bluuebunny/crossref_metadata_2025 huggingface dataset:
Pirate Histories: Rethinking the Indian Film Archive
Authors: Tanvir Kuhu
Published: January 2014

This article argues that despite their inherent illegality, forms of media piracy are an essential part of the memory of Bombay cinema. While Bombay cinema’s history is replete with its encounter with myriad pirate forms—cheaply published film dialogs and lyrics, locally produced posters, illegal music tapes, video cassettes, VCDs and DVDs—the activity of viewing, sharing, and storing cinematic objects sees a new order of proliferation online, leading to the creation of a network of private and indeed pirate archives of cinema.

Built largely of illegal material (downloaded, ripped, and copied) and the “poor image” ( Steyerl, 2009 ), the pirate archive is at odds with the official state archive of cinema that is all too aware of its role in preserving the “heritage of Indian cinema.” The pirate archive unpacks the carefully constructed and preserved hierarchy of “meaningful cinema” by including more derided forms like porn and “trash,” bringing them into the fold of history. I argue that its illicit, often incomplete, sometimes erroneous and ephemeral material then poses a challenge to the state archive’s performance of stability and its attempt to control cinematic history.
Association Between Potentially Inappropriate Medications From the Beers Criteria and the Risk of Unplanned Hospitalization in Elderly Patients
Authors: Price Sylvie D. , Holman C. D’Arcy J. , Sanfilippo Frank M. , Emery Jon D.
Published: January 2014

Background: Predisposition to adverse drug events with advancing age has led to the development of lists of potentially inappropriate medications (PIMs) to be avoided in the elderly, such as the Beers Criteria. The prevalence of Beers medications has been studied widely, but it is still unclear whether PIM use is predictive of adverse events in older people. Objectives: To examine potential associations between exposure to PIMs from the general Beers list and unplanned hospitalizations in elderly Western Australians. Methods: Using an enhanced case-time-control design and conditional logistic regression applied to the pharmaceutical claims and other linked health data of 251 305 Western Australians aged ≥65 years (1993-2005), odds ratios for unplanned hospitalization were obtained, from which attributable fractions, number and proportion of hospitalizations associated with drug exposure were derived. Results: Based on the health profiles of 383 150 hospitalized index subjects, overall PIM exposure was associated with an elevated risk of unplanned hospitalization (adjusted odds ratio = 1.18; 95% confidence interval = 1.15-1.21), this estimated risk increasing with the number of different PIMs and PIM quantity taken. Fifteen percent of unplanned hospitalizations in exposed index subjects (1980 per year) were attributed to PIM exposure. Patients taking meperidine (pethidine), nitrofurantoin, promethazine, indomethacin, and thioridazine appeared to be at particularly high risk of unplanned hospitalization, whereas temazepam, oxazepam, diazepam, digoxin, amiodarone, ferrous sulfate, and naproxen were attributed the greatest numbers of unplanned hospitalizations. Conclusions: Due caution prescribing Beers medications in the elderly seems justified, paying particular attention to PIMs listed above and to the concurrent use of multiple PIMs. Our results also support the retention of specific medications on PIM lists in future developments.
Approach to Antimicrobial Prophylaxis for Urology Procedures in the Era of Increasing Fluoroquinolone Resistance
Authors: Marino Sabo Elizabeth , Stern John J.
Published: January 2014

Objective: To evaluate rationale antimicrobial prophylaxis options in patients undergoing urologic procedures in the era of increasing fluoroquinolone resistance. Data Sources: Literature was accessed through MEDLINE (1980-October 2013) using the search terms “urologic surgical procedures,” “antibiotic prophylaxis,” and “drug resistance.” Study Selection and Data Extraction: Pertinent article titles and abstracts were reviewed by the authors in addition to reference citations from publications. All English language publications identified were evaluated. Data Synthesis: The American Urology Association guidelines recommend fluoroquinolones (FQs) as first-line agents for preoperative prophylaxis to prevent infection after urologic procedures. Since the latest publication of these guidelines in 2008, resistance within this class of drugs has been increasing especially among common urologic pathogens like Escherichia coli. Limited data are available to support non-FQ alternatives for preoperative prophylaxis, and small studies published prior to 2000 have been conducted using such regimens with success. FQs have become the mainstay of prophylaxis in this population because of ease of administration, relatively low cost, and excellent oral bioavailability; however, β-lactam class antimicrobials may be emerging as effective alternatives based on more favorable resistance profiles. Conclusions: Based on the current available literature, geographic areas with increasing FQ resistance should consider using cephalosporin agents as alternatives for prophylaxis in patients undergoing urologic procedures, reserving FQ in patients unable to tolerate β-lactams because of type-1 hypersensitivity reactions or other adverse effects.
Erythema Multiforme Secondary to Dimenhydrinate in a Patient With Previous Similar Reactions to Pamabrom
Authors: Tan Doreen Su-Yin , Sklar Grant E.
Published: January 2014

