bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular architecture of the PBP2–MreC core bacterial cell wall synthesis complex
Authors: Contreras-Martel Carlos , Martins Alexandre , Ecobichon Chantal , Trindade Daniel Maragno , Matteï Pierre-Jean , Hicham Samia , Hardouin Pierre , Ghachi Meriem El , Boneca Ivo G. , Dessen Andréa
Published: September 2017

Bacterial cell wall biosynthesis is an essential process that requires the coordinated activity of peptidoglycan biosynthesis enzymes within multi-protein complexes involved in cell division (the “divisome”) and lateral wall growth (the “elongasome”). MreC is a structural protein that serves as a platform during wall elongation, scaffolding other essential peptidoglycan biosynthesis macromolecules, such as penicillin-binding proteins. Despite the importance of these multi-partite complexes, details of their architecture have remained elusive due to the transitory nature of their interactions. Here, we present the crystal structures of the soluble PBP2:MreC core elongasome complex from Helicobacter pylori, and of uncomplexed PBP2. PBP2 recognizes the two-winged MreC molecule upon opening of its N-terminal region, revealing a hydrophobic zipper that serves as binding platform. The PBP2:MreC interface is essential both for protein recognition in vitro and maintenance of bacterial shape and growth. This work allows visualization as to how peptidoglycan machinery proteins are scaffolded, revealing interaction regions that could be targeted by tailored inhibitors.
External oxidant-free electrooxidative [3 + 2] annulation between phenol and indole derivatives
Authors: Liu Kun , Tang Shan , Huang Pengfei , Lei Aiwen
Published: September 2017

Intermolecular [3 + 2] annulation is one of the most straightforward approaches to construct five membered heterocycles. However, it generally requires the use of functionalized substrates. An ideal reaction approach is to achieve dehydrogenative [3 + 2] annulation under oxidant-free conditions. Here we show an electrooxidative [3 + 2] annulation between phenols and N-acetylindoles under undivided electrolytic conditions. Neither external chemical oxidants nor metal catalysts are required to facilitate the dehydrogenation processes. This reaction protocol provides an environmentally friendly way for the selective synthesis of benzofuroindolines. Various N-acetylindoles bearing different C-3 and C-2 substituents are suitable in this electrochemical transformation, furnishing corresponding benzofuroindolines in up to 99% yield.
Analog quantum simulation of the Rabi model in the ultra-strong coupling regime
Authors: Braumüller Jochen , Marthaler Michael , Schneider Andre , Stehli Alexander , Rotzinger Hannes , Weides Martin , Ustinov Alexey V.
Published: September 2017

The quantum Rabi model describes the fundamental mechanism of light-matter interaction. It consists of a two-level atom or qubit coupled to a quantized harmonic mode via a transversal interaction. In the weak coupling regime, it reduces to the well-known Jaynes–Cummings model by applying a rotating wave approximation. The rotating wave approximation breaks down in the ultra-strong coupling regime, where the effective coupling strength g is comparable to the energy ω of the bosonic mode, and remarkable features in the system dynamics are revealed. Here we demonstrate an analog quantum simulation of an effective quantum Rabi model in the ultra-strong coupling regime, achieving a relative coupling ratio of g/ω ~ 0.6. The quantum hardware of the simulator is a superconducting circuit embedded in a cQED setup. We observe fast and periodic quantum state collapses and revivals of the initial qubit state, being the most distinct signature of the synthesized model.
Insights into beta cell regeneration for diabetes via integration of molecular landscapes in human insulinomas
Authors: Wang Huan , Bender Aaron , Wang Peng , Karakose Esra , Inabnet William B. , Libutti Steven K. , Arnold Andrew , Lambertini Luca , Stang Micheal , Chen Herbert , Kasai Yumi , Mahajan Milind , Kinoshita Yayoi , Fernandez-Ranvier Gustavo , Becker Thomas C. , Takane Karen K. , Walker Laura A. , Saul Shira , Chen Rong , Scott Donald K. , Ferrer Jorge , Antipin Yevgeniy , Donovan Michael , Uzilov Andrew V. , Reva Boris , Schadt Eric E. , Losic Bojan , Argmann Carmen , Stewart Andrew F.
Published: September 2017

Although diabetes results in part from a deficiency of normal pancreatic beta cells, inducing human beta cells to regenerate is difficult. Reasoning that insulinomas hold the “genomic recipe” for beta cell expansion, we surveyed 38 human insulinomas to obtain insights into therapeutic pathways for beta cell regeneration. An integrative analysis of whole-exome and RNA-sequencing data was employed to extensively characterize the genomic and molecular landscape of insulinomas relative to normal beta cells. Here, we show at the pathway level that the majority of the insulinomas display mutations, copy number variants and/or dysregulation of epigenetic modifying genes, most prominently in the polycomb and trithorax families. Importantly, these processes are coupled to co-expression network modules associated with cell proliferation, revealing candidates for inducing beta cell regeneration. Validation of key computational predictions supports the concept that understanding the molecular complexity of insulinoma may be a valuable approach to diabetes drug discovery.
Loss of Endometrial Sodium Glucose Cotransporter SGLT1 is Detrimental to Embryo Survival and Fetal Growth in Pregnancy
Authors: Salker Madhuri S. , Singh Yogesh , Zeng Ni , Chen Hong , Zhang Shaqiu , Umbach Anja T , Fakhri Hajar , Kohlhofer Ursula , Quintanilla-Martinez Leticia , Durairaj Ruban R. Peter , Barros Flavio S. V. , Vrljicak Pavle , Ott Sascha , Brucker Sara Y , Wallwiener Diethelm , Vrhovac Madunić Ivana , Breljak Davorka , Sabolić Ivan , Koepsell Hermann , Brosens Jan J. , Lang Florian
Published: September 2017

