bluuebunny/crossref_metadata_2025 huggingface dataset:
Aerodynamic generation of electric fields in turbulence laden with charged inertial particles
Authors: Di Renzo M. , Urzay J.
Published: April 2018

Self-induced electricity, including lightning, is often observed in dusty atmospheres. However, the physical mechanisms leading to this phenomenon remain elusive as they are remarkably challenging to determine due to the high complexity of the multi-phase turbulent flows involved. Using a fast multi-pole method in direct numerical simulations of homogeneous turbulence laden with hundreds of millions of inertial particles, here we show that mesoscopic electric fields can be aerodynamically created in bi-disperse suspensions of oppositely charged particles. The generation mechanism is self-regulating and relies on turbulence preferentially concentrating particles of one sign in clouds while dispersing the others more uniformly. The resulting electric field varies over much larger length scales than both the mean inter-particle spacing and the size of the smallest eddies. Scaling analyses suggest that low ambient pressures, such as those prevailing in the atmosphere of Mars, increase the dynamical relevance of this aerodynamic mechanism for electrical breakdown.
Enhanced pupillary light reflex in infancy is associated with autism diagnosis in toddlerhood
Authors: Nyström Pär , Gliga Teodora , Nilsson Jobs Elisabeth , Gredebäck Gustaf , Charman Tony , Johnson Mark H. , Bölte Sven , Falck-Ytter Terje
Published: April 2018

Autism spectrum disorder (ASD) is a neurodevelopmental condition affecting around 1% of the population. We previously discovered that infant siblings of children with ASD had stronger pupillary light reflexes compared to low-risk infants, a result which contrasts sharply with the weak pupillary light reflex typically seen in both children and adults with ASD. Here, we show that on average the relative constriction of the pupillary light reflex is larger in 9–10-month-old high risk infant siblings who receive an ASD diagnosis at 36 months, compared both to those who do not and to low-risk controls. We also found that the magnitude of the pupillary light reflex in infancy is associated with symptom severity at follow-up. This study indicates an important role of sensory atypicalities in the etiology of ASD, and suggests that pupillometry, if further developed and refined, could facilitate risk assessment in infants.
Knowledge acquisition is governed by striatal prediction errors
Authors: Pine Alex , Sadeh Noa , Ben-Yakov Aya , Dudai Yadin , Mendelsohn Avi
Published: April 2018

Discrepancies between expectations and outcomes, or prediction errors, are central to trial-and-error learning based on reward and punishment, and their neurobiological basis is well characterized. It is not known, however, whether the same principles apply to declarative memory systems, such as those supporting semantic learning. Here, we demonstrate with fMRI that the brain parametrically encodes the degree to which new factual information violates expectations based on prior knowledge and beliefs—most prominently in the ventral striatum, and cortical regions supporting declarative memory encoding. These semantic prediction errors determine the extent to which information is incorporated into long-term memory, such that learning is superior when incoming information counters strong incorrect recollections, thereby eliciting large prediction errors. Paradoxically, by the same account, strong accurate recollections are more amenable to being supplanted by misinformation, engendering false memories. These findings highlight a commonality in brain mechanisms and computational rules that govern declarative and nondeclarative learning, traditionally deemed dissociable.
Author Correction: Cardioprotection induced in a mouse model of neuropathic pain via anterior nucleus of paraventricular thalamus
Authors: Cheng Yi-Fen , Chang Ya-Ting , Chen Wei-Hsin , Shih Hsi-Chien , Chen Yen-Hui , Shyu Bai-Chuang , Chen Chien-Chang
Published: April 2018

The original version of this Article contained an error in the affiliation of the second author, Ya-Ting Chang. The correct affiliations for Ya-Ting Chang are Institute of Biomedical Sciences, Academia Sinica, Taipei, 115, Taiwan and International Graduate Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei 115, Taiwan.
Publisher Correction: Spin-controlled atom–ion chemistry
Authors: Sikorsky Tomas , Meir Ziv , Ben-shlomi Ruti , Akerman Nitzan , Ozeri Roee
Published: April 2018

The original version of this Article contained an error in the third sentence of the first paragraph of the ‘Spin polarizing the Sr+ ion with ultracold atoms’ section of the Results, which incorrectly read ‘The Langevin collision rate is 1.’ The correct version adds ‘kHz’ after ‘1.’ The fifth sentence of this same paragraph originally read as “Although 87Rb has a I = 3/2 nuclear spin and a hyperfine-split ground-state manifold, 88Sr has no nuclear spin and a Zeeman split two-fold ground state”, which is incorrect. The correct version states “88Sr+” instead of “88Sr”. The first sentence of the fourth paragraph of this same section originally read as “As the collisional energies are on the mK energy scale, spin exchange between Sr+ and Rb prepared in the F = 1 state is allowed only as long as it does not require Rb to change its hyperfine state and climb the 330 m hyperfine energy gap”, which is incorrect. The correct version states “330 mK” instead of “330 m”.In the Discussion section, the text was originally incorrectly repeated.This has been corrected in both the PDF and HTML versions of the Article.
Germination heterochrony in annual plants of Salsola L.: an effective survival strategy in changing environments
Authors: Liu Hua F. , Liu Tong , Han Zhi Q. , Luo Ning , Liu Zun C. , Hao Xiao R.
Published: April 2018