Objective: To report a case of erythema multiforme secondary to dimenhydrinate and pamabrom cross-sensitivity. Case Summary: A 22-year-old Chinese female presented with a complaint of lip mucosal ulceration with necrosis and stomatitis, worsening over the past 24 hours and associated with reduced oral intake and incomplete opening of the mouth. Presentation was accompanied by a generalized rash and genital mucosal involvement. The only new systemically ingested agent was dimenhydrinate approximately 4 days prior to admission. She had no significant medical history, but was labeled to be allergic to acetaminophen. She had a positive history of 2 similar presentations secondary to Panadol Menstrual (acetaminophen and pamabrom), once 3 years ago and again 5 months prior to the current admission. An objective causality assessment revealed that the adverse drug event was “probable” to dimenhydrinate. A detailed history revealed a negative drug challenge to acetaminophen. She had previously taken plain acetaminophen and Beserol (acetaminophen and chlormezanone) with no reaction. Discussion: A comprehensive history taking facilitated the diagnosis of erythema multiforme secondary to dimenhydrinate without the need to perform invasive testing, and the removal of erroneous allergy labeling to acetaminophen. Dimenhydrinate and pamabron both contain theophylline-related structures in their chemical composition. Similar reactions to pamabrom strongly suggested cross-sensitivity to theophylline-related structures. Conclusions: To our knowledge, this is the first report of erythema multiforme due to dimenhydrinate with pamabron cross-sensitivity. We recommend that comprehensive medication-history taking be carried out for all drug-allergy patients to ensure greater informed decision making when choosing medications to use for that patient in the future.
The usefulness of game theory as a method for policy evaluation
Authors: Hermans Leon , Cunningham Scott , Slinger Jill
Published: January 2014

Most of today’s public policies are formulated and implemented in multi-actor networks. Game theory has long been around as a method that supports a careful analysis of interaction processes among actors. So far, it has not been widely applied in the evaluation field. Hence, questions regarding the usefulness of game theory as an evaluation method remain pertinent. This article addresses these questions, based on a review of literature on evaluations and game theory, and a case where game theory was used in an evaluation of coastal policy implementation in the Netherlands. The results suggest that game theory can help to open up the ‘black-box’ of policy implementation, when implementation depends on the actions of several interdependent actors. This potential lies not so much in ‘hard’ mathematical uses, but in the use of game theory as a formal modeling approach that adds structure and rigour to the study of social processes.
Using performance measurement to assess research: Lessons learned from the international agricultural research centres
Authors: Immonen Sirkka , Cooksy Leslie L.
Published: January 2014

In the past few decades performance measurement systems have been employed in the public sector to enforce accountability and enhance the efficiency and effectiveness of operations. Performance measurement systems as part of research evaluation are a special case. In this article, the suitability of performance measurement for the evaluation of research is analysed, drawing on experiences from a group of 15 international agricultural research centres that conduct research with a development mission. The performance measurement system initiated by donors was intended to become part of a streamlined monitoring and evaluation system and to enhance transparency, accountability, learning, and decision making, including decisions about future funding. The experiences showed that: (i) there were large year-to-year fluctuations that were probably related to the selected indicators rather than actual performance, therefore undermining annual conclusions about performance; (ii) using the indicator information for resource allocation influenced performance reporting and emphasized comparison between centres; and (iii) performance measurement information was not used efficiently in other evaluations. The article examines lessons drawn from the objectives, expectations and results of the performance measurement exercise for planning monitoring systems for research in multi-partner settings.
Theory-based evaluation of capacity-building interventions
Authors: Nakrošis Vitalis
Published: January 2014

Despite the increased attention of evaluation theorists and practitioners on theory-based evaluation, there is still no agreement regarding how to apply this evaluation approach in practice. In order to further advance the application of theory-based evaluation, the article elaborates a specific causal model for the in-depth evaluation of capacity-building interventions supported by the European Social Fund. This model of program outcomes is used to make a contribution claim: that better results of one set of performance management projects can be explained by their better design and more favorable conditions for their implementation compared to other similar projects. The article suggests setting some specific conditionalities – such as assessing the organizational maturity of potential beneficiaries and improving their project management systems before the start of project execution – to improve the implementation of future capacity-building interventions.
Low status groups show in-group favoritism to compensate for their low status and compete for higher status
Authors: Rubin Mark , Badea Constantina , Jetten Jolanda
Published: January 2014

The present research investigated the intergroup allocation behavior of members of low-status groups. In two studies where status relations were either relatively illegitimate (Study 1, N = 139) or legitimate (Study 2, N = 114), undergraduate students completed a minimal group resource allocation task that took into account the intergroup status hierarchy. In both studies, members of low-status groups showed two forms of in-group favoritism. They selected resource allocation choices that (a) compensated for their low status and led to intergroup fairness ( compensatory favoritism) and (b) competed with the out-group for status and led to positive distinctiveness for the in-group ( competitive favoritism). These results suggest that members of low-status groups use in-group favoritism to make their group (a) as good as the high-status out-group and (b) better than the high-status out-group. The findings support the idea that in-group favoritism can serve different functions.
Legal protections against criminal background checks in Europe
Authors: Pijoan Elena Larrauri
Published: January 2014

