bluuebunny/crossref_metadata_2025 huggingface dataset:
Ubiquitin receptors are required for substrate-mediated activation of the proteasome’s unfolding ability
Authors: Cundiff Mary D. , Hurley Christina M. , Wong Jeremy D. , Boscia Joseph A. , Bashyal Aarti , Rosenberg Jake , Reichard Eden L. , Nassif Nicholas D. , Brodbelt Jennifer S. , Kraut Daniel A.
Published: October 2019

The ubiquitin-proteasome system (UPS) is responsible for the bulk of protein degradation in eukaryotic cells, but the factors that cause different substrates to be unfolded and degraded to different extents are still poorly understood. We previously showed that polyubiquitinated substrates were degraded with greater processivity (with a higher tendency to be unfolded and degraded than released) than ubiquitin-independent substrates. Thus, even though ubiquitin chains are removed before unfolding and degradation occur, they affect the unfolding of a protein domain. How do ubiquitin chains activate the proteasome’s unfolding ability? We investigated the roles of the three intrinsic proteasomal ubiquitin receptors - Rpn1, Rpn10 and Rpn13 - in this activation. We find that these receptors are required for substrate-mediated activation of the proteasome’s unfolding ability. Rpn13 plays the largest role, but there is also partial redundancy between receptors. The architecture of substrate ubiquitination determines which receptors are needed for maximal unfolding ability, and, in some cases, simultaneous engagement of ubiquitin by multiple receptors may be required. Our results suggest physical models for how ubiquitin receptors communicate with the proteasomal motor proteins.
High susceptibility, viral dynamics and persistence of South American Zika virus in New World monkey species
Authors: Berry Neil , Ferguson Deborah , Ham Claire , Hall Jo , Jenkins Adrian , Giles Elaine , Devshi Dhruti , Kempster Sarah , Rose Nicola , Dowall Stuart , Fritzsche Martin , Bleazard Thomas , Hewson Roger , Almond Neil
Published: October 2019

South American Zika virus (ZIKV) recently emerged as a novel human pathogen, linked with neurological disorders. However, comparative ZIKV infectivity studies in New World primates are lacking. Two members of the Callitrichidae family, common marmosets (Callithrix jacchus) and red-bellied tamarins (Saguinus labiatus), were highly susceptible to sub-cutaneous challenge with the Puerto Rico-origin ZIKVPRVABC59 strain. Both exhibited rapid, high, acute viraemia with early neuroinvasion (3 days) in peripheral and central nervous tissue. ZIKV RNA levels in blood and tissues were significantly higher in New World hosts compared to Old World species (Macaca mulatta, Macaca fascicularis). Tamarins and rhesus macaques exhibited loss of zonal occludens-1 (ZO-1) staining, indicative of a compromised blood-brain barrier 3 days post-ZIKV exposure. Early, widespread dissemination across multiple anatomical sites distant to the inoculation site preceded extensive ZIKV persistence after 100 days in New and Old World lineages, especially lymphoid, neurological and reproductive sites. Prolonged persistence in brain tissue has implications for otherwise resolved human ZIKV infection. High susceptibility of distinct New World species underscores possible establishment of ZIKV sylvatic cycles in primates indigenous to ZIKV endemic regions. Tamarins and marmosets represent viable New World models for ZIKV pathogenesis and therapeutic intervention studies, including vaccines, with contemporary strains.
Pomegranate Juice and Extract Consumption Increases the Resistance to UVB-induced Erythema and Changes the Skin Microbiome in Healthy Women: a Randomized Controlled Trial
Authors: Henning Susanne M. , Yang Jieping , Lee Ru-Po , Huang Jianjun , Hsu Mark , Thames Gail , Gilbuena Irene , Long Jianfeng , Xu Yunhui , Park Esther HaeIn , Tseng Chi-Hong , Kim Jenny , Heber David , Li Zhaoping
Published: October 2019

In vitro and animal studies have demonstrated that topical application and oral consumption of pomegranate reduces UVB-induced skin damage. We therefore investigated if oral pomegranate consumption will reduce photodamage from UVB irradiation and alter the composition of the skin microbiota in a randomized controlled, parallel, three-arm, open label study. Seventy-four female participants (30–45 years) with Fitzpatrick skin type II-IV were randomly assigned (1:1:1) to 1000 mg of pomegranate extract (PomX), 8 oz of pomegranate juice (PomJ) or placebo for 12 weeks. Minimal erythema dose (MED) and melanin index were determined using a cutometer (mexameter probe). Skin microbiota was determined using 16S rRNA sequencing. The MED was significantly increased in the PomX and PomJ group compared to placebo. There was no significant difference on phylum, but on family and genus level bacterial composition of skin samples collected at baseline and after 12 week intervention showed significant differences between PomJ, PomX and placebo. Members of the Methylobacteriaceae family contain pigments absorbing UV irradiation and might contribute to UVB skin protection. However, we were not able to establish a direct correlation between increased MED and bacterial abundance. In summary daily oral pomegranate consumption may lead to enhanced protection from UV photodamage.
On-chip Fourier-transform spectrometer based on spatial heterodyning tuned by thermo-optic effect
Authors: Montesinos-Ballester Miguel , Liu Qiankun , Vakarin Vladyslav , Ramirez Joan Manel , Alonso-Ramos Carlos , Roux Xavier Le , Frigerio Jacopo , Ballabio Andrea , Talamas Enrico , Vivien Laurent , Isella Giovanni , Marris-Morini Delphine
Published: October 2019

