bluuebunny/crossref_metadata_2025 huggingface dataset:
Antioxidant and angiotensin I-converting enzyme inhibitory activities of Xuanwei ham before and after cooking and
in vitro
simulated gastrointestinal digestion
Authors: Wang Le , Li Xiang , Li Yingnan , Liu Wenying , Jia Xiaoyun , Qiao Xiaoling , Qu Chao , Cheng Xiaoyu , Wang Shouwei
Published: July 2018

Xuanwei ham is especially rich in a large amount of peptides and free amino acids under the action of protein degradation. Some of these peptides can potentially exert bioactivities of interest for human health. Traditionally, Xuanwei ham should undergo Chinese household cooking treatments before eating. However, it has not been known how its bioactivity changes after cooking and gastrointestinal digestion. Herein, Xuanwei ham is analysed before and after cooking, as well as gastrointestinal digestion being simulated so as to evaluate and compare its effect on antioxidant and angiotensin I-converting enzyme (ACE) inhibitory activities. The antioxidant activity is analysed using five different methods, and results demonstrate that cooking has some negative effects on antioxidative capacity when determined using different antioxidant methods except for a significant increment in 1,1'-diphenyl-2-picrylhydrazyl radical-scavenging activity, while ACE inhibitory activity increases significantly after cooking compared with control samples. After gastrointestinal digestion of samples, there is a significant increment of the antioxidant and ACE inhibitory activities in comparison with control and cooked samples. Particularly, after gastrointestinal digestion, free thiols content and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical-cation-scavenging activity of Xuanwei ham, respectively, increase about twice and fourfold, while ACE inhibitory activity increases about twice compared to cooked samples, reaching the value of 83.73%. Therefore, through cooking the antioxidant activity and ACE inhibitory activity of Xuanwei ham are not completely lost and a part of them is still maintained, while gastrointestinal digestion produces a significant enhancement in both bioactivities, highlighting a greater potential for a beneficial physiological effect on human health after eating it.
Structure of [60]fullerene with a mobile lithium cation inside
Authors: Aoyagi Shinobu , Miwa Kazuhira , Ueno Hiroshi , Okada Hiroshi , Matsuo Yutaka , Kokubo Ken
Published: July 2018

The structure of crystalline [60]fullerene with a lithium cation inside (Li
+
@C
60
) was determined by synchrotron radiation X-ray diffraction measurements to understand the electrostatic and thermal properties of the encapsulated Li
+
cation. Although the C
60
cages show severe orientation disorder in [Li
+
@C
60
](TFPB
−
)·C
4
H
10
O and [Li
+
@C
60
](TFSI
−
)·CH
2
Cl
2
, the Li
+
cations are rather ordered at specific positions by electrostatic interactions with coordinated anions outside the C
60
cage. The Li
+
@C
60
molecules in [Li
+
@C
60
](ClO
4
−
) with a rock-salt-type cubic structure are fully disordered with almost uniform spherical shell charge densities even at 100 K by octahedral coordination of ClO
4
−
tetrahedra and show no orientation ordering, unlike [Li
+
@C
60
](PF
6
−
) and pristine C
60
. Single-bonded (Li
+
@C
60
−
)
2
dimers in [Li
+
@C
60
−
](NiOEP)⋅CH
2
Cl
2
are thermally stable even at 400 K and form Li
+
–C bonds which are shorter than Li
+
–C bonds in [Li
+
@C
60
](PF
6
−
) and suppress the rotational motion of the Li
+
cations.
A porphyrin-centred fullerene tetramer containing an N@C
60
substituent
Authors: Macpherson Harry , Cornes Stuart , Zhou Shen , Porfyrakis Kyriakos
Published: July 2018

An N@C
60
-containing C
60
tetramer was synthesized by quadruple 1,3-dipolar cycloaddition (Prato) reaction. This molecule demonstrates the N@C
60
qubit's ability to form covalently linked arrays. Furthermore, it provides a promising scaffold with which to measure multiple qubit–qubit interactions; which must be well characterized for a functioning quantum information processing architecture.
High-density polyethylene crystals with double melting peaks induced by ultra-high-molecular-weight polyethylene fibre
Authors: Miao Weijun , Zhu Hao , Duan Tianchen , Chen Hongbing , Wu Feng , Jiang Libin , Wang Zongbao
Published: July 2018

High-density polyethylene (HDPE)/ultra-high-molecular-weight polyethylene (UHMWPE) fibre composites were prepared via solution crystallization to investigate the components of epitaxial crystal growth on a highly oriented substrate. Scanning electron microscopy morphologies of HDPE crystals on UHMWPE fibres revealed that the edge-on ribbon pattern crystals that were formed initially on UHMWPE fibres converted afterwards to a sheet shape as crystallization progressed. Wide-angle X-ray diffraction confirmed that the polymer chain oriented along the fibre axis and the orthorhombic crystal form of HDPE remained unchanged in HDPE/UHMWPE fibre composite systems. The thermal behaviour of the fibre composites measured by differential scanning calorimetry showed double melting peaks, the nature of which, as disclosed by partial melting experiments, is ascribed to bilayer components existing in the induced crystals: the inner layer is composed of more regularly folded chain crystals induced by UHMWPE fibres, and the outer layer formed on the inner one with a thinner and lower ordered crystal structure.
The underwater resonant airbag: a new wave energy converter
Authors: Farley Francis J. M.
Published: July 2018

