bluuebunny/crossref_metadata_2025 huggingface dataset:
Possible Medication-Resistant Deficits in Adult ADHD
Authors: Maruta Jun , Spielman Lisa A. , Tseretopoulos Irene D. , Hezghia Adrienne , Ghajar Jamshid
Published: June 2014

Objective: The nature of ADHD, especially in adulthood, is not well-understood. Therefore, we explored subcomponents of attention in adult ADHD. Method: Twenty-three adults with ADHD were tested on neurocognitive and visual tracking performance both while on their regular prescription stimulant medication and while abstaining from the medication for 1 day. Pairwise comparisons to 46 two-for-one matched normal controls were made to detect medication-resistant effects of ADHD, and within-participant comparisons were made to detect medication-sensitive effects in patients. Results: Even when on medication, patients performed more poorly than controls on a spatial working memory task, and on visual tracking and simple reaction time tasks immediately following other attention-demanding tasks. Patients’ visual tracking performance degraded while off-medication in a manner consistent with reduced vigilance. Conclusion: There may be persistent cognitive impairments in adult ADHD despite medication. In addition, the benefit of stimulants seems reduced under cognitive fatigue.
Impact of Social Communication Interventions on Infants and Toddlers With or At-Risk for Autism
Authors: Morgan Lindee J. , Rubin Emily , Coleman Jaumeiko J. , Frymark Tobi , Wang Beverly P. , Cannon Laura J.
Published: June 2014

This is a systematic review of the impact of communication interventions on the social communication skills of infants and toddlers with or at-risk for autism spectrum disorder (ASD). A priori clinical questions accompanied by specific inclusion and exclusion criteria informed the extensive literature search that was conducted in multiple databases (e.g., PubMed). Twenty-six studies were accepted for this review. Outcomes were reported by social communication category (i.e., joint attention, social reciprocity, and language and related cognitive skills) and communication developmental stage (i.e., prelinguistic, emerging language). Primarily positive treatment effects were revealed in the majority of outcome categories for which social communication data were available. However, the presence of intervention and outcome measure heterogeneity precluded a clear determination of intervention effects. Future research should address these issues while also evaluating multiple outcomes and adding a strong family component designed to enhance child active engagement.
Types of planning and property rights
Authors: Slaev Aleksandar D
Published: June 2014

This research contributes to the debate concerning the nature of planning in complex systems, and particularly to the theory of teleocracy (the approach based on direct provisions aimed at specific ends) and nomocracy (the approach based on rules aimed at general rather than specific ends). It draws parallels with the theory of regulation and establishes a connection between rules, regulation and the nomocratic planning of social activities. It then suggests that a property rights analysis of the forms of social coordination/organisation can be instrumental in understanding the nature of social interactions. Based on the theory of property rights, the study concludes that the use of different types of planning, regulation or market mechanisms of social coordination is closely related to the concrete form of ownership over the resources employed in any given social activity.
A Note on Improving Process Efficiency in Panel Surveys with Paradata
Authors: Kreuter Frauke , Müller Gerrit
Published: June 2014

Call scheduling is a challenge for surveys around the world. Unlike cross-sectional surveys, panel surveys can use information from prior waves to enhance call-scheduling algorithms. Past observational studies showed the benefit of calling panel cases at times that had been successful in the past. This article is the first to experimentally assign panel cases to previously beneficial call windows. The results from a large-scale national survey in Germany show modest efficiency gains measured in number of call attempts needed until first contact but no gains in efficiency to gain cooperation.
Opportunistic Behavior in a Cartel Setting
Authors: Carroll Kathleen , Humphreys Brad R.
Published: June 2014

The National Collegiate Athletic Association (NCAA) governs athletics at colleges and universities in the United States. Economists commonly view the NCAA as a cartel. We empirically reexamine evidence from the 1984 Supreme Court decision on football telecasts and find support for cartel behavior and evidence that this model does not fully explain. Our analysis indicates that the NCAA central organization may have behaved opportunistically by overregulating relative to what would maximize cartel net benefits. We provide a theoretical rationale and show that our empirical estimates are consistent with this behavior that occurs within the cartel framework.
Influence of porosity on water vapor permeability behavior of warp knitted polyester spacer fabrics
Authors: Rajan T Palani , Souza Louis D , Ramakrishnan G , Kandhavadivu P , Vigneswaran C
Published: June 2014

Linear density of filament, fabric structure, and number of loops per unit area are the major factors which influence the porosity of warp knitted spacer fabrics. The characteristics of air and water permeability of textile fabrics are chiefly influenced by the porosity of the fabric. An attempt has been made to analyze the water vapor permeability of warp knitted polyester spacer fabric. Spacer fabric face and back surface layers are constructed by polyester multifilament and the middle layer is connected to the two surface layers by polyester monofilament. The behavior of porosity and water vapor permeability were analyzed with respect to the linear density of polyester. The experimental result indicates that the water vapor permeability is highly influenced by porosity of a fabric. The statistical analysis proves the degree of correlation between polyester linear density of spacer fabric layers and their responses. The face and middle layers of fabric are highly significant with the porosity and water vapor permeability. Box–Behnken model was adopted for optimization and a better R2 value of 96.5% is achieved in porosity and the water vapor permeability is 92%.
Unlicensed Administration of Medication
Authors: Zirkel Perry A.
Published: June 2014

