bluuebunny/crossref_metadata_2025 huggingface dataset:
Down‐regulation of hepatic CYP3A1 expression in a rat model of indomethacin‐induced small intestinal ulcers
Authors: Kawauchi Shoji , Nakamura Tsutomu , Horibe Sayo , Tanahashi Toshihito , Mizuno Shigeto , Hamaguchi Tsuneo , Rikitake Yoshiyuki
Published: September 2016

The liver and the small intestine are closely related in the processes of drug absorption, metabolism and excretion via the enterohepatic circulation. Small intestinal ulcers are a serious adverse effect commonly occurring in patients taking nonsteroidal anti‐inflammatory drugs. However, the influence of small intestinal ulcers on drug metabolism has not been established. This study examined the expressional changes of cytochrome P450 (CYP) in the liver using an indomethacin‐induced small intestinal ulcer rat model and in cultured cells. After the administration of indomethacin to rats, ulcers were observed in the small intestine and expression of CYP3A1, the major isoform of hepatic CYP, was significantly down‐regulated in the liver, accompanied by increased expression of inducible nitric oxide synthase, tumor necrosis factor α, interleukin (IL)‐1β and IL‐6, in the small intestine and the liver. The indomethacin‐induced small intestinal ulceration, the increase in inflammatory mediators in the small intestine and the liver, and the down‐regulation of CYP3A1 expression in the liver were inhibited by co‐administration of ampicillin, an antibacterial agent. In the human hepatic HepG2 cell line, IL‐1β, IL‐6 and NOC‐18, an NO donor, caused down‐regulation of CYP3A4, the major isoform of human CYP3A. Thus, this study suggests that after indomethacin treatment small intestinal ulcers cause the down‐regulation of CYP3A1 in the rat liver through an increase in ulcer‐derived inflammatory mediators. Copyright © 2016 John Wiley & Sons, Ltd.
A SUMO and ubiquitin code coordinates protein traffic at replication factories
Authors: Lecona Emilio , Fernandez‐Capetillo Oscar
Published: September 2016

Post‐translational modifications regulate each step of DNA replication to ensure the faithful transmission of genetic information. In this context, we recently showed that deubiquitination of SUMO2/3 and SUMOylated proteins by USP7 helps to create a SUMO‐rich and ubiquitin‐low environment around replisomes that is necessary to maintain the activity of replication forks and for new origin firing. We propose that a two‐flag system mediates the collective concentration of factors at sites of DNA replication, whereby SUMO and Ubiquitinated‐SUMO would constitute “stay” or “go” signals respectively for replisome and accessory factors. We here discuss the findings that led to this model, which have implications for the potential use of USP7 inhibitors as anticancer agents.
Identification of key genes involved in polysaccharide bioflocculant synthesis in Bacillus licheniformis
Authors: Chen Zhen , Liu Peize , Li Zhipeng , Yu Wencheng , Wang Zhi , Yao Haosheng , Wang Yuanpeng , Li Qingbiao , Deng Xu , He Ning
Published: September 2016

The present study reports the sequenced genome of Bacillus licheniformis CGMCC 2876, which is composed of a 4,284,461 bp chromosome that contains 4,188 protein‐coding genes, 72 tRNA genes, and 21 rRNA genes. Additional analysis revealed an eps gene cluster with 16 open reading frames. Conserved Domains Database analysis combined with qPCR experiments indicated that all genes in this cluster were involved in polysaccharide bioflocculant synthesis. Phosphoglucomutase and UDP‐glucose pyrophosphorylase were supposed to be key enzymes in polysaccharide secretion in B. licheniformis. A biosynthesis pathway for the production of polysaccharide bioflocculant involving the integration of individual genes was proposed based on functional analysis. Overexpression of epsDEF from the eps gene cluster in B. licheniformis CGMCC 2876 increased the flocculating activity of the recombinant strain by 90% compared to the original strain. Similarly, the crude yield of polysaccharide bioflocculant was enhanced by 27.8%. Overexpression of the UDP‐glucose pyrophosphorylase gene not only increased the flocculating activity by 71% but also increased bioflocculant yield by 13.3%. Independent of UDP‐N‐acetyl‐D‐mannosamine dehydrogenase gene, flocculating activity, and polysaccharide yield were negatively impacted by overexpression of the UDP‐N‐acetylglucosamine 2‐epimerase gene. Overall, epsDEF and gtaB2 were identified as key genes for polysaccharide bioflocculant synthesis in B. licheniformis. These results will be useful for further engineering of B. licheniformis for industrial bioflocculant production. Biotechnol. Bioeng. 2017;114: 645–655. © 2016 Wiley Periodicals, Inc.
Development of in situ product removal strategies in biocatalysis applying scaled‐down unit operations
Authors: Heintz Søren , Börner Tim , Ringborg Rolf H. , Rehn Gustav , Grey Carl , Nordblad Mathias , Krühne Ulrich , Gernaey Krist V. , Adlercreutz Patrick , Woodley John M.
Published: September 2016

