bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect(s) of Teen Pregnancy: Reconciling Theory, Methods, and Findings
Authors: Diaz Christina J. , Fiel Jeremy E.
Published: January 2016

Although teenage mothers have lower educational attainment and earnings than women who delay fertility, causal interpretations of this relationship remain controversial. Scholars argue that there are reasons to predict negative, trivial, or even positive effects, and different methodological approaches provide some support for each perspective. We reconcile this ongoing debate by drawing on two heuristics: (1) each methodological strategy emphasizes different women in estimation procedures, and (2) the effects of teenage fertility likely vary in the population. Analyses of the Child and Young Adult Cohorts of the National Longitudinal Survey of Youth (N = 3,661) confirm that teen pregnancy has negative effects on most women’s attainment and earnings. More striking, however, is that effects on college completion and early earnings vary considerably and are most pronounced among those least likely to experience an early pregnancy. Further analyses suggest that teen pregnancy is particularly harmful for those with the brightest socioeconomic prospects and who are least prepared for the transition to motherhood.
Eliciting and measuring betrayal aversion using the BDM mechanism
Authors: Quercia Simone
Published: January 2016

Betrayal aversion has been operationalized as the evidence that subjects demand a higher risk premium to take social risks compared to natural risks. This evidence has been first shown by Bohnet and Zeckhauser (J Econ Behav 98:294–310, 2004) using an adaptation of the Becker–DeGroot–Marschak mechanism (BDM, Becker et al. Behav Sci 9:226–232, 1964). We compare their implementation of the BDM mechanism with a new version designed to facilitate subjects’ comprehension. We find that, although the two versions produce different distributions of values, the size of betrayal aversion, measured as an average treatment difference between social and natural risk settings, is not different across the two versions. We further show that our implementation is preferable to use in practice as it reduces substantially subjects’ mistakes and the likelihood of noisy valuations.
An Analysis of Inpatient Rehabilitation Approval Among Private Insurance Carriers at a Cancer Center
Authors: Fu Jack B. , Bianty Josephine R. , Wu Jimin , Ngo‐Huang An , Shin Ki Y. , Bruera Eduardo
Published: January 2016

Background

Acute inpatient rehabilitation is often used by cancer patients to assist with discharge home and/or preparation for further treatment. Private insurance patients often require approval before transfer to acute inpatient rehabilitation.

Objective

To analyze the approval rate of private insurance carriers for acute inpatient cancer rehabilitation.

Design

Retrospective analysis.

Setting

Tertiary referral‐based cancer center.

Patients

A total of 96 consecutive patients with private insurance who had acute inpatient rehabilitation authorization requests made between April 1, 2014, and September 17, 2014.

Intervention

Patient cases were assessed by a physiatrist, deemed clinically appropriate for acute inpatient rehabilitation, and submitted to private insurance payers for an approval request.

Results

In all, 84 of 96 requests (87%) for private insurance authorization for inpatient rehabilitation transfer were approved. Of the 96 cases, 14 cases (14.6%) were initially denied. Nine of 96 (9.4%) progressed to a peer‐to‐peer appeal, of which only 2 of 9 (11.1%) resulted in approval for inpatient rehabilitation transfer (P = .222). The insurance carriers represented were designated as insurance A (46 patients, 48%), insurance B (18 patients, 19%), insurance C (12 patients, 13%), and other insurances (20, 21%). Two of 46 insurance A requests were initially denied, as compared to 7 of 18 for insurance B, 0 of 12 for insurance C, and 4 of 20 for other insurances (P = .001). Patients with insurance B (P = .002, odds ratio = 14) and other insurances (P = .062, odds ratio = 5.50) were more likely to be denied inpatient rehabilitation approval compared to patients with insurance A. No significant difference between mean Functional Independence Measure scores for approved and denied patients were found for transfers (P = .239) and mobility (P = .129), respectively.

Conclusion

Access to acute inpatient rehabilitation is unfortunately limited by insurers rather than clinical indicators. Future multicenter studies and universally accepted guidelines regarding inpatient rehabilitation criteria are needed.
Discontinuation of Systematic Surveillance and Contact Precautions for Vancomycin-ResistantEnterococcus(VRE) and Its Impact on the Incidence of VREfaeciumBacteremia in Patients with Hematologic Malignancies
Authors: Almyroudis Nikolaos G. , Osawa Ryosuke , Samonis George , Wetzler M. , Wang Eunice S. , McCarthy Philip L. , Segal Brahm H.
Published: January 2016

OBJECTIVE

To study the effect of discontinuation of systematic surveillance for vancomycin-resistantEnterococcus(VRE) and contact isolation of colonized patients on the incidence of VRE bacteremia

SETTING

A hematology-oncology unit with high prevalence of VRE colonization characterized by predominantly sporadic molecular epidemiology

PARTICIPANTS

Inpatients with hematologic malignancies and recipients of hematopoietic stem cell transplantation

METHODS

The incidence of VRE bacteremia was measured prospectively during 2 different 3-year time periods; the first during active VRE surveillance and contact precautions and the second after discontinuation of these policies. We assessed the collateral impact of this policy change on the incidence of bacteremia due to methicillin-resistantStaphylococcus aureus(MRSA) andClostridium difficileinfection even though we maintained contact precautions for these organisms. Incidence of infectious events was measured as number of events per 1,000 patients days per month. Time series analysis was used to evaluate trends.

