bluuebunny/crossref_metadata_2025 huggingface dataset:
Robust Broadband Maritime Communications: Theoretical and Experimental Validation
Authors: Couillard Denis , Dahman Ghassan , GrandMaison Marie‐Eve , Poitau Gwenael , Gagnon Francois
Published: May 2018

Atmospheric ducts, which are caused by the rapid decrease in the refractive index of the lower atmosphere, have been recognized as the dominant propagation mechanism for long range maritime links. Recent advances in radio technology are making reliable high‐capacity overwater links a reality. A ray‐tracing simulation model was developed to obtain reliable prediction of maritime link performance beyond 30 km for realistic conditions. A series of static and mobile long range maritime multiple‐input multiple‐output links were tested with representative antenna heights at 1.39 (Band 3 or L‐Band) and 4.5 GHz (Band 4 or C‐Band) during periods with various levels of ducting activities, for example, sunset and sunrise times. Measured link performance and observed ducting occurrences are compared to predictions to validate the model ability to accurately predict and explain link performance for various ducting conditions. The test results agree with the model predictions and illustrate the various Received Signal Level degradation, enhancement, and fluctuations that can be expected in long range maritime links below 6 GHz. We also report on short‐term (few to several minutes) fluctuations of the received signal level at the two measurement frequency bands during high ducting activity periods. Measurements and theoretical analysis of the effect of ducting on the quality of maritime communication links indicate that both reflection‐induced and ducting‐induced disruptions are different and more frequent in higher‐frequency bands. This work opens interesting perspectives on providing more robust and more predictable communications in the presence of ducting.
DDB2 represses ovarian cancer cell dedifferentiation by suppressing ALDH1A1
Authors: Cui Tiantian , Srivastava Amit Kumar , Han Chunhua , Wu Dayong , Wani Nissar , Liu Lu , Gao Zhiqin , Qu Meihua , Zou Ning , Zhang Xiaoli , Yi Ping , Yu Jianhua , Bell Erica H. , Yang Shyh-Ming , Maloney David J. , Zheng Yanfang , Wani Altaf A. , Wang Qi-En
Published: May 2018

Cancer stem cells (CSCs), representing the root of many solid tumors including ovarian cancer, have been implicated in disease recurrence, metastasis, and therapeutic resistance. Our previous study has demonstrated that the CSC subpopulation in ovarian cancer can be limited by DNA damage-binding protein 2 (DDB2). Here, we demonstrated that the ovarian CSC subpopulation can be maintained via cancer cell dedifferentiation, and DDB2 is able to suppress this non-CSC-to-CSC conversion by repression ofALDH1A1transcription. Mechanistically, DDB2 binds to theALDH1A1gene promoter, facilitating the enrichment of histone H3K27me3, and competing with the transcription factor C/EBPβ for binding to this region, eventually inhibiting the promoter activity of theALDH1A1gene. The de-repression of ALDH1A1 expression contributes to DDB2 silencing-augmented non-CSC-to-CSC conversion and expansion of the CSC subpopulation. We further showed that treatment with a selective ALDH1A1 inhibitor blocked DDB2 silencing-induced expansion of CSCs, and halted orthotopic xenograft tumor growth. Together, our data demonstrate that DDB2, functioning as a transcription repressor, can abrogate ovarian CSC properties by downregulating ALDH1A1 expression.
Palmitic acid, but not high-glucose, induced myocardial apoptosis is alleviated by N‑acetylcysteine due to attenuated mitochondrial-derived ROS accumulation-induced endoplasmic reticulum stress
Authors: He Yang , Zhou Lingyun , Fan Zhiqiang , Liu Shikun , Fang Weijin
Published: May 2018

Pharmacological inhibition of reactive oxygen species (ROS) is a potential strategy to prevent diabetes-induced cardiac dysfunction. This study was designed to investigate precise effects of antioxidant N‑acetylcysteine (NAC) in alleviating diabetic cardiomyopathy (DCM). Echocardiography and histologic studies were performed 12 weeks after streptozocin injection. Protein levels involved in endoplasmic reticulum stress (ERS) and apoptosis were analyzed by western blotting in diabetic hearts or high-glucose (HG, 30 mM)- and palmitic acid (PA, 300 μM)-cultured neonatal rat cardiomyocytes (NRCMs). ROS generation and structural alterations of mitochondria were also assessed. We report that NAC alleviated diabetes-induced cardiac abnormality, including restored ejection fraction (EF %), fraction shortening (FS %), peak E to peak A ratio (E/A) and reduced cardiac hypertrophy and fibrosis. These effects were concomitant with blocked ERS and apoptosis, as evidenced by inactivation of phosphorylated inositol-requiring enzyme-1α (IRE1α)/spliced X-box binding protein 1 (XBP1), phosphorylated protein kinase-like kinase (PERK)/phosphorylated eukaryotic initiation factor 2α (eIF2α) and glucose-regulated protein 78 (GRP78)/activating transcription factor 6 (ATF6α)/C/EBP homologous protein (CHOP) pathways, as well as suppressed Bcl-2-associated X protein (BAX)/B-cell lymphoma-2 (Bcl-2) and cleaved caspase 3 expressions. Mechanistically, PA mediated excessive mitochondrial ROS generation and oxidative stress, which were antagonized by NAC and Mito-TEMPO, a mitochondrial ROS inhibitor. No effects were noted by addition of apocynin, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, and NADPH oxidase 4 (NOX 4) and NOX 2 expressions were not altered, indicating that PA-induced ROS generation is independent of NADPH oxidases. Most intriguingly, HG failed to promote ROS production despite its ability to promote ERS and apoptosis in NRCMs. Collectively, these findings indicate that NAC primarily abrogates PA-mediated mitochondrial ROS through ERS and therefore alleviates myocardial apoptosis but has little effect on HG-induced cardiac injury. This uncovers a potential role for NAC in formulating novel cardioprotective strategies in DCM patients.
Activation of TGF-β-activated kinase 1 (TAK1) restricts Salmonella Typhimurium growth by inducing AMPK activation and autophagy
Authors: Liu Wei , Jiang Yuanyuan , Sun Jing , Geng Shizhong , Pan Zhiming , Prinz Richard A. , Wang Chengming , Sun Jun , Jiao Xinan , Xu Xiulong
Published: May 2018

