bluuebunny/crossref_metadata_2025 huggingface dataset:
Phylogeography of the invasive Mediterranean fan worm,Sabella spallanzanii(Gmelin, 1791), in Australia and New Zealand
Authors: Ahyong Shane T. , Kupriyanova Elena , Burghardt Ingo , Sun Yanan , Hutchings Pat A. , Capa Maria , Cox Serena L.
Published: March 2017

The Mediterranean fan worm,Sabella spallanzanii(Gmelin, 1791), is a highly invasive pest species introduced to Australia and New Zealand, with the ability to alter marine ecosystems by outcompeting native species for food and space.Sabella spallanzaniihas been established in southern Australia for decades, but was discovered in Botany Bay (NSW, eastern Australia) in 2013. In New Zealand,S. spallanzaniiwas first detected in March 2008. Using cytochrome c oxidase subunit 1 (COI) sequences, we investigate the phylogeography of the Australian and New Zealand populations ofS. spallanzanii, including the possible origins of the recent incursions in both countries. Australian and New ZealandS. spallanzaniishow minimal genetic diversity (0.2% divergence) and were dominated by two main haplotypes suggesting a commonality. Our molecular data are insufficient by themselves to identify fine-scale invasion pathways in antipodeanS. spallanzanii, but the similar, minimal haplotype diversity in combination with well-constrained field survey data suggests that the New Zealand incursion originated from southern Australia, rather than as a new incursion from the Mediterranean Sea. This highlights the importance of ongoing marine biosecurity surveillance and monitoring as well as improvements to biosecurity protocols for international and domestic vessels. The origin of the eastern Australian (Botany Bay) incursion is plausibly derived from either southern Australia or as a ‘return’ from New Zealand, and requires further, more detailed investigation.
Escape behaviour of aposematic (Oophaga pumilio) and cryptic (Craugastor sp.) frogs in response to simulated predator approach
Authors: Blanchette Annelise , Becza Noémi , Saporito Ralph A.
Published: March 2017

Crypsis and aposematism are common antipredator strategies that can each be coupled with behaviours that maximize predator deterrence or avoidance. Cryptic animals employ camouflage to conceal themselves within their environment and generally rely on immobility to avoid detection by predators. Alternatively, aposematic animals tend to rely on an association between conspicuous colouration and secondary defence to deter potential predators, and tend to exhibit slow movements in response to predators. The goal of the present study was to determine how cryptic Craugastor sp. and aposematic Oophaga pumilio respond to simulated human and bird model predators. Oophaga pumilio responded more often with movement to both the human (17/22) and bird (9/25) predators than Craugastor sp. (human: 2/21; bird: 0/21). The increased movement resulted in a greater average flight initiation distance, latency to move, and distance fled in O. pumilio. These findings suggest that cryptic Craugastor sp. rely on immobility to avoid detection, whereas aposematic O. pumilio utilize movement, possibly as a mechanism to increase the visibility of their warning signals to potential predators. Furthermore, O. pumilio exhibited greater movement in response to humans, suggesting that they actively avoid trampling by large threats, rather than considering them predators.
Construction of ray-class fields by smaller generators and their applications
Authors: Koo Ja Kyung , Yoon Dong Sung
Published: March 2017

We generate ray-class fields over imaginary quadratic fields in terms of Siegel–Ramachandra invariants, which are an extension of a result of Schertz. By making use of quotients of Siegel–Ramachandra invariants we also construct ray-class invariants over imaginary quadratic fields whose minimal polynomials have relatively small coefficients, from which we are able to solve certain quadratic Diophantine equations.
Passive range of motion exercise to enhance growth in infants following the Norwood procedure: a safety and feasibility trial
Authors: Lambert Linda M. , Trachtenberg Felicia L. , Pemberton Victoria L. , Wood Janine , Andreas Shelley , Schlosser Robin , Barnard Teresa , Daniels Kaitlyn , Harrington Ann T. , Dagincourt Nicholas , Miller Thomas A. ,   for the Pediatric Heart Network Investigators
Published: March 2017

Objective

The aim of this study was to evaluate the safety and feasibility of a passive range of motion exercise programme for infants with CHD.

Study design

This non-randomised pilot study enrolled 20 neonates following Stage I palliation for single-ventricle physiology. Trained physical therapists administered standardised 15–20-minute passive range of motion protocol, for up to 21 days or until hospital discharge. Safety assessments included vital signs measured before, during, and after the exercise as well as adverse events recorded through the pre-Stage II follow-up. Feasibility was determined by the percent of days that >75% of the passive range of motion protocol was completed.

Results

A total of 20 infants were enrolled (70% males) for the present study. The median age at enrolment was 8 days (with a range from 5 to 23), with a median start of intervention at postoperative day 4 (with a range from 2 to 12). The median hospital length of stay following surgery was 15 days (with a range from 9 to 131), with an average of 13.4 (with a range from 3 to 21) in-hospital days per patient. Completion of >75% of the protocol was achieved on 88% of eligible days. Of 11 adverse events reported in six patients, 10 were expected with one determined to be possibly related to the study intervention. There were no clinically significant changes in vital signs. At pre-Stage II follow-up, weight-for-age z-score (−0.84±1.20) and length-for-age z-score (−0.83±1.31) were higher compared with historical controls from two earlier trials.