RESULTS

The incidence of VRE bacteremia remained stable after discontinuation of VRE surveillance and contact precautions. The incidence of MRSA bacteremia andClostridium difficileinfection for which we continued contact precautions also remained stable. Aggregated antibiotic utilization and nursing hours per patient days were similar between the 2 study periods.

CONCLUSION

Active surveillance and contact precautions for VRE colonization did not appear to prevent VRE bacteremia in patients with hematologic malignancies and recipients of hematopoietic stem cell transplantation with high prevalence of VRE characterized by predominantly sporadic molecular epidemiology.

Infect. Control Hosp. Epidemiol.2016;37(4):398–403
The timing of worm exclusion in dogs repeatedly infected with the cestode Echinococcus multilocularis
Authors: Kouguchi H. , Irie T. , Matsumoto J. , Nakao R. , Sugano Y. , Oku Y. , Yagi K.
Published: January 2016

Experimental Echinococcus multilocularis infection and deworming was repeated three or five times in nine dogs at various re-infection schedules. The mean number of worms decreased more than 91% in dogs with repeated infection, compared to first infection controls (n= 6). The copro-antigen assay and the egg count in the faeces suggested that the worm burden gradually decreased each time the dogs were re-infected. To examine whether such worm exclusion was a non-specific response, five dogs were sequentially infected with the parasite four times and subsequently fed freely for 6 months. Even after the 6-month interval, the five dogs that were infected five times with the parasite were still able largely to exclude the adult worms. The results suggested that the ability of worm exclusion in dogs that developed a resistance did not become rapidly extinct. Observation of the condition of faeces and the excretion of hooks in the faeces of repeatedly infected dogs revealed that the exclusion of worms started at the first week after the re-infection, and it continued during the patent period. Serum antibodies specific to the parasite antigen increased gradually until the third infection and significantly decreased during the 6-month interval. There was little enhancement of serum antibodies after the fifth infection in most dogs, although no clear correlation was observed between the antibody response and the worm burden. These findings suggested the possibility of developing a vaccine.
Differential efficacy of cognitive behavioral therapy and psychodynamic therapy for major depression: a study of prescriptive factors
Authors: Driessen E. , Smits N. , Dekker J. J. M. , Peen J. , Don F. J. , Kool S. , Westra D. , Hendriksen M. , Cuijpers P. , Van H. L.
Published: January 2016

Background

Minimal efficacy differences have been found between cognitive behavioral therapy (CBT) and psychodynamic therapies for depression, but little is known about patient characteristics that might moderate differential treatment effects. We aimed to generate hypotheses regarding such potential prescriptive factors.

Method

We conducted post-hoc model-based recursive partitioning analyses alongside a randomized clinical trial comparing the efficacy of CBT and short-term psychodynamic supportive psychotherapy (SPSP). Severely depressed patients received additional antidepressant medication. We included 233 adults seeking treatment for a major depressive episode in psychiatric outpatient clinics, who completed post-treatment assessment. Post-treatment mean Hamilton Depression Rating Scale scores constituted the main outcome measure.

Results

While treatment differences (CBT v. SPSP) were minimal in the total sample of patients (d = 0.04), model-based recursive partitioning indicated differential treatment efficacy in certain subgroups of patients. SPSP was found more efficacious among moderately depressed patients receiving psychotherapy only who showed low baseline co-morbid anxiety levels (d = −0.40) and among severely depressed patients receiving psychotherapy and antidepressant medication who reported a duration of the depressive episode of ⩾1 year (d = −0.31), while CBT was found more efficacious for such patients reporting a duration <1 year (d = 0.83).

Conclusions

Our findings are observational and need validation before they can be used to guide treatment selection, but suggest that knowledge of prescriptive factors can help improve the efficacy of psychotherapy for depression. Depressive episode duration and co-morbid anxiety level should be included as stratification variables in future randomized clinical trials comparing CBT and psychodynamic therapy.
Difference without Disagreement: Rethinking Hobbes on “Independency” and Toleration
Authors: Bejan Teresa M.
Published: January 2016

In arguments for a more tolerant Hobbes, Leviathan's endorsement of “Independency” is often Exhibit A; however, the conditionals Hobbes attached have received little attention. These—and the dangers of “contention” and sectarian “affection” they identify—are essential for understanding Hobbes's views on toleration. Together, they express a vision of “difference without disagreement” in which the accommodation of diversity in religious worship and association depends on the suppression of disagreement through sovereign- and self-discipline over speech. This expressly antievangelical ideal of toleration as a civil silence about difference presents a challenge to the more tolerant Hobbes thesis, particularly in its recent “Erastian Independency” guise. It also raises deeper questions about what might be at stake in applying the labels of “intolerant” or “tolerant” to Hobbes today.
Intoxicated Reasons, Rational Feelings: Rethinking the Early Modern English Public Sphere
Authors: Hsueh Vicki
Published: January 2016

This article examines early modern English public houses and related period miscellany—broadside ballads, conduct books, and songs—to more closely investigate the discourses and performances of drinking culture. Drinking culture, I argue, not only had a significant role in shaping the Restoration's civic culture of political participation and the emerging early modern public sphere, but also positioned emotions of pleasure and melancholy as social and political objects of care and cultivation. While the politics of pub culture and intoxication have been well documented by historians and literary scholars of early modern England and eighteenth-century America, much of this discussion has not yet been incorporated into political assessments of the public sphere and its history. Reinserting emotion and intoxication into the emergence of the public sphere helps to flesh out the history of feeling and social ritual in civic engagement.
Routinised recognition and anxiety: Understanding the deterioration in Sino-Japanese relations
Authors: Gustafsson Karl
Published: January 2016