Miniaturized optical spectrometers providing broadband operation and fine resolution have an immense potential for applications in remote sensing, non-invasive medical diagnostics and astronomy. Indeed, optical spectrometers working in the mid-infrared spectral range have garnered a great interest for their singular capability to monitor the main absorption fingerprints of a wide range of chemical and biological substances. Fourier-transform spectrometers (FTS) are a particularly interesting solution for the on-chip integration due to their superior robustness against fabrication imperfections. However, the performance of current on-chip FTS implementations is limited by tradeoffs in bandwidth and resolution. Here, we propose a new FTS approach that gathers the advantages of spatial heterodyning and optical path tuning by thermo-optic effect to overcome this tradeoff. The high resolution is provided by spatial multiplexing among different interferometers with increasing imbalance length, while the broadband operation is enabled by fine tuning of the optical path delay in each interferometer harnessing the thermo-optic effect. Capitalizing on this concept, we experimentally demonstrate a mid-infrared SiGe FTS, with a resolution better than 15 cm−1 and a bandwidth of 603 cm−1 near 7.7 μm wavelength with a 10 MZI array. This is a resolution comparable to state-of-the-art on-chip mid-infrared spectrometers with a 4-fold bandwidth increase with a footprint divided by a factor two.
Embelin Improves the Spatial Memory and Hippocampal Long-Term Potentiation in a Rat Model of Chronic Cerebral Hypoperfusion
Authors: Bhuvanendran Saatheeyavaane , Bakar Siti Najmi Syuhadaa , Kumari Yatinesh , Othman Iekhsan , Shaikh Mohd. Farooq , Hassan Zurina
Published: October 2019

Alzheimer’s disease (AD) is the second most occurring neurological disorder after stroke and is associated with cerebral hypoperfusion, possibly contributing to cognitive impairment. In the present study, neuroprotective and anti-AD effects of embelin were evaluated in chronic cerebral hypoperfusion (CCH) rat model using permanent bilateral common carotid artery occlusion (BCCAO) method. Rats were administered with embelin at doses of 0.3, 0.6 or 1.2 mg/kg (i.p) on day 14 post-surgery and tested in Morris water maze (MWM) followed by electrophysiological recordings to access cognitive abilities and synaptic plasticity. The hippocampal brain regions were extracted for gene expression and neurotransmitters analysis. Treatment with embelin at the doses of 0.3 and 0.6 mg/kg significantly reversed the spatial memory impairment induced by CCH in rats. Embelin treatment has significantly protected synaptic plasticity impairment as assessed by hippocampal long-term potentiation (LTP) test. The mechanism of this study demonstrated that embelin treatment alleviated the decreased expression of BDNF, CREB1, APP, Mapt, SOD1 and NFκB mRNA levels caused by CCH rats. Furthermore, treatment with embelin demonstrated neuromodulatory activity by its ability to restore hippocampal neurotransmitters. Overall these data suggest that embelin improve memory and synaptic plasticity impairment in CCH rats and can be a potential drug candidate for neurodegenerative disease-related cognitive disorders.
Analysis of CT morphologic features and attenuation for differentiating among transient lesions, atypical adenomatous hyperplasia, adenocarcinoma in situ, minimally invasive and invasive adenocarcinoma presenting as pure ground-glass nodules
Authors: Qi Lin , Xue Ke , Li Cheng , He Wenjie , Mao Dingbiao , Xiao Li , Hua Yanqing , Li Ming
Published: October 2019

Thin-section computed tomography (TSCT) imaging biomarkers are uncertain to distinguish progressive adenocarcinoma from benign lesions in pGGNs. The purpose of this study was to evaluate the usefulness of TSCT characteristics for differentiating among transient (TRA) lesions, atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC) presenting as pure ground-glass nodules (pGGNs). Between January 2016 and January 2018, 255 pGGNs, including 64 TRA, 22 AAH, 37 AIS, 108 MIA and 24 IAC cases, were reviewed on TSCT images. Differences in TSCT characteristics were compared among these five subtypes of pGGNs. Logistic analysis was performed to identify significant factors for predicting MIA and IAC. Progressive pGGNs were more likely to be round or oval in shape, with clear margins, air bronchograms, vascular and pleural changes, creep growth, and bubble-like lucency than were non-progressive pGGNs. The optimal cut-off values of the maximum diameter for differentiating non-progressive from progressive pGGNs and IAC from non-IAC were 6.5 mm and 11.5 mm, respectively. For the prediction of IAC vs. non-IAC and non-progressive vs. progressive adenocarcinoma, the areas under the receiver operating characteristics curves were 0.865 and 0.783 for maximum diameter and 0.784 and 0.722 for maximum CT attenuation, respectively. The optimal cut-off values of maximum CT attenuation were −532 HU and −574 HU for differentiating non-progressive from progressive pGGNs and IAC from non-IAC, respectively. Maximum diameter, maximum attenuation and morphological characteristics could help distinguish TRA lesions from MIA and IAC but not from AAH. So, CT morphologic characteristics, diameter and attenuation parameters are useful for differentiating among pGGNs of different subtypes.
Methylation of guar gum for improving mechanical and barrier properties of biodegradable packaging films
Authors: Tripathi Jyoti , Ambolikar Rupali , Gupta Sumit , Jain Dheeraj , Bahadur Jitendra , Variyar Prasad Shekhar
Published: October 2019

