bluuebunny/crossref_metadata_2025 huggingface dataset:
Autophagy-induced RelB/p52 activation mediates tumour-associated macrophage repolarisation and suppression of hepatocellular carcinoma by natural compound baicalin
Authors: Tan H-Y , Wang N , Man K , Tsao S-W , Che C-M , Feng Y
Published: October 2015

The plasticity of tumour-associated macrophages (TAMs) has implicated an influential role in hepatocellular carcinoma (HCC). Repolarisation of TAM towards M1 phenotype characterises an immune-competent microenvironment that favours tumour regression. To investigate the role and mechanism of TAM repolarisation in suppression of HCC by a natural compound baicalin, Orthotopic HCC implantation model was used to investigate the effect of baicalin on HCC; liposome-clodronate was introduced to suppress macrophage populations in mice; bone marrow-derived monocytes (BMDMs) were induced to unpolarised, M1-like, M2-like macrophages and TAM using different conditioned medium. We observed that oral administration of baicalin (50 mg/kg) completely blocked orthotopic growth of implanted HCC. Suppression of HCC by baicalin was diminished when mice macrophage was removed by clodronate treatment. Baicalin induced repolarisation of TAM to M1-like phenotype without specific toxicity to either phenotype of macrophages. Baicalin initiated TAM reprogramming to M1-like macrophage, and promoted pro-inflammatory cytokines production. Co-culturing of HCC cells with baicalin-treated TAMs resulted in reduced proliferation and motility in HCC. Baicalin had minimal effect on derivation of macrophage polarisation factors by HCC cells, while directly induced repolarisation of TAM and M2-like macrophage. This effect was associated with elevated autophagy, and transcriptional activation of RelB/p52 pathway. Suppression of autophagy or RelB abolished skewing of baicalin-treated TAM. Autophagic degradation of TRAF2 in baicalin-treated TAM might be responsible for RelB/p52 activation. Our findings unveil the essential role of TAM repolarisation in suppressive effect of baicalin on HCC, which requires autophagy-associated activation of RelB/p52.
Implication of different domains of the Leishmania major metacaspase in cell death and autophagy
Authors: Casanova M , Gonzalez I J , Sprissler C , Zalila H , Dacher M , Basmaciyan L , Späth G F , Azas N , Fasel N
Published: October 2015

Metacaspases (MCAs) are cysteine peptidases expressed in plants, fungi and protozoa, with a caspase-like histidine–cysteine catalytic dyad, but differing from caspases, for example, in their substrate specificity. The role of MCAs is subject to debate: roles in cell cycle control, in cell death or even in cell survival have been suggested. In this study, using a Leishmania major MCA-deficient strain, we showed that L. major MCA (LmjMCA) not only had a role similar to caspases in cell death but also in autophagy and this through different domains. Upon cell death induction by miltefosine or H2O2, LmjMCA is processed, releasing the catalytic domain, which activated substrates via its catalytic dyad His/Cys and a proline-rich C-terminal domain. The C-terminal domain interacted with proteins, notably proteins involved in stress regulation, such as the MAP kinase LmaMPK7 or programmed cell death like the calpain-like cysteine peptidase. We also showed a new role of LmjMCA in autophagy, acting on or upstream of ATG8, involving Lmjmca gene overexpression and interaction of the C-terminal domain of LmjMCA with itself and other proteins. These results allowed us to propose two models, showing the role of LmjMCA in the cell death and also in the autophagy pathway, implicating different protein domains.
Proteasomal inhibition sensitizes cervical cancer cells to mitomycin C-induced bystander effect: the role of tumor microenvironment
Authors: Singh S V , Ajay A K , Mohammad N , Malvi P , Chaube B , Meena A S , Bhat M K
Published: October 2015

Inaccessibility of drugs to poorly vascularized strata of tumor is one of the limiting factors in cancer therapy. With the advent of bystander effect (BE), it is possible to perpetuate the cellular damage from drug-exposed cells to the unexposed ones. However, the role of infiltrating tumor-associated macrophages (TAMs), an integral part of the tumor microenvironment, in further intensifying BE remains obscure. In the present study, we evaluated the effect of mitomycin C (MMC), a chemotherapeutic drug, to induce BE in cervical carcinoma. By using cervical cancer cells and differentiated macrophages, we demonstrate that MMC induces the expression of FasL via upregulation of PPARγ in both cell types (effector cells) in vitro, but it failed to induce bystander killing in cervical cancer cells. This effect was primarily owing to the proteasomal degradation of death receptors in the cervical cancer cells. Pre-treatment of cervical cancer cells with MG132, a proteasomal inhibitor, facilitates MMC-mediated bystander killing in co-culture and condition medium transfer experiments. In NOD/SCID mice bearing xenografted HeLa tumors administered with the combination of MMC and MG132, tumor progression was significantly reduced in comparison with those treated with either agent alone. FasL expression was increased in TAMs, and the enhanced level of Fas was observed in these tumor sections, thereby causing increased apoptosis. These findings suggest that restoration of death receptor-mediated apoptotic pathway in tumor cells with concomitant activation of TAMs could effectively restrict tumor growth.
Development of a neuroprotective peptide that preserves survival pathways by preventing Kidins220/ARMS calpain processing induced by excitotoxicity
Authors: Gamir-Morralla A , López-Menéndez C , Ayuso-Dolado S , Tejeda G S , Montaner J , Rosell A , Iglesias T , Díaz-Guerra M
Published: October 2015