Embryo implantation requires a hospitable uterine environment. A key metabolic change that occurs during the peri-implantation period, and throughout early pregnancy, is the rise in endometrial glycogen content. Glycogen accumulation requires prior cellular uptake of glucose. Here we show that both human and murine endometrial epithelial cells express the high affinity Na+-coupled glucose carrier SGLT1. Ussing chamber experiments revealed electrogenic glucose transport across the endometrium in wild type (Slc5a1+/+) but not in SGLT1 deficient (Slc5a1−/−) mice. Endometrial glycogen content, litter size and weight of offspring at birth were significantly lower in Slc5a1−/− mice. In humans, SLC5A1 expression was upregulated upon decidualization of primary endometrial stromal cells. Endometrial SLC5A1 expression during the implantation window was attenuated in patients with recurrent pregnancy loss when compared with control subjects. Our findings reveal a novel mechanism establishing adequate endometrial glycogen stores for pregnancy. Disruption of this histiotrophic pathway leads to adverse pregnancy outcome.
Pteropods are excellent recorders of surface temperature and carbonate ion concentration
Authors: Keul N. , Peijnenburg K. T. C. A. , Andersen N. , Kitidis V. , Goetze E. , Schneider R. R.
Published: September 2017

Pteropods are among the first responders to ocean acidification and warming, but have not yet been widely explored as carriers of marine paleoenvironmental signals. In order to characterize the stable isotopic composition of aragonitic pteropod shells and their variation in response to climate change parameters, such as seawater temperature, pteropod shells (Heliconoides inflatus) were collected along a latitudinal transect in the Atlantic Ocean (31° N to 38° S). Comparison of shell oxygen isotopic composition to depth changes in the calculated aragonite equilibrium oxygen isotope values implies shallow calcification depths forH.inflatus(75 m). This species is therefore a good potential proxy carrier for past variations in surface ocean properties. Furthermore, we identified pteropod shells to be excellent recorders of climate change, as carbonate ion concentration and temperature in the upper water column have dominant influences on pteropod shell carbon and oxygen isotopic composition. These results, in combination with a broad distribution and high abundance, make the pteropod species studied here,H.inflatus, a promising new proxy carrier in paleoceanography.
Knockout of the epilepsy gene Depdc5 in mice causes severe embryonic dysmorphology with hyperactivity of mTORC1 signalling
Authors: Hughes James , Dawson Ruby , Tea Melinda , McAninch Dale , Piltz Sandra , Jackson Dominique , Stewart Laura , Ricos Michael G. , Dibbens Leanne M. , Harvey Natasha L. , Thomas Paul
Published: September 2017

DEPDC5 mutations have recently been shown to cause epilepsy in humans. Evidence from in vitro studies has implicated DEPDC5 as a negative regulator of mTORC1 during amino acid insufficiency as part of the GATOR1 complex. To investigate the role of DEPDC5 in vivo we generated a null mouse model using targeted CRISPR mutagenesis. Depdc5 homozygotes display severe phenotypic defects between 12.5-15.5 dpc, including hypotrophy, anaemia, oedema, and cranial dysmorphology as well as blood and lymphatic vascular defects. mTORC1 hyperactivity was observed in the brain of knockout embryos and in fibroblasts and neurospheres isolated from knockout embryos and cultured in nutrient deprived conditions. Heterozygous mice appeared to be normal and we found no evidence of increased susceptibility to seizures or tumorigenesis. Together, these data support mTORC1 hyperactivation as the likely pathogenic mechanism that underpins DEPDC5 loss of function in humans and highlights the potential utility of mTORC1 inhibitors in the treatment of DEPDC5-associated epilepsy.
A Potent Tartrate Resistant Acid Phosphatase Inhibitor to Study the Function of TRAP in Alveolar Macrophages
Authors: Boorsma Carian E. , van der Veen T. Anienke , Putri Kurnia S. S. , de Almeida Andreia , Draijer Christina , Mauad Thais , Fejer Gyorgy , Brandsma Corry-Anke , van den Berge Maarten , Bossé Yohan , Sin Don , Hao Ke , Reithmeier Anja , Andersson Göran , Olinga Peter , Timens Wim , Casini Angela , Melgert Barbro N.
Published: September 2017

The enzyme tartrate resistant acid phosphatase (TRAP, two isoforms 5a and 5b) is highly expressed in alveolar macrophages, but its function there is unclear and potent selective inhibitors of TRAP are required to assess functional aspects of the protein. We found higher TRAP activity/expression in lungs of patients with chronic obstructive pulmonary disease (COPD) and asthma compared to controls and more TRAP activity in lungs of mice with experimental COPD or asthma. Stimuli related to asthma and/or COPD were tested for their capacity to induce TRAP. Receptor activator of NF-κb ligand (RANKL) and Xanthine/Xanthine Oxidase induced TRAP mRNA expression in mouse macrophages, but only RANKL also induced TRAP activity in mouse lung slices. Several Au(III) coordination compounds were tested for their ability to inhibit TRAP activity and [Au(4,4′-dimethoxy-2,2′-bipyridine)Cl2][PF6] (AubipyOMe) was found to be the most potent inhibitor of TRAP5a and 5b activity reported to date (IC50 1.3 and 1.8 μM respectively). AubipyOMe also inhibited TRAP activity in murine macrophage and human lung tissue extracts. In a functional assay with physiological TRAP substrate osteopontin, AubipyOMe inhibited mouse macrophage migration over osteopontin-coated membranes. In conclusion, higher TRAP expression/activity are associated with COPD and asthma and TRAP is involved in regulating macrophage migration.
Triclosan Disrupts SKN-1/Nrf2-Mediated Oxidative Stress Response in C. elegans and Human Mesenchymal Stem Cells
Authors: Yoon Dong Suk , Choi Yoorim , Cha Dong Seok , Zhang Peng , Choi Seong Mi , Alfhili Mohammad Abdulmohsen , Polli Joseph Ryan , Pendergrass DeQwon , Taki Faten A. , Kapalavavi Brahmam , Pan Xiaoping , Zhang Baohong , Blackwell T. Keith , Lee Jin Woo , Lee Myon-Hee
Published: September 2017

