bluuebunny/crossref_metadata_2025 huggingface dataset:
Recombinant L-asparaginase 1 from Saccharomyces cerevisiae: an allosteric enzyme with antineoplastic activity
Authors: Costa Iris Munhoz , Schultz Leonardo , de Araujo Bianchi Pedra Beatriz , Leite Mariana Silva Moreira , Farsky Sandra H. P. , de Oliveira Marcos Antonio , Pessoa Adalberto , Monteiro Gisele
Published: November 2016

L-asparaginase (L-ASNase) (EC 3.5.1.1) is an important enzyme for the treatment of acute lymphoblastic leukaemia. Currently, the enzyme is obtained from bacteria, Escherichia coli and Erwinia chrysanthemi. The bacterial enzymes family is subdivided in type I and type II; nevertheless, only type II have been employed in therapeutic proceedings. However, bacterial enzymes are susceptible to induce immune responses, leading to a high incidence of adverse effects compromising the effectiveness of the treatment. Therefore, alternative sources of L-ASNase may be useful to reduce toxicity and enhance efficacy. The yeast Saccharomyces cerevisiae has the ASP1 gene responsible for encoding L-asparaginase 1 (ScASNase1), an enzyme predicted as type II, like bacterial therapeutic isoforms, but it has been poorly studied. Here we characterised ScASNase1 using a recombinant enzyme purified by affinity chromatography. ScASNase1 has specific activity of 196.2 U/mg and allosteric behaviour, like type I enzymes, but with a low K0.5 = 75 μM like therapeutic type II. We showed through site-directed mutagenesis that the T64-Y78-T141-K215 residues are involved in catalysis. Furthermore, ScASNase1 showed cytotoxicity for the MOLT-4 leukemic cell lineage. Our data show that ScASNase1 has characteristics described for the two subfamilies of l-asparaginase, types I and II, and may have promising antineoplastic properties.
Motion Alters Color Appearance
Authors: Hong Sang-Wook , Kang Min-Suk
Published: November 2016

Chromatic induction compellingly demonstrates that chromatic context as well as spectral lights reflected from an object determines its color appearance. Here, we show that when one colored object moves around an identical stationary object, the perceived saturation of the stationary object decreases dramatically whereas the saturation of the moving object increases. These color appearance shifts in the opposite directions suggest that normalization induced by the object’s motion may mediate the shift in color appearance. We ruled out other plausible alternatives such as local adaptation, attention, and transient neural responses that could explain the color shift without assuming interaction between color and motion processing. These results demonstrate that the motion of an object affects both its own color appearance and the color appearance of a nearby object, suggesting a tight coupling between color and motion processing.
The Antimicrobial Susceptibility of Klebsiella pneumoniae from Community Settings in Taiwan, a Trend Analysis
Authors: Lin Wu-Pu , Wang Jann-Tay , Chang Shan-Chwen , Chang Feng-Yee , Fung Chang-Phone , Chuang Yin-Ching , Chen Yao-Shen , Shiau Yih-Ru , Tan Mei-Chen , Wang Hui-Ying , Lai Jui-Fen , Huang I-Wen , Lauderdale Tsai-Ling
Published: November 2016

Drug-resistant Klebsiella pneumoniae, especially extended-spectrum β-lactamase (ESBL)- and/or AmpC β-lactamase-producing strains, is an emerging problem worldwide. However, few data focusing on drug susceptibility of K. pneumoniae from community is available. In this study, we analyzed 1016 K. pneumoniae isolates from outpatients or those visiting emergency rooms collected during 2002–2012 from Taiwan Surveillance of Antimicrobial Resistance program. Significantly decreased susceptibilities to 3rd generation cephalosporins and ciprofloxacin were found during the study period. By 2012, susceptibility to cefotaxime and ciprofloxacin was 83.6% and 81.6%, respectively. The prevalence of ESBL-producers increased from 4.8% in 2002 to 11.9% in 2012 (P = 0.012), while that of AmpC β-lactamase-producers increased from 0% to 9.5% in the same period (P < 0.001). Phylogenic analysis of the ESBL and AmpC-β-lactamase-producers by pulsed-field gel electrophoresis and multi-locus sequence typing revealed wide genetic diversity even among the most common sequence type 11 isolates (33.0%). By multivariate analysis, later study year, elderly, and urine isolates were associated with carriage of ESBL genes, while only urine isolates were associated with carriage of AmpC β-lactamase genes. Further studies are needed to determine which antibiotics are reasonable empirical therapy options for patients presenting with severe sepsis that might be caused by K. pneumoniae.
Non-thermal atmospheric pressure plasma activates lactate in Ringer’s solution for anti-tumor effects
Authors: Tanaka Hiromasa , Nakamura Kae , Mizuno Masaaki , Ishikawa Kenji , Takeda Keigo , Kajiyama Hiroaki , Utsumi Fumi , Kikkawa Fumitaka , Hori Masaru
Published: November 2016

Non-thermal atmospheric pressure plasma is a novel approach for wound healing, blood coagulation, and cancer therapy. A recent discovery in the field of plasma medicine is that non-thermal atmospheric pressure plasma not only directly but also indirectly affects cells via plasma-treated liquids. This discovery has led to the use of non-thermal atmospheric pressure plasma as a novel chemotherapy. We refer to these plasma-treated liquids as plasma-activated liquids. We chose Ringer’s solutions to produce plasma-activated liquids for clinical applications. In vitro and in vivo experiments demonstrated that plasma-activated Ringer’s lactate solution has anti-tumor effects, but of the four components in Ringer’s lactate solution, only lactate exhibited anti-tumor effects through activation by non-thermal plasma. Nuclear magnetic resonance analyses indicate that plasma irradiation generates acetyl and pyruvic acid-like groups in Ringer’s lactate solution. Overall, these results suggest that plasma-activated Ringer’s lactate solution is promising for chemotherapy.
Coevolution of Cooperation and Partner Rewiring Range in Spatial Social Networks
Authors: Khoo Tommy , Fu Feng , Pauls Scott
Published: November 2016