This article discusses whether there is an increasing demand for criminal background checks in continental Europe. It also presents the legislative framework regulating criminal background checks in Europe where a requirement of ‘proof of a clean criminal record’ in public administration often co-exists with a situation where no specific laws regulate the rights of private employers to ask for such proof. Finally, the article suggests some legal protections for ex-offenders against the increasing use of criminal records in the job market and suggests that a law may be necessary to regulate the right of private employers to conduct criminal background checks.
Tick-tock: Is your cardiometabolic risk on the clock?
Authors: Stöhr Robert , Marx Nikolaus , Federici Massimo
Published: January 2014

Governing a large amount of cellular processes in mammalian cells is a 24-h regulatory mechanism known as the circadian clock. Through the release of neurohormonal factors, the master central clock is able to regulate the otherwise independent peripheral clocks situated in all vital organs. It has recently been shown that forced misalignment of the circadian cycles, often as a consequence of lifestyle factors, is an independent cardiometabolic risk factor and may thus potentially predispose certain groups, such as nightshift workers, to cardiovascular disease. In this review, we will analyse some of the recent advances regarding circadian clock dysfunction and the development of cardiovascular diseases. Finally, we will touch on the developing link between circadian dysfunction and myocardial infarctions.
Uncertainty and Ongoing Economic Turbulence
Authors: McCarthy Alma , Sheehan Maura
Published: January 2014

The Problem

The global financial crisis and uncertainty has the potential to significantly affect the human resource development (HRD) field in terms of investment levels in training and development; the nature, content, and focus of HRD interventions and programs; evaluation processes used to determine return on investment in HRD; and the role of HRD scholars and practitioners in assisting organizations to navigate such uncertain and turbulent economic environments. However, there is little to no debate about how HRD is responding to the crisis or how HRD scholars and practitioners can or should influence people management and development policy and practice during an era of ongoing economic turbulence.

The Solution

The current issue will address the gap that exists in our understanding of HRD during uncertain times. The issue draws together multi-level and multi-perspective insights into how HRD has responded to the uncertainty and ongoing economic turbulence. The papers are drawn from a range of different cultures and countries, across different levels of analysis, from the individual to the organization, to government and regulation. The methodologies used in the current issue papers are diverse and include quantitative, qualitative, integrative literature review, and an academic-practitioner reflection. The current issue sets out important implications for how HRD practitioners and researchers can assist the HRD field to respond to and shape organizational and government responses to the uncertainty and ongoing turbulence.

The Stakeholders

Scholars, practitioners, and policy makers interested in the human resource development field.
Investment in Training and Development in Times of Uncertainty
Authors: Sheehan Maura
Published: January 2014

The Problem

While there is some consensus in the economics literature that there is a negative association between uncertainty and investment in capital, whether this relationship applies to investment in human capital—in particular training and development (T&D)—undertaken by firms is not clear. The evidence about what has happened to T&D investment in the aftermath of the global financial and economic crisis of 2008 is very inconclusive. This article examines how uncertainty has affected overall, general, and firm-specific T&D post-2008.

The Solution

The analysis shows that T&D investment is highly sensitive to uncertainty, especially general T&D. Given the importance of T&D—especially general T&D for sustained competitive advantage—it is absolutely essential that investment is sustained, even in the presence of uncertainty. Viewing and treating T&D as an investment, rather than its current accountancy configuration, as an “expenditure,” can help to ensure T&D investment is maintained. Practitioners need to become more confident and competent in demonstrating that T&D is an investment, with the potential to generate significant returns for organizations, especially in relation to sustained competitive advantage.

The Stakeholders

The article will be of particular relevance to human-resource development, T&D practitioners, and employees, all of whom have to compete for scarce resources.
The Global Financial and Economic Crisis
Authors: MacKenzie Clíodhna , Garavan Thomas N. , Carbery Ronan
Published: January 2014

The Problem

The Global Financial and Economic Crisis1 starting in 2007 and its resultant impact has called into question the contribution of Human Resource Development (HRD) strategies and practices to the crisis. With its primary focus on the development of human resources, it could be argued that HRD aligned itself too closely with the strategic goals of organizations, often times profit centric, and failed to provide leaders with the skills, knowledge, and values required to question the decisions made by organizations in the pursuit of profit goals and the development of a culture of risk taking.

The Solution

Utilizing Cognitive Appraisal Theory (CAT), this article draws on the official reports and public inquiry hearings in the United States, United Kingdom, and Ireland into the financial crisis and finds that HRD strategies, practices, and processes are factors which may have contributed to a culture of excessive risk taking and ineffective decision making. We outline the implications for HRD theory and practice.

The Stakeholders

The research findings inform a multiplicity of stakeholders including organizational behaviorists, social psychologists, government bodies, educational organizations, and scholars researching strategic HRD in organizations.
A Review of Human Resource Development Trends and Practices in Australia
Authors: McGraw Peter
Published: January 2014

The Problem

The evolution of human resource development (HRD) practices in Australian-based organizations has been the focus of only limited rigorous longitudinal research. Consequently, HRD practitioners lack data on key trends against which to position their own initiatives.