Kinase D-interacting substrate of 220 kDa (Kidins220), also known as ankyrin repeat-rich membrane spanning (ARMS), has a central role in the coordination of receptor crosstalk and the integration of signaling pathways essential for neuronal differentiation, survival and function. This protein is a shared downstream effector for neurotrophin- and ephrin-receptors signaling that also interacts with the N-methyl-d-aspartate type of glutamate receptors (NMDARs). Failures in neurotrophic support and glutamate signaling are involved in pathologies related to excitotoxicity and/or neurodegeneration, where different components of these dynamic protein complexes result altered by a combination of mechanisms. In the case of Kidins220/ARMS, overactivation of NMDARs in excitotoxicity and cerebral ischemia triggers its downregulation, which contributes to neuronal death. This key role in neuronal life/death decisions encouraged us to investigate Kidins220/ARMS as a novel therapeutic target for neuroprotection. As the main mechanism of Kidins220/ARMS downregulation in excitotoxicity is proteolysis by calpain, we decided to develop cell-penetrating peptides (CPPs) that could result in neuroprotection by interference of this processing. To this aim, we first analyzed in detail Kidins220/ARMS cleavage produced in vitro and in vivo, identifying a major calpain processing site in its C-terminal region (between amino acids 1669 and 1670) within a sequence motif highly conserved in vertebrates. Then, we designed a 25-amino acids CPP (Tat-K) containing a short Kidins220/ARMS sequence enclosing the identified calpain site (amino acids 1668–1681) fused to the HIV-1 Tat protein basic domain, able to confer membrane permeability to attached cargoes. Transduction of cortical neurons with Tat-K reduced Kidins220/ARMS calpain processing in a dose- and time-dependent manner upon excitotoxic damage and allowed preservation of the activity of pERK1/2 and pCREB, signaling molecules central to neuronal survival and functioning. Importantly, these effects were associated to a significant increase in neuronal viability. This Kidins220/ARMS-derived peptide merits further research to develop novel neuroprotective therapies for excitotoxicity-associated pathologies.
Cell populations can use aneuploidy to survive telomerase insufficiency
Authors: Millet Caroline , Ausiannikava Darya , Le Bihan Thierry , Granneman Sander , Makovets Svetlana
Published: October 2015

Telomerase maintains ends of eukaryotic chromosomes, telomeres. Telomerase loss results in replicative senescence and a switch to recombination-dependent telomere maintenance. Telomerase insufficiency in humans leads to telomere syndromes associated with premature ageing and cancer predisposition. Here we use yeast to show that the survival of telomerase insufficiency differs from the survival of telomerase loss and occurs through aneuploidy. In yeast grown at elevated temperatures, telomerase activity becomes limiting: haploid cell populations senesce and generate aneuploid survivors—near diploids monosomic for chromosome VIII. This aneuploidy results in increased levels of the telomerase components TLC1, Est1 and Est3, and is accompanied by decreased abundance of ribosomal proteins. We propose that aneuploidy suppresses telomerase insufficiency through redistribution of cellular resources away from ribosome synthesis towards production of telomerase components and other non-ribosomal proteins. The aneuploidy-induced re-balance of the proteome via modulation of ribosome biogenesis may be a general adaptive response to overcome functional insufficiencies.
ChEC-seq kinetics discriminates transcription factor binding sites by DNA sequence and shape in vivo
Authors: Zentner Gabriel E. , Kasinathan Sivakanthan , Xin Beibei , Rohs Remo , Henikoff Steven
Published: October 2015

Chromatin endogenous cleavage (ChEC) uses fusion of a protein of interest to micrococcal nuclease (MNase) to target calcium-dependent cleavage to specific genomic loci in vivo. Here we report the combination of ChEC with high-throughput sequencing (ChEC-seq) to map budding yeast transcription factor (TF) binding. Temporal analysis of ChEC-seq data reveals two classes of sites for TFs, one displaying rapid cleavage at sites with robust consensus motifs and the second showing slow cleavage at largely unique sites with low-scoring motifs. Sites with high-scoring motifs also display asymmetric cleavage, indicating that ChEC-seq provides information on the directionality of TF-DNA interactions. Strikingly, similar DNA shape patterns are observed regardless of motif strength, indicating that the kinetics of ChEC-seq discriminates DNA recognition through sequence and/or shape. We propose that time-resolved ChEC-seq detects both high-affinity interactions of TFs with consensus motifs and sites preferentially sampled by TFs during diffusion and sliding.
Influence of H7N9 virus infection and associated treatment on human gut microbiota
Authors: Qin Nan , Zheng Beiwen , Yao Jian , Guo Lihua , Zuo Jian , Wu Lingjiao , Zhou Jiawei , Liu Lin , Guo Jing , Ni Shujun , Li Ang , Zhu Yixin , Liang Weifeng , Xiao Yonghong , Ehrlich S. Dusko , Li Lanjuan
Published: October 2015

Between March and June, 2013, forty H7N9 patients were hospitalized in our hospital. Next-generation sequencing technologies have been used to sequence the fecal DNA samples of the patient, the within sample diversity analysis, enterotyping, functional gene and metagenomic species analysis have been carried on both the patients and healthy controls. The influence of associated treatment in H7N9 infected patients is dramatic and was firstly revealed in species level due to deep sequencing technology. We found that most of the MetaGenomic Species (MGS) enriched in the control samples were Roseburia inulinivorans DSM 16841, butyrate producing bacterium SS3/4 and most of MGS enriched in the H7N9 patients were Clostridium sp. 7 2 43FAA and Enterococcus faecium. It was concluded that H7N9 viral infection and antibiotic administration have a significant effect on the microbiota community with decreased diversity and overgrowth of the bacteria such as Escherichia coli and Enterococcus faecium. Enterotype analysis showed that the communities were unstable. Treatment including antivirals, probiotics and antibiotics helps to improve the microbiota diversity and the abundance of beneficial bacteria in the gut.
Sickle cell detection using a smartphone
Authors: Knowlton S. M. , Sencan I. , Aytar Y. , Khoory J. , Heeney M. M. , Ghiran I. C. , Tasoglu S.
Published: October 2015

