bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrafast photonic reinforcement learning based on laser chaos
Authors: Naruse Makoto , Terashima Yuta , Uchida Atsushi , Kim Song-Ju
Published: August 2017

Reinforcement learning involves decision making in dynamic and uncertain environments and constitutes an important element of artificial intelligence (AI). In this work, we experimentally demonstrate that the ultrafast chaotic oscillatory dynamics of lasers efficiently solve the multi-armed bandit problem (MAB), which requires decision making concerning a class of difficult trade-offs called the exploration–exploitation dilemma. To solve the MAB, a certain degree of randomness is required for exploration purposes. However, pseudorandom numbers generated using conventional electronic circuitry encounter severe limitations in terms of their data rate and the quality of randomness due to their algorithmic foundations. We generate laser chaos signals using a semiconductor laser sampled at a maximum rate of 100 GSample/s, and combine it with a simple decision-making principle called tug of war with a variable threshold, to ensure ultrafast, adaptive, and accurate decision making at a maximum adaptation speed of 1 GHz. We found that decision-making performance was maximized with an optimal sampling interval, and we highlight the exact coincidence between the negative autocorrelation inherent in laser chaos and decision-making performance. This study paves the way for a new realm of ultrafast photonics in the age of AI, where the ultrahigh bandwidth of light wave can provide new value.
A model for relative biological effectiveness of therapeutic proton beams based on a global fit of cell survival data
Authors: Abolfath Ramin , Peeler Christopher R. , Newpower Mark , Bronk Lawrence , Grosshans David , Mohan Radhe
Published: August 2017

We introduce an approach for global fitting of the recently published high-throughput and high accuracy clonogenic cell-survival data for therapeutic scanned proton beams. Our fitting procedure accounts for the correlation between the cell-survival, the absorbed (physical) dose and the proton linear energy transfer (LET). The fitting polynomials and constraints have been constructed upon generalization of the microdosimetric kinetic model (gMKM) adapted to account for the low energy and high lineal-energy spectrum of the beam where the current radiobiological models may underestimate the reported relative biological effectiveness (RBE). The parameters (α, β) of the linear-quadratic (LQ) model calculated by the presented method reveal a smooth transition from low to high LETs which is an advantage of the current method over methods previously employed to fit the same clonogenic data. Finally, the presented approach provides insight into underlying microscopic mechanisms which, with future study, may help to elucidate radiobiological responses along the Bragg curve and resolve discrepancies between experimental data and current RBE models.
The protective action of osmolytes on the deleterious effects of gamma rays and atmospheric pressure plasma on protein conformational changes
Authors: Attri Pankaj , Kim Minsup , Sarinont Thapanut , Ha Choi Eun , Seo Hyunwoong , Cho Art E. , Koga Kazunori , Shiratani Masaharu
Published: August 2017

Both gamma rays and atmospheric pressure plasma are known to have anticancer properties. While their mechanism actions are still not clear, in some contexts they work in similar manner, while in other contexts they work differently. So to understand these relationships, we have studied Myoglobin protein after the treatment of gamma rays and dielectric barrier discharge (DBD) plasma, and analyzed the changes in thermodynamic properties and changes in the secondary structure of protein after both treatments. The thermodynamic properties were analyzed using chemical and thermal denaturation after both treatments. We have also studied the action of gamma rays and DBD plasma on myoglobin in the presence of osmolytes, such as sorbitol and trehalose. For deep understanding of the action of gamma rays and DBD plasma, we have analyzed the reactive species generated by them in buffer at all treatment conditions. Finally, we have used molecular dynamic simulation to understand the hydrogen peroxide action on myoglobin with or without osmolytes, to gain deeper insight into how the osmolytes can protect the protein structure from the reactive species generated by gamma rays and DBD plasma.
High copy and stable expression of the xylanase XynHB in Saccharomyces cerevisiae by rDNA-mediated integration
Authors: Fang Cheng , Wang Qinhong , Selvaraj Jonathan Nimal , Zhou Yuling , Ma Lixin , Zhang Guimin , Ma Yanhe
Published: August 2017

Xylanase is a widely-used additive in baking industry for enhancing dough and bread quality. Several xylanases used in baking industry were expressed in different systems, but their expression in antibiotic free vector system is highly essential and safe. In the present study, an alternative rDNA-mediated technology was developed to increase the copy number of target gene by integrating it into Saccharomyces cerevisiae genome. A xylanase-encoding gene xynHB from Bacillus sp. was cloned into pHBM367H and integrated into S. cerevisiae genome through rDNA-mediated recombination. Exogenous XynHB expressed by recombinant S. cerevisiae strain A13 exhibited higher degradation activity towards xylan than other transformants. The real-time PCR analysis on A13 genome revealed the presence of 13.64 copies of xynHB gene. Though no antibiotics have been used, the genetic stability and the xylanase activity of xynHB remained stable up to 1,011 generations of cultivation. S. cerevisiae strain A13 expressing xylanase reduced the required kneading time and increased the height and diameter of the dough size, which would be safe and effective in baking industry as no antibiotics-resistance risk. The new effective rDNA-mediated technology without using antibiotics here provides a way to clone other food related industrial enzymes for applications.
Rap1 and Cdc13 have complementary roles in preventing exonucleolytic degradation of telomere 5′ ends
Authors: Runnberg Rikard , Narayanan Saishyam , Cohn Marita
Published: August 2017

