bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of drinking water pH on the human gut microbiota and glucose regulation: results of a randomized controlled cross-over intervention
Authors: Hansen Tue H. , Thomassen Mette T. , Madsen Mia L. , Kern Timo , Bak Emilie G. , Kashani Alireza , Allin Kristine H. , Hansen Torben , Pedersen Oluf
Published: November 2018

Studies in rodent models have shown that alterations in drinking water pH affect both the composition of the gut microbiota and host glucose regulation. To explore a potential impact of electrochemically reduced alkaline (pH ≈ 9) versus neutral (pH ≈ 7) drinking water (2 L/day) on human intestinal microbiota and host glucose metabolism we conducted a randomized, non-blinded, cross-over study (two 2-week intervention periods, separated by a 3-week wash-out) in 29 healthy, non-smoking Danish men, aged 18 to 35 years, with a body mass index between 20.0 to 27.0 kg m-2. Volunteers were ineligible if they had previously had abdominal surgery, had not been weight stabile for at least two months, had received antibiotic treatment within 2 months, or had a habitual consumption of caloric or artificially sweetened beverages in excess of 1 L/week or an average intake of alcohol in excess of 7 units/week. Microbial DNA was extracted from faecal samples collected at four time points, before and after each intervention, and subjected to 16S rRNA gene amplicon sequencing (Illumina MiSeq, V4 region). Glycaemic regulation was evaluated by means of an oral glucose tolerance test.No differential effect of alkaline versus neutral drinking water was observed for the primary outcome, overall gut microbiota diversity as represented by Shannon’s index. Similarly, neither a differential effect on microbiota richness or community structure was observed. Nor did we observe a differential effect on the abundance of individual operational taxonomic units (OTUs) or genera. However, analyses of within period effects revealed a significant (false discovery rate ≤5%) increase in the relative abundance of 9 OTUs assigned to order Clostridiales, family Ruminococcaceae, genus Bacteroides, and species Prevotella copri, indicating a potential effect of quantitative or qualitative changes in habitual drinking habits. An increase in the concentration of plasma glucose at 30 minutes and the incremental area under the curve of plasma glucose from 0 30 and 0 120 minutes, respectively, was observed when comparing the alkaline to the neutral intervention. However, results did not withstand correction for multiplicity. In contrast to what has been reported in rodents, a change in drinking water pH had no impact on the composition of the gut microbiota or glucose regulation in young male adults. The study is registered at www.clinicaltrials.gov (NCT02917616).
Ongoing human chromosome end extension revealed by analysis of BioNano and nanopore data
Authors: Shao Haojing , Zhou Chenxi , Cao Minh Duc , Coin Lachlan J. M.
Published: November 2018

The majority of human chromosome ends remain incompletely assembled due to their highly repetitive structure. In this study, we use BioNano data to anchor and extend chromosome ends from two European trios as well as two unrelated Asian genomes. At least 11 BioNano assembled chromosome ends are structurally divergent from the reference genome, including both missing sequence and extensions. These extensions are heritable and in some cases divergent between Asian and European samples. Six out of nine predicted extension sequences from NA12878 can be confirmed and filled by nanopore data. We identify two multi-kilobase sequence families both enriched more than 100-fold in extension sequence (p-values < 1e-5) whose origins can be traced to interstitial sequence on ancestral primate chromosome 7. Extensive sub-telomeric duplication of these families has occurred in the human lineage subsequent to divergence from chimpanzees.
Touch engages visual spatial contextual processing
Authors: Pérez-Bellido Alexis , Pappal Ryan D. , Yau Jeffrey M.
Published: November 2018

The spatial context in which we view a visual stimulus strongly determines how we perceive the stimulus. In the visual tilt illusion, the perceived orientation of a visual grating is affected by the orientation signals in its surrounding context. Conceivably, the spatial context in which a visual grating is perceived can be defined by interactive multisensory information rather than visual signals alone. Here, we tested the hypothesis that tactile signals engage the neural mechanisms supporting visual contextual modulation. Because tactile signals also convey orientation information and touch can selectively interact with visual orientation perception, we predicted that tactile signals would modulate the visual tilt illusion. We applied a bias-free method to measure the tilt illusion while testing visual-only, tactile-only or visuo-tactile contextual surrounds. We found that a tactile context can influence visual tilt perception. Moreover, combining visual and tactile orientation information in the surround results in a larger tilt illusion relative to the illusion achieved with the visual-only surround. These results demonstrate that the visual tilt illusion is subject to multisensory influences and imply that non-visual signals access the neural circuits whose computations underlie the contextual modulation of vision.
Lung fibroblasts express a miR-19a-19b-20a sub-cluster to suppress TGF-β-associated fibroblast activation in murine pulmonary fibrosis
Authors: Souma Kunihiko , Shichino Shigeyuki , Hashimoto Shinichi , Ueha Satoshi , Tsukui Tatsuya , Nakajima Takuya , Suzuki Hiroshi I. , Shand Francis H. W. , Inagaki Yutaka , Nagase Takahide , Matsushima Kouji
Published: November 2018

