bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of table olive wastewater extract administration on the adult ovariectomised rat model of osteoporosis
Authors: Zervas Alexandros S. , Lelovas Pavlos P. , Galanos Antonios , Galanis Dimitrios , Makropoulou Maria , Beteinakis Stavros , Patsaki Anastasia , Passali Christina , Kourkoulis Stavros K. , Triantafyllou Aggeliki , Chronopoulos Efstathios , Skaltsounis Alexios L. , Dontas Ismene A.
Published: February 2021

Recent efforts for alternative non-pharmaceutical treatments for postmenopausal osteoporosis are focused on nutritional measures. The aim of this study was to investigate the effect of table olive wastewater extract (OE) administration on bone mineral density (BMD) and biomechanical strength in ovariectomised rats. Thirty mature 9-month-old female Wistar rats were separated into three groups of ten: Control, Ovariectomised (OVX) and OVX + OE. BMD was measured before ovariectomy, 3 and 6 months afterwards. At the end of the study, blood, both femurs and tibias, internal organs and abdominal fat were collected. After 3 months, the percentage changes from baseline of the total and proximal tibial BMD of the OVX + OE group were both higher compared with the OVX group (P < 0·005). Similar results were found after 6 months, when the percentage changes from baseline of the total and proximal tibial BMD of the OVX + OE group were both higher compared with the OVX group (P < 0·005). Biomechanical testing of the femurs did not reveal any statistically significant difference between the groups. Body weights throughout the study, organs’ and abdominal fat ratios to final body weight and blood results (alanine aminotransferase (ALT), gamma-glutamyltransferase (γ-GT), total cholesterol, HDL-cholesterol, LDL-cholesterol, Ca and P) were within normal limits and did not show any significant difference between the treated and untreated groups. As a conclusion, the administration of OE for 6 months protected tibial BMD loss in comparison with the untreated OVX group without causing adverse effects.
Curcumin induces mitochondrial biogenesis by increasing cyclic AMP levels via phosphodiesterase 4A inhibition in skeletal muscle
Authors: Hamidie Ronald D R , Shibaguchi Tsubasa , Yamada Tatsuya , Koma Rikuhide , Ishizawa Rie , Saito Yoko , Hosoi Tatsunori , Masuda Kazumi
Published: February 2021

Background:

Previous research has suggested that curcumin potentially induces mitochondrial biogenesis in skeletal muscle via increasing cyclic AMP (cAMP) levels. However, the regulatory mechanisms for this phenomenon remain unknown. The purpose of the present study was to clarify the mechanism by which curcumin activates cAMP-related signalling pathways that upregulate mitochondrial biogenesis and respiration in skeletal muscle.

Methods:

The effect of curcumin treatment (i.p., 100 mg/kg-BW/d for 28 d) on mitochondrial biogenesis was determined in rats. The effects of curcumin and exercise (swimming for 2 h/d for 3 d) on the cAMP signalling pathway were determined in the absence and presence of phosphodiesterase (PDE) or protein kinase A (PKA) inhibitors. Mitochondrial respiration, citrate synthase (CS) activity, cAMP content and protein expression of cAMP/PKA signalling molecules were analysed.

Results:

Curcumin administration increased cytochrome c oxidase subunit (COX-IV) protein expression, and CS and complex I activity, consistent with the induction of mitochondrial biogenesis by curcumin. Mitochondrial respiration was not altered by curcumin treatment. Curcumin and PDE inhibition tended to increase cAMP levels with or without exercise. In addition, exercise increased the phosphorylation of phosphodiesterase 4A (PDE4A), whereas curcumin treatment strongly inhibited PDE4A phosphorylation regardless of exercise. Furthermore, curcumin promoted AMP-activated protein kinase (AMPK) phosphorylation and PPAR gamma coactivator (PGC-1α) deacetylation. Inhibition of PKA abolished the phosphorylation of AMPK.

Conclusion:

The present results suggest that curcumin increases cAMP levels via inhibition of PDE4A phosphorylation, which induces mitochondrial biogenesis through a cAMP/PKA/AMPK signalling pathway. Our data also suggest the possibility that curcumin utilises a regulatory mechanism for mitochondrial biogenesis that is distinct from the exercise-induced mechanism in skeletal muscle.
Ways of looking: Lexicalizing visual paths in verbs
Authors: WNUK EWELINA
Published: February 2021

The packaging of meaning in verbs varies widely across languages since verbs are free to encode different aspects of an event. At the same time, languages tend to display recurrent preferences in lexicalization, e.g. verb-framing vs. satellite-framing in motion. It has been noted, however, that the lexicalization patterns in motion are not carried over to the domain of vision, since gaze trajectory (‘visual path’) is coded outside the main verb even in verb-framed languages. This ‘typological split’ (Matsumoto 2001), however, is not universal. This article contains the first extensive report of verb-framing in the domain of vision based on data from Maniq (Austroasiatic, Thailand). The verbs are investigated using a translation questionnaire and a picture-naming task, which tap into subtle semantic detail. Results suggest the meanings of the verbs are shaped by universal constraints linked to earth-based verticality and bodily mechanics, as well as local factors such as the environment and the cultural scenarios of which looking is a salient part. A broader look across the whole Maniq verb lexicon reveals further cases of verbally encoded spatial notions and demonstrates a pervasive cross-domain systematicity, pointing to the language system itself as an important shaping force in lexicalization.
Reproductive strategies under different environmental conditions: total output vs investment per egg in the slipper lobster Scyllarus arctus
Authors: Fernández L. , García-Soler C. , Alborés I.
Published: February 2021

