bluuebunny/crossref_metadata_2025 huggingface dataset:
The allele frequency of ALDH2*Glu504Lys and ADH1B*Arg47His for the Ryukyu islanders and their history of expansion among East Asians
Authors: Koganebuchi Kae , Haneji Kuniaki , Toma Takashi , Joh Keiichiro , Soejima Hidenobu , Fujimoto Kazuma , Ishida Hajime , Ogawa Motoyuki , Hanihara Tsunehiko , Harada Shoji , Kawamura Shoji , Oota Hiroki
Published: November 2016

Objectives

A cline of frequencies of the derived allele of the ALDH2 gene, which causes a deficiency of an enzyme and “facial flushing” in humans who drink alcohol, has been known among the people of the Japanese archipelago. This cline is conventionally explained by admixture with immigrants from the Asian continent occurring during the Yayoi period. Previous studies lack sufficient data from the peripheral regions of the indigenous Jomon people, and those data the ADH1B gene that is involved in the Class I ADH gene cluster and contains another variant leading to a functional change.

Methods

We focused on the southwestern‐most people from the Ryukyu Islands (n = 218) and those from northern Kyushu (n = 21) where the Yayoi immigrants likely arrived. We investigated both the Class I ADH and ALDH2 loci, as well as neutral genetic markers.

Results

In the Ryukyu Islands, the frequencies of the ancestral alleles in both loci were always higher than those in mainland Japan, while the frequencies of ADH1B were less than those of the derived allele. A haplotype block was not observed in ALDH2 but was in Class I ADH.

Discussion

Our data suggest that the derived allele of ALDH2 came with the Yayoi immigrants from the Asian continent to the Japanese archipelago. However, the derived allele of ADH1B is unlikely to be related to the Yayoi migration. Therefore, we postulate that the expansion of the derived allele of ADHIB in East Asia could be traced back to the last glacial period.
Utility of three anthropometric indices in assessing the cardiometabolic risk profile in children
Authors: Buchan Duncan S. , Boddy Lynne M. , Grace Fergal M. , Brown Elise , Sculthorpe Nicholas , Cunningham Conor , Murphy Marie H. , Dagger Rebecca , Foweather Lawrence , Graves Lee E. F. , Hopkins Nicola D. , Stratton Gareth , Baker Julien S.
Published: November 2016

Objectives

To evaluate the ability of BMI, WC, and WHtR to identify increased cardiometabolic risk in pre‐adolescents.

Methods

This is a cross‐sectional study involving 192 children (10.92 ± 0.58 years, 56% female) from the United Kingdom between 2010 and 2013. Receiver operating characteristic curves determined the discriminatory ability of BMI, WC and WHtR to identify individuals with increased cardiometabolic risk (increased clustered triglycerides, HDL‐cholesterol, systolic blood pressure, cardiorespiratory fitness, and glucose).

Results

A WHtR ≥ 0.5 increased the odds by 5.2 (95% confidence interval 2.6 ‐ 10.3) of having increased cardiometabolic risk. Similar associations were observed for BMI and WC. Both BMI‐z and WHtR were fair predictors of increased cardiometabolic risk, although BMI‐z demonstrated the best trade‐off between sensitivity and specificity, 76.1% and 63.6%, compared with 68.1% and 65.5% for WHtR. Cross‐validation analysis revealed that BMI‐z and WHtR correctly classified 84% of individuals (kappa score = 0.671, 95% CI 0.55, 0.79). The sensitivity of the cut‐points suggests that 89.3% of individuals were correctly classified as being at risk with only 10.7% misdiagnosed whereas the specificity of the cut‐points indicated that 77.8% of individuals were correctly identified as being healthy with 22.2% of individuals incorrectly diagnosed as being at risk.

Conclusions

Findings suggest that WHtR provides similar cardiometabolic risk estimates to age and sex adjusted BMI.
Preaxial polydactyly following early gestational exposure to the smoothened agonist, SAG, in C57BL/6J mice
Authors: Fish Eric W. , Parnell Scott E. , Sulik Kathleen K. , Baker Lorinda K. , Murdaugh Laura B. , Lamson David , Williams Kevin P.
Published: November 2016

Background

While pharmacological activation of the Hedgehog (HH) signaling pathway may have therapeutic benefits for developmental and adult diseases, its teratogenic potential is of concern. The membrane molecule Smoothened (SMO) transduces HH signaling and can be acutely modulated by antagonists and agonists. The objective of the current experiments was to determine how maternal treatment with the Smo agonist, SAG, affects the developing limb.

Methods

Pregnant C57BL/6J mice received a single injection of SAG (15, 17, or 20 mg/kg, i.p.) or its vehicle on gestational day (GD) 9.25, the time of limb bud induction. Embryos were examined on GD 15 for gross dysmorphology and skeletal staining was performed to visualize the number and type of digits on the fore‐ and hindlimbs. Additionally, in situ hybridization was performed 4 hr after GD 9.25 SAG administration to determine SAG's effects on Gli1 and Gli2 mRNA expression.

Results

The most prevalent effect of SAG was the dose‐dependent induction of pre‐axial polydactyly; defects ranged from a broad thumb to the duplication of two finger‐like digits on the preaxial side of the thumb. The highest SAG dose was effective in ca. 80% of the embryos and increased Gli1 and Gli2 mRNA expression in the limb bud, with Gli1 mRNA being the most upregulated.

