bluuebunny/crossref_metadata_2025 huggingface dataset:
Multivariate predictions of local reduced‐order‐model errors and dimensions
Authors: Moosavi Azam , Ştefănescu Răzvan , Sandu Adrian
Published: July 2017

This paper introduces multivariate input‐output models to predict the errors and bases dimensions of local parametric Proper Orthogonal Decomposition reduced‐order models. We refer to these mappings as the multivariate predictions of local reduced‐order model characteristics (MP‐LROM) models. We use Gaussian processes and artificial neural networks to construct approximations of these multivariate mappings. Numerical results with a viscous Burgers model illustrate the performance and potential of the machine learning‐based regression MP‐LROM models to approximate the characteristics of parametric local reduced‐order models. The predicted reduced‐order models errors are compared against the multifidelity correction and reduced‐order model error surrogates methods predictions, whereas the predicted reduced‐order dimensions are tested against the standard method based on the spectrum of snapshots matrix. Since the MP‐LROM models incorporate more features and elements to construct the probabilistic mappings, they achieve more accurate results. However, for high‐dimensional parametric spaces, the MP‐LROM models might suffer from the curse of dimensionality. Scalability challenges of MP‐LROM models and the feasible ways of addressing them are also discussed in this study.
Comparison of Non-Coding RNAs in Exosomes and Functional Efficacy of Human Embryonic Stem Cell- versus Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Authors: Lee Won Hee , Chen Wen-Yi , Shao Ning-Yi , Xiao Dan , Qin Xulei , Baker Natalie , Bae Hye Ryeong , Wei Tzu-Tang , Wang Yongjun , Shukla Praveen , Wu Haodi , Kodo Kazuki , Ong Sang-Ging , Wu Joseph C.
Published: July 2017

Both human embryonic stem cell-derived cardiomyocytes (ESC-CMs) and human induced pluripotent stem cell-derived CMs (iPSC-CMs) can serve as unlimited cell sources for cardiac regenerative therapy. However, the functional equivalency between human ESC-CMs and iPSC-CMs for cardiac regenerative therapy has not been demonstrated. Here, we performed a head-to-head comparison of ESC-CMs and iPSC-CMs in their ability to restore cardiac function in a rat myocardial infarction (MI) model as well as their exosomal secretome. Human ESCs and iPSCs were differentiated into CMs using small molecule inhibitors. Fluorescence-activated cell sorting analysis confirmed ∼85% and ∼83% of CMs differentiated from ESCs and iPSCs, respectively, were positive for cardiac troponin T. At a single-cell level, both cell types displayed similar calcium handling and electrophysiological properties, with gene expression comparable with the human fetal heart marked by striated sarcomeres. Sub-acute transplantation of ESC-CMs and iPSC-CMs into nude rats post-MI improved cardiac function, which was associated with increased expression of angiogenic genes in vitro following hypoxia. Profiling of exosomal microRNAs (miRs) and long non-coding RNAs (lncRNAs) revealed that both groups contain an identical repertoire of miRs and lncRNAs, including some that are known to be cardioprotective. We demonstrate that both ESC-CMs and iPSC-CMs can facilitate comparable cardiac repair. This is advantageous because, unlike allogeneic ESC-CMs used in therapy, autologous iPSC-CMs could potentially avoid immune rejection when used for cardiac cell transplantation in the future.
Correlation between the methylation of the FUT1 promoter region and FUT1 expression in the duodenum of piglets from newborn to weaning
Authors: Dai Chaohui , Sun Li , Xia Riwei , Sun Shouyong , Zhu Guoqiang , Wu Shenglong , Bao Wenbin
Published: July 2017

Alpha-(1,2)-fucosyltransferase (FUT1) gene has some influence on economically important traits and disease resistance. DNA methylation plays an important role in human diseases but is relatively poorly studied in pigs by regulating the mRNA expression of genes. The aim of this study was to analyze the influence of promoter methylation on the expression of FUT1 gene. We used bisulfite sequencing PCR (BSP) and qPCR to analyze the methylation of the FUT1 5′-flanking region and FUT1 mRNA expression in the duodenum of Sutai piglets from newborn to weaning. FUT1 contains three CpG islands upstream of the start codon, of which two are located in the putative promoter region containing multiple promoter elements and transcription factor binding sites, such as CpG islands, a CAAT box, SP1, and EARLY-SEQ 1. The CpG island between nucleotides −1762 and −580 had a low degree of methylation, and its methylation level was significantly lower in 35-day-old piglets than 8- and 18-day-old piglets (P < 0.05). FUT1 mRNA expression was significantly higher in 35-day-old piglets than 8- and 18-day-old piglets (P < 0.05). Pearson’s correlation analysis showed that the methylation of the CpG island between nucleotides −1762 and −580 of FUT1 was significantly, negatively correlated with FUT1 mRNA expression (P < 0.05). These results demonstrate that differential methylation of CpG islands negatively regulates the expression of FUT1 in the porcine duodenum, suggesting a probable influence on the resistance of piglets to infection with ETEC F18.
Congenital Anomalies of the Superior Vena Cava: Embryological Correlation, Imaging Perspectives, and Clinical Relevance
Authors: Ghandour Abed , Karuppasamy Karunakaravel , Rajiah Prabhakar
Published: July 2017

There is a wide spectrum of congenital anomalies of the superior vena cava, which are more increasingly recognized in cross-sectional imaging. Although some of these anomalies are asymptomatic, others have important clinical and interventional implications. Imaging modalities such as computed tomography and magnetic resonance imaging play an important role in the accurate characterization of these anomalies, which is essential for mapping prior to surgeries or interventions. In this article, we review a wide range of anomalies of the superior vena cava, including the embryological basis, cross-sectional imaging findings, and clinical implications, particularly from an interventional radiology perspective. We also discuss the treatments and complications of these anomalies.
Assessment of Cirrhotic Liver Enhancement with Multiphasic Computed Tomography Using a Faster Injection Rate, Late Arterial Phase, and Weight-Based Contrast Dosing
Authors: Eddy Kathleen , Costa Andreu F.
Published: July 2017

Purpose

This study aimed to update our liver computed tomography (CT) protocol according to published guidelines, and to quantitatively evaluate the effect of these modifications.

