bluuebunny/crossref_metadata_2025 huggingface dataset:
TNF-alpha-induced microglia activation requires miR-342: impact on NF-kB signaling and neurotoxicity
Authors: Brás João Paulo , Bravo Joana , Freitas Jaime , Barbosa Mário Adolfo , Santos Susana Gomes , Summavielle Teresa , Almeida Maria Inês
Published: June 2020

Growing evidences suggest that sustained neuroinflammation, caused by microglia overactivation, is implicated in the development and aggravation of several neurological and psychiatric disorders. In some pathological conditions, microglia produce increased levels of cytotoxic and inflammatory mediators, such as tumor necrosis factor alpha (TNF-α), which can reactivate microglia in a positive feedback mechanism. However, specific molecular mediators that can be effectively targeted to control TNF-α-mediated microglia overactivation, are yet to be uncovered. In this context, we aim to identify novel TNF-α-mediated micro(mi)RNAs and to dissect their roles in microglia activation, as well as to explore their impact on the cellular communication with neurons. A miRNA microarray, followed by RT-qPCR validation, was performed on TNF-α-stimulated primary rat microglia. Gain- and loss-of-function in vitro assays and proteomic analysis were used to dissect the role of miR-342 in microglia activation. Co-cultures of microglia with hippocampal neurons, using a microfluidic system, were performed to understand the impact on neurotoxicity. Stimulation of primary rat microglia with TNF-α led to an upregulation of Nos2, Tnf, and Il1b mRNAs. In addition, ph-NF-kB p65 levels were also increased. miRNA microarray analysis followed by RT-qPCR validation revealed that TNF-α stimulation induced the upregulation of miR-342. Interestingly, miR-342 overexpression in N9 microglia was sufficient to activate the NF-kB pathway by inhibiting BAG-1, leading to increased secretion of TNF-α and IL-1β. Conversely, miR-342 inhibition led to a strong decrease in the levels of these cytokines after TNF-α activation. In fact, both TNF-α-stimulated and miR-342-overexpressing microglia drastically affected neuron viability. Remarkably, increased levels of nitrites were detected in the supernatants of these co-cultures. Globally, our findings show that miR-342 is a crucial mediator of TNF-α-mediated microglia activation and a potential target to tackle microglia-driven neuroinflammation.
An encrusting kleptoparasite-host interaction from the early Cambrian
Authors: Zhang Zhifei , Strotz Luke C. , Topper Timothy P. , Chen Feiyang , Chen Yanlong , Liang Yue , Zhang Zhiliang , Skovsted Christian B. , Brock Glenn A.
Published: June 2020

Parasite–host systems are pervasive in nature but are extremely difficult to convincingly identify in the fossil record. Here we report quantitative evidence of parasitism in the form of a unique, enduring life association between tube-dwelling organisms encrusted to densely clustered shells of a monospecific organophosphatic brachiopod assemblage from the lower Cambrian (Stage 4) of South China. Brachiopods with encrusting tubes have decreased biomass (indicating reduced fitness) compared to individuals without tubes. The encrusting tubes orient tightly in vectors matching the laminar feeding currents of the host, suggesting kleptoparasitism. With no convincing parasite–host interactions known from the Ediacaran, this widespread sessile association reveals intimate parasite–host animal systems arose in early Cambrian benthic communities and their emergence may have played a key role in driving the evolutionary and ecological innovations associated with the Cambrian radiation.
A powder-metallurgy-based strategy toward three-dimensional graphene-like network for reinforcing copper matrix composites
Authors: Zhang Xiang , Xu Yixin , Wang Miaocao , Liu Enzuo , Zhao Naiqin , Shi Chunsheng , Lin Dong , Zhu Fulong , He Chunnian
Published: June 2020

Three-dimensional graphene network is a promising structure for improving both the mechanical properties and functional capabilities of reinforced polymer and ceramic matrix composites. However, direct application in a metal matrix remains difficult due to the reason that wetting is usually unfavorable in the carbon/metal system. Here we report a powder-metallurgy based strategy to construct a three-dimensional continuous graphene network architecture in a copper matrix through thermal-stress-induced welding between graphene-like nanosheets grown on the surface of copper powders. The interpenetrating structural feature of the as-obtained composites not only promotes the interfacial shear stress to a high level and thus results in significantly enhanced load transfer strengthening and crack-bridging toughening simultaneously, but also constructs additional three-dimensional hyperchannels for electrical and thermal conductivity. Our approach offers a general way for manufacturing metal matrix composites with high overall performance.
Rapid range shifts and megafaunal extinctions associated with late Pleistocene climate change
Authors: Seersholm Frederik V. , Werndly Daniel J. , Grealy Alicia , Johnson Taryn , Keenan Early Erin M. , Lundelius Ernest L. , Winsborough Barbara , Farr Grayal Earle , Toomey Rickard , Hansen Anders J. , Shapiro Beth , Waters Michael R. , McDonald Gregory , Linderholm Anna , Stafford Thomas W. , Bunce Michael
Published: June 2020

Large-scale changes in global climate at the end of the Pleistocene significantly impacted ecosystems across North America. However, the pace and scale of biotic turnover in response to both the Younger Dryas cold period and subsequent Holocene rapid warming have been challenging to assess because of the scarcity of well dated fossil and pollen records that covers this period. Here we present an ancient DNA record from Hall’s Cave, Texas, that documents 100 vertebrate and 45 plant taxa from bulk fossils and sediment. We show that local plant and animal diversity dropped markedly during Younger Dryas cooling, but while plant diversity recovered in the early Holocene, animal diversity did not. Instead, five extant and nine extinct large bodied animals disappeared from the region at the end of the Pleistocene. Our findings suggest that climate change affected the local ecosystem in Texas over the Pleistocene-Holocene boundary, but climate change on its own may not explain the disappearance of the megafauna at the end of the Pleistocene.
Loss of the transcription factor MAFB limits β-cell derivation from human PSCs
Authors: Russell Ronan , Carnese Phichitpol P. , Hennings Thomas G. , Walker Emily M. , Russ Holger A. , Liu Jennifer S. , Giacometti Simone , Stein Roland , Hebrok Matthias
Published: June 2020

