bluuebunny/crossref_metadata_2025 huggingface dataset:
Dissecting a heterotic gene through GradedPool-Seq mapping informs a rice-improvement strategy
Authors: Wang Changsheng , Tang Shican , Zhan Qilin , Hou Qingqing , Zhao Yan , Zhao Qiang , Feng Qi , Zhou Congcong , Lyu Danfeng , Cui Lingling , Li Yan , Miao Jiashun , Zhu Chuanrang , Lu Yiqi , Wang Yongchun , Wang Ziqun , Zhu Jingjie , Shangguan Yingying , Gong Junyi , Yang Shihua , Wang Wuqi , Zhang Jianfu , Xie Huaan , Huang Xuehui , Han Bin
Published: July 2019

Hybrid rice breeding for exploiting hybrid vigor, heterosis, has greatly increased grain yield. However, the heterosis-related genes associated with rice grain production remain largely unknown, partly because comprehensive mapping of heterosis-related traits is still labor-intensive and time-consuming. Here, we present a quantitative trait locus (QTL) mapping method, GradedPool-Seq, for rapidly mapping QTLs by whole-genome sequencing of graded-pool samples from F2 progeny via bulked-segregant analysis. We implement this method and map-based cloning to dissect the heterotic QTL GW3p6 from the female line. We then generate the near isogenic line NIL-FH676::GW3p6 by introgressing the GW3p6 allele from the female line Guangzhan63-4S into the male inbred line Fuhui676. The NIL-FH676::GW3p6 exhibits grain yield highly increased compared to Fuhui676. This study demonstrates that it may be possible to achieve a high level of grain production in inbred rice lines without the need to construct hybrids.
Author Correction: Arylmethylamino steroids as antiparasitic agents
Authors: Krieg Reimar , Jortzik Esther , Goetz Alice-Anne , Blandin Stéphanie , Wittlin Sergio , Elhabiri Mourad , Rahbari Mahsa , Nuryyeva Selbi , Voigt Kerstin , Dahse Hans-Martin , Brakhage Axel , Beckmann Svenja , Quack Thomas , Grevelding Christoph G. , Pinkerton Anthony B. , Schönecker Bruno , Burrows Jeremy , Davioud-Charvet Elisabeth , Rahlfs Stefan , Becker Katja
Published: July 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Global analysis reveals climatic controls on the oxygen isotope composition of cave drip water
Authors: Baker Andy , Hartmann Andreas , Duan Wuhui , Hankin Stuart , Comas-Bru Laia , Cuthbert Mark O. , Treble Pauline C. , Banner Jay , Genty Dominique , Baldini Lisa M. , Bartolomé Miguel , Moreno Ana , Pérez-Mejías Carlos , Werner Martin
Published: July 2019

The oxygen isotope composition of speleothems is a widely used proxy for past climate change. Robust use of this proxy depends on understanding the relationship between precipitation and cave drip water δ18O. Here, we present the first global analysis, based on data from 163 drip sites, from 39 caves on five continents, showing that drip water δ18O is most similar to the amount-weighted precipitation δ18O where mean annual temperature (MAT) is < 10 °C. By contrast, for seasonal climates with MAT > 10 °C and < 16 °C, drip water δ18O records the recharge-weighted δ18O. This implies that the δ18O of speleothems (formed in near isotopic equilibrium) are most likely to directly reflect meteoric precipitation in cool climates only. In warmer and drier environments, speleothems will have a seasonal bias toward the precipitation δ18O of recharge periods and, in some cases, the extent of evaporative fractionation of stored karst water.
A practical guide for mutational signature analysis in hematological malignancies
Authors: Maura Francesco , Degasperi Andrea , Nadeu Ferran , Leongamornlert Daniel , Davies Helen , Moore Luiza , Royo Romina , Ziccheddu Bachisio , Puente Xose S. , Avet-Loiseau Herve , Campbell Peter J. , Nik-Zainal Serena , Campo Elias , Munshi Nikhil , Bolli Niccolò
Published: July 2019

Analysis of mutational signatures is becoming routine in cancer genomics, with implications for pathogenesis, classification, prognosis, and even treatment decisions. However, the field lacks a consensus on analysis and result interpretation. Using whole-genome sequencing of multiple myeloma (MM), chronic lymphocytic leukemia (CLL) and acute myeloid leukemia, we compare the performance of public signature analysis tools. We describe caveats and pitfalls of de novo signature extraction and fitting approaches, reporting on common inaccuracies: erroneous signature assignment, identification of localized hyper-mutational processes, overcalling of signatures. We provide reproducible solutions to solve these issues and use orthogonal approaches to validate our results. We show how a comprehensive mutational signature analysis may provide relevant biological insights, reporting evidence of c-AID activity among unmutated CLL cases or the absence of BRCA1/BRCA2-mediated homologous recombination deficiency in a MM cohort. Finally, we propose a general analysis framework to ensure production of accurate and reproducible mutational signature data.
Comparing socioeconomic inequalities between early neonatal mortality and facility delivery: Cross-sectional data from 72 low- and middle-income countries
Authors: Lohela Terhi J. , Nesbitt Robin C. , Pekkanen Juha , Gabrysch Sabine
Published: July 2019