Lung fibroblasts play a pivotal role in pulmonary fibrosis, a devastating lung disease, by producing extracellular matrix. MicroRNAs (miRNAs) suppress numerous genes post-transcriptionally; however, the roles of miRNAs in activated fibroblasts in fibrotic lungs remain poorly understood. To elucidate these roles, we performed global miRNA-expression profiling of fibroblasts from bleomycin- and silica-induced fibrotic lungs and investigated the functions of miRNAs in activated lung fibroblasts. Clustering analysis of global miRNA-expression data identified miRNA signatures exhibiting increased expression during fibrosis progression. Among these signatures, we found that a miR-19a-19b-20a sub-cluster suppressed TGF-β-induced activation of fibroblasts in vitro. Moreover, to elucidate whether fibroblast-specific intervention against the sub-cluster modulates pathogenic activation of fibroblasts in fibrotic lungs, we intratracheally transferred the sub-cluster-overexpressing fibroblasts into bleomycin-treated lungs. Global transcriptome analysis of the intratracheally transferred fibroblasts revealed that the sub-cluster not only downregulated expression of TGF-β-associated pro-fibrotic genes, including Acta2, Col1a1, Ctgf, and Serpine1, but also upregulated expression of the anti-fibrotic genes Dcn, Igfbp5, and Mmp3 in activated lung fibroblasts. Collectively, these findings indicated that upregulation of the miR-19a-19b-20a sub-cluster expression in lung fibroblasts counteracted TGF-β-associated pathogenic activation of fibroblasts in murine pulmonary fibrosis.
The geranyl acetophenone tHGA attenuates human bronchial smooth muscle proliferation via inhibition of AKT phosphorylation
Authors: Yap Hui Min , Lee Yu Zhao , Harith Hanis Hazeera , Tham Chau Ling , Cheema Manraj Singh , Shaari Khozirah , Israf Daud Ahmad
Published: November 2018

Increased airway smooth muscle (ASM) mass is a prominent hallmark of airway remodeling in asthma. Inhaled corticosteroids and long-acting beta2-agonists remain the mainstay of asthma therapy, however are not curative and ineffective in attenuating airway remodeling. The geranyl acetophenone 2,4,6-trihydroxy-3-geranyl acetophenone (tHGA), an in-house synthetic non-steroidal compound, attenuates airway hyperresponsiveness and remodeling in murine models of asthma. The effect of tHGA upon human ASM proliferation, migration and survival in response to growth factors was assessed and its molecular target was determined. Following serum starvation and induction with growth factors, proliferation and migration of human bronchial smooth muscle cells (hBSMCs) treated with tHGA were significantly inhibited without any significant effects upon cell survival. tHGA caused arrest of hBSMC proliferation at the G1 phase of the cell cycle with downregulation of cell cycle proteins, cyclin D1 and diminished degradation of cyclin-dependent kinase inhibitor (CKI), p27Kip1. The inhibitory effect of tHGA was demonstrated to be related to its direct inhibition of AKT phosphorylation, as well as inhibition of JNK and STAT3 signal transduction. Our findings highlight the anti-remodeling potential of this drug lead in chronic airway disease.
Arabidopsis molybdenum cofactor sulfurase ABA3 contributes to anthocyanin accumulation and oxidative stress tolerance in ABA-dependent and independent ways
Authors: Watanabe Shunsuke , Sato Muneo , Sawada Yuji , Tanaka Maho , Matsui Akihiro , Kanno Yuri , Hirai Masami Yokota , Seki Motoaki , Sakamoto Atsushi , Seo Mitsunori
Published: November 2018

Arabidopsis ABA3 is an enzyme involved in the synthesis of the sulfurated form of the molybdenum (Mo) cofactor (MoCo), which is required for the enzymatic activity of so-called Mo enzymes such as aldehyde oxidase (AO) and xanthine dehydrogenase (XDH). It has been reported that AO and XDH are essential for the biosynthesis of the bioactive compounds, ABA and allantoin, respectively. However, aba3 mutants often exhibit pleiotropic phenotypes that are not explained by defects in ABA and/or allantoin biosynthesis, leading us to hypothesize that ABA3 regulates additional metabolic pathways. To reveal the currently unidentified functions of ABA3 we compared transcriptome and metabolome of the Arabidopsis aba3 mutant with those of wild type and a typical ABA-deficient mutant aba2. We found that endogenous levels of anthocyanins, members of the flavonoid group, were significantly lower in the aba3 mutant than in the wild type or the aba2 mutant under oxidative stress. In contrast, mutants defective in the AO and XDH holoenzymes accumulated significantly higher levels of anthocyanins when compared with aba3 mutant under the same conditions. Our findings shed light on a key role of ABA3 in the ABA- and allantoin-independent accumulation of anthocyanins during stress responses.
A soil-carrying lacewing larva in Early Cretaceous Lebanese amber
Authors: Pérez-de la Fuente Ricardo , Peñalver Enrique , Azar Dany , Engel Michael S.
Published: November 2018

Diverse organisms protect and camouflage themselves using varied materials from their environment. This adaptation and associated behaviours (debris-carrying) are well known in modern green lacewing larvae (Neuroptera: Chrysopidae), mostly due to the widespread use of these immature insects in pest control. However, the evolutionary history of this successful strategy and related morphological adaptations in the lineage are still far from being understood. Here we describe a novel green lacewing larva, Tyruschrysa melqart gen. et sp. nov., from Early Cretaceous Lebanese amber, carrying a preserved debris packet composed by soil particles entangled among specialised setae of extremely elongate tubular tubercles. The new morphotype has features related to the debris-carrying habit that are unknown from extant or extinct green lacewings, namely a high number of tubular tubercle pairs on the abdomen and tubular tubercle setae with mushroom-shaped endings that acted as anchoring points for debris. The current finding expands the diversity of exogenous materials used by green lacewing larvae in deep time, and represents the earliest direct evidence of debris-carrying in the lineage described to date. The debris-carrying larval habit likely played a significant role during the initial phases of diversification of green lacewings.
CCAAT/Enhancer Binding Protein β inhibits myogenic differentiation via ID3
Authors: AlSudais Hamood , Lala-Tabbert Neena , Wiper-Bergeron Nadine
Published: November 2018