Telomere DNA ends with a single-stranded 3′ overhang. Long 3′ overhangs may cause aberrant DNA damage responses and accelerate telomere attrition, which is associated with cancer and aging, respectively. Genetic studies have indicated several important players in preventing 5′ end hyper-resection, yet detailed knowledge about the molecular mechanism in which they act is still lacking. Here, we use an in vitro DNA 5′ end protection assay, to study how N. castellii Cdc13 and Rap1 protect against 5′ exonucleolytic degradation by λ-exonuclease. The homogeneous telomeric repeat sequence of N. castellii allows us to study their protection ability at exact binding sites relative to the 5′ end. We find efficient protection by both Cdc13 and Rap1 when bound close to the 5′ end. Notably, Rap1 provides protection when binding dsDNA at a distance from the 5′ end. The DNA binding domain of Rap1 is sufficient for 5′ end protection, and its wrapping loop region is essential. Intriguingly, Rap1 facilitates protection also when its binding site contains 2 nt of ssDNA, thus spanning across the ds-ss junction. These results highlight a role of Rap1 in 5′ end protection and indicate that Cdc13 and Rap1 have complementary roles in maintaining proper 3′ overhang length.
Monocyte infiltration and proliferation reestablish myeloid cell homeostasis in the mouse retina following retinal pigment epithelial cell injury
Authors: Ma Wenxin , Zhang Yikui , Gao Chun , Fariss Robert N. , Tam Johnny , Wong Wai T.
Published: August 2017

Age-related macular degeneration (AMD), a leading contributor of vision loss, currently lacks comprehensive treatment. While AMD histopathology involves retinal pigment epithelium (RPE) injury associated with immune cell infiltration, the nature of immune cell responses to RPE injury remains undefined. We induced RPE injury pharmacologically and genetically in transgenic mouse models in which microglia and systemic monocytes were separately tagged, enabling a spatial and temporal dissection of the relative contributions of microglia vs. monocytes to post-injury changes. We found that myeloid cell responses to RPE injury occur in stages: (1) an early mobilization of endogenous microglia from the inner retina to the RPE layer, followed by (2) subsequent monocyte infiltration from the retinal vasculature into the inner retina that replenishes the local myeloid cell population in a CCR2-regulated manner. These altered distributions of myeloid cells post-injury were long-lived, with recruited monocytes acquiring the distribution, markers, and morphologies of neighboring endogenous microglia in a durable manner. These findings indicate the role played by infiltrating monocytes in maintaining myeloid cell homeostasis in the retina following AMD-relevant RPE injury and provide a foundation for understanding and therapeutically modulating immune aspects in retinal disease.
Stability in metabolic phenotypes and inferred metagenome profiles before the onset of colitis-induced inflammation
Authors: Glymenaki M. , Barnes A. , Hagan S. O’ , Warhurst G. , McBain A. J. , Wilson I. D. , Kell D. B. , Else K. J. , Cruickshank S. M.
Published: August 2017

Inflammatory bowel disease (IBD) is associated with altered microbiota composition and metabolism, but it is unclear whether these changes precede inflammation or are the result of it since current studies have mainly focused on changes after the onset of disease. We previously showed differences in mucus gut microbiota composition preceded colitis-induced inflammation and stool microbial differences only became apparent at colitis onset. In the present study, we aimed to investigate whether microbial dysbiosis was associated with differences in both predicted microbial gene content and endogenous metabolite profiles. We examined the functional potential of mucus and stool microbial communities in themdr1a−/−mouse model of colitis and littermate controls using PICRUSt on 16S rRNA sequencing data. Our findings indicate that despite changes in microbial composition, microbial functional pathways were stable before and during the development of mucosal inflammation. LC-MS-based metabolic phenotyping (metabotyping) in urine samples confirmed that metabolite profiles inmdr1a−/−mice were remarkably unaffected by development of intestinal inflammation and there were no differences in previously published metabolic markers of IBD. Metabolic profiles did, however, discriminate the colitis-pronemdr1a−/−genotype from controls. Our results indicate resilience of the metabolic network irrespective of inflammation. Importantly as metabolites differentiated genotype, genotype-differentiating metabolites could potentially predict IBD risk.
High-speed manufacturing of highly regular femtosecond laser-induced periodic surface structures: physical origin of regularity
Authors: Gnilitskyi Iaroslav , Derrien Thibault J.-Y. , Levy Yoann , Bulgakova Nadezhda M. , Mocek Tomáš , Orazi Leonardo
Published: August 2017

Highly regular laser-induced periodic surface structures (HR-LIPSS) have been fabricated on surfaces of Mo, steel alloy and Ti at a record processing speed on large areas and with a record regularity in the obtained sub-wavelength structures. The physical mechanisms governing LIPSS regularity are identified and linked with the decay length (i.e. the mean free path) of the excited surface electromagnetic waves (SEWs). The dispersion of the LIPSS orientation angle well correlates with the SEWs decay length: the shorter this length, the more regular are the LIPSS. A material dependent criterion for obtaining HR-LIPSS is proposed for a large variety of metallic materials. It has been found that decreasing the spot size close to the SEW decay length is a key for covering several cm2 of material surface by HR-LIPSS in a few seconds. Theoretical predictions suggest that reducing the laser wavelength can provide the possibility of HR-LIPSS production on principally any metal. This new achievement in the unprecedented level of control over the laser-induced periodic structure formation makes this laser-writing technology to be flexible, robust and, hence, highly competitive for advanced industrial applications based on surface nanostructuring.
Giant pandas can discriminate the emotions of human facial pictures
Authors: Li Youxu , Dai Qiang , Hou Rong , Zhang Zhihe , Chen Peng , Xue Rui , Feng Feifei , Chen Chao , Liu Jiabin , Gu Xiaodong , Zhang Zejun , Qi Dunwu
Published: August 2017