The slipper lobster Scyllarus arctus is an important fishery resource in Galicia (NW Iberian Peninsula), with a large reduction of its populations in recent decades in the North-east Atlantic and Mediterranean, but only limited information on its reproduction. This study provides an analysis of the reproductive potential of this scyllarid during two breeding cycles (2008 and 2009) in the NE Atlantic (43°20′N 8°50′W). We studied several reproductive traits (fecundity, brood weight, egg weight and volume) in broods with eggs both in an early and late embryonic stage, in relation to female size and temporal variations. Total output (fecundity and weight) and egg weight were closely linked to maternal size, and this relationship remained in broods with late-stage eggs. In relation to temporal variations, our data revealed an important seasonal variability in fecundity and egg weight, showing an inverse pattern in the reproductive strategy in the first two seasons of the reproductive period, with a maximum egg weight in winter (December–February) and a maximum number of eggs produced in spring (April–May). A predictive model for realized fecundity was developed: log (FE) = 0.064 + 2.907 log (length)−0.018 Month2 + 0.174 Month, which accounted for over 90% of variation in the total data.
Do infants have abstract grammatical knowledge of word order at 17 months? Evidence from Mandarin Chinese.
Authors: ZHU Jingtao , FRANCK Julie , RIZZI Luigi , GAVARRÓ Anna
Published: February 2021

We test the comprehension of transitive sentences in very young learners of Mandarin Chinese using a combination of the weird word order paradigm with the use of pseudo-verbs and the preferential looking paradigm, replicating the experiment of Francket al.(2013) on French. Seventeen typically-developing Mandarin infants (mean age: 17.4 months) participated and the same experiment was conducted with eighteen adults. The results show that hearing well-formed NP-V-NP sentences triggered infants to fixate more on a transitive scene than on a reflexive scene. In contrast, when they heard deviant NP-NP-V sequences, no such preference pattern was found, a performance pattern that is adult-like. This is at variance with some of the results from Candanet al.(2012), who only found evidence for canonical word order comprehension at almost age 3 when considering fixation time. Furthermore, within the age range tested, performance showed no effect of age or vocabulary size.
Unilateral Stroke: Computer-based Assessment Uncovers Non-Lateralized and Contralesional Visuoattentive Deficits
Authors: Villarreal Sanna , Linnavuo Matti , Sepponen Raimo , Vuori Outi , Bonato Mario , Jokinen Hanna , Hietanen Marja
Published: February 2021

Objective:

Patients with unilateral stroke commonly show hemispatial neglect or milder contralesional visuoattentive deficits, but spatially non-lateralized visuoattentive deficits have also been reported. The aim of the present study was to compare spatially lateralized (i.e., contralesional) and non-lateralized (i.e., general) visuoattentive deficits in left and right hemisphere stroke patients.

Method:

Participants included 40 patients with chronic unilateral stroke in either the left hemisphere (LH group,n= 20) or the right hemisphere (RH group,n= 20) and 20 healthy controls. To assess the contralesional deficits, we used a traditional paper-and-pencil cancellation task (the Bells Test) and a Lateralized Targets Computer Task. To assess the non-lateralized deficits, we developed a novel large-screen (173 × 277 cm) computer method, the Ball Rain task, with moving visual stimuli and fast-paced requirements for selective attention.

Results:

There were no contralesional visuoattentive deficits according to the cancellation task. However, in the Lateralized Targets Computer Task, RH patients missed significantly more left-sided than right-sided targets in bilateral trials. This omission distribution differed significantly from those of the controls and LH patients. In the assessment of non-lateralized attention, RH and LH patients missed significantly more Ball Rain targets than controls in both the left and right hemifields.

Conclusions:

Computer-based assessment sensitively reveals various aspects of visuoattentive deficits in unilateral stroke. Patients with either right or left hemisphere stroke demonstrate non-lateralized visual inattention. In right hemisphere stroke, these symptoms can be accompanied by subtle contralesional visuoattentive deficits that have remained unnoticed in cancellation task.
Rice Inundation Assessment Using Polarimetric UAVSAR Data
Authors: Huang Xiaodong , Runkle Benjamin R. K. , Isbell Mark , Moreno‐García Beatriz , McNairn Heather , Reba Michele L. , Torbick Nathan
Published: February 2021

