bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatic triglyceride accumulation via endoplasmic reticulum stress-induced SREBP-1 activation is regulated by ceramide synthases
Authors: Kim Ye-Ryung , Lee Eun-Ji , Shin Kyong-Oh , Kim Min Hee , Pewzner-Jung Yael , Lee Yong-Moon , Park Joo-Won , Futerman Anthony H. , Park Woo-Jae
Published: November 2019

The endoplasmic reticulum (ER) is not only important for protein synthesis and folding but is also crucial for lipid synthesis and metabolism. In the current study, we demonstrate an important role of ceramide synthases (CerS) in ER stress and NAFLD progression. Ceramide is important in sphingolipid metabolism, and its acyl chain length is determined by a family of six CerS in mammals. CerS2 generates C22-C24 ceramides, and CerS5 or CerS6 produces C16 ceramide. To gain insight into the role of CerS in NAFLD, we used a high-fat diet (HFD)-induced NAFLD mouse model. Decreased levels of CerS2 and increased levels of CerS6 were observed in the steatotic livers of mice fed a HFD. In vitro experiments with Hep3B cells indicated the protective role of CerS2 and the detrimental role of CerS6 in the ER stress response induced by palmitate treatment. In particular, CerS6 overexpression increased sterol regulatory element-binding protein-1 (SREBP-1) cleavage with decreased levels of INSIG-1, leading to increased lipogenesis. Blocking ER stress abrogated the detrimental effects of CerS6 on palmitate-induced SREBP-1 cleavage. In accordance with the protective role of CerS2 in the palmitate-induced ER stress response, CerS2 knockdown enhanced ER stress and SREBP-1 cleavage, and CerS2 heterozygote livers exhibited a stronger ER stress response and higher triglyceride levels following HFD. Finally, treatment with a low dose of bortezomib increased hepatic CerS2 expression and protected the development of NAFLD following HFD. These results indicate that CerS and its derivatives impact hepatic ER stress and lipogenesis differently and might be therapeutic targets for NAFLD.
Spatial and temporal axes impact ecology of the gut microbiome in juvenile European lobster (Homarus gammarus)
Authors: Holt Corey C , van der Giezen Mark , Daniels Carly L , Stentiford Grant D , Bass David
Published: November 2019

Microbial communities within the gut can markedly impact host health and fitness. To what extent environmental influences affect the differential distribution of these microbial populations may therefore significantly impact the successful farming of the host. Using a sea-based container culture (SBCC) system for the on-growing of European lobster (Homarus gammarus), we tracked the bacterial gut microbiota over a 1-year period. We compared these communities with lobsters of the same cohort, retained in a land-based culture (LBC) system to assess the effects of the culture environment on gut bacterial assemblage and describe the phylogenetic structure of the microbiota to compare deterministic and stochastic assembly across both environments. Bacterial gut communities from SBCCs were generally more phylogenetically clustered, and therefore deterministically assembled, compared to those reared in land-based systems. Lobsters in SBCCs displayed significantly more species-rich and species-diverse gut microbiota compared to those retained in LBC. A reduction in the bacterial diversity of the gut was also associated with higher infection prevalence of the enteric viral pathogen Homarus gammarus nudivirus (HgNV). SBCCs may therefore benefit the overall health of the host by promoting the assembly of a more diverse gut bacterial community and reducing the susceptibility to disease.
Systematic chemical screening identifies disulfiram as a repurposed drug that enhances sensitivity to cisplatin in bladder cancer: a summary of preclinical studies
Authors: Kita Yuki , Hamada Akihiro , Saito Ryoichi , Teramoto Yuki , Tanaka Ryusuke , Takano Keishi , Nakayama Kenji , Murakami Kaoru , Matsumoto Keiyu , Akamatsu Shusuke , Yamasaki Toshinari , Inoue Takahiro , Tabata Yasuhiko , Okuno Yasushi , Ogawa Osamu , Kobayashi Takashi
Published: November 2019

Background

Since the standard gemcitabine and cisplatin (GC) chemotherapy for advanced bladder cancer yields limited therapeutic effect due to chemoresistance, it is a clinical challenge to enhance sensitivity to GC.

Methods

We performed high-throughput screening by using a library of known chemicals and repositionable drugs. A total of 2098 compounds were administered alone or with GC to human bladder cancer cells, and chemicals that enhanced GC effects were screened.

Results

Disulfiram (DSF), an anti-alcoholism drug, was identified as a candidate showing synergistic effects with cisplatin but not with gemcitabine in multiple cell lines. Co-administration of DSF with GC affected cellular localisation of a cisplatin efflux transporter ATP7A, increased DNA–platinum adducts and promoted apoptosis. Micellar DSF nanoparticles (DSF-NP) that stabilised DSF in vivo, enhanced the inhibitory effect of cisplatin in patient-derived and cell-based xenograft models without severe adverse effects. A drug susceptibility evaluation system by using cancer tissue-originated spheroid culture showed promise in identifying cases who would benefit from DSF with cisplatin.

Conclusions

The present study highlighted the advantage of drug repurposing to enhance the efficacy of anticancer chemotherapy. Repurposing of DSF to a chemotherapy sensitiser may provide additional efficacy with less expense by using an available drug with a well-characterised safety profile.
Use of hydrochlorothiazide and risk of skin cancer: a nationwide Taiwanese case–control study
Authors: Pottegård Anton , Pedersen Sidsel Arnspang , Schmidt Sigrun Alba Johannesdottir , Lee Chaw-Ning , Hsu Chao-Kai , Liao Tzu-Chi , Shao Shih-Chieh , Lai Edward Chia-Cheng
Published: November 2019

Background

The antihypertensive agent hydrochlorothiazide has been associated with increased risks of non-melanoma skin cancer (NMSC) and possibly some melanoma subtypes. Previous studies were, however, conducted in predominantly Caucasian populations. We therefore examined the association between hydrochlorothiazide and skin cancer risk in an Asian population.