Methods

The modified liver CT protocol employed a faster injection rate (5 vs 3 mL/s), later arterial phase (20-second vs 10-second postbolus trigger), and weight-based dosing of iodinated contrast (1.7 mL/kg vs 100 mL fixed dose). Liver and vascular attenuation values were measured on CTs of patients with cirrhosis from January to September 2015 (old protocol, n = 49) and from October to December 2015 (modified protocol, n = 31). CTs were considered adequate if liver enhancement exceeded 50 Hounsfield units (HU) in portal venous phase, or when the unenhanced phase was unavailable, if a minimum iodine concentration of 500 mg I/kg was achieved. Attenuations and iodine concentrations were compared using the t test and the number of suboptimal studies was compared with Fisher's exact test.

Results

CTs acquired with the modified protocol demonstrated higher aortic ( P = .001) and portal vein ( P < .0001) attenuations in the arterial phase as well as greater hepatic attenuation on all postcontrast phases ( P = .0006, .002, and .003 for arterial, venous, and equilibrium phases, respectively). Hepatic enhancement in the portal venous phase (61 ± 15 HU vs 51 ± 16 HU; P = .0282) and iodine concentrations (595 ± 88 mg I/kg vs 456 ± 112 mg I/kg; P < .0001) were improved, and the number of suboptimal studies was reduced from 57% to 23% ( P = .01).

Conclusions

A liver CT protocol with later arterial phase, faster injection rate, and weight-based dosing of intravenous contrast significantly improves liver enhancement and iodine concentrations in patients with cirrhosis, resulting in significantly fewer suboptimal studies.
Multiparametric Magnetic Resonance Imaging of the Prostate for Tumour Detection and Local Staging: Imaging in 1.5T and Histopathologic Correlation
Authors: Loggitsi Dimitra , Gyftopoulos Anastasios , Economopoulos Nikolaos , Apostolaki Aikaterini , Kalogeropoulos Theodoros , Thanos Anastasios , Alexopoulou Efthimia , Kelekis Nikolaos L.
Published: July 2017

Purpose

The study sought to prospectively evaluate which technique among T2-weighted images, dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), diffusion-weighted (DW) MRI, or a combination of the 2, is best suited for prostate cancer detection and local staging.

Methods

Twenty-seven consecutive patients with biopsy-proven adenocarcinoma of the prostate underwent MRI on a 1.5T scanner with a surface phased-array coil prior radical prostatectomy. Combined anatomical and functional imaging was performed with the use of T2-weighted sequences, DCE MRI, and DW MRI. We compared the imaging results with whole mount histopathology.

Results

For the multiparametric approach, significantly higher sensitivity values, that is, 53% (95% confidence interval [CI]: 41.0-64.1) were obtained as compared with each modality alone or any combination of the 3 modalities ( P < .05). The specificity for this multiparametric approach, being 90.3% (95% CI: 86.3-93.3) was not significantly higher ( P < .05) as compared with the values of the combination of T2+DCE MRI, DW+DCE MRI, or DCE MRI alone. Among the 3 techniques, DCE had the best performance for tumour detection in both the peripheral and the transition zone. High negative predictive value rates (>86%) were obtained for both tumour detection and local staging.

Conclusions

The combination of T2-weighted sequences, DCE MRI, and DW MRI yields higher diagnostic performance for tumour detection and local staging than can any of these techniques alone or even any combination of them.
Cerebral hypoperfusion is not associated with an increase in amyloid β pathology in middle‐aged or elderly people
Authors: Hansson Oskar , Palmqvist Sebastian , Ljung Hanna , Cronberg Tobias , van Westen Danielle , Smith Ruben
Published: July 2017

Introduction

It is hypothesized that cerebral hypoperfusion promotes the development of Alzheimer pathology. We therefore studied whether longstanding cerebral hypoperfusion is associated with Alzheimer pathology in nondemented humans.

Methods

Cerebral blood flow and amyloid β (18F‐Flutemetamol) positron emission tomography retention were assessed in eleven patients with unilateral occlusion of precerebral arteries resulting in chronic and uneven hypoperfusion. A subset of patients underwent tau (18F‐AV‐1451) positron emission tomography.

Results

The blood flow was significantly reduced on the affected side of the brain in patients with unilateral occlusion of the internal carotid artery or stenosis of the middle cerebral artery. However, the cortical uptake of 18F‐Flutemetamol or 18F‐AV‐1451 was not altered.

