy is designated ‘tissue engineering’ and has been successfully applied for treatment of skin, cartilage, and also bone defects. Due to the recent developments in stem cell science, this area has attracted much attention and the application has been expanding. In this review, the potential of cell‐based therapy for oral diseases is discussed with a concise review of recent developments in this field.
Does Training Matter? Evidence from Performance Management Reforms
Authors: Kroll Alexander , Moynihan Donald P.
Published: February 2015

Training is much discussed but rarely studied in public management. Using multiple waves of survey data, the authors examine the effects of training on the implementation of performance management reforms in the U.S. federal government, asking whether those exposed to training are more likely to use performance data and strategic goals when making decisions. Training is positively associated with reform implementation, but there is little evidence that this association can be explained by the development of specific capacities to overcome performance management challenges. The findings offer two implications for the practice and study of training. The authors propose that training is likely to succeed if it is designed and funded to close specific capacity gaps needed for successful reform implementation. However, it is also necessary to better understand alternative causal mechanisms by which training facilitates reform implementation, such as explaining and justifying reforms.

Practitioner Points

Training can facilitate the implementation of new policies by providing information about the policies, justifying why they are needed, and giving employees the capacity to put the new policies in place.

Using training to build specific employee capacities is more complex, resource intensive, and rare than using training to provide information and justify reforms.

Effective training in government requires not just more resources but also better understanding of the specific capacities needed and how to create them—research can help by identifying the most significant capacity gaps in policy implementation.
Citizen (Dis)satisfaction: An Experimental Equivalence Framing Study
Authors: Olsen Asmus Leth
Published: February 2015

This article introduces the importance of equivalence framing for understanding how satisfaction measures affect citizens’ evaluation of public services. Does a 90 percent satisfaction rate have a different effect than a logically equivalent 10 percent dissatisfaction rate? Two experiments were conducted on citizens’ evaluations of hospital services in a large, nationally representative sample of Danish citizens. Both experiments found that exposing citizens to a patient dissatisfaction measure led to more negative views of public service than exposing them to a logically equivalent satisfaction metric. There is some support for part of the shift in evaluations being caused by a negativity bias: dissatisfaction has a larger negative impact than satisfaction has a positive impact. Both professional experience at a hospital and prior exposure to satisfaction rates reduced the negative response to dissatisfaction rates. The results call for further study of equivalence framing of performance information.

Practitioner Points

The valence (positive/negative) of performance information can have substantial effects on citizens’ perception of public services—even if the underlying performance is exactly the same.

Presenting citizens with a dissatisfaction rate of 10 percent induces a much more negative evaluation of public services than presenting them with a logically equivalent satisfaction rate of 90 percent.

Policy makers must carefully consider how minor equivalent changes in the presentation of performance information can induce large shifts in citizens’ perceptions of public service performance.
Faddists, Enthusiasts and Canadian Divas: Broadcasting Quotas and the Supply Response
Authors: Richardson Martin , Wilkie Simon
Published: February 2015

This paper constructs a model of the recorded music market to investigate the consequences of local content requirements in broadcasting for the “internationalization” of domestic music. It models the entry decisions of bands, the contracting decisions of record companies, the airplay decisions of radio stations and the radio listening and recording purchasing decisions of consumers. The paper shows that a local content quota leads, perversely, to the increased internationalization of domestic music. A quota that also requires increased broadcasting of “new” music yields an additional welfare loss but does nothing to a record company's incentives to sign up new bands.
Fulfilment of knowledge expectations among family members of patients undergoing arthroplasty: a European perspective
Authors: Sigurdardottir Arun K. , Leino‐Kilpi Helena , Charalambous Andreas , Katajisto Jouko , Stark Åsa Johansson , Sourtzi Panayota , Zabalegui Adelaida , Valkeapää Kirsi
Published: February 2015

