bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthetic and systems biology for microbial production of commodity chemicals
Authors: Chubukov Victor , Mukhopadhyay Aindrila , Petzold Christopher J , Keasling Jay D , Martín Héctor García 
Published: April 2016

AbstractThe combination of synthetic and systems biology is a powerful framework to study fundamental questions in biology and produce chemicals of immediate practical application such as biofuels, polymers, or therapeutics. However, we cannot yet engineer biological systems as easily and precisely as we engineer physical systems. In this review, we describe the path from the choice of target molecule to scaling production up to commercial volumes. We present and explain some of the current challenges and gaps in our knowledge that must be overcome in order to bring our bioengineering capabilities to the level of other engineering disciplines. Challenges start at molecule selection, where a difficult balance between economic potential and biological feasibility must be struck. Pathway design and construction have recently been revolutionized by next-generation sequencing and exponentially improving DNA synthesis capabilities. Although pathway optimization can be significantly aided by enzyme expression characterization through proteomics, choosing optimal relative protein expression levels for maximum production is still the subject of heuristic, non-systematic approaches. Toxic metabolic intermediates and proteins can significantly affect production, and dynamic pathway regulation emerges as a powerful but yet immature tool to prevent it. Host engineering arises as a much needed complement to pathway engineering for high bioproduct yields; and systems biology approaches such as stoichiometric modeling or growth coupling strategies are required. A final, and often underestimated, challenge is the successful scale up of processes to commercial volumes. Sustained efforts in improving reproducibility and predictability are needed for further development of bioengineering.
An Adaptive Weighting Algorithm for Interpolating the Soil Potassium Content
Authors: Liu Wei , Du Peijun , Zhao Zhuowen , Zhang Lianpeng 
Published: April 2016

AbstractThe concept of spatial interpolation is important in the soil sciences. However, the use of a single global interpolation model is often limited by certain conditions (e.g., terrain complexity), which leads to distorted interpolation results. Here we present a method of adaptive weighting combined environmental variables for soil properties interpolation (AW-SP) to improve accuracy. Using various environmental variables, AW-SP was used to interpolate soil potassium content in Qinghai Lake Basin. To evaluate AW-SP performance, we compared it with that of inverse distance weighting (IDW), ordinary kriging, and OK combined with different environmental variables. The experimental results showed that the methods combined with environmental variables did not always improve prediction accuracy even if there was a strong correlation between the soil properties and environmental variables. However, compared with IDW, OK, and OK combined with different environmental variables, AW-SP is more stable and has lower mean absolute and root mean square errors. Furthermore, the AW-SP maps provided improved details of soil potassium content and provided clearer boundaries to its spatial distribution. In conclusion, AW-SP can not only reduce prediction errors, it also accounts for the distribution and contributions of environmental variables, making the spatial interpolation of soil potassium content more reasonable.
Vesicle Size Regulates Nanotube Formation in the Cell
Authors: Su Qian Peter , Du Wanqing , Ji Qinghua , Xue Boxin , Jiang Dong , Zhu Yueyao , Ren He , Zhang Chuanmao , Lou Jizhong , Yu Li , Sun Yujie 
Published: April 2016

AbstractIntracellular membrane nanotube formation and its dynamics play important roles for cargo transportation and organelle biogenesis. Regarding the regulation mechanisms, while much attention has been paid on the lipid composition and its associated protein molecules, effects of the vesicle size has not been studied in the cell. Giant unilamellar vesicles (GUVs) are often used for in vitro membrane deformation studies, but they are much larger than most intracellular vesicles and the in vitro studies also lack physiological relevance. Here, we use lysosomes and autolysosomes, whose sizes range between 100 nm and 1 μm, as model systems to study the size effects on nanotube formation both in vivo and in vitro. Single molecule observations indicate that driven by kinesin motors, small vesicles (100–200 nm) are mainly transported along the tracks while a remarkable portion of large vesicles (500–1000 nm) form nanotubes. This size effect is further confirmed by in vitro reconstitution assays on liposomes and purified lysosomes and autolysosomes. We also apply Atomic Force Microscopy (AFM) to measure the initiation force for nanotube formation. These results suggest that the size-dependence may be one of the mechanisms for cells to regulate cellular processes involving membrane-deformation, such as the timing of tubulation-mediated vesicle recycling.
Clinicopathological Characteristics and Survival Outcomes in Invasive Papillary Carcinoma of the Breast: A SEER Population-Based Study
Authors: Zheng Yi-Zi , Hu Xin , Shao Zhi-Ming 
Published: April 2016