The Solution

This article outlines, analyzes, and comments on the pattern of HRD from the mid-1990s to the present day with reference to economic turbulence and responses to it, especially since the beginning of the global financial crisis in 2007. The central themes of the review are the emergence of more “performance”-oriented approaches toward HRD assessment and evaluation, the HRD practices of multinational companies (MNCs) operating in Australia compared with locally owned organizations, and HRD practices within foreign owned MNCs from different home countries. Data for the article is drawn primarily from the analysis of three iterations of the Cranfield Network on International Human Resource Management (CRANET) Australia survey from the years 1996, 1999, and 2009.

The Stakeholders

Practical lessons are drawn from the review concerning the current focus on reactive, performance-oriented, short-term HRD practices and the neglect of more strategic long-term HRD initiatives. The results will be of interest to researchers, policymakers, and HR practitioners.
Economic Impact of a Noncomprehensive Smoke-Free Air Law
Authors: Tauras John A. , Chaloupka Frank J. , Keith Jennifer D. , Brown Deborah P. , Meyer Joy Blankley
Published: January 2014

Background. Many stakeholders were interested in the potential economic impact of Pennsylvania’s 2008 Clean Indoor Air Act (CIAA). This study focused on the examination of economic change subsequent to CIAA and, because CIAA allows certain venue exemptions among eating and drinking establishments, if the allowance of exemptions influenced that impact. Policy analysis. Prais–Winsten regressions were employed to assess effects of CIAA and law exemptions on county-level quarterly taxable sales in restaurants and drinking establishments. Regressions controlled for general economic activity, trends in eating/drinking establishment sales, seasonality, and county characteristics. Findings. Across models, CIAA had no significant negative effects on taxable sales in full-/limited-service restaurants or drinking establishments and some positive effects. CIAA exemptions for drinking establishments do not offer a clear economic benefit. Restaurant and drinking establishment taxable sales were strongly related to overall economic conditions and seasonality. Conclusion. After controlling for confounding factors, and consistent with the weight of the evidence from literature on the economic impact of smoke-free policies, our study concludes that the Pennsylvania CIAA had no negative effects on per capita restaurant and drinking establishment taxable sales. High rates of drinking establishment exemptions were not economically beneficial. This study can inform efforts to make smoke-free laws more comprehensive.
Establishing Field Relations through Shared Ideology
Authors: Shariff Fauzia
Published: January 2014

Current literature on identity and insider–outsider positioning in field relations is dominated by discussions of overt characteristics such as shared ethnicity, gender, and class. The potential for self-positioning as an ally researcher through shared ideology opens new possibilities for research methods, but its precarious nature needs to be better understood. Multisited research provides a unique context for exploring this. Through my research in rural South Asia, I have found that shared ideology is more likely to be effective in forming good research relations where the politics of struggle is local and negotiated such that daily happenings allow the researcher to overtly demonstrate empathy with the group under study.
Separation and detection of urinary proteins by two-dimensional electrophoresis on the microfluidic chip
Authors: Ni Yanan , Gan Jun , Xu Yi
Published: January 2014

A novel separating and detecting method of urinary proteins by non-gel sieving electrophoresis–free flow electrophoresis on the microfluidic chip was proposed in this article. Human serum albumin and human transferrin labeled by fluorescein isothiocyanate were mixed and taken as the synthesized urinary protein samples. Factors affected on separation, such as the rate of electric fields applied in two dimension, the addition in the buffer, the concentration, and pH of buffer, were optimized, that is, 10% (w/v) dextran, 0.5% ethanediamine, 0.2 mol L−1 Tris–boric acid, pH 9.3, the ratio of the applied electric field in two dimensions 1:4.8, respectively. Fluorescein isothiocyanate–human serum albumin and fluorescein isothiocyanate–transferrin were efficiently separated in 2 min, and the resolution of two proteins achieved was 2.2 by the designed microfluidic chip. Then, the urine samples of nephropathy patient were analyzed by the proposed non-gel sieving electrophoresis–free flow electrophoresis on the microfluidic chip. The results matched well with those detected by common clinical methods.
A comparative study of regulatory prospects for drug-device combination products in major pharmaceutical jurisdictions
Authors: Kapoor Vicky , Kaushik Deepak
Published: January 2014

In current scenario of innovative products, some of the products which hold a premier stand are those that combine, in some combination or others, elements of drugs, devices, and biologics. Drug-device combination products introduced a new change in medical product development, regulatory approval, and industrial interaction that provide valuable lessons for the development of new generations of medical products. These cutting-edge technologies have yielded the products to deliver drugs and biologics to specific targets within the body. In this paper, an introduction is given about combination products, their usefulness in the current drug delivery technologies, challenges in their regulation along with a brief history of these products, and overview of their regulatory status in major pharmaceutical jurisdictions. A brief review on regulatory path for their approval in various countries with special focus on drug device combinations along with the challenges faced by industries regarding their market approval is also given. For their market approval, the role and responsibilities of regulatory authority are addressed along with a brief description on review steps taken by Food and Drug Administration.
Successes and challenges in varicella vaccine
Authors: Papaloukas Orestis , Giannouli Georgia , Papaevangelou Vassiliki
Published: January 2014