In the recovery process of arthroplasty patients, their family members play an important role due to short hospital stay and increased age of patients. Family members need to have knowledge to be able to support the patient. The aim of this study was to explore expected and received knowledge in family members of arthroplasty patients and describe the relationships between the differences in received and expected knowledge and background factors, country, information and control preferences and access to knowledge. The study was conducted in six European countries (Cyprus, Greece, Finland, Iceland, Spain and Sweden). The study design was cross‐cultural, prospective and comparative with two measurement points: pre‐operative and at discharge from hospital. Knowledge Expectations of significant other‐scale and Krantz Health Opinion Survey were used before surgery and Received Knowledge of significant other‐scale and Access to Knowledge at discharge. Patients undergoing elective hip or knee arthroplasty in seventeen hospitals were asked to identify one family member. The sample size was decided by power calculation. A total of 615 participants answered the questionnaires at both measurements. Family members perceived to receive less knowledge than they expected to have, most unfulfilled knowledge expectations were in the financial, social and experiential dimensions of knowledge. Seventy‐four per cent of participants had unfulfilled knowledge expectations. Increased access to information from healthcare providers decreased the difference between received and expected knowledge. Compared to family members in southern Europe, those in the Nordic countries had more unfulfilled knowledge expectations and less access to information from healthcare providers. The evidence from this study highlights the need to involve the family members in the educational approach.
MicroRNA‐155 Deficiency Suppresses Th17 Cell Differentiation and Improves Locomotor Recovery after Spinal Cord Injury
Authors: Yi J. , Wang D. , Niu X. , Hu J. , Zhou Y. , Li Z.
Published: February 2015

Spinal cord injury (SCI) is considered to be primarily associated with loss of motor function and leads to activate diverse cellular mechanisms in the central nervous system to attempt to repair the damaged spinal cord tissue. Mir‐155 has been reported to be involved in both innate and adaptive immune responses. But the role of Mir‐155 in spinal cord injury is still unknown. In our current study, Mir‐155 deficiency displays increased myelin sparring and enhanced SC repair process. The number of T cells, B cells and neutrophils are all significantly lower in Mir‐155−/− group than that in WT group after SCI. IL‐17A‐producing cells and the expression of IL‐17A are markedly lower in Mir‐155−/− mice than that in WT mice. We also found higher production of IL‐17 by WT CD4+ T cells than Mir‐155−/− CD4+ T cells in vitro. In our further DC‐T cell coculture system, Mir‐155 deficiency in DCs results in significantly less IL‐17 production from T cells. Furthermore, the inhibited Th17 differentiation induced by Mir‐155 deficiency is partly dependent on increased expression of SOCS1. In conclusion, our present work provides evidence to support the concept that Mir‐155 deficiency suppresses Th17 cell differentiation and improves locomotor recovery after SCI.
Results of voluntary cardiovascular examination of elite athletes in Denmark: Proposal for Nordic collaboration
Authors: Tischer S. G. , Mattsson N. , Storgaard M. , Høfsten D. E. , Høst N. B. , Andersen L. J. , Prescott E. , Rasmusen H. K.
Published: February 2015

We investigated the cardiovascular status of elite athletes in Denmark, the extent of abnormal cardiac findings – both training related and pathologic – and how participating in cardiac examination was perceived by the athletes. A standardized protocol of questionnaires, physical examination, resting electrocardiogram, and 2D echocardiography was used. In total 1347 elite athletes were invited; 516 athletes (38%) from 30 different sports participated. Results were stored in a web‐based database for future research and long‐term follow‐up. Cardiac pathology was infrequent; eight athletes (1.6%) received a cardiac diagnosis; one athlete (0.2%) diagnosed with long QT syndrome was advised against competition level sports. In total, 60 athletes (11.6%) were referred for additional testing. The athletes presented a very low level of psychological stress before and a slight decrease immediately after the examination as measured by the REST‐Q 76 Sport questionnaire. Athletes needing further examinations did not present a higher level of stress after the initial examination compared with athletes with normal test results. Overall, very few athletes were diagnosed with a cardiac condition that increased risk of sudden cardiac death. Less than half of the invited athletes volunteered, but participation was not perceived stressful by the enrolled athletes, not even when additional testing was needed.
Circulating microRNAs in response to exercise
Authors: Xu T. , Liu Q. , Yao J. , Dai Y. , Wang H. , Xiao J.
Published: February 2015