Discussion

Our results suggest that longstanding cerebral hypoperfusion in humans does not result in accumulation of amyloid β fibrils or tau aggregates.
The relationship between the CYP19 alleles rs727479A/C, rs700518A/G, and rs700519C/T and pregnancy outcome after assisted reproductive technology in patients with polycystic ovary syndrome in a Chinese population: A population‐based study
Authors: Dou Qian , Tan Li , Ma Li‐Ying , Sun Ying‐Pu
Published: July 2017

This study investigated the relationship between the CYP19 alleles, rs727479A/C, rs700518A/G, and rs700519C/T, and pregnancy outcome after assisted reproductive technology (ART) in patients with polycystic ovary syndrome (PCOS). Between January 2012 and September 2015, 293 PCOS patients undergoing ART were randomly selected for the study. According to pregnancy outcome after ART, the patients were assigned to pregnancy and non‐pregnancy groups. CYP19 rs727479A/C, rs700518A/G and rs700519C/T genotypes were determined using the denaturing high‐performance liquid chromatography (DHPLC) method. Haplotype frequencies of the CYP19 alleles rs727479A/C, rs700518A/G and rs700519C/T were estimated using the SHEsis platform. Logistic regression analysis was employed to analyze the factors influencing the pregnancy outcome after ART. The frequency of the AC + CC genotype of rs727479A/C was higher in the pregnancy group than in the non‐pregnancy group. The frequency of the CT + TT genotype of rs700519A/G was also higher in the pregnancy group than in the non‐pregnancy group. Haplotype analysis indicated that the AAC and AGT haplotypes both exhibited unfavorable influence on the pregnancy outcome after ART. The AAT and CGT haplotypes were favorable to the pregnancy outcome after ART. Logistic regression analysis suggested that the rs727479A/C AA genotype, the rs700519C/T CC genotype and body mass index (BMI) might exert unfavorable influence on the pregnancy outcome after ART for PCOS patients. These findings indicated that the CYP19 alleles rs727479A/C and rs700519C/T might be associated with the pregnancy outcome after ART in patients with PCOS.
Yarsagumba Fungus: Health Problems in the Himalayan Gold Rush
Authors: Koirala Pranawa , Pandit Bidur , Phuyal Pratibha , Zafren Ken
Published: July 2017

Introduction

Seasonal migration of people in search of Yarsagumba fungus creates a population of collectors that faces hardship and health risks in austere high-altitude settings.

Methods

In 2016, our 4-person team performed a 2-day health-needs survey of people collecting Yarsagumba fungus near the village of Yak Kharka (4020 m) in the Manang District of Nepal.

Results

There were approximately 800 people, both male and female, from age 10 to over 60, collecting Yarsagumba fungus. They had paid high prices for permits, hoping to recoup the cost and make a profit by selling specimens of Yarsagumba, but the fungus seemed scarce in 2016, resulting in a bleak economic forecast. Most collectors were living in austere conditions, walking long hours to the collection areas early in the morning and returning in the late afternoon. Most were subsisting on 1 daily meal. Health problems, including acute mountain sickness as well as respiratory and gastrointestinal illnesses, were common. Yarsagumba has become harder to find in recent years, increasing hardships and risk of injury. Medical care was almost nonexistent.

Conclusion

As abundance decreases and demand increases, there is increasing pressure on collectors to find Yarsagumba. The collectors are an economically disadvantaged population who live in austere conditions at high altitude with poor shelter and sanitation, strenuous work, and limited availability of food. Health care resources are very limited. There are significant risks of illness, injury, and death. Targeted efforts by government entities and nongovernmental organizations might be beneficial in meeting the health needs.
Similarities Between Large Animal-Related and Motor Vehicle Crash-Related Injuries
Authors: Tremelling Abigail M. , Marley Robert A. , Marley Mackenzie B. , Woofter Christina M. , Docherty Courtney , Salvator Ann E. , Muakkassa Farid F.
Published: July 2017

Objective

Many Americans sustain large animal-related injuries (LARIs) from blunt trauma. We compare the injuries and management of LARI in our region of the United States with those of motor vehicle crashes (MVCs).

Methods

A 15-year retrospective study of trauma patients with LARI matched to MVC controls by Injury Severity Score (ISS), age, and sex was conducted. Values were statistically compared, and differences were considered statistically significant at P < .05.

Results

There were 156 LARI cases, of which 87% were related to horses, 8% to bulls, and the remainder to deer, mules, bison, cows, and rams. In the LARI group, the age was 42±18 years (mean±SD), ISS was 7±4, and 61% were females. The MVC group had a significantly longer length of hospital stay (5±5 vs 4±3 days) and blood alcohol concentration (35±84 vs 3±20 g/L). There were no significant differences in injury patterns between LARI and MVC; however, additional radiological studies (RS) were performed on MVC (9±6 vs 7±5). LARI patients were more often transferred from rural locations (39% vs 25%) and traveled further to our trauma center (40±32 vs 24±29 km) than did MVC patients.

Conclusions

LARI has a similar pattern of injury to MVC, but fewer RS. LARI typically occurred further away, requiring transfer from rural areas to our institution. We recommend a similar approach for the evaluation of LARI and MVC.
Communities and Experts Collaborate for Climate Resilience
Authors: Lamontagne Nancy
Published: July 2017

The Resilience Dialogues program provides resources and expertise to help communities build individualized plans for resilience in the face of climate change.
Climate Change Could Make Siberia an Attractive Place to Live
Authors: Hornyak Tim
Published: July 2017

Although anticipated warmer temperatures promise to render the region more comfortable for people, the transformation might turn permafrost areas into inhospitable bogs.
Xe adsorption and separation properties of a series of microporous metal–organic frameworks (MOFs) with V-shaped linkers
Authors: Banerjee Debasis , Elsaidi Sameh K. , Thallapally Praveen K.
Published: July 2017