Triclosan (TCS), an antimicrobial chemical with potential endocrine-disrupting properties, may pose a risk to early embryonic development and cellular homeostasis during adulthood. Here, we show that TCS induces toxicity in both the nematode C. elegans and human mesenchymal stem cells (hMSCs) by disrupting the SKN-1/Nrf2-mediated oxidative stress response. Specifically, TCS exposure affected C. elegans survival and hMSC proliferation in a dose-dependent manner. Cellular analysis showed that TCS inhibited the nuclear localization of SKN-1/Nrf2 and the expression of its target genes, which were associated with oxidative stress response. Notably, TCS-induced toxicity was significantly reduced by either antioxidant treatment or constitutive SKN-1/Nrf2 activation. As Nrf2 is strongly associated with aging and chemoresistance, these findings will provide a novel approach to the identification of therapeutic targets and disease treatment.
Transcriptional Output Transiently Spikes Upon Mitotic Exit
Authors: Vaňková Hausnerová Viola , Lanctôt Christian
Published: September 2017

The pulsatile nature of gene activity has recently emerged as a general property of the transcriptional process. It has been shown that the frequency and amplitude of transcriptional bursts can be subjected to extrinsic regulation. Here we have investigated if these parameters were constant throughout the cell cycle using the single molecule RNA FISH technique. We found evidence of transcriptional spikes upon mitotic exit in three different human cell lines. Recording of cell growth prior to hybridization and immuno-RNA FISH analysis revealed that these spikes were short-lived and subsided before completion of cytokinesis. The transient post-mitotic increase in transcriptional output was found to be the result of cells displaying a higher number of active alleles and/or an increased number of nascent transcripts per active allele, indicating that both the burst fraction and the amplitude of individual bursts can be increased upon mitotic exit. Our results further suggest that distinct regulatory mechanisms are at work shortly after mitotic exit and during the rest of interphase. We speculate that transcriptional spikes are associated with chromatin decondensation, a hallmark of post-mitotic cells that might alter the dynamics of transcriptional regulators and effectors.
Embryological evidence substantiates the subcoxal theory on the origin of pleuron in insects
Authors: Mashimo Yuta , Machida Ryuichiro
Published: September 2017

The lateral body plate pleuron is a significant structure in insects that contributes to the development and elaboration of wings and limbs (appendages). Although the pleuron is thought to originate from the proximal-most appendicular segment, the subcoxa, details remain unclear, and the morphological boundary between the dorsal body plate tergum and appendage (BTA) has not been clearly specified. Employing low-vacuum scanning electron microscopy (SEM) and the nano-suit method for SEM, we followed, in detail, the development of the thoracic segments of the two-spotted cricket Gryllus bimaculatus and succeeded in clearly defining the BTA. This study demonstrates the subcoxal origin of the pleuron, suggests the tergal origin of spiracles, and reveals that the wing proper originates exclusively from the tergum, whereas the wing hinge and direct muscles may be appendicular in origin, suggesting the dual origin (i.e., tergal plus appendicular origin) of wings.
Doping colloidal bcc crystals — interstitial solids and meta-stable clusters
Authors: Higler Ruben , Sprakel Joris
Published: September 2017

The addition of a small amount of dopant impurities to crystals is a common method to tune the properties of materials. Usually the doping grade is restricted by the low solubility of the dopants; increasing the doping concentration beyond this solubility limit leads to supersaturated solutions in which dopant clusters dominate the material properties, often leading to deterioration of strength and performance. Descriptions of doped solids often assume that thermal excitations of the on average perfect matrix are small. However, especially for bcc crystals close to their melting point it has recently become clear that the effects of thermal disorder are strong. Here we study the doping of weak bcc crystals of charged colloids via Brownian dynamics simulations. We find a complex phase diagram upon varying the dopant concentration. At low dopant concentrations we find an interstitial solid solution. As we increase the amount of dopants a complex meta-stable liquid-in-solid cluster phase emerges. Ultimately this phase becomes meta-stable with respect to macroscopic crystal-crystal coexistence. These results illustrate the complex behaviour that emerges when thermal excitations of the matrix drive impure crystals to a weak state.
Co@Carbon and Co 3 O4@Carbon nanocomposites derived from a single MOF for supercapacitors
Authors: Dai Engao , Xu Jiao , Qiu Junjie , Liu Shucheng , Chen Ping , Liu Yi
Published: September 2017