Next generation sequencing studies have highlighted discrepancies in β-cells which exist between mice and men. Numerous reports have identified MAF BZIP Transcription Factor B (MAFB) to be present in human β-cells postnatally, while its expression is restricted to embryonic and neo-natal β-cells in mice. Using CRISPR/Cas9-mediated gene editing, coupled with endocrine cell differentiation strategies, we dissect the contribution of MAFB to β-cell development and function specifically in humans. Here we report that MAFB knockout hPSCs have normal pancreatic differentiation capacity up to the progenitor stage, but favor somatostatin- and pancreatic polypeptide–positive cells at the expense of insulin- and glucagon-producing cells during endocrine cell development. Our results describe a requirement for MAFB late in the human pancreatic developmental program and identify it as a distinguishing transcription factor within islet cell subtype specification. We propose that hPSCs represent a powerful tool to model human pancreatic endocrine development and associated disease pathophysiology.
Insights into catalysis and regulation of non-canonical ubiquitination and deubiquitination by bacterial deamidase effectors
Authors: Wang Yong , Zhan Qi , Wang Xinlu , Li Peipei , Liu Songqing , Gao Guangxia , Gao Pu
Published: June 2020

The bacterial effector MavC catalyzes non-canonical ubiquitination of host E2 enzyme UBE2N without engaging any of the conventional ubiquitination machinery, thereby abolishing UBE2N’s function in forming K63-linked ubiquitin (Ub) chains and dampening NF-кB signaling. We now report the structures of MavC in complex with conjugated UBE2N~Ub and an inhibitor protein Lpg2149, as well as the structure of its ortholog, MvcA, bound to Lpg2149. Recognition of UBE2N and Ub depends on several unique features of MavC, which explains the inability of MvcA to catalyze ubiquitination. Unexpectedly, MavC and MvcA also possess deubiquitinase activity against MavC-mediated ubiquitination, highlighting MavC as a unique enzyme possessing deamidation, ubiquitination, and deubiquitination activities. Further, Lpg2149 directly binds and inhibits both MavC and MvcA by disrupting the interactions between enzymes and Ub. These results provide detailed insights into catalysis and regulation of MavC-type enzymes and the molecular mechanisms of this non-canonical ubiquitination machinery.
Supernumerary B chromosomes of Aegilops speltoides undergo precise elimination in roots early in embryo development
Authors: Ruban Alevtina , Schmutzer Thomas , Wu Dan D. , Fuchs Joerg , Boudichevskaia Anastassia , Rubtsova Myroslava , Pistrick Klaus , Melzer Michael , Himmelbach Axel , Schubert Veit , Scholz Uwe , Houben Andreas
Published: June 2020

Not necessarily all cells of an organism contain the same genome. Some eukaryotes exhibit dramatic differences between cells of different organs, resulting from programmed elimination of chromosomes or their fragments. Here, we present a detailed analysis of programmed B chromosome elimination in plants. Using goatgrass Aegilops speltoides as a model, we demonstrate that the elimination of B chromosomes is a strictly controlled and highly efficient root-specific process. At the onset of embryo differentiation B chromosomes undergo elimination in proto-root cells. Independent of centromere activity, B chromosomes demonstrate nondisjunction of chromatids and lagging in anaphase, leading to micronucleation. Chromatin structure and DNA replication differ between micronuclei and primary nuclei and degradation of micronucleated DNA is the final step of B chromosome elimination. This process might allow root tissues to survive the detrimental expression, or overexpression of B chromosome-located root-specific genes with paralogs located on standard chromosomes.
A flexible artificial intrinsic-synaptic tactile sensory organ
Authors: Lee Yu Rim , Trung Tran Quang , Hwang Byeong-Ung , Lee Nae-Eung
Published: June 2020

Imbuing bio-inspired sensory devices with intelligent functions of human sensory organs has been limited by challenges in emulating the preprocessing abilities of sensory organs such as reception, filtering, adaptation, and sensory memory at the device level itself. Merkel cells, which is a part of tactile sensory organs, form synapse-like connections with afferent neuron terminals referred to as Merkel cell-neurite complexes. Here, inspired by structure and intelligent functions of Merkel cell-neurite complexes, we report a flexible, artificial, intrinsic-synaptic tactile sensory organ that mimics synapse-like connections using an organic synaptic transistor with ferroelectric nanocomposite gate dielectric of barium titanate nanoparticles and poly(vinylidene fluoride-trifluoroethylene). Modulation of the post-synaptic current of the device induced by ferroelectric dipole switching due to triboelectric-capacitive coupling under finger touch allowed reception and slow adaptation. Modulation of synaptic weight by varying the nanocomposite composition of gate dielectric layer enabled tuning of filtering and sensory memory functions.
Visualizable detection of nanoscale objects using anti-symmetric excitation and non-resonance amplification
Authors: Zhu Jinlong , Udupa Aditi , Goddard Lynford L.
Published: June 2020