Previous studies have shown that giant pandas (Ailuropoda melanoleuca) can discriminate face-like shapes, but little is known about their cognitive ability with respect to the emotional expressions of humans. We tested whether adult giant pandas can discriminate expressions from pictures of half of a face and found that pandas can learn to discriminate between angry and happy expressions based on global information from the whole face. Young adult pandas (5–7 years old) learned to discriminate expressions more quickly than older individuals (8–16 years old), but no significant differences were found between females and males. These results suggest that young adult giant pandas are better at discriminating emotional expressions of humans. We showed for the first time that the giant panda, can discriminate the facial expressions of humans. Our results can also be valuable for the daily care and management of captive giant pandas.
Pre-coincidence brain activity predicts the perceptual outcome of streaming/bouncing motion display
Authors: Zhao Song , Wang Yajie , Jia Lina , Feng Chengzhi , Liao Yu , Feng Wenfeng
Published: August 2017

When two identical visual discs move toward each other on a two-dimensional visual display, they can be perceived as either “streaming through” or “bouncing off” each other after their coincidence. Previous studies have observed a strong bias toward the streaming percept. Additionally, the incidence of the bouncing percept in this ambiguous display could be increased by various factors, such as a brief sound at the moment of coincidence and a momentary pause of the two discs. The streaming/bouncing bistable motion phenomenon has been studied intensively since its discovery. However, little is known regarding the neural basis underling the perceptual ambiguity in the classic version of the streaming/bouncing motion display. The present study investigated the neural basis of the perception disambiguating underling the processing of the streaming/bouncing bistable motion display using event-related potential (ERP) recordings. Surprisingly, the amplitude of frontal central P2 (220–260 ms) that was elicited by the moving discs ~200 ms before the coincidence of the two discs was observed to be predictive of subsequent streaming or bouncing percept. A larger P2 amplitude was observed for streaming percept than the bouncing percept. These findings suggest that the streaming/bouncing bistable perception may have been disambiguated unconsciously ~200 ms before the coincidence of the two discs.
Schisandrin B reverses doxorubicin resistance through inhibiting P-glycoprotein and promoting proteasome-mediated degradation of survivin
Authors: Wang Shengpeng , Wang Anqi , Shao Min , Lin Ligen , Li Peng , Wang Yitao
Published: August 2017

Acquired drug resistance poses a great challenge in cancer therapy. Drug efflux and anti-apoptotic processes are the most two common mechanisms that confer cancer drug resistance. In this study, we found that Schisandrin B (Sch B), one of the major dibenzocyclooctadiene derivatives extracted from Chinese herbal medicine Schisandrae Chinensis Fructus, could significantly enhance the sensitivity of doxorubicin (DOX)-resistant breast cancer and ovarian cancer cells to DOX. Our results showed that Sch B increased the intracellular accumulation of DOX through inhibiting expression and activity of P-glycoprotein (P-gp). Meanwhile, Sch B could markedly downregulate the expression of anti-apoptotic protein survivin. Overexpression of survivin attenuated the sensitizing effects of Sch B, while silencing of survivin enhanced Sch B-mediated sensitizing effects. Furthermore, Sch B preferentially promoted chymotryptic activity of the proteasome in a concentration-dependent manner, and the proteasome inhibitor MG-132 prevented Sch B-induced survivin downregulation. Taken together, our findings suggest that Sch B could be a potential candidate for combating drug resistant cancer via modulating two key factors that responsible for cancer resistance.
Metabolic Reconstruction and Modeling Microbial Electrosynthesis
Authors: Marshall Christopher W. , Ross Daniel E. , Handley Kim M. , Weisenhorn Pamela B. , Edirisinghe Janaka N. , Henry Christopher S. , Gilbert Jack A. , May Harold D. , Norman R. Sean
Published: August 2017

Microbial electrosynthesis is a renewable energy and chemical production platform that relies on microbial cells to capture electrons from a cathode and fix carbon. Yet despite the promise of this technology, the metabolic capacity of the microbes that inhabit the electrode surface and catalyze electron transfer in these systems remains largely unknown. We assembled thirteen draft genomes from a microbial electrosynthesis system producing primarily acetate from carbon dioxide, and their transcriptional activity was mapped to genomes from cells on the electrode surface and in the supernatant. This allowed us to create a metabolic model of the predominant community members belonging to Acetobacterium, Sulfurospirillum, and Desulfovibrio. According to the model, the Acetobacterium was the primary carbon fixer, and a keystone member of the community. Transcripts of soluble hydrogenases and ferredoxins from Acetobacterium and hydrogenases, formate dehydrogenase, and cytochromes of Desulfovibrio were found in high abundance near the electrode surface. Cytochrome c oxidases of facultative members of the community were highly expressed in the supernatant despite completely sealed reactors and constant flushing with anaerobic gases. These molecular discoveries and metabolic modeling now serve as a foundation for future examination and development of electrosynthetic microbial communities.
Dated phylogeny and dispersal history of the butterfly subfamily Nymphalinae (Lepidoptera: Nymphalidae)
Authors: Su Chengyong , Shi Qinghui , Sun Xiaoyan , Ma Junye , Li Chunxiang , Hao Jiasheng , Yang Qun
Published: August 2017