Methods

By using Taiwan’s National Health Insurance Research Database (NHIRD), we conducted three separate case–control studies of lip cancer, non-lip non-melanoma skin cancer and melanoma. Cases (n = 29,082) with a first-ever skin cancer diagnoses (2008–2015) were matched 1:10 to population controls. We estimated odds ratios (ORs) associating hydrochlorothiazide use with skin cancer risk by using conditional logistic regression.

Results

Hydrochlorothiazide use showed no overall association with any of the three outcomes: ORs for high cumulative use of HCTZ (≥50,000 mg) were 0.86 (95% CI 0.09–7.81) for lip cancer, 1.16 (95% CI 0.98–1.37) for non-lip NMSC and 1.07 (95% CI 0.65–1.76) for melanoma. There was some evidence of a dose–response pattern for non-lip NMSC, with an OR of 1.66 (95% CI 0.82–3.33) for 100,000–149,999 mg of HCTZ. The null findings were robust across subgroup and sensitivity analyses.

Conclusion

Use of HCTZ appears safe in terms of skin cancer risk in an Asian population.
Hsp60 and IL-8 axis promotes apoptosis resistance in cancer
Authors: Kumar Sandeep , O’Malley Jordan , Chaudhary Ajay Kumar , Inigo Joseph R. , Yadav Neelu , Kumar Rahul , Chandra Dhyan
Published: November 2019

Background

Interleukin-8 (IL-8) and heat shock protein 60 (Hsp60) play crucial roles in cell survival and maintenance of cellular homoeostasis. However, cross talks between these two proteins are not defined.

Methods

IL-8 expression in tumour tissue sections was analysed by immunohistochemistry. IL-8 expression and release in cancer cells was quantified using enzyme-linked immunosorbent assay (ELISA). Apoptosis was quantified using caspase activity and Annexin-V/PI staining.

Results

We observed IL-8 release from cancer cells in response to histone deacetylase inhibitor, apicidin (Api), and non-competitive inhibitor of the sarco/endoplasmic reticulum Ca2+ ATPase, thapsigargin (TG). IL-8 release was increased upon TG-treatment. TG-induced IL-8 expression was reduced in the presence of Api in Bax-dependent manner. Increased apoptosis was associated with decreased IL-8 expression in response to combined treatment of TG and Api. TG and Api combination induced caspase-8 and caspase-9 dependent apoptosis. Hsp60 knockdown abrogated IL-8 expression induced by Api, TG, and their combination. The level of TGF-β, an upstream regulator of IL-8, was decreased upon Hsp60-silencing. Knocking down Hsp60 decreased IL-8 expression and its release in prostate cancer cell xenograft tumours in SCID mice.

Conclusion

This study describes the underlying mechanism associated with apoptosis resistance mediated via Hsp60-IL-8 axis in cancer.
Gene characterization and molecular pathway analysis of reverse thermosensitive genic male sterility in eggplant (Solanum melongena L.)
Authors: Li Bing , Chen Xueping , Wu Yanrong , Gu Aixia , Zhang Jingjing , Luo Shuangxia , Gao Xiurui , Zhao Jianjun , Pan Xiuqing , Shen Shuxing
Published: November 2019

The naturally occurring mutant eggplant line 05ms was identified with reverse thermosensitive genic male sterility (rTGMS), but its temperature-responsive fertility mechanisms remain largely unknown. Here, we studied the flower morphology, anther cellular structure, and genome-wide gene expression of this rTGMS line. Candidate genes for thermosensitive male sterility during the microspore development of 05ms and the temperature-insensitive line S63 under low-temperature (LT) and high-temperature (HT) conditions were identified. Under LT, tapetum cells were vacuolated and had delayed disintegration in 05ms. RNA-seq analysis indicated that DEGs were enriched in the KEGG pathways ‘plant hormone signal transduction’, ‘starch and sucrose metabolism’, and ‘phenylpropanoid biosynthesis’. We identified two genes,4CLL1(Sme2.5_00368.1_g00010.1) andCKI1(Sme2.5_10056.1_g00002.1), which could potentially regulate eggplant anther development and may be candidate genes for rTGMS. Finally, we propose a working model of anther abortion for rTGMS in eggplant.CKI1responds to LT stress and causes expression changes in genes related to anther development, such as4CLL1, and the cellular structure of the tapetum becomes abnormal, causing male sterility. The findings of this study explain the underlying molecular mechanisms of male sterility in eggplant rTGMS lines.
Disease transmission and introgression can explain the long-lasting contact zone of modern humans and Neanderthals
Authors: Greenbaum Gili , Getz Wayne M. , Rosenberg Noah A. , Feldman Marcus W. , Hovers Erella , Kolodny Oren
Published: November 2019