Autophagy is a conserved cellular process that functions as a first-line defense to restrict the growth of invading parasitic bacteria. As an intracellular pathogen, Salmonella (S) Typhimurium invades host cells through two Type III secretion systems (T3SS) and resides in the Salmonella-containing vacuole (SCV). When the SCV membrane is perforated and ruptured by T3SS-1, a small portion of the Salmonella egresses from the SCV and replicates rapidly in the nutrient-rich cytosol. Cytosolic Salmonella and those residing in the membrane-damaged SCV are tagged by ubiquitination and marked for autophagy through the ubiquitin-binding adaptor proteins such as p62, NDP52, and optineurin. Prior studies suggest that transient intracellular amino-acid starvation and subsequent inactivation of the mechanistic target of rapamycin (mTOR), a key molecule that phosphorylates Unc-51 like autophagy activating kinase (ULK1) and inhibits its activity, can trigger autophagy in S. Typhimurium-infected cells. Other studies suggest that energy stress in S. Typhimurium-infected cells leads to AMP-activated protein kinase (AMPK) activation and autophagy. In the present study, we report that autophagy was rapidly induced in S. Typhimurium-infected cells, as evidenced by increased LC3 lipidation and decreased p62 levels. However, S. Typhimurium infection drastically increased AKT phosphorylation but decreased S6K1T389, 4E-BPT37/46, and ULK1S757 phosphorylation, suggesting that mTOR activation by AKT is subverted. Further studies showed that AMPK was activated in S. Typhimurium-infected cells, as evidenced by increased ULK1S317 and ACCS79 phosphorylation. AMPK activation was mediated by Toll-like receptor-activated TAK1. Functional studies revealed that AMPK and TAK1 inhibitors accelerated S. Typhimurium growth in HeLa cells. Our results strongly suggest that TAK1 activation leads to AMPK activation, which activates ULK1 by phosphorylating ULK1S317 and suppressing mTOR activity and ULK1S757 phosphorylation. Our study has unveiled a previously unrecognized pathway for S. Typhimurium-induced autophagy.
Caspase-3 suppresses diethylnitrosamine-induced hepatocyte death, compensatory proliferation and hepatocarcinogenesis through inhibiting p38 activation
Authors: Shang Na , Bank Thomas , Ding Xianzhong , Breslin Peter , Li Jun , Shi Baomin , Qiu Wei
Published: May 2018

It is critical to understand the molecular mechanisms of hepatocarcinogenesis in order to prevent or treat hepatocellular carcinoma (HCC). The development of HCC is commonly associated with hepatocyte death and compensatory proliferation. However, the role of Caspase-3, a key apoptotic executor, in hepatocarcinogenesis is unknown. In this study, we used Caspase-3-deficient mice to examine the role of Caspase-3 in hepatocarcinogenesis in a chemical (diethylnitrosamine, DEN)-induced HCC model. We found that Caspase-3 deficiency significantly increased DEN-induced HCC. Unexpectedly, Caspase-3 deficiency increased apoptosis induced by DEN and the subsequent compensatory proliferation. Intriguingly, we discovered that Caspase-3 deficiency increased the activation of p38 with and without DEN treatment. Moreover, we demonstrated that TNFα and IL1α stimulated increased activation of p38 in Caspase-3 KO hepatocytes compared with wild-type hepatocytes. Finally, we found that inhibition of p38 by SB202190 abrogated enhanced hepatocyte death, compensatory proliferation and HCC induced by DEN in Caspase-3-deficient mice. Overall, our data suggest that Caspase-3 inhibits chemical-induced hepatocarcinogenesis by suppressing p38 activation and hepatocyte death.
FOXM1 contributes to taxane resistance by regulating UHRF1-controlled cancer cell stemness
Authors: Yuan Bowen , Liu Youhong , Yu Xiaohui , Yin Linglong , Peng Yuchong , Gao Yingxue , Zhu Qianling , Cao Tuoyu , Yang Yinke , Fan Xuegong , Li Xiong
Published: May 2018

Therapy-induced expansion of cancer stem cells (CSCs) has been identified as one of the most critical factors contributing to therapeutic resistance, but the mechanisms of this adaptation are not fully understood. UHRF1 is a key epigenetic regulator responsible for therapeutic resistance, and controls the self-renewal of stem cells. In the present study, taxane-resistant cancer cells were established and stem-like cancer cells were expanded. UHRF1 was overexpressed in the taxane-resistant cancer cells, which maintained CSC characteristics. UHRF1 depletion overcame taxane resistance in vitro and in vivo. Additionally, FOXM1 has been reported to play a role in therapeutic resistance and the self-renewal of CSCs. FOXM1 and UHRF1 are highly correlated in prostate cancer tissues and cells, FOXM1 regulates CSCs by regulating uhrf1 gene transcription in an E2F-independent manner, and FOXM1 protein directly binds to the FKH motifs at the uhrf1 gene promoter. This present study clarified a novel mechanism by which FOXM1 controls CSCs and taxane resistance through a UHRF1-mediated signaling pathway, and validated FOXM1 and UHRF1 as two potential therapeutic targets to overcome taxane resistance.
Caspase-mediated cleavage of the centrosomal proteins during apoptosis
Authors: Seo Mi Young , Rhee Kunsoo
Published: May 2018