Sickle cell disease affects 25% of people living in Central and West Africa and, if left undiagnosed, can cause life threatening “silent” strokes and lifelong damage. However, ubiquitous testing procedures have yet to be implemented in these areas, necessitating a simple, rapid and accurate testing platform to diagnose sickle cell disease. Here, we present a label-free, sensitive and specific testing platform using only a small blood sample (<1 μl) based on the higher density of sickle red blood cells under deoxygenated conditions. Testing is performed with a lightweight and compact 3D-printed attachment installed on a commercial smartphone. This attachment includes an LED to illuminate the sample, an optical lens to magnify the image and two permanent magnets for magnetic levitation of red blood cells. The sample is suspended in a paramagnetic medium with sodium metabisulfite and loaded in a microcapillary tube that is inserted between the magnets. Red blood cells are levitated in the magnetic field based on equilibrium between the magnetic and buoyancy forces acting on the cells. Using this approach, we were able to distinguish between the levitation patterns of sickle versus control red blood cells based on their degree of confinement.
Spectrometry of the Earth using Neutrino Oscillations
Authors: Rott C. , Taketa A. , Bose D.
Published: October 2015

The unknown constituents of the interior of our home planet have provoked the human imagination and driven scientific exploration. We herein demonstrate that large neutrino detectors could be used in the near future to significantly improve our understanding of the Earth’s inner chemical composition. Neutrinos, which are naturally produced in the atmosphere, traverse the Earth and undergo oscillations that depend on the Earth’s electron density. The Earth’s chemical composition can be determined by combining observations from large neutrino detectors with seismic measurements of the Earth’s matter density. We present a method that will allow us to perform a measurement that can distinguish between composition models of the outer core. We show that the next-generation large-volume neutrino detectors can provide sufficient sensitivity to reject extreme cases of outer core composition. In the future, dedicated instruments could be capable of distinguishing between specific Earth composition models and thereby reshape our understanding of the inner Earth in previously unimagined ways.
Lysine-specific demethylase 1 mediates epidermal growth factor signaling to promote cell migration in ovarian cancer cells
Authors: Shao Genbao , Wang Jie , Li Yuanxia , Liu Xiuwen , Xie Xiaodong , Wan Xiaolei , Yan Meina , Jin Jie , Lin Qiong , Zhu Haitao , Zhang Liuping , Gong Aihua , Shao Qixiang , Wu Chaoyang
Published: October 2015

Epigenetic abnormalities play a vital role in the progression of ovarian cancer. Lysine-specific demethylase 1 (LSD1/KDM1A) acts as an epigenetic regulator and is overexpressed in ovarian tumors. However, the upstream regulator of LSD1 expression in this cancer remains elusive. Here, we show that epidermal growth factor (EGF) signaling upregulates LSD1 protein levels in SKOV3 and HO8910 ovarian cancer cells overexpressing both LSD1 and the EGF receptor. This effect is correlated with a decrease in the dimethylation of H3K4, a major substrate of LSD1, in an LSD1-dependent manner. We also show that inhibition of PI3K/AKT, but not MEK, abolishes the EGF-induced upregulation of LSD1 and cell migration, indicating that the PI3K/PDK1/AKT pathway mediates the EGF-induced expression of LSD1 and cell migration. Significantly, LSD1 knockdown or inhibition of LSD1 activity impairs both intrinsic and EGF-induced cell migration in SKOV3 and HO8910 cells. These results highlight a novel mechanism regulating LSD1 expression and identify LSD1 as a promising therapeutic target for treating metastatic ovarian cancer driven by EGF signaling.
Filament Geometry Induced Bipolar, Complementary and Unipolar Resistive Switching under the Same Set Current Compliance in Pt/SiOx/TiN
Authors: Lim Dong-Hyeok , Kim Ga-Yeon , Song Jin-Ho , Jeong Kwang-Sik , Ko Dae-Hong , Cho Mann-Ho
Published: October 2015

The decidedly unusual co-occurrence of bipolar, complementary and unipolar resistive switching (BRS, CRS and URS, respectively) behavior under the same high set current compliance (set-CC) is discussed on the basis of filament geometry in a Pt/SiOx/TiN stack. Set-CC-dependent scaling behavior with relations Ireset ~ R0–αand Vreset ~ R0–βdifferentiates BRS under low set-CC from other switching behaviors under high set-CC due to a low α and β involving a narrow filamentary path. Because such co-occurrence is observed only in the case of a high α and β involving a wide filamentary path, such a path can be classified into three different geometries according to switching behavior in detail. From the cyclic switching and a model simulation, we conclude that the reset of BRS originates from a narrower filamentary path near the top electrode than that of CRS due to the randomness of field-driven migration even under the same set-CC. Also, we conclude that URS originates from much narrower inversed conical filamentary path. Therefore, filament-geometry-dependent electric field and/or thermal effects can precisely describe the entire switching behaviors in this experiment.
Archived DNA reveals fisheries and climate induced collapse of a major fishery
Authors: Bonanomi Sara , Pellissier Loïc , Therkildsen Nina Overgaard , Hedeholm Rasmus Berg , Retzel Anja , Meldrup Dorte , Olsen Steffen Malskær , Nielsen Anders , Pampoulie Christophe , Hemmer-Hansen Jakob , Wisz Mary Susanne , Grønkjær Peter , Nielsen Einar Eg
Published: October 2015