Conclusion

Preaxial polydactyly can be caused in the developing embryo by acute maternal administration of a Smo agonist that activates HH signaling. These results are consistent with the preaxial polydactyly induced in developmental disorders associated with mutations in HH signaling genes.Birth Defects Research 109:49–54, 2017. © 2016 Wiley Periodicals, Inc.
Using Model Organism Databases (MODs)
Authors: Engel Stacia R. , MacPherson Kevin A.
Published: November 2016

Model Organism Databases (MODs) represent the union of database technology and biology, and are essential to modern biological and medical research. Research communities are producing floods of new data, of increasingly different types and complexity. MODs assimilate this information from a wide variety of sources, organize it in a comprehensible manner, and make it freely available to the public via the Internet. MODs permit researchers to sort through massive amounts of data, providing access to key information that they might otherwise have overlooked. The protocols in this unit offer a general introduction to different types of data available in the growing number of MODs, and approaches for accessing, browsing, and querying these data. © 2016 by John Wiley & Sons, Inc.
Computational Prediction of Protein Secondary Structure from Sequence
Authors: Meng Fanchi , Kurgan Lukasz
Published: November 2016

Secondary structure of proteins refers to local and repetitive conformations, such as α‐helices and β‐strands, which occur in protein structures. Computational prediction of secondary structure from protein sequences has a long history with three generations of predictive methods. This unit summarizes several recent third‐generation predictors. We discuss their inputs and outputs, availability, and predictive performance and explain how to perform and interpret their predictions. We cover methods for the prediction of the 3‐class secondary structure states (helix, strand, and coil) as well as the 8‐class secondary structure states. Recent empirical assessments and our small‐scale analysis reveal that these predictions are characterized by high levels of accuracy, between 70% and 80%. We emphasize that modern predictors are available to end users in the form of convenient‐to‐use Web servers and stand‐alone software. © 2016 by John Wiley & Sons, Inc.
Short‐Term Wind Power Prediction for Wind Turbine via Kalman Filter Based on JIT Modeling
Authors: ISHIKAWA TOMOKI , KOJIMA TAKAAKI , NAMERIKAWA TORU
Published: November 2016

This paper addresses wind power prediction, which is known to be a key technology in energy management systems. In this paper, a 24‐h‐ahead power prediction method using a filter theory is proposed for wind power generation. The prediction method is a simple algorithm. The procedure of prediction consists of two steps: the data processing and the calculation of the predicted values. In data processing, in order to obtain the correlative data from the database, we employ just‐in‐time modeling. In the calculation of the predicted values, we propose a regression model for wind speed and wind power, and the unknown parameters are estimated using a constrained Kalman filter. Moreover, in the procedure used to estimate the unknown parameters, reduction and convergence of the variables are also guaranteed. Finally, the advantages of the proposed method over the conventional method are shown through actual prediction evaluations.
A Proposal of Identifying Optimized Layout of Devices in Electromagnetic Resonant Coupling Type Wireless Power Transfer System
Authors: DOI TATSUYA
Published: November 2016

Recently, a system for wireless power transfer (WPT) using electromagnetic resonant coupling has been evaluated and developed for practical applications such as a wireless charge system for automobiles or electronic devices. However, the efficiency of an electromagnetic resonant coupling type WPT system with LC resonators is greatly affected by the layout of the LC resonators allocated in the system. This means that there is an optimum layout for the LC resonators for transferring wireless power at higher efficiency. This paper presents a new method for identifying the optimum layout for the LC resonators in a WPT system. One of the key ideas is that the problem of finding the optimum layout is replaced by the problem of calculating the equivalent current sources in the LC resonators. The amplitude of the equivalent current sources can be calculated to solve ill‐posed system equations by using inverse analysis. First, the proposed method is described. The system equations to be solved are formulated by means of equivalent circuit techniques. Second, the proposed method is applied to a simplified model to identify the optimum layout for the LC resonators in a WPT system. Then, the results found using the proposed method are verified by comparing the ratio of receiving power with the identified layout and without the LC resonator. Finally, in order to verify the validity of the proposed method, the calculated results are compared with the experiment results using the same model.
High‐Response Torque Control of IPMSM Based on a New Coordinate System Suitable for Voltage Amplitude and Phase Control
Authors: MATSUKI YOSUKE , KAJIURA HIROAKI
Published: November 2016

This paper proposes a torque control method for interior permanent magnetic synchronous motors (IPMSMs). The proposed method controls the voltage amplitude and phase based on a new n–t coordinate system. The t‐axis is a tangent line of a constant voltage ellipse, and the n‐axis is a normal line of the ellipse. On the n–t coordinate system, the n‐axis current is not affected by the voltage phase. The n‐axis current is utilized to reduce the mutual coupling between the voltage amplitude controller and phase controller. The proposed method realizes a high torque response for the linear range and overmodulation range of the inverter, including six‐step mode. The effectiveness of the proposed method was verified by simulation and experimental results.
Improvement of Power Quality in Distribution System by Residential PV Systems
Authors: KAWASAKI SHOJI , TERADA NAOHIRO , TAOKA HISAO , KOYAMA MASAAKI
Published: November 2016