Varicella is a highly contagious disease caused by primary infection with varicella zoster virus (VZV). VZV infection, as well as varicella vaccination, induces VZV-specific antibody and T-cell-mediated immunity, essential for recovery. The immune responses developed contribute to protection following re-exposure to VZV. When cell-mediated immunity declines, as occurs with aging or immunosuppression, reactivation of VZV leads to herpes zoster (HZ). It has been almost 20 years since universal varicella vaccination has been implemented in many areas around the globe and this has resulted in a significant reduction of varicella-associated disease burden. Successes are reviewed here, whilst emphasis is put on the challenges ahead. Most countries that have not implemented routine childhood varicella vaccination have chosen to vaccinate high-risk groups alone. The main reasons for not introducing universal vaccination are discussed, including fear of age shift of peak incidence age and of HZ incidence increase. Possible reasons for not observing the predicted increase in HZ incidence are explored. The advantages and disadvantages of universal vs targeted vaccination as well as different vaccination schedules are discussed.
Azathioprine-Induced Rapid Hepatotoxicity
Authors: Horning Kristin , Schmidt Chelsea
Published: January 2014

Objective: To report a case of rapid hepatotoxicity seen within days of initiating azathioprine therapy as a possible adverse reaction. Case Summary: A 62-year-old female with Crohn’s disease was being maintained on occasional oral prednisone when more aggressive therapy became indicated. The patient was started on azathioprine and continued a prednisone taper. Liver enzymes became elevated by the third day of therapy. Peak liver enzyme values on day 10 of therapy were aspartate aminotransferase 119 U/L, alanine aminotransferase 210 U/L, and alkaline phosphatase 460 U/L. The patient did not develop any symptoms of hepatotoxicity. Azathioprine was discontinued and liver enzyme levels returned to baseline within 3 weeks. Discussion: Azathioprine hepatotoxicity has been reported previously. A MEDLINE search (1966 to August 2013) found 39 articles related to various types of azathioprine hepatotoxicity. Previous literature predominately involves male patients and a general onset of 2 to 12 months after starting azathioprine therapy. Our case involves a female patient with an onset of days. According to the Naranjo probability scale, this reaction is considered possible, whereas the Council for International Organizations of Medical Sciences Probability Scale categorized this reaction as probable. The concurrent prednisone therapy may have increased the patient’s risk of azathioprine hepatotoxicity, but is not likely the sole cause as prior to and after discontinuing azathioprine the liver enzymes remained normal despite prednisone therapy. Conclusions: Prescribers should be aware that monitoring liver enzymes when initiating azathioprine may be warranted within the first week, especially if the patient is taking corticosteroids or other high-risk medications that cause hepatotoxicity.
Bcl2 overexpression rescues the hematopoietic stem cell defects in Ku70-deficient mice by restoration of quiescence
Authors: Qing Yulan , Wang Zhengqi , Bunting Kevin D. , Gerson Stanton L.
Published: January 2014

Key Points

Loss of Ku70 results in loss of HSC quiescence, which correlates with loss of HSC maintenance. Bcl2 overexpression rescues HSC defects in Ku70−/− mice by restoring quiescence, without restoration of DNA repair capacity.
How will B-cell-receptor–targeted therapies change future CLL therapy?
Authors: Jones Jeffrey A. , Byrd John C.
Published: January 2014

For many years there has been considerable disassociation between the understood biology of chronic lymphocytic leukemia (CLL) and the therapeutics used to treat this disease. With the introduction of the first targeted CD20 antibody rituximab and its addition to chemotherapy came the first observation that minimal residual disease–negative (MRD-negative) complete responses (CRs) could be obtained with dramatically improved progression-free survival and overall survival. This advance was soon to be surpassed by the introduction of therapeutics that target B-cell receptor (BCR) signaling. New data show that BCR-inhibiting agents are very active for the treatment of relapsed CLL, despite the lack of MRD-negative CR, with durability of response being considerably more impressive than previously observed with other agents not producing MRD-negative CRs. This perspective provides a view of where these agents may take us in the future as CLL therapy evolves with this exciting new class of drugs.
Highly reinforced structure of a C-terminal dimerization domain in von Willebrand factor
Authors: Zhou Yan-Feng , Springer Timothy A.
Published: January 2014

Key Points

C-terminal cystine knot monomers in VWF are highly elongated and form antiparallel dimers. Three disulfides across the dimer interface flanked by the cystine knots in each monomer form a highly force-resistant structure.
Selectins and their ligands are required for homing and engraftment of BCR-ABL1+ leukemic stem cells in the bone marrow niche
Authors: Krause Daniela S. , Lazarides Katherine , Lewis Juliana B. , von Andrian Ulrich H. , Van Etten Richard A.
Published: January 2014

Key Points

In a mouse model, BCR-ABL1+ leukemia stem cells are more dependent on selectins and their ligands for homing and engraftment than normal HSCs. Blockade of selectin-ligand interactions might prevent leukemic engraftment and relapse in autografted patients.
Exhaled breath condensate in intubated neonates- a window into the lung’s glutathione status
Authors: Rosso Maria I , Roark Susan , Taylor Esther , Ping XiaoDu , Ward Janine M , Roche Katherine , McCracken Courtney , Brown Lou Ann S , Gauthier Theresa W
Published: January 2014

Background

Analysis of exhaled breath condensates (EBC) is a non-invasive technique to evaluate biomarkers such as antioxidants in the pediatric population, but limited data exists of its use in intubated patients, particularly newborns. Currently, tracheal aspirate (TA) serves as the gold standard collection modality in critically ill newborns, but this method remains invasive. We tested the hypothesis that glutathione status would positively correlate between EBC and TA collections in intubated newborns in the Newborn Intensive Care Unit (NICU). We also hypothesized that these measurements would be associated with alveolar macrophage (AM) glutathione status in the newborn lung.