Neanderthals and modern humans both occupied the Levant for tens of thousands of years prior to the spread of modern humans into the rest of Eurasia and their replacement of the Neanderthals. That the inter-species boundary remained geographically localized for so long is a puzzle, particularly in light of the rapidity of its subsequent movement. Here, we propose that infectious-disease dynamics can explain the localization and persistence of the inter-species boundary. We further propose, and support with dynamical-systems models, that introgression-based transmission of alleles related to the immune system would have gradually diminished this barrier to pervasive inter-species interaction, leading to the eventual release of the inter-species boundary from its geographic localization. Asymmetries between the species in the characteristics of their associated ‘pathogen packages’ could have generated feedback that allowed modern humans to overcome disease burden earlier than Neanderthals, giving them an advantage in their subsequent spread into Eurasia.
Stress breaks universal aging behavior in a metallic glass
Authors: Das Amlan , Derlet Peter M. , Liu Chaoyang , Dufresne Eric M. , Maaß Robert
Published: November 2019

Numerous disordered materials display a monotonous slowing down in their internal dynamics with age. In the case of metallic glasses, this general behavior across different temperatures and alloys has been used to establish an empirical universal superposition principle of time, waiting time, and temperature. Here we demonstrate that the application of a mechanical stress within the elastic regime breaks this universality. Using in-situ x-ray photon correlation spectroscopy (XPCS) experiments, we show that strong fluctuations between slow and fast structural dynamics exist, and that these generally exhibit larger relaxation times than in the unstressed case. On average, relaxation times increase with stress magnitude, and even preloading times of several days do not exhaust the structural dynamics under load. A model Lennard-Jones glass under shear deformation replicates many of the features revealed with XPCS, indicating that local and heterogeneous microplastic events can cause the strongly non-monotonous spectrum of relaxation times.
Transparent multispectral photodetectors mimicking the human visual system
Authors: Li Qitong , van de Groep Jorik , Wang Yifei , Kik Pieter G. , Brongersma Mark L.
Published: November 2019

Compact and lightweight photodetection elements play a critical role in the newly emerging augmented reality, wearable and sensing technologies. In these technologies, devices are preferred to be transparent to form an optical interface between a viewer and the outside world. For this reason, it is of great value to create detection platforms that are imperceptible to the human eye directly onto transparent substrates. Semiconductor nanowires (NWs) make ideal photodetectors as their optical resonances enable parsing of the multi-dimensional information carried by light. Unfortunately, these optical resonances also give rise to strong, undesired light scattering. In this work, we illustrate how a new optical resonance arising from the radiative coupling between arrayed silicon NWs can be harnessed to remove reflections from dielectric interfaces while affording spectro-polarimetric detection. The demonstrated transparent photodetector concept opens up promising platforms for transparent substrates as the base for opto-electronic devices and in situ optical measurement systems.
Real-time 3D reconstruction from single-photon lidar data using plug-and-play point cloud denoisers
Authors: Tachella Julián , Altmann Yoann , Mellado Nicolas , McCarthy Aongus , Tobin Rachael , Buller Gerald S. , Tourneret Jean-Yves , McLaughlin Stephen
Published: November 2019

Single-photon lidar has emerged as a prime candidate technology for depth imaging through challenging environments. Until now, a major limitation has been the significant amount of time required for the analysis of the recorded data. Here we show a new computational framework for real-time three-dimensional (3D) scene reconstruction from single-photon data. By combining statistical models with highly scalable computational tools from the computer graphics community, we demonstrate 3D reconstruction of complex outdoor scenes with processing times of the order of 20 ms, where the lidar data was acquired in broad daylight from distances up to 320 metres. The proposed method can handle an unknown number of surfaces in each pixel, allowing for target detection and imaging through cluttered scenes. This enables robust, real-time target reconstruction of complex moving scenes, paving the way for single-photon lidar at video rates for practical 3D imaging applications.
Tsc1 represses parvalbumin expression and fast-spiking properties in somatostatin lineage cortical interneurons
Authors: Malik Ruchi , Pai Emily Ling-Lin , Rubin Anna N , Stafford April M , Angara Kartik , Minasi Petros , Rubenstein John L. , Sohal Vikaas S , Vogt Daniel
Published: November 2019

Medial ganglionic eminence (MGE)-derived somatostatin (SST)+ and parvalbumin (PV)+ cortical interneurons (CINs), have characteristic molecular, anatomical and physiological properties. However, mechanisms regulating their diversity remain poorly understood. Here, we show that conditional loss of the Tuberous Sclerosis Complex (TSC) gene, Tsc1, which inhibits the mammalian target of rapamycin (MTOR), causes a subset of SST+ CINs, to express PV and adopt fast-spiking (FS) properties, characteristic of PV+ CINs. Milder intermediate phenotypes also occur when only one allele of Tsc1 is deleted. Notably, treatment of adult mice with rapamycin, which inhibits MTOR, reverses the phenotypes. These data reveal novel functions of MTOR signaling in regulating PV expression and FS properties, which may contribute to TSC neuropsychiatric symptoms. Moreover, they suggest that CINs can exhibit properties intermediate between those classically associated with PV+ or SST+ CINs, which may be dynamically regulated by the MTOR signaling.
Lineage tracing of acute myeloid leukemia reveals the impact of hypomethylating agents on chemoresistance selection
Authors: Caiado Francisco , Maia-Silva Diogo , Jardim Carolina , Schmolka Nina , Carvalho Tânia , Reforço Cláudia , Faria Rita , Kolundzija Branka , Simões André E. , Baubec Tuncay , Vakoc Christopher R. , da Silva Maria Gomes , Manz Markus G. , Schumacher Ton N. , Norell Håkan , Silva-Santos Bruno
Published: November 2019

