bluuebunny/crossref_metadata_2025 huggingface dataset:
Improvement of muscular atrophy by AAV–SaCas9-mediated myostatin gene editing in aged mice
Authors: Weng Shaoting , Gao Feng , Wang Juan , Li Xingyu , Chu Beibei , Wang Jiang , Yang Guoyu
Published: May 2020

Muscle mass and area usually decrease with age, and this phenomenon is known as sarcopenia. This age-related atrophy correlates with insufficient levels of muscle cells differentiate and proliferate regulated by the TGF-β signaling pathway and the expression of E3s ubiquitin-protein ligase by the aged. Sarcopenia makes a huge impact on the aging society, because it has the characteristic of high incidence, extensive adverse effects and disease aggravation gradually. Guided by a single-guide RNA (sgRNA), Cas9 nuclease has been widely used in genome editing, opening up a new pathway for sarcopenia treatment. Here, we present two rAAV9 systems, pX601-AAV-CMV:SaCas9-U6:sgRNA and pX601-AAV-EF1α:SaCas9-tRNAGLN: sgRNA, which edited myostatin efficiently. By delivering the two rAAV–SaCas9 targets to myostatin via intramuscular injection of aged mice, an increase in body weight and an increase in the number and area of myofibers were observed. Knockout of myostatin led to TGF-β signaling pathway changes, and increased MyoD, Pax7 and MyoG protein levels and increased the number of satellite cells to improve muscle cells differentiation. Moreover, knockout of myostatin prevented the atrophy of muscle cells through reduced Murf1 and MAFbx protein levels. We found that both rAAV–SaCas9 systems had gene editing efficiency, reducing the expression of myostatin by affecting the relevant signaling pathways, thereby altering the physiological status. We showed that myostatin has an important role in activating skeletal muscle proliferation and inhibiting muscular atrophy during aging. Thus, we propose that knockout of myostatin using the rAAV9–SaCas9 system has significant therapeutic potential in sarcopenia.
ZNF746/PARIS overexpression induces cellular senescence through FoxO1/p21 axis activation in myoblasts
Authors: Bae Ju-Hyeon , Jeong Hyeon-Ju , Kim Hyebeen , Leem Young-Eun , Ryu Dongryeol , Park Sang Chul , Lee Yun-Il , Cho Sung Chun , Kang Jong-Sun
Published: May 2020

Various stresses, including oxidative stress, impair the proliferative capacity of muscle stem cells leading to declined muscle regeneration related to aging or muscle diseases. ZNF746 (PARIS) is originally identified as a substrate of E3 ligase Parkin and its accumulation is associated with Parkinson’s disease. In this study, we investigated the role of PARIS in myoblast function. PARIS is expressed in myoblasts and decreased during differentiation. PARIS overexpression decreased both proliferation and differentiation of myoblasts without inducing cell death, whereas PARIS depletion enhanced myoblast differentiation. Interestingly, high levels of PARIS in myoblasts or fibroblasts induced cellular senescence with alterations in gene expression associated with p53 signaling, inflammation, and response to oxidative stress. PARIS overexpression in myoblasts starkly enhanced oxidative stress and the treatment of an antioxidant Trolox attenuated the impaired proliferation caused by PARIS overexpression. FoxO1 and p53 proteins are elevated in PARIS-overexpressing cells leading to p21 induction and the depletion of FoxO1 or p53 reduced p21 levels induced by PARIS overexpression. Furthermore, both PARIS and FoxO1 were recruited to p21 promoter region and Trolox treatment attenuated FoxO1 recruitment. Taken together, PARIS upregulation causes oxidative stress-related FoxO1 and p53 activation leading to p21 induction and cellular senescence of myoblasts.
Galectin-3 modulates epithelial cell adaptation to stress at the ER-mitochondria interface
Authors: Coppin Lucie , Jannin Arnaud , Ait Yahya Emilie , Thuillier Caroline , Villenet Céline , Tardivel Meryem , Bongiovanni Antonino , Gaston Cécile , de Beco Simon , Barois Nicolas , van Seuningen Isabelle , Durand Emmanuelle , Bonnefond Amélie , Vienne Jean-Claude , Vamecq Joseph , Figeac Martin , Vincent Audrey , Delacour Delphine , Porchet Nicole , Pigny Pascal
Published: May 2020

Cellular stress response contributes to epithelial defense in adaptation to environment changes. Galectins play a pivotal role in the regulation of this response in malignant cells. However, precise underlying mechanisms are largely unknown. Here we demonstrate that Galectin-3, a pro and anti-apoptotic lectin, is required for setting up a correct cellular response to stress by orchestrating several effects. First, Galectin-3 constitutes a key post-transcriptional regulator of stress-related mRNA regulons coordinating the cell metabolism, the mTORC1 complex or the unfolded protein response (UPR). Moreover, we demonstrated the presence of Galectin-3 with mitochondria-associated membranes (MAM), and its interaction with proteins located at the ER or mitochondrial membranes. There Galectin-3 prevents the activation and recruitment at the mitochondria of the regulator of mitochondria fission DRP-1. Accordingly, loss of Galectin-3 impairs mitochondrial morphology, with more fragmented and round mitochondria, and dynamics both in normal and cancer epithelial cells in basal conditions. Importantly, Galectin-3 deficient cells also display changes of the activity of the mitochondrial respiratory chain complexes, of the mTORC1/S6RP/4EBP1 translation pathway and reactive oxygen species levels. Regarding the ER, Galectin-3 did not modify the activities of the 3 branches of the UPR in basal conditions. However, Galectin-3 favours an adaptative UPR following ER stress induction by Thapsigargin treatment. Altogether, at the ER-mitochondria interface, Galectin-3 coordinates the functioning of the ER and mitochondria, preserves the integrity of mitochondrial network and modulates the ER stress response.
Oxidized mitochondrial DNA sensing by STING signaling promotes the antitumor effect of an irradiated immunogenic cancer cell vaccine
Authors: Fang Chunju , Mo Fei , Liu Li , Du Jing , Luo Min , Men Ke , Na Feifei , Wang Wei , Yang Hanshuo , Wei Xiawei
Published: May 2020