Developing a composite electrode containing both carbon and transition metal/metal oxide as the supercapacitor electrode can combine the merits and mitigate the shortcomings of both the components. Herein, we report a simple strategy to prepare the hybrid nanostructure of Co@Carbon and Co3O4@Carbon by pyrolysis a single MOFs precursor. Co-based MOFs (Co-BDC) nanosheets with morphology of regular parallelogram slice have been prepared by a bottom-up synthesis strategy. One-step pyrolysis of Co-BDC, produces a porous carbon layer incorporating well-dispersed Co and Co3O4nanoparticles. The as-prepared cobalt-carbon composites exhibit the thin layer morphology and large specific surface area with hierarchical porosity. These features significantly improve the ion-accessible surface area for charge storage and shorten the ion transport length in thin dimension, thus contributing to a high specific capacitance. Improved capacitance performance was successfully realized for the asymmetric supercapacitors (ASCs) (Co@Carbon//Co3O4@Carbon), better than those of the symmetric supercapacitors (SSCs) based on Co@Carbon and Co3O4@Carbon materials (i.e., Co@Carbon//Co@Carbon and Co3O4@Carbon//Co3O4@Carbon). The working voltage of the ASCs can be extended to 1.5 V and show a remarkable high power capability in aqueous electrolyte. This work provides a controllable strategy for nanostructured carbon-metal and carbon-metal oxide composite electrodes from a single precursor.
Human intestinal organoids express histo-blood group antigens, bind norovirus VLPs, and support limited norovirus replication
Authors: Zhang Dongsheng , Tan Ming , Zhong Weiming , Xia Ming , Huang Pengwei , Jiang Xi
Published: September 2017

Through pluripotent stem cell (PSC) technology, human intestinal organoids (HIOs) with remarkably similarity to the fetal intestine in cellular composition, architecture, and absorptive/secretory functions have been successfully developed, providing a useful in vitro model system to study the structure and function of human congenital gut and intestinally related diseases. We report here the usefulness of HIOs as a model system to study intestinal carbohydrate expression, virus-host interaction, and replication of human noroviruses (huNoVs). We found that fully developed HIOs express effectively various types 1 and 2 HBGAs, including Lewis, secretor, and nonsecretor antigens, distributing on the glycocalyx. Selected huNoV-like particles (VLPs) bound the glycocalyx of HIOs with matched HBGA phenotypes. Using GII.4 huNoV positive stool filtrates, we demonstrated limited huNoV replication in HIOs with corresponding HBGAs through detection of viral RNAs by RT-PCR and capsid antigens by immunostaining methods. Our data suggested that, after further improvements, HIOs can be a useful model to study intestinal glycan expression, huNoV-intestine interaction, and huNoV infection in the intestine.
Role of autophagy in cell-penetrating peptide transfection model
Authors: Dowaidar Moataz , Gestin Maxime , Cerrato Carmine Pasquale , Jafferali Mohammed Hakim , Margus Helerin , Kivistik Paula Ann , Ezzat Kariem , Hallberg Einar , Pooga Margus , Hällbrink Mattias , Langel Ülo
Published: September 2017

Cell-penetrating peptides (CPPs) uptake mechanism is still in need of more clarification to have a better understanding of their action in the mediation of oligonucleotide transfection. In this study, the effect on early events (1 h treatment) in transfection by PepFect14 (PF14), with or without oligonucleotide cargo on gene expression, in HeLa cells, have been investigated. The RNA expression profile was characterized by RNA sequencing and confirmed by qPCR analysis. The gene regulations were then related to the biological processes by the study of signaling pathways that showed the induction of autophagy-related genes in early transfection. A ligand library interfering with the detected intracellular pathways showed concentration-dependent effects on the transfection efficiency of splice correction oligonucleotide complexed with PepFect14, proving that the autophagy process is induced upon the uptake of complexes. Finally, the autophagy induction and colocalization with autophagosomes have been confirmed by confocal microscopy and transmission electron microscopy. We conclude that autophagy, an inherent cellular response process, is triggered by the cellular uptake of CPP-based transfection system. This finding opens novel possibilities to use autophagy modifiers in future gene therapy.
Anserine (beta-alanyl-3-methyl-L-histidine) improves neurovascular-unit dysfunction and spatial memory in aged AβPPswe/PSEN1dE9 Alzheimer’s-model mice
Authors: Kaneko Jun , Enya Akiko , Enomoto Kota , Ding Qiong , Hisatsune Tatsuhiro
Published: September 2017

Anserine/carnosine supplementation improves cerebral blood flow and verbal episodic memory in elderly people, as we previously reported. Anserine’s buffering activity is superior to that of carnosine at neutral pH. In human sera, carnosine but not anserine is rapidly cleaved by carnosinase, limiting its effectiveness. This study examined the effects of anserine on AβPPswe/PSEN1dE9 Alzheimer’s disease (AD) model mice over 18-months old, an age at which these mice exhibit detectable memory deficits. We found that 8 weeks of anserine treatment completely recovered the memory deficits, improved pericyte coverage on endothelial cells in the brain, and diminished chronic glial neuroinflammatory reactions in these mice. These results suggest that anserine (beta-alanyl-3-methyl-L-histidine) supplementation improved memory functions in AD-model mice by exerting a protective effect on the neurovascular units, which are composed of endothelial cells, pericytes, and supporting glial cells.
Understanding contact gating in Schottky barrier transistors from 2D channels
Authors: Prakash Abhijith , Ilatikhameneh Hesameddin , Wu Peng , Appenzeller Joerg
Published: September 2017

In this article, a novel two-path model is proposed to quantitatively explain sub-threshold characteristics of back-gated Schottky barrier FETs (SB-FETs) from 2D channel materials. The model integrates the “conventional” model for SB-FETs with the phenomenon of contact gating – an effect that significantly affects the carrier injection from the source electrode in back-gated field effect transistors. The two-path model is validated by a careful comparison with experimental characteristics obtained from a large number of back-gated WSe2 devices with various channel thicknesses. Our findings are believed to be of critical importance for the quantitative analysis of many three-terminal devices with ultrathin body channels.
Age at menarche and prevalence of preterm birth: Results from the Healthy Baby Cohort study
Authors: Li Hui , Song Lulu , Shen Lijun , Liu Bingqing , Zheng Xiaoxuan , Zhang Lina , Li Yuanyuan , Xia Wei , Lu Bin , Zhang Bin , Zhou Aifen , Cao Zhongqiang , Wang Youjie , Xu Shunqing
Published: September 2017