The time-domain simulation follows the heaving of the conical float in waves and calculates the bag shape, ballast motion, adiabatic air pressure and the flow through the turbine. There are two independent oscillators, the float with its resonance and the bag/ballast with its resonance. The coupling of the two oscillators gives rise to a wide band response with two peaks in the capture width each reaching the theoretical
λ
/2
π
. In this new wave energy converter, apart from the turbine, there are no mechanical moving parts, no joints nor pistons, no end stops nor sliding seals, no flaps nor one-way valves. The expected life of the airtight flexible bag remains to be determined, but potential manufacturers are optimistic.
Effects of anisotropy and regime of diffusion on the measurement of lattice diffusion coefficient of hydrogen in metals
Authors: Raina Arun , Sime Nathan
Published: July 2018

The lattice diffusion coefficient of hydrogen in metals is commonly measured by permeation tests. Such tests assume isotropic diffusivity with a set-up which measures permeation flux only along one direction. The measured values of the lattice diffusion coefficient are strongly influenced by the trapping of hydrogen at microstructural defects. These factors lead to highly inaccurate determination of the lattice diffusion coefficient, more so in an anisotropic medium. In this work, we present a three-dimensional (3D) diffusion equation in non-dimensional form for an anisotropic medium with source and sink terms which account for detrapping and trapping of hydrogen. The concentration of hydrogen at lattice and trap sites is assumed to be in a local equilibrium. An initial boundary value problem of the permeation test is formulated and the governing partial differential equation is implemented in a 3D finite-element code. The influence of anisotropic diffusivity on the measurement of lattice diffusion coefficient is shown by numerical simulations. Asymptotic analysis of the governing equation reveals that the lattice diffusion coefficient can only be measured in certain regimes when performing permeation tests at varying temperatures. The nonlinear behaviour of Arrhenius plots of diffusion coefficient versus inverse of temperature due to trapping is analytically and numerically predicted.
Timing of perineuronal net development in the zebra finch song control system correlates with developmental song learning
Authors: Cornez Gilles , Jonckers Elisabeth , ter Haar Sita M. , Van der Linden Annemie , Cornil Charlotte A. , Balthazart Jacques
Published: July 2018

The appearance of perineuronal nets (PNNs) represents one of the mechanisms that contribute to the closing of sensitive periods for neural plasticity. This relationship has mostly been studied in the ocular dominance model in rodents. Previous studies also indicated that PNN might control neural plasticity in the song control system of songbirds. To further elucidate this relationship, we quantified PNN expression and their localization around parvalbumin interneurons at key time-points during ontogeny in both male and female zebra finches, and correlated these data with the well-described development of song in this species. We also extended these analyses to the auditory system. The development of PNN during ontogeny correlated with song crystallization although the timing of PNN appearance in the four main telencephalic song control nuclei slightly varied between nuclei in agreement with the established role these nuclei play during song learning. Our data also indicate that very few PNN develop in the secondary auditory forebrain areas even in adult birds, which may allow constant adaptation to a changing acoustic environment by allowing synaptic reorganization during adulthood.
gpps: An ILP-based approach for inferring cancer progression with mutation losses from single cell data
Authors: Ciccolella Simone , Gomez Mauricio Soto , Patterson Murray , Vedova Gianluca Della , Hajirasouliha Iman , Bonizzoni Paola
Published: July 2018

Motivation

In recent years, the well-known Infinite Sites Assumption (ISA) has been a fundamental feature of computational methods devised for reconstructing tumor phylogenies and inferring cancer progression where mutations are accumulated through histories. However, some recent studies leveraging Single Cell Sequencing (SCS) techniques have shown evidence of mutation losses in several tumor samples [19], making the inference problem harder.

Results

We present a new tool,gpps, that reconstructs a tumor phylogeny from single cell data, allowing each mutation to be lost at most a fixed number of times.

Availability

The General Parsimony Phylogeny from Single cell (gpps) tool is open source and available athttps://github.com/AlgoLab/gppf.
Classification of electrophysiological and morphological types in mouse visual cortex
Authors: Gouwens Nathan W. , Sorensen Staci A. , Berg Jim , Lee Changkyu , Jarsky Tim , Ting Jonathan , Sunkin Susan M. , Feng David , Anastassiou Costas , Barkan Eliza , Bickley Kris , Blesie Nicole , Braun Thomas , Brouner Krissy , Budzillo Agata , Caldejon Shiella , Casper Tamara , Casteli Dan , Chong Peter , Crichton Kirsten , Cuhaciyan Christine , Tanya L. Daigle , Dalley Rachel , Dee Nick , Desta Tsega , Dingman Samuel , Doperalski Alyse , Dotson Nadezhda , Egdorf Tom , Fisher Michael , de Frates Rebecca A. , Garren Emma , Garwood Marissa , Gary Amanda , Gaudreault Nathalie , Godfrey Keith , Gorham Melissa , Gu Hong , Habel Caroline , Hadley Kristen , Harrington James , Harris Julie , Henry Alex , Hill DiJon , Josephsen Sam , Kebede Sara , Kim Lisa , Kroll Matthew , Lee Brian , Lemon Tracy , Liu Xiaoxiao , Long Brian , Mann Rusty , McGraw Medea , Mihalas Stefan , Mukora Alice , Murphy Gabe J. , Ng Lindsay , Ngo Kiet , Nguyen Thuc Nghi , Nicovich Philip R. , Oldre Aaron , Park Daniel , Parry Sheana , Perkins Jed , Potekhina Lydia , Reid David , Robertson Miranda , Sandman David , Schroedter Martin , Slaughterbeck Cliff , Soler-Llavina Gilberto , Sulc Josef , Szafer Aaron , Tasic Bosiljka , Taskin Naz , Teeter Corinne , Thatra Nivretta , Tung Herman , Wakeman Wayne , Williams Grace , Young Rob , Zhou Zhi , Farrell Colin , Peng Hanchuan , Hawrylycz Michael J. , Lein Ed , Ng Lydia , Arkhipov Anton , Bernard Amy , Phillips John W. , Zeng Hongkui , Koch Christof
Published: July 2018

