bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue dependent expression of bitter receptorTAS2R38mRNA
Authors: Douglas Jennifer E. , Lin Cailu , Mansfield Corrine J. , Arayata Charles J. , Cowart Beverly J. , Spielman Andrew I. , Adappa Nithin D. , Palmer James N. , Reed Danielle R. , Cohen Noam A.
Published: April 2018

TAS2R38is a human bitter receptor gene with a common but inactive allele and people homozygous for the inactive form cannot perceive certain bitter compounds. The frequency of the inactive and active form of this receptor is nearly equal in many human populations and heterozygotes (with one copy of the active form and another copy of the inactive form) have the most common diplotype. However, heterozygotes differ markedly in their perception of bitterness, in part perhaps because of differences inTAS2R38mRNA expression. Other tissues including the nasal sinuses express this receptor, where it contributes to pathogen defense. We asked whether heterozygotes with highTAS2R38mRNA expression in taste tissue were also likely to express moreTAS2R38mRNA in sinonasal tissue. To that end, we measuredTAS2R38bitter taste receptor mRNA by qPCR in biopsied tissue, and learned that expression amount of one is not related to the other. We confirmed the general independence of expression in other tissue expressingTAS2R38mRNA using autopsy data from the GTEx project. Taste tissueTAS2R38mRNA expression among heterozygotes is unlikely to predict expression in other tissues, perhaps reflecting tissue-dependent function and hence regulation of this protein.
Concurrent Atomic Force Spectroscopy
Authors: Pimenta-Lopes Carolina , Suay-Corredera Carmen , Velázquez-Carreras Diana , Sánchez-Ortiz David , Alegre-Cebollada Jorge
Published: April 2018

Force-spectroscopy by Atomic Force Microscopy (AFM) is the technique of choice to measure mechanical properties of molecules, cells, tissues and materials at the nano and micro scales. However, unavoidable calibration errors of AFM probes make it cumbersome to quantify modulation of mechanics. Here, we show that concurrent AFM force measurements enable relative mechanical characterization with an accuracy that is independent of calibration uncertainty, even when averaging data from multiple, independent experiments. Compared to traditional AFM, we estimate that concurrent strategies can measure differences in protein mechanical unfolding forces with a 6-fold improvement in accuracy and a 30-fold increase in throughput. Prompted by our results, we demonstrate widely applicable orthogonal fingerprinting strategies for concurrent single-molecule nanomechanical profiling of proteins.
A Nested 2-Level Cross-validation Ensemble Learning Pipeline Suggests a Negative Pressure Against Crosstalk snoRNA-mRNA Interactions in Saccharomyces Cerevisae
Authors: Soulé Antoine , Steyaert Jean-Marc , Waldispuühl Jéerôme
Published: April 2018

The growing number of RNA-mediated regulation mechanisms identified in the last decades suggests a widespread impact of RNA-RNA interactions. The efficiency of the regulation relies on highly specific and coordinated interactions, while simultaneously repressing the formation of opportunistic complexes. However, the analysis of RNA interactomes is highly challenging due to the large number of potential partners, discrepancy of the size of RNA families, and the inherent noise in interaction predictions.

We designed a recursive 2-step cross-validation pipeline to capture the specificity of ncRNA-mRNA interactomes. Our method has been designed to detect significant loss or gain of specificity between ncRNA-mRNA interaction profiles. Applied to snoRNA-mRNA in Saccharomyces Cerevisae, our results suggest the existence of a repression of ncRNA affinities with mRNAs, and thus the existence of an evolutionary pressure inhibiting such interactions.
Deletion of the Creatine Transporter in dopaminergic neurons leads to hyperactivity in mice
Authors: Abdulla Zuhair I. , Pahlevani Bahar , Pennington Jordan L. , Latushka Nikita , R. Skelton Matthew
Published: April 2018

Creatine (Cr) is required for proper neuronal function, as evidenced by the intellectual disability and epileptic phenotype seen in patients with cerebral Cr deficiency syndromes (CCDS). In addition, attention-deficit hyperactivity disorder (ADHD) is a frequent co-morbidity of Cr transporter (Crt) deficiency, the leading cause of CCDS. While the effects of the loss of Cr in the whole brain is clear, it is unknown if Cr is required for the proper function of all neurons. Of particular interest are dopaminergic neurons, as many CCDS patients have ADHD and Cr has been implicated in dopamine-associated neurodegenerative disorders, such as Parkinson’s and Huntington’s diseases. The purpose of this study was to examine the effect of a loss of the Slc6a8 (Cr transporter; Crt) gene in cells expressing the dopamine transporter (Slc6a3; DAT) on activity levels and motor function as the animals age. DAT-specific Crt-knockout (DAT-Crt) mice were tested along with control (Crt-FLOX) mice monthly from 3 to 12 months of age in locomotor activity, the challenging beam test, and spontaneous activity. DAT-Crt mice were hyperactive compared with controls and this finding persisted throughout the lifetime of the mice. No changes were observed in errors to cross a narrow bridge in the challenging beam test. In a measurement of spontaneous activity, DAT-Crt mice showed increased rearing and hind limb steps, suggesting the hyperactivity carried over to this task. Taken together, these data suggest that the lack of Cr in dopaminergic neurons causes hyperactivity while sparing motor function.