Little is known about the impact of age at menarche on preterm birth. The aim of this study was to examine the association between age at menarche and preterm birth. A total of 11,016 Chinese women who gave birth to live singleton infants were recruited from the Healthy Baby Cohort between 2012 and 2014 in the province of Hubei, China. Age at menarche was reported via face-to-face interviews and was categorized into five groups (≤11, 12, 13, 14 and ≥15 years). Gestational age was estimated using maternal last menstrual period. Preterm birth was defined as delivering a live singleton infant at <37 weeks’ gestational age. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Earlier menarche (≤11 years) was associated with an increased prevalence of preterm birth (OR: 1.67, 95% CI: 1.18, 2.36) compared with menarche age at 13 years after controlling for the potential confounders. The findings of our study suggested that a history of earlier menarche might be useful for identifying women at higher risk of preterm birth.
Nkx2.5+ Cardiomyoblasts Contribute to Cardiomyogenesis in the Neonatal Heart
Authors: Serpooshan Vahid , Liu Yuan-Hung , Buikema Jan W. , Galdos Francisco X. , Chirikian Orlando , Paige Sharon , Venkatraman Sneha , Kumar Anusha , Rawnsley David R. , Huang Xiaojing , Pijnappels Daniël A. , Wu Sean M.
Published: September 2017

During normal lifespan, the mammalian heart undergoes limited renewal of cardiomyocytes. While the exact mechanism for this renewal remains unclear, two possibilities have been proposed: differentiated myocyte replication and progenitor/immature cell differentiation. This study aimed to characterize a population of cardiomyocyte precursors in the neonatal heart and to determine their requirement for cardiac development. By tracking the expression of an embryonic Nkx2.5 cardiac enhancer, we identified cardiomyoblasts capable of differentiation into striated cardiomyocytes in vitro. Genome-wide expression profile of neonatal Nkx2.5+ cardiomyoblasts showed the absence of sarcomeric gene and the presence of cardiac transcription factors. To determine the lineage contribution of the Nkx2.5+ cardiomyoblasts, we generated a doxycycline suppressible Cre transgenic mouse under the regulation of the Nkx2.5 enhancer and showed that neonatal Nkx2.5+ cardiomyoblasts mature into cardiomyocytes in vivo. Ablation of neonatal cardiomyoblasts resulted in ventricular hypertrophy and dilation, supporting a functional requirement of the Nkx2.5+ cardiomyoblasts. This study provides direct lineage tracing evidence that a cardiomyoblast population contributes to cardiogenesis in the neonatal heart. The cell population identified here may serve as a promising therapeutic for pediatric cardiac regeneration.
Insecticidal activity and the mechanism of action of three phenylpropanoids isolated from the roots of Piper sarmentosum Roxb
Authors: Hematpoor Arshia , Liew Sook Yee , Azirun Mohd Sofian , Awang Khalijah
Published: September 2017

Hexane, dichloromethane and methanol extracts of the roots of Piper sarmentosum Roxb. were screened for toxicity towards Sitophilus oryzae (L.), Rhyzopertha dominica (F.), and Plodia interpunctella (Hübner) and the hexane extract exhibited the highest mortality percentage. Bioassay-guided fractionation of the hexane extract resulted in the isolation of asaricin 1, isoasarone 2, and trans-asarone 3. Asaricin 1 and isoasarone 2 were the most toxic compounds to Sitophilus oryzae, Rhyzopertha dominica, and Plodia interpunctella. Sitophilus oryzae and Rhyzopertha dominica exposed to asaricin 1 and isoasarone 2 required the lowest median lethal time. Insecticidal activity of trans-asarone 3 showed consistent toxicity throughout the 60 days towards all three insects as compared to asaricin 1 and isoasarone 2. Asaricin 1 and isoasarone 2 at different doses significantly reduced oviposition and adult emergence of the three insects in treated rice. Trans-asarone 3 had lowest toxicity with highest LC and LT values in all tested insects relative to its mild oviposition inhibition and progeny activity. Moreover, asaricin 1 and isoasarone 2 significantly inhibited acetylcholinesterase in comparison with trans-asarone 3 and the control. Acetylcholinesterase inhibition of Rhyzopertha dominica and Plodia interpunctella by asaricin 1 and isoasarone 2 were lower than that of Sitophilus oryzae, which correlated with their higher resistance.
Discrimination of geographical origin of cultivated Polygala tenuifolia based on multi-element fingerprinting by inductively coupled plasma mass spectrometry
Authors: Zhao Yunsheng , Ma Xiaofang , Fan Lingling , Mao Fuying , Tian Hongling , Xu Rui , Cao Zhe , Zhang Xinhui , Fu Xueyan , Sui Hong
Published: September 2017

Inorganic elements are important components of medicinal herbs, and provide valuable experimental evidence for the quality evaluation and control of traditional Chinese medicine (TCM). In this study, to investigate the relationship between the inorganic elemental fingerprint and geographical origin identification of cultivated Polygala tenuifolia, 41 elemental fingerprints of P. tenuifolia from four major polygala-producing regions (Shanxi, Hebei, Henan, and Shaanxi) were evaluated to determine the importance of inorganic elements to cultivated P. tenuifolia. A total of 15 elemental (B, Ca, Cl, Cu, Fe, K, Mg, Mn, Na, N, Mo, S, Sr, P, and Zn) concentrations of cultivated P. tenuifolia were measured using inductively coupled plasma mass spectroscopy (ICP-MS). The element composition samples were classified by radar plot, elemental fingerprint, and multivariate data analyses, such as hierarchical cluster analysis (HCA), principle component analysis (PCA), and discriminant analysis (DA). This study shows that radar plots and multivariate data analysis can satisfactorily distinguish the geographical origin of cultivated P. tenuifolia. Furthermore, PCA results revealed that N, Cu, K, Mo, Sr, Ca, and Zn are the characteristic elements of cultivated P. tenuifolia. Therefore, multi-element fingerprinting coupled with multivariate statistical techniques can be considered an effective tool to discriminate geographical origin of cultivated P. tenuifolia.
Sex steroid production associated with puberty is absent in germ cell-free salmon
Authors: Kleppe Lene , Andersson Eva , Skaftnesmo Kai Ove , Edvardsen Rolf B. , Fjelldal Per Gunnar , Norberg Birgitta , Bogerd Jan , Schulz Rüdiger W. , Wargelius Anna
Published: September 2017