In recent years, there has been growing interest in the study of coevolutionary games on networks. Despite much progress, little attention has been paid to spatially embedded networks, where the underlying geographic distance, rather than the graph distance, is an important and relevant aspect of the partner rewiring process. It thus remains largely unclear how individual partner rewiring range preference, local vs. global, emerges and affects cooperation. Here we explicitly address this issue using a coevolutionary model of cooperation and partner rewiring range preference in spatially embedded social networks. In contrast to local rewiring, global rewiring has no distance restriction but incurs a one-time cost upon establishing any long range link. We find that under a wide range of model parameters, global partner switching preference can coevolve with cooperation. Moreover, the resulting partner network is highly degree-heterogeneous with small average shortest path length while maintaining high clustering, thereby possessing small-world properties. We also discover an optimum availability of reputation information for the emergence of global cooperators, who form distant partnerships at a cost to themselves. From the coevolutionary perspective, our work may help explain the ubiquity of small-world topologies arising alongside cooperation in the real world.
Single Cell Clones Purified from Human Parotid Glands Display Features of Multipotent Epitheliomesenchymal Stem Cells
Authors: Yi TacGhee , Lee Songyi , Choi Nahyun , Shin Hyun-Soo , Kim Junghee , Lim Jae-Yol
Published: November 2016

A better understanding of the biology of tissue-resident stem cell populations is essential to development of therapeutic strategies for regeneration of damaged tissue. Here, we describe the isolation of glandular stem cells (GSCs) from a small biopsy specimen from human parotid glands. Single colony-forming unit-derived clonal cells were isolated through a modified subfractionation culture method, and their stem cell properties were examined. The isolated clonal cells exhibited both epithelial and mesenchymal stem cell (MSC)-like features, including differentiation potential and marker expression. The cells transiently displayed salivary progenitor phenotypes during salivary epithelial differentiation, suggesting that they may be putative multipotent GSCs rather than progenitor cells. Both epithelial and mesenchymal-expressing putative GSCs, LGR5+CD90+ cells, were found in vivo, mostly in inter-secretory units of human salivary glands. Following in vivo transplantation into irradiated salivary glands of mice, these cells were found to be engrafted around the secretory complexes, where they contributed to restoration of radiation-induced salivary hypofunction. These results showed that multipotent epitheliomesenchymal GSCs are present in glandular mesenchyme, and that isolation of homogenous GSC clones from human salivary glands may promote the precise understanding of biological function of bona fide GSCs, enabling their therapeutic application for salivary gland regeneration.
Manganese-mediated acceleration of age-related hearing loss in mice
Authors: Ohgami Nobutaka , Yajima Ichiro , Iida Machiko , Li Xiang , Oshino Reina , Kumasaka Mayuko Y. , Kato Masashi
Published: November 2016

Despite the fact that manganese (Mn) is known to be a neurotoxic element relevant to age-related disorders, the risk of oral exposure to Mn for age-related hearing loss remains unclear. In this study, we orally exposed wild-type young adult mice to Mn (Mn-exposed WT-mice) at 1.65 and 16.50 mg/L for 4 weeks. Mn-exposed WT-mice showed acceleration of age-related hearing loss. Mn-exposed WT-mice had neurodegeneration of spiral ganglion neurons (SGNs) with increased number of lipofuscin granules. Mn-exposed WT-mice also had increased hypoxia-inducible factor-1 alpha (Hif-1α) protein with less hydroxylation at proline 564 and decreased c-Ret protein in SGNs. Mn-mediated acceleration of age-related hearing loss involving neurodegeneration of SGNs was rescued in RET-transgenic mice carrying constitutively activated RET. Thus, oral exposure to Mn accelerates age-related hearing loss in mice with Ret-mediated neurodegeneration of SGNs.
Tracing the influence of Mediterranean climate on Southeastern Europe during the past 350,000 years
Authors: Obreht Igor , Zeeden Christian , Hambach Ulrich , Veres Daniel , Marković Slobodan B. , Bösken Janina , Svirčev Zorica , Bačević Nikola , Gavrilov Milivoj B. , Lehmkuhl Frank
Published: November 2016

Loess-palaeosol sequences are valuable archives of past environmental changes. Although regional palaeoclimatic trends and conditions in Southeastern Europe have been inferred from loess sequences, large scale forcing mechanisms responsible for their formation have yet to be determined. Southeastern Europe is a climatically sensitive region, existing under the strong influence of both Mediterranean and continental climates. Establishment of the spatial and temporal evolution and interaction of these climatic areas is essential to understand the mechanisms of loess formation. Here we present high-resolution grain-size, environmental magnetic, spectrophotometric and geochemical data from the Stalać section in the Central Balkans (Serbia) for the past ~350,000 years. The goal of this study is to determine the influence of the Mediterranean climate during this period. Data show that the Central Balkans were under different atmospheric circulation regimes, especially during Marine Isotope Stages 9 and 7, while continental climate prevailed further north. We observe a general weakening of the Mediterranean climate influence with time. Our data suggest that Marine Isotope Stage 5 was the first interglacial in the Central Balkans that had continental climate characteristics. This prominent shift in climatic conditions resulted in unexpectedly warm and humid conditions during the last glacial.
Degeneration and energy shortage in the suprachiasmatic nucleus underlies the circadian rhythm disturbance in ApoE−/− mice: implications for Alzheimer’s disease
Authors: Zhou Lan , Gao Qian , Nie Meng , Gu Jing-Li , Hao Wei , Wang Lin , Cao Ji-Min
Published: November 2016