Germination heterochrony refers to germination of seeds dispersed in a single growing season, which is different from delayed germination. We studied two year’s demographic characteristics, characteristics of fruit heteromorphism, the relationship between fruit heteromorphism and germination heterochrony, effects of moisture and temperature on germination characteristics, as well as seed longevity of four annual Salsola L. species to analyze the adaptive significance and causes of germination heterochrony. We found that the number of individuals of all populations changed drastically in one year. Approximately 41.6–100% of seedlings germinated in spring died. The number of fruit types varied with interspecies and intraspecies. Despite the wide range of germination temperature of different fruit types (0–35 °C), the germination percentage at 0–15 °C was the highest. When the soil moisture content was 20%, the germination percentage was the highest, reaching 50% within the shortest time. The contrary was the case with the decreasing of soil moisture. The seed longevity of the four species was one year. Fruit heteromorphism had no direct relationship to germination heterochrony. Germination heterochrony was caused by precipitation characteristics and short seed longevity of annual Salsola L., which was an effective survival strategy for plant to adapt to the changing environments in arid area.
E-cadherin breast tumor expression, risk factors and survival: Pooled analysis of 5,933 cases from 12 studies in the Breast Cancer Association Consortium
Authors: Horne Hisani N. , Oh Hannah , Sherman Mark E. , Palakal Maya , Hewitt Stephen M. , Schmidt Marjanka K. , Milne Roger L. , Hardisson David , Benitez Javier , Blomqvist Carl , Bolla Manjeet K. , Brenner Hermann , Chang-Claude Jenny , Cora Renata , Couch Fergus J. , Cuk Katarina , Devilee Peter , Easton Douglas F. , Eccles Diana M. , Eilber Ursula , Hartikainen Jaana M. , Heikkilä Päivi , Holleczek Bernd , Hooning Maartje J. , Jones Michael , Keeman Renske , Mannermaa Arto , Martens John W. M. , Muranen Taru A. , Nevanlinna Heli , Olson Janet E. , Orr Nick , Perez Jose I. A. , Pharoah Paul D. P. , Ruddy Kathryn J. , Saum Kai-Uwe , Schoemaker Minouk J. , Seynaeve Caroline , Sironen Reijo , Smit Vincent T. H. B. M. , Swerdlow Anthony J. , Tengström Maria , Thomas Abigail S. , Timmermans A. Mieke , Tollenaar Rob A. E. M. , Troester Melissa A. , van Asperen Christi J. , van Deurzen Carolien H. M. , Van Leeuwen Flora F. , Van’t Veer Laura J. , García-Closas Montserrat , Figueroa Jonine D.
Published: April 2018

E-cadherin (CDH1) is a putative tumor suppressor gene implicated in breast carcinogenesis. Yet, whether risk factors or survival differ by E-cadherin tumor expression is unclear. We evaluated E-cadherin tumor immunohistochemistry expression using tissue microarrays of 5,933 female invasive breast cancers from 12 studies from the Breast Cancer Consortium. H-scores were calculated and case-case odds ratios (OR) and 95% confidence intervals (CIs) were estimated using logistic regression. Survival analyses were performed using Cox regression models. All analyses were stratified by estrogen receptor (ER) status and histologic subtype. E-cadherin low cases (N = 1191, 20%) were more frequently of lobular histology, low grade, >2 cm, and HER2-negative. Loss of E-cadherin expression (score < 100) was associated with menopausal hormone use among ER-positive tumors (ever compared to never users, OR = 1.24, 95% CI = 0.97–1.59), which was stronger when we evaluated complete loss of E-cadherin (i.e. H-score = 0), OR = 1.57, 95% CI = 1.06–2.33. Breast cancer specific mortality was unrelated to E-cadherin expression in multivariable models. E-cadherin low expression is associated with lobular histology, tumor characteristics and menopausal hormone use, with no evidence of an association with breast cancer specific survival. These data support loss of E-cadherin expression as an important marker of tumor subtypes.
The delta neutrophil index (DNI) as a prognostic marker for mortality in adults with sepsis: a systematic review and meta-analysis
Authors: Ahn Chiwon , Kim Wonhee , Lim Tae Ho , Cho Youngsuk , Choi Kyu-Sun , Jang Bo-Hyoung
Published: April 2018

We performed a meta-analysis to seek evidence for the usefulness of the delta neutrophil index (DNI) as a prognostic blood biomarker for mortality in the early stage of sepsis in adults. A literature search was performed using criteria set forth in a predefined protocol. Studies of adults with sepsis that provided a DNI measurement and that had mortality as the outcome, were included. Review articles, editorials, and non-human studies were excluded. The methodological quality of identified studies was assessed independently by two authors using the Quality in Prognosis Studies (QUIPS) tool. A total of 1,822 patients from eleven studies were ultimately included. Standardized mean differences between non-survivors and survivors were compared. An elevated DNI was associated with mortality in patients with sepsis (standardized mean difference [SMD] 1.22; 95% confidence interval 0.73–1.71; I2 = 91%). After excluding two studies—one that included paediatric patients and one with a disproportionately low mortality rate—heterogeneity was minimized (SMD 0.74, 95% confidence interval 0.53–0.94; I2 = 43%). Overall, the findings suggest that high DNI values are associated with mortality in septic patients.
Extraction of cage-like sporopollenin exine capsules from dandelion pollen grains
Authors: Fan Tengfei , Park Jae Hyeon , Pham Quynh Anh , Tan Ee-Lin , Mundargi Raghavendra. C. , Potroz Michael G. , Jung Haram , Cho Nam-Joon
Published: April 2018