A series of microporous metal–organic frameworks (MOFs) constructed by using a V-shaped linker, 4,4′-sulfonyldibenzoic acid, were evaluated for their Xe gas adsorption properties.
Stacked silk-cell monolayers as a biomimetic three dimensional construct for cardiac tissue reconstruction
Authors: Mehrotra Shreya , Nandi Samit Kumar , Mandal Biman B.
Published: July 2017

A facile biomimetic fabrication technique of stacking silk-cardiomyocyte monolayers into a 3-dimensional construct for cardiac tissue repair.
Efficient and thermally stable blue-emitting Ce3+ doped LaAl(Si6−zAlz)(N10−zOz) (JEM:Ce) phosphors for white LEDs
Authors: Wang Chun-Yun , Kate Otmar Melvin ten , Takeda Takashi , Hirosaki Naoto
Published: July 2017

La2O3, LaN, Si3N4, AlN and CeO2 have been used as starting materials to synthesize Ce doped LaAl(Si6−zAlz)(N10−zOz) (z ≈ 1, termed the JEM phase) phosphors, via a solid-state reaction method in a gas pressure furnace at a high temperature.
Diagnostic value of four-dimensional CT angiography in arterial erectile dysfunction using 320-detector row dynamic volume CT
Authors: Xu Cheng-Cheng , Ruan Xin-Zhong , Tang Yi-Fan , Pan Jiao-Hai , Wang Guo-Yao , Huang Qiu-Li
Published: July 2017

The present study aims to evaluate the diagnostic value of four-dimensional CT angiography (4D-CTA) in the diagnosis of arterial erectile dysfunction (ED) using 320-detector row dynamic volume CT. Arterial ED patients attributed to arterial insufficiency were enrolled. To induce penile erection, an intracavernous injection (ICI) of corpus cavernosum with a vasoactive drug was administered. Patients were assigned into the erection hardness score (EHS) 1/2 group or EHS 3/4 group. Color duplex Doppler ultrasound (CDDU) was used to analyze blood flow spectrum. Each patient was examined using 4D-CTA. Receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of 4D-CTA in arterial ED. According to Irwin Goldstein, the EHS 3/4 group (n=38) had a shorter course of ED and low proportion with history of hypertension, hyperlipidemia, and diabetes than the EHS 1/2 group (n=35). The peak systolic velocity (PSV), end diastolic velocity (EDV), and resistant index (RI) in the EHS 3/4 group were lower than those of the EHS 1/2 group. 4D-CTA showed there were a total of 35 cases in the EHS 1/2 group (two cases missed) and 38 cases in the EHS 3/4 group (seven cases misdiagnosed). Using 4D-CTA to diagnose arterial ED, the area under the ROC curve yielded a value of 0.879, with a specificity of 93.9% and a sensitivity of 82.5%. These findings indicated that 4D-CTA using 320-detector row dynamic volume CT is a promising and reliable utility in diagnosing arterial ED.
Post-transcriptional control of gene expression following stress: the role of RNA-binding proteins
Authors: Harvey Robert , Dezi Veronica , Pizzinga Mariavittoria , Willis Anne E.
Published: July 2017

The ability of mammalian cells to modulate global protein synthesis in response to cellular stress is essential for cell survival. While control of protein synthesis is mediated by the regulation of eukaryotic initiation and elongation factors, RNA-binding proteins (RBPs) provide a crucial additional layer to post-transcriptional regulation. RBPs bind specific RNA through conserved RNA-binding domains and ensure that the information contained within the genome and transcribed in the form of RNA is exported to the cytoplasm, chemically modified, and translated prior to folding into a functional protein. Thus, this group of proteins, through mediating translational reprogramming, spatial reorganisation, and chemical modification of RNA molecules, have a major influence on the robust cellular response to external stress and toxic injury.
Nutritional modulation of metabolic inflammation
Authors: Kirwan Anna M. , Lenighan Yvonne M. , O'Reilly Marcella E. , McGillicuddy Fiona C. , Roche Helen M.
Published: July 2017

Metabolic inflammation is a very topical area of research, wherein aberrations in metabolic and inflammatory pathways probably contribute to atherosclerosis, insulin resistance (IR) and type 2 diabetes. Metabolic insults arising from obesity promote inflammation, which in turn impedes insulin signalling and reverse cholesterol transport (RCT). Key cells in the process are metabolically activated macrophages, which up-regulate both pro- and anti-inflammatory pathways in response to lipid spillover from adipocytes. Peroxisome proliferator-activated receptors and AMP-activated protein kinase (AMPK) are regulators of cellular homeostasis that influence both inflammatory and metabolic pathways. Dietary fats, such as saturated fatty acids (SFAs), can differentially modulate metabolic inflammation. Palmitic acid, in particular, is a well-characterized nutrient that promotes metabolic inflammation via the NLRP3 (the nod-like receptor containing a pyrin domain) inflammasome, which is partly attributable to AMPK inhibition. Conversely, some unsaturated fatty acids are less potent agonists of metabolic inflammation. For example, monounsaturated fatty acid does not reduce AMPK as potently as SFA and n-3 polyunsaturated fatty acids actively resolve inflammation via resolvins and protectins. Nevertheless, the full extent to which nutritional state modulates metabolic inflammation requires greater clarification.
Circular particle fusion filter applied to map matching
Authors: El Mokhtari Karim , Reboul Serge , Choquel Jean‐Bernard , Stienne Georges , Amami Benaissa , Benjelloun Mohammed
Published: July 2017