This article summarizes the California Supreme Court’s decision in American Nurses Association v. Torlakson concerning the administration of prescription medications, such as insulin injections for students with diabetes, by school personnel who are not licensed nurses. More specifically, the coverage includes (a) an overview of the legal history of this California case; (b) an analysis of the specific contours of the court’s ruling along with their applications and effects in California; and (c) a discussion of the more general legal implications for school nurses and school districts in other states.
Racial Health Disparities Among Special Health Care Needs Children With Mental Disorders
Authors: Park Chanhyun , Tan Xi , Patel Isha B. , Reiff Amanda , Balkrishnan Rajesh , Chang Jongwha
Published: June 2014

Background: A health care reform has been taking place to provide cost-effective and coordinated care. One method of achieving these goals is a patient-centered medical home (PCMH) model, which is associated with provision of quality care among children belonging to racial/ethnic minorities. Despite the potential of the PCMH for children of minority backgrounds, little is known about the extent to which minorities with mental disorders have the PCMH. Objective: The study examined racial/ethnic disparities among children with mental disorders in accessing care from the PCMH. Methods: The 2009-2010 National Survey of Children with Special Health Care Needs (CSHCN) was used for this analysis. Multivariate logistic regressions were applied to capture the racial/ethnic disparities and to analyze a composite outcome of the PCMH. Results: An estimated population size of 4 677 904 CSHCN with mental disorders was included. Among them, 59.94% of children reported to have received medical homes. Compared with white children, the odds of receiving any medical home services decreased among Hispanic children (odds ratio [OR] = 0.69; P < .05) and black children (OR = 0.70; P < .05). The likelihood of having a medical home was lower for Hispanic children than white children, when they had attention deficit hyperactivity disorder (ADHD; OR = 0.57; P < .05) and development delay (OR = 0.73; P < .05). Compared with white children with ADHD or depression having a medical home, the odds of black children with ADHD (OR = 0.63; P < .05) and depression (OR = 0.68; P < .05) having a medical home were lower. Conclusions: There were significant racial/ethnic disparities among CSHCN with mental disorders, indicating several sizeable effects of each of the 5 components on Hispanic, black, and other children compared with white children. These differences could be a potential to improve racial/ethnic disparities.
The Impact of Integrating Community Health Workers Into the Patient-Centered Medical Home
Authors: Matiz Luz Adriana , Peretz Patricia J. , Jacotin Patricia G. , Cruz Carmen , Ramirez-Diaz Erline , Nieto Andres R.
Published: June 2014

Objectives: Establishing patient-centered medical homes (PCMHs) that deliver comprehensive care can be challenging for practices serving diverse populations. Integrating community health workers (CHWs) as members of the care team is one approach to deliver such care; however, little is known about this process. We study an approach of integrating CHWs into PCMHs with predominantly Latino, pediatric asthma patients and examine the impact on care delivery. Methods: A case study was conducted to examine the integration of 8 CHWs into 5 PCMHs in an academic medical center located in a large, urban setting. Data associated with referrals to CHW practice-based education and support and to a care coordination program, as well as survey results from providers on the impact of CHWs in PCMHs were collected and analyzed over the study period. Results: More than 750 families of children with asthma received education and support from CHWs from February 2011 through December 2013. The number of referrals to the care coordination program increased 7-fold during this time ( P < .001). Of providers surveyed (n = 55), those who reported not referring to care coordination decreased from 22% to 6% and those who reported referring patients to care coordination increased from 67% to 79%. Additionally, 39% of providers reported giving a care plan to patients when prompted by the CHW. Conclusions: CHWs can be successfully integrated into the PCMH care team. They may also impact the identification of high-risk populations for care coordination and delivery of comprehensive care.
Pragmatic Liberalism and President Obama
Authors: Khan Haroon A.
Published: June 2014

This research seeks to examine the foreign policy of President Obama with special reference to Bangladesh from the point of pragmatic liberalism. Pragmatism means understanding the realities of the situation and making decisions based on thorough research of these realities. Pragmatism opposes strict adherence to ideological beliefs in pursuing foreign policy. President Obama came into power amid one of the most volatile and dangerous times in the history of the United States occupied with two foreign wars, and inherited an economy on the brink of collapse. The key features of Obama’s pragmatic liberalism in foreign policy are to promote liberal ideas as long as it does not threaten the national security interests, emphasize diplomacy in solving the conflicts, foster humanitarian issues, develop alliances and multilateral agreements, uphold the major national interests, and strengthen national security defined in terms of economic well-being. The article will analyze U.S. foreign policy toward Bangladesh based on pragmatic liberalism of President Obama.
Intermediate Work Outcomes for Adolescents With High-Incidence Disabilities
Authors: Rojewski Jay W. , Lee In Heok , Gregg Noel
Published: June 2014