Chemotherapy-resistant cancer recurrence is a major cause of mortality. In acute myeloid leukemia (AML), chemorefractory relapses result from the complex interplay between altered genetic, epigenetic and transcriptional states in leukemic cells. Here, we develop an experimental model system using in vitro lineage tracing coupled with exome, transcriptome and in vivo functional readouts to assess the AML population dynamics and associated molecular determinants underpinning chemoresistance development. We find that combining standard chemotherapeutic regimens with low doses of DNA methyltransferase inhibitors (DNMTi, hypomethylating drugs) prevents chemoresistant relapses. Mechanistically, DNMTi suppresses the outgrowth of a pre-determined set of chemoresistant AML clones with stemness properties, instead favoring the expansion of rarer and unfit chemosensitive clones. Importantly, we confirm the capacity of DNMTi combination to suppress stemness-dependent chemoresistance development in xenotransplantation models and primary AML patient samples. Together, these results support the potential of DNMTi combination treatment to circumvent the development of chemorefractory AML relapses.
Quasi Pd1Ni single-atom surface alloy catalyst enables hydrogenation of nitriles to secondary amines
Authors: Wang Hengwei , Luo Qiquan , Liu Wei , Lin Yue , Guan Qiaoqiao , Zheng Xusheng , Pan Haibin , Zhu Junfa , Sun Zhihu , Wei Shiqiang , Yang Jinlong , Lu Junling
Published: November 2019

Hydrogenation of nitriles represents as an atom-economic route to synthesize amines, crucial building blocks in fine chemicals. However, high redox potentials of nitriles render this approach to produce a mixture of amines, imines and low-value hydrogenolysis byproducts in general. Here we show that quasi atomic-dispersion of Pd within the outermost layer of Ni nanoparticles to form a Pd1Ni single-atom surface alloy structure maximizes the Pd utilization and breaks the strong metal-selectivity relations in benzonitrile hydrogenation, by prompting the yield of dibenzylamine drastically from ∼5 to 97% under mild conditions (80 °C; 0.6 MPa), and boosting an activity to about eight and four times higher than Pd and Pt standard catalysts, respectively. More importantly, the undesired carcinogenic toluene by-product is completely prohibited, rendering its practical applications, especially in pharmaceutical industry. Such strategy can be extended to a broad scope of nitriles with high yields of secondary amines under mild conditions.
Conditional quorum-sensing induction of a cyanide-insensitive terminal oxidase stabilizes cooperating populations of Pseudomonas aeruginosa
Authors: Yan Huicong , Asfahl Kyle L. , Li Na , Sun Feng , Xiao Junwei , Shen Dongsheng , Dandekar Ajai A. , Wang Meizhen
Published: November 2019

Pseudomonas aeruginosa, an opportunistic pathogen of humans, uses quorum sensing (QS) to regulate the production of extracellular products that can benefit all members of the population.P. aeruginosacan police QS-deficient cheaters by producing hydrogen cyanide, which is also QS regulated; however, the mechanism by which cooperators selectively protect themselves from the toxicity of cyanide remained unresolved. Here, we show that a cyanide-insensitive terminal oxidase encoded bycioABprovides resistance to cyanide, but only in QS-proficient strains. QS-deficient cheaters do not activatecioABtranscription. QS-mediated regulation ofcioABexpression depends on production of both cyanide by cooperators (which is QS regulated) and reactive oxygen species (ROS) from cheaters (which is not QS regulated). This type of regulatory system allows cooperating populations to respond, via ROS, to the presence of cheaters, and might allow them to defer the substantial metabolic cost of policing until cheaters are present in the population.
Essentiality of fatty acid synthase in the 2D to anchorage-independent growth transition in transforming cells
Authors: Bueno Maria J. , Jimenez-Renard Veronica , Samino Sara , Capellades Jordi , Junza Alejandra , López-Rodríguez María Luz , Garcia-Carceles Javier , Lopez-Fabuel Irene , Bolaños Juan P. , Chandel Navdeep S. , Yanes Oscar , Colomer Ramon , Quintela-Fandino Miguel
Published: November 2019

Upregulation of fatty acid synthase (FASN) is a common event in cancer, although its mechanistic and potential therapeutic roles are not completely understood. In this study, we establish a key role of FASN during transformation. FASN is required for eliciting the anaplerotic shift of the Krebs cycle observed in cancer cells. However, its main role is to consume acetyl-CoA, which unlocks isocitrate dehydrogenase (IDH)-dependent reductive carboxylation, producing the reductive power necessary to quench reactive oxygen species (ROS) originated during the switch from two-dimensional (2D) to three-dimensional (3D) growth (a necessary hallmark of cancer). Upregulation of FASN elicits the 2D-to-3D switch; however, FASN's synthetic product palmitate is dispensable for this process since cells satisfy their fatty acid requirements from the media. In vivo, genetic deletion or pharmacologic inhibition of FASN before oncogenic activation prevents tumor development and invasive growth. These results render FASN as a potential target for cancer prevention studies.
Synergized regulation of NK cell education by NKG2A and specific Ly49 family members
Authors: Zhang Xiaoqian , Feng Jin , Chen Shasha , Yang Haoyan , Dong Zhongjun
Published: November 2019