In recent years, the deterioration in the power quality of a distribution system such as the aggravation of voltage imbalance and current imbalance or the increase of harmonics has been apprehended. It is thought to be causally related to the diversification of load by progress of power electronics technology and the increase of the number of interconnection of distributed generators for home use with the reduction of the effect on the environment. The purpose of this study is development of power conditioner systems (PCSs) with a function of improvement of power quality in the distribution system. In this paper, the authors propose a control method of restraint of harmonics and improvement of voltage imbalance in the distribution system utilizing the PCSs of photovoltaic systems. Moreover, it includes a determination method of the interconnection power factor and the optimal gain of filtering operation of PCSs so as to minimize the voltage imbalance factor and so as to minimize the maximum value of voltage total harmonic distortion in the distribution system by real‐time feedback control with measured data from the information technology switches of distribution line. The numerical calculation is carried out in order to verify the validity of the proposal method.
Complex Permittivity Spectra of Various Insulating Polymers at Ultrawide‐Band Frequencies
Authors: HASEGAWA YUKA , OHKI YOSHIMICHI , FUKUNAGA KAORI , MIZUNO MAYA , SASAKI KENSUKE
Published: November 2016

Nowadays, trials to use even higher frequencies are pursued to realize high‐speed wireless communications. In order to respond to such a trend, dielectric properties of insulating polymers at high frequencies have to be clarified, although the importance of clarifying low‐frequency properties is still very high, especially for use as high‐voltage insulators. In this regard, complex permittivity spectra from 10 mHz to 4.0 THz were obtained for various insulating polymers. The spectra obtained in the very wide frequency range are important, because they can be a valuable database and they provide various pieces of important information on dielectric characteristics.
Magnetorefractive Effect for Co/Ru Multilayer Film with Antiferromagnetic Interlayer Exchange Coupling
Authors: SATO HARUHIKO , SAITO SHIN , MIZUNO SHOTA , AKAHANE KOICHI , UCHIDA HIRONAGA
Published: November 2016

The spin‐dependent scattering of conduction electron in metallic magnetic multilayers was investigated to reveal the optical properties which corresponded to the magnetization state. From the measurement of magnetorefractive effect in antiferro‐magnetically exchange coupled Co/Ru multilayers, it was found that (1) the transmittance varied around 1% at wavelength of 1550 nm during the parallel/antiparallel spin alignment changes, (2) as a result of number of repetition and Co thickness for the multilayers, transmittance difference between the parallel and antiparallel spin alignment states had trade‐off relationship with the magnitude of transmittance, and (3) asymmetric Co/Ru/Co stacking structure brought different interlayer exchange coupling fields in each layer, which resulted in magnetic field sensitive transmittance.
Guiding coral reef futures in the Anthropocene
Authors: Norström Albert V , Nyström Magnus , Jouffray Jean‐Baptiste , Folke Carl , Graham Nicholas AJ , Moberg Fredrik , Olsson Per , Williams Gareth J
Published: November 2016

Anthropogenic changes to the Earth now rival those caused by the forces of nature and have shepherded us into a new planetary epoch – the Anthropocene. Such changes include profound and often unexpected alterations to coral reef ecosystems and the services they provide to human societies. Ensuring that reefs and their services endure during the Anthropocene will require that key drivers of coral reef change – fishing, water quality, and anthropogenic climate change – stay within acceptable levels or “safe operating spaces”. The capacity to remain within these safe boundaries hinges on understanding the local, but also the increasingly global and cross‐scale, socioeconomic causes of these human drivers of change. Consequently, local and regional management efforts that are successful in the short term may ultimately fail if current decision making and institution‐building around coral reef systems remains fragmented, poorly coordinated, and unable to keep pace with the escalating speed of social, technological, and ecological change.
Distribution of phytoplankton groups within the deep chlorophyll maximum
Authors: Latasa Mikel , Cabello Ana María , Morán Xosé Anxelu G. , Massana Ramon , Scharek Renate
Published: November 2016

The fine vertical distribution of phytoplankton groups within the deep chlorophyll maximum (DCM) was studied in the NE Atlantic during summer stratification. A simple but unconventional sampling strategy allowed examining the vertical structure with ca. 2 m resolution. The distribution of Prochlorococcus, Synechococcus, chlorophytes, pelagophytes, small prymnesiophytes, coccolithophores, diatoms, and dinoflagellates was investigated with a combination of pigment‐markers, flow cytometry and optical and FISH microscopy. All groups presented minimum abundances at the surface and a maximum in the DCM layer. The cell distribution was not vertically symmetrical around the DCM peak and cells tended to accumulate in the upper part of the DCM layer. The more symmetrical distribution of chlorophyll than cells around the DCM peak was due to the increase of pigment per cell with depth. We found a vertical alignment of phytoplankton groups within the DCM layer indicating preferences for different ecological niches in a layer with strong gradients of light and nutrients. Prochlorococcus occupied the shallowest and diatoms the deepest layers. Dinoflagellates, Synechococcus and small prymnesiophytes preferred shallow DCM layers, and coccolithophores, chlorophytes and pelagophytes showed a preference for deep layers. Cell size within groups changed with depth in a pattern related to their mean size: the cell volume of the smallest group increased the most with depth while the cell volume of the largest group decreased the most. The vertical alignment of phytoplankton groups confirms that the DCM is not a homogeneous entity and indicates groups’ preferences for different ecological niches within this layer.
Herring and chicken/pork meals lead to differences in plasma levels of TCA intermediates and arginine metabolites in overweight and obese men and women
Authors: Vincent Andrew , Savolainen Otto I. , Sen Partho , Carlsson Nils‐Gunnar , Almgren Annette , Lindqvist Helen , Lind Mads Vendelbo , Undeland Ingrid , Sandberg Ann‐Sofie , Ross Alastair B.
Published: November 2016

Scope

What effect does replacing chicken or pork with herring as the main dietary source of protein have on the human plasma metabolome?