Pollen-based microcapsules such as hollow sporopollenin exine capsules (SECs) have emerged as excellent drug delivery and microencapsulation vehicles. To date, SECs have been extracted primarily from a wide range of natural pollen species possessing largely spherical geometries and uniform surface features. Nonetheless, exploring pollen species with more diverse architectural features could lead to new application possibilities. One promising class of candidates is dandelion pollen grains, which possess architecturally intricate, cage-like microstructures composed of robust sporopollenin biopolymers. Here, we report the successful extraction and macromolecular loading of dandelion SECs. Preservation of SEC morphology and successful removal of proteinaceous materials was evaluated using scanning electron microscopy (SEM), matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry, elemental CHN analysis, dynamic image particle analysis (DIPA) and confocal laser scanning microscopy (CLSM). Among the tested processing schemes, acidolysis using 85% (v/v) phosphoric acid refluxed at 70 °C for 5 hours yielded an optimal balance of intact particle yield, protein removal, and preservation of cage-like microstructure. For proof-of-concept loading, bovine serum albumin (BSA) was encapsulated within the dandelion SECs with high efficiency (32.23 ± 0.33%). Overall, our findings highlight how hollow microcapsules with diverse architectural features can be readily prepared and utilized from plant-based materials.
Increased transforming growth factor beta (TGF-β) and pSMAD3 signaling in a Murine Model for Contrast Induced Kidney Injury
Authors: Kilari Sreenivasulu , Yang Binxia , Sharma Amit , McCall Deborah L. , Misra Sanjay
Published: April 2018

We tested the hypothesis that post-contrast acute kidney injury (PC-AKI) occurs due to increase in transforming growth factor beta (Tgf-β) and pSMAD3 signaling in a murine model of PC-AKI. Mice had nephrectomy performed and twenty-eight days later, 100-μL of radio-contrast (Vispaque 320) or saline was administered via the jugular vein. Animals were sacrificed at 2, 7, and 28 days later and the serum BUN, creatinine, urine protein levels, and kidney weights were assessed. In human kidney-2 (HK-2) cells, gene and protein expression with cellular function was assessed following inhibition of TGFβR-1 plus contrast exposure. After contrast administration, the average serum creatinine is significantly elevated at all time points. The average gene expression of connective tissue growth factor (Ctgf), Tgfβ-1, matrix metalloproteinase-9 (Mmp-9), and collagen IVa (Col IVa) are significantly increased at 2 days after contrast administration (P < 0.05). Cellular proliferation is decreased and there is increased apoptosis with tubulointerstitial fibrosis. Contrast administered to HK-2 cells results in increased pSMAD3 levels and gene expression of Ctgf, Tgfβ-1, Tgfβ-2, Col IVa, Mmp-9, and caspase/7 activity with a decrease in proliferation (all, P < 0.05). TGFβR-1 inhibition decreased the expression of contrast mediated pro-fibrotic genes in HK-2 cells with no change in the proliferation and apoptosis.
Iron deficiency is associated with Hypothyroxinemia and Hypotriiodothyroninemia in the Spanish general adult population: Di@bet.es study
Authors: Maldonado-Araque Cristina , Valdés Sergio , Lago-Sampedro Ana , Lillo-Muñoz Juan Antonio , Garcia-Fuentes Eduardo , Perez-Valero Vidal , Gutierrez-Repiso Carolina , Goday Albert , Urrutia Ines , Peláez Laura , Calle-Pascual Alfonso , Castaño Luis , Castell Contxa , Delgado Elias , Menendez Edelmiro , Franch-Nadal Josep , Gaztambide Sonia , Girbés Joan , Ortega Emilio , Vendrell Joan , Chacón Matilde R. , Chaves Felipe J. , Soriguer Federico , Rojo-Martínez Gemma
Published: April 2018

Previous studies have suggested that iron deficiency (ID) may impair thyroid hormone metabolism, however replication in wide samples of the general adult population has not been performed. We studied 3846 individuals free of thyroid disease, participants in a national, cross sectional, population based study representative of the Spanish adult population. Thyroid stimulating hormone (TSH), free thyroxin (FT4) and free triiodothyronine (FT3) were analyzed by electrochemiluminescence (E170, Roche Diagnostics). Serum ferritin was analyzed by immunochemiluminescence (Architect I2000, Abbott Laboratories). As ferritin levels decreased (>100, 30–100, 15–30, <15 µg/L) the adjusted mean concentrations of FT4 (p < 0.001) and FT3 (p < 0.001) descended, whereas TSH levels remained unchanged (p = 0.451). In multivariate logistic regression models adjusted for age, sex, UI, BMI and smoking status, subjects with ferritin levels <30 µg/L were more likely to present hypothyroxinemia (FT4 < 12.0 pmol/L p5): OR 1.5 [1.1–2.2] p = 0.024, and hypotriiodothyroninemia (FT3 < 3.9 pmol/L p5): OR 1.8 [1.3–2.6] p = 0.001 than the reference category with ferritin ≥30 µg/L. There was no significant heterogeneity of the results between men, pre-menopausal and post-menopausal women or according to the iodine nutrition status. Our results confirm an association between ID and hypothyroxinemia and hypotriiodothyroninemia in the general adult population without changes in TSH.
RTS,S/AS01 malaria vaccine mismatch observed among Plasmodium falciparum isolates from southern and central Africa and globally
Authors: Pringle Julia C. , Carpi Giovanna , Almagro-Garcia Jacob , Zhu Sha Joe , Kobayashi Tamaki , Mulenga Modest , Bobanga Thierry , Chaponda Mike , Moss William J. , Norris Douglas E.
Published: April 2018