Exposure to ionizing radiation, a physical treatment that inactivates live tumor cells, has been extensively applied to enhance the antitumor responses induced by cancer cell vaccines in both animal research and human clinical trials. However, the mechanisms by which irradiated cells function as immunogenic tumor vaccines and induce effective antitumor responses have not been fully explored. Here, we demonstrate that oxidized mitochondrial DNA (mtDNA) and stimulator of interferon genes (STING) signaling play a key roles in the enhanced antitumor effect achieved with an irradiated tumor cell vaccine. Elevations in ROS and oxidized mtDNA 8-OHG content could be induced in irradiated tumor cells. Oxidized mtDNA derived from irradiated tumor cells gained access to the cytosol of dendritic cells (DCs). Oxidized mtDNA, as a DAMP or adjuvant, activated the STING-TBK1-IRF3-IFN-β pathway in DCs, which subsequently cross-presented irradiated tumor cell-derived antigens to CD8+ T cells and elicited antitumor immunity. The results of our study provide insight into the mechanism by which an irradiated cell vaccine mediates antitumor immunity, which may have implications for new strategies to improve the efficacy of irradiated vaccines.
MBNL1 regulates essential alternative RNA splicing patterns in MLL-rearranged leukemia
Authors: Itskovich Svetlana S. , Gurunathan Arun , Clark Jason , Burwinkel Matthew , Wunderlich Mark , Berger Mikaela R. , Kulkarni Aishwarya , Chetal Kashish , Venkatasubramanian Meenakshi , Salomonis Nathan , Kumar Ashish R. , Lee Lynn H.
Published: May 2020

Despite growing awareness of the biologic features underlying MLL-rearranged leukemia, targeted therapies for this leukemia have remained elusive and clinical outcomes remain dismal. MBNL1, a protein involved in alternative splicing, is consistently overexpressed in MLL-rearranged leukemias. We found that MBNL1 loss significantly impairs propagation of murine and human MLL-rearranged leukemia in vitro and in vivo. Through transcriptomic profiling of our experimental systems, we show that in leukemic cells, MBNL1 regulates alternative splicing (predominantly intron exclusion) of several genes including those essential for MLL-rearranged leukemogenesis, such as DOT1L and SETD1A. We finally show that selective leukemic cell death is achievable with a small molecule inhibitor of MBNL1. These findings provide the basis for a new therapeutic target in MLL-rearranged leukemia and act as further validation of a burgeoning paradigm in targeted therapy, namely the disruption of cancer-specific splicing programs through the targeting of selectively essential RNA binding proteins.
PTSD is associated with neuroimmune suppression: evidence from PET imaging and postmortem transcriptomic studies
Authors: Bhatt Shivani , Hillmer Ansel T. , Girgenti Matthew J. , Rusowicz Aleksandra , Kapinos Michael , Nabulsi Nabeel , Huang Yiyun , Matuskey David , Angarita Gustavo A. , Esterlis Irina , Davis Margaret T. , Southwick Steven M. , Friedman Matthew J. ,   Traumatic Stress Brain Study Group, Girgenti Matthew J. , Friedman Matthew J. , Duman Ronald S. , Krystal John H. , Duman Ronald S. , Carson Richard E. , Krystal John H. , Pietrzak Robert H. , Cosgrove Kelly P.
Published: May 2020

Despite well-known peripheral immune activation in posttraumatic stress disorder (PTSD), there are no studies of brain immunologic regulation in individuals with PTSD. [11C]PBR28 Positron Emission Tomography brain imaging of the 18-kDa translocator protein (TSPO), a microglial biomarker, was conducted in 23 individuals with PTSD and 26 healthy individuals—with or without trauma exposure. Prefrontal-limbic TSPO availability in the PTSD group was negatively associated with PTSD symptom severity and was significantly lower than in controls. Higher C-reactive protein levels were also associated with lower prefrontal-limbic TSPO availability and PTSD severity. An independent postmortem study found no differential gene expression in 22 PTSD vs. 22 controls, but showed lower relative expression of TSPO and microglia-associated genes TNFRSF14 and TSPOAP1 in a female PTSD subgroup. These findings suggest that peripheral immune activation in PTSD is associated with deficient brain microglial activation, challenging prevailing hypotheses positing neuroimmune activation as central to stress-related pathophysiology.
Naked mole-rat very-high-molecular-mass hyaluronan exhibits superior cytoprotective properties
Authors: Takasugi Masaki , Firsanov Denis , Tombline Gregory , Ning Hanbing , Ablaeva Julia , Seluanov Andrei , Gorbunova Vera
Published: May 2020

Naked mole-rat (NMR), the longest-living rodent, produces very-high-molecular-mass hyaluronan (vHMM-HA), compared to other mammalian species. However, it is unclear if exceptional polymer length of vHMM-HA is important for longevity. Here, we show that vHMM-HA (>6.1 MDa) has superior cytoprotective properties compared to the shorter HMM-HA. It protects not only NMR cells, but also mouse and human cells from stress-induced cell-cycle arrest and cell death in a polymer length-dependent manner. The cytoprotective effect is dependent on the major HA-receptor, CD44. We find that vHMM-HA suppresses CD44 protein-protein interactions, whereas HMM-HA promotes them. As a result, vHMM-HA and HMM-HA induce opposing effects on the expression of CD44-dependent genes, which are associated with the p53 pathway. Concomitantly, vHMM-HA partially attenuates p53 and protects cells from stress in a p53-dependent manner. Our results implicate vHMM-HA in anti-aging mechanisms and suggest the potential applications of vHMM-HA for enhancing cellular stress resistance.
Epithelial invagination by a vertical telescoping cell movement in mammalian salivary glands and teeth
Authors: Li Jingjing , Economou Andrew D. , Vacca Barbara , Green Jeremy B. A.
Published: May 2020