A longitudinal sample from the Educational Longitudinal Study of 2002 was used to determine differences in work outcomes between (a) individuals with learning disabilities or emotional-behavior disorders and (b) individuals with or without disabilities. Twelve factors were arranged into individual, family, school-peer, and community categories. Individuals with high-incidence disabilities were more likely to be unemployed, whereas those without disabilities were more likely to be employed for 20 hr or more per week. A limited number of risk factors were significant contributors of work outcomes. Ordered logistic regression revealed individuals with high-incidence disabilities and all women experienced less positive work outcomes. Parental discussions with children about work plans enhanced the likelihood of positive work outcomes, but only for adolescents without disabilities.
Teaching Students to Attain Annual Transition Goals Using the Take Action Goal Attainment Lessons
Authors: Martin Jodie D. , Martin James E. , Osmani Kimberly J.
Published: June 2014

This study used the Take Action goal attainment lesson package and assistive technology to teach nine high school students with mild to moderate disabilities to attain annual transition goals. The Take Action lessons increased students’ goal attainment knowledge, and this knowledge generalized to improved Plan Organizers, and slightly increased students attaining transition goals. Added weekly teacher check-ins improved adjusting plan components that did not work and goal attainment increased. Students who took action on four or five Plan Organizer components attained the most goals, and on average, students used four weekly Plan Organizers to attain a goal. Stronger interventions need to be developed to enable more students to increase the action taken on Plan Organizer components.
An Analysis of State Data Collection Protocols for Measuring Postschool Outcomes for Students With Disabilities
Authors: Gerber Paul J. , Batalo Cecilia G. , De Arment Serra T.
Published: June 2014

Indicator 14 is a federal accountability initiative that attempts to generate data on the outcomes of students with disabilities 1 year after leaving high school. Currently, there are only two areas, postsecondary education/training and employment, mandated for examination. Ultimately, the data are used to develop specific goals for 6-year State Performance Plans. This study reports the variability of the data collection instruments in areas of inquiry and number of items in the instruments of all 50 states. Commentary is made regarding the positive and negative aspects as well as missed opportunities in the data collection process for Indicator 14.
A highly compact epitope-based marker/suicide gene for easier and safer T-cell therapy
Authors: Philip Brian , Kokalaki Evangelia , Mekkaoui Leila , Thomas Simon , Straathof Karin , Flutter Barry , Marin Virna , Marafioti Teresa , Chakraverty Ronjon , Linch David , Quezada Sergio A. , Peggs Karl S. , Pule Martin
Published: June 2014

Key Points

Marker genes enable detection and selection of T cells, whereas suicide genes enable selective destruction of T cells in case of toxicity. RQR8 is a 136-amino-acid epitope-based marker/suicide gene that enables clinical selection, cell tracking, and deletion in case of toxicity.
HLA-DRB1*07:01 is associated with a higher risk of asparaginase allergies
Authors: Fernandez Christian A. , Smith Colton , Yang Wenjian , Daté Mihir , Bashford Donald , Larsen Eric , Bowman W. Paul , Liu Chengcheng , Ramsey Laura B. , Chang Tamara , Turner Victoria , Loh Mignon L. , Raetz Elizabeth A. , Winick Naomi J. , Hunger Stephen P. , Carroll William L. , Onengut-Gumuscu Suna , Chen Wei-Min , Concannon Patrick , Rich Stephen S. , Scheet Paul , Jeha Sima , Pui Ching-Hon , Evans William E. , Devidas Meenakshi , Relling Mary V.
Published: June 2014

Key Points

HLA-DRB1*07:01 is associated with asparaginase hypersensitivity and anti-asparaginase antibodies. HLA-DRB1 alleles that confer high-affinity binding to asparaginase epitopes lead to a higher frequency of hypersensitivity.
Determinants of baseline lung function and bronchodilator response in 4-year-old children
Authors: Dom Sandra , Weyler Joost J. , Droste Jos H.J. , Hagendorens Margo M. , Dierckx Elke , Bridts Chris H. , De Backer Wilfried , Oostveen Ellie
Published: June 2014

The prolonged period required for maturation of the respiratory system makes it vulnerable to environmental exposure. This study aimed to investigate the association between early-life factors and lung function in preschool children.

Children aged 4 years, who were included in a prospective birth cohort, underwent lung function testing at baseline (n=535) and after bronchodilation (n=498) by forced oscillations. Information on symptoms and exposures was collected through half-yearly questionnaires. Allergen-specific serum IgE was quantified at 1 and 4 years.

Multiple linear regression analysis showed that the baseline respiratory resistance and reactance area were larger in the children with previous wheeze, those with early-onset sensitisation to inhalant allergens and those who were smaller. Furthermore, children with previous lower respiratory tract infections exhibited higher baseline resistance values. The baseline resistance was the only independent determinant of the bronchodilator-induced change in resistance, whereas current height and baseline reactance area were independently associated with the change in reactance area.

