bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal Development of Gut Microbiota in Triclocarban Exposed Pregnant and Neonatal Rats
Authors: Kennedy Rebekah C. , Fling Russell R. , Robeson Michael S. , Saxton Arnold M. , Donnell Robert L. , Darcy John L. , Bemis David A. , Liu Jiang , Zhao Ling , Chen Jiangang
Published: September 2016

Alteration of gut microbial colonization process may influence susceptibility of the newborn/infant to infectious and chronic disease. Infectious disease risk leads to widespread use of non-prescription antimicrobials in household products such as Triclocarban (TCC), an antimicrobial compound in personal care products. TCC concentrates in and is transferred through the milk to suckling offspring. TCC exposure during gestation and lactation significantly reduced phylogenetic diversity (PD) among exposed dams and neonates. Among dams using weighted UniFrac distances, TCC induced significant dysbiosis of gut microbiota by gestational day (GD) 18, a trend that continued after delivery. Similarly, an overall restructuring of gut microbiota occurred in neonates. By postnatal day (PND) 12, communities separated based on exposure status and became significantly different at PND 16. The ability of TCC to drive microbial dysbiosis warrants future investigation to evaluate the safety of non-prescription antimicrobial use, including TCC, during critical exposure windows.
Synthesis and Evaluation of 18F-labeled Pyridaben Analogues for Myocardial Perfusion Imaging in Mice, Rats and Chinese mini-swine
Authors: Mou Tiantian , Zhao Zuoquan , You Linyi , Li Yesen , Wang Qian , Fang Wei , Lu Jie , Peng Cheng , Zhang Xianzhong
Published: September 2016

This study reports three novel 18F-labeled pyridaben analogues for potential myocardial perfusion imaging (MPI). Three precursors and the corresponding nonradioactive compounds were synthesized and characterized. The radiolabeled tracers were obtained by substituting tosyl with 18F. The total radiosynthesis time of these tracers was 70–90 min. Typical decay-corrected radiochemical yields were 47–58%, with high radiochemical purities (>98%). Tracers were evaluated as MPI agents in vitro, ex vivo and in vivo. In the mouse biodistribution study, all three radiotracers showed high initial heart uptake (34–54% ID/g at 2 min after injection) and fast liver clearance. In the microPET imaging study, [18F]Fmpp2 produced heart images with good quality in both mice and rats. In the whole-body PET/CT images of mini-swine, [18F]Fmpp2 showed excellent initial heart standardized uptake value (SUV) (7.12 at 5 min p.i.) and good retention (5.75 at 120 min p.i.). The heart/liver SUV ratios were 4.12, 5.42 and 5.99 at 30, 60 and 120 min after injection, respectively. The favorable biological properties of [18F]Fmpp2 suggest that it is worth further investigation as a potential MPI agent.
Perception and recognition of faces in adolescence
Authors: Fuhrmann D. , Knoll L. J. , Sakhardande A. L. , Speekenbrink M. , Kadosh K. C. , Blakemore S. -J.
Published: September 2016

Most studies on the development of face cognition abilities have focussed on childhood, with early maturation accounts contending that face cognition abilities are mature by 3–5 years. Late maturation accounts, in contrast, propose that some aspects of face cognition are not mature until at least 10 years. Here, we measured face memory and face perception, two core face cognition abilities, in 661 participants (397 females) in four age groups (younger adolescents (11.27–13.38 years); mid-adolescents (13.39–15.89 years); older adolescents (15.90–18.00 years); and adults (18.01–33.15 years)) while controlling for differences in general cognitive ability. We showed that both face cognition abilities mature relatively late, at around 16 years, with a female advantage in face memory, but not in face perception, both in adolescence and adulthood. Late maturation in the face perception task was driven mainly by protracted development in identity perception, while gaze perception abilities were already comparatively mature in early adolescence. These improvements in the ability to memorize, recognize and perceive faces during adolescence may be related to increasing exploratory behaviour and exposure to novel faces during this period of life.
Fully Automatic System for Accurate Localisation and Analysis of Cephalometric Landmarks in Lateral Cephalograms
Authors: Lindner Claudia , Wang Ching-Wei , Huang Cheng-Ta , Li Chung-Hsing , Chang Sheng-Wei , Cootes Tim F.
Published: September 2016

Cephalometric tracing is a standard analysis tool for orthodontic diagnosis and treatment planning. The aim of this study was to develop and validate a fully automatic landmark annotation (FALA) system for finding cephalometric landmarks in lateral cephalograms and its application to the classification of skeletal malformations. Digital cephalograms of 400 subjects (age range: 7–76 years) were available. All cephalograms had been manually traced by two experienced orthodontists with 19 cephalometric landmarks, and eight clinical parameters had been calculated for each subject. A FALA system to locate the 19 landmarks in lateral cephalograms was developed. The system was evaluated via comparison to the manual tracings, and the automatically located landmarks were used for classification of the clinical parameters. The system achieved an average point-to-point error of 1.2 mm, and 84.7% of landmarks were located within the clinically accepted precision range of 2.0 mm. The automatic landmark localisation performance was within the inter-observer variability between two clinical experts. The automatic classification achieved an average classification accuracy of 83.4% which was comparable to an experienced orthodontist. The FALA system rapidly and accurately locates and analyses cephalometric landmarks in lateral cephalograms, and has the potential to significantly improve the clinical work flow in orthodontic treatment.
Self-assembly formation of Bi-functional Co3O4/MnO2-CNTs hybrid catalysts for achieving both high energy/power density and cyclic ability of rechargeable zinc-air battery
Authors: Xu Nengneng , Liu Yuyu , Zhang Xia , Li Xuemei , Li Aijun , Qiao Jinli , Zhang Jiujun
Published: September 2016