Why do interstate relations deteriorate and become conflictual, even under conditions where one might expect improved ties? The article seeks an answer to this question through a case study of the deterioration in Sino-Japanese relations in the twenty-first century, which took place despite the existence of several factors that might be thought likely to have led to an improvement. Existing theoretical approaches cannot fully explain this puzzle. The article argues that such deteriorations can result from disruptions to states’ reciprocally performed routinised recognition, and identifies three mechanisms through which these can occur. To facilitate this argument, the article draws on scholarship on relational identity, recognition, and ontological security to develop a theory of identity construction that takes account of how self and other routinise the ways in which they recognise each other and how they react to the other’s representational practices.
Singing and vocal instruction in primary schools: an analysis from six case studies in Spain
Authors: Cuadrado Albina , Rusinek Gabriel
Published: January 2016

This is an analysis of how specialist music teachers sing and teach how to sing, based on data collected from six case studies carried out in Spanish primary schools. The study aimed at understanding classroom singing practices, and in particular the provision or absence of vocal instruction in relation with teachers’ singing models. The findings support claims for thorough vocal training in the preparation of music teachers to enable them to face the challenges of the profession. Also suggested is the need to provide them with a coherent theoretical framework about the teaching and learning of singing.
COST ANALYSIS OF INTRA PROCEDURAL RAPID ON SITE EVALUATION OF CYTOPATHOLOGY WITH ENDOBRONCHIAL ULTRASOUND
Authors: Kalluri Meena , Puttagunta Lakshmi , Ohinmaa Arto , Thanh Nguyen Xuan , Wong Eric
Published: January 2016

Background: Rapid on site evaluation (ROSE) allows immediate processing and interpretation of the aspirate in the procedural suite. It improves diagnostic yield and lowers patient care costs. There are limited data on its cost-effectiveness with endobronchial ultrasound (EBUS).

Methods: We developed an economic model with two arms, no ROSE (our current practice) and simulated ROSE. To simulate ROSE, a cytopathologist retrospectively identified the first diagnostic slide in each case. Using a decision analytic modeling technique under a hospital diagnostic unit perspective, the benefits of simulated ROSE were estimated as cost-savings. The model input was estimated from actual data, consulting experts, and the literature. The benefits were estimated as cost savings per patient and for the province of Alberta per year. Due to differences in the procedure, sarcoidosis and cancer patients were analyzed separately. The costs are shown in 2012 Canadian dollars, CAD.

Results: In our model without ROSE, the procedure cost/patient was CAD 646.00(USD 523.32) for cancer and CAD 1,170.00 (USD 947.73) for sarcoidosis. With simulated ROSE cost savings of CAD 63.00(37.00 to 89.00) [USD 51.04(29.97 to 72.10)], CAD 544.00(490.00 to 598.00) [USD 440.65(397.05 to 484.44)] for cancer and sarcoidosis, respectively. Extrapolating this to provincial data, our model estimates that EBUS with ROSE would lead to savings of CAD 50,000.00(30,000 to 71,000) [USD 40,501.24 (24,300.75 to 57,531.34)] for cancer and CAD 109,000.00 (87,000 to 130,000) [USD 88,337.07 (70,546.45 to 105,313.04) for sarcoidosis.

Conclusion: The use of ROSE with EBUS is cost saving. The projected savings were CAD 50,000.00 (USD 40,501.24) and CAD 109,000.00(USD 88,337.07) in cancer and sarcoidosis, respectively, for the province of Alberta, Canada.
A History of Maritime Radio-Navigation Positioning Systems used in Poland
Authors: Specht Cezary , Weintrit Adam , Specht Mariusz
Published: January 2016

This paper describes the genesis, the principle of operation and characteristics of selected radio-navigation positioning systems, which in addition to terrestrial methods formed a system of navigational marking constituting the primary method for determining the location in the sea areas of Poland in the years 1948–2000, and sometimes even later. The major ones are: maritime circular radiobeacons (RC), Decca-Navigator System (DNS) and Differential GPS (DGPS), as well as solutions forgotten today: AD-2 and SYLEDIS. In this paper, due to its limited volume, the authors have omitted the description of the solutions used by the Polish Navy (RYM, BRAS, JEMIOŁUSZKA, TSIKADA) and the global or continental systems (TRANSIT, GPS, GLONASS, OMEGA, EGNOS, LORAN, CONSOL) - described widely in world literature.
Increased number of cases of Chikungunya virus (CHIKV) infection imported from the Caribbean and Central America to northern Italy, 2014
Authors: ROSSINI G. , GAIBANI P. , VOCALE C. , FINARELLI A. C. , LANDINI M. P.
Published: January 2016