Method and results

A randomised crossover trial with 15 healthy obese men and women (age 24–70 years). Subjects were randomly assigned to four weeks of herring diet or a reference diet of chicken and lean pork, five meals per week, followed by a washout and the other intervention arm. Fasting blood serum metabolites were analysed at 0, 2 and 4 weeks for eleven subjects with available samples, using GC‐MS based metabolomics.

The herring diet decreased plasma citrate, fumarate, isocitrate, glycolate, oxalate, agmatine and methyhistidine and increased asparagine, ornithine, glutamine and the hexosamine glucosamine. Modelling found that the tricarboxylic acid cycle, glyoxylate, and arginine metabolism were affected by the intervention. The effect on arginine metabolism was supported by an increase in blood nitric oxide in males on the herring diet.

Conclusion

The results suggest that eating herring instead of chicken and lean pork leads to important metabolic effects, particularly on energy and amino acid metabolism. Our findings support the hypothesis that there are metabolic effects of herring intake unrelated to the long chain n‐3 polyunsaturated fatty acid content.
Reciprocal androgen receptor/interleukin‐6 crosstalk drives oesophageal carcinoma progression and contributes to patient prognosis
Authors: Dong Hongmei , Xu Jinjin , Li Weiwei , Gan Jinfeng , Lin Wan , Ke Jierong , Jiang Jiali , Du Liang , Chen Yuping , Zhong Xueyun , Zhang Dianzheng , Yeung Sai‐Ching Jim , Li Xiaotao , Zhang Hao
Published: November 2016

Oesophageal squamous cell carcinoma (ESCC), a leading lethal malignancy of the digestive tract, is characterized by marked gender disparity. Clarifying the roles of the function and regulatory pathway of the androgen receptor (AR) will improve our understanding of oesophageal cancer progression, thereby facilitating the personalized management of ESCC. Here we report evidence to show that AR is a key mediator of inflammatory signals in ESCC cancer progression. High AR expression was associated with poor overall survival in tobacco‐using ESCC patients but not in ESCC patients not using tobacco. A gain and loss of AR function enhanced and repressed ESCC cell growth, respectively, by altering cell cycle progression. In mice bearing human ESCC xenografts, silencing AR expression attenuated tumour growth, whereas AR overexpression promoted tumour growth in mice of different androgen statuses (male, female, and castrated male). Array assays revealed that the inflammatory cytokine interleukin‐6 (IL6) is a prominent AR target gene in ESCC. By directly binding to the IL6 promoter, AR enhances IL6 transcription, and IL6 can in turn activate AR expression, thus forming a reciprocal regulatory circuit to sustain STAT3 oncogenic signalling in ESCC. Moreover, high expression levels of both AR and IL6 in human ESCC predict poor clinical outcome in tobacco users. Together, these data establish that AR promotes ESCC growth and is associated with poor patient prognosis. The discovery of a positive feedback loop between IL6 and AR bridges the knowledge gaps among lifestyle factor‐associated inflammation, gender disparity, and oesophageal carcinoma. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Opioid prescription practices at discharge and 30‐day returns in children with sickle cell disease and pain
Authors: Okorji Leslie M. , Muntz Devin S. , Liem Robert I.
Published: November 2016

Background

Acute pain episodes in children with sickle cell disease (SCD) represent a leading cause of readmissions. We examined prescription practices at the time of discharge in children with SCD presenting with acute pain to determine their impact on 30‐day emergency department (ED) revisits and readmissions.

Methods

In this single‐institution, 5‐year retrospective study, we reviewed 290 encounters of patients with SCD aged 7–21 years hospitalized or discharged from the ED with acute pain. We reviewed demographic, treatment and discharge data, and 30‐day returns, defined as ED revisits and readmissions within 30 days of discharge. Bivariate and multivariable analyses were performed to evaluate the association between discharge prescription practices and 30‐day returns.

Results

Compared to hospitalizations, treat‐and‐release ED visits for acute pain were associated with a higher incidence of 30‐day returns (OR = 2.7 [95% CI: 1.5–4.8], P < 0.01). We found no association between prescribed opioid frequency (scheduled vs. as‐needed) and 30‐day returns (OR = 1.12 [95% CI: 0.62–2.02], P = 0.70). By multivariable logistic regression, the prescription of nonsteroidal anti‐inflammatory drugs (NSAIDs) only, without opioids, after treat‐and‐release ED visits was independently associated with a higher frequency of 30‐day ED revisits (OR = 6.9 [95% CI: 1.3–37.3], P = 0.03) but not readmissions.

Conclusion

Variability exists in opioid prescription practices after discharge in children with SCD and pain episodes. Prescription of NSAIDs only, without opioids, was an independent predictor of higher 30‐day ED revisits. Formalized studies to better understand factors that influence returns, including outpatient opioid management, are warranted in this population.
Risk factors for pulmonary arterial hypertension in children and young adults
Authors: Naumburg Estelle , Söderström Lars , Huber Daniel , Axelsson Inge
Published: November 2016

Objectives

Pulmonary hypertension (PH) has been linked to preterm birth explained by congenital heart defects and pulmonary diseases.