Facility delivery should reduce early neonatal mortality. We used the Slope Index of Inequality and logistic regression to quantify absolute and relative socioeconomic inequalities in early neonatal mortality (0 to 6 days) and facility delivery among 679,818 live births from 72 countries with Demographic and Health Surveys. The inequalities in early neonatal mortality were compared with inequalities in postneonatal infant mortality (28 days to 1 year), which is not related to childbirth. Newborns of the richest mothers had a small survival advantage over the poorest in unadjusted analyses (−2.9 deaths/1,000; OR 0.86) and the most educated had a small survival advantage over the least educated (−3.9 deaths/1,000; OR 0.77), while inequalities in postneonatal infant mortality were more than double that in absolute terms. The proportion of births in health facilities was an absolute 43% higher among the richest and 37% higher among the most educated compared to the poorest and least educated mothers. A higher proportion of facility delivery in the sampling cluster (e.g. village) was only associated with a small  decrease in early neonatal mortality. In conclusion, while socioeconomically advantaged mothers had much higher use of a health facility at birth, this did not appear to convey a comparable survival advantage.
Etv2 transcriptionally regulates Yes1 and promotes cell proliferation during embryogenesis
Authors: Singh Bhairab N. , Gong Wuming , Das Satyabrata , Theisen Joshua W. M. , Sierra-Pagan Javier E. , Yannopoulos Demetris , Skie Erik , Shah Pruthvi , Garry Mary G. , Garry Daniel J.
Published: July 2019

Etv2, an Ets-transcription factor, governs the specification of the earliest hemato-endothelial progenitors during embryogenesis. While the transcriptional networks during hemato-endothelial development have been well described, the mechanistic details are incompletely defined. In the present study, we described a new role for Etv2 as a regulator of cellular proliferation via Yes1 in mesodermal lineages. Analysis of an Etv2-ChIPseq dataset revealed significant enrichment of Etv2 peaks in the upstream regions of cell cycle regulatory genes relative to non-cell cycle genes. Our bulk-RNAseq analysis using the doxycycline-inducible Etv2 ES/EB system showed increased levels of cell cycle genes including E2f4 and Ccne1 as early as 6 h following Etv2 induction. Further, EdU-incorporation studies demonstrated that the induction of Etv2 resulted in a ~2.5-fold increase in cellular proliferation, supporting a proliferative role for Etv2 during differentiation. Next, we identified Yes1 as the top-ranked candidate that was expressed in Etv2-EYFP+ cells at E7.75 and E8.25 using single cell RNA-seq analysis. Doxycycline-mediated induction of Etv2 led to an increase in Yes1 transcripts in a dose-dependent fashion. In contrast, the level of Yes1 was reduced in Etv2 null embryoid bodies. Using bioinformatics algorithms, biochemical, and molecular biology techniques, we show that Etv2 binds to the promoter region of Yes1 and functions as a direct upstream transcriptional regulator of Yes1 during embryogenesis. These studies enhance our understanding of the mechanisms whereby Etv2 governs mesodermal fate decisions early during embryogenesis.
Comparative transcriptome analysis of cultivated and wild seeds of Salvia hispanica (chia)
Authors: Peláez Pablo , Orona-Tamayo Domancar , Montes-Hernández Salvador , Valverde María Elena , Paredes-López Octavio , Cibrián-Jaramillo Angélica
Published: July 2019

Salvia hispanica (chia) constituted an important crop for pre-Columbian civilizations and is considered a superfood for its rich content of essential fatty acids and proteins. In this study, we performed the first comprehensive comparative transcriptome analysis between seeds from cultivated varieties and from accessions collected from native wild populations in Mexico. From the 69,873 annotated transcripts assembled de novo, enriched functional categories and pathways revealed that the lipid metabolism was one of the most activated processes. Expression changes were detected among wild and cultivated groups and among growth conditions in transcripts responsible for triacylglycerol and fatty acid synthesis and degradation. We also quantified storage protein fractions that revealed variation concerning nutraceutical proteins such as albumin and glutelin. Genetic diversity estimated with 23,641 single nucleotide polymorphisms (SNPs) revealed that most of the variation remains in the wild populations, and that a wild-type cultivated variety is genetically related to wild accessions. Additionally, we reported 202 simple sequence repeat (SSRs) markers useful for population genetic studies. Overall, we provided transcript variation that can be used for breeding programs to further develop chia varieties with enhanced nutraceutical traits and tools to explore the genetic diversity and history of this rediscovered plant.
Immune heterogeneity of head and tail pancreatic lymph nodes in non-obese diabetic mice
Authors: Li Xiaofei , Bean Asher , Uehara Mayuko , Banouni Naima , Ben Nasr Moufida , Kasinath Vivek , Jiang Liwei , Fiorina Paolo , Abdi Reza
Published: July 2019

The pancreatic lymph node is critical to the pathogenesis of autoimmune diabetes, as it constitutes the initial site for the priming of autoreactive T cells. In this study, we compared the histopathology of the head pancreatic lymph node (HPLN) to the tail pancreatic lymph node (TPLN) in NOD mice. HPLNs and TPLNs were harvested from 4 week-, 8 week-, and 12 week-old NOD mice, and their microvasculature, extracellular matrix, and immune cell subsets were characterized. The percentages of B cells and antigen-presenting cells (APCs) were much higher in the HPLN, as compared to the TPLN. Notably, the HPLNs of 12 week-old mice were characterized by greater expansion of high endothelial venules (HEVs) and lymphatic vessels in comparison to the TPLNs. Finally, we observed a higher density of extracellular matrix (ECM) fibers surrounding the lymphatic vasculature in the HPLNs than in the TPLNs. These data for the first time demonstrate that the HPLN possesses a different immune microanatomy and organization from the TPLN. These novel observations unveil a major phenotypic difference between two types of LNs from the same organ and may highlight an independent fundamental role played by each PLN during the establishment of T1D.
Metabolic cost adaptations during training with a soft exosuit assisting the hip joint
Authors: Panizzolo Fausto A. , Freisinger Gregory M. , Karavas Nikos , Eckert-Erdheim Asa M. , Siviy Christopher , Long Andrew , Zifchock Rebecca A. , LaFiandra Michael E. , Walsh Conor J.
Published: July 2019