An experimental platform based on scaled‐down unit operations combined in a plug‐and‐play manner enables easy and highly flexible testing of advanced biocatalytic process options such as in situ product removal (ISPR) process strategies. In such a platform, it is possible to compartmentalize different process steps while operating it as a combined system, giving the possibility to test and characterize the performance of novel process concepts and biocatalysts with minimal influence of inhibitory products. Here the capabilities of performing process development by applying scaled‐down unit operations are highlighted through a case study investigating the asymmetric synthesis of 1‐methyl‐3‐phenylpropylamine (MPPA) using ω‐transaminase, an enzyme in the sub‐family of amino transferases (ATAs). An on‐line HPLC system was applied to avoid manual sample handling and to semi‐automatically characterize ω‐transaminases in a scaled‐down packed‐bed reactor (PBR) module, showing MPPA as a strong inhibitor. To overcome the inhibition, a two‐step liquid–liquid extraction (LLE) ISPR concept was tested using scaled‐down unit operations combined in a plug‐and‐play manner. Through the tested ISPR concept, it was possible to continuously feed the main substrate benzylacetone (BA) and extract the main product MPPA throughout the reaction, thereby overcoming the challenges of low substrate solubility and product inhibition. The tested ISPR concept achieved a product concentration of 26.5 gMPPA · L−1, a purity up to 70% gMPPA · gtot−1 and a recovery in the range of 80% mol · mol−1 of MPPA in 20 h, with the possibility to increase the concentration, purity, and recovery further. Biotechnol. Bioeng. 2017;114: 600–609. © 2016 Wiley Periodicals, Inc.
Biaryl Diketone Synthesis via Palladium‐catalyzed Carbonylative Coupling with Carbon Monoxide or Various Metal Carbonyls
Authors: Cho Soo Kyung , Song Ju Hyun , Hahn Jung Tae , Jung Dai il
Published: September 2016

Biaryl diketones were synthesized via palladium‐catalyzed carbonylative coupling in the presence of a palladium N‐heterocyclic carbene complex and CO or metal carbonyls. Different arylboronic acids along with various CO‐releasing molecules were tested to study the influence of structure. Generally, steric hindrance of arylboronic acids and CO‐releasing ability of various metal carbonyls played significant roles. In most cases, single ketone products were found as the side products rather than direct coupling products.
Effects of Hydrophobic Peptoid Substitutions on the Bacterial Cell Selectivity and Antimicrobial Activity of Piscidin 1
Authors: Jeong Min‐Cheol , Jeon Dasom , Shin Areum , Jin Sodam , Shin Song Yub , Park Yong Sun , Kim Yangmee
Published: September 2016

Piscidin 1 (Pis‐1) from hybrid striped bass possesses antibacterial activities with high cytotoxicity. Previously, we reported that Pis‐1[NkG], where Gly8 was substituted with positively charged Lys peptoid in Pis‐1, shows high antibacterial activity with more potent bacterial cell selectivity than parent Pis‐1 and Pis‐1[PG] with Pro substitution at Gly8. Here, we investigated the effects of hydrophobic peptoid substitutions on antimicrobial activity and cytotoxicity of Pis‐1. We designed Pis‐1[NaG] and Pis‐1[NlG] peptides, where Gly8 was replaced with alanine or leucine peptoids. Although hydrophobicity was increased in Pis‐1[NaG] and Pis‐1[NlG] compared with that in Pis‐1[NkG], Pis‐1, and Pis‐1[PG], these peptides retained high antibacterial activity and showed no hemolytic activity when used at 100 μM. All peptoid‐substituted peptides penetrated well the bacterial membrane and localized inside of the cytoplasm, while Pis‐1 and Pis‐1[PG] depolarized membrane severely. The flexible hinge structure formed by peptoid residues compared with the rigid bent structure formed by proline may explain their differential mechanisms of action. Most hydrophobic peptide, Pis‐1[NlG], showed the most efficient inhibition of LPS (lipopolysaccharide)‐induced nitric oxide production, indicating that it can be a potent antimicrobial peptide with anti‐inflammatory activities. Peptoid substitution may facilitate the development of potent peptide drugs with bacterial cell selectivity.
Simultaneous analysis of 35 specific antihypertensive adulterants in dietary supplements using LC/MS/MS
Authors: Heo Seok , Choi Ji Yeon , Yoo Geum Joo , Park Sung‐Kwan , Baek Sun Young
Published: September 2016