The RTS,S/AS01 malaria vaccine encompasses the central repeats and C-terminal of Plasmodium falciparum circumsporozoite protein (PfCSP). Although no Phase II clinical trial studies observed evidence of strain-specific immunity, recent studies show a decrease in vaccine efficacy against non-vaccine strain parasites. In light of goals to reduce malaria morbidity, anticipating the effectiveness of RTS,S/AS01 is critical to planning widespread vaccine introduction. We deep sequenced C-terminal Pfcsp from 77 individuals living along the international border in Luapula Province, Zambia and Haut-Katanga Province, the Democratic Republic of the Congo (DRC) and compared translated amino acid haplotypes to the 3D7 vaccine strain. Only 5.2% of the 193 PfCSP sequences from the Zambia-DRC border region matched 3D7 at all 84 amino acids. To further contextualize the genetic diversity sampled in this study with global PfCSP diversity, we analyzed an additional 3,809 Pfcsp sequences from the Pf3k database and constructed a haplotype network representing 15 countries from Africa and Asia. The diversity observed in our samples was similar to the diversity observed in the global haplotype network. These observations underscore the need for additional research assessing genetic diversity in P. falciparum and the impact of PfCSP diversity on RTS,S/AS01 efficacy.
Simulating SIR processes on networks using weighted shortest paths
Authors: Tolić Dijana , Kleineberg Kaj-Kolja , Antulov-Fantulin Nino
Published: April 2018

We present a framework to simulate SIR processes on networks using weighted shortest paths. Our framework maps the SIR dynamics to weights assigned to the edges of the network, which can be done for Markovian and non-Markovian processes alike. The weights represent the propagation time between the adjacent nodes for a particular realization. We simulate the dynamics by constructing an ensemble of such realizations, which can be done by using a Markov Chain Monte Carlo method or by direct sampling. The former provides a runtime advantage when realizations from all possible sources are computed as the weighted shortest paths can be re-calculated more efficiently. We apply our framework to three empirical networks and analyze the expected propagation time between all pairs of nodes. Furthermore, we have employed our framework to perform efficient source detection and to improve strategies for time-critical vaccination.
Exotic grass invasion alters microsite conditions limiting woody recruitment potential in an Australian savanna
Authors: Setterfield Samantha A. , Clifton Peter J. , Hutley Lindsay B. , Rossiter-Rachor Natalie A. , Douglas Michael M.
Published: April 2018

Andropogon gayanus Kunth. is a large African tussock grass invading Australia’s tropical savannas. Invasion results in more intense fires which increases the mortality rate of adult woody plants. Invasion may also affect community structure by altering the recruitment potential of woody plants. We investigated the effects of A. gayanus invasion on ground-level microclimate, and the carbon assimilation potential and recruitment potential of two Eucalyptus species. We compared microclimatic variables from the early wet-season and into the mid-dry season to coincide with the period of growth of A. gayanus. We assessed Eucalyptus recruitment by monitoring seedling establishment, growth and survival of experimentally sown seed, and estimating seedling density resulting from natural recruitment. A. gayanus invasion was associated with increased grass canopy height, biomass and cover. Following invasion, the understorey microclimate had significantly reduced levels of photon flux density, increased air temperatures and vapour pressure deficit. The conditions were less favourable for woody seedling with aboveground biomass of seedlings reduced by 26% in invaded plots. We estimated that invasion reduced daily carbon assimilation of woody seedlings by ~30% and reduced survivorship of Eucalyptus seedlings. Therefore, A. gayanus invasion reduces recruitment potential, contributing to the transformation of savanna to a grassland ecosystem.
Nanocrystalline Iron Monosulfides Near Stoichiometry
Authors: Roberts Dennice M. , Landin Alyssa R. , Ritter Timothy G. , Eaves Joel D. , Stoldt Conrad R.
Published: April 2018

Solids composed of iron and sulfur are earth abundant and nontoxic, and can exhibit interesting and technologically important optical, electronic, and magnetic phenomena. However, the iron-sulfur (Fe-S) phase diagram is congested in regions of slight non-stoichiometric iron vacancies, and even when the iron atomic composition changes by even a few percent at standard temperature and pressure, there are myriad stable crystal phases that form with qualitatively different electronic properties. Here, we synthesized and characterized nanocrystals of the pyrrhotite-4M structure (Fe7S8) in an anhydrous oleylamine solvent. Upon heating from 140 °C to 180 °C, the solid sequentially transformed into two kinetically trapped FeS intermediate phases before reaching the pyrrhotite-4M final product. Finally, we assessed the effects of iron vacancies using the stoichiometric end-member, troilite, as a reference system. Density functional theory calculations show that iron vacancies in troilite shift the structure from hexagonal FeS to a monoclinic structure, similar to crystal structures of pyrrhotites, and suggest that this iron deficient troilite may be a stable intermediate between the two crystal structures. The calculations predict that defects also close the band gap in iron deficient troilite.
High throughput evaluation of macrocyclization strategies for conformer stabilization
Authors: Sindhikara Dan , Borrelli Ken
Published: April 2018

While macrocyclization of a linear compound to stabilize a known bioactive conformation can be a useful strategy to increase binding potency, the difficulty of macrocycle synthesis can limit the throughput of such strategies. Thus computational techniques may offer the higher throughput required to screen large numbers of compounds. Here we introduce a method for evaluating the propensity of a macrocyclic compound to adopt a conformation similar that of a known active linear compound in the binding site. This method can be used as a fast screening tool for prioritizing macrocycles by leveraging the assumption that the propensity for the known bioactive substructural conformation relates to the affinity. While this method cannot to identify new interactions not present in the known linear compound, it could quickly differentiate compounds where the three dimensional geometries imposed by the macrocyclization prevent adoption of conformations with the same contacts as the linear compound in their conserved region. Here we report the implementation of this method using an RMSD-based structural descriptor and a Boltzmann-weighted propensity calculation and apply it retrospectively to three macrocycle linker optimization design projects. We found the method performs well in terms of prioritizing more potent compounds.
3D Reconstruction of Lipid Droplets in the Seed of Brassica napus
Authors: Yin Yongtai , Guo Liangxing , Chen Kang , Guo Zhenyi , Chao Hongbo , Wang Baoshan , Li Maoteng
Published: April 2018