α-MnO2nanotubes-supported Co3O4(Co3O4/MnO2) and its carbon nanotubes (CNTs)-hybrids (Co3O4/MnO2-CNTs) have been successfully developed through a facile two-pot precipitation reaction and hydrothermal process, which exhibit the superior bi-functional catalytic activity for both ORR and OER. The high performance is believed to be induced by the hybrid effect among MnO2nanotubes, hollow Co3O4and CNTs, which can produce a synergetic enhancement. When integrated into the practical primary and electrochemically rechargeable Zn-air batteries, such a hybrid catalyst can give a discharge peak power density as high as 450 mW cm−2. At 1.0 V of cell voltage, a current density of 324 mA cm−2is achieved. This performance is superior to all reported non-precious metal catalysts in literature for zinc-air batteries and significantly outperforms the state-of-the-art platinum-based catalyst. Particularly, the rechargeable Zn-air battery can be fabricated into all-solid-state one through a simple solid-state approach, which exhibits an excellent peak power density of 62 mW cm−2, and the charge and discharge potentials remain virtually unchanged during the overall cycles, which is comparable to the one with liquid electrolyte.
Diurnal variations of hormonal secretion, alertness and cognition in extreme chronotypes under different lighting conditions
Authors: Maierova L. , Borisuit A. , Scartezzini J.-L. , Jaeggi S. M. , Schmidt C. , Münch M.
Published: September 2016

Circadian rhythms in physiology and behavior are modulated by external factors such as light or temperature. We studied whether self-selected office lighting during the habitual waking period had a different impact on alertness, cognitive performance and hormonal secretion in extreme morning and evening chronotypes (N = 32), whose preferred bed- and wake-up times differed by several hours. The self-selected lighting condition was compared with constant bright light and a control condition in dim light. Saliva samples for hormonal analyses, subjective ratings of alertness, wellbeing, visual comfort and cognitive performance were regularly collected. Between the self-selected and the bright, but not the dim lighting condition, the onset of melatonin secretion in the evening (as marker for circadian phase) was significantly different for both chronotypes. Morning chronotypes reported a faster increase in sleepiness during the day than evening chronotypes, which was associated with higher cortisol secretion. Wellbeing, mood and performance in more difficult cognitive tasks were better in bright and self-selected lighting than in dim light for both chronotypes, whereas visual comfort was best in the self-selected lighting. To conclude, self-selection of lighting at work might positively influence biological and cognitive functions, and allow for inter-individual differences.
Identification of antisense long noncoding RNAs that function as SINEUPs in human cells
Authors: Schein Aleks , Zucchelli Silvia , Kauppinen Sakari , Gustincich Stefano , Carninci Piero
Published: September 2016

Mammalian genomes encode numerous natural antisense long noncoding RNAs (lncRNAs) that regulate gene expression. Recently, an antisense lncRNA to mouse Ubiquitin carboxyl-terminal hydrolase L1 (Uchl1) was reported to increase UCHL1 protein synthesis, representing a new functional class of lncRNAs, designated as SINEUPs, for SINE element-containing translation UP-regulators. Here, we show that an antisense lncRNA to the human protein phosphatase 1 regulatory subunit 12A (PPP1R12A), named as R12A-AS1, which overlaps with the 5′ UTR and first coding exon of the PPP1R12A mRNA, functions as a SINEUP, increasing PPP1R12A protein translation in human cells. The SINEUP activity depends on the aforementioned sense-antisense interaction and a free right Alu monomer repeat element at the 3′ end of R12A-AS1. In addition, we identify another human antisense lncRNA with SINEUP activity. Our results demonstrate for the first time that human natural antisense lncRNAs can up-regulate protein translation, suggesting that endogenous SINEUPs may be widespread and present in many mammalian species.
Polycomb repressive complex 2 facilitates the nuclear export of the influenza viral genome through the interaction with M1
Authors: Asaka Masamitsu N. , Kawaguchi Atsushi , Sakai Yuri , Mori Kotaro , Nagata Kyosuke
Published: September 2016

The organization of nuclear domains is crucial for biological events including virus infection. Newly synthesized influenza viral genome forms viral ribonucleoprotein (vRNP) complexes and is exported from the nucleus to the cytoplasm through a CRM1-dependent pathway mediated by viral proteins M1 and NS2. However, the spatio-temporal regulation of the progeny vRNP in the nucleus is still unclear. Here we found that polycomb repressive complex 2 (PRC2), which contains a methyltransferase subunit EZH2 and catalyzes histone H3K27me3 for the formation of facultative heterochromatin, is a positive factor for the virus production. Depletion of PRC2 complex showed the nuclear accumulation of vRNP and the reduction of M1-vRNP complex formation. We also found that PRC2 complex directly binds to M1 and facilitates the interaction of M1 with vRNP. In conclusion, we propose that the progeny vRNP could be recruited to facultative heterochromatin and assembled into the export complex mediated by PRC2 complex.
Portable microsystem integrates multifunctional dielectrophoresis manipulations and a surface stress biosensor to detect red blood cells for hemolytic anemia
Authors: Sang Shengbo , Feng Qiliang , Jian Aoqun , Li Huiming , Ji Jianlong , Duan Qianqian , Zhang Wendong , Wang Tao
Published: September 2016