Working hypothesis

Other factors may influence the risk of PH among adolescences and children born premature.

Study design

This national registry‐based study assess risk of PH following premature birth adjusted for known risk factors.

Patient‐subject selection and methodology

All cases born 1993–2010, identified by diagnostic codes applicable to PH and retrieved from the Swedish Registry of Congenital Heart Disease (N = 67). Six controls were randomly selected and matched to each case by year of birth and hospital by the Swedish Medical Birth Register (N = 402). Maternal and infant data related to preterm birth, pulmonary diseases, and congenital defects were retrieved. The association between preterm birth and pulmonary hypertension was calculated by conditional logistic regression taking into account potential confounding factors.

Results

One third of the cases and seven percent of the controls were born preterm in our study. Preterm birth was associated with PH, OR = 8.46 (95%CI 2.97–24.10) (P < 0.0001) even after adjusting for confounding factors. Other factors, such as acute pulmonary diseases, congenital heart defects, congenital diaphragm herniation, and chromosomal disorders were also associated with PH in the multivariate analysis.

Conclusions

Children and young adults born preterm are known to have an increased risk of PH, previously explained by congenital heart defects and pulmonary diseases. By adjusting for such factors, our study indicates that new factors may play a role in the risk of developing PH among children born preterm. Pediatr Pulmonol. 2017;52:636–641. © 2016 Wiley Periodicals, Inc.
Carcinomatous pleuritis and pericarditis accompanied by pulmonary tuberculosis
Authors: Hara Munechika , Iwakami Shin‐ichiro , Matsumoto Naohisa , Miyawaki Taichi , Wada Ryo , Takahashi Kazuhisa
Published: November 2016

Although both lung cancer and pulmonary tuberculosis (TB) commonly occur in clinical practice, little attention has been paid to their coexistence. A 62‐year‐old female was admitted with acute dyspnoea secondary to cardiac tamponade. During her admission, a mass lesion harbouring air bronchograms in the right upper lobe rapidly increased in size. Surgical lung, pericardial, and pleural specimens yielded TB from a nodule in the right upper lobe and lung adenocarcinoma from the pericardium and pleura. Anti‐tuberculous therapy was administered and gefitinib was subsequently started after the positive identification of epidermal growth factor receptor (EGFR) mutation (exon 19 deletion). The patient's general condition gradually improved with the anti‐tuberculous and the EGFR‐tyrosine kinase inhibitor (EGFR‐TKI) treatment. Dual pathology is important to consider in patients with atypical radiological appearances. In those with proven EGFR mutation positive for lung cancer and pulmonary TB, sequential anti‐tuberculous medication followed by EGFR‐TKI treatment is advised.
Advances in the development of aptamer drug conjugates for targeted drug delivery
Authors: Chen Ke , Liu Bo , Yu Bo , Zhong Wen , Lu Yi , Zhang Jiani , Liao Jie , Liu Jun , Pu Ying , Qiu Liping , Zhang Liqin , Liu Huixia , Tan Weihong
Published: November 2016

A key goal of modern medicine is target‐specific therapeutic intervention. However, most drugs lack selectivity, resulting in ‘off‐target’ side effects. To address the requirements of ‘targeted therapy,’ aptamers, which are artificial oligonucleotides, have been used as novel targeting ligands to construct aptamer drug conjugates (ApDC) that can specifically bind to a broad spectrum of targets, including diseased cells. Accordingly, the application of aptamers in targeted drug delivery has attracted broad interest due to their impressive selectivity and affinity, low immunogenicity, easy synthesis with high reproducibility, facile modification, and relatively rapid tissue penetration with no toxicity. Functionally, aptamers themselves can be used as macromolecular drugs, and they are also commonly used in biomarker discovery and targeted drug delivery. In this review, we will highlight the most recent advances in the development of aptamers and aptamer conjugates, and discuss their potential in targeted therapy. WIREs Nanomed Nanobiotechnol 2017, 9:e1438. doi: 10.1002/wnan.1438

This article is categorized under:

Diagnostic Tools > Biosensing

Diagnostic Tools > In Vitro Nanoparticle-Based Sensing

Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures
Status and trends in the development of clinical diagnostic agents
Authors: Opacic Tatjana , Paefgen Vera , Lammers Twan , Kiessling Fabian
Published: November 2016

Contrast agents (CA) are routinely used in clinical practice to improve the diagnosis of diseases and to monitor therapy response. The majority of CA comprises small molecules accumulating at pathological sites due to vascular abnormalities, such as changes in perfusion and permeability. For many diseases, high diagnostic accuracy can be achieved with contrast‐enhanced imaging. This means that new CA will only succeed in translation if they either show superior performance with respect to diagnostic accuracy, safety and cost, support a new imaging modality, or are directly linked to the refinement of therapy, e.g., as a companion diagnostic. Unfortunately, these basic demands are often not carefully considered by the scientific community, leading to concepts with low chances of clinical translation. Thus, it is not surprising that, despite steadily increasing numbers of publications, there is quite the opposite trend when it comes to the clinical approval of new diagnostics. As a matter of fact, except for PET tracers, in the last decade, only a handful of CA received FDA or EMA approval. Furthermore, several approved products were discontinued by the manufacturers because of low market potential, a competitive own product, suboptimal clinical performance, or safety concerns. This review article discusses the current status of approved diagnostic probes for clinical imaging modalities, with a focus on new trends in CA development. In this context, molecularly targeted diagnostics or probes for emerging fields, such as image‐guided surgery, nanomedicine, or theranostics, will be introduced and discussed with regard to their clinical translation. WIREs Nanomed Nanobiotechnol 2017, 9:e1441. doi: 10.1002/wnan.1441