The centrosome is the major microtubule-organizing center and plays important roles in intracellular transport, cellular morphology, and motility. In mitotic cells, centrosomes function as spindle poles to pull a set of chromosomes into daughter cells. In quiescent cells, primary cilia are originated from the centrosomes. Given its involvement in various cellular processes, it is little surprising that the organelle would also participate in apoptotic events. However, it remains elusive how the centrosome changes in structure and organization during apoptosis. Apoptosis, a programmed cell death, is required for homeostatic tissue maintenance, embryonic development, stress responses, etc. Activation of caspases generates a cascade of apoptotic pathways, explaining much of what happens during apoptosis. Here, we report the proteolytic cleavage of selected centrosomal proteins in apoptotic cells. SAS-6, a cartwheel component of centrioles, was specifically cleaved at the border of the coiled-coil domain and the disordered C-terminus. Pericentrin, a scaffold of pericentriolar material, was also cleaved during apoptosis. These cleavages were efficiently blocked by the caspase inhibitors. We propose that the caspase-dependent proteolysis of the centrosomal proteins may destabilize the configuration of a centrosome. Loss of centrosomes may be required for the formation of apoptotic microtubule networks, which are essential for apoptotic fragmentation. This work demonstrates the first centrosomal targets by caspases during apoptosis.
Mutations in six nephrosis genes delineate a pathogenic pathway amenable to treatment
Authors: Ashraf Shazia , Kudo Hiroki , Rao Jia , Kikuchi Atsuo , Widmeier Eugen , Lawson Jennifer A. , Tan Weizhen , Hermle Tobias , Warejko Jillian K. , Shril Shirlee , Airik Merlin , Jobst-Schwan Tilman , Lovric Svjetlana , Braun Daniela A. , Gee Heon Yung , Schapiro David , Majmundar Amar J. , Sadowski Carolin E. , Pabst Werner L. , Daga Ankana , van der Ven Amelie T. , Schmidt Johanna M. , Low Boon Chuan , Gupta Anjali Bansal , Tripathi Brajendra K. , Wong Jenny , Campbell Kirk , Metcalfe Kay , Schanze Denny , Niihori Tetsuya , Kaito Hiroshi , Nozu Kandai , Tsukaguchi Hiroyasu , Tanaka Ryojiro , Hamahira Kiyoshi , Kobayashi Yasuko , Takizawa Takumi , Funayama Ryo , Nakayama Keiko , Aoki Yoko , Kumagai Naonori , Iijima Kazumoto , Fehrenbach Henry , Kari Jameela A. , El Desoky Sherif , Jalalah Sawsan , Bogdanovic Radovan , Stajić Nataša , Zappel Hildegard , Rakhmetova Assel , Wassmer Sharon-Rose , Jungraithmayr Therese , Strehlau Juergen , Kumar Aravind Selvin , Bagga Arvind , Soliman Neveen A. , Mane Shrikant M. , Kaufman Lewis , Lowy Douglas R. , Jairajpuri Mohamad A. , Lifton Richard P. , Pei York , Zenker Martin , Kure Shigeo , Hildebrandt Friedhelm
Published: May 2018

No efficient treatment exists for nephrotic syndrome (NS), a frequent cause of chronic kidney disease. Here we show mutations in six different genes (MAGI2, TNS2, DLC1, CDK20, ITSN1, ITSN2) as causing NS in 17 families with partially treatment-sensitive NS (pTSNS). These proteins interact and we delineate their roles in Rho-like small GTPase (RLSG) activity, and demonstrate deficiency for mutants of pTSNS patients. We find that CDK20 regulates DLC1. Knockdown of MAGI2, DLC1, or CDK20 in cultured podocytes reduces migration rate. Treatment with dexamethasone abolishes RhoA activation by knockdown of DLC1 or CDK20 indicating that steroid treatment in patients with pTSNS and mutations in these genes is mediated by this RLSG module. Furthermore, we discover ITSN1 and ITSN2 as podocytic guanine nucleotide exchange factors for Cdc42. We generate Itsn2-L knockout mice that recapitulate the mild NS phenotype. We, thus, define a functional network of RhoA regulation, thereby revealing potential therapeutic targets.
A novel small molecule chaperone of rod opsin and its potential therapy for retinal degeneration
Authors: Chen Yuanyuan , Chen Yu , Jastrzebska Beata , Golczak Marcin , Gulati Sahil , Tang Hong , Seibel William , Li Xiaoyu , Jin Hui , Han Yong , Gao Songqi , Zhang Jianye , Liu Xujie , Heidari-Torkabadi Hossein , Stewart Phoebe L. , Harte William E. , Tochtrop Gregory P. , Palczewski Krzysztof
Published: May 2018

Rhodopsin homeostasis is tightly coupled to rod photoreceptor cell survival and vision. Mutations resulting in the misfolding of rhodopsin can lead to autosomal dominant retinitis pigmentosa (adRP), a progressive retinal degeneration that currently is untreatable. Using a cell-based high-throughput screen (HTS) to identify small molecules that can stabilize the P23H-opsin mutant, which causes most cases of adRP, we identified a novel pharmacological chaperone of rod photoreceptor opsin, YC-001. As a non-retinoid molecule, YC-001 demonstrates micromolar potency and efficacy greater than 9-cis-retinal with lower cytotoxicity. YC-001 binds to bovine rod opsin with an EC50 similar to 9-cis-retinal. The chaperone activity of YC-001 is evidenced by its ability to rescue the transport of multiple rod opsin mutants in mammalian cells. YC-001 is also an inverse agonist that non-competitively antagonizes rod opsin signaling. Significantly, a single dose of YC-001 protects Abca4
−/−
Rdh8
−/−
mice from bright light-induced retinal degeneration, suggesting its broad therapeutic potential.
Probing femtosecond lattice displacement upon photo-carrier generation in lead halide perovskite
Authors: Batignani Giovanni , Fumero Giuseppe , Srimath Kandada Ajay Ram , Cerullo Giulio , Gandini Marina , Ferrante Carino , Petrozza Annamaria , Scopigno Tullio
Published: May 2018