Rapeseed is one of the most important and widely cultured oilseed crops for food and nonfood purposes worldwide. Neutral lipids are stored in lipid droplets (LDs) as fuel for germination and subsequent seedling growth. Most of the LD detection in seeds was still in 2D levels, and some of the details might have been lost in previous studies. In the present work, the configuration of LDs in seeds was obtained by confocal imaging combined with 3D reconstruction technology in Brassica napus. The size and shape of LDs, LD numbers, cell interval spaces and cell size were observed and compared at 3D levels in the seeds of different materials with high and low oil content. It was also revealed that different cells located in the same tissue exhibited various oil contents according to the construction at the 3D level, which was not previously reported in B. napus. The present work provides a new way to understand the differential in cell populations and enhance the seed oil content at the single cell level within seeds.
Transient elevation of cytoplasmic calcium ion concentration at a single cell level precedes morphological changes of epidermal keratinocytes during cornification
Authors: Murata Teruasa , Honda Tetsuya , Egawa Gyohei , Yamamoto Yasuo , Ichijo Ryo , Toyoshima Fumiko , Dainichi Teruki , Kabashima Kenji
Published: April 2018

Epidermal keratinocytes achieve sequential differentiation from basal to granular layers, and undergo a specific programmed cell death, cornification, to form an indispensable barrier of the body. Although elevation of the cytoplasmic calcium ion concentration ([Ca2+]i) is one of the factors predicted to regulate cornification, the dynamics of [Ca2+]i in epidermal keratinocytes is largely unknown. Here using intravital imaging, we captured the dynamics of [Ca2+]i in mouse skin. [Ca2+]i was elevated in basal cells on the second time scale in three spatiotemporally distinct patterns. The transient elevation of [Ca2+]i also occurred at the most apical granular layer at a single cell level, and lasted for approximately 40 min. The transient elevation of [Ca2+]i at the granular layer was followed by cornification, which was completed within 10 min. This study demonstrates the tightly regulated elevation of [Ca2+]i preceding the cornification of epidermal keratinocytes, providing possible clues to the mechanisms of cornification.
JIB-04, A Small Molecule Histone Demethylase Inhibitor, Selectively Targets Colorectal Cancer Stem Cells by Inhibiting the Wnt/β-Catenin Signaling Pathway
Authors: Kim Min Seong , Cho Hye In , Yoon Hee Jung , Ahn Ye-Hyeon , Park Eun Jung , Jin Yan Hua , Jang Yeun Kyu
Published: April 2018

Although several epigenetic modulating drugs are suggested to target cancer stem cells (CSCs), additional identification of anti-CSC drugs is still necessary. Here we showed that JIB-04, a pan-selective inhibitor of histone demethylase(s), was identified as a small molecule that selectively target colorectal CSCs. Our data showed that JIB-04 is capable of reducing self-renewal and stemness of colorectal CSCs in three different colorectal cancer cell lines. JIB-04 significantly attenuated CSC tumorsphere formation, growth/relapse, invasion, and migration in vitro. Furthermore, JIB-04-treated colorectal cancer cells showed reduced tumorigenic activity in vivo. RNA sequencing analysis revealed that JIB-04 affected various cancer-related signaling pathways, especially Wnt/β-catenin signaling, which is crucial for the proliferation and maintenance of colorectal cancer cells. qRT-PCR and TOP/FOP flash luciferase assays showed that JIB-04 down-regulated the expression of Wnt/β-catenin-regulated target genes associated with colorectal CSC function. Overall, the effects of JIB-04 were equal to or greater than those of salinomycin, a known anti-colorectal CSC drug, despite the lower concentration of JIB-04 compared with that of salinomycin. Our results strongly suggest that JIB-04 is a promising drug candidate for colorectal cancer therapy.
Endometrial Mesenchymal Stem/Stromal Cells Modulate the Macrophage Response to Implanted Polyamide/Gelatin Composite Mesh in Immunocompromised and Immunocompetent Mice
Authors: Darzi S. , Deane J. A. , Nold C. A. , Edwards S. E. , Gough D. J. , Mukherjee S. , Gurung S. , Tan K. S. , Vashi A. V. , Werkmeister J. A. , Gargett C. E.
Published: April 2018

The immunomodulatory properties of human endometrial mesenchymal stem cells (eMSC) have not been well characterised. Initial studies showed that eMSC modulated the chronic inflammatory response to a non-degradable polyamide/gelatin mesh in a xenogeneic rat skin wound repair model, but the mechanism remains unclear. In this study, we investigated the immunomodulatory effect of eMSC on the macrophage response to polyamide/gelatin composite mesh in an abdominal subcutaneous wound repair model in C57BL6 immunocompetent and NSG (NOD-Scid-IL2Rgamma
null
) immunocompromised mice to determine whether responses differed in the absence of an adaptive immune system and NK cells. mCherry lentivirus-labelled eMSC persisted longer in NSG mice, inducing longer term paracrine effects. Inclusion of eMSC in the mesh reduced inflammatory cytokine (Il-1β, Tnfα) secretion, and in C57BL6 mice reduced CCR7+ M1 macrophages surrounding the mesh on day 3 and increased M2 macrophage marker mRNA (Arg1, Mrc1, Il10) expression at days 3 and 7. In NSG mice, these effects were delayed and only observed at days 7 and 30 in comparison with controls implanted with mesh alone. These results show that the differences in the immune status in the two animals directly affect the survival of xenogeneic eMSC which leads to differences in the short-term and long-term macrophage responses to implanted meshes.
Analysis of natural female post-mating responses of Anopheles gambiae and Anopheles coluzzii unravels similarities and differences in their reproductive ecology
Authors: Thailayil Janis , Gabrieli Paolo , Caputo Beniamino , Bascuñán Priscila , South Adam , Diabate Abdoulaye , Dabire Roch , della Torre Alessandra , Catteruccia Flaminia
Published: April 2018