Myogenesis is regulated by the coordinated expression of muscle regulatory factors, a family of transcription factors that includes MYOD, MYF5, myogenin and MRF4. Muscle regulatory factors are basic helix-loop-helix transcription factors that heterodimerize with E proteins to bind the regulatory regions of target genes. Their activity can be inhibited by members of the Inhibitor of DNA binding and differentiation (ID) family, which bind E-proteins with high affinity, thereby preventing muscle regulatory factor-dependent transcriptional responses. CCAAT/Enhancer Binding protein beta (C/EBPβ) is a transcription factor expressed in myogenic precursor cells that acts to inhibit myogenic differentiation, though the mechanism remains poorly understood. We identify Id3 as a novel C/EBPβ target gene that inhibits myogenic differentiation. Overexpression of C/EBPβ stimulates Id3 mRNA and protein expression, and is required for C/EBPβ-mediated inhibition of myogenic differentiation. Misexpression of C/EBPβ in myogenic precursors, such as in models of cancer cachexia, prevents the differentiation of myogenic precursors and we show that loss of Id3 rescues differentiation under these conditions, suggesting that the stimulation of Id3 expression by C/EBPβ is an important mechanism by which C/EBPβ inhibits myogenic differentiation.
Whole-exome sequencing identifies two novel mutations in KCNQ4 in individuals with nonsyndromic hearing loss
Authors: Jung Jinsei , Choi Hyun Been , Koh Young Ik , Rim John Hoon , Choi Hye Ji , Kim Sung Huhn , Lee Jae Hyun , An Jieun , Kim Ami , Lee Joon Suk , Joo Sun Young , Yu Seyoung , Choi Jae Young , Kang Tong Mook , Gee Heon Yung
Published: November 2018

Mutations in potassium voltage-gated channel subfamily Q member 4 (KCNQ4) are etiologically linked to a type of nonsyndromic hearing loss, deafness nonsyndromic autosomal dominant 2 (DFNA2). We performed whole-exome sequencing for 98 families with hearing loss and found mutations in KCNQ4 in five families. In this study, we characterized two novel mutations in KCNQ4: a missense mutation (c.796G>T; p.Asp266Tyr) and an in-frame deletion mutation (c.259_267del; p.Val87_Asn89del). p.Asp266Tyr located in the channel pore region resulted in early onset and moderate hearing loss, whereas p.Val87_Asn89del located in the N-terminal cytoplasmic region resulted in late onset and high frequency-specific hearing loss. When heterologously expressed in HEK 293 T cells, both mutant proteins did not show defects in protein trafficking to the plasma membrane or in interactions with wild-type (WT) KCNQ4 channels. Patch-clamp analysis demonstrated that both p.Asp266Tyr and p.Val87_Asn89del mutant channels lost conductance and were completely unresponsive to KCNQ activators, such as retigabine, zinc pyrithione, and ML213. Channels assembled from WT-p.Asp266Tyr concatemers, like those from WT-WT concatemers, exhibited conductance and responsiveness to KCNQ activators. However, channels assembled from WT-p.Val87_Asn89del concatemers showed impaired conductance, suggesting that p.Val87_Asn89del caused complete loss-of-function with a strong dominant-negative effect on functional WT channels. Therefore, the main pathological mechanism may be related to loss of K+ channel activity, not defects in trafficking.
The Hsp70 Gene Family in Solanum tuberosum: Genome-Wide Identification, Phylogeny, and Expression Patterns
Authors: Liu Jia , Pang Xin , Cheng Yuan , Yin Yuhe , Zhang Qiang , Su Wenbin , Hu Bing , Guo Qinwei , Ha Si , Zhang Jianping , Wan Hongjian
Published: November 2018

Heat shock protein 70 (Hsp70) family members play important roles in protecting plants against abiotic stresses, including salt, drought, heat, and cold. In this study, 20 putative StHsp70 genes were identified in potato (Solanum tuberosum L.) through the integration of the gene structures, chromosome locations, phylogenetic relationships, and expression profiles. These StHsp70 genes were classified into five sub-families based on phylogenetic analysis. Chromosome mapping revealed that they were unevenly and unequally distributed on 10 of the 12 chromosomes. Furthermore, segmental and tandem duplication events contributed to the expansion of the StHsp70 genes. Phylogenetic tree of the HSP70 genes from potato and other plant species revealed multiple sub-families. These findings indicated a common ancestor which had generated diverse sub-families prior to a mono-dicot split. In addition, expression analysis using RNA-seq revealed that the majority of these genes were expressed in at least one of the tested tissue, and were induced by Phytophthora infestans. Then, based on qRT-PCR analysis, the results showed that the transcript levels of some of the StHsp70 genes could be remarkably induced by such abiotic and hormone stresses, which indicated their potential roles in mediating the responses of potato plants to both abiotic and biotic stress conditions.
El Niño drives a widespread ulcerative skin disease outbreak in Galapagos marine fishes
Authors: Lamb Robert W. , Smith Franz , Aued Anaide W. , Salinas-de-León Pelayo , Suarez Jenifer , Gomez-Chiarri Marta , Smolowitz Roxanna , Giray Cem , Witman Jon D.
Published: November 2018