Fishing and climate change impact the demography of marine fishes, but it is generally ignored that many species are made up of genetically distinct locally adapted populations that may show idiosyncratic responses to environmental and anthropogenic pressures. Here, we track 80 years of Atlantic cod (Gadus morhua) population dynamics in West Greenland using DNA from archived otoliths in combination with fish population and niche based modeling. We document how the interacting effects of climate change and high fishing pressure lead to dramatic spatiotemporal changes in the proportions and abundance of different genetic populations and eventually drove the cod fishery to a collapse in the early 1970s. Our results highlight the relevance of fisheries management at the level of genetic populations under future scenarios of climate change.
Racah materials: role of atomic multiplets in intermediate valence systems
Authors: Shick A. B. , Havela L. , Lichtenstein A. I. , Katsnelson M. I.
Published: October 2015

We address the long-standing mystery of the nonmagnetic insulating state of the intermediate valence compound SmB6. Within a combination of the local density approximation (LDA) and an exact diagonalization (ED) of an effective discrete Anderson impurity model, the intermediate valence ground state with the f-shell occupation 〈n4f〉 = 5.6 is found for the Sm atom in SmB6. This ground state is a singlet and the first excited triplet state ~3 meV higher in the energy. SmB6 is a narrow band insulator already in LDA, with the direct band gap of ~10 meV. The electron correlations increase the band gap which now becomes indirect. Thus, the many-body effects are relevant to form the indirect band gap, crucial for the idea of “topological Kondo insulator" in SmB6. Also, an actinide analog PuB6 is considered and the intermediate valence singlet ground state is found for the Pu atom. We propose that [Sm, Pu]B6 belong to a new class of the intermediate valence materials with the multi-orbital “Kondo-like" singlet ground-state. Crucial role of complex spin-orbital f  n–f  n+1 multiplet structure differently hybridized with ligand states in such Racah materials is discussed.
Phase Diagram and High-Temperature Superconductivity of Compressed Selenium Hydrides
Authors: Zhang Shoutao , Wang Yanchao , Zhang Jurong , Liu Hanyu , Zhong Xin , Song Hai-Feng , Yang Guochun , Zhang Lijun , Ma Yanming
Published: October 2015

Recent discovery of high-temperature superconductivity (Tc = 190 K) in sulfur hydrides at megabar pressures breaks the traditional belief on the Tc limit of 40 K for conventional superconductors and opens up the doors in searching new high-temperature superconductors in compounds made up of light elements. Selenium is a sister and isoelectronic element of sulfur, with a larger atomic core and a weaker electronegativity. Whether selenium hydrides share similar high-temperature superconductivity remains elusive, but it is a subject of considerable interest. First-principles swarm structure predictions are performed in an effort to seek for energetically stable and metallic selenium hydrides at high pressures. We find the phase diagram of selenium hydrides is rather different from its sulfur analogy, which is indicated by the emergence of new phases and the change of relative stabilities. Three stable and metallic species with stoichiometries of HSe2, HSe and H3Se are identified above ~120 GPa and they all exhibit superconductive behaviors, of which the hydrogen-rich HSe and H3Se phases show high Tc in the range of 40–110 K. Our simulations established the high-temperature superconductive nature of selenium hydrides and provided useful route for experimental verification.
Diameter Dependence of Lattice Thermal Conductivity of Single-Walled Carbon Nanotubes: Study from Ab Initio
Authors: Yue Sheng-Ying , Ouyang Tao , Hu Ming
Published: October 2015

The effects of temperature, tube length, defects and surface functionalization on the thermal conductivity (κ) of single-walled carbon nanotubes (SWCNTs) were well documented in literature. However, diameter dependence of thermal conductivity of SWCNTs received less attentions. So far, diverse trends of the diameter dependence have been discussed by different methods and all the previous results were based on empirical interatomic potentials. In this paper, we emphasize to clarify accurate κ values of SWCNTs with different diameters and in-plane κ of graphene. All the studies were under the framework of anharmonic lattice dynamics and Boltzmann transport equation (BTE) based on first principle calculations. We try to infer the right trend of diameter dependent thermal conductivity of SWCNTs. We infer that graphene is the limitation as SWCNT with an infinite diameter. We analyzed the thermal conductivity contributions from each phonon mode in SWCNTs to explain the trend. Meanwhile, we also identify the extremely low thermal conductivity of ultra-thin SWCNTs.
Genome-wide protein-protein interactions and protein function exploration in cyanobacteria
Authors: Lv Qi , Ma Weimin , Liu Hui , Li Jiang , Wang Huan , Lu Fang , Zhao Chen , Shi Tieliu
Published: October 2015

Genome-wide network analysis is well implemented to study proteins of unknown function. Here, we effectively explored protein functions and the biological mechanism based on inferred high confident protein-protein interaction (PPI) network in cyanobacteria. We integrated data from seven different sources and predicted 1,997 PPIs, which were evaluated by experiments in molecular mechanism, text mining of literatures in proved direct/indirect evidences and “interologs” in conservation. Combined the predicted PPIs with known PPIs, we obtained 4,715 no-redundant PPIs (involving 3,231 proteins covering over 90% of genome) to generate the PPI network. Based on the PPI network, terms in Gene ontology (GO) were assigned to function-unknown proteins. Functional modules were identified by dissecting the PPI network into sub-networks and analyzing pathway enrichment, with which we investigated novel function of underlying proteins in protein complexes and pathways. Examples of photosynthesis and DNA repair indicate that the network approach is a powerful tool in protein function analysis. Overall, this systems biology approach provides a new insight into posterior functional analysis of PPIs in cyanobacteria.
Direct association between diet and the stability of human atherosclerotic plaque
Authors: Gonçalves Isabel , Andersson Georgiadou Elisavet , Mattsson Sören , Skog Göran , Pedro Luís , Fernandes e Fernandes José , Dias Nuno , Engström Gunnar , Nilsson Jan , Stenström Kristina
Published: October 2015