Anopheles gambiae and An. coluzzii, the two most important malaria vectors in sub-Saharan Africa, are recently radiated sibling species that are reproductively isolated even in areas of sympatry. In females from these species, sexual transfer of male accessory gland products, including the steroid hormone 20-hydroxyecdysone (20E), induces vast behavioral, physiological, and transcriptional changes that profoundly shape their post-mating ecology, and that may have contributed to the insurgence of post-mating, prezygotic reproductive barriers. As these barriers can be detected by studying transcriptional changes induced by mating, we set out to analyze the post-mating response of An. gambiae and An. coluzzii females captured in natural mating swarms in Burkina Faso. While the molecular pathways shaping short- and long-term mating-induced changes are largely conserved in females from the two species, we unravel significant inter-specific differences that suggest divergent regulation of key reproductive processes such as egg development, processing of seminal secretion, and mating behavior, that may have played a role in reproductive isolation. Interestingly, a number of these changes occur in genes previously shown to be regulated by the sexual transfer of 20E and may be due to divergent utilization of this steroid hormone in the two species.
Synthesis and conformational analysis of linear homo- and heterooligomers from novel 2-C-branched sugar amino acids (SAAs)
Authors: Tian Guang-Zong , Hu Jing , Zhang Heng-Xi , Rademacher Christoph , Zou Xiao-Peng , Zheng Hong-Ning , Xu Fei , Wang Xiao-Li , Linker Torsten , Yin Jian
Published: April 2018

Sugar amino acids (SAAs), as biologically interesting structures bearing both amino and carboxylic acid functional groups represent an important class of multifunctional building blocks. In this study, we develop an easy access to novel SAAs in only three steps starting from nitro compounds in high yields in analytically pure form, easily available by ceric (IV) mediated radical additions. Such novel SAAs have been applied in the assembly of total nine carbopeptoids with the form of linear homo- and heterooligomers for the structural investigations employing circular dichroism (CD) spectroscopy, which suggest that the carbopeptoids emerge a well-extended, left (or right)-handed conformation similar to polyproline II (PPII) helices. NMR studies also clearly demonstrated the presence of ordered secondary structural elements. 2D-ROESY spectra were acquired to identify
i+1
NH ↔ 
i
C
1
H,
i
C
2
H correlations which support the conformational analysis of tetramers by CD spectroscopy. These findings provide interesting information of SAAs and their oligomers as potential scaffolds for discovering new drugs and materials.
A closer look at cross-validation for assessing the accuracy of gene regulatory networks and models
Authors: Tabe-Bordbar Shayan , Emad Amin , Zhao Sihai Dave , Sinha Saurabh
Published: April 2018

Cross-validation (CV) is a technique to assess the generalizability of a model to unseen data. This technique relies on assumptions that may not be satisfied when studying genomics datasets. For example, random CV (RCV) assumes that a randomly selected set of samples, the test set, well represents unseen data. This assumption doesn’t hold true where samples are obtained from different experimental conditions, and the goal is to learn regulatory relationships among the genes that generalize beyond the observed conditions. In this study, we investigated how the CV procedure affects the assessment of supervised learning methods used to learn gene regulatory networks (or in other applications). We compared the performance of a regression-based method for gene expression prediction estimated using RCV with that estimated using a clustering-based CV (CCV) procedure. Our analysis illustrates that RCV can produce over-optimistic estimates of the model’s generalizability compared to CCV. Next, we defined the ‘distinctness’ of test set from training set and showed that this measure is predictive of performance of the regression method. Finally, we introduced a simulated annealing method to construct partitions with gradually increasing distinctness and showed that performance of different gene expression prediction methods can be better evaluated using this method.
Premyogenic progenitors derived from human pluripotent stem cells expand in floating culture and differentiate into transplantable myogenic progenitors
Authors: Sakai-Takemura Fusako , Narita Asako , Masuda Satoru , Wakamatsu Toshifumi , Watanabe Nobuharu , Nishiyama Takashi , Nogami Ken’ichiro , Blanc Matthias , Takeda Shin’ichi , Miyagoe-Suzuki Yuko
Published: April 2018

Human induced pluripotent stem cells (hiPSCs) are a potential source for cell therapy of Duchenne muscular dystrophy. To reliably obtain skeletal muscle progenitors from hiPSCs, we treated hiPS cells with a Wnt activator, CHIR-99021 and a BMP receptor inhibitor, LDN-193189, and then induced skeletal muscle cells using a previously reported sphere-based culture. This protocol greatly improved sphere formation efficiency and stably induced the differentiation of myogenic cells from hiPS cells generated from both healthy donors and a patient with congenital myasthenic syndrome. hiPSC-derived myogenic progenitors were enriched in the CD57(−) CD108(−) CD271(+) ERBB3(+) cell fraction, and their differentiation was greatly promoted by TGF-β inhibitors. TGF-β inhibitors down-regulated the NFIX transcription factor, and NFIX short hairpin RNA (shRNA) improved the differentiation of iPS cell-derived myogenic progenitors. These results suggest that NFIX inhibited differentiation of myogenic progenitors. hiPSC-derived myogenic cells differentiated into myofibers in muscles of NSG-mdx
4Cv
mice after direct transplantation. Our results indicate that our new muscle induction protocol is useful for cell therapy of muscular dystrophies.
Dissociating the effect of disruptive colouration on localisation and identification of camouflaged targets
Authors: Sharman Rebecca J. , Moncrieff Stephen J. , Lovell P. George
Published: April 2018