Improving functional properties of biopolymers for use as environment friendly packaging is an area of current interest. Biodegradable films with improved barrier and mechanical properties were prepared from methylated guar gum. Methylation resulted in structural modification of guar gum (GG) promoting greater crystallization thereby enhancing thermal stability towards decomposition. Reduction in radius of gyration (Rg), weight average molecular weight (Mw), and an increase in polydispersity index (PDI) were also observed due to methylation. Methylated guar gum (MGG) films exhibited 40% lower water vapor transmission rate (WVTR) as compared to control purified guar gum (PGG) films. Films prepared by partial replacement of PGG with MGG (10, 25, 50, 75 and 100% w/w) showed gradual improvement in percent elongation. The study gives an insight on the role of methylation in enhancing barrier and mechanical properties of GG based biodegradable films for possible application in food packaging.
Growth and single cell kinetics of the loricate choanoflagellate Diaphanoeca grandis
Authors: Eriksen Niels Thomas , Tophøj Jakob , Wollenberg Rasmus Dam , Sondergaard Teis Esben , Funch Peter , Andersen Per
Published: October 2019

Choanoflagellates are common members of planktonic communities. Some have complex life histories that involve transitions between multiple cell stages. We have grown the loricate choanoflagellate Diaphanoeca grandis on the bacterium Pantoea sp. and integrated kinetic observations at the culture level and at the single cell level. The life history of D. grandis includes a cell division cycle with a number of recognisable cell stages. Mature, loricate D. grandis were immobile and settled on the bottom substratum. Daughter cells were ejected from the lorica 30 min. after cell division, became motile and glided on the bottom substratum until they assembled a lorica. Single cell kinetics could explain overall growth kinetics in D. grandis cultures. The specific growth rate was 0.72 day−1 during exponential growth while mature D. grandis produced daughter cells at a rate of 0.9 day−1. Daughter cells took about 1.2 h to mature. D. grandis was able to abandon and replace its lorica, an event that delayed daughter cell formation by more than 2 days. The frequency of daughter cell formation varied considerably among individuals and single cell kinetics demonstrated an extensive degree of heterogeneity in D. grandis cultures, also when growth appeared to be balanced.
Crash dynamics of interdependent networks
Authors: Li Jie , Xia Chengyi , Xiao Gaoxi , Moreno Yamir
Published: October 2019

The emergence and evolution of real-world systems have been extensively studied in the last few years. However, equally important phenomena are related to the dynamics of systems’ collapse, which has been less explored, especially when they can be cast into interdependent systems. In this paper, we develop a dynamical model that allows scrutinizing the collapse of systems composed of two interdependent networks. Specifically, we explore the dynamics of the system’s collapse under two scenarios: in the first one, the condition for failure should be satisfied for the focal node as well as for its corresponding node in the other network; while in the second one, it is enough that failure of one of the nodes occurs in either of the two networks. We report extensive numerical simulations of the dynamics performed in different setups of interdependent networks, and analyze how the system behavior depends on the previous scenarios as well as on the topology of the interdependent system. Our results can provide valuable insights into the crashing dynamics and evolutionary properties of interdependent complex systems.
SPIONs/3D SiSBA-16 based Multifunctional Nanoformulation for target specific cisplatin release in colon and cervical cancer cell lines
Authors: Jermy B. Rabindran , Alomari Munther , Ravinayagam Vijaya , Almofty Sarah Ameen , Akhtar Sultan , Borgio J. Francis , AbdulAzeez Sayed
Published: October 2019

Multifunctional nanomaterials can be used for dual applications: drug delivery as well as in bioimaging. In current study, we investigated potential use of silica based supports; 3D cage type SiSBA-16 (S-16), monodispersed hydrophilic spherical silica (HYPS) and mesocellular foam (MSU-F) for cisplatin (Cp) delivery. To obtain magnetic resonance characteristics, 10 wt% iron oxide was loaded through enforced adsorption technique. For pH stimuli responsive release of Cp, 10 wt%SPIONs/S-16 was functionalized with 3-(Aminopropyl)triethoxysilane (A) and poly acrylic acid (PAA) termed as 10 wt%SPIONs/S-16-A-Cp and 10 wt%SPIONs/S-16-APAA-Cp. By TEM analysis, the average diameter of the SPIONs was found to range between 10–60 nm. VSM analysis showed saturation magnetization over S-16, HYPS and MSU-F were in the following order: 10 wt%SPIONs/HYPS (4.08 emug−1) > 10 wt%SPIONs /S-16 (2.39 emug−1) > 10 wt%SPIONs/MSU-F (0.23 emug−1). Cp release study using dialysis membrane in PBS solution over 10 wt%SPIONs/S-16 nanoformulations showed highest cumulative release (65%) than 10 wt%SPIONs/MSU-F-A-Cp (63%), 10 wt%SPIONs/HYPS-A-Cp (58%), and Cp-F127/S-16 (53%), respectively. 10 wt%SPIONs/S-16-A-Cp and 10 wt%SPIONs/S-16-APAA-Cp were evaluated for in vitro target anticancer efficiency in human cancer cell lines (colon cancer (HCT 116), cervical cancer (HeLa)) and normal cells (Human embryonic kidney cells (HEK293) using MTT and DAPI staining. 10 wt%SPIONs/S-16-A-Cp treated Hela and HCT116 cancerous cell lines showed significant control of cell growth, apoptotic activity and less cytotoxic effect as compared to Cp and 10 wt%SPIONs/S-16. Target specific Cp release in the cells shows that 10 wt%SPIONs/S-16-A-Cp can be easily upgraded for magnetic resonance imaging capability.
Three-dimensional analysis of the physiologic drift of adjacent teeth following maxillary first premolar extractions
Authors: Teng Fei , Du Fei-Yu , Chen Hui-Zhong , Jiang Ruo-Ping , Xu Tian-Min
Published: October 2019