This article is categorized under:

Therapeutic Approaches and Drug Discovery > Emerging Technologies

Diagnostic Tools > In Vivo Nanodiagnostics and Imaging
Metformin Reduces Lipogenesis Markers in Obese Mice Fed a Low‐Carbohydrate and High‐Fat Diet
Authors: de Oliveira Santana Karla Nayara , Lelis Deborah Farias , Mendes Keila Lopes , Lula Jamille Fernandes , Paraíso Alanna Fernandes , Andrade João Marcus Oliveira , Feltenberger John David , Cota Junio , da Costa Diego Vicente , de Paula Alfredo Mauricio Batista , Guimarães André Luiz Sena , Santos Sérgio Henrique Sousa
Published: November 2016

Lipogenesis is the process by which fatty acids are synthesized. In metabolic syndrome, an insulin resistant state along with high plasma levels of free fatty acids (FFA) and hyperglycemia may contribute to the lipogenic process. The aim of the present study was to investigate the effects of oral administration of metformin on the expression of lipogenic genes and glycemic profile in mice fed with low‐carbohydrate high‐fat diet by evaluating their metabolic profile. SWISS male mice were divided into 4 groups (N = 7) that were fed with standard (ST), standard plus metformin (ST + MET), low‐carbohydrate high‐fat diet (LCHFD) and low‐carbohydrate high‐fat diet plus metformin (LCHFD + MET) (100 mg kg−1 diet) diets respectively. Food intake, body weight and blood parameters, such as glucose tolerance, insulin sensitivity, glucose, HDL‐c, total cholesterol, triglycerides, ASL and ALT levels were assessed. Histological analyses were performed on hematoxylin and eosin‐stained epididymal adipose tissue histological specimens. The expression levels of peroxisome proliferator‐activated receptor (PPARγ), sterol regulatory element‐binding protein 1 (SREBP1), fatty acid synthase (FAS) and acetyl‐CoA carboxylase (ACC), were assessed by RT‐PCR. This study showed that metformin decreased adipocyte area, body weight and food consumption in obese animals when compared to the standard group. Furthermore, the expression of lipogenic markers in adipose tissue were diminished in obese animals treated with metformin. This data showed that oral administration of metformin improved glucose and lipid metabolic parameters in white adipose tissue by reducing the expression of lipogenesis markers, suggesting an important clinical application of MET in treating obesity‐related diseases in metabolic syndrome.
Midpregnancy Marriage and Divorce: Why the Death of Shotgun Marriage Has Been Greatly Exaggerated
Authors: Gibson-Davis Christina M. , Ananat Elizabeth O. , Gassman-Pines Anna
Published: November 2016

Conventional wisdom holds that births following the colloquially termed “shotgun marriage”—that is, births to parents who married between conception and the birth—are nearing obsolescence. To investigate trends in shotgun marriage, we matched North Carolina administrative data on nearly 800,000 first births among white and black mothers to marriage and divorce records. We found that among married births, midpregnancy-married births (our preferred term for shotgun-married births) have been relatively stable at about 10 % over the past quarter-century while increasing substantially for vulnerable population subgroups. In 2012, among black and white less-educated and younger women, midpregnancy-married births accounted for approximately 20 % to 25 % of married first births. The increasing representation of midpregnancy-married births among married births raises concerns about well-being among at-risk families because midpregnancy marriages may be quite fragile. Our analysis revealed, however, that midpregnancy marriages were more likely to dissolve only among more advantaged groups. Of those groups considered to be most at risk of divorce—namely, black women with lower levels of education and who were younger—midpregnancy marriages had the same or lower likelihood of divorce as preconception marriages. Our results suggest an overlooked resiliency in a type of marriage that has only increased in salience.
Brief report: Feasibility of a mindfulness and self‐compassion based mobile intervention for adolescents
Authors: Donovan Elizabeth , Rodgers Rachel F. , Cousineau Tara M. , McGowan Kayla M. , Luk Stephanie , Yates Kayla , Franko Debra L.
Published: November 2016

The aim of the study was to test the feasibility of a mindfulness and self‐compassion based program for adolescents, to be delivered though mobile phones. Twenty racially and ethnically diverse US adolescents enrolled in a study to use the app for 30 days, after which they provided satisfaction data and participated in focus groups to describe their experiences and offer suggestions for improving the app. Usage data were also captured. Results indicated that participants used the app on the majority of days over the intervention period, reported finding it helpful for managing stress, and provided suggestions for substantive areas for improvement. These findings suggest that a mobile app may be a feasible way to disseminate a mindfulness and selfcompassion based program widely among adolescents.
Prospective associations of plasma phospholipids and mild cognitive impairment/dementia among African Americans in the ARIC Neurocognitive Study
Authors: Li Danni , Misialek Jeffrey R. , Boerwinkle Eric , Gottesman Rebecca F. , Sharrett A. Richey , Mosley Thomas H. , Coresh Josef , Wruck Lisa M. , Knopman David S. , Alonso Alvaro
Published: November 2016

Introduction

The objective of this study was to investigate whether 10 phospholipids/metabolites previously identified as prospectively predictive of mild cognitive impairment (MCI) or dementia in whites would also be predictive in a mostly African‐American cohort.