Irrigated rice requires intense water management under typical agronomic practices. Cost effective tools to improve the efficiency and assessment of water use is a key need for industry and resource managers to scale ecosystem services. In this research we advance model‐based decomposition and machine learning to map inundated rice using time‐series polarimetric, L‐band Uninhabited Aerial Vehicle Synthetic Aperture Radar (UAVSAR) observations. Simultaneous ground truth observations recorded water depth inundation during the 2019 crop season using instrumented fields across the study site in Arkansas, USA. A three‐component model‐based decomposition generated metrics representing surface‐, double bounce‐, and volume‐scattering along with a shape factor, randomness factor, and the Radar Vegetation Index (RVI). These physically meaningful metrics characterized crop inundation status independent of growth stage including under dense canopy cover. Machine learning (ML) comparisons employed Random Forest (RF) using the UAVSAR derived parameters to identify cropland inundation status across the region. Outcomes show that RVI, proportion of the double‐bounce within total scattering, and the relative comparison between the double‐bounce and the volume scattering have moderate to strong mechanistic ability to identify rice inundation status with Overall Accuracy (OA) achieving 75%. The use of relative ratios further helped mitigate the impacts of far range incidence angles. The RF approach, which requires training data, achieved a higher OA and Kappa of 88% and 71%, respectively, when leveraging multiple SAR parameters. Thus, the combination of physical characterization and ML provides a powerful approach to retrieving cropland inundation under the canopy. The growth of polarimetric L‐band availability should enhance cropland inundation metrics beyond open water that are required for tracking water quantity at field scale over large areas.
Financial Feasibility of Water Conservation in Agriculture
Authors: Siderius Christian , Biemans Hester , Conway Declan , Immerzeel Walter , Jaegermeyr Jonas , Ahmad Bashir , Hellegers Petra
Published: February 2021

Global water use for food production needs to be reduced to remain within planetary boundaries, yet the financial feasibility of crucial measures to reduce water use is poorly quantified. Here, we introduce a novel method to compare the costs of water conservation measures with the added value that reallocation of water savings might generate if used for expansion of irrigation. Based on detailed water accounting through the use of a high‐resolution hydrology‐crop model, we modify the traditional cost curve approach with an improved estimation of demand and increasing marginal cost per water conservation measure combination, adding a correction to control for impacts on downstream water availability. We apply the method to three major river basins in the Indo‐Gangetic plain (Indus, Ganges and Brahmaputra), a major global food producing region but increasingly water stressed. Our analysis shows that at basin level only about 10% (Brahmaputra) to just over 20% (Indus and Ganges) of potential water savings would be realized; the equilibrium price for water is too low to make the majority of water conservation measures cost effective. The associated expansion of irrigated area is moderate, about 7% in the Indus basin, 5% in the Ganges and negligible in the Brahmaputra, but farmers' gross profit increases more substantially, by 11%. Increasing the volumetric cost of irrigation water influences supply and demand in a similar way and has little influence on water reallocation. Controlling for the impact on return flows is important and more than halves the amount of water available for reallocation.
The Greater Mekong's Climate‐Water‐Energy Nexus: How ENSO‐Triggered Regional Droughts Affect Power Supply and CO2 Emissions
Authors: Chowdhury A. F. M. Kamal , Dang Thanh Duc , Nguyen Hung T. T. , Koh Rachel , Galelli Stefano
Published: February 2021

The Greater Mekong Subregion is a transnational area bound together by the Mekong River basin and its immense hydropower resources, historically seen as the backbone of regional economic development. The basin is now punctuated by several dams, successful in attracting both international investors and fierce criticisms for their environmental and societal impacts. Surprisingly, no attention has been paid so far to the actual performance of these infrastructures: is hydropower supply robust with respect to the hydroclimatic variability characterizing Southeast Asia? When water availability is altered, what are the implications for power production costs and CO2 emissions? To answer these questions, we focus on the Laotian–Thai grid—the first international power‐trade infrastructure developed in the region—and use a power system model driven by a spatially distributed hydrological‐water management model. Simulation results over a 30‐year period show that production costs and carbon footprint are significantly affected by droughts, which reduce hydropower availability and increase reliance on thermoelectric resources. Regional droughts across the Mekong basin are of particular concern, as they reduce the export of cheap hydropower from Laos to Thailand. To put the analysis into a broader climate‐water‐energy context, we show that the El Niño Southern Oscillation modulates not only the summer monsoon, but also the power system behavior, shaping the relationship between hydroclimatological conditions, power production costs, and CO2 emissions. Overall, our results and models provide a knowledge basis for informing robust management strategies at the water‐energy scale and designing more sustainable power plans in the Greater Mekong Subregion.
Evaluating Participatory Modeling Methods for Co‐creating Pathways to Sustainability
Authors: Moallemi E. A. , de Haan F. J. , Hadjikakou M. , Khatami S. , Malekpour S. , Smajgl A. , Smith M. Stafford , Voinov A. , Bandari R. , Lamichhane P. , Miller K. K. , Nicholson E. , Novalia W. , Ritchie E. G. , Rojas A. M. , Shaikh M. A. , Szetey K. , Bryan B. A.
Published: February 2021

The achievement of global sustainability agendas, such as the Sustainable Development Goals, relies on transformational change across society, economy, and environment that are co‐created in a transdisciplinary exercise by all stakeholders. Within this context, environmental and societal change is increasingly understood and represented via participatory modeling for genuine engagement with multiple collaborators in the modeling process. Despite the diversity of participatory modeling methods to promote engagement and co‐creation, it remains uncertain what the extent and modes of participation are in different contexts, and how to select the suitable methods to use in a given situation. Based on a review of available methods and specification of potential contextual requirements, we propose a unifying framework to guide how collaborators of different backgrounds can work together and evaluate the suitability of participatory modeling methods for co‐creating sustainability pathways. The evaluation of method suitability promises the integration of concepts and approaches necessary to address the complexities of problems at hand while ensuring robust methodologies based on well‐tested evidence and negotiated among participants. Using two illustrative case studies, we demonstrate how to explore and evaluate the choice of methods for participatory modeling in varying contexts. The insights gained can inform creative participatory approaches to pathway development through tailored combinations of methods that best serve the specific sustainability context of particular case studies.
A Reasonable Mean Dynamic Topography State on Improving the Ability of Assimilating the Altimetry Observations into a Coupled Climate System Model: An Example With CAS‐ESM‐C
Authors: Dong Xiao , Zheng Fei , Lin Renping , Yang Haipeng , Zhu Jiang , Du Mengjiao , Luo Hao
Published: February 2021