Methods

Reduced glutathione (rGSH), glutathione disulfide (GSSG), and total GSH (rGSH + (2 X GSSG)) were measured in sequential EBC and TA samples from 26 intubated newborns via high performance liquid chromatography (HPLC). Additionally, AM glutathione was evaluated via immunofluorescence. Pearson’s correlation coefficient and associated 95% confidence intervals were used to quantify the associations between raw and urea-corrected concentrations in EBC and TA samples and AM staining. Statistical significance was defined as p ≤ 0.05 using two-tailed tests. The sample size was projected to allow for a correlation coefficient of 0.5, with 0.8 power and alpha of 0.05.

Results

EBC was obtainable from intubated newborns without adverse clinical events. EBC samples demonstrated moderate to strong positive correlations with TA samples in terms of rGSH, GSSG and total GSH. Positive correlations between the two sampling sites were observed in both raw and urea-corrected concentrations of rGSH, GSSG and total GSH. AM glutathione staining moderately correlated with GSSG and total GSH status in both the TA and EBC.

Conclusions

GSH status in EBC samples of intubated newborns significantly correlated with the GSH status of the TA sample and was reflective of cellular GSH status in this cohort of neonatal patients. Non-invasive EBC sampling of intubated newborns holds promise for monitoring antioxidant status such as GSH in the premature lung. Further studies are necessary to evaluate the potential relationships between EBC biomarkers in the intubated premature newborn and respiratory morbidities.
Identification and characterization of miRNAome in root, stem, leaf and tuber developmental stages of potato (Solanum tuberosum L.) by high-throughput sequencing
Authors: Lakhotia Nisha , Joshi Gopal , Bhardwaj Ankur R , Katiyar-Agarwal Surekha , Agarwal Manu , Jagannath Arun , Goel Shailendra , Kumar Amar
Published: January 2014

Background

MicroRNAs (miRNAs) are ubiquitous components of endogenous plant transcriptome. miRNAs are small, single-stranded and ~21 nt long RNAs which regulate gene expression at the post-transcriptional level and are known to play essential roles in various aspects of plant development and growth. Previously, a number of miRNAs have been identified in potato through in silico analysis and deep sequencing approach. However, identification of miRNAs through deep sequencing approach was limited to a few tissue types and developmental stages. This study reports the identification and characterization of potato miRNAs in three different vegetative tissues and four stages of tuber development by high throughput sequencing.

Results

Small RNA libraries were constructed from leaf, stem, root and four early developmental stages of tuberization and subjected to deep sequencing, followed by bioinformatics analysis. A total of 89 conserved miRNAs (belonging to 33 families), 147 potato-specific miRNAs (with star sequence) and 112 candidate potato-specific miRNAs (without star sequence) were identified. The digital expression profiling based on TPM (Transcripts Per Million) and qRT-PCR analysis of conserved and potato-specific miRNAs revealed that some of the miRNAs showed tissue specific expression (leaf, stem and root) while a few demonstrated tuberization stage-specific expressions. Targets were predicted for identified conserved and potato-specific miRNAs, and predicted targets of four conserved miRNAs, miR160, miR164, miR172 and miR171, which are ARF16 (Auxin Response Factor 16), NAM (NO APICAL MERISTEM), RAP1 (Relative to APETALA2 1) and HAM (HAIRY MERISTEM) respectively, were experimentally validated using 5′ RLM-RACE (RNA ligase mediated rapid amplification of cDNA ends). Gene ontology (GO) analysis for potato-specific miRNAs was also performed to predict their potential biological functions.

Conclusions

We report a comprehensive study of potato miRNAs at genome-wide level by high-throughput sequencing and demonstrate that these miRNAs have tissue and/or developmental stage-specific expression profile. Also, predicted targets of conserved miRNAs were experimentally confirmed for the first time in potato. Our findings indicate the existence of extensive and complex small RNA population in this crop and suggest their important role in pathways involved in diverse biological processes, including tuber development.
Whole genome comparison between table and wine grapes reveals a comprehensive catalog of structural variants
Authors: Di Genova Alex , Almeida Andrea Miyasaka , Muñoz-Espinoza Claudia , Vizoso Paula , Travisany Dante , Moraga Carol , Pinto Manuel , Hinrichsen Patricio , Orellana Ariel , Maass Alejandro
Published: January 2014

Background

Grapevine (Vitis viniferaL.) is the most important Mediterranean fruit crop, used to produce both wine and spirits as well as table grape and raisins. Wine and table grape cultivars represent two divergent germplasm pools with different origins and domestication history, as well as differential characteristics for berry size, cluster architecture and berry chemical profile, among others. ‘Sultanina’ plays a pivotal role in modern table grape breeding providing the main source of seedlessness. This cultivar is also one of the most planted for fresh consumption and raisins production. Given its importance, we sequenced it and implemented a novel strategy for thede novoassembly of its highly heterozygous genome.