Hemolytic anemia intensity has been suggested as a vital factor for the growth of certain clinical complications of sickle cell disease. However, there is no effective and rapid diagnostic method. As a powerful platform for bio-particles testing, biosensors integrated with microfluidics offer great potential for a new generation of portable point of care systems. In this paper, we describe a novel portable microsystem consisting of a multifunctional dielectrophoresis manipulations (MDM) device and a surface stress biosensor to separate and detect red blood cells (RBCs) for diagnosis of hemolytic anemia. The peripheral circuit to power the interdigitated electrode array of the MDM device and the surface stress biosensor test platform were integrated into a portable signal system. The MDM includes a preparing region, a focusing region, and a sorting region. Simulation and experimental results show the RBCs trajectories when they are subjected to the positive DEP force, allowing the successful sorting of living/dead RBCs. Separated RBCs are then transported to the biosensor and the capacitance values resulting from the variation of surface stress were measured. The diagnosis of hemolytic anemia can be realized by detecting RBCs and the portable microsystem provides the assessment to the hemolytic anemia patient.
HSPA12B Attenuated Acute Myocardial Ischemia/reperfusion Injury via Maintaining Endothelial Integrity in a PI3K/Akt/mTOR-dependent Mechanism
Authors: Kong Qiuyue , Dai Leyang , Wang Yana , Zhang Xiaojin , Li Chuanfu , Jiang Surong , Li Yuehua , Ding Zhengnian , Liu Li
Published: September 2016

Endothelial damage is a critical mediator of myocardial ischemia/reperfusion (I/R) injury. HSPA12B is an endothelial-cell-specifically expressed heat shock protein. However, the roles of HSPA12B in acute myocardial I/R injury is unknown. Here we reported that myocardial I/R upregulated HSPA12B expression in ventricular tissues and endothelial overexpression of HSPA12B in transgenic mice (Tg) limited infarct size, attenuated cardiac dysfunction and improved cardiomyocyte survival compared with their wild type littermates. These improvements were accompanied with the diminished myocardial no-reflow phenomenon, decreased microvascular leakage and better maintained endothelial tight junctions. The I/R-evoked neutrophil infiltration was also suppressed in Tg hearts compared with its wild type (WT) littermates. Moreover, Tg hearts exhibited the enhanced activation of PI3K/Akt//mTOR signaling following I/R challenge. However, pharmacological inhibition of PI3K abolished the HSPA12B-induced cardioprotection against myocardial I/R injury. The data demonstrate for the first time that the endothelial HSPA12B protected hearts against myocardial I/R injury. This cardioprotective action of HSPA12B was mediated, at least in part, by improving endothelial integrity in a PI3K/Akt/mTOR-dependent mechanism. Our study suggests that targeting endothelial HSPA12B could be an alternative approach for the management of patients with myocardial I/R injury.
Two novel AGXT mutations identified in primary hyperoxaluria type-1 and distinct morphological and structural difference in kidney stones
Authors: Wang Cui , Lu Jingru , Lang Yanhua , Liu Ting , Wang Xiaoling , Zhao Xiangzhong , Shao Leping
Published: September 2016

Primary hyperoxaluria type 1 (PH1) is a rare genetic disease characterized by excessive oxalate accumulation in plasma and urine, resulting in various phenotypes because of allelic and clinical heterogeneity. This study aimed to detect disease-associated genetic mutations in three PH1 patients in a Chinese family. All AGXT exons and 3 common polymorphisms which might synergistically interact with mutations, including P11L, I340 M and IVSI+74 bp were analyzed by direct sequencing in all family members. It demonstrated that in each of three patients, a previously reported nonsense mutation p.R333* was in cis with a novel missense mutation p.M49L in the minor allele characterized by the polymorphism of 74-bp duplication in intron 1, while the other novel missense mutation p.N72I was in trans with both p.R333* and P.M49L in the major allele. Kidney stones from two sibling patients were also observed though stereomicroscopic examination and scanning electron microscopy. Distinct morphological and inner-structure differences in calculi were noticed, suggesting clinical heterozygosity of PH1 to a certain extent. In brief, two novel missense mutations were identified probably in association with PH1, a finding which should provide an accurate tool for prenatal diagnosis, genetic counseling and screening for potential presymptomatic individuals.
Effects of Methotrexate in a Rabbit Model of In-Stent Neoatherosclerosis: An Optical Coherence Tomography Study
Authors: Zhang Ruoxi , Chen Shuyuan , Zhang Hui , Liu Qi , Xing Jianpang , Zhao Qi , Wang Yu , Yu Bo , Hou Jingbo
Published: September 2016

This study used optical coherence tomography (OCT) to investigate the effects of systemic methotrexate, in combination with a drug-eluting stent, on in-stent neoatherosclerosis in a rabbit model. Sirolimus-eluting stents were surgically implanted in the right common carotid arteries of 200 male New Zealand White rabbits; the animals received a high-fat diet, beginning one week before stent implantation. Each animal was randomly assigned to 1 of 4 groups, receiving intravenous injections of either methotrexate (0.4 mg/kg) or placebo weekly for 4 or 12 weeks. Stented arterial segments were harvested after stenting for 4 or 12 weeks, and processed for OCT and histological analysis. Prior to harvesting the arterial segments, blood was collected for the determinations of cytokine levels. Compared with the control animals, the methotrexate-treated animals showed lower rates of lipid-rich intima and per-strut low-signal intensity layers, smaller neointimal areas, and reduced neointimal thickness; larger fibrous cap thicknesses and smaller lumen areas were also seen in the animals receiving methotrexate. The levels of serum interleukin, adhesion molecules, and nuclear factor-κB p65 decreased and IL-10 level increased in the methotrexate-treated animals. Targeting the pro-inflammatory pathways may be an effective way to prevent restenosis without the long-term risk of late thrombosis.
Antiviral activities of peptide-based covalent inhibitors of the Enterovirus 71 3C protease
Authors: Tan Yong Wah , Ang Melgious Jin Yan , Lau Qiu Ying , Poulsen Anders , Ng Fui Mee , Then Siew Wen , Peng Jianhe , Hill Jeffrey , Hong Wan Jin , Chia Cheng San Brian , Chu Justin Jang Hann
Published: September 2016