In this study, based on an ocean data assimilation system for the coupled climate model CAS‐ESM‐C, how to reasonably assimilate altimetry data are explored. In sea surface height (SSH) assimilations, the mean dynamic topography (MDT) is an important factor that can coordinate the observed sea level anomalies with the modeled SSH. The SSH assimilation results are first compared through assimilation experiments using three different MDTs, including the observed reference height, the MDT from model control run, and the MDT from the assimilation experiment in CAS‐ESM‐C, with the climatological World Ocean Atlas (WOA) temperature assimilated into the coupled model. The results show that the third one can significantly improve the ability of the ocean data assimilation system to assimilate the SSH observations. Using this MDT, the SSH assimilation scheme of the ocean data assimilation system was established for the CAS‐ESM‐C, and a long‐term SSH assimilation experiment from 1994 to 2017 was carried out. The results show that the SSH assimilation performs much better than the SST assimilation in reproducing the ocean states and seasonal‐interannual variability. The improvements of SSH assimilation compared with SST assimilation may be due to the different properties of the two ocean variables. While SST is a thermodynamic variable used to evaluate the thermal condition of the ocean surface layer, SSH is a dynamic variable linked to the dynamical information of the whole ocean layer. Thus, SSH assimilation can constrain the ocean model with observed dynamic information, which is more important to the state estimation and temporal evolution of the ocean.
Identifying Agricultural Managed Aquifer Recharge Locations to Benefit Drinking Water Supply in Rural Communities
Authors: Marwaha Nisha , Kourakos George , Levintal Elad , Dahlke Helen E.
Published: February 2021

The southern Central Valley of California is one of the most productive agricultural regions in the world. Yet, decades of groundwater use beyond sustainable yield have left rural communities highly vulnerable to shortages and contamination of their drinking water supply. As state regulation begins to address these issues, a need exists to design adaptive and appropriate management systems to increase resilience of rural communities. Targeted managed aquifer recharge on agricultural land (Ag‐MAR) near rural communities is one such strategy that could potentially stabilize groundwater tables and maintain or improve groundwater quality in domestic supply wells. Here we present a geographic information system‐based multicriteria decision analysis that combines biophysical data (soils, land use, and surface water conveyance) with groundwater modeling and particle tracking to identify suitable agricultural land parcels for multibenefit groundwater recharge within well capture zones of 288 rural communities. Parcels are prioritized using a vulnerability index to change in groundwater supply, derived from well reliance and failures, pesticide applications, land subsidence, and socio‐economic data. Our analysis identifies 2,998 suitable land parcels for Ag‐MAR within the well capture zones of 149 of the 288 communities, of which 144 rely mainly on groundwater for drinking water. The majority of identified Ag‐MAR parcels serve communities ranked as having extreme or very high vulnerability to changes in groundwater supply. Our research produces new understanding of factors contributing to community vulnerability and resilience to changes in drinking water supply and can be used to discuss actions to help achieve a stable and high‐quality water supply.
The aftermath of the interplay between the endoplasmic reticulum stress response and redox signaling
Authors: Bhattarai Kashi Raj , Riaz Thoufiqul Alam , Kim Hyung-Ryong , Chae Han-Jung
Published: February 2021

The endoplasmic reticulum (ER) is an essential organelle of eukaryotic cells. Its main functions include protein synthesis, proper protein folding, protein modification, and the transportation of synthesized proteins. Any perturbations in ER function, such as increased demand for protein folding or the accumulation of unfolded or misfolded proteins in the ER lumen, lead to a stress response called the unfolded protein response (UPR). The primary aim of the UPR is to restore cellular homeostasis; however, it triggers apoptotic signaling during prolonged stress. The core mechanisms of the ER stress response, the failure to respond to cellular stress, and the final fate of the cell are not yet clear. Here, we discuss cellular fate during ER stress, cross talk between the ER and mitochondria and its significance, and conditions that can trigger ER stress response failure. We also describe how the redox environment affects the ER stress response, and vice versa, and the aftermath of the ER stress response, integrating a discussion on redox imbalance-induced ER stress response failure progressing to cell death and dynamic pathophysiological changes.
SPRTN protease-cleaved MRE11 decreases DNA repair and radiosensitises cancer cells
Authors: Na Juri , Newman Joseph A. , Then Chee Kin , Syed Junetha , Vendrell Iolanda , Torrecilla Ignacio , Ellermann Sophie , Ramadan Kristijan , Fischer Roman , Kiltie Anne E.
Published: February 2021