Epithelial bending is a fundamental process that shapes organs during development. Previously known mechanisms involve cells locally changing shape from columnar to wedge-shaped. Here we report a different mechanism that occurs without cell wedging. In mammalian salivary glands and teeth, we show that initial invagination occurs through coordinated vertical cell movement: cells towards the periphery of the placode move vertically upwards while their more central neighbours move downwards. Movement is achieved by active cell-on-cell migration: outer cells migrate with apical, centripetally polarised leading edge protrusions but remain attached to the basal lamina, depressing more central neighbours to “telescope” the epithelium downwards into underlying mesenchyme. Inhibiting protrusion formation by Arp2/3 protein blocks invagination. FGF and Hedgehog morphogen signals are required, with FGF providing a directional cue. These findings show that epithelial bending can be achieved by a morphogenetic mechanism of coordinated cell rearrangement quite distinct from previously recognised invagination processes.
Acute Stress Reduces the Social Amplification of Risk Perception
Authors: Popovic Nathalie F. , Bentele Ulrike U. , Pruessner Jens C. , Moussaïd Mehdi , Gaissmaier Wolfgang
Published: May 2020

Risk perceptions typically underlie a complex social dynamic: Risk-related information is transmitted between individuals, this information influences risk perceptions, and risk perceptions influence which information is transmitted. This can lead to a social amplification of risk. We test how stress, a widespread affective state, influences the social dynamics of risk perception. Participants (N = 146) read articles about the controversial antibacterial agent Triclosan and were then asked to inform another person about Triclosan. Before and after reading the articles, participants reported their concern about Triclosan. Stress exposure before the task led to a smaller increase in concern in response to the articles. The stronger the increase in cortisol, the smaller the increase in concern. Furthermore, participants in the stress group transmitted less negative information about Triclosan to others. In contrast, participants’ subjective feelings of stress were associated with higher concern and more alarming risk communication. We conclude that feeling stressed can amplify risk perception, whereas the endocrine stress reaction can attenuate risk perception when information about risk is exchanged in a social context.
Equine penile squamous cell carcinoma: expression of biomarker proteins and EcPV2
Authors: Arthurs Callum , Suarez-Bonnet Alejandro , Willis Claire , Xie Boyu , Machulla Natalie , Mair Tim S. , Cao Kevin , Millar Michael , Thrasivoulou Christopher , Priestnall Simon L. , Ahmed Aamir
Published: May 2020

Equine penile squamous cell carcinoma (EpSCC) is a relatively common cutaneous neoplasm with a poor prognosis. In this study, we aimed to determine the protein expression and colocalisation of FRA1, c-Myc, Cyclin D1, and MMP7 in normal (NT), tumour (T), hyperplastic epidermis and/or squamous papilloma (Hyp/Pap), poorly-differentiated (PDSCC), or well-differentiated (WDSCC) EpSCC using a tissue array approach. Further objectives were to correlate protein expression to (i) levels of inflammation, using a convolutional neural network (ii) equine papillomavirus 2 (EcPV2) infection, detected using PCR amplification. We found an increase in expression of FRA1 in EpSCC compared to NT samples. c-Myc expression was higher in Hyp/Pap and WDSCC but not PDSCC whereas MMP7 was reduced in WDSCC compared with NT. There was a significant increase in the global intersection coefficient (GIC) of FRA1 with MMP7, c-Myc, and Cyclin D1 in EpSCC. Conversely, GIC for MMP7 with c-Myc was reduced in EpSCC tissue. Inflammation was positively associated with EcPV2 infection in both NT and EpSCC but not Hyp/Pap. Changes in protein expression could be correlated with EcPV2 for Cyclin D1 and c-Myc. Our results evaluate novel biomarkers of EpSCC and a putative correlation between the expression of biomarkers, EcPV2 infection and inflammation.
Modelling hepatitis D virus RNA and HBsAg dynamics during nucleic acid polymer monotherapy suggest rapid turnover of HBsAg
Authors: Shekhtman Louis , Cotler Scott J. , Hershkovich Leeor , Uprichard Susan L. , Bazinet Michel , Pantea Victor , Cebotarescu Valentin , Cojuhari Lilia , Jimbei Pavlina , Krawczyk Adalbert , Dittmer Ulf , Vaillant Andrew , Dahari Harel
Published: May 2020

Hepatitis D virus (HDV) requires hepatitis B surface antigen (HBsAg) for its assembly and release. Current HBV treatments are only marginally effective against HDV because they fail to inhibit HBsAg production/secretion. However, monotherapy with the nucleic acid polymer REP 2139-Ca is accompanied by rapid declines in both HBsAg and HDV RNA. We used mathematical modeling to estimate HDV-HBsAg-host parameters and to elucidate the mode of action and efficacy of REP 2139-Ca against HDV in 12 treatment-naive HBV/HDV co-infected patients. The model accurately reproduced the observed decline of HBsAg and HDV, which was simultaneous. Median serum HBsAg half-life (t1/2) was estimated as 1.3 [0.9–1.8] days corresponding to a pretreatment production and clearance of ~108 [107.7–108.3] IU/day. The HDV-infected cell loss was estimated to be 0.052 [0.035–0.074] days−1 corresponding to an infected cell t1/2 = 13.3 days. The efficacy of blocking HBsAg and HDV production were 98.2 [94.5–99.9]% and 99.7 [96.0–99.8]%, respectively. In conclusion, both HBsAg production and HDV replication are effectively inhibited by REP 2139-Ca. Modeling HBsAg kinetics during REP 2139-Ca monotherapy indicates a short HBsAg half-life (1.3 days) suggesting a rapid turnover of HBsAg in HBV/HDV co-infection.
Human multi-organ chip co-culture of bronchial lung culture and liver spheroids for substance exposure studies
Authors: Schimek Katharina , Frentzel Stefan , Luettich Karsta , Bovard David , Rütschle Isabel , Boden Laura , Rambo Felix , Erfurth Hendrik , Dehne Eva-Maria , Winter Annika , Marx Uwe , Hoeng Julia
Published: May 2020