Alzheimer’s disease (AD) patients suffer sleep disorders and circadian rhythm disturbances (CRDs). The underlying mechanisms are incompletely understood, and treatments are lacking. In this study, we characterized the locomotor activity, clock gene expression, morphological degeneration and energy metabolism of suprachiasmatic nucleus (SCN), together with retinal light sensing, in ApoE−/− mice, a model for AD. Compared with the control C57BL/6J mice, ApoE−/− mice exhibited disordered circadian locomotor activity under dim light and constant darkness, with impaired re-entrainment to phase change schedules. Decreased retinal melanopsin expression, together with amyloidosis and tau deposition, was evident in ApoE−/− mice. Mitochondrial and synaptic deterioration, altered SIRT1-mediated energy metabolism and clock gene expression were also observed in ApoE−/− SCN. Supplementation with fat or ketone bodies but not glucose, or intraperitoneal administration of nicotinamide, restored the locomotor rhythmicity and circadian expression of SIRT1 and clock genes, as well as reducing neurodegeneration. Taken together, ApoE deficiency induced degeneration and a significant disturbance in the SCN rhythmicity. Decline of retinal light sensing and SCN structural and metabolic deteriorations represented the major pathologies accounting for the CRDs in ApoE−/− mice. Our curative experiments may help develop future therapies to treat the CRDs and sleep disorders in AD patients.
Identification of suitable reference gene and biomarkers of serum miRNAs for osteoporosis
Authors: Chen Jian , Li Kai , Pang Qianqian , Yang Chao , Zhang Hongyu , Wu Feng , Cao Hongqing , Liu Hongju , Wan Yumin , Xia Weibo , Wang Jinfu , Dai Zhongquan , Li Yinghui
Published: November 2016

Our objective was to identify suitable reference genes in serum miRNA for normalization and screen potential new biomarkers for osteoporosis diagnosis by a systematic study. Two types of osteoporosis models were used like as mechanical unloading and estrogen deficiency. Through a large-scale screening using microarray, qPCR validation and statistical algorithms, we first identified miR-25-3p as a suitable reference gene for both type of osteoporosis, which also showed stability during the differentiation processes of osteoblast and osteoclast. Then 15 serum miRNAs with differential expression in OVX rats were identified by microarray and qPCR validation. We further detected these 15 miRNAs in postmenopausal women and bedrest rhesus monkeys and evaluated their diagnostic value by ROC analysis. Among these miRNAs, miR-30b-5p was significantly down-regulated in postmenopausal women with osteopenia or osteoporosis; miR-103-3p, miR-142-3p, miR-328-3p were only significantly decreased in osteoporosis. They all showed positive correlations with BMD. Except miR328-3p, the other three miRNAs were also declined in the rhesus monkeys after long-duration bedrest. Their AUC values (all >0.75) proved the diagnostic potential. Our results provided a reliable normalization reference gene and verified a group of circulating miRNAs as non-invasive biomarkers in the detection of postmenopausal- and mechanical unloading- osteoporosis.
Direct and indirect ENSO modulation of winter temperature over the Asian–Pacific–American region
Authors: Leung Marco Y. T. , Zhou Wen
Published: November 2016

In this study, the direct and indirect atmospheric responses over the Asian–Pacific–American region to the El Niño–Southern Oscillation (ENSO) are documented. Since ENSO is likely to induce the northward displacement of the East Asian trough (NDEAT), some of the influence of ENSO on the Asian–Pacific–American region is possibly indirect and acts by inducing NDEAT. To separate corresponding influences of ENSO and NDEAT, partial regression is utilized. It is noted that temperature variations in the East Asian–Western Pacific region are controlled mainly by NDEAT. In contrast, ENSO demonstrates a weak direct relation to the temperature variation over the East Asian–Western Pacific region. This suggests that the influence of ENSO on this region is indirect, through modulation of NDEAT. On the other hand, temperature variation over the tropical eastern Pacific is dominated by ENSO forcing. Finally, temperature variation over the eastern North American–Western Pacific region is controlled by both ENSO and NDEAT. Nevertheless, their influences on temperature and circulation over this region tend to offset each other. This implies that temperature variation is controlled by their relative strengths.
Chromosome-specific sequencing reveals an extensive dispensable genome component in wheat
Authors: Liu Miao , Stiller Jiri , Holušová Kateřina , Vrána Jan , Liu Dengcai , Doležel Jaroslav , Liu Chunji
Published: November 2016