Mediterranean diet has been suggested to explain why coronary heart disease mortality is lower in southern than northern Europe. Dietary habits can be revealed by isotope ratio mass spectrometry (IRMS) measurement of carbon (δ13C) and nitrogen (δ15N) in biological tissues. To study if diet is associated with human plaque stability, atherosclerotic plaques from carotid endarterectomy on 56 patients (21 Portuguese and 35 Swedish) were analysed by IRMS and histology. Plaque components affecting rupture risk were measured. Swedish plaques had more apoptosis, lipids and larger cores, as well as fewer proliferating cells and SMC than the Portuguese, conferring the Swedish a more rupture-prone phenotype. Portuguese plaques contained higher δ13C and δ15N than the Swedish, indicating that Portuguese plaques were more often derived from marine food. Plaque δ13C correlated with SMC and proliferating cells and inversely with lipids, core size, apoptosis. Plaque δ15N correlated with SMC and inversely with lipids, core size and apoptosis. This is the first observational study showing that diet is reflected in plaque components associated with its vulnerability. The Portuguese plaques composition is consistent with an increased marine food intake and those plaques are more stable than those from Swedish patients. Marine-derived food is associated with plaque stability.
Protective Efficacy and Mechanism of Passive Immunization with Polyclonal Antibodies in a Sepsis Model of Staphylococcus aureus Infection
Authors: Zhang Jinyong , Yang Feng , Zhang Xiaoli , Jing Haiming , Ren Chunyan , Cai Changzhi , Dong Yandong , Zhang Yudong , Zou Quanming , Zeng Hao
Published: October 2015

Staphylococcus aureus (S. aureus) is an opportunistic bacterial pathogen responsible for a diverse spectrum of human diseases, resulting in considerable yearly mortality rates. Due to its rapid acquisition of antibiotic resistance, it becomes increasingly difficult to cure S. aureus infections with conventional antibiotics. Immunotherapy represents a promising alternative strategy to prevent and/or treat the infection. In the present study, passive immunization with polyclonal antibodies targeting three possible S. aureus antigens, Hla, SEB and MntC (termed “SAvac-pcAb”) after challenge with lethal dose of S. aureus resulted in reduced bacterial loads, inflammatory cell infiltration and decreased pathology and was able to provide nearly complete protection in a murine sepsis model. In vitro studies confirmed the direct interaction of SAvac-pcAb with S. aureus bacteria. Additional studies validated that SAvac-pcAb contained both opsonic and neutralizing antibodies that contributed to its protective efficacy. The former mediated opsonophagocytosis in a neutrophil-dependent manner, while the later inhibited the biological functions of Hla and SEB, two major virulence factors secreted by S. aureus. Critically, we demonstrated that SAvac-pcAb was cross-reactive with different clinical strains of S. aureus. These results confirmed the efficacy for treatment of S. aureus infection by passive immunization as an important therapeutic option.
Mesenchymal Stem Cells Reduce Murine Atherosclerosis Development
Authors: Frodermann Vanessa , van Duijn Janine , van Pel Melissa , van Santbrink Peter J. , Bot Ilze , Kuiper Johan , de Jager Saskia C. A.
Published: October 2015

Mesenchymal stem cells (MSCs) have regenerative properties, but recently they were also found to have immunomodulatory capacities. We therefore investigated whether MSCs could reduce atherosclerosis, which is determined by dyslipidaemia and chronic inflammation. We adoptively transferred MSCs into low-density lipoprotein-receptor knockout mice and put these on a Western-type diet to induce atherosclerosis. Initially after treatment, we found higher levels of circulating regulatory T cells. In the long-term, overall numbers of effector T cells were reduced by MSC treatment. Moreover, MSC-treated mice displayed a significant 33% reduction in circulating monocytes and a 77% reduction of serum CCL2 levels. Most strikingly, we found a previously unappreciated effect on lipid metabolism. Serum cholesterol was reduced by 33%, due to reduced very low-density lipoprotein levels, likely a result of reduced de novo hepatic lipogenesis as determined by a reduced expression of Stearoyl-CoA desaturase-1 and lipoprotein lipase. MSCs significantly affected lesion development, which was reduced by 33% in the aortic root. These lesions contained 56% less macrophages and showed a 61% reduction in T cell numbers. We show here for the first time that MSC treatment affects not only inflammatory responses but also significantly reduces dyslipidaemia in mice. This makes MSCs a potent candidate for atherosclerosis therapies.
Rearrangement of MICU1 multimers for activation of MCU is solely controlled by cytosolic Ca2+
Authors: Waldeck-Weiermair Markus , Malli Roland , Parichatikanond Warisara , Gottschalk Benjamin , Madreiter-Sokolowski Corina T. , Klec Christiane , Rost Rene , Graier Wolfgang F.
Published: October 2015

Mitochondrial Ca2+ uptake is a vital process that controls distinct cell and organelle functions. Mitochondrial calcium uptake 1 (MICU1) was identified as key regulator of the mitochondrial Ca2+ uniporter (MCU) that together with the essential MCU regulator (EMRE) forms the mitochondrial Ca2+ channel. However, mechanisms by which MICU1 controls MCU/EMRE activity to tune mitochondrial Ca2+ signals remain ambiguous. Here we established a live-cell FRET approach and demonstrate that elevations of cytosolic Ca2+ rearranges MICU1 multimers with an EC50 of 4.4 μM, resulting in activation of mitochondrial Ca2+ uptake. MICU1 rearrangement essentially requires the EF-hand motifs and strictly correlates with the shape of cytosolic Ca2+ rises. We further show that rearrangements of MICU1 multimers were independent of matrix Ca2+ concentration, mitochondrial membrane potential and expression levels of MCU and EMRE. Our experiments provide novel details about how MCU/EMRE is regulated by MICU1 and an original approach to investigate MCU/EMRE activation in intact cells.
Untangling the biological effects of cerium oxide nanoparticles: the role of surface valence states
Authors: Pulido-Reyes Gerardo , Rodea-Palomares Ismael , Das Soumen , Sakthivel Tamil Selvan , Leganes Francisco , Rosal Roberto , Seal Sudipta , Fernández-Piñas Francisca
Published: October 2015