MicroRNAs (miRNAs, miRs) are a novel class of endogenous noncoding RNAs, which post‐transcriptionally regulate gene expression via mRNA degradation or translational inhibition. miRNAs have become increasingly recognized as central players in the process of gene regulation and are responsible for a variety of essential biological processes including proliferation, differentiation and metabolism. miRNAs can be released into the circulation where they remain stable. Exercise is one of the most positive and effective means of achieving enhanced physique. This review highlights and summarizes recent progress in the field of circulating miRNAs in response to acute and chronic exercise and discusses future directions in studying circulating miRNAs in exercise‐induced adaptation. A better understanding of how circulating miRNAs participate in the physiological response to exercise would eventually help develop circulating miRNAs as therapeutic targets for improving exercise capacity in patients with heart failure and other diseases.
Bias reduction when data are rounded
Authors: Withers Christopher S. , Nadarajah Saralees
Published: February 2015

Analytical bias reduction methods are developed for univariate rounded data for the first time. Extensions are given to rounding of multivariate data, and to smooth functionals of several distributions. As a by‐product, we give for the first time the relation between rounded and unrounded multivariate cumulants. Estimators obtained by analytical bias reduction are compared with bootstrap and jackknife estimators by simulation.
Carbon and nitrogen in a Ferralsol under zero‐tillage rotations based on cover, cash or hay crops
Authors: Alburquerque M. A. , Dieckow J. , Sordi A. , Piva J. T. , Bayer C. , Molin R. , Pergher M. , Ribeiro‐Junior P. J.
Published: February 2015

To identify crop rotation systems capable of sequestering C and N to 1 metre depth in a subtropical Ferralsol of Southern Brazil managed under long‐term zero‐tillage (21 yrs), we evaluated six crop sequences: wheat (Triticum aestivum)–soybean (Glycine max) [W‐S], the baseline; oat (Avena strigosa, as cover crop)–maize (Zea mays)–wheat–soybean [O‐M‐W‐S]; vetch (Vicia villosa, as legume cover crop)–maize–wheat–soybean [V‐M‐W‐S]; vetch–maize–oat–soybean–wheat–soybean [V‐M‐O‐S‐W‐S]; ryegrass (Lolium multiflorum, for hay)–maize–ryegrass–soybean [R‐M‐R‐S]; and alfalfa (Medicago sativa, for hay)–maize [A‐M]. Compared to W‐S and to 1 metre, the hay‐based system of A‐M showed the largest C and N sequestration rates (0.50 and 0.06 Mg/ha/yr, respectively). Alfalfa, being a perennial legume under cut‐regrowth cycles, possibly added more C and N through roots. The other hay system, R‐M‐R‐S, also sequestered C efficiently (0.27 Mg/ha/yr), but not N (0.01 Mg/ha/yr). The legume‐based system of V‐M‐W‐S sequestered significant amounts of both C (0.29 Mg/ha/yr) and N (0.04 Mg/ha/yr). The grass‐based system of O‐M‐W‐S showed the lowest sequestration of C (0.09 Mg/ha/yr). In all systems, a positive relationship (R2 = 0.71) occurred between estimated addition of root C and soil C stock to 1 metre. Whenever C and N sequestration occurred, more than half of that occurred below 20 cm depth. Results suggest that adoption of legume‐based systems, perennially as A‐M or annually as V‐M‐W‐S, is efficient for C and N sequestration in subtropical zero‐tillage soils and that roots possibly contribute more to that sequestration than aboveground biomass.
Invasive mold infections in lung and heart‐lung transplant recipients: Stanford University experience
Authors: Vazquez R. , Vazquez‐Guillamet M.C. , Suarez J. , Mooney J. , Montoya J.G. , Dhillon G.S.
Published: February 2015

Background

Recipients of lung transplantation (LT) and heart‐lung transplantation (HLT) are at increased risk of infection, including invasive mold infections (IMIs). The clinical presentation, radiographic correlates, and outcomes of Aspergillus and non‐AspergillusIMIs in this population have not been well documented.