Mice lacking MHC class-I (MHC-I) display severe defects in natural killer (NK) cell functional maturation, a process designated as “education”. Whether self-MHC-I specific Ly49 family receptors and NKG2A, which are closely linked within the NK gene complex (NKC) locus, are essential for NK cell education is still unclear. Here we show, using CRISPR/Cas9-mediated gene deletion, that mice lacking all members of the Ly49 family exhibit a moderate defect in NK cell activity, while mice lacking only two inhibitory Ly49 members, Ly49C and Ly49I, have comparable phenotypes. Furthermore, the deficiency of NKG2A, which recognizes non-classical MHC-Ib molecules, mildly impairs NK cell function. Notably, the combined deletion of NKG2A and the Ly49 family severely compromises the ability of NK cells to mediate “missing-self” and “induced-self” recognition. Therefore, our data provide genetic evidence supporting that NKG2A and the inhibitory members of Ly49 family receptors synergize to regulate NK cell education.
Cryo-EM structure of a transthyretin-derived amyloid fibril from a patient with hereditary ATTR amyloidosis
Authors: Schmidt Matthias , Wiese Sebastian , Adak Volkan , Engler Jonas , Agarwal Shubhangi , Fritz Günter , Westermark Per , Zacharias Martin , Fändrich Marcus
Published: November 2019

ATTR amyloidosis is one of the worldwide most abundant forms of systemic amyloidosis. The disease is caused by the misfolding of transthyretin protein and the formation of amyloid deposits at different sites within the body. Here, we present a 2.97 Å cryo electron microscopy structure of a fibril purified from the tissue of a patient with hereditary Val30Met ATTR amyloidosis. The fibril consists of a single protofilament that is formed from an N-terminal and a C-terminal fragment of transthyretin. Our structure provides insights into the mechanism of misfolding and implies the formation of an early fibril state from unfolded transthyretin molecules, which upon proteolysis converts into mature ATTR amyloid fibrils.
Quantum simulation of chemistry with sublinear scaling in basis size
Authors: Babbush Ryan , Berry Dominic W. , McClean Jarrod R. , Neven Hartmut
Published: November 2019

We present a quantum algorithm for simulating quantum chemistry with gate complexity $$\tilde {\cal{O}}(N^{1/3}\eta ^{8/3})$$

O

̃

(

N

1
∕
3

η

8
∕
3

)

where η is the number of electrons and N is the number of plane wave orbitals. In comparison, the most efficient prior algorithms for simulating electronic structure using plane waves (which are at least as efficient as algorithms using any other basis) have complexity $$\tilde {\cal{O}}(N^{8/3}{\mathrm{/}}\eta ^{2/3})$$

O

̃

(

N

8
∕
3

∕

η

2
∕
3

)

. We achieve our scaling in first quantization by performing simulation in the rotating frame of the kinetic operator using interaction picture techniques. Our algorithm is far more efficient than all prior approaches when N ≫ η, as is needed to suppress discretization error when representing molecules in the plane wave basis, or when simulating without the Born-Oppenheimer approximation.
Travel times to hospitals in Australia
Authors: Barbieri Sebastiano , Jorm Louisa
Published: November 2019

Travel time to hospital is a key measure of health service accessibility, and impacts patients’ experiences of care and health outcomes. Methods used to estimate travel time vary across studies. In Australia the smallest geographical areas defined by the Australian Bureau of Statistics for the release of population counts are mesh blocks (MBs) and the smallest geographical areas for the release of health-related statistics are statistical areas level 2 (SA2). SA2s are built up from whole MBs. This project used the Open Source Routing Machine (OSRM) HTTP server to compute estimated travel times between the centroid of each inhabited MB and each hospital in Australia, as well as the shortest travel times between MBs and any hospital. By computing population-weighted averages across MBs, the average travel times to hospitals and the shortest travel time to any hospital were estimated for each SA2. This dataset will promote consistency across studies investigating geographic influences on health care in Australia, and the methods are applicable to generating similar datasets for other countries.
Chaotic synchronization of two optical cavity modes in optomechanical systems
Authors: Yang Nan , Miranowicz Adam , Liu Yong-Chun , Xia Keyu , Nori Franco
Published: November 2019

The synchronization of the motion of microresonators has attracted considerable attention. In previous studies, the microresonators for synchronization were studied mostly in the linear regime. While the important problem of synchronizing nonlinear microresonators was rarely explored. Here we present theoretical methods to synchronize the motions of chaotic optical cavity modes in an optomechanical system, where one of the optical modes is strongly driven into chaotic motion and transfers chaos to other weakly driven optical modes via a common mechanical resonator. This mechanical mode works as a common force acting on each optical mode, which, thus, enables the synchronization of states. We find that complete synchronization can be achieved in two identical chaotic cavity modes. For two arbitrary nonidentical chaotic cavity modes, phase synchronization can also be achieved in the strong-coupling small-detuning regime.
Author Correction: Varying levels of X chromosome coalescence in female somatic cells alters the balance of X-linked dosage compensation and is implicated in female-dominant systemic lupus erythematosus
Authors: Laskowski Agnieszka I. , Neems Daniel S. , Laster Kyle , Strojny-Okyere Chelsee , Rice Ellen L. , Konieczna Iwona M. , Voss Jessica H. , Mathew James M. , Leventhal Joseph R. , Ramsey-Goldman Rosalind , Smith Erica D. , Kosak Steven T.
Published: November 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Wideband and Large Angle Electromagnetically Induced Transparency by the Equivalent Transmission Line in a Metasurface
Authors: Ning Renxia , Li Dekai , Yang Tianlong , Chen Zhenhai , Qian Hongwen
Published: November 2019