Abbreviations

Cr

Creatine

CK

Creatine Kinase

P-Cr

Phosphocreatine

PD

Parkinson’s Disease

MPTP

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

6-OHDA

6-hydroxydopamine

Crt

Creatine Transporter

Crt-/y

ubiquitous creatine transporter knockout mouse

DAT-Crt-/y

dopamine-specific creatine transporter knockout mouse ADHD: Attention-deficit hyperactivity disorder
Corticostriatal oscillations predict high vs. low drinkers in a preclinical model of limited access alcohol consumption
Authors: Henricks Angela M. , Dwiel Lucas L. , Deveau Nicholas H. , Simon Amanda A. , Ruiz-Jaquez Metztli J. , Green Alan I. , Doucette Wilder T.
Published: April 2018

Individuals differ in their vulnerability to develop alcohol dependence that are determined by innate and environmental factors. The corticostriatal circuit is heavily involved in the development of alcohol dependence and may contain neural information regarding vulnerability to drink excessively. In the current experiment, we hypothesized that we could characterize high and low alcohol-drinking rats (HD and LD, respectively) based on corticostriatal oscillations, and that these subgroups would differentially respond to corticostriatal brain stimulation. Rats were trained to drink 10% alcohol in a limited access paradigm. In separate sessions, local field potentials (LFPs) were recorded from the nucleus accumbens shell (NAcSh) and medial prefrontal cortex (mPFC) of male Sprague-Dawley rats (n=13). Based on training alcohol consumption levels, we classified rats using a median split as HD or LD. Then, using machine-learning, we built predictive models to classify rats as HD or LD by corticostriatal LFPs and compared the model performance from real data to the performance of models built on data permutations. Additionally, we explored the impact of NAcSh or mPFC stimulation on alcohol consumption in HD vs. LD. Corticostriatal LFPs were able predict HD vs. LD group classification with greater accuracy than expected by chance (>80% accuracy). Additionally, NAcSh stimulation significantly reduced alcohol consumption in HD, but not LD (p<0.05), while mPFC stimulation did not alter drinking behavior in either HD or LD (p>0.05). These data collectively show that the corticostriatal circuit is differentially involved in regulating alcohol intake in HD vs. LD rats, and suggests that corticostriatal activity may have the potential to predict a vulnerability to develop alcohol dependence in a clinical population.
Stability Criteria for Complex Microbial Communities
Authors: Butler Stacey , O’Dwyer James
Published: April 2018

Competition and mutualism are inevitable processes in microbial ecology, and a central question is which and how many taxa will persist in the face of these interactions. Ecological theory has demonstrated that when direct, pairwise interactions among a group of species are too numerous, or too strong, then the coexistence of these species will be unstable to any slight perturbation. This instability worsens when mutualistic interactions complement competition. Here, we refine and to some extent overturn that understanding, by considering explicitly the resources that microbes consume and produce. In contrast to more complex organisms, microbial cells consume primarily abiotic resources, and mutualistic interactions are often mediated by these same abiotic resources through the mechanism of cross-feeding. Our model therefore considers the consumption and production of a set of abiotic resources by a group of microbial species. We show that if microbes consume, but do not produce resources, then any positive equilibrium will always be stable to small perturbations. We go on to show that in the presence of crossfeeding, stability is no longer guaranteed. However, stability still holds when mutualistic interations are either symmetric, or sufficiently weak.
Forecasting Future Humphrey Visual Fields Using Deep Learning
Authors: Wen Joanne C. , Lee Cecilia S. , Keane Pearse A. , Xiao Sa , Wu Yue , Rokem Ariel , Chen Philip P. , Lee Aaron Y.
Published: April 2018

Purpose

To determine if deep learning networks could be trained to forecast a future 24-2 Humphrey Visual Field (HVF).

Design

Retrospective database study.

Participants

All patients who obtained a HVF 24-2 at the University of Washington.

Methods

All datapoints from consecutive 24-2 HVFs from 1998 to 2018 were extracted from a University of Washington database. Ten-fold cross validation with a held out test set was used to develop the three main phases of model development: model architecture selection, dataset combination selection, and time-interval model training with transfer learning, to train a deep learning artificial neural network capable of generating a point-wise visual field prediction.

Main outcome measures

Mean absolute error (MAE) and difference in Mean Deviation (MD) between predicted and actual future HVF.

Results

More than 1.7 million perimetry points were extracted to the hundredth decibel from 32,443 24-2 HVFs. The best performing model with 20 million trainable parameters, CascadeNet-5, was selected. The overall MAE for the test set was 2.47 dB (95% CI: 2.45 dB to 2.48 dB). The 100 fully trained models were able to successfully predict progressive field loss in glaucomatous eyes up to 5.5 years in the future with a correlation of 0.92 between the MD of predicted and actual future HVF (p < 2.2 = 10−16) and an average difference of 0.41 dB.

Conclusions

Using unfiltered real-world datasets, deep learning networks show an impressive ability to not only learn spatio-temporal HVF changes but also to generate predictions for future HVFs up to 5.5 years, given only a single HVF.
Application of genomics to identify therapeutic targets in recurrent pediatric papillary thyroid carcinoma
Authors: Ronsley Rebecca , Rassekh S. Rod , Shen Yaoqing , Lee Anna F. , Jantzen Colleen , Halparin Jessica , Albert Catherine , Hawkins Douglas S. , Amed Shazhan , Rothstein Ralph , Mungall Andrew J. , Dix David , Blair Geoffrey , Nadel Helen , Jones Steven J.M. , Laskin Janessa , Marra Marco A. , J. Deyell Rebecca
Published: April 2018