This report describes an increased number of cases of Chikungunya virus (CHIKV) infection imported in northern Italy (Emilia-Romagna region) during the period May–September 2014, indicating that the recent spread of CHIKV and its establishment in the Caribbean and in central America, resulted in a high number of imported cases in Europe, thus representing a threat to public health. From May to September 2014, 14 imported cases of CHIKV infection were diagnosed; the patients were returning to Italy from Dominican Republic (n = 6), Haiti (n = 3), Guadeloupe (n = 2), Martinique (n = 1), Puerto Rico (n = 1) and Venezuela (n = 1). Phylogenetic analysis performed on the envelope protein (E1) gene sequences, obtained from plasma samples from two patients, indicated that the virus strain belongs to the Caribbean clade of the Asian genotype currently circulating in the Caribbean and Americas. The rise in the number of imported cases of CHIKV infection should increase healthcare professionals' awareness of the epidemiological situation and clinical presentation of CHIKV infection in order to enhance surveillance and early diagnosis in the forthcoming season of vector activity in Europe and North America.
Observed temperament from ages 6 to 36 months predicts parent- and teacher-reported attention-deficit/hyperactivity disorder symptoms in first grade
Authors: Willoughby Michael T. , Gottfredson Nisha C. , Stifter Cynthia A. ,   The Family Life Project Investigators
Published: January 2016

This study tested the prospective association between observational indicators of temperament, which were obtained across multiple assessments when children were 6–36 months of age, and parent and teacher reports of children's attention-deficit/hyperactivity disorder (ADHD) behaviors, when children were in first grade. Data were drawn from the Family Life Project and included 1,074 children for whom temperament and either parent- or teacher-reported ADHD behavioral data were available. The results of variable-centered regression models indicated that individual differences in temperament regulation, but not temperamental reactivity, was uniquely predictive of parent- and teacher-reported ADHD behaviors. Latent profile analyses were used to characterize configurations of temperamental reactivity and regulation. Person-centered regression models were subsequently estimated in which temperamental profile membership replaced continuous indicators of temperamental reactivity and regulation as predictors. The results of person-centered regression models indicated that temperamental reactivity and regulation both contributed (both alone and in combination) to the prediction of subsequent ADHD behaviors. In general, the predictive associations from early temperament to later ADHD were of modest magnitude (R2= .10–.17). Results are discussed with respect to interest in the early identification of children who are at elevated risk for later ADHD.
Fermi's paradox, extraterrestrial life and the future of humanity: a Bayesian analysis
Authors: Verendel Vilhelm , Häggström Olle
Published: January 2016

The Great Filter interpretation of Fermi's great silence asserts thatNpqis not a very large number, whereNis the number of potentially life-supporting planets in the observable universe,pis the probability that a randomly chosen such planet develops intelligent life to the level of present-day human civilization, andqis the conditional probability that it then goes on to develop a technological supercivilization visible all over the observable universe. Evidence suggests thatNis huge, which implies thatpqis very small. Hanson (1998) and Bostrom (2008) have argued that the discovery of extraterrestrial life would point towardspnot being small and therefore a very smallq, which can be seen as bad news for humanity's prospects of colonizing the universe. Here we investigate whether a Bayesian analysis supports their argument, and the answer turns out to depend critically on the choice of prior distribution.
Fully human MAP‐fusion protein selectively targets and eliminates proliferating CD64+ M1 macrophages
Authors: Hristodorov Dmitrij , Mladenov Radoslav , Fischer Rainer , Barth Stefan , Thepen Theo
Published: January 2016

Classical immunotoxins compromise a binding component (for example, a ligand, antibody or fragment thereof) and a cytotoxic component, usually derived from bacteria or plants (for example, Pseudomonas exotoxin A or ricin). Despite successful testing in vitro, the clinical development of immunotoxins has been hampered by immunogenicity and unsatisfactory safety profiles. Therefore, research has focused on fully human pro‐apoptotic components suitable for the development of cytolytic fusion proteins (CFP). We recently reported that human microtubule‐associated protein tau (MAP) can induce apoptosis when delivered to rapidly proliferating cancer cells. Here, we describe a new fully human CFP called H22(scFv)‐MAP, which specifically targets CD64+ cells. We show that H22(scFv)‐MAP can efficiently kill proliferating HL‐60 pro‐monocytic cells in vitro. In addition, the human CFP specifically eliminates polarized M1 macrophages in a transgenic mouse model of cutaneous chronic inflammation. Because M1 macrophages promote the pathogenesis of many chronic inflammatory diseases, targeting this cell population with H22(scFv)‐MAP could help to treat diseases such as atopic dermatitis, rheumatoid arthritis and inflammatory bowel disease.
Nasal vaccination stimulates CD8+ T cells for potent protection against mucosal Brucella melitensis challenge
Authors: Clapp Beata , Yang Xinghong , Thornburg Theresa , Walters Nancy , Pascual David W
Published: January 2016