AbstractTo investigate the clinicopathological characteristics and survival outcomes of invasive papillary carcinoma (IPC), we identified 233,171 female patients in the Surveillance, Epidemiology and End Results (SEER) database who had IPC (n = 524) or infiltrating ductal carcinoma (IDC) (n = 232,647). Generally, IPCs occurred in older women (≥50 years old) and presented with smaller sizes, lower grades, higher rates of oestrogen receptor (ER) and progesterone receptor (PR) positivity and reduced lymph node (LN) involvement and were less likely to be treated with mastectomy than patients with IDC. The five-year disease-specific survival (DSS) rates were significantly better in IPC than in IDC (97.5% vs. 93%, respectively; P < 0.001). In the multivariate analysis, patients with IPC showed a DSS that was similar to that of IDC (hazard ratio = 0.556, 95% confidence interval 0.289–1.070, P = 0.079). No significant difference was observed in DSS between matched IPC and IDC groups (P = 0.085). Differences in outcomes may be partially explained by differences in tumour grade, LN status and ER and PR status between the 2 groups. Gaining an improved clinical and biological understanding of IPC might result in more tailored and effective therapies in breast cancer patients.
Allosteric Partial Inhibition of Monomeric Proteases. Sulfated Coumarins Induce Regulation, not just Inhibition, of Thrombin
Authors: Verespy III Stephen , Mehta Akul Y. , Afosah Daniel , Al-Horani Rami A. , Desai Umesh R. 
Published: April 2016

AbstractAllosteric partial inhibition of soluble, monomeric proteases can offer major regulatory advantages, but remains a concept on paper to date; although it has been routinely documented for receptors and oligomeric proteins. Thrombin, a key protease of the coagulation cascade, displays significant conformational plasticity, which presents an attractive opportunity to discover small molecule probes that induce sub-maximal allosteric inhibition. We synthesized a focused library of some 36 sulfated coumarins to discover two agents that display sub-maximal efficacy (~50%), high potency (<500 nM) and high selectivity for thrombin (>150-fold). Michaelis-Menten, competitive inhibition, and site-directed mutagenesis studies identified exosite 2 as the site of binding for the most potent sulfated coumarin. Stern-Volmer quenching of active site-labeled fluorophore suggested that the allosteric regulators induce intermediate structural changes in the active site as compared to those that display ~80–100% efficacy. Antithrombin inactivation of thrombin was impaired in the presence of the sulfated coumarins suggesting that allosteric partial inhibition arises from catalytic dysfunction of the active site. Overall, sulfated coumarins represent first-in-class, sub-maximal inhibitors of thrombin. The probes establish the concept of allosteric partial inhibition of soluble, monomeric proteins. This concept may lead to a new class of anticoagulants that are completely devoid of bleeding.
RXR controlled regulatory networks identified in mouse brain counteract deleterious effects of Aβ oligomers
Authors: Nam Kyong Nyon , Mounier Anais , Fitz Nicholas F. , Wolfe Cody , Schug Jonathan , Lefterov Iliya , Koldamova Radosveta 
Published: April 2016

AbstractBexarotene, a selective agonist for Retinoid X receptors (RXR) improves cognitive deficits and amyloid-β (Aβ) clearance in mice. Here we examine if the effect of bexarotene on RXR cistrome and transcriptomes depend on APOE isoform and Aβ deposition. We found bexarotene increased RXR binding to promoter regions in cortex of APOE3 mice. Rho family GTPases and Wnt signaling pathway were highly enriched in ChIP-seq and RNA-seq datasets and members of those pathways - Lrp1, Lrp5, Sfrp5 and Sema3f were validated. The effect of APOE isoform was compared in APOE3 and APOE4 mice and we found significant overlapping in affected pathways. ChIP-seq using mouse embryonic stem cells and enrichment levels of histone marks H3K4me3 and H3K27me3 revealed that, bexarotene induced epigenetic changes, consistent with increased neuronal differentiation and in correlation with changes in transcription. Comparison of transcriptome in APOE3 and APP/APOE3 mice revealed that amyloid deposition significantly affects the response to bexarotene. In primary neurons, bexarotene ameliorated the damaged dendrite complexity and loss of neurites caused by Aβ42. Finally, we show that the disruption of actin cytoskeleton induced by Aβ42in vitro was inhibited by bexarotene treatment. Our results suggest a mechanism to establish RXR therapeutic targets with significance in neurodegeneration.
Empirical insights into the stochasticity of small RNA sequencing
Authors: Qin Li-Xuan , Tuschl Thomas , Singer Samuel 
Published: April 2016