Understanding the diversity of cell types in the brain has been an enduring challenge and requires detailed characterization of individual neurons in multiple dimensions. To profile morpho-electric properties of mammalian neurons systematically, we established a single cell characterization pipeline using standardized patch clamp recordings in brain slices and biocytin-based neuronal reconstructions. We built a publicly-accessible online database, the Allen Cell Types Database, to display these data sets. Intrinsic physiological and morphological properties were measured from over 1,800 neurons from the adult laboratory mouse visual cortex. Quantitative features were used to classify neurons into distinct types using unsupervised methods. We establish a taxonomy of morphologically- and electrophysiologically-defined cell types for this region of cortex with 17 e-types and 35 m-types, as well as an initial correspondence with previously-defined transcriptomic cell types using the same transgenic mouse lines.
A web-based, branching logic questionnaire for the automated classification of migraine
Authors: Kaiser Eric A. , Igdalova Aleksandra , Aguirre Geoffrey K. , Cucchiara Brett
Published: July 2018

Objective

To identify migraineurs and headache-free individuals with an online questionnaire and automated analysis algorithm.

Methods

We created a branching-logic, web-based questionnaire—the Penn Online Evaluation of Migraine (POEM)—to obtain standardized headache history from a previously studied cohort. Responses were analyzed with an automated algorithm to assign subjects to one of several categories based on ICHD-3 (beta) criteria. Following a pre-registered protocol, this result was compared to prior diagnostic classification by a neurologist following a direct interview.

Results

Of 118 subjects contacted, 90 (76%) completed the questionnaire; of these 31 were headache-free, 29 migraine without aura (MwoA), and 30 migraine with aura (MwA). Mean age was 41 ± 6 years and 76% were female. There were no significant demographic differences between groups. The median time to complete the questionnaire was 2.5 minutes. Sensitivity of the POEM tool was 42%, 59%, and 70%, and specificity was 100%, 84%, and 94% for headache-free, MwoA, and MwA, respectively. Sensitivity and specificity of the POEM tool for migraine overall (with or without aura), was 83% and 90%, respectively.

Conclusions

The POEM web-based questionnaire, and associated analysis routines, identifies headache-free and migraine subjects with good specificity. It may be useful for classifying subjects for large-scale research studies.

Trial Registration:https://osf.io/sq9ef
Impact of 10-valent pneumococcal conjugate vaccine on invasive pneumococcal disease and nasopharyngeal carriage in Kenya
Authors: Hammitt Laura L. , Etyang Anthony O. , Morpeth Susan C. , Ojal John , Mutuku Alex , Mturi Neema , Moisi Jennifer C. , Adetifa Ifedayo M. , Karani Angela , Akech Donald O. , Otiende Mark , Bwanaali Tahreni , Wafula Jackline , Mataza Christine , Mumbo Edward , Tabu Collins , Knoll Maria Deloria , Bauni Evasius , Marsh Kevin , Williams Thomas N. , Kamau Tatu , Sharif Shahnaaz K. , Levine Orin S. , Scott J. Anthony G.
Published: July 2018

Background

10-valent pneumococcal conjugate vaccine (PCV10), delivered at 6, 10 and 14 weeks of age, was introduced in Kenya in January 2011, accompanied by a catch-up campaign in Kilifi County for children <5 years. Coverage with ≥2 PCV10 doses in children 2-11 months was 80% in 2011 and 84% in 2016; coverage with ≥1 dose in children 12-59 months was 66% and 87%, respectively.

Methods

Clinical and microbiological surveillance for invasive pneumococcal disease (IPD) among admissions of all ages at Kilifi County Hospital was linked to the Kilifi Health and Demographic Surveillance System from 1999-2016. We calculated the incidence rate ratio (IRR) comparing the pre-vaccine and post-vaccine eras, adjusted for confounding, and reported percent reduction in IPD as 1-IRR. Annual cross-sectional surveys of nasopharyngeal carriage were conducted from 2009-2016.

Findings

Surveillance identified 667 IPD cases in 3,211,403 person-years of observation. IPD incidence in children <5 years fell sharply in 2011 following PCV10 introduction, and remained low (PCV10-type IPD: 60·8 vs 3·2/100,000 [92% reduction; 95%CI: 78, 97]; overall IPD: 81·6 vs 15·3/100,000 [68% reduction; 95%CI: 40, 83]; 1999-2010 vs 2012-2016). PCV10-type IPD also declined significantly in unvaccinated age groups (<2 months, 5-14 years, ≥15 years), with estimated reductions of 100%, 74%, and 81%, respectively. There was no significant change in the incidence of non-PCV10 type IPD. In children aged <5 years, PCV10-type carriage declined by 74% and non-PCV10-type carriage increased by 71%.