Conclusion

A passive range of motion exercise programme is safe and feasible in infants with single-ventricle physiology. Larger studies are needed to determine the optimal duration of passive range of motion and its effect on somatic growth.
Dosimetric comparison of helical tomotherapy using different techniques, simultaneous integrated boost and sequential boost for craniospinal irradiation: a single institution experience
Authors: Jia-Mahasap Bongkot , Chitapanarux Imjai , Tharavichitkul Ekkasit , Chakrabandhu Somvilai , Klunklin Pitchayaponne , Onchan Wimrak , Watcharawipha Anirut , Wanwilairat Somsak , Traisathit Patrinee
Published: March 2017

Purpose

Craniospinal irradiation (CSI) has become an important and challenging radiation technique for radiation oncologists. Helical tomotherapy (HT) seems to have dosimetric advantage for CSI compared with other radiation modalities. The purpose of this study was to compare dosimetric data between two different HT plans; simultaneous integrated boost (SIB) and sequential boost (Sq).

Method

Twelve previously treated CSI contoured datasets by SIB technique were replanned. Dosimetric comparative parameters of targets were conformity index (CI) and homogeneity index (HI). For organ at risk (OARs), the mean dose of parallel organs, D2% of serial organs and whole body integral dose (ID) were also investigated.

Result

SIB plan significantly provided more conformed dose to CSI and tumour boost while resulting in a similar CI in spinal boost region compared with Sq plan. The HI showed no differences between two plans. Radiation exposure to serial organs and ID were also significantly lower in SIB plan.

Conclusion

CSI treatment using HT, SIB technique was feasible and had more target coverage while minimising the radiation dose to healthy tissues.
The use of 3D printing within radiation therapy to improve bolus conformity: a literature review
Authors: Pugh Rebecca , Lloyd Kelly , Collins Mark , Duxbury Angela
Published: March 2017

Background and purpose

In radiotherapy (RT) bolus material is used to increase skin dose and eliminate the ‘skin-sparing’ effect. Bolus fabrication is limited to the expertise of the practitioner and is time and resource intensive for both patients and staff to construct bolus. In addition, prefabricated bolus does not always conform to irregular surfaces resulting in variations to dose distribution at the skin surface. The purpose of this paper is to ascertain whether it is feasible to improve bolus conformity within radiation therapy by using a 3D printer to fabricate bolus.

Method

A literature review was conducted that utilised Boolean terminology and included keywords; (‘3d’ OR ‘3-dimensional’ OR ‘three dimensional’) ‘bolus’ OR ‘boli’ conform*, (‘Radiation therapy’ OR ‘radiotherapy’) Printing.

Results

Several key papers were identified and critically evaluated based of the title of the feasibility of improving bolus conformity with the used of 3D printing. Several fabrication material devices were explored.

Findings

The literature advocates that fused deposition modelling fabrication device clear polylactic acid material to be an adequate product to construct 3D printed bolus and conform to irregular surfaces. 3D bolus would prove advantageous for volumetric arc therapy/intensity modulated radiation therapy techniques as literature has shown the presence of air gaps, small field sizes and large beam obliquity can result in a >10% dose reduction at skin surface.
Raising more domestic money for health: prospects for low- and middle-income countries
Authors: Elovainio Riku , Evans David B.
Published: March 2017

Since the 2007/2008 financial crisis, the rhetoric in the development assistance dialogue has shifted away from raising more international funding for health, to requesting countries to move toward self-sufficiency. This paper examines the potential of 46 countries identified by an international panel in 2009 as being of high need to raise additional funding for health from domestic sources. Economic growth alone would allow 12 of them to reach a level of health spending where their populations could have access to a very basic set of health services. All of them have the potential to raise additional domestic funds through a range of measures that have been tried successfully in other low- and middle-income countries, but they would all remain well below the eventual objective of universal health coverage without increased and predictable external financial support.
Distributing development assistance for health: simulating the implications of 11 criteria
Authors: Ottersen Trygve , Moon Suerie , Røttingen John-Arne
Published: March 2017

After years of unprecedented growth in development assistance for health (DAH), the DAH system is challenged on several fronts: by the economic downturn and stagnation of DAH, by the epidemiological transition and increase in non-communicable diseases and by the economic transition and rise of the middle-income countries. Central to any potent response is a fair and effective allocation of DAH across countries. A myriad of criteria has been proposed or is currently used, but there have been no comprehensive assessment of their distributional implications. We simulated the implications of 11 quantitative allocation criteria across countries and country categories. We found that the distributions varied profoundly. The group of low-income countries received most DAH from needs-based criteria linked to domestic capacity, while the group of upper-middle-income countries was most favoured by an income-inequality criterion. Compared to a baseline distribution guided by gross national income per capita, low-income countries received less DAH by almost all criteria. The findings can inform funders when examining and revising the criteria they use, and provide input to the broader debate about what criteria should be used.
Changes in carotid artery intima-media thickness during the cardiac cycle – a comparative study in early childhood, mid-childhood, and adulthood
Authors: Rueb Kuna , Mynard Jonathan , Liu Richard , Wake Melissa , Vuillermin Peter , Ponsonby Anne-Louise , Zannino Diana , Burgner David P.
Published: March 2017