In all vertebrates studied so far, germ cells are not required for pubertal maturation of the gonadal steroidogenic system, subsequent development of secondary sex characteristics and reproductive behavior. To explore if the absence of germ cells affects puberty or growth in Atlantic salmon, germ cell-free (GCF), dnd knockout and wild type (WT) postsmolts were stimulated to enter puberty. No GCF fish entered puberty, whereas 66.7% (males) and 30% (females) WT fish completed or entered puberty, respectively. Expression of genes related to steroidogenesis (star, cyp17a1, cyp11β, cyp19a1a), gonadal somatic cells (insl3, amh, igf3), oocytes (bmp15), gonadotropin receptors (fshr, lhcgr), and pituitary gonadotropic cells (fshb, lhb, gnrhr4) showed an immature status and failure to up-regulate gonadal sex steroid production in male and female GCF fish was also reflected in low or undetectable plasma sex steroids (11-ketotestosterone, estradiol-17β and testosterone). A gender difference (high in females, low in males) was found in the expression of star and cyp17a1 in GCF fish. No clear difference in growth was detected between GCF and immature WT fish, while growth was compromised in maturing WT males. We demonstrate for the first time in a vertebrate that germ cells are required for pubertal activation of the somatic steroidogenic cells.
Photocatalytic Properties of Tetraphenylporphyrins Immobilized on Calcium Alginate Aerogels
Authors: Solovieva Anna B. , Kopylov Alexander S. , Savko Marina A. , Zarkhina Tatiana S. , Lovskaya Darya D. , Lebedev Artyom E. , Menshutina Natalia V. , Krivandin Alexey V. , Shershnev Ilya V. , Kotova Svetlana L. , Timashev Peter S.
Published: September 2017

We have prepared photocatalytic systems based on tetraphenylporphyrins (TPP) immobilized on calcium alginate solid gels in the conditions of thermal drying on air (xerogel), freeze drying in vacuum (cryogel) and supercritical drying in the supercritical carbon dioxide (scCO2) medium (aerogel). As a test reaction to measure the prepared systems’ efficiency, we studied tryptophan photooxidation in the aqueous medium. We have demonstrated that the systems with aerogel as a carrier exhibited the highest photocatalytic efficiency. In that case, the rate constant for the test substrate (tryptophan) oxidation exceeds the corresponding rate constants of similar systems based on xerogel and cryogel by more than 5 times. Moreover, the aerogel-based photocatalytic systems demonstrated enhanced functional stability and a possibility of multiple use of such a catalyst in tryptophan oxidation. Based on the data of small-angle X-ray scattering and thermooxidative destruction, we have made a conclusion about the relationship between the high photocatalytic activity of aerogel-immobilized TPP and formation of a developed porous aerogel structure in the conditions of drying in the scCO2 medium, which is stabilized due to formation of additional complex bonds of calcium ions with fragments of glycoside rings.
Decreased Triple Network Connectivity in Patients with Recent Onset Post-Traumatic Stress Disorder after a Single Prolonged Trauma Exposure
Authors: Liu Yang , Li Liang , Li Baojuan , Feng Na , Li Lihong , Zhang Xi , Lu Hongbing , Yin Hong
Published: September 2017

The triple network model provides a common framework for understanding affective and neurocognitive dysfunctions across multiple disorders, including central executive network (CEN), default mode network (DMN), and salience network (SN). Considering the effect of traumatic experience on post-traumatic stress disorder (PTSD), this study aims to explore the alteration of triple network connectivity in a specific PTSD induced by a single prolonged trauma exposure. With an arterial spin labeling sequence, three networks were first identified using independent component analysis among 10 PTSD patients and 10 healthy survivors, who experienced the same coal mining flood disaster. Then, the triple network connectivity was analyzed and compared between PTSD and non-PTSD groups. In PTSD patients, decreased connectivity was identified in left middle frontal gyrus of CEN, left precuneus and bilateral superior frontal gyrus of DMN, and right anterior insula of SN. The decreased connectivity in left middle frontal gyrus of CEN was associated with clinical severity. Furthermore, no significant connection of SN with CEN and DMN was found in PTSD patients. The decreased triple network connectivity was found in this study, which not only supports the triple network model, but also suggests a possible neurobiological mechanism for cognitive dysfunction of this type of PTSD.
The neurotrophic effects of different human dental mesenchymal stem cells
Authors: Kolar Mallappa K. , Itte Vinay N. , Kingham Paul J. , Novikov Lev N. , Wiberg Mikael , Kelk Peyman
Published: September 2017