In conclusion, previous lower respiratory tract infections, the timing of previous wheeze, inhalant sensitisation and current height independently influence the baseline lung function of 4-year-old children, whereas baseline lung function is the principal determinant of the bronchodilator response.
Predictors of work-related sensitisation, allergic rhinitis and asthma in early work life
Authors: Kellberger Jessica , Peters-Weist Astrid S. , Heinrich Sabine , Pfeiffer Susanne , Vogelberg Christian , Roller Diana , Genuneit Jon , Weinmayr Gudrun , von Mutius Erika , Heumann Christian , Nowak Dennis , Radon Katja
Published: June 2014

Although work-related asthma and allergies are a huge burden for society, investigation of occupational exposures in early work life using an unexposed reference group is rare. Thus, the present analyses aimed to assess the potential impact of occupational exposure and other risk factors on the prevalence of work-related sensitisation and incidence of allergic rhinitis/asthma using a population-based approach and taking into account an unexposed reference group.

In SOLAR (Study on Occupational Allergy Risks) II, German participants of ISAAC (International Study of Asthma and Allergies in Childhood) phase II were followed from childhood (9–11 years) until early adulthood (19–24 years). Data on 1570 participants were available to fit predictive models.

Occupational exposure was not statistically significantly associated with disease prevalence/incidence. Sensitisation in childhood, parental asthma, environmental tobacco smoke exposure during puberty, sex and study location were statistically significant predictors of outcome.

Our results indicate that occupational exposure is of little relevance for work-related sensitisation prevalence and allergic rhinitis/asthma incidence in early work life, while other risk factors can be used to improve career guidance for adolescents. Further research on the role of a potential healthy hire effect and the impact of longer exposure duration is needed.
The effect of 3% and 6% hypertonic saline in viral bronchiolitis: a randomised controlled trial
Authors: Teunissen Jasmijn , Hochs Anne H.J. , Vaessen-Verberne Anja , Boehmer Annemie L.M. , Smeets Carien C.J.M. , Brackel Hein , van Gent René , Wesseling Judith , Logtens-Stevens Danielle , de Moor Ronald , Rosias Philippe P.R. , Potgieter Steph , Faber Marianne R. , Hendriks Han J.E. , Janssen-Heijnen Maryska L.G. , Loza Bettina F.
Published: June 2014

Bronchiolitis is a common disorder in young children that often results in hospitalisation. Except for a possible effect of nebulised hypertonic saline (sodium chloride), no evidence-based therapy is available. This study investigated the efficacy of nebulised 3% and 6% hypertonic saline compared with 0.9% hypertonic saline in children hospitalised with viral bronchiolitis.

In this multicentre, double-blind, randomised, controlled trial, children hospitalised with acute viral bronchiolitis were randomised to receive either nebulised 3%, 6% hypertonic saline or 0.9% normal saline during their entire hospital stay. Salbutamol was added to counteract possible bronchial constriction. The primary endpoint was the length of hospital stay. Secondary outcomes were need for supplemental oxygen and tube feeding.

From the 292 children included in the study (median age 3.4 months), 247 completed the study. The median length of hospital stay did not differ between the groups: 69 h (interquartile range 57), 70 h (IQR 69) and 53 h (IQR 52), for 3% (n=84) and 6% (n=83) hypertonic saline and 0.9% (n=80) normal saline, respectively, (p=0.29). The need for supplemental oxygen or tube feeding did not differ significantly. Adverse effects were similar in the three groups.

Nebulisation with hypertonic saline (3% or 6% sodium chloride) although safe, did not reduce the length of stay in hospital, duration of supplemental oxygen or tube feeding in children hospitalised with moderate-to-severe viral bronchiolitis.
MORT: a powerful foundational library for computational biology and CADD
Authors: Zhang Qian , Zhang Wei , Li Youyong , Wang Junmei , Zhang Jian , Hou Tingjun
Published: June 2014

Background

A foundational library called MORT (Molecular Objects and Relevant Templates) for the development of new software packages and tools employed in computational biology and computer-aided drug design (CADD) is described here.

Results

MORT contains several advantages compared with the other libraries. Firstly, MORT written in C++ natively supports the paradigm of object-oriented design, and thus it can be understood and extended easily. Secondly, MORT employs the relational model to represent a molecule, and it is more convenient and flexible than the traditional hierarchical model employed by many other libraries. Thirdly, a lot of functions have been included in this library, and a molecule can be manipulated easily at different levels. For example, it can parse a variety of popular molecular formats (MOL/SDF, MOL2, PDB/ENT, SMILES/SMARTS, etc.), create the topology and coordinate files for the simulations supported by AMBER, calculate the energy of a specific molecule based on the AMBER force fields, etc.

Conclusions

We believe that MORT can be used as a foundational library for programmers to develop new programs and applications for computational biology and CADD. Source code of MORT is available at http://cadd.suda.edu.cn/MORT/index.htm.
The future of antibiotics
Authors: Spellberg Brad
Published: June 2014