Extrapolation of cell culture-based test results to in vivo effects is limited, as cell cultures fail to emulate organ complexity and multi-tissue crosstalk. Biology-inspired microphysiological systems provide preclinical insights into absorption, distribution, metabolism, excretion, and toxicity of substances in vitro by using human three-dimensional organotypic cultures. We co-cultured a human lung equivalent from the commercially available bronchial MucilAir culture and human liver spheroids from HepaRG cells to assess the potential toxicity of inhaled substances under conditions that permit organ crosstalk. We designed a new HUMIMIC Chip with optimized medium supply and oxygenation of the organ cultures and cultivated them on-chip for 14 days in separate culture compartments of a closed circulatory perfusion system, demonstrating the viability and homeostasis of the tissue cultures. A single-dose treatment of the hepatotoxic and carcinogenic aflatoxin B1 impaired functionality in bronchial MucilAir tissues in monoculture but showed a protective effect when the tissues were co-cultured with liver spheroids, indicating that crosstalk can be achieved in this new human lung–liver co-culture. The setup described here may be used to determine the effects of exposure to inhaled substances on a systemic level.
Extracellular Signal-Regulated Kinases Mediate an Autoregulation of GABAB-Receptor-Activated Whole-Cell Current in Locus Coeruleus Neurons
Authors: Wu Rui-Ni , Kuo Chao-Cheng , Min Ming-Yuan , Chen Ruei-Feng , Yang Hsiu-Wen
Published: May 2020

The norepinephrine-releasing neurons in the locus coeruleus (LC) are well known to regulate wakefulness/arousal. They display active firing during wakefulness and a decreased discharge rate during sleep. We have previously reported that LC neurons express large numbers of GABABreceptors (GABABRs) located at peri-/extrasynaptic sites and are subject to tonic inhibition due to the continuous activation of GABABRs by ambient GABA, which is significantly higher during sleep than during wakefulness. In this study, we further showed using western blot analysis that the activation of GABABRs with baclofen could increase the level of phosphorylated extracellular signal-regulated kinase 1 (ERK1) in LC tissue. Recordings from LC neurons in brain slices showed that the inhibition of ERK1/2with U0126 and FR180204 accelerated the decay of whole-cell membrane current induced by prolonged baclofen application. In addition, the inhibition of ERK1/2also increased spontaneous firing and reduced tonic inhibition of LC neurons after prolonged exposure to baclofen. These results suggest a new role of GABABRs in mediating ERK1-dependent autoregulation of the stability of GABABR-activated whole-cell current, in addition to its well-known effect on gated potassium channels, to cause a tonic current in LC neurons.
Photocatalytic dye degradation and antimicrobial activities of Pure and Ag-doped ZnO using Cannabis sativa leaf extract
Authors: Chauhan Ankush , Verma Ritesh , Kumari Swati , Sharma Anand , Shandilya Pooja , Li Xiangkai , Batoo Khalid Mujasam , Imran Ahamad , Kulshrestha Saurabh , Kumar Rajesh
Published: May 2020

A facile green route has been employed for the synthesis of ZnO and Ag-doped ZnO using Cannabis sativa as a reducing and stabilizing agent. The as-synthesized nanoparticles were characterized and tested for photocatalytic dye degradation and antimicrobial activity. The results suggested that nanoparticles have shown antimicrobial activity against different human pathogenic bacteria (Escherichia coli, Klebsiella pneumonia, MRSA, Pseudomonas aeruginosa, Salmonella typhi, Staphylococcus aureus) and fungal strains (Fusarium spp. and Rosellinia necatrix). Ag-doped nanoparticles comparatively have shown better removal Congo red and methyl orange under visible light. Therefore, green synthesized nanoparticles could have beneficial applications in environmental science and biological field.
Universal principles justify the existence of concept cells
Authors: Calvo Tapia Carlos , Tyukin Ivan , Makarov Valeri A.
Published: May 2020

The widespread consensus argues that the emergence of abstract concepts in the human brain, such as a “table”, requires complex, perfectly orchestrated interaction of myriads of neurons. However, this is not what converging experimental evidence suggests. Single neurons, the so-called concept cells (CCs), may be responsible for complex tasks performed by humans. This finding, with deep implications for neuroscience and theory of neural networks, has no solid theoretical grounds so far. Our recent advances in stochastic separability of highdimensional data have provided the basis to validate the existence of CCs. Here, starting from a few first principles, we layout biophysical foundations showing that CCs are not only possible but highly likely in brain structures such as the hippocampus. Three fundamental conditions, fulfilled by the human brain, ensure high cognitive functionality of single cells: a hierarchical feedforward organization of large laminar neuronal strata, a suprathreshold number of synaptic entries to principal neurons in the strata, and a magnitude of synaptic plasticity adequate for each neuronal stratum. We illustrate the approach on a simple example of acquiring “musical memory” and show how the concept of musical notes can emerge.
Endosulfan exposure alters transcription of genes involved in the detoxification and stress responses in Physella acuta
Authors: Alonso-Trujillo María , Muñiz-González Ana-Belén , Martínez-Guitarte José-Luis
Published: May 2020