Hand, Foot and Mouth Disease is a highly contagious disease caused by a range of human enteroviruses. Outbreaks occur regularly, especially in the Asia-Pacific region, putting a burden on public healthcare systems. Currently, there is no antiviral for treating this infectious disease and the only vaccines are limited to circulation in China, presenting an unmet medical need that needs to be filled urgently. The human enterovirus 3 C protease has been deemed a plausible drug target due to its essential roles in viral replication. In this study, we designed and synthesized 10 analogues of the Rhinovirus 3 C protease inhibitor, Rupintrivir and tested their 3 C protease inhibitory activities followed by a cellular assay using human enterovirus 71 (EV71)-infected human RD cells. Our results revealed that a peptide-based compound containing a trifluoromethyl moiety to be the most potent analogue, with an EC50 of 65 nM, suggesting its potential as a lead for antiviral drug discovery.
A Francisella-like endosymbiont in the Gulf Coast tick evolved from a mammalian pathogen
Authors: Gerhart Jonathan G. , Moses Abraham S. , Raghavan Rahul
Published: September 2016

Ticks (order Ixodida) vector pathogenic bacteria that cause diseases in humans and other mammals. They also contain bacteria that are closely related to pathogens but function as endosymbionts that provide nutrients that are missing from mammalian blood—their sole food source. For instance, mammalian pathogens such as Coxiella burnetii and Francisella tularensis, as well as Coxiella-like and Francisella-like endosymbionts (CLEs and FLEs, respectively) occur in ticks worldwide. However, it is not clear whether the pathogens evolved from symbionts or symbionts from pathogens. Recent studies have indicated that C. burnetii likely originated from a tick-associated ancestor, but the origins of FLEs are not clear. In this study, we sequenced the genome of an FLE, termed FLE-Am, present in the Gulf Coast tick, Amblyomma maculatum. We show that FLE-Am likely evolved from a pathogenic strain of Francisella, indicating that tick endosymbionts can evolve from mammalian pathogens. Although the genome of FLE-Am is almost the same size as the genomes of pathogenic Francisella strains, about one-third of its protein-coding genes contain inactivating mutations. The relatively low coding capacity and extensive metabolic capabilities indicate that FLE-Am transitioned recently to its current endosymbiotic lifestyle and likely replaced an ancient endosymbiont with degraded functionality.
Structural studies of the yeast DNA damage-inducible protein Ddi1 reveal domain architecture of this eukaryotic protein family
Authors: Trempe Jean-François , Šašková Klára Grantz , Sivá Monika , Ratcliffe Colin D. H. , Veverka Václav , Hoegl Annabelle , Ménade Marie , Feng Xin , Shenker Solomon , Svoboda Michal , Kožíšek Milan , Konvalinka Jan , Gehring Kalle
Published: September 2016

The eukaryotic Ddi1 family is defined by a conserved retroviral aspartyl protease-like (RVP) domain found in association with a ubiquitin-like (UBL) domain. Ddi1 from Saccharomyces cerevisiae additionally contains a ubiquitin-associated (UBA) domain. The substrate specificity and role of the protease domain in the biological functions of the Ddi family remain unclear. Yeast Ddi1 has been implicated in the regulation of cell cycle progression, DNA-damage repair, and exocytosis. Here, we investigated the multi-domain structure of yeast Ddi1 using X-ray crystallography, nuclear magnetic resonance, and small-angle X-ray scattering. The crystal structure of the RVP domain sheds light on a putative substrate recognition site involving a conserved loop. Isothermal titration calorimetry confirms that both UBL and UBA domains bind ubiquitin, and that Ddi1 binds K48-linked diubiquitin with enhanced affinity. The solution NMR structure of a helical domain that precedes the protease displays tertiary structure similarity to DNA-binding domains from transcription regulators. Our structural studies suggest that the helical domain could serve as a landing platform for substrates in conjunction with attached ubiquitin chains binding to the UBL and UBA domains.
Halobacterial nano vesicles displaying murine bactericidal permeability-increasing protein rescue mice from lethal endotoxic shock
Authors: Balakrishnan Arjun , DasSarma Priya , Bhattacharjee Oindrilla , Kim Jong Myoung , DasSarma Shiladitya , Chakravortty Dipshikha
Published: September 2016

Bactericidal/permeability-increasing protein (BPI) had been shown to possess anti-inflammatory and endotoxin neutralizing activity by interacting with LPS of Gram-negative bacteria. The current study examines the feasibility of using murine BPI (mBPI) expressed on halophilic Archaeal gas vesicle nanoparticles (GVNPs) for the treatment of endotoxemia in high-risk patients, using a murine model of D-galactosamine-induced endotoxic shock. Halobacterium sp. NRC-1was used to express the N-terminal 199 amino acid residues of mBPI fused to the GVNP GvpC protein, and bound to the surface of the haloarchaeal GVNPs. Our results indicate that delivery of mBPIN-GVNPs increase the survival rate of mice challenged with lethal concentrations of lipopolysaccharide (LPS) and D-galactosamine. Additionally, the mBPIN-GVNP-treated mice displayed reduced symptoms of inflammation, including inflammatory anemia, recruitment of neutrophils, liver apoptosis as well as increased pro-inflammatory serum cytokine levels.
Oscillatory activity in auditory cortex reflects the perceptual level of audio-tactile integration
Authors: Plöchl Michael , Gaston Jeremy , Mermagen Tim , König Peter , Hairston W. David
Published: September 2016