Children with papillary thyroid carcinoma (PTC) may relapse despite response to radioactive iodine (RAI). Two children with multiply relapsed PTC underwent whole-genome and transcriptome sequencing. A TPM3-NTRK1 fusion was identified in one tumor, with outlier NTRK1 expression compared to the TCGA thyroid cancer compendium and to Illumina BodyMap normal thyroid. This patient demonstrated resolution of multiple pulmonary nodules without toxicity on oral TRK inhibitor therapy. A RET fusion was identified in the second tumor, another potentially actionable finding. Identification of oncogenic drivers in recurrent pediatric PTC may facilitate targeted therapy while avoiding repeated RAI.
Personalized oncogenomic analysis of metastatic adenoid cystic carcinoma: using whole-genome sequencing to inform clinical decision-making
Authors: Chahal Manik , Pleasance Erin , Grewal Jasleen , Zhao Eric , Ng Tony , Chapman Erin , Jones Martin R. , Shen Yaoqing , Mungall Karen L. , Bonakdar Melika , Taylor Gregory A. , Ma Yussanne , Mungall Andrew J. , Moore Richard A. , Lim Howard , Renouf Daniel , Yip Stephen , Jones Steven J.M. , Marra Marco A. , Laskin Janessa
Published: April 2018

Metastatic adenoid cystic carcinomas (ACCs) can cause significant morbidity and mortality. Because of their slow growth and relative rarity, there is limited evidence for systemic therapy regimens. Recently, molecular profiling studies have begun to reveal the genetic landscape of these poorly understood cancers, and new treatment possibilities are beginning to emerge. The objective is to use whole-genome and transcriptome sequencing and analysis to better understand the genetic alterations underlying the pathology of metastatic and rare ACCs and determine potentially actionable therapeutic targets. We report five cases of metastatic ACC, not originating in the salivary glands, in patients enrolled in the Personalized Oncogenomics (POG) Program at the BC Cancer Agency. Genomic workup included whole-genome and transcriptome sequencing, detailed analysis of tumor alterations, and integration with existing knowledge of drug–target combinations to identify potential therapeutic targets. Analysis reveals low mutational burden in these five ACC cases, and mutation signatures that are commonly observed in multiple cancer types. Notably, the only recurrent structural aberration identified was the well-described MYB-NFIB fusion that was present in four of five cases, and one case exhibited a closely related MYBL1-NFIB fusion. Recurrent mutations were also identified in BAP1 and BCOR, with additional mutations in individual samples affecting NOTCH1 and the epigenetic regulators ARID2, SMARCA2, and SMARCB1. Copy changes were rare, and they included amplification of MYC and homozygous loss of CDKN2A in individual samples. Genomic analysis revealed therapeutic targets in all five cases and served to inform a therapeutic choice in three of the cases to date.
Subcutaneous Injection of Pluripotent Stem Cells in Mice
Authors: Nagy Kristina Vintersten , Nagy Andras
Published: April 2018

This protocol describes the production of teratomas and teratocarcinomas used to determine the in vivo developmental potential of adult or embryonic tissues, including early-stage embryos, somites, and tail bud, as well as embryonic and other pluripotent stem cells. Resulting tumors are screened by histology and markers to assess differentiation of the tissues. Methods and sites may vary, depending on cell and tissue type. Subcutaneous injections are easy to perform and do not need surgical manipulations. Suspension of cells in Matrigel Basement Membrane (BD Biosciences) promotes their anatomical localization and is a commonly used, efficient, and reproducible approach.
Analysis of DNA Metabolism in Fission Yeast
Authors: Antequera Francisco , Humphrey Timothy C.
Published: April 2018

The fission yeast Schizosaccharomyces pombe is an excellent model organism to study DNA metabolism, in which the DNA replication and repair mechanisms are evolutionarily conserved. In this introduction we describe a range of methods commonly used to study aspects of DNA metabolism in fission yeast, focusing on approaches used for the analysis of genome stability, DNA replication, and DNA repair. We describe the use of a minichromosome, Ch16, for monitoring different aspects of genome stability. We introduce two-dimensional gel electrophoresis and immunofluorescent visualization of combed DNA molecules for the analysis of DNA replication. Further, we introduce a pulsed field gel electrophoresis (PFGE) assay to physically monitor chromosome integrity, which can be used in conjunction with a DNA double-strand break (DSB) repair assay to genetically quantitate different DSB repair and misrepair outcomes, including gross chromosomal rearrangements, in fission yeast.
Predicting landscape‐level distribution and abundance: Integrating demography, fire, elevation and landscape habitat configuration
Authors: Quintana‐Ascencio Pedro F. , Koontz Stephanie M. , Smith Stacy A. , Sclater Vivienne L. , David Aaron S. , Menges Eric S.
Published: April 2018

Demography varies in response to multiple interactive drivers at varying scales. However, these relationships are often assessed piecemeal, particularly without consideration of drivers at the landscape level.

We developed a model to predict population dynamics of an endangered, perennial herb Hypericum cumulicola across a range of landscape drivers. We estimated vital rates using 22 years of annual census data from 15 populations (10,910 and 38,313 unique observations) and additional seeding experiments, considering four landscape drivers (time‐since‐fire, patch area, patch aggregation and patch elevation).

We combined these models into integral projection models to assess population parameters. Predictions of occupancy and density were compared with an independent dataset of 33 habitat patches. We also evaluated the effect of fire‐return interval on population persistence.