We assessed the three-dimensional (3D) pattern of the physiologic drift of the remaining adjacent teeth after premolar extraction due to orthodontic reasons and the associated factors. Data were collected from 45 patients aged 17.04 ± 5.14 years who were scheduled to receive a fixed appliance after maxillary premolar extraction. Seventy-five drift models were obtained and digitalized via 3D scanning. The average physiologic drift duration was 81.66 ± 70.03 days. Angular and linear changes in the first molars, second premolars, and canines were measured using the 3D method. All the examined teeth had tipped and moved towards the extraction space, leading to space decreases. Posterior teeth primarily exhibited significant mesial tipping and displacement, without rotation or vertical changes. All canine variables changed, including distal inward rotation and extrusion. The physiologic drift tended to slow over time. Age had a limited negative effect on the mesial drift of posterior teeth, whereas crowding had a limited positive effect on canine drift. Thus, the mesial drift of molars after premolar extraction may lead to molar anchorage loss, particularly among younger patients. The pattern of the physiologic drift of maxillary canines can help relieve crowding and facilitate labially ectopic canine alignment, whereas canine drift is accelerated by more severe crowding.
AEBP1 down regulation induced cell death pathway depends on PTEN status of glioma cells
Authors: Sinha Swati , Renganathan Arun , Nagendra Prathima B. , Bhat Vasudeva , Mathew Brian Steve , Rao Manchanahalli R. Satyanarayana
Published: October 2019

Glioblastoma (GBM) is the most common aggressive form of brain cancer with overall dismal prognosis (10–12 months) despite all current multimodal treatments. Previously we identified adipocyte enhancer binding protein 1 (AEBP1) as a differentially regulated gene in GBM. On probing the role of AEBP1 over expression in glioblastoma, we found that both cellular proliferation and survival were affected upon AEBP1 silencing in glioma cells, resulting in cell death. In the present study we report that the classical caspase pathway components are not activated in cell death induced by AEBP1 down regulation in PTEN-deficient (U87MG and U138MG) cells. PARP-1 was not cleaved but over-activated under AEBP1 down regulation which leads to the synthesis of PAR in the nucleus triggering the release of AIF from the mitochondria. Subsequently, AIF translocates to the nucleus along with MIF causing chromatinolysis. AEBP1 positively regulates PI3KinaseCβ by the binding to AE-1 binding element in the PI3KinaseCβ promoter. Loss of PI3KinaseCβ expression under AEBP1 depleted condition leads to excessive DNA damage and activation of PARP-1. Furthermore, over expression of PIK3CB (in trans) in U138MG cells prevents DNA damage in these AEBP1 depleted cells. On the contrary, AEBP1 down regulation induces caspase-dependent cell death in PTEN-proficient (LN18 and LN229) cells. Ectopic expression of wild-type PTEN in PTEN-deficient U138MG cells results in the activation of canonical caspase and Akt dependent cell death. Collectively, our findings define AEBP1 as a potential oncogenic driver in glioma, with potential implications for therapeutic intervention.
Osteopenia and Osteoporosis in Patients with Bronchiectasis: Association with Respiratory Parameters, Body Composition, Muscle Strength and Bone Remodeling Biomarkers
Authors: Contreras-Bolívar V. , Olveira G. , Porras N. , Acosta E. , Rubio-Martín E. , Tapia-Guerrero M. J. , Abuin-Fernández J. , Olveira C.
Published: October 2019

The prevalence of osteopenia/osteoporosis has not been sufficiently studied in people with bronchiectasis not due to cystic fibrosis (BC), nor has its relationship with other variables (clinical, body composition and bone turnover and inflammation markers) been sufficiently studied. Our aim was to determine the prevalence of osteopenia and osteoporosis and related factors in patients with BC. We did a cross-sectional study in people with BC in a clinically stable state. Spirometric parameters, annual exacerbations and analysis with bone turnover markers (BTM) and inflammation markers were evaluated. Densitometry (DXA) was performed for body composition, bone mineral density (BMD) and handgrip strength. 123 patients were studied (65% women, mean age 49.6 ± 18.8, Body Mass Index (BMI) 24.8 ± 4.7 kg/m2). 62.8% and 62.5% of men and women, respectively, had normal bone mineral density, 30.2% and 22.2% osteopenia and 7% and 15% osteoporosis. 52 patients (56.2%) had low fat-free mass: 68.9% women and 28.6% men. Patients with decreased bone mass had significantly lower muscle strength, maximum expiratory volume in the first second (FEV1%), vitamin D, higher levels of C-terminal telopeptide of type 1 collagen (CTX) and total osteocalcin and underarboxylated osteocalcin (ucOC). We observed significant and negative correlations between BMD and the number of serious exacerbations per year CTX and undercarboxylated osteocalcin. We observed significant positive correlations between BMD, fat free mass index (FFMI) and handgrip dynamometry. The study suggest that the prevalence of osteoporosis was high in relation to the demographic characteristics. Respiratory parameters, body composition, muscle strength and bone remodeling markers were associated with a lower bone mineral density.
Morphological evidence for telocytes as stromal cells supporting satellite cell activation in eccentric contraction-induced skeletal muscle injury
Authors: Manetti Mirko , Tani Alessia , Rosa Irene , Chellini Flaminia , Squecco Roberta , Idrizaj Eglantina , Zecchi-Orlandini Sandra , Ibba-Manneschi Lidia , Sassoli Chiara
Published: October 2019