Different adaptation rates have been reported in studies involving ankle exoskeletons designed to reduce the metabolic cost of their wearers. This work aimed to investigate energetic adaptations occurring over multiple training sessions, while walking with a soft exosuit assisting the hip joint. The participants attended five training sessions within 20 days. They walked carrying a load of 20.4 kg for 20 minutes with the exosuit powered and five minutes with the exosuit unpowered. Percentage change in net metabolic cost between the powered and unpowered conditions improved across sessions from −6.2 ± 3.9% (session one) to −10.3 ± 4.7% (session five), indicating a significant effect associated with training. The percentage change at session three (−10.5 ± 4.5%) was similar to the percentage change at session five, indicating that two 20-minute sessions may be sufficient for users to fully adapt and maximize the metabolic benefit provided by the exoskeleton. Retention was also tested measuring the metabolic reduction five months after the last training session. The percent change in metabolic cost during this session (−10.1 ± 3.2%) was similar to the last training session, indicating that the adaptations resulting in reduced metabolic cost are preserved. These outcomes are relevant when evaluating exoskeletons’ performance on naïve users, with a specific focus on hip extension assistance.
Absorbing phase transition in the coupled dynamics of node and link states in random networks
Authors: Saeedian Meghdad , San Miguel Maxi , Toral Raul
Published: July 2019

We present a stochastic dynamics model of coupled evolution for the binary states of nodes and links in a complex network. In the context of opinion formation node states represent two possible opinions and link states represent positive or negative relationships. Dynamics proceeds via node and link state update towards pairwise satisfactory relations in which nodes in the same state are connected by positive links or nodes in different states are connected by negative links. By a mean-field rate equations analysis and Monte Carlo simulations in random networks we find an absorbing phase transition from a dynamically active phase to an absorbing phase. The transition occurs for a critical value of the relative time scale for node and link state updates. In the absorbing phase the order parameter, measuring global order, approaches exponentially the final frozen configuration. Finite-size effects are such that in the absorbing phase the final configuration is reached in a characteristic time that scales logarithmically with system size, while in the active phase, finite-size fluctuations take the system to a frozen configuration in a characteristic time that grows exponentially with system size. There is also a class of finite-size topological transition associated with group splitting in the network of these final frozen configurations.
Direct and indirect effects of urban gardening on aboveground and belowground diversity influencing soil multifunctionality
Authors: Tresch Simon , Frey David , Bayon Renée-Claire Le , Mäder Paul , Stehle Bernhard , Fliessbach Andreas , Moretti Marco
Published: July 2019

Urban gardens are popular green spaces that have the potential to provide essential ecosystem services, support human well-being, and at the same time foster biodiversity in cities. We investigated the impact of gardening activities on five soil functions and the relationship between plant (600 spp.) and soil fauna (earthworms: 18 spp., springtails: 39 spp.) in 85 urban gardens (170 sites) across the city of Zurich (Switzerland). Our results suggest that high plant diversity in gardens had a positive effect on soil fauna and soil multifunctionality, and that garden management intensity decreased plant diversity. Indices of biological activity in soil, such as organic and microbial carbon and bacterial abundance, showed a direct positive effect on soil multifunctionality. Soil moisture and disturbance, driven by watering and tilling, were the driving forces structuring plant and soil fauna communities. Plant indicator values proved useful to assess soil fauna community structure, even in anthropogenic plant assemblages. We conclude that to enhance soil functions, gardeners should increase plant diversity, and lower management intensity. Soil protective management practices, such as applying compost, mulch or avoiding soil tilling, should be included in urban green space planning to improve urban biodiversity and nature’s contribution to people.
Direct Observation of Long-Chain Branches in a Low-Density Polyethylene
Authors: Shinohara Ken-ichi , Yanagisawa Masahiro , Makida Yuu
Published: July 2019

Low-density polyethylene (LDPE) has short-chain branch (SCB) and long-chain branch (LCB). In particular, the influence of the structure of LCBs on polymer properties is remarkable; however, it has been difficult to precisely analyze LCB structures. In this study, we measured the chain length of LCBs and the distance between branch points of LDPE by atomic force microscopy. Consequently, three LCBs were confirmed in a main chain of 162 nm, and their length were measured as 10, 31, and 18 nm. The positions of the LCBs were 33, 70, and 78 nm from the main-chain end.
Sensitivity of planktic foraminiferal test bulk density to ocean acidification
Authors: Iwasaki S. , Kimoto K. , Sasaki O. , Kano H. , Uchida H.
Published: July 2019

The anthropogenic CO2accumulating in the ocean is lowering seawater carbonate ion concentration and may reduce calcification rates of marine calcareous organisms. Several proxies based on test weights of planktic foraminifera have been used to evaluate the impact of ocean acidification on these organisms. Unfortunately, because of the absence of a method to evaluate the bulk density of a test, the impact of seawater carbonate chemistry on test calcification is still not fully understood. In this study, we measured bulk densities of livingGlobigerina bulloides(planktic foraminifera) tests with an X-ray micro-computed tomography (XMCT) scanner and compared them with ambient seawater characteristics. Results demonstrated that test bulk densities were controlled by ambient seawater carbonate ion concentrations and that changes of test bulk densities were accompanied by changes in micron to submicron scale porosity of internal ultrastructure. These results suggest that alteration of the bulk density of foraminiferal tests due to acidification of ambient seawater can be directly observed by XMCT scanning. A useful metric of calcification intensity would therefore be physical measurements of test densities with XMCT.
Ollivier-Ricci Curvature-Based Method to Community Detection in Complex Networks
Authors: Sia Jayson , Jonckheere Edmond , Bogdan Paul
Published: July 2019