Brucellosis remains a significant zoonotic threat worldwide. Humans and animals acquire infection via their oropharynx and upper respiratory tract following oral or aerosol exposure. After mucosal infection, brucellosis develops into a systemic disease. Mucosal vaccination could offer a viable alternative to conventional injection practices to deter disease. Using a nasal vaccination approach, the ΔznuA B. melitensis was found to confer potent protection against pulmonary Brucella challenge, and reduce colonization of spleens and lungs by more than 2500‐fold, with >50% of vaccinated mice showing no detectable brucellae. Furthermore, 10‐fold more brucellae‐specific, interferon‐γ (IFN‐γ)‐producing CD8+ T cells than CD4+ T cells were induced in the spleen and respiratory lymph nodes. Evaluation of pulmonary and splenic CD8+ T cells from mice vaccinated with ΔznuA B. melitensis revealed that these expressed an activated effector memory (CD44hiCD62LloCCR7lo) T cells producing elevated levels of IFN‐γ, tumor necrosis factor‐α, perforin and granzyme B. To assess the relative importance of these increased numbers of CD8+ T cells, CD8−/− mice were challenged with virulent B. melitensis, and they showed markedly increased bacterial loads in organs in contrast to similarly challenged CD4−/− mice. Only ΔznuA B. melitensis ‐ and Rev‐1‐vaccinated CD4−/− and wild‐type mice, not CD8−/− mice, were completely protected against Brucella challenge. Determination of cytokines responsible for conferring protection showed the relative importance of IFN‐γ, but not interleukin‐17 (IL‐17). Unlike wild‐type (wt) mice, IL‐17 was greatly induced in IFN‐γ−/− mice, but IL‐17 could not substitute for IFN‐γ's protection, although an increase in brucellae dissemination was observed upon in vivo IL‐17 neutralization. These results show that nasal ΔznuA B. melitensis vaccination represents an attractive means to stimulate systemic and mucosal immune protection via CD8+ T‐cell engagement.
Replication landscape of the human genome
Authors: Petryk Nataliya , Kahli Malik , d'Aubenton-Carafa Yves , Jaszczyszyn Yan , Shen Yimin , Silvain Maud , Thermes Claude , Chen Chun-Long , Hyrien Olivier
Published: January 2016

Despite intense investigation, human replication origins and termini remain elusive. Existing data have shown strong discrepancies. Here we sequenced highly purified Okazaki fragments from two cell types and, for the first time, quantitated replication fork directionality and delineated initiation and termination zones genome-wide. Replication initiates stochastically, primarily within non-transcribed, broad (up to 150 kb) zones that often abut transcribed genes, and terminates dispersively between them. Replication fork progression is significantly co-oriented with the transcription. Initiation and termination zones are frequently contiguous, sometimes separated by regions of unidirectional replication. Initiation zones are enriched in open chromatin and enhancer marks, even when not flanked by genes, and often border ‘topologically associating domains’ (TADs). Initiation zones are enriched in origin recognition complex (ORC)-binding sites and better align to origins previously mapped using bubble-trap than λ-exonuclease. This novel panorama of replication reveals how chromatin and transcription modulate the initiation process to create cell-type-specific replication programs.
1,25D3 prevents CD8+Tc2 skewing and asthma development through VDR binding changes to the Cyp11a1 promoter
Authors: Schedel Michaela , Jia Yi , Michel Sven , Takeda Katsuyuki , Domenico Joanne , Joetham Anthony , Ning Fangkun , Strand Matthew , Han Junyan , Wang Meiqin , Lucas Joseph J. , Vogelberg Christian , Kabesch Michael , O’Connor Brian P. , Gelfand Erwin W.
Published: January 2016

Effector CD8+T cells convert from IFN-γ+(Tc1) to IL-13+(Tc2) cells in the presence of IL-4. Underlying regulatory mechanisms are not fully defined. Here, we show that addition of 1,25D3, the active form of vitamin D3, during CD8+T-cell differentiation prevents IL-4-induced conversion to IL-13-producers. Transfer of 1,25D3-treated CD8+T cells into sensitized and challenged CD8+-deficient recipients fails to restore development of lung allergic responses. 1,25D3 alters vitamin D receptor (VDR) recruitment to theCyp11a1promoterin vitroandin vivoin the presence of IL-4. As a result, protein levels and enzymatic activity of CYP11A1, a steroidogenic enzyme regulating CD8+T-cell conversion, are decreased. An epistatic effect betweenCYP11A1andVDRpolymorphisms may contribute to the predisposition to childhood asthma. These data identify a role for 1,25D3 in the molecular programming of CD8+T-cell conversion to an IL-13-secreting phenotype through regulation of steroidogenesis, potentially governing asthma susceptibility.
TSPO ligand residence time: a new parameter to predict compound neurosteroidogenic efficacy
Authors: Costa Barbara , Da Pozzo Eleonora , Giacomelli Chiara , Barresi Elisabetta , Taliani Sabrina , Da Settimo Federico , Martini Claudia
Published: January 2016

The pharmacological activation of the cholesterol-binding Translocator Protein (TSPO) leads to an increase of endogenous steroids and neurosteroids determining benefic pleiotropic effects in several pathological conditions, including anxiety disorders. The relatively poor relationship between TSPO ligand binding affinities and steroidogenic efficacies prompted us to investigate the time (Residence Time, RT) that a number of compounds with phenylindolylglyoxylamide structure (PIGAs) spends in contact with the target. Here, given the poor availability of TSPO ligand kinetic parameters, a kinetic radioligand binding assay was set up and validated for RT determination using a theoretical mathematical model successfully applied to other ligand-target systems. TSPO ligand RT was quantified and the obtained results showed a positive correlation between the period for which a drug interacts with TSPO and the compound ability to stimulate steroidogenesis. Specifically, the TSPO ligand RT significantly fitted both with steroidogenic efficacy (Emax) and with area under the dose-response curve, a parameter combining drug potency and efficacy. A positive relation between RT and anxiolytic activity of three compounds was evidenced. In conclusion, RT could be a relevant parameter to predict the steroidogenic efficacy and thein vivoanxiolytic action of new TSPO ligands.
ACT-PRESTO: Rapid and consistent tissue clearing and labeling method for 3-dimensional (3D) imaging
Authors: Lee Eunsoo , Choi Jungyoon , Jo Youhwa , Kim Joo Yeon , Jang Yu Jin , Lee Hye Myeong , Kim So Yeun , Lee Ho-Jae , Cho Keunchang , Jung Neoncheol , Hur Eun Mi , Jeong Sung Jin , Moon Cheil , Choe Youngshik , Rhyu Im Joo , Kim Hyun , Sun Woong
Published: January 2016