Cerium oxide nanoparticles (nanoceria; CNPs) have been found to have both pro-oxidant and anti-oxidant effects on different cell systems or organisms. In order to untangle the mechanisms which underlie the biological activity of nanoceria, we have studied the effect of five different CNPs on a model relevant aquatic microorganism. Neither shape, concentration, synthesis method, surface charge (ζ-potential), nor nominal size had any influence in the observed biological activity. The main driver of toxicity was found to be the percentage of surface content of Ce3+ sites: CNP1 (58%) and CNP5 (40%) were found to be toxic whereas CNP2 (28%), CNP3 (36%) and CNP4 (26%) were found to be non-toxic. The colloidal stability and redox chemistry of the most and least toxic CNPs, CNP1 and CNP2, respectively, were modified by incubation with iron and phosphate buffers. Blocking surface Ce3+ sites of the most toxic CNP, CNP1, with phosphate treatment reverted toxicity and stimulated growth. Colloidal destabilization with Fe treatment only increased toxicity of CNP1. The results of this study are relevant in the understanding of the main drivers of biological activity of nanoceria and to define global descriptors of engineered nanoparticles (ENPs) bioactivity which may be useful in safer-by-design strategies of nanomaterials.
Structural and functional analysis of cell adhesion and nuclear envelope nano-topography in cell death
Authors: Kwon Hyuk-Kwon , Lee Jae-Hyeok , Shin Hyeon-Jun , Kim Jae-Ho , Choi Sangdun
Published: October 2015

The cell death mechanisms of necrosis and apoptosis generate biochemical and morphological changes in different manners. However, the changes that occur in cell adhesion and nuclear envelope (NE) topography, during necrosis and apoptosis, are not yet fully understood. Here, we show the different alterations in cell adhesion function, as well as the topographical changes occurring to the NE, during the necrotic and apoptotic cell death process, using the xCELLigence system and atomic force microscopy (AFM). Studies using xCELLigence technology and AFM have shown that necrotic cell death induced the expansion of the cell adhesion area, but did not affect the speed of cell adhesion. Necrotic nuclei showed a round shape and presence of nuclear pore complexes (NPCs). Moreover, we found that the process of necrosis in combination with apoptosis (termed nepoptosis here) resulted in the reduction of the cell adhesion area and cell adhesion speed through the activation of caspases. Our findings showed, for the first time, a successful characterization of NE topography and cell adhesion during necrosis and apoptosis, which may be of importance for the understanding of cell death and might aid the design of future drug delivery methods for anti-cancer therapies.
Valley depolarization in monolayer WSe2
Authors: Yan Tengfei , Qiao Xiaofen , Tan Pingheng , Zhang Xinhui
Published: October 2015

We have systematically examined the circular polarization of monolayer WSe2 at different temperature, excitation energy and exciton density. The valley depolarization in WSe2 is experimentally confirmed to be governed by the intervalley electron-hole exchange interaction. More importantly, a non-monotonic dependence of valley circular polarization on the excitation power density has been observed, providing the experimental evidence for the non-monotonic dependence of exciton intervalley scattering rate on the excited exciton density. The physical origination of our experimental observations has been proposed to be in analogy to the D′yakonov-Perel′ mechanism that is operative in conventional GaAs quantum well systems. Our experimental results are fundamentally important for well understanding the valley pseudospin relaxation in atomically thin transition metal dichalcogenides.
Increased male fertility using fertility-related biomarkers
Authors: Kwon Woo-Sung , Rahman Md Saidur , Ryu Do-Yeal , Park Yoo-Jin , Pang Myung-Geol
Published: October 2015

Conventional semen analyses are used to evaluate male factor fertility/infertility in humans and other animals. However, their clinical value remains controversial. Therefore, new tools that more accurately assess male fertility based on sperm function and fertilization mechanism are of interest worldwide. While protein markers in spermatozoa that might help differentiate fertile and infertile sperm have been identified, studies are in their infancy and the markers require validation in field trials. In the present study, to discover more sensitive biomarkers in spermatozoa for predicting male fertility, we assessed protein expression in capacitated spermatozoa. The results demonstrated that cytochrome b-c1 complex subunit 2 (UQCRC2) was abundantly expressed in high-litter size spermatozoa (>3-fold). On the other hand, equatorin, beta-tubulin, cytochrome b-c1 complex subunit 1 (UQCRC1), speriolin, Ras-related protein Rab-2A (RAB2A), spermadhesin AQN-3 and seminal plasma sperm motility inhibitor were abundantly expressed in low-litter size spermatozoa (>3-fold). Moreover, RAB2A and UQCRC1 expression negatively correlated with litter size, while UQCRC2 expression positively correlated with litter size. Finally, the putative biomarkers predicted litter size in field trials. Our study suggests that biomarkers present in spermatozoa after capacitation can help differentiate superior male fertility from below-average fertility with high sensitivity.
New Insights into the RNA-Binding and E3 Ubiquitin Ligase Activities of Roquins
Authors: Zhang Qi , Fan Lixin , Hou Feng , Dong Aiping , Wang Yun-Xing , Tong Yufeng
Published: October 2015