Interpretation

Introduction of PCV10 in Kenya resulted in a substantial reduction in PCV10-type IPD in children and adults without significant replacement disease. These findings suggest that routine infant PCV10 immunization programmes with catch-up campaigns will provide substantial direct and indirect protection in low-income settings in tropical Africa.
Modern wolves trace their origin to a late Pleistocene expansion from Beringia
Authors: Loog Liisa , Thalmann Olaf , Sinding Mikkel-Holger S. , Schuenemann Verena J. , Perri Angela , Germonpré Mietje , Bocherens Herve , Witt Kelsey E. , Samaniego Castruita Jose A. , Velasco Marcela S. , Lundstrøm Inge K. C. , Wales Nathan , Sonet Gontran , Frantz Laurent , Schroeder Hannes , Budd Jane , Jimenez Elodie-Laure , Fedorov Sergey , Gasparyan Boris , Kandel Andrew W. , Lázničková-Galetová Martina , Napierala Hannes , Uerpmann Hans-Peter , Nikolskiy Pavel A. , Pavlova Elena Y. , Pitulko Vladimir V. , Herzig Karl-Heinz , Malhi Ripan S. , Willerslev Eske , Hansen Anders J. , Dobney Keith , Gilbert M. Thomas P. , Krause Johannes , Larson Greger , Eriksson Anders , Manica Andrea
Published: July 2018

Grey wolves (Canis lupus) are one of the few large terrestrial carnivores that maintained a wide geographic distribution across the Northern Hemisphere throughout the Pleistocene and Holocene. Recent genetic studies have suggested that, despite this continuous presence, major demographic changes occurred in wolf populations between the late Pleistocene and early Holocene, and that extant wolves trace their ancestry to a single late Pleistocene population. Both the geographic origin of this ancestral population and how it became widespread remain a mystery. Here we analyzed a large dataset of novel modern and ancient mitochondrial wolf genomes, spanning the last 50,000 years, using a spatially and temporally explicit modeling framework to show that contemporary wolf populations across the globe trace their ancestry to an expansion from Beringia at the end of the Last Glacial Maximum - a process most likely driven by the significant ecological changes that occurred across the Northern Hemisphere during this period. This study provides direct ancient genetic evidence that long-range migration has played an important role in the population history of a large carnivore and provides an insight into how wolves survived the wave of megafaunal extinctions at the end of the last glaciation. Moreover, because late Pleistocene grey wolves were the likely source from which all modern dogs trace their origins, the demographic history described in this study has fundamental implications for understanding the geographical origin of the dog.
Metabolically activated macrophages in mammary adipose tissue link obesity to triple-negative breast cancer
Authors: Tiwari Payal , Blank Ariane , Cui Chang , Schoenfelt Kelly Q. , Zhou Guolin , Xu Yanfei , Shah Ajay M. , Khan Seema A. , Rosner Marsha Rich , Becker Lev
Published: July 2018

Obesity is associated with increased incidence and severity of triple-negative breast cancer (TNBC); however, mechanisms underlying this relationship are incompletely understood. Macrophages, which accumulate in adipose tissue and are activated during obesity, are an attractive mechanistic link. Here, we show that, during obesity, murine and human mammary adipose tissue macrophages adopt a pro-inflammatory, metabolically- activated (MMe) macrophage phenotype that promotes TNBC stem-like markers and functions, including increased tumorsphere growthin vitroand tumor-initiating potentialin vivo. We demonstrate that MMe macrophages release cytokines in an NADPH oxidase 2 (NOX2)-dependent manner that signal through glycoprotein 130 (GP130) on TNBC cells to promote their stem-like properties. Accordingly, deletingNox2in myeloid cells or depleting GP130 in TNBC cells attenuates the ability of obesity to drive TNBC tumor formation. Our studies implicate MMe macrophage accumulation in mammary adipose tissue during obesity as a mechanism for promoting TNBC stemness and tumorigenesis.

HIGHLIGHTS

⁘

Obesity promotes TNBC tumor formation and stemness.

⁘

Mammary adipose tissue macrophages are metabolically activated (MMe) in obese mice and humans.

⁘

MMe macrophages in mammary adipose tissue contribute to obesity-induced stemness.

⁘

MMe macrophages promote TNBC stemness through GP130 signaling.
Bcl6 promotes neurogenic conversion through transcriptional repression of multiple self-renewal-promoting extrinsic pathways
Authors: Bonnefont Jerome , Tiberi Luca , van den Ameele Jelle , Potier Delphine , Gaber Zachary B , Lin Xionghui , Bilheu Angéline , Herpoel Adèle , Velez Bravo Fausto D. , Guillemot François , Aerts Stein , Vanderhaeghen Pierre
Published: July 2018

During neurogenesis, progenitors switch from self-renewal to differentiation through the interplay of intrinsic and extrinsic cues, but how these are integrated remains poorly understood. Here we combine whole genome transcriptional and epigenetic analyses with in vivo functional studies and show that Bcl6, a transcriptional repressor known to promote neurogenesis, acts as a key driver of the neurogenic transition through direct silencing of a selective repertoire of genes belonging to multiple extrinsic pathways promoting self-renewal, most strikingly the Wnt pathway. At the molecular level, Bcl6 acts through both generic and pathway-specific mechanisms. Our data identify a molecular logic by which a single cell-intrinsic factor ensures robustness of neural cell fate transition by decreasing responsiveness to the extrinsic pathways that favor self-renewal.
Stout camphor tree genome fills gaps in understanding of flowering plant genome and gene family evolution
Authors: Chaw Shu-Miaw , Liu Yu-Ching , Wang Han-Yu , Wu Yu-Wei , Ivy Lin Chan-Yi , Wu Chung-Shien , Ke Huei-Mien , Chang Lo-Yu , Hsu Chih-Yao , Yang Hui-Ting , Sudianto Edi , Hsu Ming-Hung , Wu Kun-Pin , Wang Ning-Ni , Leebens-Mack Jim , Tsai Isheng. J.
Published: July 2018