Navigation in constrained areas such as ports or dense urban environments is often exposed to global navigation satellite system (GNSS) satellites masking caused by the infrastructures. In this case, the GNSS positioning is inaccurate or unavailable and proprioceptive sensors are generally used to temporarily localise the vehicle on a map. However, the drift of these sensors rapidly causes the navigation system to fail. In this study, the navigation is computed using magnetometer and GNSS observations defined in an absolute reference frame. The heading measurements are coupled with a digital map of the road network in order to localise the vehicle in a map matching process. The contribution of this study is the proposition of a particle filter that fuses the position and direction observations to estimate the vehicle position. In this context, when the GNSS signal is masked, the observations of direction are used to compute the vehicle position. The proposed filter is defined in both circular and linear domains in order to take into account the nature of the observations. The proposed approach is assessed on real and synthetic data.
Stem cell-released oncolytic herpes simplex virus has therapeutic efficacy in brain metastatic melanomas
Authors: Du Wanlu , Seah Ivan , Bougazzoul Oumaima , Choi GiHun , Meeth Katrina , Bosenberg Marcus W. , Wakimoto Hiroaki , Fisher David , Shah Khalid
Published: July 2017

Significance

This study provides an insight into stem cell-based oncolytic virus therapies for advanced melanoma tumors that have metastasized into the brain by developing clinically relevant mouse tumor models and testing the fate and efficacy of oncolytic herpes simplex virus-armed mesenchymal stem cells in such models. This study therefore overcomes the hurdles of systemic delivery of oncolytic viruses and provides a clinically applicable therapeutic platform to target melanoma brain metastasis.
Relations of Demographic and Clinical Factors With Cardiovascular Autonomic Function in a Population-Based Study: An Assessment By Quantile Regression
Authors: Sluyter John D , Hughes Alun D , Camargo Carlos A , Lowe Andrew , Scragg Robert K R
Published: July 2017

BACKGROUND

The relationships of many factors with cardiovascular autonomic function (CVAF) outcome parameters may not be uniform across the entire distribution of the outcome. We examined how demographic and clinical factors varied with different subgroups of CVAF parameters.

METHODS

Quantile regression was applied to a cross-sectional analysis of 4,167 adults (56% male; age range, 50–84 years) from 4 ethnic groups (3,419 New Zealand European, 303 Pacific, 227 Maori, and 218 South Asian) and without diagnosed cardiac arrhythmia. Pulse rate variability (root mean square of successive differences (RMSSD) and SD of pulse intervals) and baroreflex sensitivity were response variables. Independent variables were age, sex, ethnicity, brachial and aortic blood pressure (BP) variables, body mass index (BMI), and diabetes.

RESULTS

Ordinary linear regression showed that age, sex, Pacific and Maori ethnicity, BP variables, BMI, and diabetes were associated with CVAF parameters. But quantile regression revealed that, across CVAF percentiles, the slopes for these relationships: (i) varied by more than 10-fold in several cases and sometimes changed direction and (ii) noticeably differed in magnitude often (by >3–fold in several cases) compared to ordinary linear regression coefficients. For instance, age was inversely associated with RMSSD at the 10th percentile of this parameter (β = −0.12 ms/year, 95% confidence interval = −0.18 to −0.09 ms/year) but had a positive relationship at the 90th percentile (β = 3.17 ms/year, 95% confidence interval = 2.50 to 4.04 ms/year).

CONCLUSIONS

The relationships of demographic and clinical factors with CVAF parameters are, in many cases, not uniform. Quantile regression provides an improved assessment of these associations.
How Goal Specificity Shapes Motivation: A Reference Points Perspective
Authors: Wallace Scott G , Etkin Jordan
Published: July 2017

Consumers often pursue goals that lack specific end states, such as goals to lose as much weight as possible or to pay off as much debt as possible. Yet despite considerable interest in the consequences of setting nonspecific (vs. specific) goals, how goal specificity affects motivation throughout goal pursuit is less well understood. The current research explores the role of reference points in shaping goal specificity’s effects. We propose that goal specificity alters what reference point consumers spontaneously adopt during goal pursuit: for specific goals, the end state tends to be more salient, but for nonspecific goals, the initial state should be more salient. Five studies investigate how this difference in focal reference points shapes (1) the relationship between goal progress and motivation, (2) when (i.e., at what level of goal progress) goal specificity produces the greatest difference in motivation, and (3) the underlying process driving these effects. Our findings advance understanding of the relationship between goal specificity, goal progress, and motivation, and in doing so, underscore the critical role that reference points play in goal-directed behavior. In addition, the findings offer practical insight into how best to set important financial, health, and other consumer goals to enhance motivation.
Disentangling metabolic functions of bacteria in the honey bee gut
Authors: Kešnerová Lucie , Mars Ruben A. T. , Ellegaard Kirsten M. , Troilo Michaël , Sauer Uwe , Engel Philipp
Published: July 2017

It is presently unclear how much individual community members contribute to the overall metabolic output of a gut microbiota. To address this question, we used the honey bee, which harbors a relatively simple and remarkably conserved gut microbiota with striking parallels to the mammalian system and importance for bee health. Using untargeted metabolomics, we profiled metabolic changes in gnotobiotic bees that were colonized with the complete microbiota reconstituted from cultured strains. We then determined the contribution of individual community members in mono-colonized bees, and recapitulated our findings usingin vitrocultures. Our results show that the honey bee gut microbiota utilizes a wide range of pollen-derived substrates including flavonoids and outer pollen wall components, suggesting a key role for degradation of recalcitrant secondary plant metabolites and pollen digestion. In turn, multiple species were responsible for the accumulation of organic acids and polyphenol degradation products, and a specific gut symbiont,Bifidobacterium asteroides, stimulated the production of host hormones known to impact bee development. While we found evidence for cross-feeding interactions, ∼80% of the identified metabolic changes were also observed in mono-colonized bees withLactobacillibeing responsible for the largest share of the metabolic output. These results suggest that bacteria in the honey bee gut colonize largely independent metabolic niches, which may be a general characteristic of gut microbiomes. Our study reveals diverse metabolic functions of gut bacteria that are likely to contribute to bee health, and provide fundamental insights into how metabolic functions are partitioned within gut communities.