Climate change increases local climatic variation and unpredictability, which can alter ecological interactions and trigger wildlife disease outbreaks. Here we describe an unprecedented multi-species outbreak of wild fish disease driven by a climate perturbation. The 2015–16 El Niño generated a +2.5 °C sea surface temperature anomaly in the Galapagos Islands lasting six months. This coincided with a novel ulcerative skin disease affecting 18 teleost species from 13 different families. Disease signs included scale loss and hemorrhagic ulcerated patches of skin, fin deterioration, lethargy, and erratic behavior. A bacterial culture isolated from skin lesions of two of the affected fish species was identified by sequencing of the 16S rRNA gene as a Rahnella spp. Disease prevalence rates were linearly correlated with density in three fish species. In January 2016, disease prevalence reached 51.1% in the ring-tailed damselfish Stegastes beebei (n = 570) and 18.7% in the king angelfish Holacanthus passer (n = 318), corresponding to 78% and 86% decreases in their populations relative to a 4.5-year baseline, respectively. We hypothesize that this outbreak was precipitated by the persistent warm temperatures and lack of planktonic productivity that characterize extreme El Niño events, which are predicted to increase in frequency with global warming.
Strong association between vertebral endplate defect and Modic change in the general population
Authors: Määttä Juhani H. , Rade Marinko , Freidin Maxim B. , Airaksinen Olavi , Karppinen Jaro , Williams Frances M. K.
Published: November 2018

Modic change (MC) is considered an independent risk factor for low back pain (LBP) but its aetiology remains unclear. In this cross-sectional, large-scale population-based study we sought to characterise associations between endplate defect (ED) and MC in a population sample of broad age range. The study population consisted of 831 twin volunteers (including 4155 discs and 8310 endplates) from TwinsUK. Lumbar T2-weighted MR images were coded for ED and MC. Total endplate (TEP) score was calculated at each intervertebral disc while receiver operating curves (ROC) were calculated to define critical endplate values predictive of MC. MC was detected in 32.1% of the subjects, with a significantly higher prevalence at lower lumbar levels (3.5% at L1/2-L3/4 vs. 15.9% at L4/5-L5/S1, p < 0.001). TEP score was strongly and independently associated with MC at each lumbar level (risk estimates from 1.49 to 2.44; all p ≤ 0.001) after adjustment for age, sex, BMI and twin pairing. ROC analysis showed a TEP score cut-off of 6 above which there was a significantly higher prevalence of MC. In conclusion, ED were strongly associated with MC at every lumbar level. These findings support the hypothesis that endplate defect is a major initiating factor for the cascade of events that may include disc degeneration (DD) and MC.
Evoked Alpha Power is Reduced in Disconnected Consciousness During Sleep and Anesthesia
Authors: Darracq Matthieu , Funk Chadd M. , Polyakov Daniel , Riedner Brady , Gosseries Olivia , Nieminen Jaakko O. , Bonhomme Vincent , Brichant Jean-Francois , Boly Melanie , Laureys Steven , Tononi Giulio , Sanders Robert D.
Published: November 2018

Sleep and anesthesia entail alterations in conscious experience. Conscious experience may be absent (unconsciousness) or take the form of dreaming, a state in which sensory stimuli are not incorporated into conscious experience (disconnected consciousness). Recent work has identified features of cortical activity that distinguish conscious from unconscious states; however, less is known about how cortical activity differs between disconnected states and normal wakefulness. We employed transcranial magnetic stimulation–electroencephalography (TMS–EEG) over parietal regions across states of anesthesia and sleep to assess whether evoked oscillatory activity differed in disconnected states. We hypothesized that alpha activity, which may regulate perception of sensory stimuli, is altered in the disconnected states of rapid eye movement (REM) sleep and ketamine anesthesia. Compared to wakefulness, evoked alpha power (8–12 Hz) was decreased during disconnected consciousness. In contrast, in unconscious states of propofol anesthesia and non-REM (NREM) sleep, evoked low-gamma power (30–40 Hz) was decreased compared to wakefulness or states of disconnected consciousness. These findings were confirmed in subjects in which dream reports were obtained following serial awakenings from NREM sleep. By examining signatures of evoked cortical activity across conscious states, we identified novel evidence that suppression of evoked alpha activity may represent a promising marker of sensory disconnection.
Modulation of acoustomechanical instability and bifurcation behavior of soft materials
Authors: Xin Fengxian , Lu Tian Jian
Published: November 2018

We demonstrate acoustically triggered giant deformation of soft materials, and reveal the snap-through instability and bifurcation behavior of soft materials in nonlinear deformation regime in response to combined loading of mechanical and acoustic radiation forces. Our theoretical results suggest that acoustomechanical instability and bifurcation can be readily modulated by varying either the mechanical or acoustic force. This modulation functionality arises from the sensitivity of acoustic wave propagation to nonlinear deformation of soft material, particularly to ratio of initial geometrical size of soft material to acoustic wavelength in the material. The tunable acoustomechanical instability and bifurcation behavior of soft materials enables innovative design of programmable mechanical metamaterials. PACS numbers: 43.35.+d, 43.25.+y, 46.70.De, 61.41.+e.
Experimental screening studies on rabies virus transmission and oral rabies vaccination of the Greater Kudu (Tragelaphus strepsiceros)
Authors: Hassel Rainer , Vos Ad , Clausen Peter , Moore Susan , van der Westhuizen Jolandie , Khaiseb Siegfried , Kabajani Juliet , Pfaff Florian , Höper Dirk , Hundt Boris , Jago Mark , Bruwer Floris , Lindeque Pauline , Finke Stefan , Freuling Conrad M. , Müller Thomas
Published: November 2018