Disruptive camouflage features contrasting areas of pigmentation across the animals’ surface that form false edges which disguise the shape of the body and impede detection. In many taxa these false edges feature local contrast enhancement or edge enhancement, light areas have lighter edges and dark areas have darker edges. This additional quality is often overlooked in existing research. Here we ask whether disruptive camouflage can have benefits above and beyond concealing location. Using a novel paradigm, we dissociate the time courses of localisation and identification of a target in a single experiment. We measured the display times required for a stimulus to be located or identified (the critical duration). Targets featured either uniform, disruptive or edge enhanced disruptive colouration. Critical durations were longer for identifying targets with edge enhanced disruptive colouration camouflage even when presented against a contrasting background, such that all target types were located equally quickly. For the first time, we establish empirically that disruptive camouflage not only conceals location, but also disguises identity. This shows that this form of camouflage can be useful even when animals are not hidden. Our findings offer insights into how edge enhanced disruptive colouration undermines visual perception by disrupting object recognition.
Local Moment Instability of Os in Honeycomb Li2.15Os0.85O3
Authors: Wallace M. K. , LaBarre P. G. , Li Jun , Pi S.-T. , Pickett W. E. , Dessau D. S. , Haskel D. , Ramirez A. P. , Subramanian M. A.
Published: April 2018

Compounds with honeycomb structures occupied by strong spin orbit coupled (SOC) moments are considered to be candidate Kitaev quantum spin liquids. Here we present the first example of Os on a honeycomb structure, Li2.15(3)Os0.85(3)O3 (C2/c, a = 5.09 Å, b = 8.81 Å, c = 9.83 Å, β = 99.3°). Neutron diffraction shows large site disorder in the honeycomb layer and X-ray absorption spectroscopy indicates a valence state of Os (4.7 ± 0.2), consistent with the nominal concentration. We observe a transport band gap of Δ = 243 ± 23 meV, a large van Vleck susceptibility, and an effective moment of 0.85 μB, much lower than expected from 70% Os(+5). No evidence of long range order is found above 0.10 K but a spin glass-like peak in ac-susceptibility is observed at 0.5 K. The specific heat displays an impurity spin contribution in addition to a power law ∝T(0.63±0.06). Applied density functional theory (DFT) leads to a reduced moment, suggesting incipient itineracy of the valence electrons, and finding evidence that Li over stoichiometry leads to Os(4+)−Os(5+) mixed valence. This local picture is discussed in light of the site disorder and a possible underlying quantum spin liquid state.
The origin, type and hydrocarbon generation potential of organic matter in a marine-continental transitional facies shale succession (Qaidam Basin, China)
Authors: Wang Guo-Cang , Sun Min-Zhuo , Gao Shu-Fang , Tang Li
Published: April 2018

This organic-rich shale was analyzed to determine the type, origin, maturity and depositional environment of the organic matter and to evaluate the hydrocarbon generation potential of the shale. This study is based on geochemical (total carbon content, Rock-Eval pyrolysis and the molecular composition of hydrocarbons) and whole-rock petrographic (maceral composition) analyses. The petrographic analyses show that the shale penetrated by the Chaiye 2 well contains large amounts of vitrinite and sapropelinite and that the organic matter within these rocks is type III and highly mature. The geochemical analyses show that these rocks are characterized by high total organic carbon contents and that the organic matter is derived from a mix of terrestrial and marine sources and highly mature. These geochemical characteristics are consistent with the results of the petrographic analyses. The large amounts of organic matter in the Carboniferous shale succession penetrated by the Chaiye 2 well may be due to good preservation under hypersaline lacustrine and anoxic marine conditions. Consequently, the studied shale possesses very good hydrocarbon generation potential because of the presence of large amounts of highly mature type III organic matter.
Day length is associated with physical activity and sedentary behavior among older women
Authors: Schepps Mitchell A. , Shiroma Eric J. , Kamada Masamitsu , Harris Tamara B. , Lee I-Min
Published: April 2018

Physical activity may be influenced by one’s physical environment, including day length and weather. Studies of physical activity, day length, and weather have primarily used self-reported activity, broad meteorological categorization, and limited geographic regions. We aim to examine the association of day length and physical activity in a large cohort of older women, covering a wide geographic range. Participants (N = 16,741; mean (SD) age = 72.0 (SD = 5.7) years) were drawn from the Women’s Health Study and lived throughout the United States. Physical activity was assessed by accelerometer (ActiGraph GT3X+) between 2011 and 2015. Day length and weather information were obtained by matching weather stations to the participants’ location using National Oceanic and Atmospheric Administration databases. Women who experienced day lengths greater than 14 hours had 5.5% more steps, 9.4% more moderate-to-vigorous physical activity, and 1.6% less sedentary behavior, compared to women who experienced day lengths less than 10 hours, after adjusting for age, accelerometer wear, temperature, and precipitation. Day length is associated with physical activity and sedentary behavior in older women, and needs to be considered in programs promoting physical activity as well as in the analyses of accelerometer data covering wide geographic regions.
Discrimination of positional isomers by ion mobility mass spectrometry: application to organic semiconductors
Authors: Duez Quentin , Romain Maxime , Tonneaux Corentin , De Winter Julien , Lemaur Vincent , Cornil Jérôme , Poriel Cyril , Gerbaux Pascal
Published: April 2018

Ion mobility mass spectrometry is introduced as a versatile technique for positional isomerism discrimination in the field of organic-based optoelectronics.
Nonconventional regeneration of redox enzymes – a practical approach for organic synthesis?
Authors: Zhang Wuyuan , Hollmann Frank
Published: April 2018