Cross-modal interactions between sensory channels have been shown to depend on both the spatial disparity and the perceptual similarity between the presented stimuli. Here we investigate the behavioral and neural integration of auditory and tactile stimulus pairs at different levels of spatial disparity. Additionally, we modulated the amplitudes of both stimuli in either a coherent or non-coherent manner. We found that both auditory and tactile localization performance was biased towards the stimulus in the respective other modality. This bias linearly increases with stimulus disparity and is more pronounced for coherently modulated stimulus pairs. Analyses of electroencephalographic (EEG) activity at temporal–cortical sources revealed enhanced event-related potentials (ERPs) as well as decreased alpha and beta power during bimodal as compared to unimodal stimulation. However, while the observed ERP differences are similar for all stimulus combinations, the extent of oscillatory desynchronization varies with stimulus disparity. Moreover, when both stimuli were subjectively perceived as originating from the same direction, the reduction in alpha and beta power was significantly stronger. These observations suggest that in the EEG the level of perceptual integration is mainly reflected by changes in ongoing oscillatory activity.
Attribution of hydrological change in Heihe River Basin to climate and land use change in the past three decades
Authors: Luo Kaisheng , Tao Fulu , Moiwo Juana P. , Xiao Dengpan
Published: September 2016

The contributions of climate and land use change (LUCC) to hydrological change in Heihe River Basin (HRB), Northwest China were quantified using detailed climatic, land use and hydrological data, along with the process-based SWAT (Soil and Water Assessment Tool) hydrological model. The results showed that for the 1980s, the changes in the basin hydrological change were due more to LUCC (74.5%) than to climate change (21.3%). While LUCC accounted for 60.7% of the changes in the basin hydrological change in the 1990s, climate change explained 57.3% of that change. For the 2000s, climate change contributed 57.7% to hydrological change in the HRB and LUCC contributed to the remaining 42.0%. Spatially, climate had the largest effect on the hydrology in the upstream region of HRB, contributing 55.8%, 61.0% and 92.7% in the 1980s, 1990s and 2000s, respectively. LUCC had the largest effect on the hydrology in the middle-stream region of HRB, contributing 92.3%, 79.4% and 92.8% in the 1980s, 1990s and 2000s, respectively. Interestingly, the contribution of LUCC to hydrological change in the upstream, middle-stream and downstream regions and the entire HRB declined continually over the past 30 years. This was the complete reverse (a sharp increase) of the contribution of climate change to hydrological change in HRB.
Candida albicans Dbf4-dependent Cdc7 kinase plays a novel role in the inhibition of hyphal development
Authors: Lai Wei-Chung , Chang Tschen-wei , Wu Chang Hao , Yang Shu-Ya , Lee Tai-Lin , Li Wan Chen , Chien Ting , Cheng Yu-Che , Shieh Jia-Ching
Published: September 2016

Candida albicans is an opportunistic human fungal pathogen. The ability to switch among multiple cellular forms is key to its pathogenesis. The Dbf4-dependent protein kinase gene CDC7 is conserved due to its role in initiating DNA replication. Because a C. albicans Cdc7 (Cacdc7) homozygous null was not viable, we generated a C. albicans strain with a deleted C. albicans CDC7 (CaCDC7) allele and an expression-repressible allele. Surprisingly, cells of the strain grew as hyphae under the repressed conditions. The in vitro kinase assays confirmed that CaCdc7 (K232) and CaCdc7 (T437) are critical for catalytic and phosphoacceptor of activation activity, respectively. C. albicans cells formed hyphae when expressing either the catalytically inactive CaCdc7 (K232R) or the phosphoacceptor-deficient CaCdc7 (T437A). While CaCdc7 interacted with CaDbf4, cells of the strain in which CaCDC7 was repressed were not rescued by constitutively expressing C. albicans DBF4 or vice versa. We conclude that CaDBF4-dependent CaCDC7 is an essential gene suppressing the hyphal development.
Increased PKCα activity by Rack1 overexpression is responsible for chemotherapy resistance in T-cell acute lymphoblastic leukemia-derived cell line
Authors: Lei Jie , Li Qi , Gao Ying , Zhao Lei , Liu Yanbo
Published: September 2016

Chemoresistant mechanisms in T-cell acute lymphoblastic leukemia (T-ALL) patients are not clarified. The apoptotic signaling mediated by receptor of activated C kinase 1 (Rack1), protein kinase C (PKC) and FEM1 homolog b (FEM1b) was investigated in two T-ALL-derived cell lines (Jurkat and CCRF-CEM) following treatment with chemotherapy drugs vincristine and prednisone. Serum starvation or chemotherapeutic drugs significantly reduced Rack1 level and PKC activation, while promoted cellular apoptosis in both cell lines. Rack1 overexpression protected T-ALL cell against starvation or chemotherapeutic drug-induced apoptosis. Moreover, Rack1 overexpression reduced the level of cytochrome c and active caspase 3 as well as FEM1b and apoptotic protease activating factor-1 (Apaf-1), and inhibited induction of cellular apoptosis in chemotherapeutic drug-treated Jurkat cell. Interaction of Rack1 and PKCα, not PKCβ, was detected in both cell lines. Of note, Rack1 overexpression abrogated reduction of PKC kinase activity in chemotherapeutic drug-treated T-ALL cell. PKC kinase inhibitor Go6976 or siPKCα inhibited downregulation of FEM1b and/or Apaf-1, and thus increased cellular apoptosis in Rack1-overexpressed T-ALL cell receiving chemotherapeutic drugs. Accordingly, our data provided evidence that increased Rack1-mediated upregulation of PKC kinase activity may be responsible for the development of chemoresistance in T-ALL-derived cell line potentially by reducing FEM1b and Apaf-1 level.
Mechanism Underlying Time-dependent Cross-phenomenon between Concentration-response Curves and Concentration Addition Curves: A Case Study of Sulfonamides-Erythromycin mixtures on Escherichia coli
Authors: Sun Haoyu , Ge Hongming , Zheng Min , Lin Zhifen , Liu Ying
Published: September 2016