Rabies in the Greater Kudu (Tragelaphus strepsiceros)in Namibia is unique and found in such magnitude as has not been reported elsewhere in southern Africa. Reasons as to why Kudus appear to be exceptionally susceptible to rabies still remain speculative at best. Because the current severe rabies endemic in Kudus continues to have an enormous negative impact on the Namibian agricultural sector, we set out to question existing dogmas regarding the epidemiology of the disease in a unique experimental setting. In addition, we explored effective measures to protect these antelopes. Although we were able to confirm high susceptibly of kudus for rabies and sporadic horizontal rabies virus transmission to contact animals, we contend that these observations cannot plausibly explain the rapid spread of the disease in Kudus over large territories. Since parenteral vaccination of free-roaming Kudus is virtually impossible, oral rabies vaccination using modified life virus vaccines with a high safety profile would be the ultimate solution to the problem. In a proof-of-concept study using a 3rd generation oral rabies virus vaccine construct (SPBN GASGAS) we found evidence that Kudus can be vaccinated by the oral route and protected against a subsequent rabies infection. In a second phase, more targeted studies need to be initiated by focusing on optimizing oral vaccine uptake and delivery.
Computational characterization and control of electrical conductivity of nanowire composite network under mechanical deformation
Authors: Hwang Jinyoung , Sohn Hiesang , Lee Sang Hyun
Published: November 2018

Quantitative models to predict the electrical performance of 1-D nanowire (NW) composite networks under external deformation such as bending and patterning are developed by Monte-Carlo based computations, and appropriate solutions are addressed to enhance the tolerance of the sheet resistance (Rs) of the NW networks under the deformation. In addition, several strategies are employed to improve further the robustness of the sheet resistance against the network deformation. In the case of bending, outstanding bending durability of a hybrid NW network coated on a 2-D sheet is confirmed with a numerical model, and a network of NWs aligned unidirectionally toward bend axis is introduced to alleviate the sheet resistance degradation. In the case of a narrowly patterned channel, the conductivity enhancement of a network of NWs aligned in parallel to the channel with reduced channel is validated, and a network made with two types of NWs with different lengths is suggested to enhance the tolerance of the electrical conductivity. The results offer useful design guidelines to the use of the 1-D NW percolation network for flexible transparent conducting electrodes.
Embryonic Stem Cells Derived Kidney Organoids as Faithful Models to Target Programmed Nephrogenesis
Authors: Tan Zenglai , Shan Jingdong , Rak-Raszewska Aleksandra , Vainio Seppo J.
Published: November 2018

The kidney is a complex organ that is comprised of thousands of nephrons developing through reciprocal inductive interactions between metanephric mesenchyme (MM) and ureteric bud (UB). The MM undergoes mesenchymal to epithelial transition (MET) in response to the signaling from the UB. The secreted protein Wnt4, one of the Wnt family members, is critical for nephrogenesis as mouse Wnt4−/− mutants fail to form pretubular aggregates (PTA) and therefore lack functional nephrons. Here, we generated mouse embryonic stem cell (mESC) line lacking Wnt4 by applying the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated systems 9 (Cas9). We describe here, differentiation of the wild type and Wnt4 knockout mESCs into kidney progenitors, and such cells induced to undergo nephrogenesis by the mouse E11.5 UB mediated induction. The wild type three-dimensional (3D) self-organized organoids depict appropriately segmented nephron structures, while the Wnt4-deficient organoids fail to undergo the MET, as is the case in the phenotype of the Wnt4 knockout mouse model in vivo. In summary, we have established a platform that combine CRISPR/Cas9 and kidney organoid technologies to model kidney development in vitro and confirmed that mutant organoids are able to present similar actions as in the in vivo studies.
Biomarker Phenotype for Early Diagnosis and Triage of Sepsis to the Pediatric Intensive Care Unit
Authors: Mickiewicz Beata , Thompson Graham C. , Blackwood Jaime , Jenne Craig N. , Winston Brent W. , Vogel Hans J. , Joffe Ari R.
Published: November 2018

Early diagnosis and triage of sepsis improves outcomes. We aimed to identify biomarkers that may advance diagnosis and triage of pediatric sepsis. Serum and plasma samples were collected from young children (1–23 months old) with sepsis on presentation to the Pediatric Intensive Care Unit (PICU-sepsis, n = 46) or Pediatric Emergency Department (PED-sepsis, n = 58) and PED-non-sepsis patients (n = 19). Multivariate analysis was applied to distinguish between patient groups. Results were compared to our results for older children (2–17 years old). Common metabolites and protein-mediators were validated as potential biomarkers for a sepsis-triage model to differentiate PICU-sepsis from PED-sepsis in children age 1 month-17 years. Metabolomics in young children clearly separated the PICU-sepsis and PED-sepsis cohorts: sensitivity 0.71, specificity 0.93, and AUROC = 0.90 ± 0.03. Adding protein-mediators to the model did not improve performance. The seven metabolites common to the young and older children were used to create the sepsis-triage model. Validation of the sepsis-triage model resulted in sensitivity: 0.83 ± 0.02, specificity: 0.88 ± 0.05 and AUROC 0.93 ± 0.02. The metabolic-based biomarkers predicted which sepsis patients required care in a PICU versus those that could be safely cared for outside of a PICU. This has potential to inform appropriate triage of pediatric sepsis, particularly in EDs with less experience evaluating children.
Ca2+ efflux via plasma membrane Ca2+-ATPase mediates chemotaxis in ascidian sperm
Authors: Yoshida Kaoru , Shiba Kogiku , Sakamoto Ayako , Ikenaga Jumpei , Matsunaga Shigeru , Inaba Kazuo , Yoshida Manabu
Published: November 2018