The hexaploid wheat genotype Chinese Spring (CS) has been used worldwide as the reference base for wheat genetics and genomics, and significant resources have been used by the international community to generate a reference wheat genome based on this genotype. By sequencing flow-sorted 3B chromosome from a hexaploid wheat genotype CRNIL1A and comparing the obtained sequences with those available for CS, we detected that a large number of sequences in the former were missing in the latter. If the distribution of such sequences in the hexaploid wheat genome is random, CRNILA sequences missing in CS could be as much as 159.3 Mb even if only fragments of 50 bp or longer were considered. Analysing RNA sequences available in the public domains also revealed that dispensable genes are common in hexaploid wheat. Together with those extensive intra- and interchromosomal rearrangements in CS, the existence of such dispensable genes is another factor highlighting potential issues with the use of reference genomes in various studies. Strong deviation in distributions of these dispensable sequences among genotypes with different geographical origins provided the first evidence indicating that they could be associated with adaptation in wheat.
Bone augmentation after ectopic implantation of a cell-free collagen-hydroxyapatite scaffold in the mouse
Authors: Calabrese Giovanna , Giuffrida Raffaella , Forte Stefano , Salvatorelli Lucia , Fabbi Claudia , Figallo Elisa , Gulisano Massimo , Parenti Rosalba , Magro Gaetano , Colarossi Cristina , Memeo Lorenzo , Gulino Rosario
Published: November 2016

The bone grafting is the classical way to treat large bone defects. Among the available techniques, autologous bone grafting is still the most used but, however, it can cause complications such as infection and donor site morbidity. Alternative and innovative methods rely on the development of biomaterials mimicking the structure and properties of natural bone. In this study, we characterized a cell-free scaffold, which was subcutaneously implanted in mice and then analyzed bothin vivoandex vivoafter 1, 2, 4, 8 and 16 weeks, respectively. Two types of biomaterials, made of either collagen alone or collagen plus magnesium-enriched hydroxyapatite have been used. The results indicate that bone augmentation and angiogenesis could spontaneously occur into the biomaterial, probably by the recruitment of host cells, and that the composition of the scaffolds is crucial. In particular, the biomaterial more closely mimicking the native bone drives the process of bone augmentation more efficiently. Gene expression analysis and immunohistochemistry demonstrate the expression of typical markers of osteogenesis by the host cells populating the scaffold. Our data suggest that this biomaterial could represent a promising tool for the reconstruction of large bone defects, without using exogenous living cells or growth factors.
Chondrogenic Potential of Peripheral Blood Derived Mesenchymal Stem Cells Seeded on Demineralized Cancellous Bone Scaffolds
Authors: Wang Shao-Jie , Jiang Dong , Zhang Zheng-Zheng , Huang Ai-Bing , Qi Yan-Song , Wang Hai-Jun , Zhang Ji-Ying , Yu Jia-Kuo
Published: November 2016

As a cell source with large quantity and easy access, peripheral blood mesenchymal stem cells (PBMSCs) were isolated and seeded in porcine demineralized cancellous bone (DCB) scaffolds, cultured in chondrogenic medium and evaluated for in vitro chondrogenesis. Bone marrow MSCs (BMMSCs) and articular cartilage chondrocytes (ACCs) underwent the same process as controls. The morphology, viability and proliferation of PBMSCs in DCB scaffolds were similar to those of BMMSCs and ACCs. PBMSCs and BMMSCs showed similar chondrogenesis potential with consistent production of COL 2 and SOX 9 protein and increased COL 2 and AGC mRNA expressions at week 3 but the COL 2 protein production was still less than that of ACCs. Minimal increase of hypertrophic markers was found in all groups. Relatively higher ALP and lower COL 10 mRNA expressions were found in both MSCs groups at week 3 than that in ACCs, whereas no significant difference of COL 1 and SOX 9 mRNA and MMP 13 protein was found among all groups. To conclude, PBMSCs shared similar proliferation and chondrogenic potential with BMMSCs in DCB scaffolds and could be an alternative to BMMSCs for cartilage tissue engineering. Further optimization of chondrogenesis system is needed regardless of the promising results.
Significant glial alterations in response to iron loading in a novel organotypic hippocampal slice culture model
Authors: Healy Sinead , McMahon Jill , Owens Peter , FitzGerald Una
Published: November 2016

Aberrant iron deposition in the brain is associated with neurodegenerative disorders including Multiple Sclerosis, Alzheimer’s disease and Parkinson’s disease. To study the collective response to iron loading, we have used hippocampal organotypic slices as a platform to develop a novel ex vivo model of iron accumulation. We demonstrated differential uptake and toxicity of iron after 12 h exposure to 10 μM ferrous ammonium sulphate, ferric citrate or ferrocene. Having established the supremacy of ferrocene in this model, the cultures were then loaded with 0.1–100 μM ferrocene for 12 h. One μM ferrocene exposure produced the maximal 1.6-fold increase in iron compared with vehicle. This was accompanied by a 1.4-fold increase in ferritin transcripts and mild toxicity. Using dual-immunohistochemistry, we detected ferritin in oligodendrocytes, microglia, but rarely in astrocytes and never in neurons in iron-loaded slice cultures. Moreover, iron loading led to a 15% loss of olig2-positive cells and a 16% increase in number and greater activation of microglia compared with vehicle. However, there was no appreciable effect of iron loading on astrocytes. In what we believe is a significant advance on traditional mono- or dual-cultures, our novel ex vivo slice-culture model allows characterization of the collective response of brain cells to iron-loading.
Sulfated hyaluronan alters fibronectin matrix assembly and promotes osteogenic differentiation of human bone marrow stromal cells
Authors: Vogel Sarah , Arnoldini Simon , Möller Stephanie , Schnabelrauch Matthias , Hempel Ute
Published: November 2016