Author summary

Honey bees are important pollinators that harbor a simple gut microbiota with striking parallels to the mammalian system. This makes them relevant models to study gut microbiota functions and its impact on host health. We applied untargeted metabolomics to characterize metabolic changes induced by the gut microbiota, and to characterize contributions of the major community members. We find that the gut microbiota digests recalcitrant substrates derived from the bees’ pollen-diet. Most metabolic changes could be explained by the activity of individual community members suggesting substrate specificity and independent metabolic niches. Our study provides novel insights into the functional understanding of the bee gut microbiota and provides a framework for applying untargeted metabolomics to disentangle metabolic functions of gut bacteria.
Characterising maize viruses associated with maize lethal necrosis symptoms in sub Saharan Africa
Authors: Adams I.P. , Braidwood L.A. , Stomeo F. , Phiri N. , Uwumukiza B. , Feyissa B. , Mahuku G. , Wangi A. , Smith J. , Mumford R. , Boonham N.
Published: July 2017

Maize lethal necrosis disease (MLN) is an emerging disease in East Africa caused by the introduction ofMaize chlorotic mottle virus(MCMV). Recent activity seeking to limit spread of the disease is reliant on effective diagnostics. Traditional diagnostics applied on samples with typical field symptoms of MLN have often given negative results using ELISA or PCR for MCMV andSugarcane mosaic virus(SCMV). Samples collected in the field with typical MLN symptoms were examined using next generation sequencing (NGS). SCMV was found to be more prevalent than suggested by targeted diagnostics. Additionally, the panel of samples were found to be infected with a range of other viruses, seven of which are described here for the first time. Although not previously identified in the region,Maize yellow mosaic virus(MYMV) was the most prevalent virus after MCMV. The development of targeted diagnostics for emerging viruses is complicated when the extent of field variation is unknown, something that can be negated by using NGS methods. As a result we explored MinION technology which may be more readily deployable in resource poor settings. The results show that this sequencer can diagnose known viruses and future iterations have the potential to identify novel viruses.
Platform for Closed Loop Neuromodulation Based on Dual Mode Biosignals
Authors: Mirza Khalid B. , Kulasekeram Nishanth , Cork Simon , Bloom Stephen , Nikolic Konstantin , Toumazou Christofer
Published: July 2017

Closed loop neuromodulation, where the stimulation is controlled autonomously based on physiological events, has been more effective than open loop techniques. In the few existing closed loop implementations which have a feedback, indirect non-neurophysiological biomarkers have been typically used (e.g. heart rate, stomach distension). Although these biomarkers enable automatic initiation of neural stimulation, they do not enable intelligent control of stimulation dosage. In this paper, we present a novel closed loop neuromodulation platform based on a dual signal mode that is detecting electrical and chemical signatures of neural activity. We demonstrated it on a case of vagus nerve stimulation (VNS). Vagal chemical (pH) signal is detected and used for initiatisng VNS and vagal compound action potential (CAP) signals are used to determine the stimulation dosage and pattern. Although we used the paradigm of appetite control and neurometabolic therapies, the platform developed here can be utilised for prototyping closed loop neuromodulation systems before adapting the final System-on-Chip (SoC) design.
Inert and seed-competent tau monomers suggest structural origins of aggregation
Authors: Mirbaha Hilda , Chen Dailu , Morozova Olga A. , Ruff Kiersten M. , Sharma Apurwa , Liu Xiaohua , Pappu Rohit V. , Colby David W. , Mirzaei Hamid , Joachimiak Lukasz A. , Diamond Marc I.
Published: July 2017

Tauopathies feature progressive accumulation of tau amyloids. Pathology may begin when these amplify from a protein template, or seed, whose structure is unknown. We have purified and characterized distinct forms of tau monomer—inert (Mi) and seed-competent (Ms). Recombinant Mstriggered intracellular tau aggregation, induced tau fibrillizationin vitro, and self-assembled. Msfrom Alzheimer’s disease also seeded aggregation and self-assembledin vitroto form seed-competent multimers. We used crosslinking with mass spectrometry to probe structural differences in Mivs. Ms. Crosslinks informed models of local peptide structure within the repeat domain which suggest relative inaccessibility of residues that drive aggregation (VQIINK/VQIVYK) in Mi, and exposure in Ms. Limited proteolysis supported this idea. Although tau monomer has been considered to be natively unstructured, our findings belie this assumption and suggest that initiation of pathological aggregation could begin with conversion of tau monomer from an inert to a seed-competent form.
Intragenic differential expression in archaea transcriptomes revealed by computational analysis of tiling microarrays
Authors: Khan Atlas , Vêncio Ricardo Z. N.
Published: July 2017