The origin and dispersal history of the large butterfly subfamily Nymphalinae are not fully understood, due to internal phylogenetic and time calibration issues. We conducted phylogenetic and dating analyses using mitochondrial and nuclear genes of biogeographically diverse groups of the Nymphalinae in order to resolve some controversial relationships and the paleobiogeographic pattern of the subfamily. Our results support the sister relationship of Vanessa (Tribe Nymphalini) and the Nymphalis-group, and the grouping of the three old-world genera (Rhinopalpa, Kallimoides and Vanessula) within Tribe Victorinini. Molecular dating analyses invoking two additional calibrations under the butterfly-host plant coevolutionary scenarios result in a relatively deeper divergence of the subfamily’s two major clades (Nymphalini and the Kallimoids), compatible with the Cretaceous floral turnover scenario during the so-called Cretaceous Terrestrial Revolution. Phylobiogeographic analyses reveal that the Oriental region is probably the center of early divergences for Nymphalinae after the Cretaceous-Paleogene (K-Pg) mass extinction, followed by repeated dispersals into the rest of the Old World and the New World during various periods beginning in Eocene. The biogeographic history indicates that temperature changes and host-plant diversification may have facilitated the dispersals of this butterfly subfamily, with accelerated global colonization during the middle to late Miocene.
Optimal Target Level of Low-density Lipoprotein Cholesterol for Vascular Function in Statin Naïve Individuals
Authors: Matsui Shogo , Kajikawa Masato , Hida Eisuke , Maruhashi Tatsuya , Iwamoto Yumiko , Iwamoto Akimichi , Oda Nozomu , Kishimoto Shinji , Hidaka Takayuki , Kihara Yasuki , Chayama Kazuaki , Goto Chikara , Aibara Yoshiki , Nakashima Ayumu , Yusoff Farina Binti Mohamad , Noma Kensuke , Higashi Yukihito
Published: August 2017

We investigated (1) the relationship between low-density lipoprotein cholesterol (LDL-C) and vascular function in patients receiving and those not receiving statin therapy and (2) optimal level of LDL-C for maintenance of vascular function. Flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) were inversely correlated with LDL-C in the 957 statin naïve subjects but not in the 392 subjects receiving statin therapy. In statin naïve subjects, non-high LDL-C (≤100 mg/dL) was independently associated with a decrease in adjusted odds ratio of the low tertile of FMD (OR: 0.62, 95% CI: 0.45–0.85; P = 0.003) and NID (OR: 0.69, 95% CI: 0.50–0.96; P = 0.03). Adjusted odds ratio of the low tertile of FMD was significantly lower in the low LDL-C group (≤70 mg/dL) (OR: 0.47, 95% CI, 0.27–0.81; P = 0.006) and in the moderate LDL-C group (70.1–100 mg/dL) (OR: 0.66, 95% CI, 0.48–0.94; P = 0.02) than in the high LDL-C group (>100 mg/dL). There was no significant difference in FMD between the low LDL-C group and moderate LDL-C group. There were significant relationships of FMD and NID with LDL-C levels in statin naïve subjects. In a general population, LDL-C of ≤100 mg/dL may be the optimal target level for maintenance of endothelial function.
Detection of magnetized quark-nuggets, a candidate for dark matter
Authors: VanDevender J. Pace , VanDevender Aaron P. , Sloan T. , Swaim Criss , Wilson Peter , Schmitt Robert. G. , Zakirov Rinat , Blum Josh , Cross James L. , McGinley Niall
Published: August 2017

Quark nuggets are theoretical objects composed of approximately equal numbers of up, down, and strange quarks and are also called strangelets and nuclearites. They have been proposed as a candidate for dark matter, which constitutes ~85% of the universe’s mass and which has been a mystery for decades. Previous efforts to detect quark nuggets assumed that the nuclear-density core interacts directly with the surrounding matter so the stopping power is minimal. Tatsumi found that quark nuggets could well exist as a ferromagnetic liquid with a ~1012-T magnetic field. We find that the magnetic field produces a magnetopause with surrounding plasma, as the earth’s magnetic field produces a magnetopause with the solar wind, and substantially increases their energy deposition rate in matter. We use the magnetopause model to compute the energy deposition as a function of quark-nugget mass and to analyze testing the quark-nugget hypothesis for dark matter by observations in air, water, and land. We conclude the water option is most promising.
Whole genome-based phylogeny of reptile-associated Helicobacter indicates independent niche adaptation followed by diversification in a poikilothermic host
Authors: Gilbert Maarten J. , Duim Birgitta , Timmerman Arjen J. , Zomer Aldert L. , Wagenaar Jaap A.
Published: August 2017

Reptiles have been shown to host a significant Helicobacter diversity. In order to survive, reptile-associated Helicobacter lineages need to be adapted to the thermally dynamic environment encountered in a poikilothermic host. The whole genomes of reptile-associated Helicobacter lineages can provide insights in Helicobacter host adaptation and coevolution. These aspects were explored by comparing the genomes of reptile-, bird-, and mammal-associated Helicobacter lineages. Based on average nucleotide identity, all reptile-associated Helicobacter lineages in this study could be considered distinct species. A whole genome-based phylogeny showed two distinct clades, one associated with chelonians and one associated with lizards. The phylogeny indicates initial adaptation to an anatomical niche, which is followed by an ancient host jump and subsequent diversification. Furthermore, the ability to grow at low temperatures, which might reflect thermal adaptation to a reptilian host, originated at least twice in Helicobacter evolution. A putative tricarballylate catabolism locus was specifically present in Campylobacter and Helicobacter isolates from reptiles. The phylogeny of reptile-associated Helicobacter parallels host association, indicating a high level of host specificity. The high diversity and deep branching within these clades supports long-term coevolution with, and extensive radiation within the respective reptilian host type.
Myosin isoform expressed in metastatic prostate cancer stimulates cell invasion
Authors: Maly Ivan V. , Domaradzki Tera M. , Gosy Victoria A. , Hofmann Wilma A.
Published: August 2017