Identification of community structures in complex network is of crucial importance for understanding the system’s function, organization, robustness and security. Here, we present a novel Ollivier-Ricci curvature (ORC) inspired approach to community identification in complex networks. We demonstrate that the intrinsic geometric underpinning of the ORC offers a natural approach to discover inherent community structures within a network based on interaction among entities. We develop an ORC-based community identification algorithm based on the idea of sequential removal of negatively curved edges symptomatic of high interactions (e.g., traffic, attraction). To illustrate and compare the performance with other community identification methods, we examine the ORC-based algorithm with stochastic block model artificial networks and real-world examples ranging from social to drug-drug interaction networks. The ORC-based algorithm is able to identify communities with either better or comparable performance accuracy and to discover finer hierarchical structures of the network. This opens new geometric avenues for analysis of complex networks dynamics.
No Effect of Ego Depletion on Risk Taking
Authors: Koppel Lina , Andersson David , Västfjäll Daniel , Tinghög Gustav
Published: July 2019

We investigated the effect of ego depletion on risk taking. Specifically, we conducted three studies (total n = 1,716) to test the prediction that ego depletion results in decisions that are more strongly in line with prospect theory, i.e., that ego depletion reduces risk taking for gains, increases risk taking for losses, and increases loss aversion. Ego depletion was induced using two of the most common manipulations from previous literature: the letter ‘e’ task (Studies 1 and 3) and the Stroop task (Study 2). Risk taking was measured using a series of standard, incentivized economic decision-making tasks assessing risk preferences in the gain domain, risk preferences in the loss domain, and loss aversion. None of the studies revealed a significant effect of ego depletion on risk taking. Our findings cast further doubts about the ability of ego-depletion manipulations to affect actual behavior in experimental settings.
Harnessing Synthetic Ecology for commercial algae production
Authors: Reynolds Sam A. , Davey Matthew P. , Aldridge David C.
Published: July 2019

Synthetic Ecology is a novel concept describing the design of de novo ecological communities for a designated purpose. This study is a proof of concept for harnessing Synthetic Ecology in expanding the scale of commercially relevant micro algae (Chlorella vulgaris) cultivation using stable Synthetic Ecologies in open environments as opposed to vulnerable monocultures. We focused on whether the grazing activity of zebra mussels (Dreissena polymorpha) would result in a consistent, and commercially favourable, dominance of Chlorella in cultures that were also inoculated with a competing and potentially invasive cyanobacteria (Synechocystis sp. PCC6803). The key result of this study was that in axenic mixed species co-cultures, zebra mussels had a significantly greater negative effect on Synechocystis cell numbers than Chlorella (P < 0.0001). The zebra mussels’ putative preference for Synechocystis over Chlorella suggests they could be used to maintain the dominance of Chlorella in outdoor cultivation systems prone to contamination by invasive cyanobacteria.
Neural crest stem cells from human epidermis of aged donors maintain their multipotency in vitro and in vivo
Authors: Moghadasi Boroujeni Samaneh , Koontz Alison , Tseropoulos Georgios , Kerosuo Laura , Mehrotra Pihu , Bajpai Vivek K. , Selvam Surya Rajan , Lei Pedro , Bronner Marianne E. , Andreadis Stelios T.
Published: July 2019

Neural crest (NC) cells are multipotent stem cells that arise from the embryonic ectoderm, delaminate from the neural tube in early vertebrate development and migrate throughout the developing embryo, where they differentiate into various cell lineages. Here we show that multipotent and functional NC cells can be derived by induction with a growth factor cocktail containing FGF2 and IGF1 from cultures of human inter-follicular keratinocytes (KC) isolated from elderly donors. Adult NC cells exhibited longer doubling times as compared to neonatal NC cells, but showed limited signs of cellular senescence despite the advanced age of the donors and exhibited significantly younger epigenetic age as compared to KC. They also maintained their multipotency, as evidenced by their ability to differentiate into all NC-specific lineages including neurons, Schwann cells, melanocytes, and smooth muscle cells (SMC). Notably, upon implantation into chick embryos, adult NC cells behaved similar to their embryonic counterparts, migrated along stereotypical pathways and contributed to multiple NC derivatives in ovo. These results suggest that KC-derived NC cells may provide an easily accessible, autologous source of stem cells that can be used for treatment of neurodegenerative diseases or as a model system for studying disease pathophysiology and drug development.
Physical activity participation and the risk of chronic diseases among South Asian adults: a systematic review and meta-analysis
Authors: Paudel Susan , Owen Alice J. , Owusu-Addo Ebenezer , Smith Ben J.
Published: July 2019