Extracellular matrix (ECM) composition and structural integrity is one of many factors that influence cellular differentiation. Fibronectin (FN) which is in many tissues the most abundant ECM protein forms a unique fibrillary network. FN homes several binding sites for sulfated glycosaminoglycans (sGAG), such as heparin (Hep), which was previously shown to influence FN conformation and protein binding. Synthetically sulfated hyaluronan derivatives (sHA) can serve as model molecules with a well characterized sulfation pattern to study sGAG-FN interaction. Here is shown that the low-sulfated sHA (sHA1) interacts with FN and influences fibril assembly. The interaction of FN fibrils with sHA1 and Hep, but not with non-sulfated HA was visualized by immunofluorescent co-staining. FRET analysis of FN confirmed the presence of more extended fibrils in human bone marrow stromal cells (hBMSC)-derived ECM in response to sHA1 and Hep. Although both sHA1 and Hep affected FN conformation, exclusively sHA1 increased FN protein level and led to thinner fibrils. Further, only sHA1 had a pro-osteogenic effect and enhanced the activity of tissue non-specific alkaline phosphatase. We hypothesize that the sHA1-triggered change in FN assembly influences the entire ECM network and could be the underlying mechanism for the pro-osteogenic effect of sHA1 on hBMSC.
Dense encoding of natural odorants by ensembles of sparsely activated neurons in the olfactory bulb
Authors: Gschwend Olivier , Beroud Jonathan , Vincis Roberto , Rodriguez Ivan , Carleton Alan
Published: November 2016

Sensory information undergoes substantial transformation along sensory pathways, usually encompassing sparsening of activity. In the olfactory bulb, though natural odorants evoke dense glomerular input maps, mitral and tufted (M/T) cells tuning is considered to be sparse because of highly odor-specific firing rate change. However, experiments used to draw this conclusion were either based on recordings performed in anesthetized preparations or used monomolecular odorants presented at arbitrary concentrations. In this study, we evaluated the lifetime and population sparseness evoked by natural odorants by capturing spike temporal patterning of neuronal assemblies instead of individual M/T tonic activity. Using functional imaging and tetrode recordings in awake mice, we show that natural odorants at their native concentrations are encoded by broad assemblies of M/T cells. While reducing odorant concentrations, we observed a reduced number of activated glomeruli representations and consequently a narrowing of M/T tuning curves. We conclude that natural odorants at their native concentrations recruit M/T cells with phasic rather than tonic activity. When encoding odorants in assemblies, M/T cells carry information about a vast number of odorants (lifetime sparseness). In addition, each natural odorant activates a broad M/T cell assembly (population sparseness).
Deletion of Lkb1 in adult mice results in body weight reduction and lethality
Authors: Shan Tizhong , Xiong Yan , Kuang Shihuan
Published: November 2016

Liver kinase B1 (Lkb1) plays crucial roles in development, metabolism and survival. As constitutive knockout of Lkb1 in mice leads to embryonic lethality, whether Lkb1 is required for the growth and survival of adult mice is unclear. Here we address this question using a tamoxifen-inducible Lkb1 knockout (KO) mouse model: Rosa26-CreER: Lkb1flox/flox (abbreviated as Rosa-Lkb1). The Rosa-Lkb1 mice exhibited body weight reduction and died within 6 weeks after tamoxifen induction. The body weight reduction was due to reduced weight of various tissues but the brown and white adipose tissues underwent much more pronounced weight reduction relative to the overall body weight reduction. Accordingly, the Rosa-Lkb1 mice had increased blood glucose levels and were intolerant to glucose challenge. Expression levels of adipogenic and lipogenic genes in adipose tissues were also dramatically reduced by Lkb1 deletion. Additionally, Lkb1 deletion reduced lipid deposition and increased expression of mitochondrial (Pgc1a, Cox5b and Cox7a) and hepatic gluconeogenesis related genes (Pepck) in liver. Finally, the Rosa-Lkb1 mice had much reduced oxygen consumption, carbon dioxide production, and energy expenditure. These results demonstrate that Lkb1 plays an important role in maintaining body weight, liver and adipose tissue function, blood glucose homeostasis and survival in adult mice.
A Comprehensive Characterization of the Function of LincRNAs in Transcriptional Regulation Through Long-Range Chromatin Interactions
Authors: Cai Liuyang , Chang Huidan , Fang Yaping , Li Guoliang
Published: November 2016

LincRNAs are emerging as important regulators with various cellular functions. However, the mechanisms behind their role in transcriptional regulation have not yet been fully explored. In this report, we proposed to characterize the diverse functions of lincRNAs in transcription regulation through an examination of their long-range chromatin interactions. We found that the promoter regions of lincRNAs displayed two distinct patterns of chromatin states, promoter-like and enhancer-like, indicating different regulatory functions for lincRNAs. Notably, the chromatin interactions between lincRNA genes and other genes suggested a potential mechanism for lincRNAs in the regulation of other genes at the RNA level because the transcribed lincRNAs could function at local spaces on other genes that interact with the lincRNAs at the DNA level. These results represent a novel way to predict the functions of lincRNAs. The GWAS-identification of SNPs within the lincRNAs revealed that some lincRNAs were disease-associated, and the chromatin interactions with those lincRNAs suggested that they were potential target genes of these lincRNA-associated SNPs. Our study provides new insights into the roles that lincRNAs play in transcription regulation.
TiO2 nanotubes wrapped with reduced graphene oxide as a high-performance anode material for lithium-ion batteries
Authors: Zheng Peng , Liu Ting , Su Ying , Zhang Lifeng , Guo Shouwu
Published: November 2016