When a spermatozoon shows chemotactic behavior, transient [Ca2+]i increases in the spermatozoon are induced by an attractant gradient. The [Ca2+]i increase triggers a series of stereotypic responses of flagellar waveforms that comprise turning and straight-swimming. However, the molecular mechanism of [Ca2+]i modulation controlled by the attractants is not well defined. Here, we examined receptive mechanisms for the sperm attractant, SAAF, in the ascidian, Ciona intestinalis, and identified a plasma membrane Ca2+-ATPase (PMCA) as a SAAF-binding protein. PMCA is localized in sperm flagella membranes and seems to interact with SAAF through basic amino acids located in the second and third extracellular loops. ATPase activity of PMCA was enhanced by SAAF, and PMCA inhibitors, 5(6)-Carboxyeosin diacetate and Caloxin 2A1, inhibited chemotactic behavior of the sperm. Furthermore, Caloxin 2A1 seemed to inhibit efflux of [Ca2+]i in the sperm, and SAAF seemed to competitively reduce the effect of Caloxin 2A1. On the other hand, chemotactic behavior of the sperm was disordered not only at low-Ca2+, but also at high-Ca2+ conditions. Thus, PMCA is a potent candidate for the SAAF receptor, and direct control of Ca2+ efflux via PMCA is a fundamental mechanism to mediate chemotactic behavior in the ascidian spermatozoa.
Biotic resistance and vegetative propagule pressure co-regulate the invasion success of a marine clonal macrophyte
Authors: Balestri Elena , Vallerini Flavia , Menicagli Virginia , Barnaba Sara , Lardicci Claudio
Published: November 2018

Propagule pressure is considered a major driver of plant invasion success. Great propagule pressure would enable invasive species to colonize new areas overcoming the resistance of native species. Many highly invasive aquatic macrophytes regenerate from vegetative propagules, but few studies have experimentally investigated the importance of propagule pressure and biotic resistance, and their interaction, in determining invasion success. By manipulating both recipient habitat and the input of vegetative propagules of the invasive seaweed Caulerpa cylindracea in mesocosm, we examined whether higher propagule pressure would overcome the resistance of a native congeneric (Caulerpa prolifera) and influence its performance. With the native, C. cylindracea population frond number decreased irrespectively of pressure level. High propagule pressure did not increase stolon length and single plant size decreased due to the effects of intra- and interspecific competition. Native biomass decreased with increasing C. cylindracea propagule pressure. These results indicate that higher propagule pressure may fail in enhancing C. cylindracea invasion success in habitats colonized by the native species, and they suggest that biotic resistance and propagule pressure co-regulate the invasion process. These findings emphasize the need to preserve/restore native seaweed populations and may help to design effective management actions to prevent further C. cylindracea spread.
von Willebrand factor deficiency does not influence angiotensin II-induced abdominal aortic aneurysm formation in mice
Authors: Portier Irina , Martinod Kimberly , Desender Linda , Vandeputte Nele , Deckmyn Hans , Vanhoorelbeke Karen , De Meyer Simon F.
Published: November 2018

Abdominal aortic aneurysm (AAA) refers to a localized dilation of the abdominal aorta that exceeds the normal diameter by 50%. AAA pathophysiology is characterized by progressive inflammation, vessel wall destabilization and thrombus formation. Our aim was to investigate the potential involvement of von Willebrand factor (VWF), a thrombo-inflammatory plasma protein, in AAA pathophysiology using a dissection-based and angiotensin II infusion-induced AAA mouse model. AAA formation was induced in both wild-type and VWF-deficient mice by subcutaneous implantation of an osmotic pump, continuously releasing 1000 ng/kg/min angiotensin II. Survival was monitored, but no significant difference was observed between both groups. After 28 days, the suprarenal aortic segment of the surviving mice was harvested. Both AAA incidence and severity were similar in wild-type and VWF-deficient mice, indicating that AAA formation was not significantly influenced by the absence of VWF. Although VWF plasma levels increased after the infusion period, these increases were not correlated with AAA progression. Also detailed histological analyses of important AAA hallmarks, including elastic degradation, intramural thrombus formation and leukocyte infiltration, did not reveal differences between both groups. These data suggest that, at least in the angiotensin II infusion-induced AAA mouse model, the role of VWF in AAA pathophysiology is limited.
Cardol triene inhibits dengue infectivity by targeting kl loops and preventing envelope fusion
Authors: Kanyaboon Parichat , Saelee Thanaphon , Suroengrit Aphinya , Hengphasatporn Kowit , Rungrotmongkol Thanyada , Chavasiri Warinthorn , Boonyasuppayakorn Siwaporn
Published: November 2018