We present reference-quality genome assembly and annotation for the stout camphor tree (SCT;Cinnamomum kanehirae[Laurales, Lauraceae]), the first sequenced member of the Magnoliidae comprising four orders (Laurales, Magnoliales, Canellales, and Piperales) and over 9,000 species. Phylogenomic analysis of 13 representative seed plant genomes indicates that magnoliid and eudicot lineages share more recent common ancestry relative to monocots. Two whole genome duplication events were inferred within the magnoliid lineage, one before divergence of Laurales and Magnoliales and the other within the Lauraceae. Small scale segmental duplications and tandem duplications also contributed to innovation in the evolutionary history ofCinnamomum. For example, expansion of terpenoid synthase subfamilies within the Laurales spawned the diversity ofCinnamomummonoterpenes and sesquiterpenes.
The equivocal mean age of parents in a cohort
Authors: Bienvenu François
Published: July 2018

The mean age at childbirth is an important notion in demography, ecology and evolution, where it is used as a measure of generation time. A standard way to quantify it is to compute the mean age of the parents of all offspring produced by a cohort, and the resulting measure is thought to represent the mean age at which a typical parent produces offspring. In this note, I explain why this interpretation is problematic. I also introduce a new measure of the mean age at reproduction and show that it can be very different from the mean age of parents of offspring of a cohort. In particular, the mean age of parents of offspring of a cohort systematically overestimates the mean age at reproduction, and can even be greater than the expected lifespan of parents.
Shared expression of Crassulacean acid metabolism (CAM) genes predates the origin of CAM in the genusYucca
Authors: Heyduk Karolina , Ray Jeremy N. , Ayyampalayam Saaravanaraj , Moledina Nida , Borland Anne , Harding Scott A. , Tsai Chung-Jui , Mack Jim Leebens
Published: July 2018

Highlight:

Although large differences in metabolism exist between C3and CAM species, we find that many CAM genes have shared expression patterns regardless of photosynthetic pathway, suggesting ancestral propensity for CAM.

Crassulacean acid metabolism (CAM) is a carbon-concentrating mechanism that has evolved numerous times across flowering plants and is thought to be an adaptation to water limited environments. CAM has been investigated from physiological and biochemical perspectives, but little is known about how plants evolve from C3to CAM at the genetic or metabolic level. Here we take a comparative approach in analyzing time-course data of C3, CAM, and C3+CAM intermediateYucca(Asparagaceae) species. RNA samples were collected over a 24-hour period from both well-watered and drought-stressed plants and were clustered based on time-dependent expression patterns. Metabolomic data reveals differences in carbohydrate metabolism and antioxidant response between the CAM and C3species, suggesting changes to metabolic pathways are important for CAM evolution and function. However, all three species share expression profiles of canonical CAM pathway genes, regardless of photosynthetic pathway. Despite differences in transcript and metabolite profiles between the C3and CAM species, shared time-structured expression of CAM genes in both CAM and C3Yuccaspecies suggests ancestral expression patterns required for CAM may have predated its origin inYucca.
Sex makes them sleepy: host reproductive status induces diapause in a parasitoid population experiencing harsh winters
Authors: Tougeron K. , Brodeur J. , van Baaren J. , Renault D. , Le Lann C.
Published: July 2018

When organisms coevolve, any change in one species can induce phenotypic changes in traits and ecology of the other species. The role such interactions play in ecosystems is central, but their mechanistic bases remain underexplored. Upper trophic level species have to synchronize their life-cycle to both abiotic conditions and to lower trophic level species’ phenology and phenotypic variations. We tested the effect of host seasonal strategy on parasitoid diapause induction by using a holocyclic clone of the pea aphidAcyrthosiphon pisumproducing asexual and sexual morphs that are viviparous females (i.e. laying embryos) and oviparous females (laying eggs), respectively, the latter being only present at the end of the growing season.Aphidius erviparasitoids from populations of contrasted climatic origin (harsh vs. mild winter areas) were allowed to parasitize each morph in a split-brood design and developing parasitoids were next reared under either fall-like or summer-like temperature-photoperiod conditions. We next examined aspects of the host physiological state by comparing the relative proportion of forty-seven metabolites and lipid reserves in both morphs produced under the same conditions. We found that oviparous morphs are cuesper sefor diapause induction; parasitoids entered diapause at higher levels when developing in oviparous hosts (19.4 ± 3.0%) than in viviparous ones (3.6 ± 1.3%), under summer-like conditions (i.e., when oviparous aphids appear in the fields). This pattern was only observed in parasitoids from the harsh winter area since low diapause levels were observed in the other population, suggesting local adaptations to overwintering cues. Metabolomics analyses show parasitoids’ response to be mainly influenced by the host’s physiology, with higher proportion of polyols and sugars, and more fat reserves being found in oviparous morphs. Host quality thus varies across the seasons and represents one of the multiple environmental parameters affecting parasitoid diapause. Our results underline strong coevolutionary processes between hosts and parasitoids in their area of origin, likely leading to phenological synchronization, and we point out the importance of such bottom-up effects for trait expression, and for the provision of ecosystem services such as biological control in the context of climate change.
MICU1 modulates MCU ion selectivity and tolerance to manganese stress
Authors: Wettmarshausen Jennifer , Goh Valerie , Tripathi Utkarsh , Leimpek Anja , Cheng Yiming , Pittis Alexandros A. , Gabaldón Toni , Mokranjac Dejana , Perocchi Fabiana
Published: July 2018