South Asia specific reviews on the role of physical activity (PA) domains on chronic disease prevention are lacking. This study aimed to systematically review published literature to identify the association between PA domains and chronic diseases and to provide summary estimates of the strength of association. Nine electronic databases were searched using the predefined inclusion criteria which included population (South Asian adults 40 years or older), exposure (PA or sedentary behaviour) and outcome (type 2 diabetes mellitus, breast cancer, colorectal cancer, coronary heart disease, stroke, vascular disease and musculoskeletal diseases and their markers). A random-effects meta-analysis was carried out for cardiometabolic outcomes whereas narrative synthesis was completed for other outcome variables. Inactive or less active South Asian adults were at 31% higher risk of being hypertensive. Likewise, the risk of cardiometabolic outcomes was 1.34 times higher among inactive adults. Household PA was found to have a protective effect  on breast cancer risk. Total and leisure time PA had a protective effect on osteoporosis among males and females respectively. Contemporary studies with a longitudinal design, representative samples, valid and reliable assessment of different domains are needed to establish the role of PA in chronic disease prevention in the region.
Computer-based tools provide new insight into the key factors that cause physiological disorders of pistachio rootstocks cultured in vitro
Authors: Nezami-Alanagh Esmaeil , Garoosi Ghasem-Ali , Landín Mariana , Gallego Pedro Pablo
Published: July 2019

During the in vitro culture of plants some physiological disorders caused major problems that have been associated with culture media composition. The objective of this study was to better understand the abnormal physiological response of two pistachio rootstocks to changes in culture media ingredients. On this purpose, two computer-based tools were employed: design of experiment (DOE) and neurofuzzy logic. DOE was employed to generate a five-dimensional IV-design spaces allowing to reduce the number of treatments from 6,250 to 61. The second one, an artificial intelligence (AI) tool, neurofuzzy logic, was used to understand the cause-effect relationships between the factors studied (25) and seven physiological disorders including shoot-tip necrosis (STN), leaf necrosis (LN), leaf color (LC), basal callus (BC) formation, shoot fasciation (SF), hyperhydricity and epinasty, typically described during pistachio in vitro culture. Four out of the seven disorders were successfully modeled, being significantly affected by a limited number of factors. STN and BC were significantly affected by the concentration of EDTA−. However, while a low concentration of EDTA− reduces the STN, promotes BC. LN and LC were strongly alleviated by high amounts of thiamine-HCl. Undoubtedly, the results demonstrate the importance of recording and using data related to physiological disorders along with growth parameters when developing suitable culture media for plant tissues. The computer-based tools have been useful to: i) well sample experimental design; ii) reduce the final number of treatments and the experimental work; iii) identify the key factors affecting each disorder; iv) get insight about the causes that promote the appearance of physiological disorders. Our findings demonstrate that the recently AI designed POM media, although not optimal, is the most suitable (favouring growth and limiting physiological abnormalities) media for in vitro culture of pistachio compared to those media, currently used.
Delayed recruiting of TPD52 to lipid droplets – evidence for a “second wave” of lipid droplet-associated proteins that respond to altered lipid storage induced by Brefeldin A treatment
Authors: Chen Yuyan , Frost Sarah , Khushi Matloob , Cantrill Laurence C. , Yu Hong , Arthur Jonathan W. , Bright Robert K. , Groblewski Guy E. , Byrne Jennifer A.
Published: July 2019

Tumor protein D52 (TPD52) is amplified and overexpressed in breast and prostate cancers which are frequently characterised by dysregulated lipid storage and metabolism. TPD52 expression increases lipid storage in mouse 3T3 fibroblasts, and co-distributes with the Golgi marker GM130 and lipid droplets (LDs). We examined the effects of Brefeldin A (BFA), a fungal metabolite known to disrupt the Golgi structure, in TPD52-expressing 3T3 cells, and in human AU565 and HMC-1-8 breast cancer cells that endogenously express TPD52. Five-hour BFA treatment reduced median LD numbers, but increased LD sizes. TPD52 knockdown decreased both LD sizes and numbers, and blunted BFA’s effects on LD numbers. Following BFA treatment for 1–3 hours, TPD52 co-localised with the trans-Golgi network protein syntaxin 6, but after 5 hours BFA treatment, TPD52 showed increased co-localisation with LDs, which was disrupted by microtubule depolymerising agent nocodazole. BFA treatment also increased perilipin (PLIN) family protein PLIN3 but reduced PLIN2 detection at LDs in TPD52-expressing 3T3 cells, with PLIN3 recruitment to LDs preceding that of TPD52. An N-terminally deleted HA-TPD52 mutant (residues 40–184) almost exclusively targeted to LDs in both vehicle and BFA treated cells. In summary, delayed recruitment of TPD52 to LDs suggests that TPD52 participates in a temporal hierarchy of LD-associated proteins that responds to altered LD packaging requirements induced by BFA treatment.
Underestimated Risks of Infantile Infectious Disease from the Caregiver’s Typical Handling Practices of Infant Formula
Authors: Cho Tae Jin , Hwang Ji Yeon , Kim Hye Won , Kim Yong Ki , Il Kwon Jeong , Kim Young Jun , Lee Kwang Won , Kim Sun Ae , Rhee Min Suk
Published: July 2019