Recent advances, in high-throughput technologies allows whole transcriptome analysis, providing a complete and panoramic view of intragenic differential expression in eukaryotes. However, intragenic differential expression in prokaryotes still mystery and incompletely understood. In this study, we investigated and collected the evidence for intragenic differential expression in several archaeal transcriptomes such as,Halobacterium salinarumNRC-1,Pyrococcus furiosus, Methanococcus maripaludis, andSulfolobus solfataricus, based on computational methods; specifically, by well-known self-organizing map (SOM) for cluster analysis, which transforms high dimensional data into low dimensional. We found 104 (3.86%) of genes in Halobacterium salinarum NRC-1, 59 (2.56%) of genes inPyrococcus furiosus,43 (2.41%) of genesMethanococcus maripaludisand 13 (0.42%) of genes inSulfolobus solfataricushave two or more clusters, i.e., showed the intragenic differential expression at different conditions.
Genome-wide profiling of transcribed enhancers during macrophage activation
Authors: Denisenko Elena , Guler Reto , Mhlanga Musa , Suzuki Harukazu , Brombacher Frank , Schmeier Sebastian
Published: July 2017

Macrophages are sentinel cells essential for tissue homeostasis and host defence. Owing to their plasticity, macrophages acquire a range of functional phenotypes in response to microenvironmental stimuli, of which M(IFN-γ) and M(IL-4/IL-13) are well-known for their opposing pro- and anti-inflammatory roles. Enhancers have emerged as regulatory DNA elements crucial for transcriptional activation of gene expression. Using cap analysis of gene expression and epigenetic data, we identify on large-scale transcribed enhancers in mouse macrophages, their time kinetics and target protein-coding genes. We observe an increase in target gene expression, concomitant with increasing numbers of associated enhancers and find that genes associated to many enhancers show a shift towards stronger enrichment for macrophage-specific biological processes. We infer enhancers that drive transcriptional responses of genes upon M(IFN-γ) and M(IL-4/IL-13) macrophage activation and demonstrate stimuli-specificity of regulatory associations. Finally, we show that enhancer regions are enriched for binding sites of inflammation-related transcription factors, suggesting a link between stimuli response and enhancer transcriptional control. Our study provides new insights into genome-wide enhancer-mediated transcriptional control of macrophage genes, including those implicated in macrophage activation, and offers a detailed genome-wide catalogue to further elucidate enhancer regulation in macrophages.
Cell Type-Specific Survey of Epigenetic Modifications by Tandem Chromatin Immunoprecipitation Sequencing
Authors: Mito Mari , Kadota Mitsutaka , Tanaka Kaori , Furuta Yasuhide , Abe Kuniya , Iwasaki Shintaro , Nakagawa Shinichi
Published: July 2017

Background

The nervous system of higher eukaryotes is composed of numerous types of neurons and glia that together orchestrate complex neuronal responses. However, this complex pool of cells typically poses analytical challenges in investigating gene expression profiles and their epigenetic basis for specific cell types. Here, we developed a novel method that enables cell type-specific analyses of epigenetic modifications using tandem chromatin immunoprecipitation sequencing (tChIP-Seq).

Results

FLAG-tagged histone H2B, a constitutive chromatin component, was first expressed inCamk2a-positive pyramidal cortical neurons and used to purify chromatin in a cell type-specific manner. Subsequent chromatin immunoprecipitation using antibodies against H3K4me3—an active promoter mark—allowed us to survey neuron-specific coding and non-coding transcripts. Indeed, tChIP-Seq identified hundreds of genes associated with neuronal functions and genes with unknown functions expressed in cortical neurons.

Conclusions

tChIP-Seq thus provides a versatile approach to investigating the epigenetic modifications of particular cell typesin vivo.
RiceTSV3Encoding Obg-like GTPase Protein is Essential for Chloroplast Development during the Early Leaf Stage under Cold Stress
Authors: Lin Dongzhi , Jiang Quan , Ma Xiaojing , Zheng Kailun , Gong Xiaodi , Teng Sheng , Xu Jianlong , Dong Yanjun
Published: July 2017

The Spo0B-associated GTP-binding (Obg) proteins occupy a wide variety of roles in the viability of nearly all bacteria. Its detailed roles in higher plants have not yet been elucidated. A novel rice thermo-sensitive virescent mutanttsv3was identified in this study that displayed albino phenotype at 20°C before the 3-leaf stage while being normal green at 32°C or even at 20°C after the 4-leaf stage. The mutant phenotype was aligned with altered chlorophyll (Chl) content and chloroplast development. Map-based cloning and complementation test showed thatTSV3encoded a kind of small GTP binding protein. Subcellular localization revealed that TSV3 was in chloroplast.TSV3transcripts were highly expressed in leaves and weak or undetectable in other tissues, suggesting the tissue-specific expression. Intsv3mutant, the transcriptional levels of certain genes associated with biogenesis of chloroplast ribosomes 50S subunit were severely decreased at the 3-leaf-stage under cold stress, but could be recovered to normal levels at a higher temperature (32°C). The observations from this study indicated that the rice nuclear-encodedTSV3plays important roles in chloroplast development at early leaf stage under cold stress.
C-State: An interactive web app for simultaneous multi-gene visualization and comparative epigenetic pattern search
Authors: Sowpati Divya Tej , Srivastava Surabhi , Dhawan Jyotsna , Mishra Rakesh K
Published: July 2017

Background

Comparative epigenomic analysis across multiple genes presents a bottleneck for bench biologists working with NGS data. Despite the development of standardized peak analysis algorithms, the identification of novel epigenetic patterns and their visualization across gene subsets remains a challenge.