Although telocytes (TCs) have been proposed to play a “nursing” role in resident satellite cell (SC)-mediated skeletal muscle regeneration, currently there is no evidence of TC-SC morpho-functional interaction following tissue injury. Hence, we explored the presence of TCs and their relationship with SCs in an ex vivo model of eccentric contraction (EC)-induced muscle damage. EC-injured muscles showed structural/ultrastructural alterations and changes in electrophysiological sarcolemnic properties. TCs were identified in control and EC-injured muscles by either confocal immunofluorescence (i.e. CD34+CD31− TCs) or transmission electron microscopy (TEM). In EC-injured muscles, an extended interstitial network of CD34+ TCs/telopodes was detected around activated SCs displaying Pax7+ and MyoD+ nuclei. TEM revealed that TCs invaded the SC niche passing with their telopodes through a fragmented basal lamina and contacting the underlying activated SCs. TC-SC interaction after injury was confirmed in vitro by culturing single endomysial sheath-covered myofibers and sprouting TCs and SCs. EC-damaged muscle-derived TCs showed increased expression of the recognized pro-myogenic vascular endothelial growth factor-A, and SCs from the same samples exhibited increased MyoD expression and greater tendency to fuse into myotubes. Here, we provide the essential groundwork for further investigation of TC-SC interactions in the setting of skeletal muscle injury and regenerative medicine.
Silicon-Nanographite Aerogel-Based Anodes for High Performance Lithium Ion Batteries
Authors: Phadatare Manisha , Patil Rohan , Blomquist Nicklas , Forsberg Sven , Örtegren Jonas , Hummelgård Magnus , Meshram Jagruti , Hernández Guiomar , Brandell Daniel , Leifer Klaus , Sathyanath Sharath Kumar Manjeshwar , Olin Håkan
Published: October 2019

To increase the energy storage density of lithium-ion batteries, silicon anodes have been explored due to their high capacity. One of the main challenges for silicon anodes are large volume variations during the lithiation processes. Recently, several high-performance schemes have been demonstrated with increased life cycles utilizing nanomaterials such as nanoparticles, nanowires, and thin films. However, a method that allows the large-scale production of silicon anodes remains to be demonstrated. Herein, we address this question by suggesting new scalable nanomaterial-based anodes. Si nanoparticles were grown on nanographite flakes by aerogel fabrication route from Si powder and nanographite mixture using polyvinyl alcohol (PVA). This silicon-nanographite aerogel electrode has stable specific capacity even at high current rates and exhibit good cyclic stability. The specific capacity is 455 mAh g−1 for 200th cycles with a coulombic efficiency of 97% at a current density 100 mA g−1.
Simulated microgravity-mediated reversion of murine lymphoma immune evasion
Authors: Bradley Jillian H. , Barwick Shannon , Horn Gillian Q. , Ullrich Elizabeth , Best Brianna , Arnold Jennifer P. , Gregg Randal K.
Published: October 2019

No human has returned to the moon since the end of the Apollo program 47 years ago, however, new missions are planned for an orbital outpost. Space radiation and the potential for cancer remain as important issues to the future of human space exploration. While improved shield technologies and protective biologicals are under development, little is known concerning the interaction between cancer cells and host immunity in microgravity. As a hallmark of cancer, tumor cells employ mechanisms of immune evasion to avoid elimination by protective CD4+ and CD8+ T cells. We showed that a murine lymphoma was able to produce a soluble factor that inhibited the function of dendritic cells in activating the CD4+ T cells. Culture of the lymphoma cells in simulated microgravity (SMG), and not Static conditions, restored the CD4+ T cell response and augmented CD8+ T cell-mediated destruction of the cancer cells in vitro and in vivo. Thus, SMG impaired the mechanism of tumor escape and rendered the cancer cells more susceptible to T cell-mediated elimination. The stress of microgravity may expose the most critical components of a tumor’s escape mechanism for astronaut protection and the generation of new cancer therapeutics for patients on Earth.
A novel 3D nanofibre scaffold conserves the plasticity of glioblastoma stem cell invasion by regulating galectin-3 and integrin-β1 expression
Authors: Saleh Ali , Marhuenda Emilie , Fabre Christine , Hassani Zahra , Weille Jan de , Boukhaddaoui Hassan , Guelfi Sophie , Maldonado Igor Lima , Hugnot Jean- Philippe , Duffau Hugues , Bauchet Luc , Cornu David , Bakalara Norbert
Published: October 2019

Glioblastoma Multiforme (GBM) invasiveness renders complete surgical resection impossible and highly invasive Glioblastoma Initiating Cells (GICs) are responsible for tumour recurrence. Their dissemination occurs along pre-existing fibrillary brain structures comprising the aligned myelinated fibres of the corpus callosum (CC) and the laminin (LN)-rich basal lamina of blood vessels. The extracellular matrix (ECM) of these environments regulates GIC migration, but the underlying mechanisms remain largely unknown. In order to recapitulate the composition and the topographic properties of the cerebral ECM in the migration of GICs, we have set up a new aligned polyacrylonitrile (PAN)-derived nanofiber (NF) scaffold. This system is suitable for drug screening as well as discrimination of the migration potential of different glioblastoma stem cells. Functionalisation with LN increases the spatial anisotropy of migration and modulates its mode from collective to single cell migration. Mechanistically, equally similar to what has been observed for mesenchymal migration of GBM in vivo, is the upregulation of galectin-3 and integrin-β1 in Gli4 cells migrating on our NF scaffold. Downregulation of Calpain-2 in GICs migrating in vivo along the CC and in vitro on LN-coated NF underlines a difference in the turnover of focal adhesion (FA) molecules between single-cell and collective types of migration.
Mycoplasma hyopneumoniae surface-associated proteases cleave bradykinin, substance P, neurokinin A and neuropeptide Y
Authors: Jarocki Veronica Maria , Raymond Benjamin Bernard Armando , Tacchi Jessica Leigh , Padula Matthew Paul , Djordjevic Steven Philip
Published: October 2019