Understanding the structural organization of organs and organisms at the cellular level is a fundamental challenge in biology. This task has been approached by reconstructing three-dimensional structure from images taken from serially sectioned tissues, which is not only labor-intensive and time-consuming but also error-prone. Recent advances in tissue clearing techniques allow visualization of cellular structures and neural networks inside of unsectioned whole tissues or the entire body. However, currently available protocols require long process times. Here, we present the rapid and highly reproducible ACT-PRESTO (active clarity technique-pressure related efficient and stable transfer of macromolecules into organs) method that clears tissues or the whole body within 1 day while preserving tissue architecture and protein-based signals derived from endogenous fluorescent proteins. Moreover, ACT-PRESTO is compatible with conventional immunolabeling methods and expedites antibody penetration into thick specimens by applying pressure. The speed and consistency of this method will allow high-content mapping and analysis of normal and pathological features in intact organs and bodies.
Ranking of Molecular Biomarker Interaction with Targeted DNA Nucleobases via Full Atomistic Molecular Dynamics
Authors: Zhang Wenjun , Wang Ming L. , Cranford Steven W.
Published: January 2016

DNA-based sensors can detect disease biomarkers, including acetone and ethanol for diabetes and H2S for cardiovascular diseases. Before experimenting on thousands of potential DNA segments, we conduct full atomistic steered molecular dynamics (SMD) simulations to screen the interactions between different DNA sequences with targeted molecules to rank the nucleobase sensing performance. We study and rank the strength of interaction between four single DNA nucleotides (Adenine (A), Guanine (G), Cytosine (C) and Thymine (T)) on single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) with acetone, ethanol, H2S and HCl. By sampling forward and reverse interaction paths, we compute the free-energy profiles of eight systems for the four targeted molecules. We find that dsDNA react differently than ssDNA to the targeted molecules, requiring more energy to move the molecule close to DNA as indicated by the potential of mean force (PMF). Comparing the PMF values of different systems, we obtain a relative ranking of DNA base for the detection of each molecule. Via the same procedure, we could generate a library of DNA sequences for the detection of a wide range of chemicals. A DNA sensor array built with selected sequences differentiating many disease biomarkers can be used in disease diagnosis and monitoring.
Leucine zipper motif in RRS1 is crucial for the regulation of Arabidopsis dual resistance protein complex RPS4/RRS1
Authors: Narusaka Mari , Toyoda Kazuhiro , Shiraishi Tomonori , Iuchi Satoshi , Takano Yoshitaka , Shirasu Ken , Narusaka Yoshihiro
Published: January 2016

Arabidopsis thaliana leucine-rich repeat-containing (NLR) proteins RPS4 and RRS1, known as dual resistance proteins, confer resistance to multiple pathogen isolates, such as the bacterial pathogens Pseudomonas syringae and Ralstonia solanacearum and the fungal pathogen Colletotrichum higginsianum. RPS4 is a typical Toll/interleukin 1 Receptor (TIR)-type NLR, whereas RRS1 is an atypical TIR-NLR that contains a leucine zipper (LZ) motif and a C-terminal WRKY domain. RPS4 and RRS1 are localised near each other in a head-to-head orientation. In this study, direct mutagenesis of the C-terminal LZ motif in RRS1 caused an autoimmune response and stunting in the mutant. Co-immunoprecipitation analysis indicated that full-length RPS4 and RRS1 are physically associated with one another. Furthermore, virus-induced gene silencing experiments showed that hypersensitive-like cell death triggered by RPS4/LZ motif-mutated RRS1 depends on EDS1. In conclusion, we suggest that the RRS1-LZ motif is crucial for the regulation of the RPS4/RRS1 complex.
A Genome-wide study of blood pressure in African Americans accounting for gene-smoking interaction
Authors: Taylor Jacquelyn Y. , Schwander Karen , Kardia Sharon L. R. , Arnett Donna , Liang Jingjing , Hunt Steven C. , Rao D.C. , Sun Yan V.
Published: January 2016

Cigarette smoking has been shown to be a health hazard. In addition to being considered a negative lifestyle behavior, studies have shown that cigarette smoking has been linked to genetic underpinnings of hypertension. Because African Americans have the highest incidence and prevalence of hypertension, we examined the joint effect of genetics and cigarette smoking on health among this understudied population. The sample included African Americans from the genome wide association studies of HyperGEN (N = 1083, discovery sample) and GENOA (N = 1427, replication sample), both part of the FBPP. Results suggested that 2 SNPs located on chromosomes 14 (NEDD8; rs11158609; raw p = 9.80 × 10−9, genomic control-adjusted p = 2.09 × 10−7) and 17 (TTYH2; rs8078051; raw p = 6.28 × 10−8, genomic control-adjusted p = 9.65 × 10−7) were associated with SBP including the genetic interaction with cigarette smoking. These two SNPs were not associated with SBP in a main genetic effect only model. This study advances knowledge in the area of main and joint effects of genetics and cigarette smoking on hypertension among African Americans and offers a model to the reader for assessing these risks. More research is required to determine how these genes play a role in expression of hypertension.
Spatiotemporal dynamics of random stimuli account for trial-to-trial variability in perceptual decision making
Authors: Park Hame , Lueckmann Jan-Matthis , von Kriegstein Katharina , Bitzer Sebastian , Kiebel Stefan J.
Published: January 2016