A classical structure for a U-shaped metasurface exhibiting a wideband and large angle electromagnetically induced transparency (EIT) effect in the terahertz range is proposed. One horizontal and two vertical strips, which represent the bright and dark modes, respectively, are created for the U-shaped structure. The finite integration time domain (FITD) and equivalent circuit method are compared with the EIT result. The EIT effect is affected by the length of the vertical bar and by the distance from the vertical bar to the symmetry axis. The results show that the asymmetry of the main structure in the x and y axes makes it easier to achieve the EIT effect. In addition, by changing the incident angle, the EIT effect always exists until the angle of the incidental electromagnetic wave is 85 degrees. These results have many potential applications for terahertz filtering, large-angle switching and sensors.
Characterizing the Role of HMG-CoA Reductase in Aryl Hydrocarbon Receptor-Mediated Liver Injury in C57BL/6 Mice
Authors: Dornbos Peter , Jurgelewicz Amanda , Fader Kelly A. , Williams Kurt , Zacharewski Timothy R. , LaPres John J.
Published: November 2019

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor. The prototypical ligand of the AHR is an environmental contaminant called 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD exposure is associated with many adverse health outcomes in humans including non-alcoholic fatty liver disease (NAFLD). Previous studies suggest that AHR ligands alter cholesterol homeostasis in mice through repression of genes involved in cholesterol biosynthesis, such as Hmgcr, which encodes the rate-limiting enzyme of cholesterol biosynthesis called 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCR). In this study, we sought to characterize the impact of HMGCR repression in TCDD-induced liver injury. C57BL/6 mice were exposed to TCDD in the presence or absence of simvastatin, a competitive inhibitor of HMGCR. Simvastatin exposure decreased TCDD-induced hepatic lipid accumulation in both sexes, but was most prominent in females. Simvastatin and TCDD (S + T) co-treatment increased hepatic AHR-battery gene expression and liver injury in male, but not female, mice. In addition, the S + T co-treatment led to an increase in hepatic glycogen content that coincides with heavier liver in female mice. Results from this study suggest that statins, which are amongst the most prescribed pharmaceuticals, may protect from AHR-mediated steatosis, but alter glycogen metabolism and increase the risk of TCDD-elicited liver damage in a sex-specific manner.
Mesoporous bimetallic Fe/Co as highly active heterogeneous Fenton catalyst for the degradation of tetracycline hydrochlorides
Authors: Li Junchao , Li Xuhua , Han Jindong , Meng Fansheng , Jiang Jinyuan , Li Jiao , Xu Chunlian , Li Yun
Published: November 2019

Mesoporous bimetallic Fe/Co was prepared as a Fenton-like catalyst to degrade the tetracycline hydrochlorides (TC). The nanocasting strategy with KIT-6 as a hard template was carried out to synthesize the mesoporous bimetallic catalyst. The mesoporous bimetallic Fe/Co catalyst was characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), nitrogen adsorption-desorption isotherms, and Brunauer-Emmett-Teller (BET) method. The results showed that the catalyst has significant nanofeatures; the surface area, pore size, and particle size were 113.8 m2g−1, 4 nm, and 10 nm, respectively. In addition, the effects of the operating parameters, such as the iron-to-cobalt ratio, pH, H2O2, and initial TC concentrations on its catalytic performance were investigated. The best operating parameters were as follows: iron-to-cobalt ratio = 2:1 to 1:1, pH = 5–9, H2O2: 30 mmol, initial TC less than 30 mg/L. Furthermore, the mesoporous bimetallic Fe/Co showed a good performance for degrading TC, achieving a removal rate of 86% of TC after 3 h under the reaction conditions of H2O2 = 30 mmol, mesoporous bimetallic Fe/Co = 0.6 g/L, TC = 30 mg/L, pH = 7.0, and temperature = 25.5 °C. The mesoporous bimetallic Fe/Co catalyst shows good stability and reusability. This work demonstrated that mesoporous bimetallic Fe/Co has excellent catalytic efficiency, smaller amounts of leached ions, and wider pH range, which enhance its potential applications.
Aluminium incorporation in polar, semi- and non-polar AlGaN layers: a comparative study of x-ray diffraction and optical properties
Authors: Dinh Duc V. , Hu Nan , Honda Yoshio , Amano Hiroshi , Pristovsek Markus
Published: November 2019

Growth of AlxGa1−xN layers (0 ≤ x ≤ 1) simultaneously on polar (0001), semipolar ($$10\bar{{\rm{1}}}$$
10

1
¯

3) and ($$11\bar{{\rm{2}}}2$$
11

2
¯

2
), as well as nonpolar ($$10\bar{{\rm{1}}}0$$
10

1
¯

0
) and ($$11\bar{{\rm{2}}}0$$
11

2
¯

0
) AlN templates, which were grown on planar sapphire substrates, has been investigated by metal-organic vapour phase epitaxy. By taking into account anisotropic in-plane strain of semi- and non-polar layers, their aluminium incorporation has been determined by x-ray diffraction analysis. Optical emission energy of the layers was obtained from room-temperature photoluminescence spectra, and their effective bandgap energy was estimated from room-temperature pseudo-dielectric functions. Both x-ray diffraction and optical data consistently show that aluminium incorporation is comparable on the polar, semi- and non-polar planes.
Extracellular vesicle integrins act as a nexus for platelet adhesion in cerebral microvessels
Authors: Bagi Zsolt , Couch Yvonne , Broskova Zuzana , Perez-Balderas Francisco , Yeo Tianrong , Davis Simon , Fischer Roman , Sibson Nicola R. , Davis Benjamin G. , Anthony Daniel C.
Published: November 2019