Why can we not see nanoscale objects under a light microscope? The textbook answers are that their relative signals are weak and their separation is smaller than Abbe’s resolution limit. Thus, significant effort has gone into developing ultraviolet imaging, oil and solid immersion objectives, nonlinear methods, fluorescence dyes, evanescent wave tailoring, and point-spread function engineering. In this work, we introduce a new optical sensing framework based on the concepts of electromagnetic canyons and non-resonance amplification, to directly view on a widefield microscope λ/31-scale (25-nm radius) objects in the near-field region of nanowire-based sensors across a 726-μm × 582-μm field of view. Our work provides a simple but highly efficient framework that can transform conventional diffraction-limited optical microscopes for nanoscale visualization. Given the ubiquity of microscopy and importance of visualizing viruses, molecules, nanoparticles, semiconductor defects, and other nanoscale objects, we believe our proposed framework will impact many science and engineering fields.
In-situ measurements of fabrication induced strain in diamond photonic-structures using intrinsic colour centres
Authors: Knauer Sebastian , Hadden John P. , Rarity John G.
Published: June 2020

Diamond has established itself as an ideal material for photonics and optomechanics, due to its broad-band transparency and hardness. In addition, colour centres hosted within its lattice such as the nitrogen-vacancy (NV) centre, have become leading candidates for use in quantum information processing, and quantum sensors. The fabrication of nanoscale devices coupled to high quality NVs has been an outstanding challenge due to their sensitivity to magnetic, electric and strain fields within their local environment. In this work, we show how the NV centre’s ground state electron spin can be used as an embedded atomic-scale probe of the local strain caused by focused ion beam milling of nanoscale devices. This technique can thus be used to measure, and optimise material and device fabrication processes to allow diamond to reach its full potential.
Spermidine Enhanced Free Polyamine Levels and Expression of Polyamine Biosynthesis Enzyme Gene in Rice Spikelets under Heat Tolerance before Heading
Authors: Zhou Rong , Hu Qijuan , Pu Qiong , Chen Moxian , Zhu Xiuru , Gao Cong , Zhou Guixiang , Liu Lijun , Wang Zhiqing , Yang Jianchang , Zhang Jianhua , Cao Yunying
Published: June 2020

High temperatures (HT) before heading strongly inhibit the development of spikelets in rice. Spermidine (Spd) can improve rice’s resistance to HT stress; however, the mechanism underlying this effect has not been elucidated. This study investigated several parameters, including yield, superoxide anion (O2.-), protective enzyme activities, and polyamine content, in a heat-sensitive genotype, Shuanggui 1. The yield and yield components decreased dramatically when subjected to HT stress, while this reduction could be partially recovered by exogenous Spd. Spd also slowed the generation rate of O2.- and increased protective enzyme, superoxide dismutase (SOD) and catalase (CAT) activities both under normal and high temperatures, which suggested that Spd may participate in the antioxidant system. Furthermore, genes involved in polyamine synthesis were analyzed. The results show that HT before heading significantly increased the expression of arginine decarboxylase OsADC1, Spd synthase OsSPDS1 and OsSPDS3 and had little effect on the expression of the S-adenosylmethionine decarboxylase OsSAMDC2 and ornithine decarboxylase OsODC1. In addition, exogenous Spd considerably reduced the expression of OsSAMDC2, OsSPDS1 and OsSPDS3 under HT but not the expression of OsADC1. The above mentioned results indicate that the exogenous Spd could help young rice spikelets to resist HT stress by reducing the expression of OsSAMDC2, OsSPDS1 and OsSPDS3, resulting in higher levels of endogenous Spd and Spm, which were also positively correlated with yield. In conclusion, the adverse effect of HT stress on young spikelets seems to be alleviated by increasing the amounts of Spd and Spm, which provides guidance for adaptation to heat stress during rice production.
Neutral excitation density-functional theory: an efficient and variational first-principles method for simulating neutral excitations in molecules
Authors: Roychoudhury Subhayan , Sanvito Stefano , O’Regan David D.
Published: June 2020

We introduce neutral excitation density-functional theory (XDFT), a computationally light, generally applicable, first-principles technique for calculating neutral electronic excitations. The concept is to generalise constrained density functional theory to free it from any assumptions about the spatial confinement of electrons and holes, but to maintain all the advantages of a variational method. The task of calculating the lowest excited state of a given symmetry is thereby simplified to one of performing a simple, low-cost sequence of coupled DFT calculations. We demonstrate the efficacy of the method by calculating the lowest single-particle singlet and triplet excitation energies in the well-known Thiel molecular test set, with results which are in good agreement with linear-response time-dependent density functional theory (LR-TDDFT). Furthermore, we show that XDFT can successfully capture two-electron excitations, in principle, offering a flexible approach to target specific effects beyond state-of-the-art adiabatic-kernel LR-TDDFT. Overall the method makes optical gaps and electron-hole binding energies readily accessible at a computational cost and scaling comparable to that of standard density functional theory. Owing to its multiple qualities beneficial to high-throughput studies where the optical gap is of particular interest; namely broad applicability, low computational demand, and ease of implementation and automation, XDFT presents as a viable candidate for research within materials discovery and informatics frameworks.
Fine-tuning of Genome-Wide Polygenic Risk Scores and Prediction of Gestational Diabetes in South Asian Women
Authors: Lamri Amel , Mao Shihong , Desai Dipika , Gupta Milan , Paré Guillaume , Anand Sonia S.
Published: June 2020