The mitochondrial calcium uniporter is a highly selective ion channel composed of species-and tissue-specific structural and regulatory subunits. However, the contribution of each component to uniporter-mediated activity still remains unclear. Here, we employ an evolutionary and synthetic biology approach to investigate the functional inter-dependence between the pore-forming subunit MCU and the EF-hand protein MICU1. Using phylogenetic profiling and genetic complementation analyses, we show that MCU and MICU1 constitute the minimal eukaryotic unit of the uniporter, pointing towards a strong selective pressure behind their co-occurrence. Heterologous reconstitution of MCU-mediated and MICU1-gated mitochondrial calcium entryin vivoin yeast cells demonstrates that MICU1per seis essential to protect yeast from MCU-dependent manganese cytotoxicity. Accordingly, MICU1 deletion significantly sensitizes human HEK-293 cells to manganese-induced stress. Our study identifies a critical role of MICU1 in the regulation of MCU ion selectivity, with potential implications for patients with MICU1 deficiency.
Global DNA methylation remodeling during direct reprogramming of fibroblasts to neurons
Authors: Luo Chongyuan , Lee Qian Yi , Wapinski Orly L. , Castanon Rosa , Nery Joseph R. , Cullen Sean M. , Goodell Margaret A. , Chang Howard Y. , Wernig Marius , Ecker Joseph R.
Published: July 2018

Direct reprogramming of fibroblasts to neurons induces widespread cellular and transcriptional reconfiguration. In this study, we characterized global epigenomic changes during direct reprogramming using whole-genome base-resolution DNA methylome (mC) sequencing. We found that the pioneer transcription factor Ascl1 alone is sufficient for inducing the uniquely neuronal feature of non-CG methylation (mCH), but co-expression of Brn2 and Mytl1 was required to establish a global mCH pattern reminiscent of mature cortical neurons. Ascl1 alone induced strong promoter CG methylation (mCG) of fibroblast specific genes, while BAM overexpression additionally targets a competing myogenic program and directs a more faithful conversion to neuronal cells. Ascl1 induces local demethylation at its binding sites. Surprisingly, co-expression with Brn2 and Mytl1 inhibited the ability of Ascl1 to induce demethylation, suggesting a contextual regulation of transcription factor - epigenome interaction. Finally, we found thatde novomethylation by DNMT3A is required for efficient neuronal reprogramming.
The ecological cocktail party: Measuring brain activity during an auditory oddball task with background noise
Authors: Scanlon Joanna E. M. , Cormier Danielle L. , Townsend Kimberley A. , Kuziek Jonathan W.P. , Mathewson Kyle E.
Published: July 2018

Most experiments using EEG recordings take place in highly isolated and restricted environments, limiting their applicability to real-life scenarios. New technologies for mobile EEG are changing this by allowing EEG recording to take place outside of the laboratory. However, before results from experiments performed outside the laboratory can be fully understood, the effects of ecological stimuli on brain activity during cognitive tasks must be examined. In this experiment, participants performed an auditory oddball task while also listening to concurrent background noises of silence, white noise and outdoor ecological sounds, as well as a condition in which the tones themselves were at a low volume. We found a significantly increased N1 and decreased P2 when participants performed the task with outdoor sounds and white noise in the background, with the largest differences in the outdoor sound condition. This modulation in the N1 and P2 replicates what we have previously found outside while people ride bicycles (Scanlon et al., 2017b). No behavioural differences were found in response to the target tones. We interpret these modulations in early ERPs as indicative of sensory filtering of background sounds, and that ecologically valid sounds require more filtering than synthetic sounds. Our results reveal that much of what we understand about the brain will need to be updated as we step outside the lab.
The splicing factor U2AF1 contributes to cancer progression through a non-canonical role in translation regulation
Authors: Palangat Murali , Anastasakis Dimitrios , Liang Fei , Lindblad Katherine E. , Bradley Robert , Hourigan Christopher S. , Hafner Markus , Larson Daniel R.
Published: July 2018

Somatic mutations in the genes encoding components of the spliceosome occur frequently in human neoplasms, including myeloid dysplasias and leukemias and less often in solid tumors. One of the affected factors, U2AF1, is involved in splice site selection, and the most common change, S34F, alters a conserved nucleic acid binding domain, recognition of the 3’-splice site, and alternative splicing of many mRNAs. However, the role that this mutation plays in oncogenesis is still unknown. Here, we have uncovered a non-canonical function of U2AF1, showing that it binds mature mRNA in the cytoplasm and negatively regulates mRNA translation. This splicing-independent role of U2AF1 is altered by the S34F mutation, and polysomal profiling indicates the mutation affects translation of hundreds of mRNA. One functional consequence is increased synthesis of the secreted chemokine interleukin 8 which contributes to metastasis, inflammation, and cancer progression in mice and humans.
Entomophthovirus: An insect-derived iflavirus that infects a behavior manipulating fungal pathogen of dipterans
Authors: Coyle Maxwell C. , Elya Carolyn N. , Bronski Michael , Eisen Michael B.
Published: July 2018