Endosulfan is a persistent pesticide that has been in use for more than five decades. During this time, it has contaminated soil, air, and water reservoirs worldwide. It is extremely toxic and harmful to beneficial non-target invertebrates, aquatic life, and even humans upon consumption, which is one of the many dangers of this pesticide since it biomagnifies in the food chain. The effects of three endosulfan concentrations (1, 10, and 100 µg/L) on the freshwater snail Physella acuta, an invasive cosmopolitan species, were examined over a week-long exposure period. Alterations in the expression of ten genes related to stress and xenobiotic detoxification were measured against the endogenous controls rpL10 and GAPDH by Real-Time polymerase chain reaction. Four genes are described here for the first time in this species, namely Hsp60, Grp78, GSTk1, and GSTm1. The rest of genes were Hsp90, sHsp16.6, cyp2u1, cyp3a7, cyp4f22, and MRP1. cyp2u1, sHsp16.6, and Grp78 expression were all altered by endosulfan. These results suggest a low pesticide concentration activates the acute response in P. acuta by affecting detoxification and stress responses and alter endoplasmic reticulum function and lipid metabolism. Furthermore, the newly identified genes extend the number of processes and cellular locations that can be analyzed in this organism.
Elevated primary productivity triggered by mixing in the quasi-cul-de-sac Taiwan Strait during the NE monsoon
Authors: Huang Ting-Hsuan , Chen Chen-Tung Arthur , Bai Yan , He Xianqiang
Published: May 2020

The Taiwan Strait (TS) connects two of the largest marginal seas in the world, namely the East China Sea (ECS) and the South China Sea (SCS). When the NE monsoon prevails, the fresh, nutrient-rich but P-limited China Coastal Current (CCC) flows southward. Yet, part of the CCC turns eastward after entering the TS and then turns back toward the ECS. In the southern TS, part of the salty, N-limited, northward TS current (TSC) in the eastern part of the strait turns westward and eventually returns to the SCS. That is, the TS acts like a quasi-cul-de-sac during the NE monsoon season. Based on 822 samples from 28 cruises, the highest Chl. a concentration occurs at a salinity around 32 even though the nutrient concentration is not the highest. Mixing the cold-fresh-eutrophic CCC water and the warm-salty-oligotrophic TSC water results in a more suitable condition for biological uptake in both the southern ECS and the northern SCS.
Seasonal fluctuation of beak and feather disease virus (BFDV) infection in wild Crimson Rosellas (Platycercus elegans)
Authors: Martens Johanne M. , Stokes Helena S. , Berg Mathew L. , Walder Ken , Bennett Andrew T. D.
Published: May 2020

Understanding patterns of pathogen emergence can help identify mechanisms involved in transmission dynamics. Beak and feather disease virus (BFDV) poses a major threat world-wide to wild and captive parrots. Yet data from wild birds on seasonal fluctuations in prevalence and infection intensity, and thereby the potential high-risk times for virus transmission, have been lacking. We screened wild Crimson Rosellas (Platycercus elegans) for BFDV in blood and cloacal swabs. Prevalence in blood samples and cloacal swabs, as well as viral load varied with Julian date and in blood, were highest after the breeding season. Breeding birds had lower viral load and lower BFDV prevalence in blood than non-breeding birds (10.1% prevalence in breeding vs. 43.2% in non-breeding birds). BFDV prevalence was much higher in younger (<3 years) than older (≥3 years) birds for both blood samples (42.9% vs. 4.5%) and cloacal swabs (56.4% vs. 12.3%). BFDV status in blood and cloacal samples was not correlated within individuals. We show that, at least inP. elegans, BFDV infection seems to occur year-round, with seasonal changes in prevalence and load found in our samples. Our analyses suggest that the seasonal changes were associated primarily with the breeding season. We also discuss age and sex as important predictors of BFDV infection.
Association analysis in a Latin American population revealed ethnic differences in rheumatoid arthritis-associated SNPs in Caucasian and Asian populations
Authors: Castro-Santos P. , Verdugo R. A. , Alonso-Arias R. , Gutiérrez M. A. , Suazo J. , Aguillón J. C. , Olloquequi J. , Pinochet C. , Lucia A. , Quiñones L. A. , Díaz-Peña R.
Published: May 2020

Large genome-wide association studies (GWAS) have increased our knowledge of the genetic risk factors of rheumatoid arthritis (RA). However, little is known about genetic susceptibility in populations with a large admixture of Amerindian ancestry. The aim of the present study was to test the generalizability of previously reported RA loci in a Latin American (LA) population with admixed ancestry. We selected 128 single nucleotide polymorphisms (SNPs) in linkage equilibrium, with high association to RA in multiple populations of non-Amerindian origin. Genotyping of 118 SNPs was performed in 313 RA patients/487 healthy control subjects by mid-density arrays of polymerase chain reaction (PCR). Some of the identified associations were validated in an additional cohort (250 cases/290 controls). One marker, the SNP rs2451258, located upstream of T Cell Activation RhoGTPase Activating Protein (TAGAP) gene, showed significant association with RA (p = 5 × 10−3), whereas 18 markers exhibited suggestive associations (p < 0.05). Haplotype testing showed association of some groups of adjacent SNPs around the signal transducer and activator of transcription 4 (STAT4) gene (p = 9.82 × 10−3 to 2.04 × 10−3) with RA. Our major finding was little replication of previously reported genetic associations with RA. These results suggest that performing GWAS and admixture mapping in LA populations has the potential to reveal novel loci associated with RA. This in turn might help to gain insight into the ‘pathogenomics’ of this disease and to explore trans-population differences for RA in general.
Structural investigation of borosilicate glasses containing lanthanide ions
Authors: Fabian M. , Gergely F. , Osan J. , Cendak T. , Kesari S. , Rao R.
Published: May 2020