The landscape drivers had interactive effects on vital rates and demography. Occupancy was predicted for most patches, including many that were unoccupied. Abundances were poorly predicted, primarily because projections were unreliable for patches having intermediate areas and aggregation. When these patches were removed, the model explained 42% of the variance in abundance. Projected population growth was greater and extinction risk lower under more frequent fire‐return intervals, at higher elevations, and in larger and more aggregated patches. Our modelling suggests that fire can be prescribed less often in larger than smaller patches to support a viable metapopulation of H. cumulicola.

Synthesis. The integration of landscape‐level drivers and detailed demographic data is a valuable tool for understanding species abundances, distributions and dynamics at large scales. We evaluated the effect of interactions among fire, patch elevation, area and aggregation on the demography of a rare and endangered plant. Our findings reinforce the importance of regional dynamics. These drivers and their interactions suggest locations that can support higher vital rates, occupancy and abundance, and what fire‐return intervals are optimal depending on landscape characteristics. This approach demonstrates a link between plant demography and landscape variables, although further work is needed to improve ecological predictions.
Review article: A primer for clinical researchers in the emergency department: Part VI. Measuring what matters: Core outcome sets in emergency medicine research
Authors: Craig Simon , Graudins Andis , Dalziel Stuart R , Powell Colin VE , Babl Franz E
Published: April 2018

In this series we address important topics for clinicians who participate in research as part of their work in the ED. The overarching goal of clinical research is to improve care and determine which treatment is best. Yet, defining and measuring outcomes – what is ‘best’ – can be one of the most difficult steps in the design of a study, in particular when answers to research questions cannot be captured in simple binary results. This article addresses how to choose outcome measures and highlights the increasingly important concept of core outcome sets.
microRNA‐181a inhibits ocular neovascularization by interfering with vascular endothelial growth factor expression
Authors: Yang Chun , Tahiri Houda , Cai Chenrongrong , Gu Muqing , Gagnon Carmen , Hardy Pierre
Published: April 2018

Aim

Excess angiogenesis or neovascularization plays a key role in the pathophysiology of several ocular diseases such as retinopathy of prematurity, diabetic retinopathy, and exudative age‐related macular degeneration. microRNA‐181a (miR‐181a) was found highly expressed in retina and choroidal tissues. This study intends to investigate the role of miR‐181a in the regulation of ocular neovascularization in different pathophysiological conditions.

Method

We performed the RNA sequence to identify the microRNAs components of anti‐angiogenic lymphocyte‐derived microparticles (LMPs). The effect of miR‐181a on human retinal endothelial cells proliferation was assessed in vitro. The impact of miR‐181a on angiogenesis was confirmed using in vitro angiogenesis assay, ex vivo choroidal explant, and in vivo retinal neovascularization. The expression of major angiogenic factors was assessed by real‐time qPCR.

Results

RNA sequence revealed that miR‐181a is selectively enriched in LMPs. Importantly, the inhibition of miR‐181a significantly abrogated the effect of LMPs on endothelial viability, but overexpression of miR‐181a reduced endothelial cell viability in a dose‐dependent manner. miR‐181a strongly inhibited in vitro angiogenesis and ex vivo choroidal neovascularization. The strong anti‐angiogenic effect of miR‐181a was also displayed on the retinal neovascularization of the in vivo mouse model of oxygen‐induced retinopathy. In keeping with its effect, several angiogenesis‐related genes were dysregulated in the miR‐181a overexpressed endothelial cells.

Conclusion

These data may open unexpected avenues for the development of miR‐181a as a novel therapeutic strategy that would be particularly useful and relevant for the treatment of neovascular diseases.
Prognosis of multi‐level N2‐positive non‐small cell lung cancer according to lymph node staging using endobronchial ultrasound‐transbronchial biopsy
Authors: Yoon Hee‐Young , Lee Jae Cheol , Kim Sang‐We , Kim Hyeong Ryul , Kim Yong‐Hee , Choi Se Hoon , Kim Su San , Song Si Yeol , Choi Eun Kyung , Jang Se Jin , Choi Chang‐Min
Published: April 2018

Background

The optimal treatment for stage IIIA‐N2 non‐small cell lung cancer (NSCLC) remains controversial, and multidisciplinary team approaches are needed. Downstaging after induction therapy is a good prognostic factor in surgical patients; however, re‐evaluation of nodal status before surgery is challenging. The aim of this study was to evaluate the prognosis of patients with multi‐level N2 NSCLC who received surgery or chemoradiation therapy (CRT) according to restaging using endobronchial ultrasound‐transbronchial aspiration (EBUS‐TBNA).

Methods

This was a single center, prospective study that included 16 patients with biopsy‐proven multi‐level N2 disease on initial EBUS‐TBNA that was restaged using EBUS‐TBNA after induction therapy. Cases downstaged after rebiopsy were treated surgically. Three‐year progression‐free survival (PFS) and locoregional PFS were determined using Kaplan–Meier analysis.

Results

Of the 16 patients (median age 58 years, male 63%), eight had persistent N2 disease and eight showed N2 clearance on restaging using EBUS‐TBNA. Ten patients underwent surgery, including two patients without N2 clearance. Recurrence and locoregional recurrence occurred in eight and five patients, respectively. The three‐year PFS was longer in patients with N2 clearance than in those with N2 persistent disease (57.1% vs. 37.5%). Patients with N2 clearance also had longer three‐year locoregional PFS than those with N2 persistent disease (71.4% vs. 62.5%).