Gestational diabetes Mellitus (GDM) affects 1 in 7 births and is associated with numerous adverse health outcomes for both mother and child. GDM is suspected to share a large common genetic background with type 2 diabetes (T2D). The aim of our study was to characterize different GDM polygenic risk scores (PRSs) and test their association with GDM using data from the South Asian Birth Cohort (START). PRSs were derived for 832 South Asian women from START using the pruning and thresholding (P + T), LDpred, and GraBLD methods. Weights were derived from a multi-ethnic and a white Caucasian study of the DIAGRAM consortium. GDM status was defined using South Asian-specific glucose values in response to an oral glucose tolerance test. Association with GDM was tested using logistic regression. Results were replicated in South Asian women from the UK Biobank (UKB) study. The top ranking P + T, LDpred and GraBLD PRSs were all based on DIAGRAM’s multi-ethnic study. The best PRS was highly associated with GDM in START (AUC = 0.62, OR = 1.60 [95% CI = 1.44–1.69]), and in South Asian women from UKB (AUC = 0.65, OR = 1.69 [95% CI = 1.28–2.24]). Our results highlight the importance of combining genome-wide genotypes and summary statistics from large multi-ethnic studies to optimize PRSs in South Asians.
Palynological Age Control and Paleoenvironments of the Paleogene Strata in Eastern Dahomey Basin, Southwestern Nigeria
Authors: Bolaji Taiwo A. , Ndukwe Otobong S. , Oyebamiji Ajibola R. , Ikegwuonu Okechukwu N.
Published: June 2020

Paleogene deposits are extensively exposed in the Eastern Dahomey (Benin) sedimentary Basin in southwestern Nigeria. Outcrop logging and sampling of lithological sections were systematically carried out at the Ibese Quarry, in order to re-establish the age of sediments and reconstruct their depositional environment using samples rich in organic-walled microfossils. Two formations were recognized; the Ewekoro and Akinbo Formations. Two main lithological units were identified; limestones and carbonaceous shales. Minor lithologies include ferrugineous sandstones and glauconite. Results from the palynological examination show that terrestrial palynomorphs (spores and pollen) dominate over the marine dinoflagellates cyst species in the samples recovered from the Ewekoro Formation, while samples from the Akinbo Formation recorded high abundance with less diversity of the marine dinoflagellates cysts over the terrestrial sporomorph. Age determination/correlation was achieved based on selected stratigraphic index taxa recovered. The samples from Ewekoro Formation were dated as late Early Paleocene to early Middle Paleocene, based on the presence of the following pollen key-taxa: Proxapertites operculatus, Retidiporites magdalenensis, Spinizonocolpites baculatus, Mauritidiites crassiexinus, Scabratriporites simpliformis, and Echitriporites trianguliformis. The samples from the Akinbo Formation were assigned late Middle Paleocene to late Paleocene, based on the presence of the following pollen key-taxa: Proxapertites operculatus/cursus, Grimsdalea polygonalis, Retibrevitricolpites triangulatus, Psilatricolporites operculatus, Retistephanocolpites williamsi, Bombacidites sp., Apectodinium homomorphum, and Apectodinium quinquelatum. The environmentally significant palynomorph species indicated differences in paleodepositional environments, ranging from shallow marine in the Ewekoro Formation at the base, up the stratigraphic sequence, to marginal marine (estuarine) depositional environment in the overlying Akinbo Formation.
Liver colour scoring index, carotenoids and lipid content assessment as a proxy for lumpfish (Cyclopterus lumpus L.) health and welfare condition
Authors: Eliasen Kirstin , Patursson Esbern J. , McAdam Bruce J. , Pino Enrique , Morro Bernat , Betancor Monica , Baily Johanna , Rey Sonia
Published: June 2020

Ensuring lumpfish health and welfare in salmon farms is vital to reduce the high mortality rates reported and to guarantee a high delousing efficiency. Recent observations of farmed lumpfish livers have shown colours ranging from pale (colours 1 and 2), through bright orange (colours 3 and 4), to dark reddish-brown (colours 5 and 6), some of which may be related to welfare condition. To characterize the status of lumpfish deployed in four Faroese salmon farms, several welfare indicators were assessed: a weight-length relationship, scoring of external physical damage, and after dissection, stomach content and liver colour scoring. Liver samples were weighed, stored and analysed for lipid content, lipid classes, total pigments, fatty acid profile and histopathology to explain the differences between the mentioned liver colours. Bright orange livers, liver colours 3 and 4, were related to increased levels of carotenoid pigments rather than levels of lipids and appear to reflect good fish welfare. However, dark reddish-brown colours, liver colours 5 and 6, were associated with very low levels of triacyl glycerides in the liver, indicating use of lipid reserves and poor welfare condition. Histopathology confirmed that the dark reddish-brown livers, liver colours 5 and 6, formed a distinct group. Thus, liver colour was shown to be a good welfare indicator and should be monitored in farms.
Comparative Effects of Alpha- and Gamma-Tocopherol on Mitochondrial Functions in Alzheimer’s Disease In Vitro Model
Authors: Pahrudin Arrozi Aslina , Shukri Siti Nur Syazwani , Wan Ngah Wan Zurinah , Mohd Yusof Yasmin Anum , Ahmad Damanhuri Mohd Hanafi , Jaafar Faizul , Makpol Suzana
Published: June 2020