Electronic properties and lattice vibrations are expected to be strongly correlated in metal-halide perovskites, due to the soft fluctuating nature of their crystal lattice. Thus, unveiling electron–phonon coupling dynamics upon ultrafast photoexcitation is necessary for understanding the optoelectronic behavior of the semiconductor. Here, we use impulsive vibrational spectroscopy to reveal vibrational modes of methylammonium lead-bromide perovskite under electronically resonant and non-resonant conditions. We identify two excited state coherent phonons at 89 and 106 cm−1, whose phases reveal a shift of the potential energy minimum upon ultrafast photocarrier generation. This indicates the transition to a new geometry, reached after approximately 90 fs, and fully equilibrated within the phonons lifetime of about 1 ps. Our results unambiguously prove that these modes drive the crystalline distortion occurring upon photo-excitation, demonstrating the presence of polaronic effects.
Distinct epigenetic landscapes underlie the pathobiology of pancreatic cancer subtypes
Authors: Lomberk Gwen , Blum Yuna , Nicolle Rémy , Nair Asha , Gaonkar Krutika Satish , Marisa Laetitia , Mathison Angela , Sun Zhifu , Yan Huihuang , Elarouci Nabila , Armenoult Lucile , Ayadi Mira , Ordog Tamas , Lee Jeong-Heon , Oliver Gavin , Klee Eric , Moutardier Vincent , Gayet Odile , Bian Benjamin , Duconseil Pauline , Gilabert Marine , Bigonnet Martin , Garcia Stephane , Turrini Olivier , Delpero Jean-Robert , Giovannini Marc , Grandval Philippe , Gasmi Mohamed , Secq Veronique , De Reyniès Aurélien , Dusetti Nelson , Iovanna Juan , Urrutia Raul
Published: May 2018

Recent studies have offered ample insight into genome-wide expression patterns to define pancreatic ductal adenocarcinoma (PDAC) subtypes, although there remains a lack of knowledge regarding the underlying epigenomics of PDAC. Here we perform multi-parametric integrative analyses of chromatin immunoprecipitation-sequencing (ChIP-seq) on multiple histone modifications, RNA-sequencing (RNA-seq), and DNA methylation to define epigenomic landscapes for PDAC subtypes, which can predict their relative aggressiveness and survival. Moreover, we describe the state of promoters, enhancers, super-enhancers, euchromatic, and heterochromatic regions for each subtype. Further analyses indicate that the distinct epigenomic landscapes are regulated by different membrane-to-nucleus pathways. Inactivation of a basal-specific super-enhancer associated pathway reveals the existence of plasticity between subtypes. Thus, our study provides new insight into the epigenetic landscapes associated with the heterogeneity of PDAC, thereby increasing our mechanistic understanding of this disease, as well as offering potential new markers and therapeutic targets.
Elucidating the genetic architecture of reproductive ageing in the Japanese population
Authors: Horikoshi Momoko , Day Felix R. , Akiyama Masato , Hirata Makoto , Kamatani Yoichiro , Matsuda Koichi , Ishigaki Kazuyoshi , Kanai Masahiro , Wright Hollis , Toro Carlos A. , Ojeda Sergio R. , Lomniczi Alejandro , Kubo Michiaki , Ong Ken K. , Perry John. R. B.
Published: May 2018

Population studies elucidating the genetic architecture of reproductive ageing have been largely limited to European ancestries, restricting the generalizability of the findings and overlooking possible key genes poorly captured by common European genetic variation. Here, we report 26 loci (all P < 5 × 10–8) for reproductive ageing, i.e. puberty timing or age at menopause, in a non-European population (up to 67,029 women of Japanese ancestry). Highlighted genes for menopause include GNRH1, which supports a primary, rather than passive, role for hypothalamic-pituitary GnRH signalling in the timing of menopause. For puberty timing, we demonstrate an aetiological role for receptor-like protein tyrosine phosphatases by combining evidence across population genetics and pre- and peri-pubertal changes in hypothalamic gene expression in rodent and primate models. Furthermore, our findings demonstrate widespread differences in allele frequencies and effect estimates between Japanese and European associated variants, highlighting the benefits and challenges of large-scale trans-ethnic approaches.
CD4+ T cells are activated in regional lymph nodes and migrate to skin to initiate lymphedema
Authors: García Nores Gabriela D. , Ly Catherine L. , Cuzzone Daniel A. , Kataru Raghu P. , Hespe Geoffrey E. , Torrisi Jeremy S. , Huang Jung Ju , Gardenier Jason C. , Savetsky Ira L. , Nitti Matthew D. , Yu Jessie Z. , Rehal Sonia , Mehrara Babak J.
Published: May 2018

T cell-mediated responses have been implicated in the development of fibrosis, impaired lymphangiogenesis, and lymphatic dysfunction in secondary lymphedema. Here we show that CD4+ T cells are necessary for lymphedema pathogenesis by utilizing adoptive transfer techniques in CD4 knockout mice that have undergone tail skin and lymphatic excision or popliteal lymph node dissection. We also demonstrate that T cell activation following lymphatic injury occurs in regional skin-draining lymph nodes after interaction with antigen-presenting cells such as dendritic cells. CD4+ T cell activation is associated with differentiation into a mixed T helper type 1 and 2 phenotype, as well as upregulation of adhesion molecules and chemokines that promote migration to the skin. Most importantly, we find that blocking T cell release from lymph nodes using a sphingosine-1-phosphate receptor modulator prevents lymphedema, suggesting that this approach may have clinical utility.
IgG-single-chain TRAIL fusion proteins for tumour therapy
Authors: Siegemund Martin , Schneider Felix , Hutt Meike , Seifert Oliver , Müller Ines , Kulms Dagmar , Pfizenmaier Klaus , Kontermann Roland E.
Published: May 2018