Conclusions

EBUS‐TBNA could be an effective diagnostic method for restaging in multi‐level N2 NSCLC patients after induction CRT. As this was a pilot study, further large‐scale randomized studies are needed.
Introduction to the Specific Aims Page of a Grant Proposal
Authors: Monte Andrew A. , Libby Anne M.
Published: April 2018

Grant writing starts with crafting an effective specific aims page. This page should be a succinct combination of sales pitch and science. The specific aims page demonstrates a problem and a gap in current knowledge and suggests a solution. It proposes aims that work toward a defended solution and reveal the impact of the proposal on the problem, the field, and future research. The language must be efficient and persuasive; the presentation must drive a reviewer to support the proposal. Here we present a recipe for an effective specific aims page.
Physician Age and Performance on the American Board of Emergency Medicine ConCert Examination
Authors: Marco Catherine A. , Wahl Robert P. , House Hans R. , Goyal Deepi G. , Keim Samuel M. , Ma O. John , Joldersma Kevin B. , Johnston Mary M. , Harvey Anne L.
Published: April 2018

Objective

This study was undertaken to expand on results from a 2014 study on the association between physician age and performance on the American Board of Emergency Medicine (ABEM) ConCert examination.

Methods

This was a retrospective, longitudinal growth study comparing performance on the ConCert examination and physicians’ ages at the time of examination. All examination attempts from 1990 to 2016 made by residency‐trained physicians were eligible for inclusion. Multilevel growth models were constructed to examine the relationship between age at time of examination and performance, controlling for physician characteristics.

Results

The study group included 15,533 examination attempts by 12,786 physicians. The mean (±SD) age of the physicians across all examination administrations was 45.02 (±5.18) years (range = 35 to 72 years). The mean (±SD) ConCert examination score across all administrations was 85.39 (±5.71; range = 51 to 100). Among first‐time ConCert examination takers, older age was associated with lower examination scores (r = –0.25, p < 0.0001). Across all examination attempts, age was negatively correlated to examination scores (r = –0.24; p < 0.0001).

Conclusions

After physician characteristics were controlled for, there was an association between advancing age and declining performance on the ABEM ConCert examination. This information may be important to the individual physician to develop targeted competency assessment and professional development.
Intrauterine vaccination induces a dose‐sensitive primary humoral response with limited evidence of recall potential
Authors: Pasternak Jonathan Alexander , Hamonic Glenn , Van Kessel Jill , Wheler Colette L. , Dyck Michael K. , Wilson Heather L.
Published: April 2018

Problem

Induction of the local mucosal immune system within the reproductive tract is widely considered to be a key component in the development of effective prophylactic vaccines to control the spread of sexually transmitted infections. Here, we examine the capacity of the upper reproductive tract to act as a site of immune induction following.

Method of study

Two vaccines formulated with a triple adjuvant combination and either recombinant bovine herpesvirus (tgD) protein or ovalbumin (OVA) were delivered at varying doses to the uterine lumen of rabbits and the resulting immune response evaluated after 32 days.

Results

Intrauterine vaccination produced a dose‐dependent induction of both antigen‐specific IgG and IgA in serum. Both uterine and broncheoalveolar lavage of the high and medium‐dose vaccine group contained a significant increase in both anti‐OVA and anti‐tgD IgG, but no significant quantities of antigen‐specific IgA were observed. The restimulation of splenocytes from the high‐dose vaccine group with ovalbumin (OVA) only resulted in a small but significant increase in gene expression of the Th1 cytokines (IL2/IFNγ) in the absence of an observable increase in proliferation.

Conclusion

Collectively, the results confirm the capacity of the uterine immune system to generate a primary response following stimulation.
Determinants of canopy gap characteristics in rehabilitating coastal dune forests
Authors: Rolo Victor , Olivier Pieter I. , van Aarde Rudi J.
Published: April 2018

Questions

What drives canopy gap formation in regenerating coastal dune forest? Does canopy gap size frequency distribution differ between new and old‐growth forests? Can canopy gaps divert regenerating trajectories?

Location

Rehabilitating coastal dune forest, KwaZulu‐Natal, South Africa.

Methods

We mapped canopy gaps in regenerating dune forest patches of varying age, which develop after seeding of the pioneer Vachellia kosiensis, and a reference forest by means of unsupervised classification of multi‐spectral satellite images. We tested if gap formation can be explained by abiotic (exposure to winds) and/or biotic (tree density at early stages) variables. We calculated the scaling exponent of a power‐law model to quantify if gap size frequency differed between new and old‐growth forests. Finally, we measured canopy openness, tree height and number of stems to validate canopy gap classification and assess the consequences of canopy gaps on regenerating trajectories.

Results

Exposure to winds and tree density at early stages were both significant predictors of gap presence. Gaps were more likely to be present along dune ridges and areas with low tree density than valleys and areas with high tree density at early stages. Large gaps were common in both new and old‐growth forests. The scaling exponent was positively related to regeneration age, indicating a reduction in gap size as the forest aged. Areas with open canopies had shorter individual trees that were more likely to be multi‐stemmed than areas with closed canopies.