Through electrostatic interaction and high-temperature reduction methods, rGO was closely coated onto the surface of TiO2nanotubes. Even at a high temperature of 700 °C, the nanotube morphology of TiO2(anatase) was preserved because of the assistance of rGO, which provides a framework that prevents the tubes from breaking into particles and undergoing a phase transformation. The rGO/TiO2nanotubes deliver a high capacity (263 mAh g−1at the end of 100 cycles at 0.1 A g−1), excellent rate performance (151 mAh g−1at 2 A g−1and 102 mAh g−1at 5 A g−1), and good cycle stability (206 mAh g−1after 500 cycles at 0.5 A g−1). These characteristics arise from the GO/TiO2nanotubes’ advanced structure. First, the closely coated rGO and Ti3+in the tubes give rise to a high electro-conductivity of the nanotubes. Additionally, the Li+ions can rapidly transfer into the electrode via the nanotubes’ empty inner diameter and short tube wall.
Screening for diabetic retinopathy using new mydriasis-free, full-field flicker ERG recording device
Authors: Fukuo Motonobu , Kondo Mineo , Hirose Akira , Fukushima Harumi , Ikesugi Kengo , Sugimoto Masahiko , Kato Kumiko , Uchigata Yasuko , Kitano Shigehiko
Published: November 2016

Diabetic retinopathy (DR) is a leading cause of blindness among working-age adults. Therefore, it is important to detect DR accurately during mass screening. The purpose of this study was to determine whether a small, hand-held, mydriasis-free, full-field flicker electroretinographic (ERGs) device called RETevalcan be used to screen for DR. To accomplish this, we recorded full-field flicker ERGs with this device from 48 normal eyes and 118 eyes with different severities of DR in patients with diabetes mellitus (DM). This system delivered a constant flash retinal luminance by adjusting the flash luminance that compensated for changes in the pupil size. Our results showed that there were significant correlations between the severity of DR and the implicit times (P < 0.001;r = 0.55) and the amplitudes (P = 0.001;r = −0.29). When the implicit time was used for the index, the area under the receiver operating characteristic curve was 0.84 for the detection of DR, and was 0.89 for the detection of DR requiring ophthalmic treatments. These results suggest that the implicit times of the flicker ERGs recorded by the small, mydryasis-free ERG system can be used as an adjunctive tool to screen for DR.
Mutually Exclusive Uncertainty Relations
Authors: Xiao Yunlong , Jing Naihuan
Published: November 2016

The uncertainty principle is one of the characteristic properties of quantum theory based on incompatibility. Apart from the incompatible relation of quantum states, mutually exclusiveness is another remarkable phenomenon in the information- theoretic foundation of quantum theory. We investigate the role of mutual exclusive physical states in the recent work of stronger uncertainty relations for all incompatible observables by Mccone and Pati and generalize the weighted uncertainty relation to the product form as well as their multi-observable analogues. The new bounds capture both incompatibility and mutually exclusiveness, and are tighter compared with the existing bounds.
Phenotypic differentiation of Streptococcus pyogenes populations is induced by recombination-driven gene-specific sweeps
Authors: Bao Yun-Juan , Shapiro B. Jesse , Lee Shaun W. , Ploplis Victoria A. , Castellino Francis J.
Published: November 2016

Genomic recombination plays an important role in driving adaptive evolution and population differentiation in bacteria. However, controversy exists as to the effects of recombination on population diversity and differentiation, i.e., recombination is frequent enough to sweep through the population at selected gene loci (gene-specific sweeps), or the recombination rate is low without interfering genome-wide selective sweeps. Observations supporting either view are sparse. Pathogenic bacteria causing infectious diseases are promising candidates to provide observations of recombination. However, phenotype-associated differentiations are usually vague among them due to diverse disease manifestations. Here we report a population genomic study of the group A Streptococcus pyogenes (GAS), a human pathogen with highly recombining genomes. By employing a genome-wide association study on single nucleotide polymorphisms (SNPs), we demonstrate a phenotypic differentiation of GAS, represented by separate clustering of two sublineages associated with niche-specific infections, i.e., skin infection and pharyngitis-induced acute rheumatic fever. By quantifying SNPs associated with the differentiation in a statistical and phylogenetic context, we propose that the phenotype-associated differentiation arose through recombination-driven gene-specific sweeps, rather than genome-wide sweeps. Our work provides a novel paradigm of phenotype-associated differentiation induced by gene-specific sweeps in a human pathogen and has implications for understanding of driving forces of bacterial evolution.
An Innovative Metal Ions Sensitive “Test Paper” Based on Virgin Nanoporous Silicon Wafer: Highly Selective to Copper(II)
Authors: Li Shaoyuan , Chen Xiuhua , Ma Wenhui , Ding Zhao , Zhang Cong , Chen Zhengjie , He Xiao , Shang Yudong , Zou Yuxin
Published: November 2016

Developing an innovative “Test Paper” based on virgin nanoporous silicon (NPSi) which shows intense visible emission and excellent fluorescence stability. The visual fluorescence quenching “Test Paper” was highly selective and sensitive recognizing Cu2+at μmol/L level. Within the concentration range of 5 × 10−7~50 × 10−7mol/L, the linear regression equation of IPL = 1226.3-13.6[CCu2+] (R = 0.99) was established for Cu2+quantitative detection. And finally, Cu2+fluorescence quenching mechanism of NPSi prober was proposed by studying the surface chemistry change of NPSi and metal ions immersed-NPSi using XPS characterization. The results indicate that SiHxspecies obviously contribute to the PL emission of NPSi, and the introduce of oxidization state and the nonradiative recombination center are responsible for the PL quenching. These results demonstrate how virgin NPSi wafer can serve as Cu2+sensor. This work is of great significant to promote the development of simple instruments that could realize rapid, visible and real-time detection of various toxic metal ions.
Continuous, One-pot Synthesis and Post-Synthetic Modification of NanoMOFs Using Droplet Nanoreactors
Authors: Jambovane Sachin R. , Nune Satish K. , Kelly Ryan T. , McGrail B. Peter , Wang Zheming , Nandasiri Manjula I. , Katipamula Shanta , Trader Cameron , Schaef Herbert T.
Published: November 2016