Antibiotic resistance continues to spread even as society is experiencing a market failure of new antibiotic research and development (R&D). Scientific, economic, and regulatory barriers all contribute to the antibiotic market failure. Scientific solutions to rekindle R&D include finding new screening strategies to identify novel antibiotic scaffolds and transforming the way we think about treating infections, such that the goal is to disarm the pathogen without killing it or modulate the host response to the organism without targeting the organism for destruction. Future economic strategies are likely to focus on ‘push’ incentives offered by public-private partnerships as well as increasing pricing by focusing development on areas of high unmet need. Such strategies can also help protect new antibiotics from overuse after marketing. Regulatory reform is needed to re-establish feasible and meaningful traditional antibiotic pathways, to create novel limited-use pathways that focus on highly resistant infections, and to harmonize regulatory standards across nations. We need new antibiotics with which to treat our patients. But we also need to protect those new antibiotics from misuse when they become available. If we want to break the cycle of resistance and change the current landscape, disruptive approaches that challenge long-standing dogma will be needed.
Treatment for infections with carbapenem-resistant Enterobacteriaceae: what options do we still have?
Authors: Yamamoto Michele , Pop-Vicas Aurora E
Published: June 2014

The global spread of carbapenem-resistant Enterobacteriaceae (CRE) is increasingly becoming a major challenge in clinical and public health settings. To date, the treatment for serious CRE infections remains difficult. The intelligent use of antimicrobials and effective infection control strategies is crucial to prevent further CRE spread. Early consultation with experts in the treatment of infections with multidrug-resistant organisms is valuable in patient management. This brief review will focus on the current, yet limited, treatment options for CRE infections.
Tight glycemic control in the ICU - is the earth flat?
Authors: Steil Garry M , Agus Michael SD
Published: June 2014

Tight glycemic control in the ICU has been shown to reduce mortality in some but not all prospective randomized control trials. Confounding the interpretation of these studies are differences in how the control was achieved and underlying incidence of hypoglycemia, which can be expected to be affected by the introduction of continuous glucose monitoring (CGM). In this issue of Critical Care, a consensus panel provides a list of the research priorities they believe are needed for CGM to become routine practice in the ICU. We reflect on these recommendations and consider the implications for using CGM today.
A BRCA1-mutation associated DNA methylation signature in blood cells predicts sporadic breast cancer incidence and survival
Authors: Anjum Shahzia , Fourkala Evangelia-Ourania , Zikan Michal , Wong Andrew , Gentry-Maharaj Aleksandra , Jones Allison , Hardy Rebecca , Cibula David , Kuh Diana , Jacobs Ian J , Teschendorff Andrew E , Menon Usha , Widschwendter Martin
Published: June 2014

Background

BRCA1 mutation carriers have an 85% risk of developing breast cancer but the risk of developing non-hereditary breast cancer is difficult to assess. Our objective is to test whether a DNA methylation (DNAme) signature derived from BRCA1 mutation carriers is able to predict non-hereditary breast cancer.

Methods

In a case/control setting (72 BRCA1 mutation carriers and 72 BRCA1/2 wild type controls) blood cell DNA samples were profiled on the Illumina 27 k methylation array. Using the Elastic Net classification algorithm, a BRCA1-mutation DNAme signature was derived and tested in two cohorts: (1) The NSHD (19 breast cancers developed within 12 years after sample donation and 77 controls) and (2) the UKCTOCS trial (119 oestrogen receptor positive breast cancers developed within 5 years after sample donation and 122 controls).

Results

We found that our blood-based BRCA1-mutation DNAme signature applied to blood cell DNA from women in the NSHD resulted in a receiver operating characteristics (ROC) area under the curve (AUC) of 0.65 (95% CI 0.51 to 0.78, P = 0.02) which did not validate in buccal cells from the same individuals. Applying the signature in blood DNA from UKCTOCS volunteers resulted in AUC of 0.57 (95% CI 0.50 to 0.64; P = 0.03) and is independent of family history or any other known risk factors. Importantly the BRCA1-mutation DNAme signature was able to predict breast cancer mortality (AUC = 0.67; 95% CI 0.51 to 0.83; P = 0.02). We also found that the 1,074 CpGs which are hypermethylated in BRCA1 mutation carriers are significantly enriched for stem cell polycomb group target genes (P <10-20).

Conclusions

A DNAme signature derived from BRCA1 carriers is able to predict breast cancer risk and death years in advance of diagnosis. Future studies may need to focus on DNAme profiles in epithelial cells in order to reach the AUC thresholds required of preventative measures or early detection strategies.
Development and validation of a new high-throughput method to investigate the clonality of HTLV-1-infected cells based on provirus integration sites
Authors: Firouzi Sanaz , López Yosvany , Suzuki Yutaka , Nakai Kenta , Sugano Sumio , Yamochi Tadanori , Watanabe Toshiki
Published: June 2014

Transformation and clonal proliferation of T-cells infected with human T-cell leukemia virus type-I (HTLV-1) cause adult T-cell leukemia. We took advantage of next-generation sequencing technology to develop and internally validate a new methodology for isolating integration sites and estimating the number of cells in each HTLV-1-infected clone (clone size). Initial analysis was performed with DNA samples from infected individuals. We then used appropriate controls with known integration sites and clonality status to confirm the accuracy of our system, which indeed had the least errors among the currently available techniques. Results suggest potential clinical and biological applications of the new method.
Split luciferase complementation assay to detect regulated protein-protein interactions in rice protoplasts in a large-scale format
Authors: Fujikawa Yukichi , Nakanishi Takahiro , Kawakami Hiroko , Yamasaki Kanako , Sato Masa H , Tsuji Hiroyuki , Matsuoka Makoto , Kato Naohiro
Published: June 2014

Background

The rice interactome, in which a network of protein-protein interactions has been elucidated in rice, is a useful resource to identify functional modules of rice signal transduction pathways. Protein-protein interactions occur in cells in two ways, constitutive and regulative. While a yeast-based high-throughput method has been widely used to identify the constitutive interactions, a method to detect the regulated interactions is rarely developed for a large-scale analysis.