The human MRE11/RAD50/NBS1 (MRN) complex plays a crucial role in sensing and repairing DNA DSB. MRE11 possesses dual 3′−5′ exonuclease and endonuclease activity and forms the core of the multifunctional MRN complex. We previously identified a C-terminally truncated form of MRE11 (TR-MRE11) associated with post-translational MRE11 degradation. Here we identified SPRTN as the essential protease for the formation of TR-MRE11 and characterised the role of this MRE11 form in its DNA damage response (DDR). Using tandem mass spectrometry and site-directed mutagenesis, the SPRTN-dependent cleavage site for MRE11 was identified between 559 and 580 amino acids. Despite the intact interaction of TR-MRE11 with its constitutive core complex proteins RAD50 and NBS1, both nuclease activities of truncated MRE11 were dramatically reduced due to its deficient binding to DNA. Furthermore, lack of the MRE11 C-terminal decreased HR repair efficiency, very likely due to abolished recruitment of TR-MRE11 to the sites of DNA damage, which consequently led to increased cellular radiosensitivity. The presence of this DNA repair-defective TR-MRE11 could explain our previous finding that the high MRE11 protein expression by immunohistochemistry correlates with improved survival following radical radiotherapy in bladder cancer patients.
The immune-inflammatory response of oligodendrocytes in a murine model of preterm white matter injury: the role of TLR3 activation
Authors: Boccazzi Marta , Van Steenwinckel Juliette , Schang Anne-Laure , Faivre Valérie , Le Charpentier Tifenn , Bokobza Cindy , Csaba Zsolt , Verderio Claudia , Fumagalli Marta , Mani Shyamala , Gressens Pierre
Published: February 2021

A leading cause of preterm birth is the exposure to systemic inflammation (maternal/fetal infection), which leads to neuroinflammation and white matter injury (WMI). A wide range of cytokines and chemokines are expressed and upregulated in oligodendrocytes (OLs) in response to inflammation and numerous reports show that OLs express several receptors for immune related molecules, which enable them to sense inflammation and to react. However, the role of OL immune response in WMI is unclear. Here, we focus our study on toll-like receptor-3 (TLR3) that is activated by double-strand RNA (dsRNA) and promotes neuroinflammation. Despite its importance, its expression and role in OLs remain unclear. We used an in vivo mouse model, which mimics inflammation-mediated WMI of preterm born infants consisting of intraperitoneal injection of IL-1β from P1 to P5. In the IL-1β-treated animals, we observed the upregulation of Tlr3, IL-1β, IFN-β, Ccl2, and Cxcl10 in both PDGFRα+ and O4+ sorted cells. This upregulation was higher in O4+ immature OLs (immOLs) as compared to PDGFRα+ OL precursor cells (OPCs), suggesting a different sensitivity to neuroinflammation. These observations were confirmed in OL primary cultures: cells treated with TLR3 agonist Poly(I:C) during differentiation showed a stronger upregulation of Ccl2 and Cxcl10 compared to cells treated during proliferation and led to decreased expression of myelin genes. Finally, OLs were able to modulate microglia phenotype and function depending on their maturation state as assessed by qPCR using validated markers for immunomodulatory, proinflammatory, and anti-inflammatory phenotypes and by phagocytosis and morphological analysis. These results show that during inflammation the response of OLs can play an autonomous role in blocking their own differentiation: in addition, the immune activation of OLs may play an important role in shaping the response of microglia during inflammation.
Targeting autophagy enhances atezolizumab-induced mitochondria-related apoptosis in osteosarcoma
Authors: Liu Zhuochao , Wang Hongyi , Hu Chuanzhen , Wu Chuanlong , Wang Jun , Hu Fangqiong , Fu Yucheng , Wen Junxiang , Zhang Weibin
Published: February 2021

In this study, we identified the multifaceted effects of atezolizumab, a specific monoclonal antibody against PD-L1, in tumor suppression except for restoring antitumor immunity, and investigated the promising ways to improve its efficacy. Atezolizumab could inhibit the proliferation and induce immune-independent apoptosis of osteosarcoma cells. With further exploration, we found that atezolizumab could impair mitochondria of osteosarcoma cells, resulting in increased release of reactive oxygen species and cytochrome-c, eventually leading to mitochondrial-related apoptosis via activating JNK pathway. Nevertheless, the excessive release of reactive oxygen species also activated the protective autophagy of osteosarcoma cells. Therefore, when we combined atezolizumab with autophagy inhibitors, the cytotoxic effect of atezolizumab on osteosarcoma cells was significantly enhanced in vitro. Further in vivo experiments also confirmed that atezolizumab combined with chloroquine achieved the most significant antitumor effect. Taken together, our study indicates that atezolizumab can induce mitochondrial-related apoptosis and protective autophagy independently of the immune system, and targeting autophagy is a promising combinatorial approach to amplify its cytotoxicity.
Molecular imaging of the kinetics of hyperactivated ERK1/2-mediated autophagy during acquirement of chemoresistance
Authors: Bishnu Aniketh , Phadte Pratham , Dhadve Ajit , Sakpal Asmita , Rekhi Bharat , Ray Pritha
Published: February 2021