AbstractThe choice of stochasticity distribution for modeling the noise distribution is a fundamental assumption for the analysis of sequencing data and consequently is critical for the accurate assessment of biological heterogeneity and differential expression. The stochasticity of RNA sequencing has been assumed to follow Poisson distributions. We collected microRNA sequencing data and observed that its stochasticity is better approximated by gamma distributions, likely because of the stochastic nature of exponential PCR amplification. We validated our findings with two independent datasets, one for microRNA sequencing and another for RNA sequencing. Motivated by the gamma distributed stochasticity, we provided a simple method for the analysis of RNA sequencing data and showed its superiority to three existing methods for differential expression analysis using three data examples of technical replicate data and biological replicate data.
Predicting the response of olfactory sensory neurons to odor mixtures from single odor response
Authors: Marasco Addolorata , De Paris Alessandro , Migliore Michele 
Published: April 2016

AbstractThe response of olfactory receptor neurons to odor mixtures is not well understood. Here, using experimental constraints, we investigate the mathematical structure of the odor response space and its consequences. The analysis suggests that the odor response space is 3-dimensional, and predicts that the dose-response curve of an odor receptor can be obtained, in most cases, from three primary components with specific properties. This opens the way to an objective procedure to obtain specific olfactory receptor responses by manipulating mixtures in a mathematically predictable manner. This result is general and applies, independently of the number of odor components, to any olfactory sensory neuron type with a response curve that can be represented as a sigmoidal function of the odor concentration.
PTP1B inhibitor promotes endothelial cell motility by activating the DOCK180/Rac1 pathway
Authors: Wang Yuan , Yan Feng , Ye Qing , Wu Xiao , Jiang Fan 
Published: April 2016

AbstractPromoting endothelial cell (EC) migration is important not only for therapeutic angiogenesis, but also for accelerating re-endothelialization after vessel injury. Several recent studies have shown that inhibition of protein tyrosine phosphatase 1B (PTP1B) may promote EC migration and angiogenesis by enhancing the vascular endothelial growth factor receptor-2 (VEGFR2) signalling. In the present study, we demonstrated that PTP1B inhibitor could promote EC adhesion, spreading and migration, which were abolished by the inhibitor of Rac1 but not RhoA GTPase. PTP1B inhibitor significantly increased phosphorylation of p130Cas and the interactions among p130Cas, Crk and DOCK180; whereas the phosphorylation levels of focal adhesion kinase, Src, paxillin, or Vav2 were unchanged. Gene silencing of DOCK180, but not Vav2, abrogated the effects of PTP1B inhibitor on EC motility. The effects of PTP1B inhibitor on EC motility and p130Cas/DOCK180 activation persisted in the presence of the VEGFR2 antagonist. In conclusion, we suggest that stimulation of the DOCK180 pathway represents an alternative mechanism of PTP1B inhibitor-stimulated EC motility, which does not require concomitant VEGFR2 activation as a prerequisite. Therefore, PTP1B inhibitor may be a useful therapeutic strategy for promoting EC migration in cardiovascular patients in which the VEGF/VEGFR functions are compromised.
A Tricholoma matsutake Peptide with Angiotensin Converting Enzyme Inhibitory and Antioxidative Activities and Antihypertensive Effects in Spontaneously Hypertensive Rats
Authors: Geng Xueran , Tian Guoting , Zhang Weiwei , Zhao Yongchang , Zhao Liyan , Wang Hexiang , Ng Tzi Bun 
Published: April 2016