The current gold standard treatment for peripheral nerve injury is nerve grafting but this has disadvantages such as donor site morbidity. New techniques focus on replacing these grafts with nerve conduits enhanced with growth factors and/or various cell types such as mesenchymal stem cells (MSCs). Dental-MSCs (D-MSCs) including stem cells obtained from apical papilla (SCAP), dental pulp stem cells (DPSC), and periodontal ligament stem cells (PDLSC) are potential sources of MSCs for nerve repair. Here we present the characterization of various D-MSCs from the same human donors for peripheral nerve regeneration. SCAP, DPSC and PDLSC expressed BDNF, GDNF, NGF, NTF3, ANGPT1 and VEGFA growth factor transcripts. Conditioned media from D-MSCs enhanced neurite outgrowth in an in vitro assay. Application of neutralizing antibodies showed that brain derived neurotrophic factor plays an important mechanistic role by which the D-MSCs stimulate neurite outgrowth. SCAP, DPSC and PDLSC were used to treat a 10 mm nerve gap defect in a rat sciatic nerve injury model. All the stem cell types significantly enhanced axon regeneration after two weeks and showed neuroprotective effects on the dorsal root ganglia neurons. Overall the results suggested SCAP to be the optimal dental stem cell type for peripheral nerve repair.
Timing and localization of human dystrophin isoform expression provide insights into the cognitive phenotype of Duchenne muscular dystrophy
Authors: Doorenweerd Nathalie , Mahfouz Ahmed , van Putten Maaike , Kaliyaperumal Rajaram , t’ Hoen Peter A. C. , Hendriksen Jos G. M. , Aartsma-Rus Annemieke M. , Verschuuren Jan J. G. M. , Niks Erik H. , Reinders Marcel J. T. , Kan Hermien E. , Lelieveldt Boudewijn P. F.
Published: September 2017

Duchenne muscular dystrophy (DMD) is a muscular dystrophy with high incidence of learning and behavioural problems and is associated with neurodevelopmental disorders. To gain more insights into the role of dystrophin in this cognitive phenotype, we performed a comprehensive analysis of the expression patterns of dystrophin isoforms across human brain development, using unique transcriptomic data from Allen Human Brain and BrainSpan atlases. Dystrophin isoforms show large changes in expression through life with pronounced differences between the foetal and adult human brain. The Dp140 isoform was expressed in the cerebral cortex only in foetal life stages, while in the cerebellum it was also expressed postnatally. The Purkinje isoform Dp427p was virtually absent. The expression of dystrophin isoforms was significantly associated with genes implicated in neurodevelopmental disorders, like autism spectrum disorders or attention-deficit hyper-activity disorders, which are known to be associated to DMD. We also identified relevant functional associations of the different isoforms, like an association with axon guidance or neuron differentiation during early development. Our results point to the crucial role of several dystrophin isoforms in the development and function of the human brain.
Immune Response of A Novel ATR-AP205-001 Conjugate Anti-hypertensive Vaccine
Authors: Hu Xiajun , Deng Yihuan , Chen Xiao , Zhou Yanzhao , Zhang Hongrong , Wu Hailang , Yang Shijun , Chen Fen , Zhou Zihua , Wang Min , Qiu Zhihua , Liao Yuhua
Published: September 2017

We developed a virus-like particle (VLP)-based therapeutic vaccine against angiotensin II receptor type 1, ATR-AP205-001, which could significantly reduce the blood pressure and protect target organs of hypertensive animals. In this study, we focused on the immunological effect and safety of the VLP-based vaccine. By comparing to the depolymerized dimeric vaccine ATR-Dimer-001, we found that ATR-AP205-001 reached subcapsular sinus of lymph node shortly after administration, followed by accumulation on follicle dendritic cells via follicle B cell transportation, while ATR-Dimer-001 vaccine showed no association with FDCs. ATR-AP205-001 vaccine strongly activated dendritic cells, which promoted T cells differentiation to follicular helper T cells. ATR-AP205-001 vaccine induced powerful germinal center reaction, which was translated to a boost of specific antibody production and long-lasting B cell memory, far superior to ATR-Dimer-001 vaccine. Moreover, neither cytotoxic T cells, nor Th1/Th17 cell-mediated inflammation was observed in ATR-AP205-001 vaccine, similar to ATR-Dimer-001 vaccine. We concluded that ATR-AP205-001 vaccine quickly induced potent humoral immunity through collaboration of B cells, follicular dendritic cells and follicular helper T cells, providing an effective and safe intervention for hypertension in the future clinical application.
Human Cancer Cells Signal Their Competitive Fitness Through MYC Activity
Authors: Di Giacomo Simone , Sollazzo Manuela , de Biase Dario , Ragazzi Moira , Bellosta Paola , Pession Annalisa , Grifoni Daniela
Published: September 2017

MYC-mediated cell competition is a cell-cell interaction mechanism known to play an evolutionary role during development fromDrosophilato mammals. Cells expressing low levels of MYC, calledlosers, are committed to die by nearby cells with high MYC activity, calledwinners, that overproliferate to compensate for cell loss, so that the fittest cells be selected for organ formation. Given MYC’s consolidated role in oncogenesis, cell competition is supposed to be relevant to cancer, but its significance in human malignant contexts is largely uncharacterised. Here we show stereotypical patterns of MYC-mediated cell competition in human cancers: MYC-upregulating cells and apoptotic cells were indeed repeatedly found at the tumour-stroma interface and within the tumour parenchyma. Cell death amount in the stromal compartment and MYC protein level in the tumour were highly correlated regardless of tumour type and stage. Moreover, we show that MYC modulation in heterotypic co-cultures of human cancer cells is sufficient as to subvert their competitive state, regardless of genetic heterogeneity. Altogether, our findings suggest that the innate role of MYC-mediated cell competition in development is conserved in human cancer, with malignant cells using MYC activity to colonise the organ at the expense of less performant neighbours.
Intermediate and low abundant protein analysis of vitamin D deficient obese and non-obese subjects by MALDI-profiling
Authors: Al-Daghri Nasser M. , Torretta Enrica , Capitanio Daniele , Fania Chiara , Guerini Franca Rosa , Sabico Shaun B. , Clerici Mario , Gelfi Cecilia
Published: September 2017