Alterations in key kinases and signaling pathways can fine-tune autophagic flux to promote the development of chemoresistance. Despite empirical evidences of strong association between enhanced autophagic flux with acquired chemoresistance, it is still not understood whether an ongoing autophagic flux is required for both initiation, as well as maintenance of chemoresistance, or is sufficient for one of the either steps. Utilizing indigenously developed cisplatin–paclitaxel-resistant models of ovarian cancer cells, we report an intriguing oscillation in chemotherapy-induced autophagic flux across stages of resistance, which was found to be specifically elevated at the early stages or onset of chemoresistance. Conversely, the sensitive cells and cells at late stages of resistance showed stalled and reduced autophagic flux. This increased flux at early stages of resistance was found to be dictated by a hyperactive ERK1/2 signaling, which when inhibited either pharmacologically (U0126/Trametinib) or genetically, reduced p62 degradation, number of LC3+veLAMP1+ve puncta, autophagolysosome formation, and led to chemo-sensitization and apoptosis. Inhibition of ERK1/2 activation also altered the level of UVRAG and Rab7, the two key proteins involved in autophagosome–lysosome fusion. Noninvasive imaging of autophagic flux using a novel autophagy sensor (mtFL-p62 fusion reporter) showed that combinatorial treatment of platinum–taxol along with Trametinib/chloroquine blocked autophagic flux in live cells and tumor xenografts. Interestingly, Trametinib was found to be equally effective in blocking autophagic flux as chloroquine both in live cells and tumor xenografts. Combinatorial treatment of Trametinib and platinum–taxol significantly reduced tumor growth. This is probably the first report of real-time monitoring of chemotherapy-induced autophagy kinetics through noninvasive bioluminescence imaging in preclinical mouse model. Altogether our data suggest that an activated ERK1/2 supports proper completion of autophagic flux at the onset of chemoresistance to endure initial chemotherapeutic insult and foster the development of a highly chemoresistant phenotype, where autophagy becomes dispensable.
Micron-sized iron oxide particles for both MRI cell tracking and magnetic fluid hyperthermia treatment
Authors: Dallet Laurence , Stanicki Dimitri , Voisin Pierre , Miraux Sylvain , Ribot Emeline J.
Published: February 2021

Iron oxide particles (IOP) are commonly used for Cellular Magnetic Resonance Imaging (MRI) and in combination with several treatments, like Magnetic Fluid Hyperthermia (MFH), due to the rise in temperature they provoke under an Alternating Magnetic Field (AMF). Micrometric IOP have a high sensitivity of detection. Nevertheless, little is known about their internalization processes or their potential heat power. Two micrometric commercial IOP (from Bangs Laboratories and Chemicell) were characterized by Transmission Electron Microscopy (TEM) and their endocytic pathways into glioma cells were analyzed. Their Specific Absorption Rate (SAR) and cytotoxicity were evaluated using a commercial AMF inductor. T2-weighted imaging was used to monitor tumor growth in vivo after MFH treatment in mice. The two micron-sized IOP had similar structures and r2 relaxivities (100 mM−1 s−1) but involved different endocytic pathways. Only ScreenMAG particles generated a significant rise in temperature following AMF (SAR = 113 W g−1 Fe). After 1 h of AMF exposure, 60% of ScreenMAG-labeled cells died. Translated to a glioma model, 89% of mice responded to the treatment with smaller tumor volume 42 days post-implantation. Micrometric particles were investigated from their characterization to their intracellular internalization pathways and applied in one in vivo cancer treatment, i.e. MFH.
Greedy control of cascading failures in interdependent networks
Authors: Turalska Malgorzata , Swami Ananthram
Published: February 2021

Complex systems are challenging to control because the system responds to the controller in a nonlinear fashion, often incorporating feedback mechanisms. Interdependence of systems poses additional difficulties, as cross-system connections enable malicious activity to spread between layers, increasing systemic risk. In this paper we explore the conditions for an optimal control of cascading failures in a system of interdependent networks. Specifically, we study the Bak–Tang–Wiesenfeld sandpile model incorporating a control mechanism, which affects the frequency of cascades occurring in individual layers. This modification allows us to explore sandpile-like dynamics near the critical state, with supercritical region corresponding to infrequent large cascades and subcritical zone being characterized by frequent small avalanches. Topological coupling between networks introduces dependence of control settings adopted in respective layers, causing the control strategy of a given layer to be influenced by choices made in other connected networks. We find that the optimal control strategy for a layer operating in a supercritical regime is to be coupled to a layer operating in a subcritical zone, since such condition corresponds to reduced probability of inflicted avalanches. However this condition describes a parasitic relation, in which only one layer benefits. Second optimal configuration is a mutualistic one, where both layers adopt the same control strategy. Our results provide valuable insights into dynamics of cascading failures and and its control in interdependent complex systems.
Food and nutrition of Gaur (Bos gaurus C.H. Smith, 1827) at the edge of Khao Yai National Park, Thailand
Authors: Chaiyarat Rattanawat , Prasopsin Suphat , Bhumpakphan Naris
Published: February 2021

The presence of gaur (Bos gaurus) at the border of Khao Yai National Park (KYNP) in Thailand has resulted in a dramatic increase in the number of individuals’ crop feeding. This study examines the feeding adaptations of gaur at the edge of the protected area and assesses whether gaur response to increased nutrient availability in crop plants compared to natural forage. During the day, gaur mostly utilized forest areas in KYNP and entered the agricultural areas at night. Gaur ate 43 natural forage species. Natural forage species contain high levels of crude protein and lipid, but they are found in small quantities and scattered areas when compared to crop plants, especially Zea mays L., that are available in large quantity and are heavily foraged on by gaur. However, greater understanding of the electivity index and nutrition of forage species along the edge of the protected area can be used to reduce the gaur-human conflict by keeping gaur in KYNP. Reducing the large monoculture areas that is the food sources of gaur along the edge may reduce or prevent gaur leaving the park and can be applied to advance conservation actions.
Publisher Correction: Anthropogenic Pb contribution in soils of Southeast China estimated by Pb isotopic ratios
Authors: Li Jianwu , Hao Guoshuang , Wang Xudong , Ruan Li , Zhou Jinjie
Published: February 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Understanding active sites in molecular (photo)electrocatalysis through complementary vibrational spectroelectrochemistry
Authors: Ly Khoa H. , Weidinger Inez M.
Published: February 2021