We discovered a virus infecting Entomophthora muscae, a behavior-manipulating fungal pathogen of dipterans. The virus, which we name Entomophthovirus, is a capsid-forming, positive-strand RNA virus in the viral family iflaviridae, whose known members almost exclusively infect insects. We show that the virus RNA is expressed at high levels in fungal cells in vitro and during in vivo infections of Drosophila melanogaster, and that virus particles are present in E. muscae. Two close relatives of the virus had been previously described as insect viruses based on the presence of viral genomes in transcriptomes assembled from RNA extracted from wild dipterans. By analyzing sequencing data from these earlier reports, we show that both dipteran samples were co-infected with E. muscae. We also find the virus in RNA sequencing data from samples of two other species of dipterans, Musca domestica and Delia radicum, known to be infected with E. muscae. These data establish that Entomophthovirus is widely, and seemingly obligately, associated with E. muscae. As other members of the iflaviridae cause behavioral changes in insects, we speculate on the possibility that Entomophthovirus plays a role in E. muscae involved host manipulation.
A novel generic dictionary-based denoising method for improving noisy and densely packed nuclei segmentation in 3D time-lapse fluorescence microscopy images
Authors: Nasser Lamees , Boudier Thomas
Published: July 2018

Time-lapse fluorescence microscopy is an essential technique for quantifying various characteristics of cellular processes,i.e. cell survival, migration, and differentiation. To perform high-throughput quantification of cellular processes, nuclei segmentation and tracking should be performed in an automated manner. Nevertheless, nuclei segmentation and tracking are challenging tasks due to embedded noise, intensity inhomogeneity, shape variation as well as a weak boundary of nuclei. Although several nuclei segmentation approaches have been reported in the literature, dealing with embedded noise remains the most challenging part of any segmentation algorithm. We propose a novel denoising algorithms, based on sparse coding, that can both enhance very faint and noisy nuclei but simultaneously detect nuclei position accurately. Furthermore our method is based on a limited number of parameters,with only one being critical, which is the approximate size of the objects of interest. We also show that our denoising method coupled with classical segmentation method works properly in the context of the most challenging cases. To evaluate the performance of the proposed method, we tested our method on two datasets from the cell tracking challenge. Across all datasets, the proposed method achieved satisfactory results with 96.96% recall forC.elegansdataset. Besides, inDrosophiladataset, our method achieved very high recall (99.3%).
Drugs modulating stochastic gene expression affect the erythroid differentiation process
Authors: Guillemin Anissa , Duchesne Ronan , Crauste Fabien , Gonin-Giraud Sandrine , Gandrillon Olivier
Published: July 2018

Background

To understand how a metazoan cell makes the decision to differentiate, we assessed the role of stochastic gene expression (SGE) during the erythroid differentiation process. Our hypothesis is that stochastic gene expression has a role in single-cell decision-making. In agreement with this hypothesis, we and others recently showed that SGE significantly increased during differentiation. However, evidence for the causative role of SGE is still lacking. Such demonstration would require being able to experimentally manipulate SGE levels and analyze the resulting impact of these variations on cell differentiation.

Result

We identified three drugs that modulate SGE in primary erythroid progenitor cells. Artemisinin and Indomethacin simultaneously decreased SGE and reduced the amount of differentiated cells. Inversely, α-methylene-γ-butyrolactone-3 (MB-3) simultaneously increased the level of SGE and the amount of differentiated cells. We then used a dynamical modelling approach which confirmed that differentiation rates were indeed affected by the drug treatment.

Conclusion

Using single-cell analysis and modeling tools, we provide experimental evidence that in a physiologically relevant cellular system, control of SGE can directly modify differentiation, supporting a causal link between the two.
Not one hormone or another: Aggression differentially affects progesterone and testosterone in a South American ovenbird
Authors: Adreani Nicolas M. , Goymann Wolfgang , Mentesana Lucia
Published: July 2018

Behaviors such as territorial interactions among individuals can modulate vertebrate physiology and vice versa. Testosterone has been pointed out as a key hormone that can be rapidly affected by aggressive interactions. However, experimental evidence for such a link is mixed. In addition, behaviors can elicit changes in multiple hormones, which in turn have the potential to synergistically feedback to behavior. For example testosterone and progesterone can act interdependently in modulating male behavior. However, if aggression can affect progesterone levels in males remain unknown and – to the best of our knowledge – no one has yet tackled if and how aggressive behavior simultaneously affects testosterone and progesterone in free-living animals. We addressed these questions by performing simulated territorial intrusion experiments measuring both hormones and their ratio in male rufous horneros (Aves, Furnarius rufus) during the mating and parental care periods. Aggression affected testosterone and progesterone differentially depending on the period of testing: challenged birds had higher levels of progesterone during the mating period and lower levels of testosterone during parental care compared to controls. Challenged individuals had similar progesterone to testosterone ratios during both periods and these ratios were higher than those of control birds. In summary, territorial aggression triggered hormonal pathways differentially depending on the stage of the breeding cycle, but equally altered their ratio independent of it. Our results indicate that multiple related hormones could be playing a role rather than each hormone alone in response to social interactions.
Identification of salivary and plasma biomarkers for obesity in children by non-targeted metabolomic analysis
Authors: Goodson J. Max , Hardt Marcus , Hartman Mor-Li , Schulte Fabian , Tavares Mary , Mutawa Al-Sabiha , Ariga Jitendra , Soparkar Pramod , Behbehani Jawad , Behbehani Kazem , Razzaque Mohammed
Published: July 2018

Chemical compounds in the saliva most likely to be associated with obesity are identified in a metabolomic analysis of paired whole saliva and plasma samples from 68 children (10-year old) who have also been evaluated for their gingival redness.

Results

Through metabolomic analysis119 compounds were found only in saliva, 210 only in plasma and 126 in both. The most common plasma metabolites were lipids. The most common saliva metabolites were peptides. Amino acids and their metabolites were common in both samples.