Single-chain formats of TNF-related apoptosis inducing ligand (scTRAIL) can serve as effector components of tumour-associated antigen-targeted as well as non-targeted fusion proteins, being characterized by high tumour cell-specific induction of apoptosis through death receptor activation. We studied the suitability of immunoglobulin G as a scaffold for oligovalent and bispecific TRAIL fusion proteins. Thus, we developed novel targeted hexa- and dodecavalent IgG-scTRAIL molecules by fusing scTRAIL to the C-terminus of either light (LC-scTRAIL) or heavy immunoglobulin chain (HC-scTRAIL), or to both ends (LC/HC-scTRAIL) of the anti-EGFR IgG antibody hu225. The binding specificity to EGFR and death receptors was retained in all IgG-scTRAIL formats and translated into high antigen-specific bioactivity on EGFR-positive Colo205, HCT116 and WM1366 tumour cell lines, with or without sensitization to apoptosis by bortezomib. In vivo, therapeutic potential was assessed for one of the targeted variants, HC-scTRAIL, compared to the non-targeted Fc-scTRAIL. Both molecules showed a significant reduction of tumour volume and synergism with a Smac mimetic in a Colo205 xenograft tumour model. The IgG-scTRAIL format allows directing a defined, highly bioactive form of TRAIL to a wide variety of tumour antigens, enabling customized solutions for a patient-specific targeted cancer therapy with a reduced risk of side effects.
Layer-by-layer siRNA/poly(L-lysine) Multilayers on Polydopamine-coated Surface for Efficient Cell Adhesion and Gene Silencing
Authors: Hong Cheol Am , Son Ho Yeon , Nam Yoon Sung
Published: May 2018

For tissue engineering applications, small interfering RNA (siRNA) is an attractive agent for controlling cellular functions and differentiation. Although polyionic condensation of nucleic acids with polycations has been widely used for gene delivery, siRNA is not strongly associated with cationic carriers due to its low charge density and rigid molecular structures. The use of an excess amount of cationic carriers is often used for siRNA condensation, though they can induce severe cytotoxicity. Here we introduce the self-assembly of siRNA with mild polyelectrolytes into multilayers for efficient gene silencing during cell proliferation. The multilayers were prepared through the sequential layer-by-layer deposition of siRNA and poly-L-lysine (PLL) on a polydopamine-coated substrate. The cells, grown on the siRNA/PLL multilayers, exhibited a remarkable inhibition of the expression of target genes as compared to the use of scrambled siRNA. The gene silencing efficiency depends on the number of siRNA layers within a multilayer. This result indicates that siRNA/PLL multilayers can be potentially utilized for efficient surface-mediated siRNA delivery.
Novel haloarchaeon Natrinema thermophila having the highest growth temperature among haloarchaea with a large genome size
Authors: Kim Yeon Bee , Kim Joon Yong , Song Hye Seon , Lee Changsu , Ahn Seung Woo , Lee Se Hee , Jung Min Young , Rhee Jin-Kyu , Kim Juseok , Hyun Dong-Wook , Bae Jin-Woo , Roh Seong Woon
Published: May 2018

Environmental temperature is one of the most important factors for the growth and survival of microorganisms. Here we describe a novel extremely halophilic archaeon (haloarchaea) designated as strain CBA1119Tisolated from solar salt. Strain CBA1119Thad the highest maximum and optimal growth temperatures (66 °C and 55 °C, respectively) and one of the largest genome sizes among haloarchaea (5.1 Mb). It also had the largest number of strain-specific pan-genome orthologous groups and unique pathways among members of the genusNatrinemain the classHalobacteria. A dendrogram based on the presence/absence of genes and a phylogenetic tree constructed based on OrthoANI values highlighted the particularities of strain CBA1119Tas compared to otherNatrinemaspecies and other haloarchaea members. The large genome of strain CBA1119Tmay provide information on genes that confer tolerance to extreme environmental conditions, which may lead to the discovery of other thermophilic strains with potential applications in industrial biotechnology.
Sensory representation of an auditory cued tactile stimulus in the posterior parietal cortex of the mouse
Authors: Mohan Hemanth , Gallero-Salas Yasir , Carta Stefano , Sacramento João , Laurenczy Balazs , Sumanovski Lazar T. , de Kock Christiaan P. J. , Helmchen Fritjof , Sachidhanandam Shankar
Published: May 2018

Sensory association cortices receive diverse inputs with their role in representing and integrating multi-sensory content remaining unclear. Here we examined the neuronal correlates of an auditory-tactile stimulus sequence in the posterior parietal cortex (PPC) using 2-photon calcium imaging in awake mice. We find that neuronal subpopulations in layer 2/3 of PPC reliably represent texture-touch events, in addition to auditory cues that presage the incoming tactile stimulus. Notably, altering the flow of sensory events through omission of the cued texture touch elicited large responses in a subset of neurons hardly responsive to or even inhibited by the tactile stimuli. Hence, PPC neurons were able to discriminate not only tactile stimulus features (i.e., texture graininess) but also between the presence and omission of the texture stimulus. Whereas some of the neurons responsive to texture omission were driven by looming-like auditory sounds others became recruited only with tactile sensory experience. These findings indicate that layer 2/3 neuronal populations in PPC potentially encode correlates of expectancy in addition to auditory and tactile stimuli.
Embryonic POU5F1 is Required for Expanded Bovine Blastocyst Formation
Authors: Daigneault Bradford W. , Rajput Sandeep , Smith George W. , Ross Pablo J.
Published: May 2018