During metastasis, tumor cells migrate out of their original tissue to invade other organs. Secretion of exosomes and metalloproteases is essential for extracellular matrix remodeling, enabling migration through tissue barriers. Metastatic prostate cancer is differentiated by expression of the rare isoform A of the molecular motor myosin IC, however the function of this isoform remained unknown. Here we show that it contributes causatively to the invasive motility of prostate cancer cells. We found that the isoform associates with metalloprotease-containing exosomes and stimulates their secretion. While the data show that myosin IC is involved in prostate cancer cell migration, migration outside extracellular matrix in vitro proves little affected specifically by isoform A. Nevertheless, this isoform stimulates invasion through extracellular matrix, pointing to a critical role in secretion. Both the secretion and invasion depend on the integrity of the motor and lipid-binding domains of the protein. Our results demonstrate how myosin IC isoform A is likely to function in metastasis, driving secretion of exosomes that enable invasion of prostate cancer cells across extracellular matrix barriers. The new data identify a molecule suitable for a mechanistically grounded development into a marker and target for prognosis, detection, and treatment of invasive prostate cancer.
Unconventional fractional quantum Hall effect in bilayer graphene
Authors: Jacak Janusz Edward
Published: August 2017

Recent experimental progress in Hall measurements in bilayer graphene in the so-called open-face configuration of boron nitride encapsulated samples, together with the earlier technique of suspended samples, allows for precise observation of the fractional quantum Hall effect (FQHE) in all 4 subbands of the Lowest Landau level (with n = 0 and n = 1) and in the next LL subbands (with n = 2) in the bilayer system. Many newly observed FQHE features do not agree with a conventional model of composite fermions and reveal a different hierarchy in comparison to monolayer graphene or GaAs 2DEG. We explain the peculiarity of the FQHE hierarchy in the bilayer system in the framework of a topological approach, which includes the composite fermion model as its special case. Inclusion of a topological effect caused by the hopping of electrons between the two sheets in the bilayer system allowed for an explanation of the FQHE hierarchy in the graphene bilayer in satisfactory accordance with the experimental observations.
Metabolomic and Lipidomic Profiling Identifies The Role of the RNA Editing Pathway in Endometrial Carcinogenesis
Authors: Altadill Tatiana , Dowdy Tyrone M. , Gill Kirandeep , Reques Armando , Menon Smrithi S. , Moiola Cristian P. , Lopez-Gil Carlos , Coll Eva , Matias-Guiu Xavier , Cabrera Silvia , Garcia Angel , Reventos Jaume , Byers Stephen W. , Gil-Moreno Antonio , Cheema Amrita K. , Colas Eva
Published: August 2017

Endometrial cancer (EC) remains the most common malignancy of the genital tract among women in developed countries. Although much research has been performed at genomic, transcriptomic and proteomic level, there is still a significant gap in the metabolomic studies of EC. In order to gain insights into altered metabolic pathways in the onset and progression of EC carcinogenesis, we used high resolution mass spectrometry to characterize the metabolomic and lipidomic profile of 39 human EC and 17 healthy endometrial tissue samples. Several pathways including lipids, Kynurenine pathway, endocannabinoids signaling pathway and the RNA editing pathway were found to be dysregulated in EC. The dysregulation of the RNA editing pathway was further investigated in an independent set of 183 human EC tissues and matched controls, using orthogonal approaches. We found that ADAR2 is overexpressed in EC and that the increase in expression positively correlates with the aggressiveness of the tumor. Furthermore, silencing of ADAR2 in three EC cell lines resulted in a decreased proliferation rate, increased apoptosis, and reduced migration capabilities in vitro. Taken together, our results suggest that ADAR2 functions as an oncogene in endometrial carcinogenesis and could be a potential target for improving EC treatment strategies.
Identification of the N-terminal transmembrane domain of StarD7 and its importance for mitochondrial outer membrane localization and phosphatidylcholine transfer
Authors: Horibata Yasuhiro , Ando Hiromi , Satou Motoyasu , Shimizu Hiroaki , Mitsuhashi Satomi , Shimizu Yasuo , Itoh Masahiko , Sugimoto Hiroyuki
Published: August 2017

StarD7 facilitates phosphatidylcholine (PC) transfer to mitochondria, and is essential for mitochondrial homeostasis. However, the molecular mechanism for PC transfer by protein remains poorly understood. Herein, we describe a putative novel transmembrane (TM) domain C-terminal to the mitochondria-targeting signal (MTS) sequence at the N-terminus of StarD7. The mature form of StarD7 is integrated and/or associated onto the outer leaflet of the outer mitochondrial membrane (OMM) in HEPA-1 and HepG2 cells. A truncated form of StarD7 lacking the TM domain is distributed in the inner space of the mitochondria, and cannot reverse mitochondrial abnormalities, such as complex formation and PC content, when re-expressed in StarD7-KO HEPA-1 cells. Re-expression of wild StarD7 can compensate these mitochondrial functions of StarD7-KO HEPA-1 cells. The precursor form of StarD7 is cleaved between Met76 and Ala77, and Ala77 and Ala78 in the TM domain to produce the mature form. These results suggest that StarD7 is anchored onto the OMM through its N-terminal TM domain, and the C-terminal START domain may extend into the cytoplasm and shuttle PC between the ER and OMM at the ER-mitochondria contact sites.
Targeted inhibition of RAGE in substantia nigra of rats blocks 6-OHDA–induced dopaminergic denervation
Authors: Gasparotto Juciano , Ribeiro Camila Tiefensee , Bortolin Rafael Calixto , Somensi Nauana , Rabelo Thallita Kelly , Kunzler Alice , Souza Natália Cabral , Pasquali Matheus Augusto de Bittencourt , Moreira José Claudio Fonseca , Gelain Daniel Pens
Published: August 2017