Results

We developed a fast and interactive web app, C-State (Chromatin-State), to query and plot chromatin landscapes across multiple loci and cell types. C-State has an interactive, JavaScript- based graphical user interface and runs locally in modern web browsers that are pre-installed on all computers, thus eliminating the need for cumbersome data transfer, pre-processing and prior programming knowledge.

Conclusions

C-State is unique in its ability to extract and analyze multi-gene epigenetic information. It allows for powerful GUI-based pattern searching and visualization. We include a case study to demonstrate its potential for identifying user-defined epigenetic trends in context of gene expression profiles.
Targeted re-sequencing of coding DNA sequences for SNP discovery in non-model species
Authors: Förster Daniel W. , Bull James K. , Lenz Dorina , Autenrieth Marijke , Paijmans Johanna L. A. , Kraus Robert H. S. , Nowak Carsten , Bayerl Helmut , Kühn Ralph , Saveljev Alexander P. , Sindičić Magda , Hofreiter Michael , Schmidt Krzysztof , Fickel Jörns
Published: July 2017

Hybridization capture coupled with high-throughput sequencing can be used to gain information about nuclear sequence variation at hundreds to thousands of loci. A cross-species approach makes use of molecular data of one species to enrich target loci in other (related) species. This is particularly valuable for non-model organisms, for which often noa prioriknowledge exists regarding these loci. Here, we have adopted cross-species capture to obtain data for 809 nuclear coding DNA sequences (CDS) in a non-model organism, the Eurasian lynxLynx lynx, using baits designed with the help of the published genome of a related model organism (the domestic catFelis catus). In this manner, we were able to survey intraspecific variation at hundreds of nuclear loci across the European range ofL. lynx. A large set of bi-allelic candidate SNPs was then tested in a high throughput SNP-genotyping platform (Fluidigm), which we reduced to a final 96 SNP-panel based on assay performance and reliability; validation was carried out with additional samples not included in the SNP discovery phase. The 96 SNP-panel developed from CDS performed very successfully in the identification of individuals and in population genetic structure inference (incl. the assignment of individuals to their source population). In keeping with recent studies, our results show that genic SNPs can be valuable for genetic monitoring of wildlife species.
confFuse: high-confidence fusion gene detection across tumor entities
Authors: Huang Zhiqin , Jones David T.W. , Wu Yonghe , Lichter Peter , Zapatka Marc
Published: July 2017

Background

Fusion genes play an important role in the tumorigenesis of many cancers. Next-generation sequencing (NGS) technologies have been successfully applied in fusion gene detection for the last several years, and a number of NGS-based tools have been developed for identifying fusion genes during this period. Most fusion gene detection tools based on RNA-seq data report a large number of candidates (mostly false positives), making it hard to prioritize candidates for experimental validation and further analysis. Selection of reliable fusion genes for downstream analysis becomes very important in cancer research. We therefore developed confFuse, a scoring algorithm to reliably select high-confidence fusion genes which are likely to be biologically relevant.

Results

ConfFuse takes multiple parameters into account in order to assign each fusion candidate a confidence score, of which score ≥8 indicates high-confidence fusion gene predictions. These parameters were manually curated based on our experience and on certain structural motifs of fusion genes. Compared with alternative tools, based on 96 published RNA-seq samples from different tumor entities, our method can significantly reduce the number of fusion candidates (301 high-confidence from 8,083 total predicted fusion genes) and keep high detection accuracy (recovery rate 85.7%). Validation of 18 novel, high-confidence fusions detected in three breast tumor samples resulted in a 100% validation rate.

Conclusions

ConfFuse is a novel downstream filtering method that allows selection of highly reliable fusion gene candidates for further downstream analysis and experimental validations. confFuse is available athttps://github.com/Zhiqin-HUANG/confFuse.
Interplay between antibiotic efficacy and drug-induced lysis underlies enhanced biofilm formation at subinhibitory drug concentrations
Authors: Yu Wen , Hallinen Kelsey , Wood Kevin B.
Published: July 2017

Subinhibitory concentrations of antibiotics have been shown to enhance biofilm formation in multiple bacterial species. While antibiotic exposure has been associated with modulated expression in many biofilm-related genes, the mechanisms of drug-induced biofilm formation remain a focus of ongoing research efforts and may vary significantly across species. In this work, we investigate antibiotic-induced biofilm formation inE. faecalis, a leading cause of nosocomial infections. We show that biofilm formation is enhanced by subinhibitory concentrations of cell wall synthesis inhibitors, but not by inhibitors of protein, DNA, folic acid, or RNA synthesis. Furthermore, enhanced biofilm is associated with increased cell lysis, an increase in extracellular DNA (eDNA), and an increase in the density of living cells in the biofilm. In addition, we observe similar enhancement of biofilm formation when cells are treated with non-antibiotic surfactants that induce cell lysis. These findings suggest that antibiotic-induced biofilm formation is governed by a trade-off between drug toxicity and the beneficial effects of cell lysis. To understand this trade-off, we developed a simple mathematical model that predicts changes to antibiotic-induced biofilm formation due to external perturbations, and we verify these predictions experimentally. Specifically, we demonstrate that perturbations that reduce eDNA (DNase treatment) or decrease the number of living cells in the planktonic phase (a second antibiotic) decrease biofilm induction, while chemical inhibitors of cell lysis increase relative biofilm induction and shift the peak to higher antibiotic concentrations. Overall, our results offer experimental evidence linking cell wall synthesis inhibitors, cell lysis, increased eDNA, and biofilm formation inE. faecaliswhile also providing a predictive, quantitative model that sheds light on the interplay between cell lysis and antibiotic efficacy in developing biofilms.