Conclusion

Canopy gaps are an important component of new and old‐growth coastal dune forests dynamics. Although gaps are filled during forest development, changes in individual life‐history strategies and morphology may alter regeneration trajectories. However, because their effect is partly controlled by the exposure to wind and tree density at early stages, it can also be manipulated by management to ensure nucleation, which could accelerate forest recovery.
The Emergence of Forgiveness in Young Children
Authors: Oostenbroek Janine , Vaish Amrisha
Published: April 2018

Humans depend greatly on our cooperative relationships. Thus, when our relationships are damaged by transgressions, they need to be repaired. Such repair requires that the transgressor show remorse and the victim forgive. Previous research demonstrates that as transgressors, young children show remorse and attempt to repair the harm they caused. However, it remains unclear when children, as victims, forgive remorseful transgressors. In Study 1, 5‐, but not 4‐year‐olds, (n = 20 each) were more forgiving of a remorseful transgressor (who did not explicitly apologize) than an unremorseful transgressor. In Study 2, 4‐year‐olds (n = 20) were more forgiving of an apologetic than unapologetic transgressor. Thus, from early in ontogeny, humans are motivated to repair damaged relationships and thus uphold cooperation.
Tabata protocol: a review of its application, variations and outcomes
Authors: Viana Ricardo Borges , de Lira Claudio Andre Barbosa , Naves João Pedro Araújo , Coswig Victor Silveira , Del Vecchio Fabrício Boscolo , Gentil Paulo
Published: April 2018

Purpose

The great popularity of the Tabata Protocol is accompanied by an uncomfortable lack of consistency and criteria in its use, which results in many controversies in the results obtained from its utilization. The purpose of this study was to analyse the studies that based their interventions on the Tabata Protocol and to provide a critical analysis of its use.

Methods

A systematic literature search was conducted in PubMed and Scopus. All articles published between 1996 and October 2017 that cited at least one of the original studies of Tabata et al. were considered. Inclusion criteria were as follows: original articles, human trials and English language.

Results

Thirty studies were included for analysis. Almost 37% of the studies (n = 11) used a variation of the Tabata Protocol on a cycle ergometer. Only five studies stated the use of the original Tabata Protocol. Exercise intensity was controlled by percentage of iO2max (n = 8) or iO2peak (n = 3), number of bouts performed (n = 3), all out (n = 10), rate of perceived exertion (n = 1), self‐perception of paces (n = 1), maximal power output (n = 1), aerobic power (n = 1) and other forms (n = 2).

Conclusion

Based on our results, variations of the Tabata Protocol seem to be indicated to provide increases in aerobic power that are similar to traditional aerobic training while being less time consuming. These adaptations seem to be mainly due to peripheral adaptations. Moreover, the use of Tabata Protocols to promote weight loss is not substantiated by the reviewed studies.
Curcumin enhances the anti‐cancer effects of Paris Saponin II in lung cancer cells
Authors: Man Shuli , Zhang Lili , Cui Jingxia , Yang Li , Ma Long , Gao Wenyuan
Published: April 2018

Objectives

To investigate the synergistic mechanisms of Paris Saponin II (PSII) and Curcumin (CUR) in lung cancer.

Materials and Methods

The combination changed the cellular uptake of CUR and PSII, apoptosis, cell cycle arrest and cytokine levels were analysed on different lung cancer cells.

Results

The combination displayed a synergistic anti‐cancer effect through promoting the cellular uptake of CUR on different lung cancer cells. Hoechst H33258 staining and FACS assay indicated that the combination of PSII and CUR induced cell cycle arrest and apoptosis. Western blot and cytokine antibody microarray suggested that the combination activated death receptors such as DR6, CD40/CD40L, FasL and TNF‐α to induce cancer cells apoptosis, and up‐regulated IGFBP‐1 leading to inhibition of PI3K/Akt pathway and increase of p21 and p27, which therefore induced a G2 phase arrest in NCI‐H446 cells. Meanwhile, the combination suppressed PCNA and NF‐κB pathway in 4 kinds of lung cancer cells. They activated the phosphorylation of p38 and JNK, and inhibited PI3K in NCI‐H460 and NCI‐H446 cells, enhanced the phosphorylation of JNK in NCI‐H1299 cells, and increased the phosphorylation of p38 and ERK, and suppressed PI3K in NCI‐H520 cells.

Conclusions

PSII combined with CUR had a synergistic anti‐cancer effect on lung cancer cells. These findings provided a rationale for using the combination of curcumin and PSII in the treatment of lung cancer in future.
The Case for Local and Sustainable Seafood: A Georgia Example
Authors: Tookes Jennifer Sweeney , Barlett Peggy , Yandle Tracy
Published: April 2018

Growing demand for local, sustainable food is supporting an explosion of direct marketing throughout the United States (U.S.). Despite recent scholarship on ethics and sustainability issues in seafood, these are less commonly addressed among the consumers participating in the local food movement. This paper examines the interplay between demand for local and ethically sourced foods and the implications for seafood sustainability in the U.S. south, asking: what are Georgia consumer perceptions of local and sustainable foods, to what extent do they consider seafood in the local food movement, and how can Georgia fisheries fit within these understandings and preferences? We refashion a values‐based supply chain model to encapsulate consumers’ preferences, and propose a three‐tiered, process based model of involvement for seafood consumers. In sum, we argue that sustainable seafood deserves a more prominent place in the local food movement.
Employers’ responses to the HIV epidemic in sub‐Saharan Africa: Revisiting the evidence
Authors: Deane Kevin , Stevano Sara , Johnston Deborah
Published: April 2018

Do employers have a role to play to support people living with HIV? The literature on sub‐Saharan Africa points to the existence of a positive business case that sees firms as incentivized to provide HIV‐related services to HIV positive workers However, the evidence is narrow and incomplete, with the business case holding for a limited number of formal sector skilled workers, leaving out most people living with HIV. If employers are to play a role, policy‐makers need to create conducive conditions for positive responses, in addition to—not in replacement of—strengthening public healthcare systems.
DNA methylation of the BRD2 promoter is associated with juvenile myoclonic epilepsy in Caucasians
Authors: Pathak Shilpa , Miller James , Morris Emily C. , Stewart William C. L. , Greenberg David A.
Published: April 2018