The receptor for advanced glycation endproducts (RAGE) is a pattern-recognition receptor associated with inflammation in most cell types. RAGE up-regulates the expression of proinflammatory mediators and its own expression via activation of NF-kB. Recent works have proposed a role for RAGE in Parkinson’s disease (PD). In this study, we used the multimodal blocker of RAGE FPS-ZM1, which has become available recently, to selectively inhibit RAGE in the substantia nigra (SN) of rats intracranially injected with 6-hydroxydopamine (6-OHDA). FPS-ZM1 (40 μg per rat), injected concomitantly with 6-OHDA (10 μg per rat) into the SN, inhibited the increase in RAGE, activation of ERK1/2, Src and nuclear translocation of NF-kB p65 subunit in the SN. RAGE inhibition blocked glial fibrillary acidic protein and Iba-1 upregulation as well as associated astrocyte and microglia activation. Circulating cytokines in serum and CSF were also decreased by FPS-ZM1 injection. The loss of tyrosine hydroxylase and NeuN-positive neurons was significantly inhibited by RAGE blocking. Finally, FPS-ZM1 attenuated locomotory and exploratory deficits induced by 6-OHDA. Our results demonstrate that RAGE is an essential component in the neuroinflammation and dopaminergic denervation induced by 6-OHDA in the SN. Selective inhibition of RAGE may offer perspectives for therapeutic approaches.
Extracting Intercellular Signaling Network of Cancer Tissues using Ligand-Receptor Expression Patterns from Whole-tumor and Single-cell Transcriptomes
Authors: Zhou Joseph X. , Taramelli Roberto , Pedrini Edoardo , Knijnenburg Theo , Huang Sui
Published: August 2017

Many behaviors of cancer, such as progression, metastasis and drug resistance etc., cannot be fully understood by genetic mutations or intracellular signaling alone. Instead, they are emergent properties of the cell community which forms a tumor. Studies of tumor heterogeneity reveal that many cancer behaviors critically depend on intercellular communication between cancer cells themselves and between cancer-stromal cells by secreted signaling molecules (ligands) and their cognate receptors. We analyzed public cancer transcriptome database for changes in cell-cell interactions as the characteristic of malignancy. We curated a list (>2,500 ligand-receptor pairs) and identified their joint enrichment in tumors from TCGA pan-cancer data. From single-cell RNA-Seq data for a case of melanoma and the specificity of the ligand-receptor interactions and their gene expression measured in individual cells, we constructed a map of a cell-cell communication network that indicates what signal is exchanged between which cell types in the tumor. Such networks establish a new formal phenotype of cancer which captures the cell-cell communication structure - it may open new opportunities for identifying molecular signatures of coordinated behaviors of cancer cells as a population - in turn may become a determinant of cancer progression potential and prognosis.
Microbiota in the coelomic fluid of two common coastal starfish species and characterization of an abundant Helicobacter-related taxon
Authors: Nakagawa Satoshi , Saito Hikari , Tame Akihiro , Hirai Miho , Yamaguchi Hideyuki , Sunata Takashi , Aida Masanori , Muto Hisashi , Sawayama Shigeki , Takaki Yoshihiro
Published: August 2017

Marine invertebrates associate with diverse microorganisms. Microorganisms even inhabit coelomic fluid (CF), namely, the fluid filling the main body cavity of echinoderms. The CF microbiota potentially impacts host health and disease. Here, we analysed the CF microbiota in two common coastal starfish species, Patiria pectinifera and Asterias amurensis. Although microbial community structures were highly variable among individual starfish, those of P. pectinifera were compositionally similar to those in the surrounding seawater. By contrast, many A. amurensis individuals harboured unique microbes in the CF, which was dominated by the unclassified Thiotrichales or previously unknown Helicobacter-related taxon. In some individuals, the Helicobacter-related taxon was the most abundant genus-level taxon, accounting for up to 97.3% of reads obtained from the CF microbial community. Fluorescence in situ hybridization using a Helicobacter-related-taxon-specific probe suggested that probe-reactive cells in A. amurensis were spiral-shaped, morphologically similar to known Helicobacter species. Electron microscopy revealed that the spiral cells had a prosthecate-like polar appendage that has never been reported in Helicobacter species. Although culture of Helicobacter-related taxon was unsuccessful, this is the first report of the dominance of a Helicobacter-related taxon in invertebrates and non-digestive organs, reshaping our knowledge of the phylogeography of Helicobacter-related taxa.
Repetition suppression to objects is modulated by stimulus-specific expectations
Authors: Utzerath Christian , St. John-Saaltink Elexa , Buitelaar Jan , de Lange Floris P.
Published: August 2017