Metal-organic frameworks (MOFs); also known as porous coordination polymers (PCP) are a class of porous crystalline materials constructed by connecting metal clusters via organic linkers. The possibility of functionalization leads to virtually infinite MOF designs using generic modular methods. Functionalized MOFs can exhibit interesting physical and chemical properties including accelerated adsorption kinetics and catalysis. Although there are discrete methods to synthesize well-defined nanoscale MOFs, rapid and flexible methods are not available for continuous, one-pot synthesis and post-synthetic modification (functionalization) of MOFs. Here, we show a continuous, scalable nanodroplet-based microfluidic route that not only facilitates the synthesis of MOFs at a nanoscale, but also offers flexibility for direct functionalization with desired functional groups (e.g., -COCH3, fluorescein isothiocyanate; FITC). In addition, the presented route of continuous manufacturing of functionalized nanosized MOFs takes significantly less time compared to state-of-the-art batch methods currently available (1 hrvs.several days). We envisage our approach to be a breakthrough method for synthesizing complex functionalized nanomaterials (metal, metal oxides, quantum dots and MOFs) that are not accessible by direct batch processing and expand the range of a new class of functionalized MOF-based functional nanomaterials.
Functional and structural dissection of the tape measure protein of lactococcal phage TP901-1
Authors: Mahony Jennifer , Alqarni Mona , Stockdale Stephen , Spinelli Silvia , Feyereisen Marine , Cambillau Christian , Sinderen Douwe van
Published: November 2016

The tail tape measure protein (TMP) of tailed bacteriophages (also called phages) dictates the tail length and facilitates DNA transit to the cell cytoplasm during infection. Here, a thorough mutational analysis of the TMP from lactococcal phage TP901-1 (TMPTP901-1) was undertaken. We generated 56 mutants aimed at defining TMPTP901-1 domains that are essential for tail assembly and successful infection. Through analysis of the derived mutants, we determined that TP901-1 infectivity requires the N-terminal 154 aa residues, the C-terminal 60 residues and the first predicted hydrophobic region of TMPTP901-1 as a minimum. Furthermore, the role of TMPTP901-1 in tail length determination was visualized by electron microscopic imaging of TMP-deletion mutants. The inverse linear correlation between the extent of TMPTP901-1-encoding gene deletions and tail length of the corresponding virion provides an estimate of TMPTP901-1 regions interacting with the connector or involved in initiator complex formation. This study represents the most thorough characterisation of a TMP from a Gram-positive host-infecting phage and provides essential advances to understanding its role in virion assembly, morphology and infection.
RNA-seq analyses of the midgut from blood- and serum-fed Ixodes ricinus ticks
Authors: Perner Jan , Provazník Jan , Schrenková Jana , Urbanová Veronika , Ribeiro José M. C. , Kopáček Petr
Published: November 2016

Adult females of the genus Ixodes imbibe blood meals exceeding about 100 times their own weight within 7‒9 days. During this period, ticks internalise components of host blood by endocytic digest cells that line the tick midgut epithelium. Using RNA-seq, we aimed to characterise the midgut transcriptome composition in adult Ixodes ricinus females during early and late phase of engorgement. To address specific adaptations to the haemoglobin-rich diet, we compared the midgut transcriptomes of genetically homogenous female siblings fed either bovine blood or haemoglobin-depleted serum. We noted that tick gut transcriptomes are subject to substantial temporal-dependent expression changes between day 3 and day 8 of feeding. In contrast, the number of transcripts significantly affected by the presence or absence of host red blood cells was low. Transcripts relevant to the processes associated with blood-meal digestion were analysed and involvement of selected encoded proteins in the tick midgut physiology discussed. A total of 7215 novel sequences from I. ricinus were deposited in public databases as an additional outcome of this study. Our results broaden the current knowledge of tick digestive system and may lead to the discovery of potential molecular targets for efficient tick control.
Sulforaphane improves chemotherapy efficacy by targeting cancer stem cell-like properties via the miR-124/IL-6R/STAT3 axis
Authors: Wang Xingxing , Li Yuan , Dai Yi , Liu Qinqiang , Ning Shilong , Liu Jiao , Shen Zhaoxia , Zhu Dongmei , Jiang Fei , Zhang Jianping , Li Zhong
Published: November 2016

Gastric carcinoma (GC) is the second leading cause of cancer-related mortality worldwide. The efficacy of standard chemotherapy for GC, such as cisplatin (CDDP), is dissatisfactory partly due to the toxic/side-effects. Sulforaphane (SFN), which exhibits effective anti-cancer functions, is a phytochemical converted from cruciferous plants. Our present study aimed to identify whether SFN could enhance the anti-cancer effects of low-dose CDDP and to determine the underlying mechanisms. Herein, co-exposure of SFN and CDDP significantly inhibited the viabilities of gastric cancer cells. For the molecular mechanisms, CDDP alone increased the cancer stem cell (CSC)-like properties in gastric cancer cells via activating the interleukin-6 (IL-6)/IL-6 receptor (IL-6R)/signal transducer and activator of transcription 3 (STAT3) signaling. However, SFN could activate the microRNA-124 (miR-124), which directly targets the 3′-untranslated regions (UTR) of the IL-6R and STAT3. Moreover, knockdown of miR-124 eliminated the effects of SFN on CSC-like properties in GC cells, and in turn enhanced the anti-cancer effects of low-dose CDDP. These findings not only suggested a mechanism whereby SFN enhanced the anti-cancer functions of CDDP, but also helped to regard SFN as a potential chemotherapeutic factor in gastric cancer.
Novel Synthetic Techniques for Nanomaterials
Authors: Prado-Gonjal Jesús , Heuguet Romain , Marinel Sylvain , Morán Emilio , Schmidt Rainer
Published: November 2016