Methods

We repeatedly measured 188 phospholipids/metabolites in plasma samples of 221 participants of the Atherosclerosis Risk in Communities study, 97% African American, who were followed between 2004–2006 and 2011–2013.

Results

After a mean follow‐up of 7.3 years, 77 were classified as having MCI and 18 as having dementia. Our study failed to replicate previous findings in this mostly African American cohort, in that the 10 phospholipids/metabolites only achieved a C statistic/AUC of 0.609 in predicting development of MCI or dementia (compared to 0.96) and 0.607 in distinguishing normal from MCI or dementia at the follow‐up visit.

Conclusion

A panel of 10 phospholipids/metabolites previously associated with incident dementia was not predictive of MCI or dementia in an independent cohort.
Why so GLUMM? Detecting depression clusters through graphing lifestyle-environs using machine-learning methods (GLUMM)
Authors: Dipnall J.F. , Pasco J.A. , Berk M. , Williams L.J. , Dodd S. , Jacka F.N. , Meyer D.
Published: November 2016

Background

Key lifestyle-environ risk factors are operative for depression, but it is unclear how risk factors cluster. Machine-learning (ML) algorithms exist that learn, extract, identify and map underlying patterns to identify groupings of depressed individuals without constraints. The aim of this research was to use a large epidemiological study to identify and characterise depression clusters through “Graphing lifestyle-environs using machine-learning methods” (GLUMM).

Methods

Two ML algorithms were implemented: unsupervised Self-organised mapping (SOM) to create GLUMM clusters and a supervised boosted regression algorithm to describe clusters. Ninety-six “lifestyle-environ” variables were used from the National health and nutrition examination study (2009–2010). Multivariate logistic regression validated clusters and controlled for possible sociodemographic confounders.

Results

The SOM identified two GLUMM cluster solutions. These solutions contained one dominant depressed cluster (GLUMM5-1, GLUMM7-1). Equal proportions of members in each cluster rated as highly depressed (17%). Alcohol consumption and demographics validated clusters. Boosted regression identified GLUMM5-1 as more informative than GLUMM7-1. Members were more likely to: have problems sleeping; unhealthy eating; ≤ 2 years in their home; an old home; perceive themselves underweight; exposed to work fumes; experienced sex at ≤ 14 years; not perform moderate recreational activities. A positive relationship between GLUMM5-1 (OR: 7.50, P < 0.001) and GLUMM7-1 (OR: 7.88, P < 0.001) with depression was found, with significant interactions with those married/living with partner (P = 0.001).

Conclusion

Using ML based GLUMM to form ordered depressive clusters from multitudinous lifestyle-environ variables enabled a deeper exploration of the heterogeneous data to uncover better understandings into relationships between the complex mental health factors.
Honoring Earth and Space Scientists
Authors:   AGU
Published: November 2016

AGU members and others in the news
A novel mechanism for host-mediated photoprotection in endosymbiotic foraminifera
Authors: Petrou Katherina , Ralph Peter J , Nielsen Daniel A
Published: November 2016

Light underpins the health and function of coral reef ecosystems, where symbiotic partnerships with photosynthetic algae constitute the life support system of the reef. Decades of research have given us detailed knowledge of the photoprotective capacity of phototrophic organisms, yet little is known about the role of the host in providing photoprotection in symbiotic systems. Here we show that the intracellular symbionts within the large photosymbiotic foraminifera Marginopora vertebralis exhibit phototactic behaviour, and that the phototactic movement of the symbionts is accomplished by the host, through rapid actin-mediated relocation of the symbionts deeper into the cavities within the calcium carbonate test. Using a photosynthetic inhibitor, we identified that the infochemical signalling for host regulation is photosynthetically derived, highlighting the presence of an intimate communication between the symbiont and the host. Our results emphasise the central importance of the host in photosymbiotic photoprotection via a new mechanism in foraminifera that can serve as a platform for exploring host–symbiont communication in other photosymbiotic organisms.
Trade-offs between microbiome diversity and productivity in a stratified microbial mat
Authors: Bernstein Hans C , Brislawn Colin , Renslow Ryan S , Dana Karl , Morton Beau , Lindemann Stephen R , Song Hyun-Seob , Atci Erhan , Beyenal Haluk , Fredrickson James K , Jansson Janet K , Moran James J
Published: November 2016

Productivity is a major determinant of ecosystem diversity. Microbial ecosystems are the most diverse on the planet yet very few relationships between diversity and productivity have been reported as compared with macro-ecological studies. Here we evaluated the spatial relationships of productivity and microbiome diversity in a laboratory-cultivated photosynthetic mat. The goal was to determine how spatial diversification of microorganisms drives localized carbon and energy acquisition rates. We measured sub-millimeter depth profiles of net primary productivity and gross oxygenic photosynthesis in the context of the localized microenvironment and community structure, and observed negative correlations between species richness and productivity within the energy-replete, photic zone. Variations between localized community structures were associated with distinct taxa as well as environmental profiles describing a continuum of biological niches. Spatial regions in the photic zone corresponding to high primary productivity and photosynthesis rates had relatively low-species richness and high evenness. Hence, this system exhibited negative species–productivity and species–energy relationships. These negative relationships may be indicative of stratified, light-driven microbial ecosystems that are able to be the most productive with a relatively smaller, even distributions of species that specialize within photic zones.
Fitness costs restrict niche expansion by generalist niche-constructing pathogens
Authors: Lang Julien , Vigouroux Armelle , El Sahili Abbas , Kwasiborski Anthony , Aumont-Nicaise Magali , Dessaux Yves , Shykoff Jacqui Anne , Moréra Solange , Faure Denis
Published: November 2016