Repeated exposure to the same stimulus results in an attenuated brain response in cortical regions that are activated during the processing of that stimulus. This phenomenon, called repetition suppression (RS), has been shown to be modulated by expectation. Typically, this is achieved by varying the probability of stimulus repetitions (Prep) between blocks of an experiment, generating an abstract expectation that ‘things will repeat’. Here, we examined whether stimulus-specific expectations also modulate RS. We designed a task where expectation and repetition are manipulated independently, using stimulus-specific expectations. We investigated to which extent such stimulus-specific expectations modulated the visual evoked response to objects in lateral occipital cortex (LOC) and primary visual cortex (V1), using functional magnetic resonance imaging (fMRI). In LOC, we found that RS interacted with expectation, such that repetition suppression was more pronounced for unexpected relative to expected stimuli. Additionally, we found that the response of stimulus-preferring voxels in V1 was generally decreased when stimuli were expected. These results suggest that stimulus-specific expectations about objects modulate LOC and propagate back to the earliest cortical station processing visual input.
Reconfiguration of quantum states in $${\mathscr{P}}{\mathscr{T}}$$-symmetric quasi-one-dimensional lattices
Authors: Ryu Jung-Wan , Myoung Nojoon , Park Hee Chul
Published: August 2017

We demonstrate mesoscopic transport through quantum states in quasi-1D lattices maintaining the combination of parity and time-reversal symmetries by controlling energy gain and loss. We investigate the phase diagram of the non-Hermitian system where transitions take place between unbroken and broken $${\mathscr{P}}{\mathscr{T}}$$
P
T
-symmetric phases via exceptional points. Quantum transport in the lattice is measured only in the unbroken phases in the energy band–but not in the broken phases. The broken phase allows for spontaneous symmetry-broken states where the cross-stitch lattice is separated into two identical single lattices corresponding to conditionally degenerate eigenstates. These degeneracies show a lift-up in the complex energy plane, caused by the non-Hermiticity with $${\mathscr{P}}{\mathscr{T}}$$
P
T
-symmetry.
Modern dust aerosol availability in northwestern China
Authors: Wang Xunming , Cheng Hong , Che Huizheng , Sun Jimin , Lu Huayu , Qiang Mingrui , Hua Ting , Zhu Bingqi , Li Hui , Ma Wenyong , Lang Lili , Jiao Linlin , Li Danfeng
Published: August 2017

The sources of modern dust aerosols and their emission magnitudes are fundamental for linking dust with climate and environment. Using field sample data, wind tunnel experiments and statistical analysis, we determined the contributions of wadis, gobi (stony desert), lakebeds, riverbeds, and interdunes to modern dust aerosol availability in the three important potential dust sources including the Tarim Basin, Qaidam Basin, and Ala Shan Plateau of China. The results show that riverbeds are the dominant landscape for modern dust aerosol availabilities in the Qaidam Basin, while wadis, gobi, and interdunes are the main landscapes over the Ala Shan Plateau and Tarim Basin. The Ala Shan Plateau and Tarim Basin are potential dust sources in northwestern China, while the Qaidam Basin is not a major source of the modern dust aerosols nowadays, and it is not acting in a significant way to the Loess Plateau presently. Moreover, most of modern dust aerosol emissions from China originated from aeolian processes with low intensities rather than from major dust events.
Nanomechanics of multidomain neuronal cell adhesion protein contactin revealed by single molecule AFM and SMD
Authors: Mikulska-Ruminska Karolina , Kulik Andrej J. , Benadiba Carine , Bahar Ivet , Dietler Giovanni , Nowak Wieslaw
Published: August 2017

Contactin-4 (CNTN4) is a complex cell adhesion molecule (CAM) localized at neuronal membranes, playing a key role in maintaining the mechanical integrity and signaling properties of the synapse. CNTN4 consists of six immunoglobulin C2 type (IgC2) domains and four fibronectin type III (FnIII) domains that are shared with many other CAMs. Mutations in CNTN4 gene have been linked to various psychiatric disorders. Toward elucidating the response of this modular protein to mechanical stress, we studied its force-induced unfolding using single molecule atomic force microscopy (smAFM) and steered molecular dynamics (SMD) simulations. Extensive smAFM and SMD data both indicate the distinctive mechanical behavior of the two types of modules distinguished by unique force-extension signatures. The data also reveal the heterogeneity of the response of the individual FNIII and IgC2 modules, which presumably plays a role in the adaptability of CNTN4 to maintaining cell-cell communication and adhesion properties under different conditions. Results show that extensive sampling of force spectra, facilitated by robot-enhanced AFM, can help reveal the existence of weak stabilizing interactions between the domains of multidomain proteins, and provide insights into the nanomechanics of such multidomain or heteromeric proteins.
Comparative metabonomics of Wenxin Keli and Verapamil reveals differential roles of gluconeogenesis and fatty acid β-oxidation in myocardial injury protection
Authors: Jiang Miaomiao , Wang Qiuying , Chen Jingrui , Wang Yanan , Fan Guanwei , Zhu Yan
Published: August 2017

Metabonomics/metabolomics is a rapid technology for comprehensive profiling of small molecule metabolites in cells, tissues, or whole organisms, the application of which has led to understanding pathophysiologic mechanisms of cardiometabolic diseases, defining predictive biomarkers for those diseases, and also assessing the efficacious effects of incident drugs. In this study, proton nuclear magnetic resonance (NMR)-based metabonomics was employed to identify the metabolic changes in rat plasma caused by myocardial ischemia-reperfusion injury (MIRI), and to compare the metabolic regulatory differences between traditional Chinese medicine Wenxin Keli (WXKL) and Western medicine verapamil. The results revealed that energy-substrate metabolism were significantly disturbed by ischemia-reperfusion (I/R) in myocardium and bulk of the key metabolites could be further modulated by verapamil and/or WXKL. Lipid metabolism and amino acid transamination occurred mainly following the treatment of verapamil, whereas glucose oxidation and BCAA degradation were prominently ameliorated by WXKL to content the energy demands of heart. Moreover, both WXKL and verapamil improved the secretions of taurine and ketone bodies to overcome the oxidative stress and the shortage of energy sources induced by ischemia-reperfusion.
Convenient and effective ICGylation of magnetic nanoparticles for biomedical applications
Authors: Park Hye Sun , Kim Jongwoo , Cho Mi Young , Lee Hyunseung , Nam Sang Hwan , Suh Yung Doug , Hong Kwan Soo
Published: August 2017