Mycoplasma hyopneumoniae is an economically-devastating and geographically-widespread pathogen that colonises ciliated epithelium, and destroys mucociliary function. M. hyopneumoniae devotes ~5% of its reduced genome to encode members of the P97 and P102 adhesin families that are critical for colonising epithelial cilia, but mechanisms to impair mucociliary clearance and manipulate host immune response to induce a chronic infectious state have remained elusive. Here we identified two surface exposed M. hyopneumoniae proteases, a putative Xaa-Pro aminopeptidase (MHJ_0659; PepP) and a putative oligoendopeptidase F (MHJ_0522; PepF), using immunofluorescence microscopy and two orthogonal proteomic methodologies. MHJ_0659 and MHJ_0522 were purified as polyhistidine fusion proteins and shown, using a novel MALDI-TOF MS assay, to degrade four pro-inflammatory peptides that regulate lung homeostasis; bradykinin (BK), substance P (SP), neurokinin A (NKA) and neuropeptide Y (NPY). These findings provide insight into the mechanisms used by M. hyopneumoniae to influence ciliary beat frequency, impair mucociliary clearance, and initiate a chronic infectious disease state in swine, features that are a hallmark of disease caused by this pathogen.
Untargeted metabolomic analysis of the carotenoid-based orange coloration in Haliotis gigantea using GC-TOF-MS
Authors: Wei Xiaohui , Chen Nan , Tang Bin , Luo Xuan , You Weiwei , Ke Caihuan
Published: October 2019

Seafood coloration is typically considered an indicator of quality and nutritional value by consumers. One such seafood is the Xishi abalone (Haliotis gigantea), which displays muscle color polymorphism wherein a small subset of individuals display orange coloration of muscles due to carotenoid enrichment. However, the metabolic basis for carotenoid accumulation has not been thoroughly investigated in marine mollusks. Here, GC-TOF-MS-based untargeted metabolite profiling was used to identify key pathways and metabolites involved in differential carotenoid accumulation in abalones with variable carotenoid contents. Cholesterol was the most statistically significant metabolite that differentiated abalones with orange muscles against those with common white muscles. This observation is likely due to the competitive interactions between cholesterol and carotenoids during cellular absorption. In addition, the accumulation of carotenoids was also related to fatty acid contents. Overall, this study indicates that metabolomics can reflect physiological changes in organisms and provides a useful framework for exploring the mechanisms underlying carotenoid accumulation in abalone types.
Dihydromyricetin affects BDNF levels in the nervous system in rats with comorbid diabetic neuropathic pain and depression
Authors: Ge Huixiang , Guan Shu , Shen Yulin , Sun Mengyun , Hao Yuanzhen , He Lingkun , Liu Lijuan , Yin Cancan , Huang Ruoyu , Xiong Wei , Gao Yun
Published: October 2019

Diabetic neuropathic pain (DNP) and depression (DP) are the common complications in patients with diabetes. The purpose of our research was to observe whether brain-derived neurotrophic factor (BDNF) levels and tropomyosin receptor kinase B (TrkB) in the nervous system have effects on rats with comorbid DNP and DP, and to determine whether dihydromyricetin (DHM) may influence BDNF/ TrkB pathway to mitigatethe comorbidity. The study showed that DHM treatment could attenuates pain and depressive behavior in DNP and DP combined rats. Compared with the control group, the expression level of BDNF/TrkB in the hippocampus of DNP + DP group were reduced, while the expression levels in the spinal cord and DRG were increased. However, after treatment with DHM, those changes were reversed. Compared with the control group, the level of IL-1β and TNF-α in the hippocampus, spinal cord and DRG in the DNP + DP group was significantly increased, and DHM treatment could reduce the increase. Thus our study indicated that DHM can relief symptoms of DNP and DP by suppressing the BDNF/TrkB pathway and the proinflammatory factor, and BDNF/TrkB pathway may be an effective target for treatment of comorbid DNP and DP.
HspX promotes the polar localization of mycobacterial protein aggregates
Authors: Zhang Yi-Wei , Zhu Jun-Hao , Wang Zhen-Qi , Wu You , Meng Xianbin , Zheng Xuhui , Javid Babak
Published: October 2019

Misfolding of translated proteins occurs in all domains of life. In most cells, misfolded proteins coalesce in discrete aggregates at distinct cellular locations. In many bacteria, including mycobacteria, protein aggregates are located at the cellular pole. Yet the mechanism by which aggregates are sorted to the mycobacterial pole is not known. Here, we show that in Mycobacterium smegmatis, the small heat shock protein HspX plays a critical role in the polar localization of aggregates of a model fluorescent misfolded protein, GLR103. HspX itself has a polar localization, which is dependent on its N-terminal domain. In a strain deleted for hspX, GLR103 is less liable to aggregation and no longer localizes to the pole, and redirecting HspX to the septum radically disrupts the normal polar localization of GLR103 aggregates. To further investigate the role of HspX in native protein aggregation, we performed semi-quantitative mass-spectrometry of mycobacterial protein aggregates in wild-type, hspX-deleted and hspX-overexpressing strains. We identified a subset of proteins that appeared to be HspX-dependent for aggregate formation. Furthermore, we demonstrate that for validated native protein aggregates, sorting to the cellular pole following proteotoxic stress required HspX. In summary, we have identified the cellular function of HspX in Mycobacterium smegmatis as both a pro-aggregase and polar sortase.
Modulatory Effect of Protein and Carotene Dietary Levels on Pig gut Microbiota
Authors: González-Prendes Rayner , Pena Ramona Natacha , Solé Emma , Seradj Ahmad Reza , Estany Joan , Ramayo-Caldas Yuliaxis
Published: October 2019