Surrogate indicators were identified by computing correlations between saliva and plasma. 29 of the 126 found in both saliva and plasma had significant positive correlation and only 4 of those (urate, creatinine, pipecolate and hydroxyproline) were associated with obesity as potential surrogate biomarkers. The uremic toxin N1-Methyl-2-pyridone-5-carboxamide (2PY) was also elevated in the saliva of obese children. 21 biochemicals were elevated in both obesity and gingivitis suggesting that some biochemical pathways for gingivitis and obesity are shared.

Of the metabolites found only in saliva, 35 were associated with obesity (p<0.01). The most significant was phosphate. Saliva had 53 dipeptides, seven of which were associated with obesity. Two volatile amines (putrescine and cadaverine) and their amino acid precursors (ornithine and lysine) were also associated with obesity.

Of the metabolites found only in plasma, 64 were associated with obesity (p<0.01). Significant increases in branched-chain and aromatic amino acids, significant reductions in serotonin, serine, and glycine and increased androgen metabolism are changes observed in 10-year old obese children that have also been reported with adult patients having type II diabetes.

Conclusions

Salivary urate may be a valuable measure of metabolic disease particularly in association with fructose consumption. Elevated salivary creatinine levels and presence of 2PY suggests a possible association of obesity with developing kidney disease in obese children. Though not a surrogate variable, salivary phosphate, (AUROC= 0.8) could also be an important indicator of obesity. Cadaverine, putrescine and dipeptides are also likely oral bacterial products that could help define the metabolic pathways responsible for obesity. The results of this study indicate that salivary metabolites can be important indicators of developing metabolic disease in children and provide a biochemical signature in the pathways that lead to obesity.
Survival and development of potato psyllid (Hemiptera: Triozidae) on Convolvulaceae: effects of a plant-fungus symbiosis (Periglandula)
Authors: Kaur N. , Cooper W.R. , Duringer J.M. , Badillo-Vargas I.E. , Esparza-Díaz G. , Rashed A. , Horton D.R.
Published: July 2018

Plant species in the family Solanaceae are the usual hosts of potato psyllid, Bactericera cockerelli (Šulc) (Hemiptera: Psylloidea: Triozidae). However, the psyllid has also been shown to develop on some species of Convolvulaceae (bindweeds and morning glories). Developmental success on Convolvulaceae is surprising given the rarity of psyllid species worldwide associated with this plant family. We assayed 14 species of Convolvulaceae across four genera (Convolvulus, Calystegia, Ipomoea, Turbina) to identify species that allow development of potato psyllid. Two populations of psyllids were assayed (Texas, Washington). The Texas population overlaps extensively with native Convolvulaceae, whereas Washington State is noticeably lacking in Convolvulaceae. Results of assays were overlain on a phylogenetic analysis of plant species to examine whether Convolvulaceae distantly related to the typical host (potato) were less likely to allow development than species of Convolvulaceae more closely related. Survival was independent of psyllid population and location of the plant species on our phylogenetic tree. We then examined whether presence of a fungal symbiont of Convolvulaceae (Periglandula spp.) affected psyllid survival. These fungi associate with Convolvulaceae and produce a class of mycotoxins (ergot alkaloids) that may confer protection against plant-feeding arthropods. Periglandula was found in 11 of our 14 species, including in two genera (Convolvulus, Calystegia) not previously known to host the symbiont. Of these 11 species, leaf tissues from five contained large quantities of two classes of ergot alkaloids (clavines, amides of lysergic acid) when evaluated by LC-MS/MS. All five species also harbored Periglandula. No ergot alkaloids were detected in species free of the fungal symbiont. Potato psyllid rapidly died on species found to harbor Periglandula and fungus-produced alkaloids, but survived on species in which the mutualism was absent. These results support the hypothesis that a plant-fungus symbiotic relationship affects the suitability of certain Convolvulaceae to potato psyllid.
Head-to-Head Comparison of Three Methods of Quantifying Competitive Fitness inC. elegans
Authors: Crombie Timothy A. , Saber Sayran , Saxena Ayush Shekhar , Egan Robyn , Baer Charles F.
Published: July 2018

Organismal fitness is relevant in many contexts in biology. The most meaningful experimental measure of fitness iscompetitivefitness, when two or more entities (e.g., genotypes) are allowed to compete directly. In theory, competitive fitness is simple to measure: an experimental population is initiated with the different types in known proportions and allowed to evolve under experimental conditions to a predefined endpoint. In practice, there are several obstacles to obtaining robust estimates of competitive fitness in multicellular organisms, the most pervasive of which is simply the time it takes to count many individuals of different types from many replicate populations. Methods by which counting can be automated in high throughput are desirable, but for automated methods to be useful, the bias and technical variance associated with the method must be (a) known, and (b) sufficiently small relative to other sources of bias and variance to make the effort worthwhile.

The nematodeCaenorhabditis elegansis an important model organism, and the fitness effects of genotype and environmental conditions are often of interest. We report a comparison of three experimental methods of quantifying competitive fitness, in which wild-type strains are competed against GFP-marked competitors under standard laboratory conditions. Population samples were split into three replicates and counted (1) “by eye” from a saved image, (2) from the same image using CellProfiler image analysis software, and (3) with a large particle flow cytometer (a “worm sorter”). From 720 replicate samples, neither the frequency of wild-type worms nor the among-sample variance differed significantly between the three methods. CellProfiler and the worm sorter provideat leasta tenfold increase in sample handling speed with little (if any) bias or increase in variance.