High level radioactive actinides are produced as a side product in reprocessing spent nuclear fuel, for which safe long-term-inert immobilizer matrices are needed. Borosilicate glasses are of great potential amongst the candidates of suitable inert materials for radioactive waste immobilization. Understanding the effects of actinide addition to a borosilicate glass matrix is of great importance in view of waste immobilization. Here we present structural studies of a simplified glass-matrix, − 55SiO2·10B2O3·25Na2O·5BaO·5ZrO2 - upon adding lanthanide (Ln-)oxides: CeO2, Nd2O3, Eu2O3, in two different concentrations 10% and 30w% each, to investigate the effects of lanthanides (Ln) taken as chemical surrogates for actinides. Neutron diffraction combined with of Reverse Monte Carlo simulations show that all investigated glass structures comprise tetrahedral SiO4, trigonal BO3 and tetrahedral BO4 units, forming mixed [4]Si-O-[3]B and [4]Si-O-[4]B linkages. 11B Magic Angle Spinning Nuclear Magnetic Resonance is indicative of simultaneous presence of trigonal BO3 and tetrahedral BO4 units, with spectral fractions strongly dependent on the Ln addition. Ln-addition promote the BO3 + O-→[BO4]– isomerization resulting in lower fraction of boron in BO3, as compared to BO4 units. Raman spectra, in full agreement with neutron diffraction, confirm that the basic network structure consists of BO3/trigonal and SiO4/BO4 tetrahedral units. Second neighbour atomic pair correlations reveal Ce, Nd, Eu to be accommodated in both Si and B sites, supporting that the borosilicate-matrix well incorporates Ln-ions and is likely to similarly incorporate actinides, opening a way to radioactive nuclear waste immobilization of this group of elements in a borosilicate glass matrix.
Clinical efficacy of Stereotactic Body Radiation Therapy (SBRT) for adrenal gland metastases: A multi-center retrospective study from China
Authors: Zhao Xianzhi , Zhu Xiaofei , Zhuang Hongqing , Guo Xueling , Song Yongchun , Ju Xiaoping , Wang Ping , Yuan Zhiyong , Zhang Huojun
Published: May 2020

To evaluate the efficacy and safety of CyberKnife Stereotactic Body Radiation Therapy (SBRT) in the treatment of adrenal gland metastases (AGM), we designed a large-scale multicenter retrospective study to report the safety and efficacy of SBRT for inoperable AGM. In this study, 75 (61 males, 14 females) patients with 84 AGM and Karnofsky performance score ≥70 were treated by SBRT from October 2006 to January 2017. Of these, the purpose of treatment were controlling all known metastatic sites for 21 patients while 54 for palliation of bulky adrenal metastases. The efficacy and safety of SBRT were evaluated during follow-up. Potential factors predictive of local control (LC) and overall survival (OS) were identified by univariate and multivariate analysis. Median follow-up time was 12.7 months (range 1.8–96.4). The complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) rates were 23.8%, 23.8%, 31.0% and 21.4%, respectively. The 0.5, 1, and 2-year LC rates were 93.6%, 83.8%, and 62.1%, respectively; OS rates on the same follow-up intervals were 93.7%, 62.5%, and 49.6%, respectively, and the corresponding PFS rates were 48.5%, 33.9%, and 16.0%, respectively. The treatment was well tolerated with 2 patients reporting grade-3 diarrhea and fatigue, respectively. Multivariate analysis showed that simultaneous treatment of SBRT for other metastatic lesions, the number of AGM, initiation of systemic therapy, and the maximum diameter of AGM were predictive of LC rates. Moreover, patients with AGM < 5 cm had a superior OS compared with those with AGM ≥ 5 cm (28.0 months vs. 17.6 months, P = 0.032). SBRT is an effective therapeutic option for treatment of AGM with high LC rates with minimal toxicity.
Stokes flow around an obstacle in viscous two-dimensional electron liquid
Authors: Gusev G. M. , Jaroshevich A. S. , Levin A. D. , Kvon Z. D. , Bakarov A. K.
Published: May 2020

The electronic analog of the Poiseuille flow is the transport in a narrow channel with disordered edges that scatter electrons in a diffuse way. In the hydrodynamic regime, the resistivity decreases with temperature, referred to as the Gurzhi effect, distinct from conventional Ohmic behaviour. We studied experimentally an electronic analog of the Stokes flow around a disc immersed in a two-dimensional viscous liquid. The circle obstacle results in an additive contribution to resistivity. If specular boundary conditions apply, it is no longer possible to detect Poiseuille type flow and the Gurzhi effect. However, in flow through a channel with a circular obstacle, the resistivity decreases with temperature. By tuning the temperature, we observed the transport signatures of the ballistic and hydrodynamic regimes on the length scale of disc size. Our experimental results confirm theoretical predictions.
Co-delivery of Doxorubicin and Curcumin with Polypeptide Nanocarrier for Synergistic Lymphoma Therapy
Authors: Guo Wei , Song Yuanyuan , Song Wantong , Liu Yingmin , Liu Zhihe , Zhang Dawei , Tang Zhaohui , Bai Ou
Published: May 2020