In this study we investigated the impact of dietary protein and carotene levels on microbial functions and composition during the last month of purebred fattening Duroc pigs. Fecal microbiota was characterized using 16S ribosomal RNA sequencing at two points of live, 165 (T1) and 195 (T2) days. From 70 to 165 days of age, 32 pigs were divided into two groups fed either a standard-protein (SP) or a low-protein (LP) diet. In the last month (165–195 days), all pigs received a LP diet, either carotene-enriched (CE) or not (NC). Significant differences were observed between T1 and T2 at Amplicon Sequences Variants (ASVs), phylum and genus levels. In T1 group,Prevotella,FaecalibacteriumandTreponemawere the genera most influenced by dietary protein, together with predicted functions related with the degradation of protein. In contrast, the CE diet did not impact the microbiome diversity, although 160 ASVs were differentially abundant between CE and NC groups at T2. Weak stability of enterotype clusters across time-points was observed as consequence of medium-term dietary interventions. Our results suggest that during the last month of fattening, dietary protein have a stronger effect than carotenes on the modulation of the compositional and functional structure of the pig microbiota.
Wastewater leakage in West Texas revealed by satellite radar imagery and numerical modeling
Authors: Zheng Weiyu , Kim Jin-Woo , Ali Syed Tabrez , Lu Zhong
Published: October 2019

Wastewater, a byproduct of oil and gas production, is injected into disposal wells. Using Interferometric Synthetic Aperture Radar (InSAR) to observe ground deformation in the Ken Regan field, West Texas, we detected surface uplift that occurred near a wastewater disposal well from 2007 to 2011. High correlation between the observed deformation and the injection volume suggests that the uplift was caused by wastewater disposal in the well. Inverse elastic models were first used to calculate the injection depth and volume. Given the initial estimates of wastewater injection, forward poroelastic finite element models were applied to simulate stress/strain and displacement fields and to estimate the effective injection volume and depth, so as to ultimately understand the subsurface geomechanical processes and provide insight into the local hydrologic properties of the strata in the well location. Results from both elastic and poroelastic models indicate that the effective injection depth is much shallower than the depth reported to the Texas Railroad Commission (RRC). The most reasonable explanation is that the well was experiencing leakage due to casing failures and/or sealing problem(s). The Rustler Aquifer, within the zone of the effective injection depth, has been used as a source of freshwater for irrigation and livestock; wastewater leaked into this aquifer may possibly contaminate that freshwater. Our analysis that exploits remote sensing data and numerical models provides a clue as to understanding the subsurface hydrogeological process responding to the oil and gas activities and an indirect leakage monitoring method to supplement current infrequent leakage detection.
Dry Spells and Extreme Precipitation are The Main Trigger of Landslides in Central Europe
Authors: Tichavský Radek , Ballesteros-Cánovas Juan Antonio , Šilhán Karel , Tolasz Radim , Stoffel Markus
Published: October 2019

Landslides are frequently triggered by extreme meteorological events which has led to concern and debate about their activity in a future greenhouse climate. It is also hypothesized that dry spells preceding triggering rainfall may increase slope predisposition to sliding, especially in the case of clay-rich soils. Here we combined dendrogeomorphic time series of landslides and climatic records to test the possible role of dry spells and extreme downpours on process activity in the Outer Western Carpathians (Central Europe). To this end, we tested time series of past frequencies and return periods of landslide reactivations at the regional scale with a Generalized Linear Mixed (GLM) model to explore linkages between landslide occurrences and triggering climate variables. Results show that landslide reactivations are concentrated during years in which spring and summer precipitation sums were significantly higher than usual, and that triggering mechanisms vary between different types of landslides (i.e. complex, shallow or flow-like). The GLM model also points to the susceptibility of landslide bodies to the combined occurrence of long, dry spells followed by large precipitation. Such situations are likely to increase in frequency in the future as climate models predict an enhancement of heatwaves and dry spells in future summers, that would be interrupted by less frequent, yet more intense storms, especially also in mountain regions.
CD206+ tumor-associated macrophages promote proliferation and invasion in oral squamous cell carcinoma via EGF production
Authors: Haque A. S. M. Rafiul , Moriyama Masafumi , Kubota Keigo , Ishiguro Noriko , Sakamoto Mizuki , Chinju Akira , Mochizuki Keita , Sakamoto Taiki , Kaneko Naoki , Munemura Ryusuke , Maehara Takashi , Tanaka Akihiko , Hayashida Jun-Nosuke , Kawano Shintaro , Kiyoshima Tamotsu , Nakamura Seiji
Published: October 2019

Tumor-associated macrophages (TAMs) promote tumor progression and inhibit anti-tumor immune response by producing various mediators and preferentially express CD163, CD204, and CD206. However, the role of these TAM subsets in oral squamous cell carcinoma (OSCC) remains unclear. Here we investigated the expression and function of TAM subsets in OSCC, especially in cancer cell proliferation. Biopsy sample from 44 patients with OSCC were examined for the expression of TAM markers and EGF by immunohistochemistry. EGF production of TAM subsets isolated from OSCC patients was assessed by flow cytometry. We also examined the effect of conditioned medium from TAM subsets on the proliferation of OSCC cells. CD163+ cells were detected diffusely all over the tumor and connective tissue area, while CD204+ and CD206+ cells were mainly detected in/around the tumors. Flow cytometric analysis found that CD206+ TAMs strongly produced EGF compared with CD163+ and CD204+ TAMs. Cell proliferation and invasion of OSCC cells cultured with conditioned medium of CD206+ TAMs were strongly enhanced and inhibited by anti-EGFR. The number of CD206+ TAMs positively correlated with worse clinical prognosis. Our results revealed differences in localization and EGF production among these TAM subsets. CD206+ TAMs might play a critical role in the proliferation of OSCC via EGF production.
Depth-dependent transcriptomic response of diatoms during spring bloom in the western subarctic Pacific Ocean
Authors: Suzuki Shigekatsu , Kataoka Takafumi , Watanabe Tsuyoshi , Yamaguchi Haruyo , Kuwata Akira , Kawachi Masanobu
Published: October 2019