Methods

LT and HLT recipients diagnosed with IMIs between 1990 and 2012 were identified using the Stanford Translational Research Integrated Database Environment and Stanford LT and HLT clinical database. Recipient clinical and radiographic characteristics were obtained via retrospective review of medical records and compared between Aspergillus and non‐Aspergillus mold recipients. Risk factors for mortality were identified using multivariate logistic regression analysis.

Results

During the study period, 87 (14%) transplant recipients were diagnosed with IMIs. Aspergillus species were isolated in 63 (72%) and non‐Aspergillus molds in 24 (28%) recipients. No significant difference was seen in presenting symptoms or radiographic findings between Aspergillus and non‐Aspergillus mold recipients. Median time to diagnosis was 363 days in the Aspergillus group and 419 days in the non‐Aspergillus group, with dissemination occurring only within the non‐Aspergillus group (12.5%). Overall 90‐day and 1‐year mortality following IMI was 24% and 44%. One‐year mortality was increased in the non‐Aspergillus group (39.5% vs. 60.5%, P = 0.03).

Conclusions

There is significant overlap in risk factors, presentation, and radiographic patterns in IMI in LT or HLT recipients. Non‐Aspergillus molds were more likely to present late, with disseminated disease, and portend increased 1‐year mortality.
Mechanisms of growth and patterns of gene expression in oxygen‐deprived rice coleoptiles
Authors: Narsai Reena , Edwards Joshua M. , Roberts Thomas H. , Whelan James , Joss Gregory H. , Atwell Brian J.
Published: February 2015

Coleoptiles of rice (Oryza sativa) seedlings grown under water commonly elongate by up to 1 mm h−1 to reach the atmosphere. We initially analysed this highly specialized phenomenon by measuring epidermal cell lengths along the coleoptile axis to determine elongation rates. This revealed a cohort of cells in the basal zone that elongated rapidly following emergence from the embryo, reaching 200 μm within 12 h. After filming coleoptiles in vivo for a day, kinematic analysis was applied. Eight time‐sliced ‘segments’ were defined by their emergence from the embryo at four‐hourly intervals, revealing a mathematically simple growth model. Each segment entering the coleoptile from the embryo elongated at a constant velocity, resulting in accelerating growth for the entire organ. Consistent with the epidermal cell lengths, relative rates of elongation (mm mm−1 h−1) were tenfold greater in the small, newly emerged basal segments than the older distal tip segments. This steep axial gradient defined two contrasting growth zones (bases versus tips) in which we measured ATP production and protein, RNA and DNA content, and analysed the global transcriptome under steady‐state normoxia, hypoxia (3% O2) and anoxia. Determination of the transcriptome revealed tip‐specific induction of genes encoding TCP [Teosinte Branched1 (Tb1) of maize, Cycloidea (Cyc), and Proliferating Cell Factor (Pcf)] transcription factors, RNA helicases, ribosomal proteins and proteins involved in protein folding, whilst expression of F–box domain‐containing proteins in the ubiquitin E3–SCF complex (Skp, Cullin, F‐box containing complex) was induced specifically in bases under low oxygen conditions. We ascribed the sustained elongation under hypoxia to hypoxia‐specific responses such as controlled suppression of photosystem components and induction of RNA binding/splicing functions, indicating preferential allocation of energy to cell extension.
Oxygen cost of exercise hyperpnoea is greater in women compared with men
Authors: Dominelli Paolo B. , Render Jacqueline N. , Molgat‐Seon Yannick , Foster Glen E. , Romer Lee M. , Sheel A. William
Published: February 2015

Key points

The oxygen cost of breathing represents a significant fraction of total oxygen uptake during intense exercise.

At a given ventilation, women have a greater work of breathing compared with men, and because work is linearly related to oxygen uptake we hypothesized that their oxygen cost of breathing would also be greater.

For a given ventilation, women had a greater absolute oxygen cost of breathing, and this represented a greater fraction of total oxygen uptake.

Regardless of sex, those who developed expiratory flow limitation had a greater oxygen cost of breathing at maximal exercise.