Abstract. Background: Carotid intima-media thickness (CIMT), an ultrasonographic marker of cardiovascular risk, is increasingly used in adults and children. The choice of specific images used to quantify CIMT from a cine sequence is often based on image quality rather than on a consistent point in the cardiac cycle. This methodological study quantified the imprecision that may be introduced by variation of CIMT during the cardiac cycle. Probands and methods: Data from four-year-olds, 11 to 12-year-olds, and adults (n=30 each age group) were selected retrospectively from two population-derived studies. Far wall CIMT of the right common carotid artery was measured at end-diastole and peak systole using standardized protocols. All images were analysed using semi-automated edge-detection software. Results: In all age groups CIMT varied significantly during the cardiac cycle and was largest at end-diastole. The mean difference in CIMT between end-diastole and peak systole was greater in four-year-olds (38 μm; 95 % confidence interval (CI) 33 to 43 μm) and 11 to 12-year-olds (31 μm; CI 26 to 36 μm) than in adults (18 μm; CI 16 to 22 μm). Carotid IMT increased by 8.8 % (CI 7.7 to 9.8 %), 6.9 % (CI 5.8 to 8.1 %), and 3.8 % (CI 3.1 to 4.5 %) between minimum and maximum arterial diameter in four-year-olds, 11 to 12-year-olds, and adults, respectively. The greatest variation in CIMT during the cardiac cycle was observed in children (up to 14 %). Conclusions: Inconsistent timing of CIMT measurement during the cardiac cycle is an avoidable source of imprecision, especially in children, in whom inter-individual differences are smallest. As CIMT is largest at end-diastole, this is the most appropriate time point for consistent and comparable measurements to be made.
Controversies of Women’s Sexual Arousal and	Desire
Authors: Chivers Meredith L. , Brotto Lori A.
Published: March 2017

Abstract. The past three decades have seen an unprecedented increase in empirical research on women’s sexual response. In this review, we critically examine current controversies and assumptions associated with the nature of women’s sexual arousal and desire. We focus specifically on four assumptions: (1) the assumption that women should be aroused by stimuli that align with their stated preferences, (2) the assumption that women’s physiological and self-reported arousal should perfectly align, (3) the assumption that sexual desire precedes sexual arousal, and (4) the assumption that a single pharmaceutical compound will adequately restore women’s sexual response to her level of satisfaction. Engaging a gendered psychological framework for conceptualizing women’s sexuality, we emphasize the need for models of women’s sexual response to be sensitive to the sexed biological processes and gendered psychosocial factors that contribute to a woman’s unique sexual experience.
Salusin-β contributes to oxidative stress and inflammation in diabetic cardiomyopathy
Authors: Zhao Ming-Xia , Zhou Bing , Ling Li , Xiong Xiao-Qing , Zhang Feng , Chen Qi , Li Yue-Hua , Kang Yu-Ming , Zhu Guo-Qing
Published: March 2017

Salusin-β accelerates inflammatory responses in vascular endothelial cells, and increases oxidative stress in vascular smooth muscle cells. Plasma salusin-β levels were increased in diabetic patients. This study was designed to determine whether salusin-β is involved in the pathogenesis of diabetic cardiomyopathy (DCM), and whether knockdown of salusin-β attenuates cardiac inflammation and oxidative stress in rats with DCM. H9c2 or neonatal rat cardiomyocytes were incubated with 33.3 mM of glucose to mimic the high glucose (HG) in diabetes. Streptozotocin and high-fat diet were used to induce type 2 diabetes in rats. HG induced salusin-β expression in H9c2 cells. Salusin-β caused greater responses of oxidative stress, NFκB activation and inflammation in HG-treated H9c2 cells than these in control H9c2 cells. Diphenyleneiodonium (a NAD(P)H oxidase inhibitor) or N-acetylcysteine (an antioxidant) inhibited the salusin-β-induced NFκB activation and inflammation. Bay11-7082 (a NFκB inhibitor) attenuated salusin-β-induced inflammation but not oxidative stress. Knockdown of salusin-β prevented the HG-induced oxidative stress, NFκB activation and inflammation in neonatal rat cardiomyocytes. Silencing salusin-β with adenoviruse-mediated shRNA had no significant effects on blood glucose and insulin resistance, but attenuated ventricular dysfunction in diabetic rats. Oxidative stress, NFκB activation, inflammation, salusin-β upregulation in myocardium of diabetic rats were prevented by knockdown of salusin-β. These results indicate that salusin-β contributes to inflammation in DCM via NOX2/ROS/NFκB signaling, and that knockdown of salusin-β attenuates cardiac dysfunction, oxidative stress and inflammation in DCM.
Radiation-inducible miR-770-5p sensitizes tumors to radiation through direct targeting of PDZ-binding kinase
Authors: Lee Hyung Chul , Her Nam-Gu , Kang Donghee , Jung Seung Hee , Shin Jinwook , Lee Minyoung , Bae In Hwa , Kim Young-Nyun , Park Heon Joo , Ko Young-Gyu , Lee Jae-Seon
Published: March 2017

Radiotherapy represents the most effective non-surgical modality in cancer treatment. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression, and are involved in many biological processes and diseases. To identify miRNAs that influence the radiation response, we performed miRNA array analysis using MCF7 cells at 2, 8, and 24 h post irradiation. We demonstrated that miR-770-5p is a novel radiation-inducible miRNA. When miR-770-5p was overexpressed, relative cell number was reduced due to increased apoptosis in MCF7 and A549 cells. Transcriptomic and bioinformatic analyses revealed that PDZ-binding kinase (PBK) might be a possible target of miR-770-5p for regulation of radiosensitivity. PBK regulation mediated by direct targeting of miR-770-5p was demonstrated using luciferase reporter assays along with wild-type and mutant PBK-3′untranslated region constructs. Radiation sensitivity increased and decreased in miR-770-5p- and anti-miR-770-5p-transfected cells, respectively. Consistent with this result, transfection of short interfering RNA against PBK inhibited cell proliferation, while ectopic expression of PBK restored cell survival from miR-770-5p-induced cell death. In addition, miR-770-5p suppressed tumor growth, and miR-770-5p and PBK levels were inversely correlated in xenograft model mice. Altogether, these data demonstrated that miR-770-5p might be a useful therapeutic target miRNA that sensitizes tumors to radiation via negative regulation of PBK.
Profiling protein expression in circulating tumour cells using microfluidic western blotting
Authors: Sinkala Elly , Sollier-Christen Elodie , Renier Corinne , Rosàs-Canyelles Elisabet , Che James , Heirich Kyra , Duncombe Todd A. , Vlassakis Julea , Yamauchi Kevin A. , Huang Haiyan , Jeffrey Stefanie S. , Herr Amy E.
Published: March 2017