Dengue virus causes a global burden that specific chemotherapy has not been established. A previous report suggested that anacardic acid inhibited hepatitis C virus infection. Here, we explored structure activity relationship of anacardic acid, cardanol, and cardol homologues with anti-DENV cellular infectivities. Cardol triene showed the highest therapeutic index at 29.07 with the CC50 and EC50 of 207.30 ± 5.24 and 7.13 ± 0.72 µM, respectively. Moreover, we observed that the more unsaturated the hydrocarbon tail, the higher the CC50s in all head groups. High CC50s were also found in HepG-2, THP-1, and HEK-293 cell lines where cardol triene CC50s were 140.27 ± 8.44, 129.77 ± 12.08, and 92.80 ± 3.93 µM, respectively. Cardol triene expressed pan-dengue inhibition with the EC50s of 5.35 to 8.89 µM and kl loops of dengue envelope proteins were major targets. The strong binding energy at T48, E49, A50, P53, K128, V130, L135, M196, L198, Q200, W206, L207, I270, and L277 prevented cellular pH-dependent fusion. Zika virus kl loops were aligned in the closed position preventing cardol triene to bind and inhibit fusion and infectivity. This study showed for the first time that cardol triene had a potential for further development as anti-dengue inhibitors.
First observation of direct methane emission to the atmosphere from the subglacial domain of the Greenland Ice Sheet
Authors: Christiansen Jesper Riis , Jørgensen Christian Juncher
Published: November 2018

During a 2016 field expedition to the West Greenland Ice Sheet, a striking observation of significantly elevated CH4 concentrations of up to 15 times the background atmospheric concentration were measured directly in the air expelled with meltwater at a subglacial discharge point from the Greenland Ice Sheet. The range of hourly subglacial CH4 flux rate through the discharge point was estimated to be 3.1 to 134 g CH4 hr−1. These measurements are the first observations of direct emissions of CH4 from the subglacial environment under the Greenlandic Ice Sheet to the atmosphere and indicate a novel emission pathway of CH4 that is currently a non-quantified component of the Arctic CH4 budget.
Complete chloroplast genome sequence of Dryopteris fragrans (L.) Schott and the repeat structures against the thermal environment
Authors: Gao Rui , Wang Wenzhong , Huang Qingyang , Fan Ruifeng , Wang Xu , Feng Peng , Zhao Guangming , Bian Shuang , Ren Hongli , Chang Ying
Published: November 2018

Dryopteris fragrans (L.) Schott is a fern growing on the surface of hot rocks and lava. It is exposed to sunlight directly and bears local hot environment. We sequenced the complete nucleotide sequence of its chloroplast (cp) genome. The cp genome was 151,978 bp in length, consisting of a large single-copy region (85,332 bp), a small single-copy region (31,947 bp) and a pair of inverted repeats (17,314 bp). The cp genome contained 112 genes and 345 RNA editing sites in protein-coding genes. Simple sequence repeats (SSRs) and long repeat structure pairs (30–55 bp) were identified. The number and percent of repeat structures are extremely high in ferns. Thermal denaturation experiments showed its cp genome to have numerous, dispersed and high GC percent repeat structures, which conferred the strongest thermal stability. This repeat-heavy genome may provide the molecular basis of how D. fragrans cp survives its hot environment.
Small Mountainous Rivers Generate High-Frequency Internal Waves in Coastal Ocean
Authors: Osadchiev A. A.
Published: November 2018

High-frequency internal waves propagating offshore in small river plumes are regularly observed at satellite imagery in many world regions. In this work we describe a mechanism of generation of these internal waves by discharges of small and rapid rivers inflowing to coastal sea. Friction between river runoff at high velocity and the subjacent sea of one order of magnitude lower velocity causes abrupt deceleration of a freshened flow and increase of its depth, i.e., a hydraulic jump is formed. Transition from supercritical to subcritical flow conditions induces generation of high-frequency internal waves that propagate off a river mouth at a stratified layer between a buoyant river plume and subjacent ambient sea and influence turbulence and mixing at this layer. Basing on in situ and satellite data we estimated wavelengths, phase speeds, and frequencies of internal waves generated in small river plumes located off the northeastern coast of the Black Sea. This process is typical for many other world mountainous regions where numerous and closely spaced small and rapid rivers inflow to sea during high discharge periods and can strongly influence, first, structure and dynamics of river plumes and, second, physical, biological, and geochemical processes in adjacent coastal areas.
Water-repellent Hybrid Nanowire and Micro-scale Denticle Structures on Flexible Substrates of Effective Air Retention
Authors: Jo Sungwon , Ahn Seongbin , Lee Heungsoo , Jung Chul-Min , Song Simon , Kim Dong Rip
Published: November 2018

The air retention capability of a superhydrophobic surface plays the crucial role of drag reduction in an aqueous environment. Here, fabrication of water-repellent hybrid structural surfaces by synthesizing superhydrophobic nanowires with a high aspect ratio on micro-scale denticle structures to improve their air holding capacity in water is reported. The hybrid structure is realized by carrying out polymer molding of denticle structures on flexible substrates, hydrothermal growth of nanowires, and subsequent ultra-thin film coating. This technique is readily applicable to large areas, and the fabricated substrates are attachable onto curved surfaces. Our engineered, super water-repellent hybrid structures are found to effectively maintain air bubbles on their surfaces in a highly shear flow condition with a wall shear stress of up to 33.4 Pa, due to the combined effects of the micro-scale denticle structure, which reduces flow resistance, and the superhydrophobic, high-aspect-ratio nanowire structure, which enhances the capillary force to maintain the air bubbles. Our results show the importance of developing superhydrophobic structures of improved air retention capability.
Evaluation of Insecticides induced hormesis on the demographic parameters of Myzus persicae and expression changes of metabolic resistance detoxification genes
Authors: Sial Muhammad Umair , Zhao Zhenzhen , Zhang Lan , Zhang Yanning , Mao Liangang , Jiang Hongyun
Published: November 2018