The greater oxygen cost of breathing in women indicates that a greater fraction of total oxygen uptake (and possibly cardiac output) is directed to the respiratory muscles, which may influence blood flow distribution during exercise.

We compared the oxygen cost of breathing () in healthy men and women over a wide range of exercise ventilations (). Eighteen subjects (nine women) completed 4 days of testing. First, a step‐wise maximal cycle exercise test was completed for the assessment of spontaneous breathing patterns. Next, subjects were familiarized with the voluntary hyperpnoea protocol used to estimate . During the final two visits, subjects mimicked multiple times (four to six) the breathing patterns associated with five or six different exercise stages. Each trial lasted 5 min, and on‐line pressure–volume and flow–volume loops were superimposed on target loops obtained during exercise to replicate the work of breathing accurately. At ∼55 l min−1 , was significantly greater in women. At maximal ventilation, the absolute was not different (P > 0.05) between the sexes, but represented a significantly greater fraction of whole‐body in women (13.8 ± 1.5 vs. 9.4 ± 1.1% ). During heavy exercise at 92 and 100% , the unit cost of was +0.7 and +1.1 ml O2 l−1 greater in women (P < 0.05). At , men and women who developed expiratory flow limitation had a significantly greater than those who did not (435 ± 44 vs. 331 ± 30 ml O2 min−1). In conclusion, women have a greater for a given , and this represents a greater fraction of whole‐body . The greater in women may have implications for the integrated physiological response to exercise.
Observe-Based Projective Synchronization of Chaotic Complex Modified Van Der Pol-Duffing Oscillator With Application to Secure Communication
Authors: Liu Ping , Song Hongjun , Li Xiang
Published: February 2015

This paper addresses the projective synchronization (PS) of the complex modified Van der Pol-Duffing (MVDPD for short) chaotic oscillator by using the nonlinear observer control and also discusses its applications to secure communication in theory. First, we construct the complex MVDPD oscillator and analysis its chaotic behavior. Moreover, an observer design method is applied to achieve PS of two identical MVDPD chaotic oscillators with complex offset terms, which are synchronized to the desired scale factor. The unpredictability of the scaling factor could further enhance the security of the communication. Finally, numerical simulations are given to demonstrate the effectiveness and feasibility of the proposed synchronization approach and also verify the success application to the proposed scheme’s in the secure communication.
Simulations of polydisperse magnetorheological fluids: A structural and kinetic investigation
Authors: Fernández-Toledano J. C. , Ruiz-López J. A. , Hidalgo-Álvarez R. , de Vicente J.
Published: February 2015

A simulation method is proposed to explore the effect of particle size polydispersity in magnetorheology including Brownian motion. The method aims to extend the classical particle-level simulation methodology developed by Klingenberg et al. [J. Chem. Phys. 91, 7888–7895 (1989)] for the case of polydisperse magnetorheological (MR) fluids. The simulation study concerns the aggregation kinetics at rest as well as the rheological behavior under start-up of steady shear and dynamic oscillatory shear tests at increasing strain amplitudes. Results demonstrate that the effect of polydispersity is only relevant at the transition regime between magnetostatic to hydrodynamic control of the suspension structure. The yielding behavior is correlated to the structural characteristics (radial distribution functions, pair correlation functions, and angular connectivities) of the MR fluids before the onset of flow. A more abrupt transition is observed for polydisperse MR fluids because interparticle links are weaker in this case if compared to monodisperse suspensions in spite of the fact that polydisperse MR fluids exhibit a larger connectivity.
The many faces of hepatocellular carcinoma
Authors: Faltas Bishoy M.
Published: February 2015

Hepatocellular carcinoma has substantial heterogeneity at the cell, marker, and genetic level.
Beam me up, Scotty: The future of ablation
Authors: Stecker Eric C.
Published: February 2015

Noninvasive ablation of arrhythmias could become a reality with ion beam technology.
p53-Derived Host Restriction of HIV-1 Replication by Protein Kinase R-Mediated Tat Phosphorylation and Inactivation
Authors: Yoon Cheol-Hee , Kim Sang-Yoon , Byeon Se Eun , Jeong Yideul , Lee Jinjoo , Kim Kwang Pyo , Park Jinseu , Bae Yong-Soo
Published: February 2015