Circulating extracellular vesicles (EVs) regulate signaling pathways via receptor-ligand interactions and content delivery, after attachment or internalization by endothelial cells. However, they originate from diverse cell populations and are heterogeneous in composition. To determine the effects of specific surface molecules, the use of synthetic EV mimetics permits the study of specific EV receptor-ligand interactions. Here, we used endogenous EVs derived from the circulation of rats, as well as ligand-decorated synthetic microparticles (MPs) to examine the role of integrin αvβ3 in platelet adhesion under flow in structurally intact cerebral arteries. At an intraluminal pressure of 50 mmHg and flow rate of 10 µl/min, platelets were delivered to the artery lumen and imaged with whole-field fluorescent microscopy. Under basal conditions very few platelets bound to the endothelium. However, adhesion events were markedly increased following the introduction of arginine-glycine-aspartate (RGD)-labelled synthetic MPs or endogenously-derived EVs from experimental stroke animals carrying excess RGD proteins, including vitronectin, CD40-ligand and thrombospondin-1. These data, which were generated in a dynamic and physiologically relevant system, demonstrate the importance of vesicle-carried RGD ligands in platelet adherence to the cerebrovascular endothelium and highlight the ability of synthetic EVs to isolate and identify key components of the molecular handshake between EVs and their targets.
High prevalence of obesity-related hypertension among adults aged 40 to 79 years in Southwest China
Authors: Zhang Yang , Hou Li-Sha , Tang Wei-Wei , Xu Fan , Xu Rong-Hua , Liu Xin , Liu Ya , Liu Jian-Xiong , Yi Yan-Jing , Hu Tai-Shang , Hu Rong , Wang Tzung-Dau , Huang Xiao-Bo
Published: November 2019

This study aimed to assess the prevalence and related factors of obesity-related hypertension among adults aged 40 to 79 years in Southwest China. From September 2013 to March 2014, a multi-stage, stratified sampling method was conducted on 10,589 people aged 40 to 79 years and living in Chengdu and Chongqing investigated by using a questionnaire and performing physical and biochemical measurements. The prevalence of obesity-related hypertension and hypertension overall (systolic ≥130 mmHg and/or diastolic ≥80 mmHg or treated hypertension) was 22.8% and 57.4%, respectively, among all participants. For obesity-related hypertension, the prevalence was higher in women than in men (24.7% versus 19.4%, p < 0.001). For people in the age ranges of 40–49, 50–59, 60–69, and ≥70, the prevalence of obesity-related hypertension were 11.8%, 22.6%, 30.7%, and 36.6%, respectively. Participants with obesity-related hypertension as opposed to those with non-obesity-related hypertension had a higher prevalence of hypertriglyceridemia, high low-density lipoprotein cholesterolemia, diabetes, and hyperuricemia (all p < 0.05). Multivariate logistic regression analysis showed that age, female gender, current smoking, hypertriglyceridemia, diabetes and family history of hypertension were all positively correlated with obesity-related hypertension, whereas higher education level and having spouse were negatively correlated with obesity-related hypertension. The prevalence of obesity-related hypertension was high among adults aged 40 to 79 years in Southwest China. Cardiometabolic abnormalities among participants with obesity-related hypertension were more serious and frequently present than in those with non-obesity-related hypertension. Aggressive and holistic strategies aiming at the prevention and treatment of obesity-related hypertension are needed.
Developmental conditions modulate DNA methylation at the glucocorticoid receptor gene with cascading effects on expression and corticosterone levels in zebra finches
Authors: Jimeno Blanca , Hau Michaela , Gómez-Díaz Elena , Verhulst Simon
Published: November 2019

Developmental conditions can impact the adult phenotype via epigenetic changes that modulate gene expression. In mammals, methylation of the glucocorticoid receptor geneNr3c1has been implicated as mediator of long-term effects of developmental conditions, but this evidence is limited to humans and rodents, and few studies have simultaneously tested for associations between DNA methylation, gene expression and phenotype. Adverse environmental conditions during early life (large natal brood size) or adulthood (high foraging costs) exert multiple long-term phenotypic effects in zebra finches, and we here test for effects of these manipulations on DNA methylation and expression of theNr3c1gene in blood. Having been reared in a large brood induced higher DNA methylation of theNr3c1regulatory region in adulthood, and this effect persisted over years.Nr3c1expression was negatively correlated with methylation at 2 out of 8 CpG sites, and was lower in hard foraging conditions, despite foraging conditions having no effect onNr3c1methylation at our target region.Nr3c1expression also correlated with glucocorticoid traits: higher expression level was associated with lower plasma baseline corticosterone concentrations and enhanced corticosterone reactivity. Our results suggest that methylation of theNr3c1regulatory region can contribute to the mechanisms underlying the emergence of long-term effects of developmental conditions in birds, but in our system current adversity dominated over early life experiences with respect to receptor expression.
Ferroelectric switching in ferroelastic materials with rough surfaces
Authors: Lu Guangming , Li Suzhi , Ding Xiangdong , Sun Jun , Salje Ekhard K. H.
Published: November 2019

Electric switching of non-polar bulk crystals is shown to occur when domain walls are polar in ferroelastic materials and when rough surfaces with steps on an atomic scale promote domain switching. All domains emerging from surface nuclei possess polar domain walls. The progression of domains is then driven by the interaction of the electric field with the polarity of domain boundaries. In contrast, smooth surfaces with higher activation barriers prohibit effective domain nucleation. We demonstrate the existence of an electrically driven ferroelectric hysteresis loop in a non-ferroelectric, ferroelastic bulk material.
Tissue-specific expression profiles and positive selection analysis in the tree swallow (Tachycineta bicolor) using a de novo transcriptome assembly
Authors: Bentz Alexandra B. , Thomas Gregg W. C. , Rusch Douglas B. , Rosvall Kimberly A.
Published: November 2019