Highlighting vibrational spectroelectrochemistry for the investigation of synthetic molecular (photo) electrocatalysts for key energy conversion reactions.
Efficient and low-scaling linear-response time-dependent density functional theory implementation for core-level spectroscopy of large and periodic systems
Authors: Bussy Augustin , Hutter Jürg
Published: February 2021

New and efficient LR-TDDFT implementation for core spectroscopy in large and periodic systems.
High-resolution UV spectroscopy of 1-indanol
Authors: Hernandez-Castillo A. O. , Bischoff Johannes , Lee Ju Hyeon , Langenhan Jennifer , Karra Mallikarjun , Meijer Gerard , Eibenberger-Arias Sandra
Published: February 2021

We report on rotationally resolved laser induced fluorescence (LIF) and vibrationally resolved resonance-enhanced multiphoton ionization (REMPI) spectroscopy of the chiral molecule 1-indanol.
Non-collinear antiferromagnetism to compensated ferrimagnetism in Ti(Fe1−xCox)2 (x = 0, 0.5 and 1) alloys: experiment and theory
Authors: Samatham S. Shanmukharao , Patel Akhilesh Kumar , Lukoyanov Alexey V. , Suresh K. G. , Nirmala R.
Published: February 2021

The manifestation of the structural and magnetic properties of Co substituted TiFe2 is investigated using powder X-ray diffraction, magnetization and density functional theory calculations.
Topochemical polymerizations for the solid-state synthesis of organic polymers
Authors: Hema Kuntrapakam , Ravi Arthi , Raju Cijil , Pathan Javed R. , Rai Rishika , Sureshan Kana M.
Published: February 2021

This review summarizes the different categories of topochemical polymerizations for the synthesis of fully-organic polymers and their design strategies.
Grand challenges in the nitrogen cycle
Authors: Lehnert Nicolai , Musselman Bradley W. , Seefeldt Lance C.
Published: February 2021

In this Viewpoint, we address limitations within our current understanding of the complex chemistry of the enzymes in the Nitrogen Cycle. Understanding of these chemical processes plays a key role in limiting anthropogenic effects on our environment.
Hydrodeoxygenation and hydrogenolysis of biomass-based materials using FeNi catalysts and magnetic induction
Authors: Mustieles Marin Irene , De Masi Déborah , Lacroix Lise-Marie , Fazzini Pier-Francesco , van Leeuwen Piet W. N. M. , Asensio Juan M. , Chaudret Bruno
Published: February 2021

Magnetically induced catalysis in solution for the valorization of biomass-derived compounds using FeNi3@Ni nanoparticles.
Direct synthesis of imines from nitro compounds and biomass-derived carbonyl compounds over nitrogen-doped carbon material supported Ni nanoparticles
Authors: Li Bo , Wang Yanxin , Chi Quan , Yuan Ziliang , Liu Bing , Zhang Zehui
Published: February 2021

A kind of nitrogen-doped carbon material and MgO co-supported Ni nanoparticle catalyst has been developed and demonstrates high activity, selectivity and stability.
An ESIPT-based colorimetric and fluorescent probe with large Stokes shift for the sensitive detection of hypochlorous acid and its bioimaging in cells
Authors: Ren Haixian , Huo Fangjun , Yin Caixia
Published: February 2021

Hypochlorous acid (HOCl), with a low physiological concentration, plays a vital role in killing the pathogens and anti-inflammation in the human immune system.
A simple, high-throughput method of protein and label removal from extracellular vesicle samples
Authors: Welsh Joshua A. , Killingsworth Bryce , Kepley Julia , Traynor Tim , McKinnon Kathy , Savage Jason , Appel Deven , Aldape Kenneth , Camphausen Kevin , Berzofsky Jay A. , Ivanov Alexander R. , Ghiran Ionita H. , Jones Jennifer C.
Published: February 2021

Proposed pipeline to increase of the clinical utility extracellular vesicles (EVs) as translational biomarkers.
Self-sustaining enzyme nanocapsules perform on-site chemical reactions
Authors: Machtakova Marina , Han Shen , Yangazoglu Yeliz , Lieberwirth Ingo , Thérien-Aubin Héloïse , Landfester Katharina
Published: February 2021

Self-sustaining enzyme nanocapsules were prepared by the interfacial crosslinking of enzymes droplets. They acted both as nanoreactors and a transport module, and were used to transport reagents and perform reactions in different environments.
Controlled mutation in the replication of synthetic oligomers
Authors: Núñez-Villanueva Diego , Hunter Christopher A.
Published: February 2021

The use of two different covalent base-pairs introduces sequence mutations at a controlled rate in the covalent template-directed synthesis of oligotriazoles, a step towards evolvable synthetic polymers.
Circularly polarized luminescence from structurally coloured polymer films
Authors: Ni Baining , Li Yi , Liu Wei , Li Baozong , Li Hongkun , Yang Yonggang
Published: February 2021