Circulating tumour cells (CTCs) are rare tumour cells found in the circulatory system of certain cancer patients. The clinical and functional significance of CTCs is still under investigation. Protein profiling of CTCs would complement the recent advances in enumeration, transcriptomic and genomic characterization of these rare cells and help define their characteristics. Here we describe a microfluidic western blot for an eight-plex protein panel for individual CTCs derived from estrogen receptor-positive (ER+) breast cancer patients. The precision handling and analysis reveals a capacity to assay sparingly available patient-derived CTCs, a biophysical CTC phenotype more lysis-resistant than breast cancer cell lines, a capacity to report protein expression on a per CTC basis and two statistically distinct GAPDH subpopulations within the patient-derived CTCs. Targeted single-CTC proteomics with the capacity for archivable, multiplexed protein analysis offers a unique, complementary taxonomy for understanding CTC biology and ascertaining clinical impact.
A genome-wide screen identifies YAP/WBP2 interplay conferring growth advantage on human epidermal stem cells
Authors: Walko Gernot , Woodhouse Samuel , Pisco Angela Oliveira , Rognoni Emanuel , Liakath-Ali Kifayathullah , Lichtenberger Beate M. , Mishra Ajay , Telerman Stephanie B. , Viswanathan Priyalakshmi , Logtenberg Meike , Renz Lisa M. , Donati Giacomo , Quist Sven R. , Watt Fiona M.
Published: March 2017

Individual human epidermal cells differ in their self-renewal ability. To uncover the molecular basis for this heterogeneity, we performed genome-wide pooled RNA interference screens and identified genes conferring a clonal growth advantage on normal and neoplastic (cutaneous squamous cell carcinoma, cSCC) human epidermal cells. The Hippo effector YAP was amongst the top positive growth regulators in both screens. By integrating the Hippo network interactome with our data sets, we identify WW-binding protein 2 (WBP2) as an important co-factor of YAP that enhances YAP/TEAD-mediated gene transcription. YAP and WPB2 are upregulated in actively proliferating cells of mouse and human epidermis and cSCC, and downregulated during terminal differentiation. WBP2 deletion in mouse skin results in reduced proliferation in neonatal and wounded adult epidermis. In reconstituted epidermis YAP/WBP2 activity is controlled by intercellular adhesion rather than canonical Hippo signalling. We propose that defective intercellular adhesion contributes to uncontrolled cSCC growth by preventing inhibition of YAP/WBP2.
Natural variation in CTB4a enhances rice adaptation to cold habitats
Authors: Zhang Zhanying , Li Jinjie , Pan Yinghua , Li Jilong , zhou Lei , Shi Hongli , Zeng Yawen , Guo Haifeng , Yang Shuming , Zheng Weiwei , Yu Jianping , Sun Xingming , Li Gangling , Ding Yanglin , Ma Liang , Shen Shiquan , Dai Luyuan , Zhang Hongliang , Yang Shuhua , Guo Yan , Li Zichao
Published: March 2017

Low temperature is a major factor limiting rice productivity and geographical distribution. Improved cold tolerance and expanded cultivation to high-altitude or high-latitude regions would help meet growing rice demand. Here we explored a QTL for cold tolerance and cloned the gene, CTB4a (cold tolerance at booting stage), encoding a conserved leucine-rich repeat receptor-like kinase. We show that different CTB4a alleles confer distinct levels of cold tolerance and selection for variation in the CTB4a promoter region has occurred on the basis of environmental temperature. The newly generated cold-tolerant haplotype Tej-Hap-KMXBG was retained by artificial selection during temperate japonica evolution in cold habitats for low-temperature acclimation. Moreover, CTB4a interacts with AtpB, a beta subunit of ATP synthase. Upregulation of CTB4a correlates with increased ATP synthase activity, ATP content, enhanced seed setting and improved yield under cold stress conditions. These findings suggest strategies to improve cold tolerance in crop plants.
Long-acting protein drugs for the treatment of ocular diseases
Authors: Ghosh Joy G. , Nguyen Andrew A. , Bigelow Chad E. , Poor Stephen , Qiu Yubin , Rangaswamy Nalini , Ornberg Richard , Jackson Brittany , Mak Howard , Ezell Tucker , Kenanova Vania , de la Cruz Elisa , Carrion Ana , Etemad-Gilbertson Bijan , Caro Roxana Garcia , Zhu Kan , George Vinney , Bai Jirong , Sharma-Nahar Radhika , Shen Siyuan , Wang Yiqin , Subramanian Kulandayan K. , Fassbender Elizabeth , Maker Michael , Hanks Shawn , Vrouvlianis Joanna , Leehy Barrett , Long Debby , Prentiss Melissa , Kansara Viral , Jaffee Bruce , Dryja Thaddeus P. , Roguska Michael
Published: March 2017