Roquins are a family of highly conserved RNA-binding proteins that also contain a RING-type E3 ubiquitin ligase domain. They repress constitutive decay elements containing mRNAs and play a critical role in RNA homeostasis and immunological self-tolerance. Here we present the crystal structures of the RNA-binding region of Roquin paralog RC3H2 in both apo- and RNA-bound forms. The RNA-binding region has a bipartite architecture composed of ROQ and HEPN domains and can bind to stem-loop and double-stranded RNAs simultaneously. The two domains undergo a large orientation change to accommodate RNA duplex binding. We profiled E2 ubiquitin-conjugating enzymes that pair with Roquins and found that RC3H1 and RC3H2 interact with two sets of overlapping but not identical E2 enzymes to drive the assembly of polyubiquitin chains of different linkages. Crystal structures, small-angle X-ray scattering and E2 profiling revealed that while the two paralogs are highly homologous, RC3H2 and RC3H1 are different in their structures and functions. We also demonstrated that RNA duplex binding to RC3H2 cross-talks with its E3 ubiquitin ligase function using an in vitro auto-ubiquitination assay.
Raman technologies in cancer diagnostics
Authors: Austin Lauren A. , Osseiran Sam , Evans Conor L.
Published: October 2015

This review explores Raman technologies with a particular emphasis on their utility for cancer diagnostic applications.
Spontaneous reaction between an uncharged lithium iron silicate cathode and a LiPF6-based electrolyte
Authors: Arthur Zachary , Chiu Hsien-Chieh , Lu Xia , Chen Ning , Emond Vincent , Zaghib Karim , Jiang De-Tong , Demopoulos George P.
Published: October 2015

The reaction between an uncharged Li2FeSiO4 (LFS) cathode and a LiPF6-EC/DMC electrolyte is revealed by in situ XANES in coin cells.
A pillar[6]arene-based [2]pseudorotaxane in solution and in the solid state and its photo-responsive self-assembly behavior in solution
Authors: Xia Danyu , Wei Peifa , Shi Bingbing , Huang Feihe
Published: October 2015

A pillar[6]arene-based [2]pseudorotaxane was obtained in solution and studied in the solid state, and its photo-responsive self-assembly behavior in solution was investigated.
Iodide surface decoration: a facile and efficacious approach to modulating the band energy level of semiconductors for high-performance visible-light photocatalysis
Authors: Huang Hongwei , Xiao Ke , Yu Shixin , Dong Fan , Zhang Tierui , Zhang Yihe
Published: October 2015

Iodide surface decoration enables the wide-band-gap Bi2O2CO3 to possess a continuously tunable band gap and profoundly boosted visible-light photocatalytic performance for dye degradation and NO removal.
Supramolecular rulers enabling selective detection of pure short ssDNA via chiral self-assembly
Authors: Kocsis Istvan , Rotaru Alexandru , Legrand Yves-Marie , Grosu Ion , Barboiu Mihail
Published: October 2015

TPA propellers appear to be compatible with the general requirements for amplified chiral supramolecular rulers used to determine the number of base pairs of short ssDNAs.
Fe– and Co–P4-embedded graphenes as electrocatalysts for the oxygen reduction reaction: theoretical insights
Authors: Feng Liyan , Liu Yuejie , Zhao Jingxiang
Published: October 2015

Fe–P4-embedded graphene exhibits high catalytic activity for the ORR in alkaline media.
Proton transport mechanism of imidazole, triazole and phosphoric acid mixtures from ab initio molecular dynamics simulations
Authors: Pahari Swagata , Roy Sudip
Published: October 2015

We have performed first principles molecular dynamics simulations to elucidate the mechanism and role of 1,2,3-triazole in proton transport while it is mixed with phosphoric acid (PA) and a phosphoric acid imidazole mixture.
Targeted water soluble copper–tetrazolate complexes: interactions with biomolecules and catecholase like activities
Authors: Saha Manideepa , Das Mriganka , Nasani Rajendar , Choudhuri Indrani , Yousufuddin Muhammed , Nayek Hari Pada , Shaikh Mobin M. , Pathak Biswarup , Mukhopadhyay Suman
Published: October 2015

Two new copper–tetrazolate complexes are synthesized and their interaction with DNA, bovine serum albumin (BSA) and catecholase like activity are explored. Interactions of the complexes with DNA are also investigated using DFT.
Exact matrix treatment of an osmotic ensemble model of adsorption and pressure induced structural transitions in metal organic frameworks
Authors: Dunne Lawrence J. , Manos George
Published: October 2015

Here we present an exactly treated quasi-one dimensional statistical mechanical osmotic ensemble model of pressure and adsorption induced breathing structural transformations of metal–organic frameworks (MOFs).
A new approach in the synthesis of La1−xGdxFeO3perovskite nanoparticles – structural and magnetic characterization
Authors: Wiglusz R. J. , Kordek K. , Małecka M. , Ciupa A. , Ptak M. , Pazik R. , Pohl P. , Kaczorowski D.
Published: October 2015

A series of highly crystalline orthoferrite nanoparticles (type La1−xGdxFeO3, wherex= 0 to 1) were prepared using the self-combustion method.
Synthesis, and crystal and electronic structure of sodium metal phosphate for use as a hybrid capacitor in non-aqueous electrolyte
Authors: Sundaram Manickam Minakshi , Watcharatharapong Teeraphat , Chakraborty Sudip , Ahuja Rajeev , Duraisamy Shanmughasundaram , Rao Penki Tirupathi , Munichandraiah Nookala
Published: October 2015

A mixed sodium transition metal phosphate served as an active electrode material for a hybrid supercapacitor, offering new possibilities for sodium hybrid devices.
Magnetocaloric properties of TbN, DyN and HoN nanopowders prepared by the plasma arc discharge method
Authors: Shinde K. P. , Jang S. H. , Kim J. W. , Kim D. S. , Ranot M. , Chung K. C.
Published: October 2015