Objective

Juvenile myoclonic epilepsy (JME) is a common adolescent‐onset genetic generalized epilepsy (GGE) syndrome. Multiple linkage and association studies have found that BRD2 influences the expression of JME. The BRD2‐JME connection is further corroborated by our murine model; Brd2 haploinsufficiency produces characteristics that typify the clinical hallmarks of JME. Neither we, nor several large‐scale studies of JME, found JME‐related BRD2 coding mutations. Therefore, we investigated noncoding BRD2 regions, seeking the origin of BRD2's JME influence. BRD2's promoter harbors a JME‐associated single nucleotide polymorphism (rs3918149) and a CpG (C‐phosphate‐G dinucleotides) island (CpG76), making it a potential “hotspot” for JME‐associated epigenetic variants. Methylating promoter CpG sites causes gene silencing, often resulting in reduced gene expression. We tested for differences in DNA methylation at CpG76 in 3 different subgroups: (1) JME patients versus their unaffected family members, (2) JME versus patients with other forms of GGE, and (3) Caucasian versus non‐Caucasian JME patients.

Methods

We used DNA pyrosequencing to analyze the methylation status of 10 BRD2 promoter CpG sites in lymphoblastoid cells from JME patients of Caucasian and non‐Caucasian origin, unaffected family members, and also non‐JME GGE patients. We also measured global methylation levels and DNA methyl transferase 1 (DNMT1) transcript expression in JME families by standard methods.

Results

CpG76 is highly methylated in JME patients compared to unaffected family members. In families with non‐JME GGE, we found no relationship between promoter methylation and epilepsy. In non‐Caucasian JME families, promoter methylation was mostly not associated with epilepsy. This makes the BRD2 promoter a JME‐specific, ethnicity‐specific, differentially methylated region. Global methylation was constant across groups.

Significance

BRD2 promoter methylation in JME, and the lack of methylation in unaffected relatives, in non‐JME GGE patients, and in non‐Caucasian JME, demonstrate that methylation specificity is a possible seizure susceptibility motif in JME risk and suggests JME therapeutics targeting BRD2.
Soil quality indicator response to land‐use change from annual to perennial bioenergy cropping systems in Germany
Authors: Ruf Thorsten , Makselon Jennifer , Udelhoven Thomas , Emmerling Christoph
Published: April 2018

Production of biomass feedstock for methanation in Europe has focused on silages of maize and cereals. As ecological awareness has increased in the last several years, more attention is being focused on perennial energy crops (PECs). Studies of specific PECs have shown that their cultivation may enhance agrobiodiversity and increase soil organic carbon stocks while simultaneously providing valuable feedstock for methanation. This study was designed to compare soil quality indicators under annual energy crops (AECs), PECs and permanent grassland (PGL) on the landscape level in south‐western Germany. At a total 25 study sites, covering a wide range of parent materials, the cropping systems were found adjacent to each other. Stands were commercially managed, and PECs included different species such as the Cup Plant, Tall Wheatgrass, Giant Knotweed, Miscanthus, Virginia Mallow and Reed Canary Grass. Soil sampling was carried out for the upper 20 cm of soil. Several soil quality indicators, including soil organic carbon (Corg), soil microbial biomass (Cmic), and aggregate stability, showed that PECs were intermediate between AEC and PGL systems. At landscape level, mean Corg content for (on average) 6.1‐year‐old stands of PEC was 22.37 (±7.53) g kg−1, compared to 19.23 (±8.08) and 32.08 (±10.11) for AEC and PGL. Cmic contents were higher in PECs (356 ± 241 μg C g−1) compared to AECs (291 ± 145) but significantly lower than under PGL (753 ± 417). The aggregate stability increased by almost 65% in PECs compared to AEC but was still 57% lower than in PGL. Indicator differences among cropping systems were more pronounced when inherent differences in the parent material were accounted for in the comparisons. Overall, these results suggest that the cultivation of PECs has positive effects on soil quality indicators. Thus, PECs may offer potential to make the production of biomass feedstock more sustainable.
Physical frailty and mortality risk in Japanese older adults
Authors: Yuki Atsumu , Otsuka Rei , Tange Chikako , Nishita Yukiko , Tomida Makiko , Ando Fujiko , Shimokata Hiroshi
Published: April 2018

Aim

The association between frailty and increased mortality risk is unknown. The present study assessed the longitudinal relationship between frailty and mortality risk in Japanese community‐dwelling older adults.

Methods

Participants included 841 randomly chosen community‐dwelling Japanese individuals, including 175 older adults aged 65–88 years with incomplete data at the baseline examination (July 2006–July 2008). Participants were followed from baseline to 31 December 2015 (mean 7.9 years). Frailty was diagnosed according to frailty criteria, including unintentional weight loss (shrinking), exhaustion, low activity, low grip strength and low gait speed. Information on deaths was obtained from a population dynamics survey. The relationship between frailty and mortality was assessed using Kaplan–Meier survival curves and Cox proportional hazards regression. The Cox proportional hazards model was used to control for potential confounders, including age at baseline, body fat, education, the Mini‐Mental State Examination score, the Center for Epidemiologic Studies Depression Scale score, total physical activity, total caloric intake, alcohol intake, current smoking, household income and the number of current diseases.