Protein drugs that neutralize vascular endothelial growth factor (VEGF), such as aflibercept or ranibizumab, rescue vision in patients with retinal vascular diseases. Nonetheless, optimal visual outcomes require intraocular injections as frequently as every month. Here we report a method to extend the intravitreal half-life of protein drugs as an alternative to either encapsulation or chemical modifications with polymers. We combine a 97-amino-acid peptide of human origin that binds hyaluronan, a major macromolecular component of the eye’s vitreous, with therapeutic antibodies and proteins. When administered to rabbit and monkey eyes, the half-life of the modified proteins is increased ∼3–4-fold relative to unmodified proteins. We further show that prototype long-acting anti-VEGF drugs (LAVAs) that include this peptide attenuate VEGF-induced retinal changes in animal models of neovascular retinal disease ∼3–4-fold longer than unmodified drugs. This approach has the potential to reduce the dosing frequency associated with retinal disease treatments.
Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functions
Authors: Frank-Bertoncelj Mojca , Trenkmann Michelle , Klein Kerstin , Karouzakis Emmanuel , Rehrauer Hubert , Bratus Anna , Kolling Christoph , Armaka Maria , Filer Andrew , Michel Beat A. , Gay Renate E. , Buckley Christopher D. , Kollias George , Gay Steffen , Ospelt Caroline
Published: March 2017

A number of human diseases, such as arthritis and atherosclerosis, include characteristic pathology in specific anatomical locations. Here we show transcriptomic differences in synovial fibroblasts from different joint locations and that HOX gene signatures reflect the joint-specific origins of mouse and human synovial fibroblasts and synovial tissues. Alongside DNA methylation and histone modifications, bromodomain and extra-terminal reader proteins regulate joint-specific HOX gene expression. Anatomical transcriptional diversity translates into joint-specific synovial fibroblast phenotypes with distinct adhesive, proliferative, chemotactic and matrix-degrading characteristics and differential responsiveness to TNF, creating a unique microenvironment in each joint. These findings indicate that local stroma might control positional disease patterns not only in arthritis but in any disease with a prominent stromal component.
Single-mode dispersive waves and soliton microcomb dynamics
Authors: Yi Xu , Yang Qi-Fan , Zhang Xueyue , Yang Ki Youl , Li Xinbai , Vahala Kerry
Published: March 2017

Dissipative Kerr solitons are self-sustaining optical wavepackets in resonators. They use the Kerr nonlinearity to both compensate dispersion and offset optical loss. Besides providing insights into nonlinear resonator physics, they can be applied in frequency metrology, precision clocks, and spectroscopy. Like other optical solitons, the dissipative Kerr soliton can radiate power as a dispersive wave through a process that is the optical analogue of Cherenkov radiation. Dispersive waves typically consist of an ensemble of optical modes. Here, a limiting case is studied in which the dispersive wave is concentrated into a single cavity mode. In this limit, its interaction with the soliton induces hysteresis behaviour in the soliton’s spectral and temporal properties. Also, an operating point of enhanced repetition-rate stability occurs through balance of dispersive-wave recoil and Raman-induced soliton-self-frequency shift. The single-mode dispersive wave can therefore provide quiet states of soliton comb operation useful in many applications.
Observation of the reversed Cherenkov radiation
Authors: Duan Zhaoyun , Tang Xianfeng , Wang Zhanliang , Zhang Yabin , Chen Xiaodong , Chen Min , Gong Yubin
Published: March 2017

Reversed Cherenkov radiation is the exotic electromagnetic radiation that is emitted in the opposite direction of moving charged particles in a left-handed material. Reversed Cherenkov radiation has not previously been observed, mainly due to the absence of both suitable all-metal left-handed materials for beam transport and suitable couplers for extracting the reversed Cherenkov radiation signal. In this paper, we develop an all-metal metamaterial, consisting of a square waveguide loaded with complementary electric split ring resonators. We demonstrate that this metamaterial exhibits a left-handed behaviour, and we directly observe the Cherenkov radiation emitted predominantly near the opposite direction to the movement of a single sheet electron beam bunch in the experiment. These observations confirm the reversed behaviour of Cherenkov radiation. The reversed Cherenkov radiation has many possible applications, such as novel vacuum electronic devices, particle detectors, accelerators and new types of plasmonic couplers.
Dramatic response of metaplastic breast cancer to chemo-immunotherapy
Authors: Adams Sylvia
Published: March 2017

Frequent overexpression of programmed death-ligand 1 has recently been demonstrated in metaplastic breast cancer, which is a rare breast cancer subtype with limited treatment options. This report describes the clinical course of a patient with metastatic metaplastic breast cancer who had a remarkable response to anti-programmed death-1 therapy with pembrolizumab in combination with nab-paclitaxel. Tissue correlates are presented including tumor-infiltrating lymphocytes and high-programmed death-ligand 1 expression in the tumor.
Fast learning in free-foraging bumble bees is negatively correlated with lifetime resource collection
Authors: Evans Lisa J. , Smith Karen E. , Raine Nigel E.
Published: March 2017

Despite widespread interest in the potential adaptive value of individual differences in cognition, few studies have attempted to address the question of how variation in learning and memory impacts their performance in natural environments. Using a novel split-colony experimental design we evaluated visual learning performance of foraging naïve bumble bees (Bombus terrestris) in an ecologically relevant associative learning task under controlled laboratory conditions, before monitoring the lifetime foraging performance of the same individual bees in the field. We found appreciable variation among the 85 workers tested in both their learning and foraging performance, which was not predicted by colony membership. However, rather than finding that foragers benefited from enhanced learning performance, we found that fast and slow learners collected food at comparable rates and completed a similar number of foraging bouts per day in the field. Furthermore, bees with better learning abilities foraged for fewer days; suggesting a cost of enhanced learning performance in the wild. As a result, slower learning individuals collected more resources for their colony over the course of their foraging career. These results demonstrate that enhanced cognitive traits are not necessarily beneficial to the foraging performance of individuals or colonies in all environments.
Altering the coffee-ring effect by adding a surfactant-like viscous polymer solution
Authors: Seo Changdeok , Jang Daeho , Chae Jongjin , Shin Sehyun
Published: March 2017