The impact on infant caregiver as a reservoir of pathogens has not been exploited with perspective to powdered infant formula (PIF). Here we reveal novel route of pathogen transfer through hand-spoon-PIF unexpectedly occurred by even typical practices of caregivers, handling of PIF and storage of feeding-spoon in PIF container. Hand-spoon-PIF contamination route was simulated to analyze the transfer and subsequent survival of pathogens. Major pathogens associated with infantile fatal diseases (Cronobacter sakazakii, Salmonella enterica, Staphylococcus aureus) were readily transmitted to PIF from skin (3−6 log CFU/hand) via spoons following long-term survival of transferred pathogens (3 weeks; use-by date of PIF) as the excessive level of infectious dose, highlighting direct onset of diseases. Low bacterial load on skin (ca. 1 log CFU/hand) could prevent cross-contamination of PIF, however, at least 72 h survival of transferred pathogen on spoons demonstrated the probability on re-contamination of PIF. To our knowledge, this is the first study to investigate the cross-contamination of utensils in contact with powdered-foods. Bacterial load on hands is the key determinant of pathogen transfer and the extent of risk are species-dependent. These evidential results redefine risk of caregivers’ practices and facilitate incorporation of cross-contamination into risk-assessment as underestimated route of infection.
A Peptoid Delivers CoQ-derivative to Plant Mitochondria via Endocytosis
Authors: Asfaw Kinfemichael Geressu , Liu Qiong , Maisch Jan , Münch Stephan W. , Wehl Ilona , Bräse Stefan , Bogeski Ivan , Schepers Ute , Nick Peter
Published: July 2019

Controlled delivery of molecules interfering specifically with target activities in a cell of interest can be a powerful tool for experimental manipulation, because it can be administered at a defined time point and does not require genetic transformation, which in some systems is difficult and time consuming. Peptides as versatile tools that can be tailored for binding numerous binding partners, are of special interest. However, their passage through membranes, their intracellular targeting, and their sensitivity to proteases is limiting. The use of peptoids, where cationic amino-acid side chains are linked to nitrogen (rather than to carbon) of the peptide bond, can circumvent these limitations, because they are not cleavable by proteases. In the current work, we provide a proof-of-concept that such Trojan Peptoids, the plant PeptoQ, can be used to target a functional cargo (i.e. a rhodamine-labelled peptoid and a coenzyme Q10 derivative) into mitochondria of tobacco BY-2 cells as experimental model. We show that the uptake is specific for mitochondria, rapid, dose-dependent, and requires clathrin-mediated endocytosis, as well as actin filaments, while microtubules seem to be dispensable. Viability of the treated cells is not affected, and they show better survival under salt stress, a condition that perturbs oxidative homeostasis in mitochondria. In congruence with improved homeostasis, we observe that the salt induced accumulation of superoxide is mitigated and even inverted by pretreatment with PeptoQ. Using double labelling with appropriate fluorescent markers, we show that targeting of this Trojan Peptoid to the mitochondria is not based on a passage through the plasma membrane (as thought hitherto), but on import via endocytotic vesicles and subsequent accumulation in the mitochondrial intermembrane space, from where it can enter the matrix, e.g. when the permeability of the inner membrane is increased under salt stress.
Macroangiopathy is a positive predictive factor for response to immunotherapy
Authors: Deike-Hofmann Katerina , Gutzweiler Lukas , Reuter Julia , Paech Daniel , Hassel Jessica C. , Sedlaczek Oliver , Radbruch Alexander , Schlemmer Heinz-Peter , Bäumer Philipp
Published: July 2019

Immunotherapies demand for predictive biomarkers to avoid unnecessary adverse effects and costs. Analytic morphomics is the technique to use body composition measures as imaging biomarkers for underlying pathophysiology to predict prognosis or outcome to therapy. We investigated different body composition measures to predict response to immunotherapy. This IRB approved retrospective analysis encompassed 147 patients with ipilimumab therapy. Degree of macroangiopathy was quantified with the newly defined total plaque index (TPI), i.e. the body height corrected sum of the soft and hard plaque volume of the infrarenal aorta on portalvenous CT scans. Furthermore, mean psoas density (MPD), different adipose tissue parameters as well as degree of cerebral microangiopathy were extracted from the imaging data. Subsequent multivariate Cox regression analysis encompassed TPI, MPD, serum LDH, S100B, age, gender, number of immunotherapy cycles as well as extent of distant metastases. TPI and MPD correlated positively with PFS in multivariate analysis (p = 0.03 and p = 0.001, respectively). Furthermore, single visceral organ and/or soft tissue involvement significantly decreased progression risk (p = 0.01), whereas increased S100B level showed a trend towards PFS shortening (p = 0.05). In conclusion, degree of macroangiopathy and sarcopenia were independent predictors for outcome to immunotherapy and of equivalent significance compared to other clinical biomarkers.
Characterization of Plasmodium infections among inhabitants of rural areas in Gabon
Authors: Woldearegai Tamirat Gebru , Lalremruata Albert , Nguyen The Trong , Gmeiner Markus , Veletzky Luzia , Tazemda-Kuitsouc Gildas B. , Matsiegui Pierre Blaise , Mordmüller Benjamin , Held Jana
Published: July 2019

Plasmodium infections in endemic areas are often asymptomatic, can be caused by different species and contribute significantly to transmission. We performed a cross-sectional study in February/March 2016 including 840 individuals ≥ 1 year living in rural Gabon (Ngounié and Moyen-Ogooué). Plasmodium parasitemia was measured by high-sensitive, real-time quantitative PCR. In a randomly chosen subset of P. falciparum infections, gametocyte carriage and prevalence of chloroquine-resistant genotypes were analysed. 618/834 (74%) individuals were positive for Plasmodium 18S-rRNA gene amplification, of these 553 (66.3%) carried P. falciparum, 193 (23%) P. malariae, 74 (8.9%) P. ovale curtisi and 38 (4.6%) P.ovale wallikeri. Non-falciparum infections mostly presented as mixed infections. P. malariae monoinfected individuals were significantly older (median age: 60 years) than coinfected (20 years) or P. falciparum monoinfected individuals (23 years). P. falciparum gametocyte carriage was confirmed in 109/223 (48.9%) individuals, prevalence of chloroquine-resistant genotypes was high (298/336, 89%), including four infections with a new SVMNK genotype. In rural Gabon, Plasmodium infections with all endemic species are frequent, emphasizing that malaria control efforts shall cover asymptomatic infections also including non-falciparum infections when aiming for eradication.
Scaling in the space-time of the Internet
Authors: Papp István , Varga Levente , Afifi Mounir , Gere István , Néda Zoltán
Published: July 2019