Vitamin E acts as an antioxidant and reduces the level of reactive oxygen species (ROS) in Alzheimer’s disease (AD). Alpha-tocopherol (ATF) is the most widely studied form of vitamin E besides gamma-tocopherol (GTF) which also shows beneficial effects in AD. The levels of amyloid-beta (Aβ) and amyloid precursor protein (APP) increased in the brains of AD patients, and mutations in the APP gene are known to enhance the production of Aβ. Mitochondrial function was shown to be affected by the increased level of Aβ and may induce cell death. Here, we aimed to compare the effects of ATF and GTF on their ability to reduce Aβ level, modulate mitochondrial function and reduce the apoptosis marker in SH-SY5Y cells stably transfected with the wild-type or mutant form of the APP gene. The Aβ level was measured by ELISA, the mitochondrial ROS and ATP level were quantified by fluorescence and luciferase assay respectively whereas the complex V enzyme activity was measured by spectrophotometry. The expressions of genes involved in the regulation of mitochondrial membrane permeability such as voltage dependent anion channel (VDAC1), adenine nucleotide translocase (ANT), and cyclophilin D (CYPD) were determined by quantitative real-time polymerase chain reaction (qRT-PCR), while the expressions of cyclophilin D (CypD), cytochrome c, Bcl2 associated X (BAX), B cell lymphoma-2 (Bcl-2), and pro-caspase-3 were determined by western blot. Our results showed that mitochondrial ROS level was elevated accompanied by decreased ATP level and complex V enzyme activity in SH-SY5Y cells expressing the mutant APP gene (p < 0.05). Treatment with both ATF and GTF reduced the mitochondrial ROS level with maximum reduction was observed in the cells treated with high concentrations of ATF and GTF (p < 0.05). However, only GTF at 80 µM significantly increase the ATP level and complex V enzyme activity (p < 0.05). VDAC1 and CYPD were downregulated and CypD protein was significantly overexpressed in cells transfected with the wild-type (WT) and mutant APP gene (p < 0.05). Cytochrome c release, the ratio of BAX/Bcl-2, and pro-caspase-3 expression increased in cells expressing mutated APP gene (p < 0.05). The expression of CypD and pro-caspase 3 protein, and the ratio of BAX/Bcl-2 were increased in the following order; SH-SY5Y-APP-WT < SH-SY5Y-APP Swe <SH-SY5Y-APP Swe/Ind. Treatment with both ATF and GTF reduced the release of cytochrome c and the ratio of BAX/Bcl-2. However, only GTF significantly reduced the expression of CypD and pro-caspase-3, suggestive of its unique role in AD. In conclusion, GTF has an effect that was not shown by ATF and thus suggest its potential role in the development of therapeutic agents for AD.
Ultra-rapid glutathionylation of chymotrypsinogen in its molten globule-like conformation: A comparison to archaeal proteins
Authors: Bocedi Alessio , Gambardella Giorgia , Cattani Giada , Bartolucci Simonetta , Limauro Danila , Pedone Emilia , Iavarone Federica , Castagnola Massimo , Ricci Giorgio
Published: June 2020

Chymotrypsinogen, when reduced and taken to its molten globule-like conformation, displays a single cysteine with an unusual kinetic propensity toward oxidized glutathione (GSSG) and other organic thiol reagents. A single residue, identified by mass spectrometry like Cys1, reacts with GSSG about 1400 times faster than an unperturbed protein cysteine. A reversible protein-GSSG complex and a low pKa (8.1 ± 0.1) make possible such astonishing kinetic property which is absent toward other natural disulfides like cystine, homocystine and cystamine. An evident hyper-reactivity toward 5,5′-dithiobis-(2-nitrobenzoic acid) (DTNB) and 1-chloro-2,4-dinitrobenzene (CDNB) was also found for this specific residue. The extraordinary reactivity toward GSSG is absent in two proteins of the thermophilic archaeon Sulfolobus solfataricus, an organism lacking glutathione: the Protein Disulphide Oxidoreductase (SsPDO) and the Bacterioferritin Comigratory Protein 1 (Bcp1) that displays Cys residues with an even lower pKa value (7.5 ± 0.1) compared to chymotrypsinogen. This study, which also uses single mutants in Cys residues for Bcp1, proposes that this hyper-reactivity of a single cysteine, similar to that found in serum albumin, lysozyme, ribonuclease, may have relevance to drive the “incipit” of the oxidative folding of proteins from organisms where the glutathione/oxidized glutathione (GSH/GSSG) system is present.
Parthenium hysterophorus steps up Ca-regulatory pathway in defence against highlight intensities
Authors: Ahmad Javed , Baig M. Affan , Amna  , Alaraidh Ibrahim A. , Alsahli Abdulaziz A. , Qureshi M. Irfan
Published: June 2020

Parthenium hysterophorus exhibits tolerance to a great extent against abiotic stresses including high light intensities. In this study, P. hysterophorus was subjected to three different light intensities viz. control (CL, 250 µmol photons m−2 s−1), moderately high (ML, 500 µmol photons m−2 s−1) and high (HL, 1000 µmol photons m−2 s−1) for assessment of biochemical and physiological responses at 3 and 5 days after treatment (DAT). Proteomic responses were also observed at 5 DAT. Level of oxidative stress marker, abundance of H2O2 and O2− was highest in leaves exposed to HL followed by ML treatment. Biomass accumulation, photosynthetic parameters, chloroplast and mitochondrial integrity were also affected by both ML and HL treatments. Differential protein expression data showed modulation of thirty-eight proteins in ML and HL intensities. P. hysterophorus exhibited good ability to survive in ML then HL treatment as demonstrated by enhancement of the antioxidant system and photosynthesis. Furthermore, P. hysterophorus mobilized some key proteins related to calcium signaling, which in turn coordinate physiological homeostasis under stress. Proline and total soluble sugar content were high under stress; however, results of simulated experiment of our study indicate such accumulation of osmolytes may inhibit photon-availability to chloroplast. These results clarify our understanding of the mechanisms underlying the light stress tolerance of P. hysterophorus.
Biochar and fulvic acid amendments mitigate negative effects of coastal saline soil and improve crop yields in a three year field trial
Authors: Sun Yun-peng , Yang Jing-song , Yao Rong-jiang , Chen Xiao-bing , Wang Xiang-ping
Published: June 2020