AbstractHypertension is a major risk factor for cardiovascular disease. A crude water extract of the fruiting bodies of a highly prized mushroom Tricholoma matsutakei exerted an antihypertensive action on spontaneously hypertensive rats (SHRs) at a dosage of 400 mg/kg. An angiotensin converting enzyme (ACE) inhibitory peptide with an IC50 of 0.40 μM was purified from the extract and designated as TMP. Its amino acid sequence was elucidated to be WALKGYK through LC-MS/MS analysis. The Lineweaver-Burk plot suggested that TMP was a non-competitive inhibitor of ACE. A short-term assay of antihypertensive activity demonstrated that TMP at the dosage of 25 mg/kg could significantly lower the systolic blood pressure (SBP) of SHRs. TMP exhibited remarkable stability over a wide range of temperatures and pH values. It also demonstrated 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity. The aforementioned activities of TMP were corroborated by utilizing the synthetic peptide. Hence T. matsutake can be used as a functional food to help prevent hypertension- associated diseases.
Super Stable Ferroelectrics with High Curie Point
Authors: Gao Zhipeng , Lu Chengjia , Wang Yuhang , Yang Sinuo , Yu Yuying , He Hongliang 
Published: April 2016

AbstractFerroelectric materials are of great importance in the sensing technology due to the piezoelectric properties. Thermal depoling behavior of ferroelectrics determines the upper temperature limit of their application. So far, there is no piezoelectric material working above 800 °C available. Here, we show Nd2Ti2O7with a perovskite-like layered structure has good resistance to thermal depoling up to 1400 °C. Its stable behavior is because the material has only 180° ferroelectric domains, complex structure change at Curie point (Tc) and their sintering temperature is below their Tc, which avoided the internal stresses produced by the unit cell volume change at Tc. The phase transition at Tcshows a first order behavior which involving the tilting and rotation of the octahedron. The Curie – Weiss temperature is calculated, which might explain why the thermal depoling starts at about 1400 °C.
Effect of pH on the structure and drug release profiles of layer-by-layer assembled films containing polyelectrolyte, micelles, and graphene oxide
Authors: Han Uiyoung , Seo Younghye , Hong Jinkee 
Published: April 2016

AbstractLayer by layer (lbl) assembled multilayer thin films are used in drug delivery systems with attractive advantages such as unlimited selection of building blocks and free modification of the film structure. In this paper, we report the fundamental properties of lbl films constructed from different substances such as PS-b-PAA amphiphilic block copolymer micelles (BCM) as nano-sized drug vehicles, 2D-shaped graphene oxide (GO), and branched polyethylenimine (bPEI). These films were fabricated by successive lbl assembly as a result of electrostatic interactions between the carboxyl group of BCM and amine group of functionalized GO or bPEI under various pH conditions. We also compared the thickness, roughness, morphology and degree of adsorption of the (bPEI/BCM) films to those in the (GO/BCM) films. The results showed significant difference because of the distinct pH dependence of each material. In addition, drug release rates of the GO/BCM film were more rapid those of the (bPEI/BCM) film in pH 7.4 and pH 2 PBS buffer solutions. In (bPEI/BCM/GO/BCM) film, the inserted GO layers into bPEI/BCM multilayer induced rapid drug release. We believe that these materials & pH dependent film properties allow developments in the control of coating techniques for biological and biomedical applications.
The roles of thermal insulation and heat storage in the energy performance of the wall materials: a simulation study
Authors: Long Linshuang , Ye Hong 
Published: April 2016

AbstractA high-performance envelope is the prerequisite and foundation to a zero energy building. The thermal conductivity and volumetric heat capacity of a wall are two thermophysical properties that strongly influence the energy performance. Although many case studies have been performed, the results failed to give a big picture of the roles of these properties in the energy performance of an active building. In this work, a traversal study on the energy performance of a standard room with all potential wall materials was performed for the first time. It was revealed that both heat storage materials and insulation materials are suitable for external walls. However, the importances of those materials are distinct in different situations: the heat storage plays a primary role when the thermal conductivity of the material is relatively high, but the effect of the thermal insulation is dominant when the conductivity is relatively low. Regarding internal walls, they are less significant to the energy performance than the external ones, and they need exclusively the heat storage materials with a high thermal conductivity. These requirements for materials are consistent under various climate conditions. This study may provide a roadmap for the material scientists interested in developing high-performance wall materials.
Loss-of-function Mutation in PMVK Causes Autosomal Dominant Disseminated Superficial Porokeratosis
Authors: Wang Jiuxiang , Liu Ying , Liu Fei , Huang Changzheng , Han Shanshan , Lv Yuexia , Liu Chun-Jie , Zhang Su , Qin Yayun , Ling Lei , Gao Meng , Yu Shanshan , Li Chang , Huang Mi , Liao Shengjie , Hu Xuebin , Lu Zhaojing , Liu Xiliang , Jiang Tao , Tang Zhaohui , Zhang Huiping , Guo An-Yuan , Liu Mugen 
Published: April 2016