Decisions in everyday life are prone to error. Standard models typically assume that errors during perceptual decisions are due to noise. However, it is unclear how noise in the sensory input affects the decision. Here we show that there are experimental tasks for which one can analyse the exact spatio-temporal details of a dynamic sensory noise and better understand variability in human perceptual decisions. Using a new experimental visual tracking task and a novel Bayesian decision making model, we found that the spatio-temporal noise fluctuations in the input of single trials explain a significant part of the observed responses. Our results show that modelling the precise internal representations of human participants helps predict when perceptual decisions go wrong. Furthermore, by modelling precisely the stimuli at the single-trial level, we were able to identify the underlying mechanism of perceptual decision making in more detail than standard models.
Bright and photostable push-pull pyrene dye visualizes lipid order variation between plasma and intracellular membranes
Authors: Niko Yosuke , Didier Pascal , Mely Yves , Konishi Gen-ichi , Klymchenko Andrey S.
Published: January 2016

Imaging lipid organization in cell membranes requires advanced fluorescent probes. Here, we show that a recently synthesized push-pull pyrene (PA), similarly to popular probe Laurdan, changes the emission maximum as a function of lipid order, but outperforms it by spectroscopic properties. In addition to red-shifted absorption compatible with common 405 nm diode laser, PA shows higher brightness and much higher photostability than Laurdan in apolar membrane environments. Moreover, PA is compatible with two-photon excitation at wavelengths >800 nm, which was successfully used for ratiometric imaging of coexisting liquid ordered and disordered phases in giant unilamellar vesicles. Fluorescence confocal microscopy in Hela cells revealed that PA efficiently stains the plasma membrane and the intracellular membranes at >20-fold lower concentrations, as compared to Laurdan. Finally, ratiometric imaging using PA reveals variation of lipid order within different cellular compartments: plasma membranes are close to liquid ordered phase of model membranes composed of sphingomyelin and cholesterol, while intracellular membranes are much less ordered, matching well membranes composed of unsaturated phospholipids without cholesterol. These differences in the lipid order were confirmed by fluorescence lifetime imaging (FLIM) at the blue edge of PA emission band. PA probe constitutes thus a new powerful tool for biomembrane research.
Predicting future uncertainty constraints on global warming projections
Authors: Shiogama H. , Stone D. , Emori S. , Takahashi K. , Mori S. , Maeda A. , Ishizaki Y. , Allen M. R.
Published: January 2016

Projections of global mean temperature changes (ΔT) in the future are associated with intrinsic uncertainties. Much climate policy discourse has been guided by “current knowledge” of the ΔTs uncertainty, ignoring the likely future reductions of the uncertainty, because a mechanism for predicting these reductions is lacking. By using simulations of Global Climate Models from the Coupled Model Intercomparison Project Phase 5 ensemble as pseudo past and future observations, we estimate how fast and in what way the uncertainties of ΔT can decline when the current observation network of surface air temperature is maintained. At least in the world of pseudo observations under the Representative Concentration Pathways (RCPs), we can drastically reduce more than 50% of the ΔTs uncertainty in the 2040 s by 2029 and more than 60% of the ΔTs uncertainty in the 2090 s by 2049. Under the highest forcing scenario of RCPs, we can predict the true timing of passing the 2 °C (3 °C) warming threshold 20 (30) years in advance with errors less than 10 years. These results demonstrate potential for sequential decision-making strategies to take advantage of future progress in understanding of anthropogenic climate change.
Seasonal divergence in the interannual responses of Northern Hemisphere vegetation activity to variations in diurnal climate
Authors: Wu Xiuchen , Liu Hongyan , Li Xiaoyan , Liang Eryuan , Beck Pieter S. A. , Huang Yongmei
Published: January 2016

Seasonal asymmetry in the interannual variations in the daytime and nighttime climate in the Northern Hemisphere (NH) is well documented, but its consequences for vegetation activity remain poorly understood. Here, we investigate the interannual responses of vegetation activity to variations of seasonal mean daytime and nighttime climate in NH (>30 °N) during the past decades using remote sensing retrievals, FLUXNET and tree ring data. Despite a generally significant and positive response of vegetation activity to seasonal mean maximum temperature ("Equation missing") in ~22–25% of the boreal (>50 °N) NH between spring and autumn, spring-summer progressive water limitations appear to decouple vegetation activity from the mean summer "Equation missing", particularly in climate zones with dry summers. Drought alleviation during autumn results in vegetation recovery from the marked warming-induced drought limitations observed in spring and summer across 24–26% of the temperate NH. Vegetation activity exhibits a pervasively negative correlation with the autumn mean minimum temperature, which is in contrast to the ambiguous patterns observed in spring and summer. Our findings provide new insights into how seasonal asymmetry in the interannual variations in the mean daytime and nighttime climate interacts with water limitations to produce spatiotemporally variable responses of vegetation growth.
Rsite2: an efficient computational method to predict the functional sites of noncoding RNAs
Authors: Zeng Pan , Cui Qinghua
Published: January 2016