China with large area of land planted with crops are suffering secondary salinization in coastal area for the lack of fresh water and saltwater intrusion to the groundwater. The purpose of this study was to investigate the effects of biochar (BC) and fulvic acid (FA) on the amelioration of coastal saline soil and their impact on crop yields under maize-barley rotation system. A three year field experiment was conducted in a saline soil on a farm in coastal area of east Jiangsu Province, China. A maize-barley rotation system had been carried out for ten years with local conventional management before the experiment. The saline soil was amended with BC at rates of 0, 7.5 t ha−1 (BC1), 15 t ha−1 (BC2) and 30 t ha−1 (BC3) alone or combined with fulvic acid (1.5 t ha−1) compared with control. Fertilizers were applied under normal planting strategies. The BC was added only once during the four growing seasons, and the FA was applied before each sowing. Soil salinity changed significantly during the three year field experiment. This was mainly due to the great quantity of rain during the period of maize cultivation. Although Na+, Cl− and SO42− in BC and /or FA treatments significantly decreased, the pH value increased up to 9.0 as the CO32− + HCO3−content increased. Total organic carbon (TOC) and phosphorus (TP) responded positively to biochar addition rate. BC applied with appropriate rate at 15 t ha−1 (BC2) in combination with FA showed optimal effects on soil salinity amelioration, soil physics properties regulation, soil nutrition improvement and crop yields increase. The TOC and TP was 5.2 g kg−1 and 507 mg kg−1 in BC2 + FA treatment, which were lower than BC3 and BC3 + FA treatments. However, the highest total grain yield was obtained in the BC2 + FA treatment, and the total yield was increased by 62.9% over the CK. This study emphasizes that using combined organic amendment of BC with FA for profitable and sustainable use of salt-affected soils would be practicable.
Sad mood and poor sleep are related to task-unrelated thoughts and experience of diminished cognitive control
Authors: Marcusson-Clavertz David , Kjell Oscar N. E. , Kim Jinhyuk , Persson Stefan D. , Cardeña Etzel
Published: June 2020

Previous studies have indicated that a sad mood and sleep deprivation increase mind wandering, but it is unclear whether these associations reflect reduced effort in concentrating on the task at hand or diminished cognitive control. In an internet-based experiment, participants completed a sleep disturbance questionnaire followed by a complex span task and a 2-back task with thought-sampling probes. Subsequently, participants underwent a positive, neutral, or negative mood induction prior to repeating the 2-back. The results (N = 504) replicated the finding of increased task-unrelated thoughts following sad mood induction, B = 0.56 (SE = 0.14), p < 0.01, d = 0.31. Unguided thoughts were increased following sad mood induction, B = 0.31 (0.13), p = 0.02, but working memory did not significantly moderate this association (p = 0.31). People reported a lower degree of trying to concentrate on the 2-back after the sad mood induction, B = −0.07 (0.04), p = 0.04, but actual performance was not affected (p = 0.46). Sleep disturbances showed small associations with task-unrelated, B = 0.23 (0.08), p < 0.01, and unguided thoughts, B = 0.32 (0.08), p < 0.01. This study strengthens the evidence that a sad mood and poor sleep relate to mind wandering.
Host genotype and exercise exhibit species-level selection for members of the gut bacterial communities in the mouse digestive system
Authors: Dowden R. A. , McGuinness L. R. , Wisniewski P. J. , Campbell S. C. , Guers J. J. , Oydanich M. , Vatner S. F. , Häggblom M. M. , Kerkhof L. J.
Published: June 2020

The mammalian gut microbiome can potentially impact host health and disease state. It is known that the mouse-genome, eating-behavior, and exercise-status promotes higher taxonomic rank-level alterations (e.g. family to phyla-level) of the gut microbiota. Here, host genotype or activity status was investigated to determine if selection of individual bacterial species or strains could be discerned within the murine digestive system. For this study, the fecal bacterial community of adenylyl cyclase 5 knock-out (AC5KO, n = 7) mice or their wild-type (WT, n = 10) littermates under exercise or sedentary conditions were profiled by sequencing rRNA operons. AC5KO mice were chosen since this genotype displays enhanced longevity/exercise capacity and protects against cardiovascular/metabolic disease. Profiling of rRNA operons using the Oxford MinION yielded 65,706 2-D sequences (after size selection of 3.7–5.7 kb) which were screened against an NCBI 16S rRNA gene database. These sequences were binned into 1,566 different best BLAST hits (BBHs) and counted for each mouse sample. Non-metric multidimensional scaling (NMDS) of the gut microbial community demonstrated clustering by physical activity (p = 0.001) but not by host genotype. Additionally, sequence similarity and phylogenetic analysis demonstrated that different bacterial species (closely related to Muribaculum intestinale and Parasutterella excrementihominis) inhabit AC5KO or WT mice depending on activity status. Other bacterial species of the gut microbiota did not follow such patterning (e.g. Turicibacter sanguinis and Turicimonas muris). Our results support the need of improved taxonomic resolution for better characterization of bacterial communities to deepen our understanding of the role of the gut microbiome on host health.
Up regulation of the Hippo signalling effector YAP1 is linked to early biochemical recurrence in prostate cancers
Authors: Marx Andreas , Schumann Aljoscha , Höflmayer Doris , Bady Elena , Hube-Magg Claudia , Möller Katharina , Tsourlakis Maria Christina , Steurer Stefan , Büscheck Franziska , Eichenauer Till , Clauditz Till S. , Graefen Markus , Simon Ronald , Sauter Guido , Izbicki Jakob R. , Huland Hartwig , Heinzer Hans , Haese Alexander , Schlomm Thorsten , Bernreuther Christian , Lebok Patrick , Polonski Adam
Published: June 2020