Results

A split luciferase complementation assay was applied to detect the regulated interactions in rice. A transformation method of rice protoplasts in a 96-well plate was first established for a large-scale analysis. In addition, an antibody that specifically recognizes a carboxyl-terminal fragment ofRenillaluciferase was newly developed. A pair of antibodies that recognize amino- and carboxyl- terminal fragments ofRenillaluciferase, respectively, was then used to monitor quality and quantity of interacting recombinant-proteins accumulated in the cells. For a proof-of-concept, the method was applied to detect the gibberellin-dependent interaction between GIBBERELLIN INSENSITIVE DWARF1 and SLENDER RICE 1.

Conclusions

A method to detect regulated protein-protein interactions was developed towards establishment of the rice interactome.
Renin modulates HIV replication in T cells
Authors: Chandel Nirupama , Ayasolla Kamesh , Lan Xiqian , Rai Partab , Mikulak Joanna , Husain Mohammad , Malhotra Ashwani , McGowan Joseph , Singhal Pravin C
Published: June 2014

HIV is known to subvert cellular machinery to enhance its replication. Recently, HIV has been reported to enhance TC renin expression. We hypothesized that HIV induces and maintains high renin expression to promote its own replication in TCs. Renin enhanced HIV replication in TCs in a dose-dependent manner. (P)RR-deficient TCs, as well as those lacking renin, displayed attenuated NF-κB activity and HIV replication. TCs treated with renin and Hpr displayed activation of the (P)RR-PLZF protein signaling cascade. Renin, HIV, and Hpr activated the PI3K pathway. Both renin and Hpr cleaved Agt (a renin substrate) to Ang I and also cleaved Gag polyproteins (protease substrate) to p24. Furthermore, aliskiren, a renin inhibitor, reduced renin- and Hpr-induced cleavage of Agt and Gag polyproteins. These findings indicate that renin contributes to HIV replication in TCs via the (P)RR-PLZF signaling cascade and through cleavage of the Gag polyproteins.
Hepatocytes induce Foxp3+ regulatory T cells by Notch signaling
Authors: Burghardt Sven , Claass Benjamin , Erhardt Annette , Karimi Khalil , Tiegs Gisa
Published: June 2014

The liver plays a pivotal role in maintaining immunological tolerance, although the exact molecular mechanism is still largely unknown. The induction of systemic tolerance by liver resident APCs has been attributed to peripheral deletion and to the induction of Tregs. HCs, the parenchymal cells in the liver, could function as nonprofessional APCs and interact and establish cell–cell contact with T lymphocytes. We hypothesized that HCs from healthy or regenerated livers may contribute to induction of functional Tregs. Here, we show that murine HCs induced Foxp3+ Tregs within CD4+ T cells in vitro, which increased in the presence of TGF-β. Interestingly, a further Foxp3+ Treg expansion was observed if HCs were isolated from regenerated livers. Additionally, the induction of Foxp3+ Tregs was associated with the Notch signaling pathway, as the ability of HCs to enhance Foxp3 was abolished by γ-secretase inhibition. Furthermore, HC-iTregs showed ability to suppress the proliferative response of CD4+ T cells to anti-CD3 stimulation in vitro. Thus, HCs may play a pivotal role in the induction of tolerance via Notch-mediated conversion of CD4+ T cells into Foxp3+ Tregs upon TCR stimulation.
Word use in first-person accounts of schizophrenia
Authors: Fineberg S. K. , Deutsch-Link S. , Ichinose M. , McGuinness T. , Bessette A. J. , Chung C. K. , Corlett P. R.
Published: June 2014

Background

Language use is often disrupted in patients with schizophrenia; novel computational approaches may provide new insights.

Aims

To test word use patterns as markers of the perceptual, cognitive and social experiences characteristic of schizophrenia.

Method

Word counting software was applied to first-person accounts of schizophrenia and mood disorder.

Results

More third-person plural pronouns (‘they’) and fewer first-person singular pronouns (‘I’) were used in schizophrenia than mood disorder accounts. Schizophrenia accounts included fewer words related to the body and ingestion, and more related to religion. Perceptual and causal language were negatively correlated in schizophrenia accounts but positively correlated in mood disorder accounts.

Conclusions

Differences in pronouns suggest decreased self-focus or perhaps even an understanding of self as other in schizophrenia. Differences in how perceptual and causal words are correlated suggest that long-held delusions represent a decreased coupling of explanations with sensory experience over time.
Diffusion tensor imaging predictors of treatment outcomes in major depressive disorder
Authors: Korgaonkar Mayuresh S. , Williams Leanne M. , Song Yun Ju , Usherwood Tim , Grieve Stuart M.
Published: June 2014

Background

Functional neuroimaging studies implicate anterior cingulate and limbic dysfunction in major depressive disorder (MDD) and responsiveness to antidepressants. Diffusion tensor imaging (DTI) enables characterisation of white matter tracts that relate to these regions.