Noncoding RNAs (ncRNAs) represent a big class of important RNA molecules. Given the large number of ncRNAs, identifying their functional sites is becoming one of the most important topics in the post-genomic era, but available computational methods are limited. For the above purpose, we previously presented a tertiary structure based method, Rsite, which first calculates the distance metrics defined in Methods with the tertiary structure of an ncRNA and then identifies the nucleotides located within the extreme points in the distance curve as the functional sites of the given ncRNA. However, the application of Rsite is largely limited because of limited RNA tertiary structures. Here we present a secondary structure based computational method, Rsite2, based on the observation that the secondary structure based nucleotide distance is strongly positively correlated with that derived from tertiary structure. This makes it reasonable to replace tertiary structure with secondary structure, which is much easier to obtain and process. Moreover, we applied Rsite2 to three ncRNAs (tRNA (Lys), Diels-Alder ribozyme and RNase P) and a list of human mitochondria transcripts. The results show that Rsite2 works well with nearly equivalent accuracy as Rsite but is much more feasible and efficient. Finally, a web-server, the source codes and the dataset of Rsite2 are available at http://www.cuialb.cn/rsite2.
Effect of Different Mulches under Rainfall Concentration System on Corn Production in the Semi-arid Areas of the Loess Plateau
Authors: Ren Xiaolong , Zhang Peng , Chen Xiaoli , Guo Jingjing , Jia Zhikuan
Published: January 2016

The ridge and furrow farming system for rainfall concentration (RC) has gradually been popularized to improve the water availability for crops and to increase the water use efficiency (WUE), thereby stabilizing high yields. In the RC system, plastic-covered ridges are rainfall harvesting zones and furrows are planting zones. In this study, we optimized the mulching patterns for RC planting to mitigate the risks of drought during crop production in semi-arid agricultural areas. We conducted a four-year field study to determine the effects on corn production of mulching with 0.08-mm plastic film, maize straw, 8% biodegradable film, liquid film, bare furrow and conventional flat (CF) farming. We found that RC significantly increased (P > 0.05) the soil moisture storage in the top 0–100 cm layer and the topsoil temperature (0–10 cm) during the corn-growing season. Combining RC with mulching further improved the rain-harvesting, moisture-retaining and yield-increasing effects in furrows. Compared with CF, the four-year average yield increased by 1497.1 kg ha–1 to 2937.3 kg ha–1 using RC with mulch treatments and the WUE increased by 2.3 kg ha–1 mm–1 to 5.1 kg ha–1 mm–1.
Time series analysis of the association between ambient temperature and cerebrovascular morbidity in the elderly in Shanghai, China
Authors: Zhang Xian-Jing , Ma Wei-Ping , Zhao Nai-Qing , Wang Xi-Ling
Published: January 2016

Research on the association between ambient temperature and cerebrovascular morbidity is scarce in China. In this study, we applied mixed generalized additive model (MGAM) to daily counts of cerebrovascular disease of Shanghai residents aged 65 years or older from 2007–2011, stratified by gender. Weighted daily mean temperature up to lags of one week was smoothed by natural cubic spline and was added into the model to assess both linear and nonlinear effects of temperature. We found that when the mean temperature increased by 1 °C, the male cases of cerebrovascular disease reduced by 0.95% (95% Confidence Interval (CI): 0.80%, 1.10%) or reduced by 0.34% (95% CI: −0.68, 1.36%) in conditions of temperature was below or above 27 °C. However, for every 1 °C increase in temperature, the female cases of cerebrovascular disease increased by 0.34% (95% CI: −0.26%, 0.94%) or decreased by 0.92% (95% CI: 0.72, 1.11%) in conditions of temperature was below or above 8 °C, respectively. Temperature and cerebrovascular morbidity is negatively associated in Shanghai. MGAM is recommended in assessing the association between environmental hazards and health outcomes in time series studies.
Simple and effective exercise design for assessing in vivo mitochondrial function in clinical applications using 31P magnetic resonance spectroscopy
Authors: Sleigh Alison , Lupson Victoria , Thankamony Ajay , Dunger David B. , Savage David B. , Carpenter T. Adrian , Kemp Graham J.
Published: January 2016

The growing recognition of diseases associated with dysfunction of mitochondria poses an urgent need for simple measures of mitochondrial function. Assessment of the kinetics of replenishment of the phosphocreatine pool after exercise using 31P magnetic resonance spectroscopy can provide an in vivo measure of mitochondrial function; however, the wider application of this technique appears limited by complex or expensive MR-compatible exercise equipment and protocols not easily tolerated by frail participants or those with reduced mental capacity. Here we describe a novel in-scanner exercise method which is patient-focused, inexpensive, remarkably simple and highly portable. The device exploits an MR-compatible high-density material (BaSO4) to form a weight which is attached directly to the ankle and a one-minute dynamic knee extension protocol produced highly reproducible measurements of post-exercise PCr recovery kinetics in both healthy subjects and patients. As sophisticated exercise equipment is unnecessary for this measurement, our extremely simple design provides an effective and easy-to-implement apparatus that is readily translatable across sites. Its design, being tailored to the needs of the patient, makes it particularly well suited to clinical applications and we argue the potential of this method for investigating in vivo mitochondrial function in new cohorts of growing clinical interest.