A uniform deposition of the suspended particles in an evaporating droplet is necessary in many research fields. Such deposition is difficult to achieve, because the coffee-ring effect dominates the internal flow in a droplet. The present study adopts a biocompatible, surfactant-like polymer (Polyethylene glycol, PEG) to break the coffee-ring effect and obtain a relatively uniform deposition of the microparticles with yielding multi-ring pattern over a droplet area. Movements of the suspended particles in evaporating droplets and deposition patterns of them on a glass substrate were analyzed with microscopic images and video files. The PEG in the droplets successfully altered the coffee-ring effect because of the surface tension variation, which induced a centripetal Marangoni flow. Balancing these two phenomena apparently generated the Marangoni vortex. For PEG solution droplets, the pinning–depinning process during evaporation was periodically repeated and multiple rings were regularly formed. In conclusion, adding a surfactant-like viscous polymer in a droplet could provide a uniform coating of suspended particles, such as cells and various biomaterials, which would be essentially required for droplet assays of biomedical applications.
Proteomic analysis reveals a role of melatonin in promoting cucumber seed germination under high salinity by regulating energy production
Authors: Zhang Na , Zhang Hai-Jun , Sun Qian-Qian , Cao Yun-Yun , Li Xingsheng , Zhao Bing , Wu Ping , Guo Yang-Dong
Published: March 2017

Seed germination is a critical and complex process in the plant life cycle. Although previous studies have found that melatonin can promote seed germination under salt stress, the involvement of melatonin in the regulation of proteomic changes remains poorly understood. In this study, a total of 157 proteins were significantly influenced (ratio ≥ 2 or ≤ −2) by melatonin during seed germination under salt stress using a label-free quantitative technique. Our GO analysis revealed that several pathways were obviously regulated by melatonin, including ribosome biosynthesis, lipid metabolism, carbohydrate metabolism, and storage protein degradation. Not only stress-tolerant proteins but also proteins that produce ATP as part of glycolysis, the citric acid cycle, and the glyoxylate cycle were upregulated by melatonin. Overall, this study provides new evidence that melatonin alleviates the inhibitory effects of NaCl stress on seed germination by promoting energy production. This study is the first to provide insights at the proteomic level into the molecular mechanism of melatonin in response to salt stress in cucumber seeds. This may be helpful to further understand the role of melatonin in cucumber seed germination under stress conditions.
Spin-dependent thermoelectric effects in Fe-C6 doped monolayer MoS2
Authors: Zhu Lin , Zou Fei , Gao Guoying , Yao Kailun
Published: March 2017

By using the non-equilibrium Green’s function with density functional theory, we have studied the thermal spin transport properties of Fe-C6 cluster doped monolayer MoS2. The results show that the device has a perfect Seebeck effect under temperature difference without gate voltage or bias voltage. Moreover, we also find the thermal colossal magnetoresistance effect, which is as high as 107%. The competition between spin up electrons and spin down holes of the parallel spin configuration leads to peculiar behavior of colossal magnetoresistance and thermo-current, which is essential for the design of thermal transistors. These results are useful in future MoS2-based multifunctional spin caloritronic devices.
Selective intracellular vaporisation of antibody-conjugated phase-change nano-droplets in vitro
Authors: Ishijima A. , Minamihata K. , Yamaguchi S. , Yamahira S. , Ichikawa R. , Kobayashi E. , Iijima M. , Shibasaki Y. , Azuma T. , Nagamune T. , Sakuma I.
Published: March 2017

While chemotherapy is a major mode of cancer therapeutics, its efficacy is limited by systemic toxicities and drug resistance. Recent advances in nanomedicine provide the opportunity to reduce systemic toxicities. However, drug resistance remains a major challenge in cancer treatment research. Here we developed a nanomedicine composed of a phase-change nano-droplet (PCND) and an anti-cancer antibody (9E5), proposing the concept of ultrasound cancer therapy with intracellular vaporisation. PCND is a liquid perfluorocarbon nanoparticle with a liquid–gas phase that is transformable upon exposure to ultrasound. 9E5 is a monoclonal antibody targeting epiregulin (EREG). We found that 9E5-conjugated PCNDs are selectively internalised into targeted cancer cells and kill the cells dynamically by ultrasound-induced intracellular vaporisation. In vitro experiments show that 9E5-conjugated PCND targets 97.8% of high-EREG-expressing cancer cells and kills 57% of those targeted upon exposure to ultrasound. Furthermore, direct observation of the intracellular vaporisation process revealed the significant morphological alterations of cells and the release of intracellular contents.
A complex intragenic rearrangement of ERCC8 in Chinese siblings with Cockayne syndrome
Authors: Xie Hua , Li Xiaoyan , Peng Jiping , Chen Qian , Gao ZhiJie , Song Xiaozhen , Li WeiYu , Xiao Jianqiu , Li Caihua , Zhang Ting , Gusella James F. , Zhong Jianmin , Chen Xiaoli
Published: March 2017