A strategy for the preparation of structurally coloured polymer films with strong circularly polarized luminescence and enhanced fluorescence efficiency based on cholesteric liquid crystals is presented for the first time.
Fluorescence sensors for detection of water based on tetraphenylethene–anthracene possessing both solvatofluorochromic properties and aggregation-induced emission (AIE) characteristics
Authors: Mise Yuta , Imato Keiichi , Ogi Takashi , Tsunoji Nao , Ooyama Yousuke
Published: February 2021

TPE-(An-CHO)4 has been developed as an SFC (solvatofluorochromism)/AIEE (aggregation-induced emission enhancement)-based fluorescence sensor for detection of water over a wide range from low to high water content regions in solvents.
Recent insight into the role of RING-finger E3 ligases in glioma
Authors: Cao Yang , Zhou Hang , Chen Xiaoyu , Li Yin , Hu Junwen , Zhou Guoyang , Wang Lin
Published: February 2021

The ubiquitin proteasome system (UPS) serves as the major posttranslational modification system for the maintenance of protein homeostasis. The ubiquitin ligases (E3s) are responsible for the recognition and recruitment of specific substrate proteins for polyubiquitination. Really interesting new gene (RING) finger E3s account for the majority of E3s. The human genome encodes more than 600 RING E3s, which are divided into three subclasses: single polypeptide E3s, cullin-RING ligases (CRLs) and other multisubunit E3s. The abnormal regulation of RING E3s has been reported to disrupt normal biological processes and induce the occurrence of many human malignancies. Glioma is the most common type of malignant primary brain tumor. In the last few decades, patient prognosis has improved as novel targeted therapeutic agents have developed. In this review, we will summarize the current knowledge about the dysregulation of RING E3s and the altered stability of their substrates in glioma. We will further introduce and discuss the current status and future perspectives of the application of small inhibitors and proteolysis-targeting chimeric molecules (PROTACs) interfering with RING E3s as potential anticancer agents for glioma.
Cryptography‐based deep artificial structure for secure communication using IoT‐enabled cyber‐physical system
Authors: Kannan Chakrapani , Dakshinamoorthy Muralidharan , Ramachandran Manikandan , Patan Rizwan , Kalyanaraman Hariharan , Kumar Ambeshwar
Published: February 2021

Internet of things (IoTs) enabled cyber‐physical systems is a system that provides communication between physical devices and cyber environment. They run independently without any user interaction. Because the IoT devices are vulnerable to a variety of attacks, security is a noteworthy factor in the development process during communication. To improve secure communication with minimum time consumption, a novel technique called jackknife regressive Schmidt Samoa cryptography‐based deep artificial structure learning (JRSSC‐DASL) is introduced. Initially, the data is monitored by IoT devices and is collected from the dataset. The proposed deep artificial structure learning technique trains the gathered data with multiple layers. Then, the collected data is analysed in the first hidden layer with the help of the jackknife regression function by learning the feature and it classifies the data with higher accuracy. The classified data is sent to the next hidden layer where encryption is performed using Schmidt Samoa (SS) encryption algorithm. Then, the encrypted data is sent to the cloud server where the decryption is performed using the SS decryption algorithm. The cloud server obtains the original data and it is stored in their database for further processing. This process enhances the security of data communication and achieves high data confidentiality with less processing time. Experimental estimation is performed on the factors such as classification accuracy, confidentiality rate, processing time and memory usage to the number of data sensed from IoT device. Conferred results reveal that the proposed JRSSC‐DASL technique has high confidentiality rate and minimum processing time as well as memory usage when compared to state‐of‐the‐art methods.
Exploiting UAV‐emitted jamming to improve physical‐layer security: A 3D trajectory control perspective
Authors: Ren Mengmeng , Chen Jian , Zhou Yuchen , Yang Long
Published: February 2021

This study investigates the physical‐layer security of a terrestrial communication system in the presence of potential unmanned aerial vehicle (UAV) eavesdroppers (UEDs). Due to the line‐of‐sight channels of ground‐to‐air links and the broadcast characteristics of wireless channels, the UEDs have a better chance to eavesdrop terrestrial communication systems compared with the conventional ground eavesdroppers. It indicates that the emerging of UEDs brings new challenges to secure transmissions in terrestrial communication systems. In this study, a UAV is recruited to wisely jam the UEDs by adopting a dynamic three‐dimensional (3D) trajectory, in order to protect the legitimate transmission. To maximally improve the average secrecy rate, the joint optimization of the 3D trajectory of the UAV jammer and legitimate user scheduling as a non‐convex mixed‐integer optimization problem is formulated. To efficiently solve such a challenging problem, a novel enhanced genetic algorithm (EGA), where a combined encoding method and a fitness‐based crossover method are developed to improve the convergence performance, is proposed. Simulation results demonstrate the superior performance of the proposed EGA in terms of the average secrecy rate.
Fractional‐order controllers for irrational systems
Authors: Guel‐Cortez Adrian‐Josue , Méndez‐Barrios César‐Fernando , Kim Eun‐jin , Sen Mihir
Published: February 2021

In this contribution, fractional‐order controllers of the type PDμ and PIλ are applied to a class of irrational transfer function models that appear in large‐scale systems, such as networks of mechanical/electrical elements and distributed parameter systems. More precisely, by considering the fractional‐order controller in the Laplace domain with , a stability analysis in the parameter‐space is presented. Furthermore, as a way to measure the controller robustness, the controller's fragility analysis using the parameter‐space is derived. Finally, several applications that demonstrate the utility of our results are included.