POU5F1 is a transcription factor and master regulator of cell pluripotency with indispensable roles in early embryo development and cell lineage specification. The role of embryonic POU5F1 in blastocyst formation and cell lineage specification differs between mammalian species but remains completely unknown in cattle. The CRISPR/Cas9 system was utilized for targeted disruption of the POU5F1 gene by direct injection into zygotes. Disruption of the bovine POU5F1 locus prevented blastocyst formation and was associated with embryonic arrest at the morula stage. POU5F1 knockout morulas developed at a similar rate as control embryos and presented a similar number of blastomeres by day 5 of development. Initiation of SOX2 expression by day 5 of development was not affected by lack of POU5F1. On the other hand, CDX2 expression was aberrant in embryos lacking POU5F1. Notably, the phenotype observed in bovine POU5F1 knockout embryos reveals conserved functions associated with loss of human embryonic POU5F1 that differ from Pou5f1- null mice. The similarity observed in transcriptional regulation of early embryo development between cattle and humans combined with highly efficient gene editing techniques make the bovine a valuable model for human embryo biology with expanded applications in agriculture and assisted reproductive technologies.
Author Correction: Heart Failure Phenotypes Induced by Knockdown of DAPIT in Zebrafish: A New Insight into Mechanism of Dilated Cardiomyopathy
Authors: Nagata Yoji , Yamagishi Masakazu , Konno Tetsuo , Nakanishi Chiaki , Asano Yoshihiro , Ito Shin , Nakajima Yuri , Seguchi Osamu , Fujino Noboru , Kawashiri Masa-aki , Takashima Seiji , Kitakaze Masafumi , Hayashi Kenshi
Published: May 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Consistent prediction of GO protein localization
Authors: Spetale Flavio E. , Arce Debora , Krsticevic Flavia , Bulacio Pilar , Tapia Elizabeth
Published: May 2018

The GO-Cellular Component (GO-CC) ontology provides a controlled vocabulary for the consistent description of the subcellular compartments or macromolecular complexes where proteins may act. Current machine learning-based methods used for the automated GO-CC annotation of proteins suffer from the inconsistency of individual GO-CC term predictions. Here, we present FGGA-CC+, a class of hierarchical graph-based classifiers for the consistent GO-CC annotation of protein coding genes at the subcellular compartment or macromolecular complex levels. Aiming to boost the accuracy of GO-CC predictions, we make use of the protein localization knowledge in the GO-Biological Process (GO-BP) annotations to boost the accuracy of GO-CC prediction. As a result, FGGA-CC+ classifiers are built from annotation data in both the GO-CC and GO-BP ontologies. Due to their graph-based design, FGGA-CC+ classifiers are fully interpretable and their predictions amenable to expert analysis. Promising results on protein annotation data from five model organisms were obtained. Additionally, successful validation results in the annotation of a challenging subset of tandem duplicated genes in the tomato non-model organism were accomplished. Overall, these results suggest that FGGA-CC+ classifiers can indeed be useful for satisfying the huge demand of GO-CC annotation arising from ubiquitous high throughout sequencing and proteomic projects.
Single Nucleotide Polymorphisms in the G-Protein Coupled Receptor Kinase 5 (GRK5) Gene are associated with Plasma LDL-Cholesterol Levels in Humans
Authors: Lutz Stefan Z. , Falcenberg Mathias , Machicao Fausto , Peter Andreas , Kächele Martin , Randrianarisoa Elko , Lehn-Stefan Angela , Wagner Robert , Machann Jürgen , Schick Fritz , Heni Martin , Ullrich Axel , Fritsche Andreas , Stefan Norbert , Häring Hans-Ulrich , Staiger Harald , Kantartzis Konstantinos
Published: May 2018

Genetically modified mice models suggest an important role for G-protein-coupled receptor kinase 5 (GRK5) in the pathophysiology of obesity and related disorders. We investigated whether single nucleotide polymorphisms (SNPs) in the gene encoding GRK5 affect cardiometabolic traits in humans. We genotyped 3 common SNPs in intron 1 (rs1980030, rs10466210, rs9325562) and one SNP in intron 3 (rs10886471) of GRK5 in 2332 subjects at risk for type 2 diabetes. Total- and visceral fat mass were measured by magnetic resonance (MR) tomography and liver fat content by 1H-MR spectroscopy. Insulin secretion and sensitivity were estimated during an OGTT and measured during the euglycemic, hyperinsulinemic clamp (n = 498). Carriers of the minor allele of rs10466210 and rs1980030 had higher total- and LDL-cholesterol levels (p = 0.0018 and p = 0.0031, respectively, for rs10466210; p = 0.0035 and p = 0.0081, respectively, for rs1980030), independently of gender, age, BMI and lipid-lowering drugs. The effects of rs10466210 withstood Bonferroni correction. Similar associations were observed with apolipoprotein B levels (p = 0.0034 and p = 0.0122, respectively). Carriers of the minor allele of rs10466210 additionally displayed a trend for higher intima-media thickness of the carotid artery (p = 0.075). GRK5 may represent a novel target for strategies aiming at lowering LDL-cholesterol levels and at modifying cardiovascular risk.
Early Salmonella Typhimurium infection in pigs disrupts Microbiome composition and functionality principally at the ileum mucosa
Authors: Argüello Héctor , Estellé Jordi , Zaldívar-López Sara , Jiménez-Marín Ángeles , Carvajal Ana , López-Bascón Mª Asunción , Crispie Fiona , O’Sullivan Orla , Cotter Paul D. , Priego-Capote Feliciano , Morera Luis , Garrido Juan J.
Published: May 2018