Cockayne syndrome is an autosomal recessive disorder principally characterized by postnatal growth failure and progressive neurological dysfunction, due primarily to mutations in ERCC6 and ERCC8. Here, we report our diagnostic experience for two patients in a Chinese family suspected on clinical grounds to have Cockayne syndrome. Using multiple molecular techniques, including whole exome sequencing, array comparative genomic hybridization and quantitative polymerase chain reaction, we identified compound heterozygosity for a maternal splicing variant (chr5:60195556, NM_000082:c.618-2A > G) and a paternal complex deletion/inversion/deletion rearrangement removing exon 4 of ERCC8, confirming the suspected pathogenesis in these two subjects. Microhomology (TAA and AGCT) at the breakpoints indicated that microhomology-mediated FoSTeS events were involved in this complex ERCC8 rearrangement. This diagnostic experience illustrates the value of high-throughput genomic technologies combined with detailed phenotypic assessment in clinical genetic diagnosis.
Universality of Schmidt decomposition and particle identity
Authors: Sciara Stefania , Lo Franco Rosario , Compagno Giuseppe
Published: March 2017

Schmidt decomposition is a widely employed tool of quantum theory which plays a key role for distinguishable particles in scenarios such as entanglement characterization, theory of measurement and state purification. Yet, its formulation for identical particles remains controversial, jeopardizing its application to analyze general many-body quantum systems. Here we prove, using a newly developed approach, a universal Schmidt decomposition which allows faithful quantification of the physical entanglement due to the identity of particles. We find that it is affected by single-particle measurement localization and state overlap. We study paradigmatic two-particle systems where identical qubits and qutrits are located in the same place or in separated places. For the case of two qutrits in the same place, we show that their entanglement behavior, whose physical interpretation is given, differs from that obtained before by different methods. Our results are generalizable to multiparticle systems and open the way for further developments in quantum information processing exploiting particle identity as a resource.
A Novel Inhibitor IDPP Interferes with Entry and Egress of HCV by Targeting Glycoprotein E1 in a Genotype-Specific Manner
Authors: Lee Myungeun , Yang Jaewon , Jo Eunji , Lee Ji-Young , Kim Hee-Young , Bartenschlager Ralf , Shin Eui-Cheol , Bae Yong-Soo , Windisch Marc P.
Published: March 2017

Despite recent advances in curing chronic hepatitis C (CHC), the high economic burden to therapy, viral drug resistance, difficult to treat hepatitis C virus (HCV) genotypes and patient groups are still of concern. To address this unmet medical needs, we devised strategies to identify novel viral interventions through target-free high-throughput screening of small molecules utilizing a phenotypic-based HCV infection assay. Thereby, a very potent (EC50 46 ± 26 pM) iminodipyridinopyrimidine (IDPP) drug candidate was selected, and confirmed in primary human hepatocytes (EC50 0.5 nM). IDPP mainly targets a post-attachment step of HCV without affecting endosomal acidification, prevents the secretion of infectious particles and viral cell-to-cell spread. The putative molecular target of IDPP is glycoprotein E1, as revealed by selection for viral drug resistance (Gly-257-Arg). IDPP was synergistic in combination with FDA-approved HCV drugs and inhibited pre-existing resistant HCV strains induced by today’s therapies. Interestingly, IDPP exclusively inhibited HCV genotype 2. However, we identified the genotype-specificity determining region in E1 and generated HCV genotype 1 susceptible to IDPP by changing one amino acid in E1 (Gln-257-Gly). Together, our results indicate an opportunity to provide an alternative treatment option for CHC and will shed light on the poorly understood function of HCV glycoprotein E1.
Characterization of Thin Film Materials using SCAN meta-GGA, an Accurate Nonempirical Density Functional
Authors: Buda I. G. , Lane C. , Barbiellini B. , Ruzsinszky A. , Sun J. , Bansil A.
Published: March 2017

We discuss self-consistently obtained ground-state electronic properties of monolayers of graphene and a number of ’beyond graphene’ compounds, including films of transition-metal dichalcogenides (TMDs), using the recently proposed strongly constrained and appropriately normed (SCAN) meta-generalized gradient approximation (meta-GGA) to the density functional theory. The SCAN meta-GGA results are compared with those based on the local density approximation (LDA) as well as the generalized gradient approximation (GGA). As expected, the GGA yields expanded lattices and softened bonds in relation to the LDA, but the SCAN meta-GGA systematically improves the agreement with experiment. Our study suggests the efficacy of the SCAN functional for accurate modeling of electronic structures of layered materials in high-throughput calculations more generally.
CLARITY reveals dynamics of ovarian follicular architecture and vasculature in three-dimensions
Authors: Feng Yi , Cui Peng , Lu Xiaowei , Hsueh Brian , Möller Billig Fredrik , Zarnescu Yanez Livia , Tomer Raju , Boerboom Derek , Carmeliet Peter , Deisseroth Karl , Hsueh Aaron J. W.
Published: March 2017