Tumor suppressor p53 has been suggested to be a host restriction factor against HIV-1 replication, but the detailed molecular mechanism has remained elusive for decades. Here, we demonstrate that p53-mediated HIV-1 suppression is attributed to double-stranded RNA (dsRNA)-dependent protein kinase (PKR)-mediated HIV-1
trans
-activator (Tat) phosphorylation and inactivation. p53 silencing significantly enhanced HIV-1 replication in infected cells. Ectopic expression of p53 suppressed Tat activity, which was rescued by PKR silencing. In addition, ectopic expression of PKR abolished Tat activity in p53
−/−
and eIF2α
CA
cells. Finally, we found that HIV-1 infection activates p53, followed by the induction and activation of PKR. PKR directly interacted with HIV-1 Tat and phosphorylates the first exon of Tat exclusively at five Ser/Thr residues (T23, T40, S46, S62, and S68), which inhibits Tat-mediated provirus transcription in three critical steps: (i) phosphorylation near the arginine-rich motif (ARM) inhibits Tat translocation into the nucleus, (ii) accumulation of Tat phosphorylation abolishes Tat–Tat-responsive region (TAR) binding, and (iii) Tat phosphorylation at T23 and/or T40 obliterates the Tat-cyclin T1 interaction. These five Ser/Thr sites on Tat were highly conserved in HIV-1 strains prevalent in Europe and the United States. Taken together, our findings indicate that p53-derived host restriction of HIV-1 replication is likely attributable, at least in part, to a noncanonical p53/PKR/Tat phosphorylation and inactivation pathway in HIV-1 infection and AIDS pathogenesis.

IMPORTANCE
HIV-1-mediated disease progression to AIDS lasts for years to decades after primary infection. Host restriction and associated viral latency have been studied for several decades. p53 has been suggested as an important host restriction factor against HIV-1 replication. However, the detailed molecular mechanism is still unclear. In the present study, we found that the p53-mediated HIV-1 restriction is attributed to a p53/PKR/Tat-inactivation pathway. HIV-1 infection activated p53, which subsequently induced PKR expression and activation. PKR directly phosphorylated Tat exclusively at five specific Ser/Thr residues, which was accompanied by significant suppression of HIV-1 replication. Accumulation of Tat phosphorylation at these sites inhibited Tat function by blocking Tat nuclear localization, Tat binding to TAR, and Tat-cyclin T1 interaction. Our findings provide a better understanding of the p53-derived host restriction mechanism against HIV-1 replication in AIDS pathogenesis and may contribute to further research focusing on the investigation of potential therapeutic targets for HIV-1.
CceR and AkgR Regulate Central Carbon and Energy Metabolism in Alphaproteobacteria
Authors: Imam Saheed , Noguera Daniel R. , Donohue Timothy J.
Published: February 2015

Many pathways of carbon and energy metabolism are conserved across the phylogeny, but the networks that regulate their expression or activity often vary considerably among organisms. In this work, we show that two previously uncharacterized transcription factors (TFs) are direct regulators of genes encoding enzymes of central carbon and energy metabolism in the alphaproteobacteriumRhodobacter sphaeroides. The LacI family member CceR (RSP_1663) directly represses genes encoding enzymes in the Entner-Doudoroff pathway, while activating those encoding the F1F0ATPase and enzymes of the tricarboxylic acid (TCA) cycle and gluconeogenesis, providing a direct transcriptional network connection between carbon and energy metabolism. We identified bases that are important for CceR DNA binding and showed that DNA binding by this TF is inhibited by 6-phosphogluconate. We also showed that the GntR family TF AkgR (RSP_0981) directly activates genes encoding several TCA cycle enzymes, and we identified conditions where its activity is increased. The properties of single and double ΔCceR and ΔAkgR mutants illustrate that these 2 TFs cooperatively regulate carbon and energy metabolism. Comparative genomic analysis indicates that CceR and AkgR orthologs are found in other alphaproteobacteria, where they are predicted to have a conserved function in regulating central carbon metabolism. Our characterization of CceR and AkgR has provided important new insight into the networks that control central carbon and energy metabolism in alphaproteobacteria that can be exploited to modify or engineer new traits in these widespread and versatile bacteria.