Obesity is a pathological condition caused by genetic and environmental factors, including vitamin D deficiency, which increases the risk of developing cardiovascular disorders and diabetes. This case-control study was designed to verify whether serum profiles could be identified differentiating obese and non-obese Saudis characterized by vitamin D deficiency and pathological levels of triglycerides, high-density lipoprotein cholesterol and high total cholesterol levels. The serum protein profiles of 64 vitamin D deficient (serum 25(OH)D < 50nmol/L) individuals with metabolic syndrome and with (n = 31; BMI ≥ 30) or without (n = 33; BMI < 30) obesity were analyzed by a quantitative label-free mass spectrometry approach (MALDI-profiling), combined with different serum immunodepletion strategies (Human7 and Human14 immuno-chromatographies), to analyze the intermediate- and low-abundant protein components. The analysis of intermediate-abundant proteins (Human7) in obese vs. non-obese subjects identified 14 changed peaks (p < 0.05) in the m/z range 1500–35000. Furthermore, the Human14 depletion provided new profiles related to obesity (121 changed peaks). Among changed peaks, 11 were identified in the m/z range 1500–4000 Da by high-resolution tandem mass spectrometry, belonging to apolipoprotein CIII, apolipoprotein B100, alpha-1-antichymotrypsin and complement C3. Data herein show that distinct protein profiles identify specific peptides belonging to lipid metabolism and inflammation processes that are associated with obesity and vitamin D deficiency.
Evaluation of the heterogeneous tissue distribution of erlotinib in lung cancer using matrix-assisted laser desorption ionization mass spectrometry imaging
Authors: Tsubata Yukari , Hayashi Mitsuhiro , Tanino Ryosuke , Aikawa Hiroaki , Ohuchi Mayu , Tamura Kenji , Fujiwara Yasuhiro , Isobe Takeshi , Hamada Akinobu
Published: September 2017

Although drug distribution in tumor tissues has a significant impact on efficacy, conventional pharmacokinetic analysis has some limitations with regard to its ability to provide a comprehensive assessment of drug tissue distribution. Erlotinib is a tyrosine kinase inhibitor that acts on the epidermal growth factor receptor; however, it is unclear how this drug is histologically distributed in lung cancer. We used matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze erlotinib distribution in the tumor and normal lung tissues of a mouse xenograft model and patient with non-small cell lung cancer. LC-MS/MS showed that the erlotinib tissue concentration in the xenograft tumor tissue was clearly lower than that in the normal tissue at the time of maximum blood concentration. MALDI-MSI showed the heterogeneous distribution of erlotinib at various levels in the murine tissues; interestingly, erlotinib was predominantly localized in the area of viable tumor compared to the necrotic area. In the patient-derived tissue, MALDI-MSI showed that there were different concentrations of erlotinib distributed within the same tissue. For drug development and translational research, the imaging pharmacokinetic study used the combination of MALDI-MSI and LC-MS/MS analyses may be useful in tissues with heterogeneous drug distribution.
Ultra-sensitive graphene sensor for measuring high vacuum pressure
Authors: Il Ahn Sung , Ra Jung Ju , Young Choi So , Hwa Son Min , Jin Hong Yu , Park Jung-Chul
Published: September 2017

We demonstrate here that several different graphene nanoribbon (GNR) samples can be separated from the GNR mixture synthesized by conventional methods. The sheet resistance of the purified GNR gradually decreased with decreasing pressure at 30 °C, whereas it increased at 100 °C. A hypothesis based on van der Waals attractive interactions between GNR sheets was introduced to explain this finding. This hypothesis verified by the shifted main peaks in vacuum X-ray diffraction spectra: 0.022 nm and 0.041 nm shifts were observed for reduced graphene oxide (RGO) and GNR, respectively. Theoretical calculations indicated that, for RGO, the shifted distance was similar to the calculated distance. The response of the GNR sensor to pressure changes occurred rapidly (in seconds). The normalized response time of each sample indicated that sensor using GNR reduced the tailing of the response time by shortening the diffusion path of gas molecules. The sensitivity of the GNR sensor was three times that of RGO in the given pressure range. Moreover, the sensitivity of GNR was much larger than those of the most popularly studied pressure sensors using Piezoresistivity, and the sensor could detect vacuum pressures of 8 × 10–7 Torr.
Environmental perturbation of the circadian clock during pregnancy leads to transgenerational mood disorder-like behaviors in mice
Authors: Zhang Peng , Li Guang , Li Hui , Tan XiaoQiu , Cheng Hai-Ying Mary
Published: September 2017

It remains unknown whether chronic circadian disturbance (CCD) during pregnancy can lead to mood disorders in the offspring. Here we show that pregnant mice in the F0 generation that were exposed to CCD stress displayed depression-like behaviors, and produced offspring in the F1 and F2 generations that also exhibited mood-associated behavioral phenotypes despite the lack of direct stressful experiences during their postnatal or adult period. Prenatal CCD stress was correlated with the elevation of plasma corticosterone levels in F1 mice. Furthermore, the diurnal expression profiles of core circadian clock genes were disrupted in the suprachiasmatic nucleus of F1 mice. Proteomics analysis revealed that prenatal CCD stress resulted in distinct changes in protein expression in the hypothalamus of female F1 mice, in particular proteins that were associated with cellular activities, metabolism, development and diseases. Sex-specific differences in melanocortin 4 receptor expression were apparent in the CCD F1 generation. We conclude that maternal exposure to chronic circadian disturbance during pregnancy can lead to sex-specific mood disorders that persist for at least two filial generations. The underlying mechanisms may depend on transgenerational changes in plasma corticosterone levels, circadian pacemaking, and hypothalamic protein expression.