Optimal distribution of heterogeneous organelles and cell types within an organ is essential for physiological processes. Unique for the ovary, hormonally regulated folliculogenesis, ovulation, luteal formation/regression and associated vasculature changes lead to tissue remodeling during each reproductive cycle. Using the CLARITY approach and marker immunostaining, we identified individual follicles and corpora lutea in intact ovaries. Monitoring lifetime changes in follicle populations showed age-dependent decreases in total follicles and percentages of advanced follicles. Follicle development from primordial to preovulatory stage was characterized by 3 × 105-fold increases in volume, decreases in roundness, and decreased clustering of same stage follicles. Construction of follicle-vasculature relationship maps indicated age- and gonadotropin-dependent increases in vasculature and branching surrounding follicles. Heterozygous mutant mice with deletion of hypoxia-response element in the vascular endothelial growth factor A (VEGFA) promoter showed defective ovarian vasculature and decreased ovulatory responses. Unilateral intrabursal injection of axitinib, an inhibitor of VEGF receptors, retarded neo-angiogenesis that was associated with defective ovulation in treated ovaries. Our approach uncovers unique features of ovarian architecture and essential roles of vasculature in organizing follicles to allow future studies on normal and diseased human ovaries. Similar approaches could also reveal roles of neo-angiogenesis during embryonic development and tumorigenesis.
Odd Chain Fatty Acids; New Insights of the Relationship Between the Gut Microbiota, Dietary Intake, Biosynthesis and Glucose Intolerance
Authors: Jenkins Benjamin J. , Seyssel Kevin , Chiu Sally , Pan Pin-Ho , Lin Shih-Yi , Stanley Elizabeth , Ament Zsuzsanna , West James A. , Summerhill Keith , Griffin Julian L. , Vetter Walter , Autio Kaija J. , Hiltunen Kalervo , Hazebrouck Stéphane , Stepankova Renata , Chen Chun-Jung , Alligier Maud , Laville Martine , Moore Mary , Kraft Guillaume , Cherrington Alan , King Sarah , Krauss Ronald M. , de Schryver Evelyn , Van Veldhoven Paul P. , Ronis Martin , Koulman Albert
Published: March 2017

Recent findings have shown an inverse association between circulating C15:0/C17:0 fatty acids with disease risk, therefore, their origin needs to be determined to understanding their role in these pathologies. Through combinations of both animal and human intervention studies, we comprehensively investigated all possible contributions of these fatty acids from the gut-microbiota, the diet, and novel endogenous biosynthesis. Investigations included an intestinal germ-free study and a C15:0/C17:0 diet dose response study. Endogenous production was assessed through: a stearic acid infusion, phytol supplementation, and a Hacl1−/− mouse model. Two human dietary intervention studies were used to translate the results. Finally, a study comparing baseline C15:0/C17:0 with the prognosis of glucose intolerance. We found that circulating C15:0/C17:0 levels were not influenced by the gut-microbiota. The dose response study showed C15:0 had a linear response, however C17:0 was not directly correlated. The phytol supplementation only decreased C17:0. Stearic acid infusion only increased C17:0. Hacl1−/− only decreased C17:0. The glucose intolerance study showed only C17:0 correlated with prognosis. To summarise, circulating C15:0 and C17:0 are independently derived; C15:0 correlates directly with dietary intake, while C17:0 is substantially biosynthesized, therefore, they are not homologous in the aetiology of metabolic disease. Our findings emphasize the importance of the biosynthesis of C17:0 and recognizing its link with metabolic disease.
A conformational change within the WAVE2 complex regulates its degradation following cellular activation
Authors: Joseph Noah , Biber Guy , Fried Sophia , Reicher Barak , Levy Omer , Sabag Batel , Noy Elad , Barda-Saad Mira
Published: March 2017

WASp family Verprolin-homologous protein-2 (WAVE2), a member of the Wiskott-Aldrich syndrome protein (WASp) family of actin nucleation promoting factors, is a central regulator of actin cytoskeleton polymerization and dynamics. Multiple signaling pathways operate via WAVE2 to promote the actin-nucleating activity of the actin-related protein 2/3 (Arp2/3) complex. WAVE2 exists as a part of a pentameric protein complex known as the WAVE regulatory complex (WRC), which is unstable in the absence of its individual proteins. While the involvement of WAVE2 in actin polymerization has been well documented, its negative regulation mechanism is poorly characterized to date. Here, we demonstrate that WAVE2 undergoes ubiquitylation in a T-cell activation dependent manner, followed by proteasomal degradation. The WAVE2 ubiquitylation site was mapped to lysine 45, located at the N-terminus where WAVE2 binds to the WRC. Using Förster resonance energy transfer (FRET), we reveal that the autoinhibitory conformation of the WRC maintains the stability of WAVE2 in resting cells; the release of autoinhibition following T-cell activation facilitates the exposure of WAVE2 to ubiquitylation, leading to its degradation. The dynamic conformational structures of WAVE2 during cellular activation dictate its degradation.
miR-18a counteracts AKT and ERK activation to inhibit the proliferation of pancreatic progenitor cells
Authors: Li Xuyan , Zhang Zhenwu , Li Yunchao , Zhao Yicheng , Zhai Wenjun , Yang Lin , Kong Delin , Wu Chunyan , Chen Zhenbao , Teng Chun-Bo
Published: March 2017

Activation of endogenous stem/progenitor cells to repair injured tissues is an ideal option for disease treatment. However, adult pancreatic progenitor cells remain in a quiescent state in vivo. Thus, it is difficult to stimulate proliferation and differentiation in these progenitor cells, and the cause remains elusive. miR-17-92 cluster miRNAs are highly conserved in mammals and are expressed in multiple tissue stem/progenitor cells, but their role in pancreatic progenitor cells are less well known. In the present study, we demonstrate that miR-18a, but not the other members of the miR-17-92 gene cluster, inhibits the proliferation of pancreatic progenitor cells in vitro and ex vivo. miR-18a inhibits proliferation of adult pancreatic progenitor cells through arresting the cell cycle at G1 stage, indicating that miR-18a plays a role in keeping the adult pancreatic progenitor cells in quiescence. miR-18a inhibits pancreatic progenitor proliferation by targeting the gene expressions of connective tissue growth factor (CTGF), neural precursor cell expressed, developmentally down-regulated 9 (Nedd9), and cyclin dependent kinase 19 (CDK19), as well as by suppressing activation of the proliferation-related signaling pathways phosphatidylinositol 3-kinase–protein kinase B (PI3K/AKT) and extracellular signal-regulated kinase (ERK).