Salmonella is a major foodborne pathogen which successfully infects animal species for human consumption such as swine. The pathogen has a battery of virulence factors which it uses to colonise and persist within the host. The host microbiota may play a role in resistance to, and may also be indirectly responsible from some of the consequences of, Salmonella infection. To investigate this, we used 16S rRNA metagenomic sequencing to determine the changes in the gut microbiota of pigs in response to infection by Salmonella Typhimurium at three locations: ileum mucosa, ileum content and faeces. Early infection (2 days post-infection) impacted on the microbiome diversity at the mucosa, reflected in a decrease in representatives of the generally regarded as desirable genera (i.e., Bifidobacterium and Lactobacillus). Severe damage in the epithelium of the ileum mucosa correlated with an increase in synergistic (with respect to Salmonella infection; Akkermansia) or opportunistically pathogenic bacteria (Citrobacter) and a depletion in anaerobic bacteria (Clostridium spp., Ruminococcus, or Dialliser). Predictive functional analysis, together with metabolomic analysis revealed changes in glucose and lipid metabolism in infected pigs. The observed changes in commensal healthy microbiota, including the growth of synergistic or potentially pathogenic bacteria and depletion of beneficial or competing bacteria, could contribute to the pathogen’s ability to colonize the gut successfully. The findings from this study could be used to form the basis for further research aimed at creating intervention strategies to mitigate the effects of Salmonella infection.
Amelioration of Experimental autoimmune encephalomyelitis and DSS induced colitis by NTG-A-009 through the inhibition of Th1 and Th17 cells differentiation
Authors: Acharya Suman , Timilshina Maheshwor , Jiang Liyuan , Neupane Sabita , Choi Dong-Young , Park Sang Won , Lee Sang Yeul , Jeong Byeong-Seon , Kim Jung-Ae , Nam Tae-gyu , Chang Jae-Hoon
Published: May 2018

CD4+T cells are the central for the mammalian adaptive immune system. Naïve CD4+T cells mainly differentiate in to pro-inflammatory Th1, Th2 and Th17 cells upon antigenic stimulation. IFN-γ secreting Th1 cells and IL-17 secreting Th17 cells are found to play key roles in autoimmune diseases like multiple sclerosis (MS) and ulcerative colitis (UC). In this study we found NTG-A-009, 6-aminopyridin-3-ol, has great inhibitory effect onin vitrodifferentiation of Th1 and Th17 cells without affecting regulatory T cells. Moreover, NTG-A-009 had no effect on CD4+T cell proliferation and viability.In vivotreatment has shown that NTG-A-009 has ameliorated experimental autoimmune encephalomyelitis (EAE) and dextran sulfate sodium (DSS) induced colitis through the inhibition of Th1 and Th17 cells differentiation. Mechanistically, NTG-A-009 suppressed Th1 and Th17 cells differentiation via the modulation of JAK/STAT signaling pathway. Thus, our data demonstrated that NTG-A-009 ameliorated inflammation through the inhibition of Th1 and Th17 cells generation making it a potential therapeutic candidate for the treatment of inflammatory diseases.
A Simulation Model for Coupled Heat Transfer and Moisture Transport under the Action of Heat Source in Unsaturated Soils
Authors: Jin Hua , Guo Yi , Deng Hongkai , Qi Xin , Gui Jinpeng
Published: May 2018

Ground source heat pump (GSHP) system has been installed as the air-conditioning system worldwide due to it has the characteristics of high efficiency, easy access and environmental protection. Since ground heat exchanger (GHE) plays a key role in the performance of GSHPs, many models of GHE have been proposed to simulate temperature distribution around the borehole. However, most of these models depict only the heat conduction process between buried pipes and surrounding soil based on the line source model or cylindrical source model. And these models do not consider water transfer under the action of heat source, which can cause some prediction errors. The objective of this study is to provide a numerical model to simulate the spatiotemporal distribution of temperature and moisture caused by a GHE with constant temperature in unsaturated soils. The numerical model is developed by establishing two tridiagonal matrices and adopting Thomas algorithm to achieve the programming. The experiment is operated at the Taiyuan University of Technology and the comparisons between modeled and experimental data prove the high accuracy of this model. The model shows significant engineering values in designs and operations of GSHP.
Photonic glass for high contrast structural color
Authors: Shang Guoliang , Maiwald Lukas , Renner Hagen , Jalas Dirk , Dosta Maksym , Heinrich Stefan , Petrov Alexander , Eich Manfred
Published: May 2018

Non-iridescent structural colors based on disordered arrangement of monodisperse spherical particles, also called photonic glass, show low color saturation due to gradual transition in the reflectivity spectrum. No significant improvement is usually expected from particles optimization, as Mie resonances are broad for small dielectric particles with moderate refractive index. Moreover, the short range order of a photonic glass alone is also insufficient to cause sharp spectral features. We show here, that the combination of a well-chosen particle geometry with the short range order of a photonic glass has strong synergetic effects. Using a first-order approximation and an Ewald sphere construction the reflectivity of such structures can be related to the Fourier transform of the permittivity distribution. The Fourier transform required for a highly saturated color can be achieved by tailoring the substructure of the motif. We show that this can be obtained by choosing core-shell particles with a non-monotonous refractive index distribution from the center of the particle through the shell and into the background material. The first-order theoretical predictions are confirmed by numerical simulations.
Identification and tissue distribution of chemosensory protein and odorant binding protein genes in Tropidothorax elegans Distant (Hemiptera: Lygaeidae)
Authors: Song Yue-Qin , Sun Hui-Zhong , Du Jun
Published: May 2018