Oxidoreductases have become useful tools in the hands of chemists to perform selective and mild oxidation and reduction reactions.
Structure evolution and luminescence properties of lithium(i)–sulfonate complexes constructed from multifunctional arenedisulfonic acids
Authors: Ge Zhong-Yi , Zhu Zhi-Biao , Deng Zhao-Peng , Huo Li-Hua , Gao Shan
Published: April 2018

Eight new lithium(i) complexes constructed from multifunctional arenedisulfonic acids have been synthesized. The structural evolution and luminescence properties of these complexes can be attributed to the coordination modes and anion types of ligands.
Phonon-mediated stabilization and softening of 2D transition metal carbides: case studies of Ti2CO2 and Mo2CO2
Authors: Fu Zhongheng , Legut Dominik , Germann Timothy C. , Si Chen , Du Shiyu , Francisco Joseph S. , Zhang Ruifeng
Published: April 2018

We build up the relationship among electronic structures, electronic band energies/elastic energies and the instability modes of MXenes.
Hydrogen adsorption trends on Al-doped Ni2P surfaces for optimal catalyst design
Authors: Hakala Mikko , Laasonen Kari
Published: April 2018

Nanoparticles of nickel phosphide are promising materials to replace the currently used rare Pt-group metals at cathode-side electrodes in devices for electrochemical hydrogen production.
Physical mechanism of photoinduced intermolecular charge transfer enhanced by fluorescence resonance energy transfer
Authors: Zong Huan , Wang Jiangcai , Mu Xijiao , Xu Xuefeng , Li Jing , Wang Xiaoyuan , Long Feixiang , Wang Jiaxi , Sun Mengtao
Published: April 2018

Photoinduced intermolecular charge transfer (PICT) and fluorescence resonance energy transfer (FRET) in donor–acceptor systems have been investigated experimentally and theoretically.
Quantum spin Hall insulator BiXH (XH = OH, SH) monolayers with a large bulk band gap
Authors: Hu Xing-Kai , Lyu Ji-Kai , Zhang Chang-Wen , Wang Pei-Ji , Ji Wei-Xiao , Li Ping
Published: April 2018

A large bulk band gap is critical for the application of two-dimensional topological insulators (TIs) in spintronic devices operating at room temperature.
Epitaxial and atomically thin graphene–metal hybrid catalyst films: the dual role of graphene as the support and the chemically-transparent protective cap
Authors: Abdelhafiz Ali , Vitale Adam , Buntin Parker , deGlee Ben , Joiner Corey , Robertson Alex , Vogel Eric M. , Warner Jamie , Alamgir Faisal M.
Published: April 2018

Revolutionary catalyst protection by single layer graphene capping, tremendous catalyst lifetime longevity and activity enhancement towards oxygen reduction reaction.
Ionic liquids vs. microporous solids as reusable reaction media for the catalytic C–H functionalization of indoles with alcohols
Authors: Cirujano Francisco G. , Stalpaert Maxime , Vos Dirk E. De
Published: April 2018

High performance reusable catalysts and reaction media are evaluated for the green alkylation of indoles with alcohols under mild and solvent-free conditions.
Activation of CN bonds by high-valent group 6 metal chlorides, including the conversion of an α-diimine into a functionalized imidazolium
Authors: Bartalucci Niccolò , Bortoluzzi Marco , Zacchini Stefano , Pampaloni Guido , Marchetti Fabio
Published: April 2018

The direct interactions of WCl6and MoCl5with α-diimines (and also a carbodiimide in the case of MoCl5) have been explored, leading to unusual reaction pathways.
Enhancing photovoltaic performance of DSSCs sensitized with Ru-II complexes by D–π–A configured carbazole based co-sensitizers
Authors: Naik Praveen , Elmorsy Mohamed R. , Su Rui , El-Shafei Ahmed , Adhikari Airody Vasudeva
Published: April 2018

Simple D–π–A architectured carbazole based dyes, P1–4, were employed as co-sensitizers in DSSCs sensitized with Ru-II complexes, viz.NCSU-10 and N3. The results revealed that, the NCSU-10 sensitized devices displayed improved photovoltaic performance when co-sensitized with P1 and P3.
An ammonia detecting mechanism for organic transistors as revealed by their recovery processes
Authors: Zhou Xu , Niu Kaifeng , Wang Zi , Huang Lizhen , Chi Lifeng
Published: April 2018

An ammonia detecting mechanism that involved pre-doping and de-doping was revealed by the recovery process of an organic transistor.
Catalytic metal-based systems for controlled statistical copolymerisation of lactide with a lactone
Authors: Stirling E. , Champouret Y. , Visseaux M.
Published: April 2018

A comprehensive survey of the recent developments of metal-based catalysts for the ROcoP of lactide with another lactone is presented.
Normal, ICAR and photomediated butadiene-ATRP with iron complexes
Authors: Vasu Vignesh , Kim Joon-Sung , Yu Hyun-Seok , Bannerman William I. , Johnson Mark E. , Asandei Alexandru D.
Published: April 2018

FeX2 or FeX3 (X = Cl ≫ Br) alone or with P ≫ X > O > N > C ligands and bromoester initiators enable the successful ATRP of butadiene in toluene at 110 °C.
Designed synthesis of organosilica nanoparticles for enzymatic biodiesel production
Authors: Kalantari Mohammad , Yu Meihua , Jambhrunkar Manasi , Liu Yang , Yang Yannan , Huang Xiaodan , Yu Chengzhong
Published: April 2018

Benzene-bridged dendritic mesoporous organosilica nanoparticles significantly improve the catalytic activity and stability of lipase.