The Internet on the router level, is a complex network embedded in a geographical space. We provide experimental evidences suggesting that the average travel time for a message, with fixed length, increases roughly as the square root of the geographical distance. To understand this scaling law and other measurable topological properties of the Internet as a graph, we introduce and study a simple network model. The model is based on a few realistic socio-economic facts/assumptions and qualitatively reproduces the experimentally observed stylized facts.
The Bivalent Rewarding and Aversive properties of Δ9-tetrahydrocannabinol are Mediated Through Dissociable Opioid Receptor Substrates and Neuronal Modulation Mechanisms in Distinct Striatal Sub-Regions
Authors: Norris Christopher , Szkudlarek Hanna J. , Pereira Brian , Rushlow Walter , Laviolette Steven R.
Published: July 2019

The primary psychoactive compound in cannabis, Δ9-tetrahydrocannabinol (THC), is capable of producing bivalent rewarding and aversive affective states through interactions with the mesolimbic system. However, the precise mechanisms underlying the dissociable effects of THC are not currently understood. In the present study, we identify anatomically dissociable effects of THC within the rat nucleus accumbens (NAc), using an integrative combination of behavioral pharmacology and in vivo neuronal electrophysiology. We report that the rewarding vs. aversive stimulus properties of THC are both anatomically and pharmacologically dissociable within distinct anterior vs. posterior sub-regions of the NAc. While the rewarding effects of THC were dependent upon local μ-opioid receptor signaling, the aversive effects of THC were processed via a κ-opioid receptor substrate. Behaviorally, THC in the posterior NASh induced deficits in social reward and cognition whereas THC in the anterior NAc, potentiated opioid-related reward salience. In vivo neuronal recordings demonstrated that THC decreased medium spiny neuron (MSN) activity in the anterior NAc and increased the power of gamma (γ) oscillations. In contrast, THC increased MSN activity states in the posterior NASh and decreased γ-oscillation power. These findings reveal critical new insights into the bi-directional neuronal and pharmacological mechanisms controlling the dissociable effects of THC in mesolimbic-mediated affective processing.
The relationship between biomechanics of pharyngoesophageal segment and tracheoesophageal phonation
Authors: Zhang Teng , Cook Ian , Szczęśniak Michał , Maclean Julia , Wu Peter , Nguyen Duong Duy , Madill Catherine
Published: July 2019

This study examined the relationship between biomechanical features of the pharyngoesophageal (PE) segment, acoustic characteristics of tracheoesophageal (TE) phonation, and patients’ satisfaction with TE phonation. Fifteen patients using TE phonation after total laryngectomy completed the Voice Symptom Scale (VoiSS) and underwent acoustic voice analysis for cepstral peak prominence (CPP) and relative intensity. High resolution manometry (HRM) combined with videofluoroscopy was used to evaluate PE segment pressure and calculate the pressure gradient (ΔP), which was the pressure difference between the upper oesophagus and a point two centimetres above the vibrating PE segment. The upper oesophageal sphincter (UOS) minimal diameters were measured by Endolumenal Functional Lumen Imaging Probe (EndoFLIP). HRM detected rapid pressure changes at the level of the 4th – 6th cervical vertebra. CPP, relative intensity, and ΔP were significant predictors of satisfactory TE phonation. ΔP was a significant predictor of CPP and intensity. Minimal UOS diameter was a significant predictor of relative intensity of TE phonation. In two patients with unsuccessful TE phonation, endoscopic dilatation subsequently restored TE phonation. These findings suggest that sufficient ΔP and large UOS diameter are required for satisfactory TE phonation. Endoscopic dilatation increasing UOS diameter may provide a new approach to treat unsuccessful TE phonation.
Flexible organic synaptic device based on poly (methyl methacrylate):CdSe/CdZnS quantum-dot nanocomposites
Authors: Koo Bon Min , Sung Sihyun , Wu Chaoxing , Song Jin-Won , Kim Tae Whan
Published: July 2019

A synaptic device that functionally mimics a biological synapse is a promising candidate for use as an electronic element in a neuromorphic system. In this study, flexible electronic synaptic devices based on poly (methyl methacrylate) (PMMA):CdSe/CdZnS core-shell quantum-dot (QD) nanocomposites are demonstrated. The current-voltage characteristics for the synaptic devices under consecutive voltage sweeps show clockwise hysteresis, which is a critical feature of an artificial synaptic device. The effect of the CdSe/CdZnS QD concentration on the device performance is studied. The flexible electronic synaptic devices under bending show the similar and stable electrical performances. The memory retention measurements show that the e-synapse exhibits long-term potentiation and depression. The carrier transport mechanisms are analyzed, and thermionic emission and space-charge-limited-current conduction are found to be dominant.
Adenosine A2A receptor stimulation restores cell functions and differentiation in Niemann-Pick type C-like oligodendrocytes
Authors: De Nuccio Chiara , Bernardo Antonietta , Ferrante Antonella , Pepponi Rita , Martire Alberto , Falchi Mario , Visentin Sergio , Popoli Patrizia , Minghetti Luisa
Published: July 2019