Insecticide induced-hormesis is a bi-phasic phenomenon generally characterized by low-dose induction and high-dose inhibition. It has been linked to insect pest outbreaks and insecticide resistance, which have importance in the integrated pest management (IPM). In this paper, hormesis effects of four insecticides on demographic parameters and expression of genes associated with metabolic resistance were evaluated in a field collected population of the green peach aphid, Myzus persicae Sulzer. The bioassay results showed that imidacloprid was more toxic than acetamiprid, deltamethrin and lambda-cyhalothrin. After exposure to sublethal doses of acetamiprid and imidacloprid for four generations, significant prolonged nymphal duration and increased fecundity were observed. Subsequently, mean generation time (T) and gross reproductive rate (GRR) was significantly increased. Moreover, expression of CYP6CY3 gene associated with resistance to neonicotinoids was increased significantly compared to the control. For pyrethriods, across generation exposure to sublethal doses of lambda cyhalothrin and deltamethrin prolonged the immature development duration. However, the expression of E4 gene in M. persicase was decreased by deltamethrin exposure but increased by lambda cyhalothrin. Based on results, demographic fitness parameters were effected by hormetic dose and accompanied with detoxifying genes alteration, hence, which would be evaluated in developing optimized insect pest management strategies.
RETRACTED ARTICLE: Non-coding RNAome of RPE cells under oxidative stress suggests unknown regulative aspects of Retinitis pigmentosa etiopathogenesis
Authors: Donato Luigi , Scimone Concetta , Rinaldi Carmela , D’Angelo Rosalia , Sidoti Antonina
Published: November 2018

The discovery of thousands of non-coding RNAs has revolutionized molecular biology, being implicated in several biological processes and diseases. To clarify oxidative stress role on Retinitis pigmentosa, a very heterogeneous and inherited ocular disorder group characterized by progressive retinal degeneration, we realized a comparative transcriptome analysis of human retinal pigment epithelium cells, comparing two groups, one treated with oxLDL and one untreated, in four time points (1 h, 2 h, 4 h, 6 h). Data analysis foresaw a complex pipeline, starting from CLC Genomics Workbench, STAR and TopHat2/TopHat-Fusion alignment comparisons, followed by transcriptomes assembly and expression quantification. We then filtered out non-coding RNAs and continued the computational analysis roadmap with specific tools and databases for long non-coding RNAs (FEELnc), circular RNAs (CIRCexplorer, UROBORUS, CIRI, KNIFE, CircInteractome) and piwi-interacting RNAs (piRNABank, piRNA Cluster, piRBase, PILFER). Finally, all detected non-coding RNAs underwent pathway analysis by Cytoscape software. Eight-hundred and fifty-four non-coding RNAs, between long non-coding RNAs and PIWI-interacting, were differentially expressed throughout all considered time points, in treated and untreated samples. These non-coding RNAs target host genes involved in several biochemical pathways are related to compromised response to oxidative stress, visual functions, synaptic impairment of retinal neurotransmission, impairment of the interphotoreceptor matrix and blood – retina barrier, all leading to retinal cell death. These data suggest that non-coding RNAs could play a relevant role in Retinitis pigmentosa etiopathogenesis.
Monitoring Mechanical, Electronic, and Catalytic Trends in a Titanium Metal Organic Framework Under the Influence of Guest-Molecule Encapsulation Using Density Functional Theory
Authors: Dong Hieu C. , Nguyen Ha L. , Le Hung M. , Thoai Nam , Kawazoe Yoshiyuki , Nguyen-Manh Duc
Published: November 2018

In this study, we conduct a density functional theory investigation to study the mechanical stability of a titanium-based metal organic framework (MOF-901), which was hypothetically assumed to possess 2D characteristics. It is systematically found that the encapsulation of methanol enhances the mechanical stability of MOF-901 as the elastic tensors Cij of MOF-901∙nMeOH are higher than the corresponding Cij quantities reported for solvent-free MOF-901. Moreover, the 2D characteristics of MOF-901 is confirmed by verifying the negative values of C33. At the same time, the band gap of MOF-901 is observed to be solvent-dependent. In its pure form, MOF-901 possesses a direct gap (Eg) of 2.07 eV, with the valence and conduction bands mainly constituted by electrons of 4-aminobenzoate linkers. Introducing methanol into MOF-901 causes distortion to the 4-aminobenzoate geometry, thereby induces electronic degeneracy to the conduction bands. Consequently, Eg is narrowed to 1.84 eV with 5.7 wt% MeOH or 1.63 eV with 11.4 wt% MeOH. Hence, it is possible to tailor the band gap of MOF-901 by controlling methanol guest, which only acquires van der Waals interaction to the framework. In addition, our theoretical prediction shows a Ti(IV) site can undergo electronic hopping to become Ti(III) under the effect of visible light (~440–443 nm). Then, Ti(III) is capable of breaking the C-Br bond in ethyl α-bromophenylacetate spontaneously, which in turn activates the polymerization of methyl methacrylate with an energy barrier of 0.30 eV.