Results

The fully adjusted hazard ratio for all‐cause mortality in the frailty group was 2.63 (95% confidence interval, 1.28–5.39; P for trend <0.01). The age‐ and sex‐adjusted hazard ratio for mortality of cancer in the frailty group was 3.33 (95% confidence interval, 1.15–9.62; P for trend <0.05).

Conclusion

Complications of frailty, which include shrinking, exhaustion, low activity, weakness, and slowness, appear to be significant risks for mortality in Japanese older adults. Geriatr Gerontol Int 2018; 18: 1085–1092.
Factor XI deficiency is not associated with an increased risk of pneumonia and pneumonia‐related mortality
Authors: Salomon O. , Preis M. , Abu Shtaya A. , Kotler A. , Stein N. , Saliba W.
Published: April 2018

Introduction

Drugs targeting factor XI (FXI) shows promising results in reducing postoperative VTE. Recently, researchers have shown that FXI knockout mice had a worse outcome when infected with pathogens for pneumonia, raising concerns about the safety of these drugs.

Aim

To investigate the effect of FXI deficiency on the incidence of pneumonia and outcomes of pneumonia in humans.

Methods

Using the computerized database of the largest healthcare provider in Israel, we identified adults who were tested for FXI activity between January of 2002 and December of 2014 (n = 10 193). Patients were followed up until December of 2016 for the occurrence of pneumonia and pneumonia requiring hospitalization as a proxy of severe pneumonia.

Results

A total of 8958 (87.9%) had normal FXI activity, 804 (7.9%) had partial deficiency and 431 (4.2%) had severe deficiency; 722 individuals had pneumonia during 70 881 person‐years of follow‐up (incidence rate: 10.2 per 1000 person‐years). Compared to those with normal FXI activity, the adjusted HR for pneumonia was 0.87 (95% CI, 0.67‐1.14), and 0.95 (0.69‐1.30) for those with partial and severe FXI deficiency, respectively. Overall, 256 individuals were hospitalized for pneumonia during 72 209 person‐years of follow‐up (incidence rate: 3.5 per 1000 person‐years). The corresponding HR for severe pneumonia was 1.0 (0.70‐1.48) and 0.86 (0.53‐1.40) in those with partial and severe FXI deficiency, respectively. FXI deficiency was not significantly associated with 30‐day and 90‐day mortality among patients with pneumonia.

Conclusion

FXI deficiency was not associated with an increased risk of pneumonia, pneumonia severity or short‐term mortality among patients with pneumonia.
PRICE DISPERSION AND DEMAND UNCERTAINTY: EVIDENCE FROM U.S. SCANNER DATA
Authors: Eden Benjamin
Published: April 2018

I use the Prescott (1975) hotels model to explain variations in price dispersion across items sold by supermarkets in Chicago. The effect of uncertainty about aggregate demand on price dispersion is highly significant and quantitatively important: My estimates suggest that more than 40% of the cross‐sectional standard deviation of log prices is due to demand uncertainty. I also find that price dispersion measures are negatively correlated with the average price but are not negatively correlated with the revenues from selling the good (across stores and weeks) and with the number of stores that sell the good.
The effect of substrate temperature on microstructural evolution and hardenability of tungsten carbide coating in hot filament chemical vapor deposition
Authors: Sabzi Masoud , Mousavi Anijdan Seyyed Hashem , Asadian Mohsen
Published: April 2018

Effect of substrate temperature on microstructural evolution and hardenability of tungsten carbide coating produced by hot filament chemical vapor deposition (HFCVD) process was studied. Annealed sheets of 316L stainless steels were used as the substrate. HFCVD technique, with substrate temperatures of 400 and 500°C, was used to deposit tungsten carbide coating on these sheets. Field Emission Scanning Electron Microscope (FE‐SEM) was used to study the evolution of microstructure. X‐Ray Diffraction spectroscopy was used to analyze the phases formed and Raman spectroscopy was employed to differentiate molecular composition of the coatings. The amount of the porosity of the coatings was measured and Vickers hardness measurement was used for hardness assessment. Results show that the tungsten carbide coatings have a honeycomb structure and increasing the temperature of the substrate increases the amount of porosity of the coating. XRD results showed that 3 different crystalline structures containing W, WC, and W2C were formed in the coating deposited on the 316L stainless steel. Increasing the temperature of the deposition has increased the intensity of the peaks in the XRD results. Raman spectroscopy results indicated the presence of a carbon in the tungsten carbide coatings. Finally, microhardness of the tungsten carbide coating increases with increasing the temperature of the substrate.
Examining the effects of the Durunuri programme on low‐wage workers' social insurance coverage in South Korea
Authors: Park Mikyung , Cho Rosa Minhyo
Published: April 2018

This study examined the effects of the Durunuri programme in Korea, a Making Work Pay policy initiated in 2012 that subsidises social insurance contributions of low‐wage workers in workplaces with fewer than 10 employees. Using a nationally representative sample of Korean low‐wage workers between the years 2010 and 2015, the study employs a difference‐in‐differences method to isolate the effect of the Durunuri programme on workers' subscription rate to the national pension and employment insurance programmes. Results indicated that, compared with ineligible low‐wage workers in workplaces with 10 or more but fewer than 30 employees, eligible low‐wage workers in workplaces with fewer than 10 employees were found to experience an increase in the odds of being subscribed to both the national pension and employment insurance programmes during the first, second and third year following implementation of the Durunuri programme. Policy implications as well as future policy modifications are further discussed.