The transcriptional coactivator YAP1 controls the balance between cell proliferation and apoptosis. YAP1 overexpression is linked to poor prognosis in many cancer types, yet its role in prostate cancer is unknown. Here, we applied YAP1 immunohistochemistry to a tissue microarray containing 17,747 clinical prostate cancer specimens. Cytoplasmic and nuclear YAP1 staining was seen in 81% and 63% of tumours. For both cytoplasmic and nuclear YAP1 staining, high levels were associated with advanced tumour stage, classical and quantitative Gleason grade, positive nodal stage, positive surgical margin, high KI67 labelling index, and early biochemical recurrence (p < 0.0001 each). The prognostic role of YAP1 staining was independent of established prognostic features in multivariate models (p < 0.001). Comparison with previously studied molecular markers identified associations between high YAP1 staining, TMPRSS2:ERG fusion (p < 0.0001), high androgen receptor (AR) expression (p < 0.0001), high Ki67 labelling index (p < 0.0001), and PTEN and 8p deletions (p < 0.0001 each). In conclusion, high YAP1 protein expression is an independent predictor of unfavourable disease course in prostate cancer. That cytoplasmic and nuclear YAP1 staining is equally linked to phenotype and prognosis fits well to a model where YAP1 activation during tumour progression includes up regulation, cytoplasmic accumulation and subsequent translocation to the nucleus.
Relationship between Energy Dosage and Apoptotic Cell Death by Modulated Electro-Hyperthermia
Authors: Kao Patrick Hung-Ju , Chen Chia-Hung , Tsang Yuk-Wah , Lin Chen-Si , Chiang Hsin-Chien , Huang Cheng-Chung , Chi Mau-Shin , Yang Kai-Lin , Li Wen-Tyng , Kao Shang-Jyh , Minnaar Carrie Anne , Chi Kwan-Hwa , Wang Yu-Shan
Published: June 2020

Modulated electro-hyperthermia (mEHT) is a form of mild hyperthermia (HT) used for cancer treatment. The principle utility of HT is the ability not only to increase cell temperature, but also to increase blood flow and associated pO2 to the microenvironment. While investigational evidence has shown the unique ability of mEHT to elicit apoptosis in cancer cells, in vivo and in vitro, the same trait has not been observed with conventional HT. There is dissension as to what allows mEHT to elicit apoptosis despite heating to only mild temperatures, with the predominant opinion in favor of increased temperature at a cellular level as the driving force. For this study, we hypothesized that in addition to temperature, the amount of electrical energy delivered is a major factor in induction of apoptosis by mEHT. To evaluate the impact of electrical energy on apoptosis, we divided generally practiced mEHT treatment into 3 phases: Phase I (treatment start to 10 min. mark): escalation from 25 °C to 37 °C Phase II (10 min. mark to 15 min. mark): escalation from 37 °C to 42 °C Phase III (15 min. mark to 45 min. mark): maintenance at 42 °C Combinations of mEHT at 18 W power, mEHT at 7.5 W power, water bath, and incubator were applied to each of the three phases. Power output was recorded per second and calculated as average power per second. Total number of corresponding Joules emitted per each experiment was also recorded. The biological effect of apoptotic cell death was assayed by annexin-V assay. In group where mEHT was applied for all three phases, apoptosis rate was measured at 31.18 ± 1.47%. In group where mEHT was only applied in Phases II and III, apoptosis rate dropped to 20.2 ± 2.1%. Where mEHT was only applied in Phase III, apoptosis was 6.4 ± 1.7%. Interestingly, when mEHT was applied in Phases I and II, whether Phase III was conducted in either water bath at 42 °C or incubator at 37 °C, resulted in nearly identical apoptosis rates, 26 ± 4.4% and 25.9 ± 3.1%, respectively. These results showed that accumulation of mEHT at high-powered setting (18 W/sec) during temperature escalation (Phase I and Phase II), significantly increased apoptosis of tested cancer cells. The data also showed that whereas apoptosis rate was significantly increased during temperature escalation by higher power (18 W/sec), apoptosis was limited during temperature maintenance with lower power (7.5 W/sec). This presents that neither maintenance of 42 °C nor accumulation of Joules by mEHT has immediate correlating effect on apoptosis rate. These findings may offer a basis for direction of clinical application of mEHT treatment.
Hierarchical biota-level and taxonomic controls on the chemistry of fossil melanosomes revealed using synchrotron X-ray fluorescence
Authors: Rossi Valentina , Webb Samuel M. , McNamara Maria E.
Published: June 2020

Fossil melanosomes, micron-sized granules rich in melanin in vivo, provide key information for investigations of the original coloration, taxonomy and internal anatomy of fossil vertebrates. Such studies rely, in part, on analysis of the inorganic chemistry of preserved melanosomes and an understanding of melanosome chemical taphonomy. The extent to which the preserved chemistry of fossil melanosomes is biased by biotic and abiotic factors is, however, unknown. Here we report the discovery of hierarchical controls on the inorganic chemistry of melanosomes from fossil vertebrates from nine biotas. The chemical data are dominated by a strong biota-level signal, indicating that the primary taphonomic control is the diagenetic history of the host sediment. This extrinsic control is superimposed by a biological, tissue-level control; tissue-specific chemical variation is most likely to survive in fossils where the inorganic chemistry of preserved melanosomes is distinct from that of the host sediment. Comparative analysis of our data for fossil and modern amphibians reveals that most fossil specimens show tissue-specific melanosome chemistries that differ from those of extant analogues, strongly suggesting alteration of original melanosome chemistry. Collectively, these findings form a predictive tool for the identification of fossil deposits with well-preserved melanosomes amenable to studies of fossil colour and anatomy.
Real-time Colorimetric Quantitative Molecular Detection of Infectious Diseases on Smartphone-based Diagnostic Platform
Authors: Yin Kun , Pandian Vikram , Kadimisetty Karteek , Zhang Xin , Ruiz Carlos , Cooper Kumarasen , Liu Changchun
Published: June 2020