Previous studies have identified a phenomenon in which the concentration-response curves (CRCs) for mixtures cross the curves for concentration addition model when predicting or judging joint toxic actions. However, mechanistic investigations of this phenomenon are extremely limited. In this study, a similar phenomenon was observed when we determined the joint toxic actions of sulfonamides (SAs) and erythromycin (ERY) on Escherichia coli (E. coli), which we named the “cross-phenomenon”, and it was characterized by antagonism in the low-concentration range, addition in the medium-concentration range, and synergism in the high-concentration range. The mechanistic investigation of the cross-phenomenon was as follows: SAs and ERY could form a double block to inhibit the bacterial growth by exhibiting a synergistic effect; however, the hormetic effect of SAs on E. coli led to antagonism in the low-concentration range, resulting from the stimulation of sdiA mRNA expression by SAs, which increased the expression of the efflux pump (AcrAB-TolC) to discharge ERY. Furthermore, this cross-phenomenon was observed to be a time-dependent process induced by the increase of both the concentration and extent of stimulation of sdiA mRNA with exposure time. This work explains the dose-dependent and time-dependent cross-phenomenon and provides evidence regarding the interaction between hormesis and cross-phenomenon.
Protein oxidation and degradation caused by particulate matter
Authors: Lai Ching-Huang , Lee Chun-Nin , Bai Kuan-Jen , Yang You-Lan , Chuang Kai-Jen , Wu Sheng-Ming , Chuang Hsiao-Chi
Published: September 2016

Particulate matter (PM) modulates the expression of autophagy; however, the role of selective autophagy by PM remains unclear. The objective of this study was to determine the underlying mechanisms in protein oxidation and degradation caused by PM. Human epithelial A549 cells were exposed to diesel exhaust particles (DEPs), urban dust (UD) and carbon black (CB; control particles). Cell survival and proliferation were significantly reduced by DEPs and UD in A549 cells. First, benzo(a)pyrene diolepoxide (BPDE) protein adduct was caused by DEPs at 150 μg/ml. Methionine oxidation (MetO) of human albumin proteins was induced by DEPs, UD and CB; however, the protein repair mechanism that converts MetO back to methionine by methionine sulfoxide reductases A (MSRA) and B3 (MSRB3) was activated by DEPs and inhibited by UD, suggesting that oxidized protein was accumulating in cells. As to the degradation of oxidized proteins, proteasome and autophagy activation was induced by CB with ubiquitin accumulation, whereas proteasome and autophagy activation was induced by DEPs without ubiquitin accumulation. The results suggest that CB-induced protein degradation may be via an ubiquitin-dependent autophagy pathway, whereas DEP-induced protein degradation may be via an ubiquitin-independent autophagy pathway. A distinct proteotoxic effect may depend on the physicochemistry of PM.
SlARF2a plays a negative role in mediating axillary shoot formation
Authors: Xu Tao , Liu Xin , Wang Rong , Dong Xiufen , Guan Xiaoxi , Wang Yanling , Jiang Yun , Shi Zihang , Qi Mingfang , Li Tianlai
Published: September 2016

SlARF2a is expressed in most plant organs, including roots, leaves, flowers and fruits. A detailed expression study revealed that SlARF2a is mainly expressed in the leaf nodes and cross-sections of the nodes indicated that SlARF2a expression is restricted to vascular organs. Decapitation or the application of 6-benzylaminopurine (BAP) can initially promote axillary shoots, during which SlARF2a expression is significantly reduced. Down-regulation of SlARF2a expression results in an increased frequency of dicotyledons and significantly increased lateral organ development. Stem anatomy studies have revealed significantly altered cambia and phloem in tomato plants expressing down-regulated levels of ARF2a, which is associated with obvious alterations in auxin distribution. Further analysis has revealed that altered auxin transport may occur via altered pin expression. To identify the interactions of AUX/IAA and TPL with ARF2a, four axillary shoot development repressors that are down-regulated during axillary shoot development, IAA3, IAA9, SlTPL1 and SlTPL6, were tested for their direct interactions with ARF2a. Although none of these repressors are directly involved in ARF2a activity, similar expression patterns of IAA3, IAA9 and ARF2a implied they might work tightly in axillary shoot formation and other developmental processes.
Myelinating glia differentiation is regulated by extracellular matrix elasticity
Authors: Urbanski Mateusz M. , Kingsbury Lyle , Moussouros Daniel , Kassim Imran , Mehjabeen Saraf , Paknejad Navid , Melendez-Vasquez Carmen V.
Published: September 2016

The mechanical properties of living tissues have a significant impact on cell differentiation, but remain unexplored in the context of myelin formation and repair. In the PNS, the extracellular matrix (ECM) incorporates a basal lamina significantly denser than the loosely organized CNS matrix. Inhibition of non-muscle myosin II (NMII) enhances central but impairs peripheral myelination and NMII has been implicated in cellular responses to changes in the elasticity of the ECM. To directly evaluate whether mechanotransduction plays a role in glial cell differentiation, we cultured Schwann cells (SC) and oligodendrocytes (OL) on matrices of variable elastic modulus, mimicking either their native environment or conditions found in injured tissue. We found that a rigid, lesion-like matrix inhibited branching and differentiation of OL in NMII-dependent manner. By contrast, SC developed normally in both soft and stiffer matrices. Although SC differentiation was not significantly affected by changes in matrix stiffness alone, we found that expression of Krox-20 was potentiated on rigid matrices at high laminin concentration. These findings are relevant to the design of biomaterials to promote healing and regeneration in both CNS and PNS, via transplantation of glial progenitors or the implantation of tissue scaffolds.
Loss of Lysyl Oxidase-like 3 Attenuates Embryonic Lung Development in Mice
Authors: Zhang Jian , Liu Ziyi , Zhang Tingting , Lin Zhuchun , Li Zhenzu , Zhang Aizhen , Sun Xiaoyang , Gao Jiangang
Published: September 2016