IMPORTANCETo extract and conserve energy from nutrients, cells coordinate a set of metabolic pathways into integrated networks. Many pathways that conserve energy or interconvert metabolites are conserved across cells, but the networks regulating these processes are often highly variable. In this study, we characterize two previously unknown transcriptional regulators of carbon and energy metabolism that are conserved in alphaproteobacteria, a group of abundant, environmentally and biotechnologically important organisms. We identify the genes they regulate, the DNA sequences they recognize, the metabolite that controls the activity of one of the regulators, and conditions where they are required for growth. We provide important new insight into conserved cellular networks that can also be used to improve a variety of hosts for converting feedstock into valuable products.
α-2,3-Sialyltransferase Expression Level Impacts the Kinetics of Lipooligosaccharide Sialylation, Complement Resistance, and the Ability of Neisseria gonorrhoeae to Colonize the Murine Genital Tract
Authors: Lewis Lisa A. , Gulati Sunita , Burrowes Elizabeth , Zheng Bo , Ram Sanjay , Rice Peter A.
Published: February 2015

Neisseria meningitidisandNeisseria gonorrhoeaemodify the terminal lacto-N-neotetraose moiety of their lipooligosaccharide (LOS) with sialic acid. N. gonorrhoeae LOS sialylation blocks killing by complement, which is mediated at least in part by enhanced binding of the complement inhibitor factor H (FH). The role of LOS sialylation in resistance of N. meningitidis to serum killing is less well defined. Sialylation in each species is catalyzed by the enzyme LOS α-2,3-sialyltransferase (Lst). Previous studies have shown increased Lst activity in N. gonorrhoeae compared to N. meningitidis due to an ~5-fold increase inlsttranscription. Using isogenic N. gonorrhoeae strains engineered to express gonococcallstfrom either the N. gonorrhoeae or N. meningitidislstpromoter, we show that decreased expression oflst(driven by the N. meningitidis promoter) reduced LOS sialylation as determined by less incorporation of tritium-labeled cytidine monophospho-N-acetylneuraminic acid (CMP-NANA; the donor molecule for sialic acid). Diminished LOS sialylation resulted in reduced rates of FH binding and increased pathway activation compared to N. gonorrhoeae promoter-drivenlstexpression. The N. meningitidislstpromoter generated sufficient Lst to sialylate N. gonorrhoeae LOSin vivo, and the level of sialylation after 24 h in the mouse genital tract was sufficient to mediate resistance to human serumex vivo. Despite demonstrable LOS sialylationin vivo, gonococci harboring the N. meningitidislstpromoter were outcompeted by those with the N. gonorrhoeaelstpromoter during coinfection of the vaginal tract of estradiol-treated mice. These data highlight the importance of highlstexpression levels for gonococcal pathogenesis.

IMPORTANCE Neisseria gonorrhoeaehas become resistant to nearly every therapeutic antibiotic used and is listed as an “urgent threat” by the Centers for Disease Control and Prevention. Novel therapies are needed to combat drug-resistant N. gonorrhoeae. Gonococci express an α-2,3-sialyltransferase (Lst) that can scavenge sialic acid from the host and use it to modify lipooligosaccharide (LOS). Sialylation of gonococcal LOS converts serum-sensitive strains to serum resistance, decreases antibody binding, and combats killing by neutrophils and antimicrobial peptides. Mutant N. gonorrhoeae that lack Lst (cannot sialylate LOS) are attenuated in a mouse model. Lst expression levels differ among N. gonorrhoeae strains, and N. gonorrhoeae typically expresses more Lst thanNeisseria meningitidis. Here we examined the significance of differentiallstexpression levels and determined that the level of LOS sialylation is critical to the ability of N. gonorrhoeae to combat the immune system and survive in an animal model. LOS sialylation may be an ideal target for novel therapies.