Tree swallows (Tachycineta bicolor) are one of the most commonly studied wild birds in North America. They have advanced numerous research areas, including life history, physiology, and organismal responses to global change; however, transcriptomic resources are scarce. To further advance the utility of this system for biologists across disciplines, we generated a transcriptome for the tree swallow using six tissues (brain, blood, ovary, spleen, liver, and muscle) collected from breeding females. Wede novoassembled 207,739 transcripts, which we aligned to 14,717 high confidence protein-coding genes. We then characterized each tissue with regard to its unique genes and processes and applied this transcriptome to two fundamental questions in evolutionary biology and endocrinology. First, we analyzed 3,015 single-copy orthologs and identified 46 genes under positive selection in the tree swallow lineage, including those with putative links to adaptations in this species. Second, we analyzed tissue-specific expression patterns of genes involved in sex steroidogenesis and processing. Enzymes capable of synthesizing these behaviorally relevant hormones were largely limited to the ovary, whereas steroid binding genes were found in nearly all other tissues, highlighting the potential for local regulation of sex steroid-mediated traits. These analyses provide new insights into potential sources of phenotypic variation in a free-living female bird and advance our understanding of fundamental questions in evolutionary and organismal biology.
Pain Inhibits GRPR Neurons via GABAergic Signaling in the Spinal Cord
Authors: Bardoni Rita , Shen Kai-Feng , Li Hui , Jeffry Joseph , Barry Devin M. , Comitato Antonella , Li Yun-Qing , Chen Zhou-Feng
Published: November 2019

It has been known that algogens and cooling could inhibit itch sensation; however, the underlying molecular and neural mechanisms remain poorly understood. Here, we show that the spinal neurons expressing gastrin releasing peptide receptor (GRPR) primarily comprise excitatory interneurons that receive direct and indirect inputs from C and Aδ fibers and form contacts with projection neurons expressing the neurokinin 1 receptor (NK1R). Importantly, we show that noxious or cooling agents inhibit the activity of GRPR neurons via GABAergic signaling. By contrast, capsaicin, which evokes a mix of itch and pain sensations, enhances both excitatory and inhibitory spontaneous synaptic transmission onto GRPR neurons. These data strengthen the role of GRPR neurons as a key circuit for itch transmission and illustrate a spinal mechanism whereby pain inhibits itch by suppressing the function of GRPR neurons.
Systematic review and meta-analysis of docetaxel perioperative chemotherapy regimens in gastric and esophagogastric tumors
Authors: Uson Junior Pedro Luiz Serrano , Santos Vanessa Montes , Bugano Diogo Diniz Gomes , Victor Elivane da Silva , Rother Edna Terezinha , Maluf Fernando Cotait
Published: November 2019

FLOT regimen became the standard perioperative treatment in several centers around the world for esophagogastric tumors despite concerns about toxicity. In addition, FLOT has never been compared with other docetaxel-based regimens. To address this question, we conducted a systematic review of PubMed, Embase and Web of Science including prospective or retrospective studies of docetaxel based perioperative regimen in gastric and esophagogastric tumors. Data regarding chemotherapy regimens, efficacy and toxicity were extracted. Outcomes were compared using a random effects model. Of 548 abstracts, 16 were considered eligible. Comparing the studies with meta-analysis we can see that the regimens are similar in terms of pathological complete response, resection rate, progression free survival and overall survival in one year, without significant heterogeneity. The meta-regression of docetaxel dose failed to show any association with dose ranging between 120–450 mg/m². Regarding the toxicity of the regimens it is noted that the regimens are quite toxic (up to 50–70% of grade 3–4 neutropenia). The results of this meta-analysis with a combined sample size of more than 1,000 patients suggest that docetaxel perioperative regimens are equivalent in outcomes. Prospective trials addressing modified regimens should be performed to provide less toxic strategies and be applicable to all patients.
Peripapillary microvasculature in patients with diabetes mellitus: An optical coherence tomography angiography study
Authors: Shin Yong-Il , Nam Ki Yup , Lee Seong Eun , Lee Min-Woo , Lim Hyung-Bin , Jo Young-Joon , Kim Jung-Yeul
Published: November 2019

To evaluate changes in peripapillary microvascular parameters in diabetes mellitus (DM) patients using optical coherence tomography angiography (OCTA). Seventy-one diabetic patients (40 in the no diabetic retinopathy [DR] group and 31 in the non-proliferative DR [NPDR] group) and 50 control subjects. OCTA (Zeiss HD-OCT 5000 with AngioPlex) 6 × 6 mm scans centered on the optic disc were analyzed. Peripapillary vessel density (VD), perfusion density (PD) in superficial capillary plexus (SCP) were automatically calculated. The average macular ganglion cell-inner plexiform layer (mGC-IPL) and peripapillary retinal nerve fiber layer (pRNFL) thicknesses of the no DR and NPDR groups were significantly thinner than those of the control group. The no DR and NPDR groups showed lower peripapillary VD and PD in SCP compared with the control group. Using univariate regression analyses, the average mGC-IPL thickness, the pRNFL thickness, the no DR group and NPDR group were significant factors that affected the peripapillary VD and PD in SCP. Multivariate regression analyses showed that the grade of DR was a significant factor affecting the peripapillary VD and PD in SCP. OCTA revealed that peripapillary microvascular parameters in the no DR and NPDR groups were lower than those of normal controls. The peripapillary VD and PD in SCP were correlated with the mGC-IPL thickness, the pRNFL thickness, and the no DR and NPDR groups. Changes in peripapillary OCTA parameters may help with understanding the pathophysiology of DM and evaluating a potentially valuable biomarker for patients with subclinical DR.