Tropidothorax elegans Distant (Hemiptera: Lygaeidae) is an insect pest that inflicts damage to vegetables and flowering plants across China. The olfactory system regulates insect behavior, such as feeding, mating, oviposition and predator avoidance. Odorant-binding proteins (OBPs) and the chemosensory proteins (CSPs) are two groups of small soluble proteins that initiate olfactory signal transduction in insects. In this study, we generated antennal transcriptomes of male and female T. elegans, and identified 19 putative OBP (14 classic OBPs and five plus-C OBPs) and seven CSP genes. Through real-time quantitative PCR analysis, we found that 14 of the 19 OBP genes were highly expressed in the antennae of both adult females and males, and 3 OBP genes were expressed higher in the antennae of males than females. Some OBP genes were also highly expressed in the legs or wings. Three CSP genes were highly expressed in the antennae of both sexes, and TeleCSP7 showed higher expression in male antennae compare to females. Interestingly, one CSP gene, TeleCSP2, was expressed in all olfactory tissues. Our results provide molecular insights into further investigating of the olfactory system of an important plant pest, T. elegans.
Noninvasive low-cycle fatigue characterization at high depth with photoacoustic eigen-spectrum analysis
Authors: Gao Xiaoxiang , Tao Chao , Zhu Rong , Liu Xiaojun
Published: May 2018

In this work, photoacoustic eigen-spectrum analysis was proposed for noninvasively characterizing the mechanical properties of materials. We theoretically predicted the relationship between the photoacoustic eigen-spectra of cylindrical optical absorbers and their mechanical properties. Experimental measurements of eigen-spectra extracted from photoacoustic coda waves agreed well with the theoretical predictions. We then applied the photoacoustic eigen-spectrum analysis for contactless monitoring of low-cycle fatigue damage. Experiments showed that the photoacoustic eigen-spectra were closely related to the degree of low-cycle fatigue. This study might enhance the contrast of photoacoustic imaging ford mechanical characterization.
The anxiolytic-like effects of ginsenoside Rg3 on chronic unpredictable stress in rats
Authors: Xu Jia-ning , Chen Li-fang , Su Jun , Liu Zhi-li , Chen Jie , Lin Qing-fen , Mao Wei-dong , Shen Dong
Published: May 2018

The present study is to evaluate the anxiolytic-like activities underlying ginsenoside Rg3 (GRg3). The anxiolytic-like activities were induced by GRg3 (20 and 40 mg/kg, i.g), evidenced by blocking the decreased time and entries in the open arms in elevated plus maze test and by reversing the increased latency to feed in novelty-suppressed feeding test. In addition, the decreased levels on progesterone, allopregnanolone, serotonin (5-HT) in the prefrontal cortex and hippocampus of chronic unpredictable stress (CUS) were blocked by GRg3 (20 and 40 mg/kg, i.g). Furthermore, the increased corticotropin releasing hormone, corticosterone and adrenocorticotropic hormone were blocked by GRg3 (20 and 40 mg/kg, i.g). Collectively, the anxiolytic-like effects produced by GRg3 were associated with the normalization of neurosteroids biosynthesis, serotonergic system as well as HPA axis dysfunction.
Association between urinary sodium excretion and uric acid, and its interaction on the risk of prehypertension among Chinese young adults
Authors: Wang Yang , Hu Jia-Wen , Qu Peng-Fei , Wang Ke-Ke , Yan Yu , Chu Chao , Zheng Wen-Ling , Xu Xian-Jing , Lv Yong-Bo , Ma Qiong , Gao Ke , Yuan Yue , Li Hao , Yuan Zu-Yi , Mu Jian-Jun
Published: May 2018

High uric acid (UA) level and high salt intake are reportedly associated with cardiovascular disease. This study investigated the association between UA and urinary sodium excretion, as well as its interaction on the risk of prehypertension. A total of 1869 participants without hypertension were recruited from a previously established cohort in Shaanxi Province, China. The participants were classified as normotensive or prehypertensive on the basis of their blood pressure. Increasing quartiles of sodium excretion were associated with high urinary UA/creatinine levels in prehypertensive participants. Estimated sodium excretion positively correlated with urinary UA/creatinine excretions in the prehypertensive group. In addition, the multivariate-adjusted odds ratios for prehypertension compared with normotension were 1.68 (1.27–2.22) for sodium excretion and 1.71 (1.21–2.42) for serum UA. Increasing sodium excretion and serum UA were associated with higher risk of prehypertension. Compared with the lowest quartiles, the highest sodium excretion and serum UA quartiles entailed 3.48 times greater risk of prehypertension. Sodium excretion is associated with urinary UA excretion in prehypertensive participants. The present study shows that high levels of salt intake and serum UA simultaneously are associated with a higher risk of prehypertension.
CRISPR/Cas9 system targeting regulatory genes of HIV-1 inhibits viral replication in infected T-cell cultures
Authors: Ophinni Youdiil , Inoue Mari , Kotaki Tomohiro , Kameoka Masanori
Published: May 2018

The CRISPR/Cas9 system provides a novel and promising tool for editing the HIV-1 proviral genome. We designed RNA-guided CRISPR/Cas9 targeting the HIV-1 regulatory genestatandrevwith guide RNAs (gRNA) selected from each gene based on CRISPR specificity and sequence conservation across six major HIV-1 subtypes. Each gRNA was cloned into lentiCRISPRv2 before co-transfection to create a lentiviral vector and transduction into target cells. CRISPR/Cas9 transduction into 293 T and HeLa cells stably expressing Tat and Rev proteins successfully abolished the expression of each protein relative to that in non-transduced and gRNA-absent vector-transduced cells. Tat functional assays showed significantly reduced HIV-1 promoter-driven luciferase expression aftertat-CRISPR transduction, while Rev functional assays revealed abolished gp120 expression afterrev-CRISPR transduction. The target gene was mutated at the Cas9 cleavage site with high frequency and various indel mutations. Conversely, no mutations were detected at off-target sites and Cas9 expression had no effect on cell viability. CRISPR/Cas9 was further tested in persistently and latently HIV-1-infected T-cell lines, in which p24 levels were significantly suppressed even after cytokine reactivation, and multiplexing all six gRNAs further increased efficiency. Thus, the CRISPR/Cas9 system targeting HIV-1 regulatory genes may serve as a favorable means to achieve functional cures.