Aims

To examine whether DTI measures of anterior cingulate and limbic white matter are useful prognostic biomarkers for MDD.

Method

Of the 102 MDD out-patients from the International Study to Predict Optimized Treatment for Depression (iSPOT-D) who provided baseline magnetic resonance imaging (MRI) data, 74 completed an 8-week course of antidepressant medication (randomised to escitalopram, sertraline or extended-release venlafaxine) and were included in the present analyses. Thirty-four matched controls also provided DTI data. Fractional anisotropy was measured for five anterior cingulate–limbic white matter tracts: cingulum cingulate and hippocampus bundle, fornix, stria terminalis and uncinate fasciculus. (Trial registered at ClinicalTrials.gov: NCT00693849.)

Results

A cross-validated logistic regression model demonstrated that altered connectivity for the cingulum part of the cingulate and stria terminalis tracts significantly predicted remission independent of demographic and clinical measures with 62% accuracy. Prediction improved to 74% when age was added to this model.

Conclusions

Anterior cingulate–limbic white matter is a useful predictor of antidepressant treatment outcome in MDD.
Recovery From SIADH-Associated Osteoporosis: A Case Report
Authors: Sejling Anne-Sophie , Thorsteinsson Anne-Luise , Pedersen-Bjergaard Ulrik , Eiken Pia
Published: June 2014

Introduction:

Recent studies show an association between hyponatremia and osteoporosis. We have previously reported a case of severe male osteoporosis due to chronic syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Here, we provide a follow-up on this case after cure of the condition that further supports the causal relationship.

The Case:

A 38-year-old man had been diagnosed with severe osteoporosis most likely due to chronic SIADH. The SIADH was believed to be idiopathic. A magnetic resonance imaging scan, however, revealed a tumor in the sinus, and biopsies showed an esthesioneuroblastoma, immunohistochemically positive for antidiuretic hormone (ADH). After the tumor was removed, ADH and sodium levels normalized. A dual-energy x-ray absorptiometry scan performed 7 months after the patient's last surgery showed a significant spontaneous improvement in bone mineral density in the lumbar vertebrae.

Conclusion:

This case provides evidence for a causal relationship between SIADH and chronic hyponatremia and impaired bone metabolism that can lead to severe secondary osteoporosis. The effect on bone metabolism is at least partially reversible.
Molecularly defined unfolded protein response subclasses have distinct correlations with fatty liver disease in zebrafish
Authors: Vacaru Ana M. , Di Narzo Antonio Fabio , Howarth Deanna L. , Tsedensodnom Orkhontuya , Imrie Dru , Cinaroglu Ayca , Amin Salma , Hao Ke , Sadler Kirsten C.
Published: June 2014

The unfolded protein response (UPR) is a complex network of sensors and target genes that ensure efficient folding of secretory proteins in the endoplasmic reticulum (ER). UPR activation is mediated by three main sensors, which regulate the expression of hundreds of targets. UPR activation can result in outcomes ranging from enhanced cellular function to cell dysfunction and cell death. How this pathway causes such different outcomes is unknown. Fatty liver disease (steatosis) is associated with markers of UPR activation and robust UPR induction can cause steatosis; however, in other cases, UPR activation can protect against this disease. By assessing the magnitude of activation of UPR sensors and target genes in the liver of zebrafish larvae exposed to three commonly used ER stressors (tunicamycin, thapsigargin and Brefeldin A), we have identified distinct combinations of UPR sensors and targets (i.e. subclasses) activated by each stressor. We found that only the UPR subclass characterized by maximal induction of UPR target genes, which we term a stressed-UPR, induced steatosis. Principal component analysis demonstrated a significant positive association between UPR target gene induction and steatosis. The same principal component analysis showed significant correlation with steatosis in samples from patients with fatty liver disease. We demonstrate that an adaptive UPR induced by a short exposure to thapsigargin prior to challenging with tunicamycin reduced both the induction of a stressed UPR and steatosis incidence. We conclude that a stressed UPR causes steatosis and an adaptive UPR prevents it, demonstrating that this pathway plays dichotomous roles in fatty liver disease.
Intravital correlated microscopy reveals differential macrophage and microglial dynamics during resolution of neuroinflammation
Authors: van Ham Tjakko J. , Brady Colleen A. , Kalicharan Ruby D. , Oosterhof Nynke , Kuipers Jeroen , Veenstra-Algra Anneke , Sjollema Klaas A. , Peterson Randall T. , Kampinga Harm H. , Giepmans Ben N. G.
Published: June 2014