AbstractDisseminated superficial porokeratosis (DSP) is a rare keratinization disorder of the epidermis. It is characterized by keratotic lesions with an atrophic center encircled by a prominent peripheral ridge. We investigated the genetic basis of DSP in two five-generation Chinese families with members diagnosed with DSP. By whole-exome sequencing, we sequencing identified a nonsense variation c.412C > T (p.Arg138*) in the phosphomevalonate kinase gene (PMVK), which encodes a cytoplasmic enzyme catalyzing the conversion of mevalonate 5-phosphate to mevalonate 5-diphosphate in the mevalonate pathway. By co-segregation and haplotype analyses as well as exclusion testing of 500 normal control subjects, we demonstrated that this genetic variant was involved in the development of DSP in both families. We obtained further evidence from studies using HaCaT cells as models that this variant disturbed subcellular localization, expression and solubility of PMVK. We also observed apparent apoptosis in and under the cornoid lamella of PMVK-deficient lesional tissues, with incomplete differentiation of keratinocytes. Our findings suggest that PMVK is a potential novel gene involved in the pathogenesis of DSP and PMVK deficiency or abnormal keratinocyte apoptosis could lead to porokeratosis.
Antidepressant-like Effects of LPM580153, A Novel Potent Triple Reuptake Inhibitor
Authors: Zhang Fangxi , Shao Jing , Tian Jingwei , Zhong Yan , Ye Liang , Meng Xiangjing , Liu Qiaofeng , Wang Hongbo 
Published: April 2016

AbstractThe purpose of this study was to characterize a novel compound, 4-[2-(dimethylamino)-1-(1-hydroxycyclohexyl) ethyl] phenyl 3-nitrophenyl ether, designated LPM580153. We used several well-validated animal models of depression to assess the antidepressant-like activity of LPM580153, followed by a neurotransmitter uptake assay and a corticosterone-induced cell injury model to explore its mechanism of action. In mice, LPM580153 reduced immobility time in the tail suspension test, and in rats subjected to chronic unpredictable mild stress it reversed reductions in body weight gain and ameliorated anhedonia. The neurotransmitter uptake assay results demonstrated that LPM580153 inhibited the uptake of serotonin, norepinephrine and dopamine. Furthermore, LPM580153 protected the SH-SY5Y cells against the cytotoxic activity of corticosterone, an action that might be related to the role of LPM580153 in increasing the protein levels of BDNF, p-ERK1/2, p-AKT, p-CREB and p-mTOR. Together, these findings indicate that LPM580153 is a novel triple reuptake inhibitor with robust antidepressant-like effects.
Production of FAME biodiesel in E. coli by direct methylation with an insect enzyme
Authors: Sherkhanov Saken , Korman Tyler P. , Clarke Steven G , Bowie James U. 
Published: April 2016

AbstractMost biodiesel currently in use consists of fatty acid methyl esters (FAMEs) produced by transesterification of plant oils with methanol. To reduce competition with food supplies, it would be desirable to directly produce biodiesel in microorganisms. To date, the most effective pathway for the production of biodiesel in bacteria yields fatty acid ethyl esters (FAEEs) at up to ~1.5 g/L. A much simpler route to biodiesel produces FAMEs by direct S-adenosyl-L-methionine (SAM) dependent methylation of free fatty acids, but FAME production by this route has been limited to only ~16 mg/L. Here we employ an alternative, broad spectrum methyltransferase, Drosophila melanogaster Juvenile Hormone Acid O-Methyltransferase (DmJHAMT). By introducing DmJHAMT in E. coli engineered to produce medium chain fatty acids and overproduce SAM, we obtain medium chain FAMEs at titers of 0.56 g/L, a 35-fold increase over titers previously achieved. Although considerable improvements will be needed for viable bacterial production of FAMEs and FAEEs for biofuels, it may be easier to optimize and transport the FAME production pathway to other microorganisms because it involves fewer enzymes.