Results

Our approach produced a draft genome of 466 Mb, recovering 82% of the genes present in the grapevine reference genome; in addition, we identified 240 novel genes. A large number of structural variants and SNPs were identified. Among them, 45 (21 SNPs and 24 INDELs) were experimentally confirmed in ‘Sultanina’ and six SNPs in other 23 table grape varieties. Transposable elements corresponded toca.80% of the repetitive sequences involved in structural variants and more than 2,000 genes were affected in their structure by these variants. Some of these genes are likely involved in embryo development, suggesting that they may contribute to seedlessness, a key trait for table grapes.

Conclusions

This work produced the first structural variants and SNPs catalog for grapevine, constituting a novel and very powerful tool for genomic studies in this key fruit crop, particularly useful to support marker assisted breeding in table grapes.
Identification and characterization of CBL and CIPK gene families in canola (Brassica napus L.)
Authors: Zhang Hanfeng , Yang Bo , Liu Wu-Zhen , Li Hongwei , Wang Lei , Wang Boya , Deng Min , Liang Wanwan , Deyholos Michael K , Jiang Yuan-Qing
Published: January 2014

Background

Canola (Brassica napus L.) is one of the most important oil-producing crops in China and worldwide. The yield and quality of canola is frequently threatened by environmental stresses including drought, cold and high salinity. Calcium is a ubiquitous intracellular secondary messenger in plants. Calcineurin B-like proteins (CBLs) are Ca2+ sensors and regulate a group of Ser/Thr protein kinases called CBL-interacting protein kinases (CIPKs). Although the CBL-CIPK network has been demonstrated to play crucial roles in plant development and responses to various environmental stresses in Arabidopsis, little is known about their function in canola.

Results

In the present study, we identified seven CBL and 23 CIPK genes from canola by database mining and cloning of cDNA sequences of six CBLs and 17 CIPKs. Phylogenetic analysis of CBL and CIPK gene families across a variety of species suggested genome duplication and diversification. The subcellular localization of three BnaCBLs and two BnaCIPKs were determined using green fluorescence protein (GFP) as the reporter. We also demonstrated interactions between six BnaCBLs and 17 BnaCIPKs using yeast two-hybrid assay, and a subset of interactions were further confirmed by bimolecular fluorescence complementation (BiFC). Furthermore, the expression levels of six selected BnaCBL and 12 BnaCIPK genes in response to salt, drought, cold, heat, ABA, methyl viologen (MV) and low potassium were examined by quantitative RT-PCR and these CBL or CIPK genes were found to respond to multiple stimuli, suggesting that the canola CBL-CIPK network may be a point of convergence for several different signaling pathways. We also performed a comparison of interaction patterns and expression profiles of CBL and CIPK in Arabidospsis, canola and rice, to examine the differences between orthologs, highlighting the importance of studying CBL-CIPK in canola as a prerequisite for improvement of this crop.

Conclusions

Our findings indicate that CBL and CIPK family members may form a dynamic complex to respond to different abiotic or hormone signaling. Our comparative analyses of the CBL-CIPK network between canola, Arabidopsis and rice highlight functional differences and the necessity to study CBL-CIPK gene functions in canola. Our data constitute a valuable resource for CBL and CPK genomics.
Conserved CO-FT regulons contribute to the photoperiod flowering control in soybean
Authors: Fan Chengming , Hu Ruibo , Zhang Xiaomei , Wang Xu , Zhang Wenjing , Zhang Qingzhe , Ma Jinhua , Fu Yong-Fu
Published: January 2014

Background

CO and FT orthologs, belonging to the BBX and PEBP family, respectively, have important and conserved roles in the photoperiod regulation of flowering time in plants. Soybean genome experienced at least three rounds of whole genome duplications (WGDs), which resulted in multiple copies of about 75% of genes. Subsequent subfunctionalization is the main fate for paralogous gene pairs during the evolutionary process.