In this work, we describe the use of novel environmentally friendly industrial processing techniques to produce nano-sized crystallite powders and fabricate bulk ceramic pellets of functional materials. We present the application of a microwave (MW)-assisted synthesis process to fabricate the un-doped and doped ceria phases CeO2−δ, Ce0.8Gd0.1Sm0.1O1.9, Ce0.85Gd0.15O1.925, Ce0.85Sm0.15O1.925 and Ce0.8Sm0.18Ca0.02O1.9 for potential application in solid oxide fuel cells. We find that the composition Ce0.8Sm0.18Ca0.02O1.9 may be most beneficial owing to the highest ionic conductivities encountered in the corresponding sintered ceramics. As a next step, we tested a MW-assisted sintering process to fabricate dense Ce0.8Sm0.18Ca0.02O1.9 pellets. We find that both the synthesis and sintering process can be achieved by using MW heat sources and the entire fabrication process may be regarded a “green ceramic processing”.
Adsorption and Desorption on Nanostructured Materials
Authors: Gill Rohama , Nadeem QuratulAin , Bououdina Mohamed
Published: November 2016

Release of toxic pollutants from industries, whether in the form of liquids or gases, has adversely affected the quality of the environment. To remediate the environment from such pollutants, a large number of conventional methods and advanced technologies have been developed and adopted. Amongst these innumerable methods, adsorption has emerged as one of the most significant processes to remove pollutants of a diverse nature. The present work is based on the ability of nanostructured materials as adsorbents for various gaseous and liquid pollutants. The mechanism of adsorption and desorption is elaborated along with factors that are responsible for the occurrence of such processes. The role of nano-sized carbonaceous, metallic, magnetic, metal oxides, clays, silicon and polymer-based materials, is highlighted as advanced nanosorbents to eradicate pollutants such as noxious gases, organic/inorganic chemicals, dyes, heavy metals, etc. released in the environment as a result of anthropogenic activities.
Nanomaterials for Heavy Metal Removal
Authors: Azzaza S. , Kumar R. Thinesh , Vijaya J. Judith , Bououdina M.
Published: November 2016

Wastewater containing heavy metal ions is considered as a serious environmental problem for human society. Advances in nanoscale science and engineering provide new opportunities to develop more cost-effective and environmentally acceptable water treatment technologies. Nanomaterials have a number of physicochemical properties that make them particularly attractive as nanoadsorbents for decontamination of wastewaters from heavy metals. These materials are capable of removing heavy metal ions at low concentrations with high selectivity and adsorption capacity. The use of various nanoadsorbents in treating contaminated water, mainly including carbon-based nanomaterials, iron-based nanomaterials and photocatalytic nanomaterials, was overviewed; their advantages and drawbacks in such applications were evaluated.
Pretreatment Processes for the Analysis of Organic Pollutants with Nanomaterials
Authors: Amiri Amirhassan
Published: November 2016

It is necessary to monitor organic pollutants in environmental samples because many of these compounds can pose threats to human health and the ecosystem. Despite advances in analytical instruments, the direct analysis of organic contaminants is not always possible owing to the low concentrations of the analytes and matrix interferences. Therefore, one or more pretreatment steps are necessary with the goal of enrichment, clean-up and signal enhancement. On the other hand, sample preparation still consumes the most time and labour in the analytical procedure, so attempts are being made to improve this step in terms of speed, reliability and sensitivity. In recent years, separation technology based on nanomaterials has received considerable attention. The incorporation of nanoparticles in the sample treatment step, in general, helps to simplify this step. This chapter aims to study the different applications of nanomaterials in the sample preparation procedures of organic pollutants, which allows simplification of the method and the possibility of treating small amounts of sample.
Application of Nanomaterials in Membrane Technology
Authors: Kar Soumitra , Bindal R. C.
Published: November 2016

This chapter discusses the reciprocal impact of analytical science and nanotechnology and demonstrates how this technology can be expected to reinforce the responsibility of chemists in the field of analytical chemistry. Does analytical nanotechnology constitute the last step in the technical trend for miniaturization via the macro-to-micro-to-nano sequence? It obviously does. However, the “nanoscale” concept has introduced a new scenario where physicochemical principles, laws and properties are quite different from those of the macro and micro worlds. Since then, this concept has been gaining interest, but it is only in recent years that a great development effort has been made to obtain analytical technologies that are able to do direct analysis, using miniaturized equipment, with reduced amounts of solvents, on-site and with reduced energy costs and wastes. These improvements were linked to advances in other research areas (e.g., microelectronics, material sciences, biochemistry and, recently, nanotechnology). To this end, this chapter defines the limits of actual nanotechnological approaches and uses selected examples to illustrate the major relationships between analytical science and nanotechnology, for example: the design and use of nanodevices; the use of nanoparticles (and nanostructures) in analytical processes; and the extraction of accurate chemical information from the nano-world.