Many brain diseases involve activation of resident and peripheral immune cells to clear damaged and dying neurons. Which immune cells respond in what way to cues related to brain disease, however, remains poorly understood. To elucidate these in vivo immunological events in response to brain cell death we used genetically targeted cell ablation in zebrafish. Using intravital microscopy and large-scale electron microscopy, we defined the kinetics and nature of immune responses immediately following injury. Initially, clearance of dead cells occurs by mononuclear phagocytes, including resident microglia and macrophages of peripheral origin, whereas amoeboid microglia are exclusively involved at a later stage. Granulocytes, on the other hand, do not migrate towards the injury. Remarkably, following clearance, phagocyte numbers decrease, partly by phagocyte cell death and subsequent engulfment of phagocyte corpses by microglia. Here, we identify differential temporal involvement of microglia and peripheral macrophages in clearance of dead cells in the brain, revealing the chronological sequence of events in neuroinflammatory resolution. Remarkably, recruited phagocytes undergo cell death and are engulfed by microglia. Because adult zebrafish treated at the larval stage lack signs of pathology, it is likely that this mode of resolving immune responses in brain contributes to full tissue recovery. Therefore, these findings suggest that control of such immune cell behavior could benefit recovery from neuronal damage.
Zebrafish models in translational research: tipping the scales toward advancements in human health
Authors: Phillips Jennifer B. , Westerfield Monte
Published: June 2014

Advances in genomics and next-generation sequencing have provided clinical researchers with unprecedented opportunities to understand the molecular basis of human genetic disorders. This abundance of information places new requirements on traditional disease models, which have the potential to be used to confirm newly identified pathogenic mutations and test the efficacy of emerging therapies. The unique attributes of zebrafish are being increasingly leveraged to create functional disease models, facilitate drug discovery, and provide critical scientific bases for the development of new clinical tools for the diagnosis and treatment of human disease. In this short review and the accompanying poster, we highlight a few illustrative examples of the applications of the zebrafish model to the study of human health and disease.
Macrophage-pathogen interactions in infectious diseases: new therapeutic insights from the zebrafish host model
Authors: Torraca Vincenzo , Masud Samrah , Spaink Herman P. , Meijer Annemarie H.
Published: June 2014

Studying macrophage biology in the context of a whole living organism provides unique possibilities to understand the contribution of this extremely dynamic cell subset in the reaction to infections, and has revealed the relevance of cellular and molecular processes that are fundamental to the cell-mediated innate immune response. In particular, various recently established zebrafish infectious disease models are contributing substantially to our understanding of the mechanisms by which different pathogens interact with macrophages and evade host innate immunity. Transgenic zebrafish lines with fluorescently labeled macrophages and other leukocyte populations enable non-invasive imaging at the optically transparent early life stages. Furthermore, there is a continuously expanding availability of vital reporters for subcellular compartments and for probing activation of immune defense mechanisms. These are powerful tools to visualize the activity of phagocytic cells in real time and shed light on the intriguing paradoxical roles of these cells in both limiting infection and supporting the dissemination of intracellular pathogens. This Review will discuss how several bacterial and fungal infection models in zebrafish embryos have led to new insights into the dynamic molecular and cellular mechanisms at play when pathogens encounter host macrophages. We also describe how these insights are inspiring novel therapeutic strategies for infectious disease treatment.
The zebrafish as a tool to identify novel therapies for human cardiovascular disease
Authors: Asnani Aarti , Peterson Randall T.
Published: June 2014

Over the past decade, the zebrafish has become an increasingly popular animal model for the study of human cardiovascular disease. Because zebrafish embryos are transparent and their genetic manipulation is straightforward, the zebrafish has been used to recapitulate a number of cardiovascular disease processes ranging from congenital heart defects to arrhythmia to cardiomyopathy. The use of fluorescent reporters has been essential to identify two discrete phases of cardiomyocyte differentiation necessary for normal cardiac development in the zebrafish. These phases are analogous to the differentiation of the two progenitor heart cell populations in mammals, termed the first and second heart fields. The small size of zebrafish embryos has enabled high-throughput chemical screening to identify small-molecule suppressors of fundamental pathways in vasculogenesis, such as the BMP axis, as well as of common vascular defects, such as aortic coarctation. The optical clarity of zebrafish has facilitated studies of valvulogenesis as well as detailed electrophysiological mapping to characterize the early cardiac conduction system. One unique aspect of zebrafish larvae is their ability to oxygenate through diffusion alone, permitting the study of mutations that cause severe cardiomyopathy phenotypes such as silent heart and pickwickm171, which mimic titin mutations observed in human dilated cardiomyopathy. Above all, the regenerative capacity of zebrafish presents a particularly exciting opportunity to discover new therapies for cardiac injury, including scar formation following myocardial infarction. This Review will summarize the current state of the field and describe future directions to advance our understanding of human cardiovascular disease.
Unexpected [3 + 2] Cycloaddition of Diphenyldienamine with C60 via Single Electron Transfer and Hydrogen Shift of the Radical Cation Intermediate
Authors: Ikuma Naohiko , Yamamoto Hiroyuki , Kokubo Ken , Oshima Takumi
Published: June 2014

Novel single electron transfer (SET) reaction of dienamine with C60 is presented. The generated dienamine radical cation underwent a 1,6-hydrogen shift followed by a radical–ion coupling with a C60 radical anion to give pyrrolidinofullerene. The radical process was proven by spin-trapping experiments as well as DFT calculations.