The traditional chemotherapy, including Adriamycin (Doxorubicin, DOX), is widely used and is part of the first-line chemotherapy of invasive B cell lymphoma. DOX is nonselective cytotoxic drug and has many adverse effects, which limit its clinical application in combination with other anti-cancer drugs. Optimization of the delivery system targeting tumor microenvironment could be a feasible approach that may have significant clinical significance. Further, combination of DOX with other anticancer drugs, such as curcumin, can enhance the synergistic effects, possibly through epigenetic mechanisms. Hence, we evaluated the efficacy and toxicity of novel nanoparticles that enable the co-delivery of DOX and curcumin in the treatment of invasive B cell lymphoma both in vivo and vitro. The polymer nano materials [mPEG-b-P(Glu-co-Phe)] was used to co-load DOX and curcumin (CUR): L-DOX + CUR. DOX signal was measured to determine the ability of the drugs entering the cells by flow cytometry, and the different enrichment areas in the cells were directly observed by confocal microscope. The toxicity of LDOX + CUR was tested by CCK-8 assay in different cells, and the synergistic coefficients were calculated. The cell apoptosis and the possible mechanisms of apoptosis pathways regulation by L-DOX + CUR were examined using flow cytometry and Western Blot. The MTD (maximum tolerable dose) test was performed in mice. Tumor-bearing SCID mice (i.e., BJAB cell) were used to evaluate the in vivo efficacy of L-DOX + CUR. L-DOX + CUR, was prepared successfully, and the mole ratio of DOX and CUR fixed in 1.0:1.2. (DOX loading rate 9.7%, CUR loading rate 8.1%). L-DOX + CUR exhibited increased intracellular delivery and the main enrichment area of DOX was nucleus. L-DOX + CUR increased cytotoxicity, induced higher rates of apoptosis, and had synergistic effect, especially in BJAB cells (min CI 0.019). It even had epigenetic effect and affected miRNA levels favorably by down-regulating miR-21, miR-199a and up-regulating miR-98 and miR-200c. Additionally, L-DOX + CUR increased MTD in Kunming mice (i.e., 25 mg/kg), compared to DOX (10 mg/kg) and L-DOX (20 mg/kg). In BJAB cell bearing SCID mice, L-DOX + CUR treatment suppressed tumor growth compared to DOX or L-DOX alone, and exhibited less weight loss in mice. We developed new polymer nanoparticles-mPEG-b-P (Glu-co-Phe) co-loaded with DOX and DUR. L-DOX + CUR exhibited synergistic cytotoxic and apoptotic effects on invasive B cell lymphoma. Treatment of L-DOX + CUR potentiated tumor killing in xenografts and reduced toxicity in vivo.
Author Correction: Finding Plastic Patches in Coastal Waters using Optical Satellite Data
Authors: Biermann Lauren , Clewley Daniel , Martinez-Vicente Victor , Topouzelis Konstantinos
Published: May 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Direct evidence of Neanderthal fibre technology and its cognitive and behavioral implications
Authors: Hardy B. L. , Moncel M.-H. , Kerfant C. , Lebon M. , Bellot-Gurlet L. , Mélard N.
Published: May 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
A reaction-triggered luminescent Ce4+/Tb3+ MOF probe for the detection of SO2 and its derivatives
Authors: Wang Li , Chen Yang
Published: May 2020

A novel reaction-responsive Ce4+/Tb3+ luminescent probe was designed and synthesized for sensing gaseous sulfur dioxide and its derivatives in human serum.
Mussel-inspired hydrogels: from design principles to promising applications
Authors: Zhang Chao , Wu Baiheng , Zhou Yongsen , Zhou Feng , Liu Weimin , Wang Zuankai
Published: May 2020

This review presents the recent progress of mussel-inspired hydrogels from fundamental interaction mechanisms and design principles to promising applications.
Assembly of miscible supramolecular network blends using DDA·AAD hydrogen-bonding interactions of pendent side-chains
Authors: Coubrough Heather M. , Reynolds Matthew , Goodchild James A. , Connell Simon D. A. , Mattsson Johan , Wilson Andrew J.
Published: May 2020

Miscible blends of poly(methyl methacrylate) and polystyrene polymers are assembled through triple hydrogen bonding between complementary ureidoimidazole and amidoisocytosine heterodimers.
Sensitive mass spectrometric analysis of carbonyl metabolites in human urine and fecal samples using chemoselective modification
Authors: Lin Weifeng , Conway Louis P. , Block Annika , Sommi Greta , Vujasinovic Miroslav , Löhr J.-Matthias , Globisch Daniel
Published: May 2020

51 carbonyl-containing metabolites were validated in human urine and feces samples using an advanced chemoselective metabolite-capturing method for mass spectrometric analysis.
Fast, direct and in situ monitoring of lipid oxidation in an oil-in-water emulsion by near infrared spectroscopy
Authors: Daoud Samar , Waschatko Gustav , Bou-Maroun Elias , Cayot Philippe
Published: May 2020

Near infrared spectroscopy for a fast, online and accurate analysis of early stages of lipid oxidation in emulsions type products.
A new chemiluminescence method for the determination of 8-hydroxyguanine based on l-histidine bound nickel nanoparticles
Authors: Yan Xi-Luan , Jiang Meng-Meng , Hu Ying , Wu Le , Zhao Kun , Xue Xin-Xin , Zheng Xiang-Juan
Published: May 2020

A new chemiluminescence aptasensor is constructed based on the synergistic interaction of Ni NPs@l-histidine@aptamer@MBs, which shows great potential for sensitive and efficient assay of 8-hydroxyguanine in the real urine samples of cancer patients.
Synergistically enhanced hydrogen evolution reaction by ruthenium nanoparticles dispersed on N-doped carbon hollow nanospheres
Authors: Li Ji-Sen , Huang Meng-Jie , Chen Xiao-Nan , Kong Ling-Xin , Zhou Yu-Wei , Wang Ming-Yu , Li Jun-Lei , Wu Ze-Xing , Xu Xiu-Feng
Published: May 2020

Ultrafine Ru nanoparticles dispersed on 3D N-doped carbon hollow nanospheres were firstly prepared by a feasible templating strategy.
Incorporating luminescence-concentrating upconversion nanoparticles and DNA walkers into optical tweezers assisted imaging: a highly stable and ultrasensitive bead supported assay
Authors: Li Cheng-Yu , Zhang Ting , Kang Ya-Feng , Qi Chu-Bo , Zheng Bei , Xu Chun-Miao , Lin Yi , Pang Dai-Wen , Tang Hong-Wu
Published: May 2020

Luminescence-concentrating upconversion nanoparticles, optical tweezers, and DNA walkers are incorporated to establish a new single bead supported imaging assay.
NO release regulated by doxorubicin as the green light-harvesting antenna
Authors: Fraix Aurore , Parisi Cristina , Failla Mariacristina , Chegaev Konstantin , Spyrakis Francesca , Lazzarato Loretta , Fruttero Roberta , Gasco Alberto , Sortino Salvatore
Published: May 2020