Niemann Pick type C (NPC) disease is a rare neurovisceral disorder. Mutations in npc1 gene induce an intracellular accumulation of unesterified cholesterol in the endosomal/lysosomal system causing cell death. We recently showed that stimulation of adenosine A2A receptors (A2AR) restores cholesterol accumulation in late endosomes/lysosomes in human NPC fibroblasts and neural cell lines transiently transfected with NPC1 siRNA, suggesting that these receptors might be targeted to contrast the disease. Since NPC1 disease is characterized by dysmyelination and maturational arrest of oligodendrocyte progenitors (OPs), in this study, we investigated whether A2AR stimulation could promote oligodendrocyte differentiation and myelin formation, thus overcoming these important neurological abnormalities. We developed a NPC1 pharmacological model, in which primary cultures of OPs are exposed to a cholesterol transport inhibitor to induce a NPC1-like phenotype characterized by several typical features such as (i) cholesterol accumulation, (ii) altered mitochondrial morphology and membrane potential, (iii) defect of autophagy and (iv) maturation arrest. The A2AR agonist CGS21680 normalized all NPC1-like features. The ability of CGS21680 of rescuing OP from maturational arrest and promoting their differentiation to mature OL, suggests that A2AR stimulation might be exploited to correct dysmyelination in NPC1, further supporting their therapeutic potential in the disease.
Impact of floral characters, pollen limitation, and pollinator visitation on pollination success in different populations of Caragana korshinskii Kom
Authors: Chen Min , Zhao Xue-yong
Published: July 2019

Caragana korshinskii Kom. has a significant function in desert-grassland revegetation in arid regions. Plant reproduction in arid regions can be restricted due to inadequate pollen receipt and reduced pollen transfer. An assessment of pollination success as a result of pollen limitation and pollinator visitation in various C. korshinskii populations is presently lacking. We thus tested three different treatments (pollen addition, control, and procedural control) to elucidate how pollen limitation affects seed numbers per flower in C. korshinskii. We also determined the effect of pollinator visit frequency on seeds per flower. Our results demonstrated that there was a higher proportion of open flowers and mature fruits in the managed population than in the natural population. Pollen addition significantly increased seed number per flower, and pollen limitation was determined to be a significant limiting factor in seed production. Furthermore, Apis mellifera was determined to be the principal pollinator, and pollinator visitation frequency was significantly correlated with open flower number. Our findings also demonstrated that pollinator visitation rate and seed production were positively correlated. Management and pollinator visitation could affect seed production, which may explain the higher seeds per flower in the managed population compared with the natural population.
Improved surface passivation and reduced parasitic absorption in PEDOT:PSS/c-Si heterojunction solar cells through the admixture of sorbitol
Authors: Halbich Marc-Uwe , Zielke Dimitri , Gogolin Ralf , Sauer-Stieglitz Rüdiger , Lövenich Wilfried , Schmidt Jan
Published: July 2019

We examine the impact of sorbitol admixture to the hole-conduction polymer PEDOT:PSS [poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate)] on the characteristics of PEDOT:PSS/crystalline silicon heterojunction solar cells. We fabricate solar cells where the PEDOT:PSS layer is deposited as a hole-collecting contact at the cell rear, whereas the electron-collecting front is conventionally processed by means of phosphorus diffusion. Surprisingly, we observe that the admixture of the infrared-transparent sorbitol not only improves the short-circuit density of the solar cells due to the reduction of the infrared parasitic absorption, but also improves the passivation quality of PEDOT:PSS on silicon and hence the open-circuit voltage of the solar cells. The series resistance is not influenced by the admixture of sorbitol up to 4.0 wt.% sorbitol admixture in the PEDOT:PSS dispersion, but shows a pronounced increase for larger sorbitol contents. The optimal sorbitol content concerning efficiency is hence 4.0 wt.%, leading to an energy conversion efficiency of 20.4% at one sun, which is more than 1% absolute higher compared to the efficiency of the reference cells without sorbitol.
Actin stabilizing compounds show specific biological effects due to their binding mode
Authors: Wang Shuaijun , Crevenna Alvaro H. , Ugur Ilke , Marion Antoine , Antes Iris , Kazmaier Uli , Hoyer Maria , Lamb Don C. , Gegenfurtner Florian , Kliesmete Zane , Ziegenhain Christoph , Enard Wolfgang , Vollmar Angelika , Zahler Stefan
Published: July 2019

Actin binding compounds are widely used tools in cell biology. We compare the biological and biochemical effects of miuraenamide A and jasplakinolide, a structurally related prototypic actin stabilizer. Though both compounds have similar effects on cytoskeletal morphology and proliferation, they affect migration and transcription in a distinctive manner, as shown by a transcriptome approach in endothelial cells. In vitro, miuraenamide A acts as an actin nucleating, F-actin polymerizing and stabilizing compound, just like described for jasplakinolide. However, in contrast to jasplakinolide, miuraenamide A competes with cofilin, but not gelsolin or Arp2/3 for binding to F-actin. We propose a binding mode of miuraenamide A, explaining both its similarities and its differences to jasplakinolide. Molecular dynamics simulations suggest that the bromophenol group of miurenamide A interacts with residues Tyr133, Tyr143, and Phe352 of actin. This shifts the D-loop of the neighboring actin, creating tighter packing of the monomers, and occluding the binding site of cofilin. Since relatively small changes in the molecular structure give rise to this selectivity, actin binding compounds surprisingly are promising scaffolds for creating actin binders with specific functionality instead of just “stabilizers”.