Rapid diagnostics of infectious diseases and accurate identification of their causative pathogens play a crucial role in disease prevention, monitoring, and treatment. Conventional molecular detection of infectious pathogens requires expensive equipment and well-trained personnel, thus limiting its use in centralized clinical laboratories. To address this challenge, a portable smartphone-based quantitative molecular detection platform, termed “smart connected pathogen tracer” (SCPT), has been developed for pathogen monitoring and disease surveillance. The platform takes advantage of synergistically enhanced colorimetric loop-mediated isothermal amplification (LAMP) assay and smartphone-based color analysis, enabling simple, rapid and reliable nucleic acid quantification without need for expensive fluorescence detection equipment. The SCPT platform has been successfully applied to quantitatively detect: i) HPV DNA in saliva and clinical vaginal swab samples, and ii) HIV RNA in plasma samples with comparable sensitivity to state-of-art machine. It has also been demonstrated for disease spatiotemporal mapping and pathogen tracking by wireless connection and web-based surveillance. Such simple, cost-affordable, portable molecular detection platform has great potential for on-site early disease detection, remote healthcare monitoring, and epidemic surveillance.
Topographic distinction in long-term value signals between presumed dopamine neurons and presumed striatal projection neurons in behaving monkeys
Authors: Enomoto Kazuki , Matsumoto Naoyuki , Inokawa Hitoshi , Kimura Minoru , Yamada Hiroshi
Published: June 2020

Nigrostriatal dopamine (DA) projections are anatomically organized along the dorsolateral-ventromedial axis, conveying long-term value signals to the striatum for shaping actions toward multiple future rewards. The present study examines whether the topographic organization of long-term value signals are observed upon activity of presumed DA neurons and presumed striatal projection neurons (phasically active neurons, PANs), as predicted based on anatomical literature. Our results indicate that DA neurons in the dorsolateral midbrain encode long-term value signals on a short timescale, while ventromedial midbrain DA neurons encode such signals on a relatively longer timescale. Activity of the PANs in the dorsal striatum is more heterogeneous for encoding long-term values, although significant differences in long-term value signals were observed between the caudate nucleus and putamen. These findings suggest that topographic DA signals for long-term values are not simply transferred to striatal neurons, possibly due to the contribution of other projections to the striatum.
1,25(OH)2VitD3 supplementation enhances suppression of grass pollen-induced allergic asthma by subcutaneous and sublingual immunotherapy in a mouse model
Authors: Hesse Laura , Petersen Arjen H. , Oude Elberink Joanne N. G. , van Oosterhout Antoon J. M. , Nawijn Martijn C.
Published: June 2020

Allergen specific immunotherapy (AIT) can provide long-term alleviation of symptoms for allergic disease but is hampered by suboptimal efficiency. We and others have previously shown that 1,25(OH)2-VitaminD3 (VitD3) can improve therapeutic efficacy of AIT. However, it is unknown whether VitD3 supplementation has similar effects in sublingual and subcutaneous immunotherapy. Therefore, we aimed to test VitD3 supplementation in both grass pollen (GP) subcutaneous-IT (SCIT) and sublingual-IT (SLIT) in a mouse model for allergic airway inflammation. To this end, GP-sensitized BALB/c mice received GP-SCIT or GP-SLIT with or without 10 ng VitD3, followed by intranasal GP challenges and measurement of airway hyperresponsiveness (AHR) and inflammation. VitD3 supplementation of GP-SCIT resulted in enhanced induction of GP-specific (sp)-IgG2a and suppression of spIgE after challenge. In addition, eosinophil numbers were reduced and levels of IL10 and Amphiregulin were increased in lung tissue. In GP-SLIT, VitD3 supplementation resulted in enhanced sp-IgG2a levels in serum, enhanced suppression of eosinophils and increased IL10 levels in lung tissue, as well as suppression of AHR to methacholine. These data show that VitD3 increases efficacy of both SCIT and SLIT, by enhancing induction of blocking antibodies and suppression of airway inflammation, underscoring the relevance of proficient VitD3 levels for successful AIT.
A copper-dependent compound restores ampicillin sensitivity in multidrug-resistant Staphylococcus aureus
Authors: Crawford Cameron L. , Dalecki Alex G. , Perez Mildred D. , Schaaf Kaitlyn , Wolschendorf Frank , Kutsch Olaf
Published: June 2020

Multi-drug resistant Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), has become a worldwide, major health care problem. While initially restricted to clinical settings, drug resistant S. aureus is now one of the key causative agents of community-acquired infections. We have previously demonstrated that copper dependent inhibitors (CDIs), a class of antibiotics that are only active in the presence of copper ions, are effective bactericidal agents against MRSA. A second-generation CDI, APT-6K, exerted bactericidal activity at nanomolar concentrations. At sub-bactericidal concentrations, it effectively synergized with ampicillin to reverse drug resistance in multiple MRSA strains. APT-6K had a favorable therapeutic index when tested on eukaryotic cells (TI: > 30) and, unlike some previously reported CDIs, did not affect mitochondrial activity. These results further establish inhibitors that are activated by the binding of transition metal ions as a promising class of antibiotics, and for the first time, describe their ability to reverse existing drug resistance against clinically relevant antibiotics.