Nanoprobes used for biomedical applications usually require surface modifications with amphiphilic surfactants or inorganic coating materials to enhance their biocompatibility. We proposed a facile synthetic approach for the phase transfer of hydrophobic magnetic nanoparticles by the direct adherence of fluorescent probes, without any chemical modifications, for use as a magnetic resonance (MR)/near-infrared (NIR) fluorescence bimodal imaging contrast agent. Indocyanine green (ICG) was used not only as an optical component for NIR imaging, but also as a surfactant for phase transfer with no superfluous moiety: we therefore called the process “ICGylation”. Cell labeling and tracking in vivo with ICGylated magnetic nanoparticles were successfully performed by MR/NIR dual-mode imaging for three days, which showed remarkable biostability without any additional surface functionalization. We expect that this novel MR/NIR contrast agent demonstrating sensitive detection and simultaneous imaging capability can be used in diverse fields, such as the imaging and tracking of immune cells to confirm immunotherapeutic efficacy. The approach used could also be applied to other kinds of nanoparticles, and it would promote the development of advanced functional multimodal nanobioprobes.
Rapid and high-efficiency discrimination of different sialic acid species using dipeptide-based fluorescent sensors
Authors: Lu Qi , Zhan Mimi , Deng Lijing , Qing Guangyan , Sun Taolei
Published: August 2017

A novel fluorescence sensing matrix is developed by combining six dipeptide-based fluorescent sensors, which allows rapid discrimination of different sialic acid species.
Cellulose ionics: switching ionic diode responses by surface charge in reconstituted cellulose films
Authors: Aaronson Barak D. B. , Wigmore David , Johns Marcus A. , Scott Janet L. , Polikarpov Igor , Marken Frank
Published: August 2017

Cellulose films as well as chitosan-modified cellulose films of approximately 5 μm thickness, reconstituted from ionic liquid media onto a poly(ethylene-terephthalate) (PET, 6 μm thickness) film with a 5, 10, 20, or 40 μm diameter laser-drilled microhole, show significant current rectification in aqueous NaCl.
Sunlight assisted direct amide formation via a charge-transfer complex
Authors: Cohen Irit , Mishra Abhaya K. , Parvari Galit , Edrei Rachel , Dantus Mauricio , Eichen Yoav , Szpilman Alex M.
Published: August 2017

We report on the use of charge-transfer complexes between amines and carbon tetrachloride, as a novel way to activate the amine for photochemical reactions.
Nucleophilic trifluoromethylation of electron-deficient arenes
Authors: Pike Jack A. , Walton James W.
Published: August 2017

A new trifluoromethylation of arenes is presented, which proceeds via a Ru(ii) π–arene complex and is carried out under mild reaction conditions.
Hysteretic spin crossover driven by anion conformational change
Authors: Phukkaphan Natnaree , Cruickshank Dyanne L. , Murray Keith S. , Phonsri Wasinee , Harding Phimphaka , Harding David J.
Published: August 2017

An air stable FeIII complex showing a wide hysteresis near room temperature is described. The origin of the cooperativity is an unprecedented anion conformational change.
Giant lattice expansion by quantum stress and universal atomic forces in semiconductors under instant ultrafast laser excitation
Authors: Chen Nian-Ke , Han Dong , Li Xian-Bin , Liu Feng , Bang Junhyeok , Wang Xue-Peng , Chen Qi-Dai , Wang Hai-Yu , Zhang Shengbai , Sun Hong-Bo
Published: August 2017

Electronic excitation induced stress and force may provide a new route to manipulate the structure of materials using ultrafast lasers.
Comprehensive benchmarking of density matrix functional approximations
Authors: Rodríguez-Mayorga Mauricio , Ramos-Cordoba Eloy , Via-Nadal Mireia , Piris Mario , Matito Eduard
Published: August 2017

Density matrix functional approximations under the microscope: they should pass a series of ten tests including the energy and other relevant properties.
Long-range Li ion diffusion in NASICON-type Li1.5Al0.5Ge1.5(PO4)3 (LAGP) studied by 7Li pulsed-gradient spin-echo NMR
Authors: Hayamizu Kikuko , Seki Shiro
Published: August 2017

PGSE NMR showed parameter-dependent 7Li diffusion for a solid conductor LAGP in micrometer space, suggesting disperse mobility of Li ions.
Ergothioneine and related histidine derivatives in the gas phase: tautomer structures determined by IRMPD spectroscopy and theory
Authors: Peckelsen Katrin , Martens Jonathan , Czympiel Lisa , Oomens Jos , Berden Giel , Gründemann Dirk , Meijer Anthony J. H. M. , Schäfer Mathias
Published: August 2017

Gas-phase analysis of ergothioneine molecular ions allows differentiating thiol from thione tautomer structures.
Systematic size mediated trapping of anions of varied dimensionality within a dimeric capsular assembly of a flexible neutral bis-urea platform
Authors: Manna Utsab , Kayal Santanu , Nayak Biswajit , Das Gopal
Published: August 2017

The systematic and consistent size mediated recognition of spherical, planar and tetrahedral anions is observed within a neutral cation-sealed dimeric capsular assembly of a meta-difunctionalized organic bis-urea receptor in solid and solution states.