Results

The phylogenic relationships revealed that CO orthologs were widespread in the plant kingdom while FT orthologs were present only in angiosperms. Twenty-eight CO homologous genes and twenty-four FT homologous genes were gained in the soybean genome. Based on the collinear relationship, the soybean ancestral CO ortholog experienced three WGD events, but only two paralogous gene pairs (GmCOL1/2 and GmCOL5/13) survived in the modern soybean. The paralogous gene pairs, GmCOL1/2 or GmCOL5/13, showed similar expression patterns in pair but different between pairs, indicating that they functionally diverged. GmFTL1 to 7 were derived from the same ancestor prior to the whole genome triplication (WGT) event, and after the Legume WGD event the ancestor diverged into two branches, GmFTL3/5/7 and GmFTL1/2/4/6. GmFTL7 were truncated in the N-terminus compared to other FT-lineage genes, but ubiquitously expressed. Expressions of GmFTL1 to 6 were higher in leaves at the flowering stage than that at the seedling stage. GmFTL3 was expressed at the highest level in all tissues except roots at the seedling stage, and its circadian pattern was different from the other five ones. The transcript of GmFTL6 was highly accumulated in seedling roots. The circadian rhythms of GmCOL5/13 and GmFT1/2/4/5/6 were synchronized in a day, demonstrating the complicate relationship of CO-FT regulons in soybean leaves. Over-expression of GmCOL2 did not rescue the flowering phenotype of the Arabidopsis co mutant. However, ectopic expression of GmCOL5 did rescue the co mutant phenotype. All GmFTL1 to 6 showed flower-promoting activities in Arabidopsis.

Conclusions

After three recent rounds of whole genome duplications in the soybean, the paralogous genes of CO-FT regulons showed subfunctionalization through expression divergence. Then, only GmCOL5/13 kept flowering-promoting activities, while GmFTL1 to 6 contributed to flowering control. Additionally, GmCOL5/13 and GmFT1/2/3/4/5/6 showed similar circadian expression profiles. Therefore, our results suggested that GmCOL5/13 and GmFT1/2/3/4/5/6 formed the complicate CO-FT regulons in the photoperiod regulation of flowering time in soybean.
Metabolic engineering of Pseudomonas sp. strain VLB120 as platform biocatalyst for the production of isobutyric acid and other secondary metabolites
Authors: Lang Karsten , Zierow Jessica , Buehler Katja , Schmid Andreas
Published: January 2014

Background

Over the recent years the production of Ehrlich pathway derived chemicals was shown in a variety of hosts such as Escherichia coli, Corynebacterium glutamicum, and yeast. Exemplarily the production of isobutyric acid was demonstrated in Escherichia coli with remarkable titers and yields. However, these examples suffer from byproduct formation due to the fermentative growth mode of the respective organism. We aim at establishing a new aerobic, chassis for the synthesis of isobutyric acid and other interesting metabolites using Pseudomonas sp. strain VLB120, an obligate aerobe organism, as host strain.

Results

The overexpression of kivd, coding for a 2-ketoacid decarboxylase from Lactococcus lactis in Ps. sp. strain VLB120 enabled for the production of isobutyric acid and isobutanol via the valine synthesis route (Ehrlich pathway). This indicates the existence of chromosomally encoded alcohol and aldehyde dehydrogenases catalyzing the reduction and oxidation of isobutyraldehyde. In addition we showed that the strain possesses a complete pathway for isobutyric acid metabolization, channeling the compound via isobutyryl-CoA into valine degradation. Three key issues were addressed to allow and optimize isobutyric acid synthesis: i) minimizing isobutyric acid degradation by host intrinsic enzymes, ii) construction of suitable expression systems and iii) streamlining of central carbon metabolism finally leading to production of up to 26.8 ± 1.5 mM isobutyric acid with a carbon yield of 0.12 ± 0.01 g gglc
-1.

Conclusion

The combination of an increased flux towards isobutyric acid using a tailor-made expression system and the prevention of precursor and product degradation allowed efficient production of isobutyric acid in Ps. sp. strain VLB120. This will be the basis for the development of a continuous reaction process for this bulk chemicals.
A comparison of adipose and bone marrow-derived mesenchymal stromal cell secreted factors in the treatment of systemic inflammation
Authors: Elman Jessica S , Li Matthew , Wang Fangjing , Gimble Jeffrey M , Parekkadan Biju
Published: January 2014

Background

Bone marrow-derived mesenchymal stromal cells (BMSCs) are a cell population of intense exploration for therapeutic use in inflammatory diseases. Secreted factors released by BMSCs are responsible for the resolution of inflammation in several pre-clinical models. New studies have uncovered that adipose tissue also serves as a reservoir of multipotent, non-hematopoietic stem cells, termed adipose-derived stromal/stem cells (ASCs), with many common characteristics to BMSCs. We hypothesized that ASC and BMSC secreted factors would lead to a comparable benefit in the context of generalized inflammation.

Findings

Proteomic profiling of conditioned media revealed that BMSCs express significantly higher levels of sVEGFR1 and sTNFR1, two soluble cytokine receptors with known therapeutic activity in sepsis. In a prophylactic study of endotoxin-induced inflammation in mice, we observed that BMSC secreted factors provided a greater survival benefit and tissue protection of endotoxemic mice compared to ASCs. Neutralization of sVEGFR1 and sTNFR1 did not significantly affect the survival benefit experienced by mice treated with BMSC secreted factors.

Conclusions

Our findings suggest that BMSCs may be more effective as a cell therapeutic for use in endotoxic shock and that ASCs may be positioned for continued exploration in immunomodulatory diseases. Soluble cytokine receptors can distinguish stromal cells from different tissue origins, though they may not be the sole contributors to the therapeutic benefit of BMSCs. Furthermore, other secreted factors not discussed in this study may also differentiate these stromal cell populations from one another.