We report for the first time the synthesis of nanopowders of TbN, DyN and HoN crystallized in a cubic structure by the plasma arc discharge (PAD) method and investigate their magnetocaloric properties for magnetic refrigeration applications.
Structural flexibility in crystallized matter: from history to applications
Authors: Férey Gérard
Published: October 2015

The large reversible flexibility of hybrid crystallized matter is relatively new.
The first scorpionate ligand based on diazaphosphole
Authors: Mlateček Martin , Dostál Libor , Růžičková Zdeňka , Honzíček Jan , Holubová Jana , Erben Milan
Published: October 2015

A new tripod ligand phenyl-tris(1,2,4-diazaphospholyl)borate has been prepared and its coordination behaviour toward transition and non-transition metals was studied.
Supports and modified nano-particles for designing model catalysts
Authors: O'Brien C. P. , Dostert K.-H. , Hollerer M. , Stiehler C. , Calaza F. , Schauermann S. , Shaikhutdinov S. , Sterrer M. , Freund H.-J.
Published: October 2015

In order to design catalytic materials, we need to understand the essential causes for material properties resulting from its composite nature. In this paper we discuss two, at first sight, diverse aspects: (a) the effect of the oxide–metal interface on metal nanoparticle properties and (b) the consequences of metal particle modification after activation on the selectivity of hydrogenation reactions. However, these two aspects are intimately linked. The metal nanoparticle’s electronic structure changes at the interface as a catalyst is brought to different reaction temperatures due to morphological modifications in the metal and, as we will discuss, these changes in the chemistry lead to changes in the reaction path. As the morphology of the particle varies, facets of different orientations and sizes are exposed, which may lead to a change in the surface chemistry as well. We use two specific reactions to address these issues in some detail. To the best of our knowledge, the present paper reports the first observations of this kind for well-defined model systems. The changes in the electronic structure of Au nanoparticles due to their size and interaction with a supporting oxide are revealed as a function of temperature using CO2 activation as a probe. The presence of spectator species (oxopropyl), formed during an activation step of acrolein hydrogenation, strongly controls the selectivity of the reaction towards hydrogenation of the unsaturated CO bond vs. the CC bond on Pd(111) when compared with oxide-supported Pd nanoparticles.
Graphene-promoted acetalisation of glycerol under acid-free conditions
Authors: Oger Nicolas , Lin Yuting F. , Le Grognec Erwan , Rataboul Franck , Felpin François-Xavier
Published: October 2015

Uncovered properties of graphene for the acetalisation of glycerol with both aldehydes and ketones under acid-free conditions allow the synthesis of fuel bio-additive candidates.
Multi-layered, membrane-integrated microfluidics based on replica molding of a thiol–ene epoxy thermoset for organ-on-a-chip applications
Authors: Sticker Drago , Rothbauer Mario , Lechner Sarah , Hehenberger Marie-Therese , Ertl Peter
Published: October 2015

Versatile microfabrication of biocompatible OSTEMER using replica and microinjection molding enables fabrication of complex multi-layered micropump and 3D multi-membrane cell chips.
Prebiotic network evolution: six key parameters
Authors: Nghe Philippe , Hordijk Wim , Kauffman Stuart A. , Walker Sara I. , Schmidt Francis J. , Kemble Harry , Yeates Jessica A. M. , Lehman Niles
Published: October 2015

Akin to biological networks, prebiotic chemical networks can evolve and we have identified six key parameters that govern their evolution.
Temporal-spatially transformed synthesis and formation mechanism of gold bellflowers
Authors: Lin Jing , Zhang Molly G. , Tang Yuxia , Wen Bronte , Hu Hao , Song Jibing , Liu Yijing , Huang Peng , Chen Xiaoyuan
Published: October 2015

We synthesized gold nanourchins, gold microspheres, and gold bellflowers in monophasic, biphasic, and triphasic systems, respectively, and investigated their formation mechanisms.
Superabsorption of light by nanoparticles
Authors: Ladutenko Konstantin , Belov Pavel , Peña-Rodríguez Ovidio , Mirzaei Ali , Miroshnichenko Andrey E. , Shadrivov Ilya V.
Published: October 2015

It is possible to overcome the fundamental limit of light absorption by a nanoparticle using carefully designed Mie resonances.
A new approach for crystallization of copper(ii) oxide hollow nanostructures with superior catalytic and magnetic response
Authors: Singh Inderjeet , Landfester Katharina , Chandra Amreesh , Muñoz-Espí Rafael
Published: October 2015

Copper(ii) oxide hollow nanostructures for catalytic reduction ofp-nitrophenol top-aminophenol.
Strong interactions with polyethylenimine-coated human serum albumin nanoparticles (PEI-HSA NPs) alter α-synuclein conformation and aggregation kinetics
Authors: Mohammad-Beigi Hossein , Shojaosadati Seyed Abbas , Marvian Amir Tayaranian , Pedersen Jannik Nedergaard , Klausen Lasse Hyldgaard , Christiansen Gunna , Pedersen Jan Skov , Dong Mingdong , Morshedi Dina , Otzen Daniel E.
Published: October 2015

The feature article focuses on the interaction between nanoparticles and α-synuclein, whose aggregation is central in the development of Parkinson′s Disease.
Defective ZnFe2O4 nanorods with oxygen vacancy for photoelectrochemical water splitting
Authors: Kim Ju Hun , Jang Youn Jeong , Kim Jin Hyun , Jang Ji-Wook , Choi Sun Hee , Lee Jae Sung
Published: October 2015

A 1D ZnFe2O4 photoanode is treated under a hydrogen or vacuum atmosphere to improve the photoelectrochemical water oxidation activity up to 20 times. This post-treatment creates oxygen vacancies in the ZnFe2O4 lattice that serve as a source of electron donors and passivates surface trap sites, and as a result improves charge transfer.