A novel NO photodonor operates through excitation with highly biocompatible green light of the widely used chemotherapeutic agent doxorubicin as the light-harvesting antenna without precluding its typical red emission and DNA binding properties.
Synthesis and electrical properties of single crystalline black phosphorus nanoribbons
Authors: Yu Ying , Yao Jiadong , Niu Xinyue , Xing Boran , Liu Yali , Wu Xiaoxiang , Li Mengge , Yan Xiaoyuan , Sha Jian , Wang Yewu
Published: May 2020

Single crystal black phosphorus nanoribbons along the zigzag direction have been successfully grown by chemical vapor transport.
Halogenide anions as halogen and hydrogen bond acceptors in iodopyridinium halogenides
Authors: Fotović Luka , Stilinović Vladimir
Published: May 2020

Structures of iodopyridinium halogenides have demonstrated why iodide, the weakest halogen bond acceptor among the halogenides, preferentially forms halogen bonds.
In situ selective ligand transformation from Si–H to Si–OH for synergistic assembly of hydrogen-bonded metal–organic frameworks
Authors: Yuan Baoling , Tang Yuan , Gou Gaozhang , Dan Wenyan , Li Liangchun
Published: May 2020

Two isoreticular silicon-based hydrogen-bonded metal–organic frameworks (HMOFs) have been synthesized by in situ selective transformation of the ligand from hydrosilane to silanol.
Selenium substitution effects on excited-state properties and photophysics of uracil: a MS-CASPT2 study
Authors: Peng Qin , Zhu Yun-Hua , Zhang Teng-Shuo , Liu Xiang-Yang , Fang Wei-Hai , Cui Ganglong
Published: May 2020

We have employed the MS-CASPT2 approach to explore selenium substitution effects on the excited state properties and photophysics of uracil.
More complex, less complicated? Explicit solvation of hydroxyl groups for the analysis of VCD spectra
Authors: Weirich Luisa , Blanke Katharina , Merten Christian
Published: May 2020

With increasing size of the molecules, hydrogen bonding induced solvent effects on the IR and VCD spectra become more negligible.
FB-REDA: fragment-based decomposition analysis of the reorganization energy for organic semiconductors
Authors: Lin Kun-Han , Corminboeuf Clémence
Published: May 2020

We present a fragment-based decomposition analysis tool (FB-REDA) for the reorganisation energy (λ) in the framework of fragment-mode analysis. FB-REDA provides useful insight into rational design low-λ organic semiconductors.
The first molecular characterisation of blue- and red-light photoreceptors from Methylobacterium radiotolerans
Authors: Consiglieri Eleonora , Xu Qian-zhao , Zhao Kai-Hong , Gärtner Wolfgang , Losi Aba
Published: May 2020

Pink-pigmented facultative methylotrophs from the phyllosphere are extremely rich in photosensors and are here proven to be photochemically functional.
Linking genomics and metabolomics to chart specialized metabolic diversity
Authors: van der Hooft Justin J. J. , Mohimani Hosein , Bauermeister Anelize , Dorrestein Pieter C. , Duncan Katherine R. , Medema Marnix H.
Published: May 2020

Microbial and plant specialized metabolites play key roles in mediating ecological interactions between organisms. Analysis and integration of genomics and metabolomics data facilitates charting their immense chemical diversity.
Macroporous polymer resin with conjugated side-chains: an efficient Ag nanoparticle support for preparing a photocatalyst
Authors: Wang Lin , Chen Xuejiao , Duan Yandong , Luo Qingzhi , Wang Desong
Published: May 2020

Ag NPs loaded on macroporous resin with conjugated side-chains can absorb broad wavelength light, transfer electrons to Ag and immobilize “Ag” by amino groups, all of which facilitate the photocatalytic activity and stability for 4-NP reduction.
Phosphine vapor-assisted construction of heterostructured Ni2P/NiTe2 catalysts for efficient hydrogen evolution
Authors: Li Yibing , Tan Xin , Tan Hao , Ren Hangjuan , Chen Sheng , Yang Wanfeng , Smith Sean C. , Zhao Chuan
Published: May 2020

A PH3 vapor-assisted phase and structure engineering strategy to convert non-active NiTe into super-active Ni2P/NiTe2 catalysts for hydrogen evolution reaction.
Biophotonics of diversely coloured peacock tail feathers
Authors: Freyer Pascal , Stavenga Doekele G.
Published: May 2020

The diversity of peacock tail feather colours is explained by multilayer modelling.
Agriculture waste valorisation as a source of antioxidant phenolic compounds within a circular and sustainable bioeconomy
Authors: Jimenez-Lopez C. , Fraga-Corral M. , Carpena M. , García-Oliveira P. , Echave J. , Pereira A. G. , Lourenço-Lopes C. , Prieto M. A. , Simal-Gandara J.
Published: May 2020

Agro-food industrial waste is currently being accumulated, pushing scientists to find recovery strategies to obtain bioactive compounds within a circular bioeconomy. Target phenolic compounds have shown market potential by means of optimization extraction techniques.
A method for determining the uniquely high molecular weight of chitin extracted from raw shrimp shells using ionic iquids
Authors: Wineinger Hannah B. , Shamshina Julia L. , Kelly Adrian , King Catherine , Rogers Robin D.
Published: May 2020

Because the very high molecular weight of biopolymers extracted from biomass using ionic liquids (ILs) cannot be accurately determined using conventional methodologies, we have developed a new method forMwdetermination based on static light scattering (SLS) in IL solution.
Mechanochemical insertion of cobalt into porphyrinoids using Co2(CO)8 as a cobalt source
Authors: Damunupola Dinusha , Chaudhri Nivedita , Atoyebi Adewole O. , Brückner Christian
Published: May 2020

The scopes and limits of a solvent-free mechanochemical method to prepare a range of cobalt porphyrinoids is described.