Lysyl oxidase-like 3 (LOXL3), a human disease gene candidate, is a member of the lysyl oxidase (LOX) family and is indispensable for mouse palatogenesis and vertebral column development. Our previous study showed that the loss of LOXL3 resulted in a severe cleft palate and spinal deformity. In this study, we investigated a possible role for LOXL3 in mouse embryonic lung development. LOXL3-deficient mice displayed reduced lung volumes and weights, diminished saccular spaces and deformed and smaller thoracic cavities. Excess elastic fibres were detected in LOXL3-deficient lungs, which might be related to the increased LOXL4 expression. Increased transforming growth factor β1 (TGFβ1) expression might be involved in the up-regulation of LOXL4 in LOXL3-deficient lungs. We concluded that the loss of LOXL3 attenuates mouse embryonic lung development.
Defining a Radiomic Response Phenotype: A Pilot Study using targeted therapy in NSCLC
Authors: Aerts Hugo J. W. L. , Grossmann Patrick , Tan Yongqiang , Oxnard Geoffrey R. , Rizvi Naiyer , Schwartz Lawrence H. , Zhao Binsheng
Published: September 2016

Medical imaging plays a fundamental role in oncology and drug development, by providing a non-invasive method to visualize tumor phenotype. Radiomics can quantify this phenotype comprehensively by applying image-characterization algorithms, and may provide important information beyond tumor size or burden. In this study, we investigated if radiomics can identify a gefitinib response-phenotype, studying high-resolution computed-tomography (CT) imaging of forty-seven patients with early-stage non-small cell lung cancer before and after three weeks of therapy. On the baseline-scan, radiomic-feature Laws-Energy was significantly predictive for EGFR-mutation status (AUC = 0.67, p = 0.03), while volume (AUC = 0.59, p = 0.27) and diameter (AUC = 0.56, p = 0.46) were not. Although no features were predictive on the post-treatment scan (p > 0.08), the change in features between the two scans was strongly predictive (significant feature AUC-range = 0.74–0.91). A technical validation revealed that the associated features were also highly stable for test-retest (mean ± std: ICC = 0.96 ± 0.06). This pilot study shows that radiomic data before treatment is able to predict mutation status and associated gefitinib response non-invasively, demonstrating the potential of radiomics-based phenotyping to improve the stratification and response assessment between tyrosine kinase inhibitors (TKIs) sensitive and resistant patient populations.
Porcine milk-derived exosomes promote proliferation of intestinal epithelial cells
Authors: Chen Ting , Xie Mei-Ying , Sun Jia-Jie , Ye Rui-Song , Cheng Xiao , Sun Rui-Ping , Wei Li-Min , Li Meng , Lin De-Lin , Jiang Qing-Yan , Xi Qian-Yun , Zhang Yong-Liang
Published: September 2016

Milk-derived exosomes were identified as a novel mechanism of mother-to-child transmission of regulatory molecules, but their functions in intestinal tissues of neonates are not well-studied. Here, we characterized potential roles of porcine milk-derived exosomes in the intestinal tract. In vitro, treatment with milk-derived exosomes (27 ± 3 ng and 55 ± 5 ng total RNA) significantly promoted IPEC-J2 cell proliferation by MTT, CCK8, EdU fluorescence and EdU flow cytometry assays. The qRT-PCR and Western blot analyses indicated milk-derived exosomes (0.27 ± 0.03 μg total RNA) significantly promoted expression of CDX2, IGF-1R and PCNA and inhibited p53 gene expression involved in intestinal proliferation. Additionally, six detected miRNAs were significantly increased in IPEC-J2 cell, while FAS and SERPINE were significantly down-regulated relative to that in control. In vivo, treated groups (0.125 μg and 0.25 μg total RNA) significantly raised mice’ villus height, crypt depth and ratio of villus length to crypt depth of intestinal tissues, significantly increased CDX2, PCNA and IGF-1R’ expression and significantly inhibited p53′ expression. Our study demonstrated that milk-derived exosomes can facilitate intestinal cell proliferation and intestinal tract development, thus giving a new insight for milk nutrition and newborn development and health.
Ce3+/Yb3+/Er3+ triply doped bismuth borosilicate glass: a potential fiber material for broadband near-infrared fiber amplifiers
Authors: Chu Yushi , Ren Jing , Zhang Jianzhong , Peng Gangding , Yang Jun , Wang Pengfei , Yuan Libo
Published: September 2016

Erbium doped bismuth borosilicate (BBS) glasses, possessing the broadest 1.55 μm near infrared (NIR) emission band among oxide glasses, stand out as excellent fiber material for optical fiber amplifiers. In this work, we demonstrate that both broadened and enhanced NIR emission of Er3+ can be obtained by sensibly combining the effects such as mixed glass former effect, phonon-assisted energy transfer (PAET) and de-excitation effect induced by codopant. Specially, by codoping CeO2 in a controlled manner, it leads to not only much improved optical quality of the glasses, enhanced NIR emission, but also significantly suppressed energy transfer up-conversion (ETU) luminescence which is detrimental to the NIR emission. Cerium incorporated in the glasses exists overwhelmingly as the trivalent oxidation state Ce3+ and its effects on the luminescence properties of Er3+ are discussed. Judd-Ofelt analysis is used to evaluate gain amplification of the glasses. The result indicates that Ce3+/Yb3+/Er3+ triply doped BBS glasses are promising candidate for erbium doped fiber amplifiers. The strategy described here can be readily extended to other rare-earth ions (REs) to improve the performance of REs doped fiber lasers and amplifiers.
Antidepressive and BDNF effects of enriched environment treatment across ages in mice lacking BDNF expression through promoter IV
Authors: Jha S , Dong B E , Xue Y , Delotterie D F , Vail M G , Sakata K
Published: September 2016