Diatoms play important roles in primary production and carbon transportation in various environments. Large-scale diatom bloom occurs worldwide; however, metabolic responses of diatoms to environmental conditions have been little studied. Here, we targeted the Oyashio region of the western subarctic Pacific where diatoms bloom every spring and investigated metabolic response of major diatoms to bloom formation by comparing metatranscriptomes between two depths corresponding to different bloom phases. Thalassiosira nordenskioeldii and Chaetoceros debilis are two commonly occurring species at the study site. The gene expression profile was drastically different between the surface (late decline phase of the bloom; 10 m depth) and the subsurface chlorophyll maximum (SCM, initial decline phase of the bloom; 30 m depth); in particular, both species had high expression of genes for nitrate uptake at the surface, but for ammonia uptake at the SCM. Our culture experiments using T. nordenskioeldii imitating the environmental conditions showed that gene expression for nitrate and ammonia transporters was induced by nitrate addition and active cell division, respectively. These results indicate that the requirement for different nitrogen compounds is a major determinant of diatom species responses during bloom maturing.
Mesocarnivores affect hispid cotton rat (Sigmodon hispidus) body mass
Authors: Morris Gail , Conner L. Mike
Published: October 2019

Predator communities are changing worldwide: large carnivores are declining while mesocarnivores (medium-sized mammalian predators) are increasing in number and ecological influence. Predator choice of prey is not random and different predators select prey with different characteristics. Changes in predator communities can change predation patterns experienced by prey. Little is known about how mesocarnivore communities influence prey morphology. We used 14 years of mark-recapture data to investigate how mesocarnivore exclusion affected body mass of hispid cotton rats (Sigmodon hispidus). Finding adult male cotton rats were 9% heavier with mesocarnivore exclusion, we developed hypotheses to explain this observation. Greater adult male body mass in exclosures resulted from: (1) a non-significant trend of increased survival of large males, (2) faster juvenile male growth during the fall and a similar non-significant trend among adult males, and (3) spatial partitioning by size among males. Taxa-specific predation rates (i.e., rates of predation by snakes, raptors, or mesocarnivores) did not differ among male body mass classes. Mesocarnivores disproportionately preyed on large females while raptors targeted small females, but female body mass was not influenced by mesocarnivore exclusion. Changes in predator communities can result in multiple small effects that collectively result in large differences in prey morphology.
Dewatering Behavior of a Wood-Cellulose Nanofibril Particulate System
Authors: Amini Ezatollah , Tajvidi Mehdi , Bousfield Douglas W. , Gardner Douglas J. , Shaler Stephen M.
Published: October 2019

The novel use of aqueous suspensions of cellulose nanofibrils (CNF) as an adhesive/binder in lignocellulosic-based composite manufacture requires the removal of a considerable amount of water from the furnish during processing, necessitating thorough understanding of the dewatering behavior referred to as “contact dewatering”. The dewatering behavior of a wood-CNF particulate system (wet furnish) was studied through pressure filtration tests, centrifugation, and characterization of hard-to-remove (HR) water, i.e. moisture content in the wet furnish at the transition between constant rate part and the falling rate part of evaporative change in mass from an isothermal thermogravimetric analysis (TGA). The effect of wood particle size thereby particle specific surface area on the dewatering performance of wet furnish was investigated. Permeability coefficients of wet furnish during pressure filtration experiments were also determined based on Darcy’s law for volumetric flow through a porous medium. Results revealed that specific particle surface area has a significant effect on the dewatering of wet furnish where dewatering rate significantly increased at higher specific particle surface area levels. While the permeability of the systems decreased over time in almost all cases, the most significant portion of dewatering occurred at very early stages of dewatering (less than 200 seconds) leading to a considerable increase in instantaneous dewatering when CNF particles come in contact with wood particles.
Fine mapping of Brassica napus blackleg resistance gene Rlm1 through bulked segregant RNA sequencing
Authors: Fu Fuyou , Liu Xunjia , Wang Rui , Zhai Chun , Peng Gary , Yu Fengqun , Fernando W. G. Dilantha
Published: October 2019

The fungal pathogen Leptosphaeria maculans causes blackleg disease on canola and rapeseed (Brassica napus) in many parts of the world. A B. napus cultivar, ‘Quinta’, has been widely used for the classification of L. maculans into pathogenicity groups. In this study, we confirmed the presence of Rlm1 in a DH line (DH24288) derived from B. napus cultivar ‘Quinta’. Rlm1 was located on chromosome A07, between 13.07 to 22.11 Mb, using a BC1 population made from crosses of F1 plants of DH16516 (a susceptible line) x DH24288 with bulked segregant RNA Sequencing (BSR-Seq). Rlm1 was further fine mapped in a 100 kb region from 19.92 to 20.03 Mb in the BC1 population consisting of 1247 plants and a F2 population consisting of 3000 plants using SNP markers identified from BSR-Seq through Kompetitive Allele-Specific PCR (KASP). A potential resistance gene, BnA07G27460D, was identified in this Rlm1 region. BnA07G27460D encodes a serine/threonine dual specificity protein kinase, catalytic domain and is homologous to STN7 in predicted genes of B. rapa and B. oleracea, and A. thaliana. Robust SNP markers associated with Rlm1 were developed, which can assist in introgression of Rlm1 and confirm the presence of Rlm1 gene in canola breeding programs.