We investigated the molecular and ecological mechanisms involved in niche expansion, or generalism, versus specialization in sympatric plant pathogens. Nopaline-type and octopine-type Agrobacterium tumefaciens engineer distinct niches in their plant hosts that provide different nutrients: nopaline or octopine, respectively. Previous studies revealed that nopaline-type pathogens may expand their niche to also assimilate octopine in the presence of nopaline, but consequences of this phenomenon on pathogen dynamics in planta were not known. Here, we provided molecular insight into how the transport protein NocT can bind octopine as well as nopaline, contributing to niche expansion. We further showed that despite the ability for niche expansion, nopaline-type pathogens had no competitive advantage over octopine-type pathogens in co-infected plants. We also demonstrated that a single nucleotide polymorphism in the nocR gene was sufficient to allow octopine assimilation by nopaline-type strains even in absence of nopaline. The evolved nocR bacteria had higher fitness than their ancestor in octopine-rich transgenic plants but lower fitness in tumors induced by octopine-type pathogens. Overall, this work elucidates the specialization of A. tumefaciens to particular opine niches and explains why generalists do not always spread despite the advantage associated with broader nutritional niches.
Seismic evidence for a cold serpentinized mantle wedge beneath Mount St Helens
Authors: Hansen S. M. , Schmandt B. , Levander A. , Kiser E. , Vidale J. E. , Abers G. A. , Creager K. C.
Published: November 2016

Mount St Helens is the most active volcano within the Cascade arc; however, its location is unusual because it lies 50 km west of the main axis of arc volcanism. Subduction zone thermal models indicate that the down-going slab is decoupled from the overriding mantle wedge beneath the forearc, resulting in a cold mantle wedge that is unlikely to generate melt. Consequently, the forearc location of Mount St Helens raises questions regarding the extent of the cold mantle wedge and the source region of melts that are responsible for volcanism. Here using, high-resolution active-source seismic data, we show that Mount St Helens sits atop a sharp lateral boundary in Moho reflectivity. Weak-to-absent PmP reflections to the west are attributed to serpentinite in the mantle-wedge, which requires a cold hydrated mantle wedge beneath Mount St Helens (<∼700 °C). These results suggest that the melt source region lies east towards Mount Adams.
Altruistic punishment does not increase with the severity of norm violations in the field
Authors: Balafoutas Loukas , Nikiforakis Nikos , Rockenbach Bettina
Published: November 2016

The degree of human cooperation among strangers is a major evolutionary puzzle. A prominent explanation is that cooperation is maintained because many individuals have a predisposition to punish those violating group-beneficial norms. A critical condition for cooperation to evolve in evolutionary models is that punishment increases with the severity of the violation. Here we present evidence from a field experiment with real-life interactions that, unlike in lab experiments, altruistic punishment does not increase with the severity of the violation, regardless of whether it is direct (confronting a violator) or indirect (withholding help). We also document growing concerns for counter-punishment as the severity of the violation increases, indicating that the marginal cost of direct punishment increases with the severity of violations. The evidence suggests that altruistic punishment may not provide appropriate incentives to deter large violations. Our findings thus offer a rationale for the emergence of formal institutions for promoting large-scale cooperation among strangers.
Altered structural and effective connectivity in anorexia and bulimia nervosa in circuits that regulate energy and reward homeostasis
Authors: Frank G K W , Shott M E , Riederer J , Pryor T L
Published: November 2016

Anorexia and bulimia nervosa are severe eating disorders that share many behaviors. Structural and functional brain circuits could provide biological links that those disorders have in common. We recruited 77 young adult women, 26 healthy controls, 26 women with anorexia and 25 women with bulimia nervosa. Probabilistic tractography was used to map white matter connectivity strength across taste and food intake regulating brain circuits. An independent multisample greedy equivalence search algorithm tested effective connectivity between those regions during sucrose tasting. Anorexia and bulimia nervosa had greater structural connectivity in pathways between insula, orbitofrontal cortex and ventral striatum, but lower connectivity from orbitofrontal cortex and amygdala to the hypothalamus (P<0.05, corrected for comorbidity, medication and multiple comparisons). Functionally, in controls the hypothalamus drove ventral striatal activity, but in anorexia and bulimia nervosa effective connectivity was directed from anterior cingulate via ventral striatum to the hypothalamus. Across all groups, sweetness perception was predicted by connectivity strength in pathways connecting to the middle orbitofrontal cortex. This study provides evidence that white matter structural as well as effective connectivity within the energy-homeostasis and food reward-regulating circuitry is fundamentally different in anorexia and bulimia nervosa compared with that in controls. In eating disorders, anterior cingulate cognitive–emotional top down control could affect food reward and eating drive, override hypothalamic inputs to the ventral striatum and enable prolonged food restriction.