Reduced promoter IV-driven expression of brain-derived neurotrophic factor (BDNF) is implicated in stress and major depression. We previously reported that defective promoter IV (KIV) caused depression-like behavior in young adult mice, which was reversed more effectively by enriched environment treatment (EET) than antidepressants. The effects of promoter IV-BDNF deficiency and EET over the life stages remain unknown. Since early-life development (ED) involves dynamic epigenetic processes, we hypothesized that EET during ED would provide maximum antidepressive effects that would persist later in life due to enhanced, long-lasting BDNF induction. We tested this hypothesis by determining EET effects across three life stages: ED (0–2 months), young adult (2–4 months), and old adult (12–14 months). KIV mice at all life stages showed depression-like behavior in the open-field and tail-suspension tests compared with wild-type mice. Two months of EET reduced depression-like behavior in ED and young adult, but not old adult mice, with the largest effect in ED KIV mice. This effect lasted for 1 month after discontinuance of EET only in ED mice. BDNF protein induction by EET in the hippocampus and frontal cortex was also the largest in ED mice and persisted only in the hippocampus of ED KIV mice after discontinuance of EET. No gender-specific effects were observed. The results suggest that defective promoter IV causes depression-like behavior, regardless of age and gender, and that EET during ED is particularly beneficial to individuals with promoter IV-BDNF deficiency, while additional treatment may be needed for older adults.
Gels with sense: supramolecular materials that respond to heat, light and sound
Authors: Jones Christopher D. , Steed Jonathan W.
Published: September 2016

A comprehensive review of “smart” supramolecular gels, exploring the physical and chemical mechanisms responsible for thermo-, photo- and mechano-switchable behaviours.
Smart Inorganic Polymers
Authors: Caminade Anne-Marie , Hey-Hawkins Evamarie , Manners Ian
Published: September 2016

Guest editors Anne-Marie Caminade, Evamarie Hey-Hawkins and Ian Manners introduce the Smart Inorganic Polymers issue of Chemical Society Reviews
Calixarenes with naphthalene units: calix[4]naphthalenes and hybrid[4]arenes
Authors: Boinski T. , Cieszkowski A. , Rosa B. , Leśniewska B. , Szumna A.
Published: September 2016

A facile, one-step synthesis of new calix[4]naphthalenes and the conformational and complexation properties of the homomacrocycles and the hybrid macrocycle are presented.
Biasing hydrogen bond donating host systems towards chemical warfare agent recognition
Authors: Hiscock Jennifer R. , Wells Neil J. , Ede Jayne A. , Gale Philip A. , Sambrook Mark R.
Published: September 2016

Selectivity in hydrogen bond-driven recognition events is biased via electrostatic repulsion to favour complexation of neutral Chemical Warfare Agent over anionic guests.
Access to site-specific Fc–cRGD peptide conjugates through streamlined expressed protein ligation
Authors: Frutos S. , Jordan J. B. , Bio M. M. , Muir T. W. , Thiel O. R. , Vila-Perelló M.
Published: September 2016

Conjugation of peptides to the Fc fragment of antibodies is a powerful strategy to generate long acting biotherapeutics. We show here an efficient route to obtain fully active, site-specific conjugates of synthetic bioactive peptides using a split intein based approach.
Correction: Total synthesis of fellutamides, lipopeptide proteasome inhibitors. More sustainable peptide bond formation
Authors: Pirrung Michael C. , Zhang Fa , Ambadi Sudhakar , Gangadhara Rao Y.
Published: September 2016

Correction for ‘Total synthesis of fellutamides, lipopeptide proteasome inhibitors. More sustainable peptide bond formation’ by Michael C. Pirrung, et al., Org. Biomol. Chem., 2016, 14, 8367–8375.
Microwave-assisted synthesis of nitrogen-doped activated carbon as an oxygen reduction catalyst in microbial fuel cells
Authors: Wang Haiman , Li Da , Liu Jia , Liu Luchang , Zhou Xiangtong , Qu Youpeng , Zhang Jie , Feng Yujie
Published: September 2016

Nitrogen-doped activated carbon with superior ORR electrocatalytic activity and higher stability toward domestic wastewater was synthesized by a simple microwave-assisted method.
Adhesion characteristics of nano/micro-sized particles with dual ligands with different interaction distances
Authors: Yoon J. H. , Kim D. K. , Key J. , Lee S. W. , Lee S. Y.
Published: September 2016

Dual ligand conjugated particle for targeted delivery. Rotational dislodging force on the ligand–receptor interaction. Optimal receptor and ligand ratio exist.
Theoretical study of a tunable and strain-controlled nanoporous graphenylene membrane for multifunctional gas separation
Authors: Zhu Lei , Jin Yakang , Xue Qingzhong , Li Xiaofang , Zheng Haixia , Wu Tiantian , Ling Cuicui
Published: September 2016

A tunable, multifunctional graphenylene gas separation membrane, wherein the size of the nanopore can be precisely regulated by tensile strain.
Internal polymer pore functionalization through coated particle templating affords fluorine-free green functional textiles
Authors: Stucki M. , Kellenberger C. R. , Loepfe M. , Stark W. J.
Published: September 2016

Green, fluorine-free and fully porous functional membranes were prepared from coated limestone particles in an elastomer at m2scales.
Facile synthesis of benzothiadiazole-based chromophores for enhanced performance of second-order nonlinear optical materials
Authors: Li Ming , Zhang Hui , Zhang Yan , Hou Baoshan , Li Chuangyang , Wang Xibin , Zhang Ji , Xiao LingHan , Cui Zhanchen , Ao Yuhui
Published: September 2016

Incorporation of electron-deficient benzothiadiazole as auxiliary acceptor efficiently improved the electro-optical properties of chromophores.