A sensitive and specific LC/MS/MS method was developed for the simultaneous analysis of 35 compounds used for treating hypertension as adulterants in dietary supplements. The method was validated for specificity, linearity, accuracy, precision, limit of detection, limit of quantitation, stability and recovery. The limit of detection and limit of quantitation ranged from 0.20 to 20.0 and 0.50 to 60.0 ng/g, respectively. The linearity was good (r2 > 0.999), with intra‐ and interday precision levels of 0.43–7.87% and 0.65–9.95% and the intra‐ and interday accuracies of 84.36–115.82% and 83.78–118.69%, respectively. The stability (relative standard deviation) was <14.75%. The mean recovery was 80.81–117.86% (relative standard deviation <10.00%). Ninety‐seven commercial dietary supplements available in South Korea were analyzed. While none contained detectable amounts of the 35 antihypertensive compounds, the developed LC/MS/MS procedure can be used for routine analysis to monitor illegal adulteration in various forms of dietary supplements.
Primary cutaneous B‐cell lymphoma other than marginal zone: clinicopathologic analysis of 161 cases: Comparison with current classification and definition of prognostic markers
Authors: Lucioni Marco , Berti Emilio , Arcaini Luca , Croci Giorgio A. , Maffi Aldo , Klersy Catherine , Goteri Gaia , Tomasini Carlo , Quaglino Pietro , Riboni Roberta , Arra Mariarosa , Dallera Elena , Grandi Vieri , Alaibac Mauro , Ramponi Antonio , Rattotti Sara , Cabras Maria Giuseppina , Franceschetti Silvia , Fraternali‐Orcioni Giulio , Zerbinati Nicola , Onida Francesco , Ascani Stefano , Fierro Maria Teresa , Rupoli Serena , Gambacorta Marcello , Zinzani Pier Luigi , Pimpinelli Nicola , Santucci Marco , Paulli Marco
Published: September 2016

Categorization of primary cutaneous B‐cell lymphomas (PCBCL) other than marginal zone (MZL) represents a diagnostic challenge with relevant prognostic implications. The 2008 WHO lymphoma classification recognizes only primary cutaneous follicular center cell lymphoma (PCFCCL) and primary cutaneous diffuse large B‐cell lymphoma, leg type (PCDLBCL‐LT), whereas the previous 2005 WHO/EORTC classification also included an intermediate form, namely PCDLBCL, other. We conducted a retrospective, multicentric, consensus‐based revision of the clinicopathologic characteristics of 161 cases of PCBCL other than MZL. Upon the histologic features that are listed in the WHO classification, 96 cases were classified as PCFCCL and 25 as PCDLBCL‐LT; 40 further cases did not fit in the former subgroups in terms of cytology and/or architecture, thus were classified as PCDLBCL, not otherwise specified (PCDLBCL‐NOS). We assigned all the cases a histogenetic profile, based on the immunohistochemical detection of CD10, BCL6, and MUM1, and a “double hit score” upon positivity for BCL2 and MYC. PCDLBCL‐NOS had a clinical presentation more similar to PCFCCL, whereas the histology was more consistent with the picture of a diffuse large B‐cell lymphoma, as predominantly composed of centroblasts but with intermixed a reactive infiltrate of small lymphocytes. Its behavior was intermediate between the other two forms, particularly when considering only cases with a “non‐germinal B‐cell” profile, whereas “germinal center” cases resembled PCFCCL. Our data confirmed the aggressive behavior of PCDLBC‐LT, which often coexpressed MYC and BCL2. The impact of single factors on 5‐year survival was documented, particularly histogenetic profile in PCDLBCL and BCL2 translocation in PCFCCL. Our study confirms that a further group—PCDLBCL‐NOS—exists, which can be recognized through a careful combination of histopathologic criteria coupled with adequate clinical information.
D2‐resected stage IIIc gastric cancer patients benefit from adjuvant chemoradiotherapy
Authors: Peng Jin , Wei Yuehua , Zhou Fuxiang , Dai Jing , Zhong Yahua , Xie Conghua , Qin Yue'e , Gong Jun , Xiong Bin , Zhou Yunfeng
Published: September 2016

Although adjuvant chemoradiotherapy has been an important part in the treatment of gastric cancer, whether or not adjuvant radiation can benefit patients undergoing resection with D2 lymph node dissection remains controversial. This retrospective study aimed to evaluate the role of adjuvant chemoradiotherapy on patients with D2‐resected gastric cancer. A total of 337 patients with resected gastric cancer treated at Zhongnan Hospital of Wuhan University from 2004 to 2012 were retrospectively analyzed. Eligible patients were divided into the adjuvant chemoradiotherapy group (CRT; n = 124) and the adjuvant chemotherapy group (CT; n = 213). The primary endpoints were disease‐free survival (DFS) and overall survival (OS), with toxicity as the secondary endpoint. A subgroup analysis was performed based on clinical staging. The two groups were comparable in baseline characteristic, except for the number of lymph nodes dissected. The median OSs in the CRT and CT groups were 51.0 months and 48.6 months, respectively (P = 0.251), and the median DFSs were 40.7 months and 31.2 months, respectively (P = 0.112). Subgroup analysis revealed that the median OSs in patients at stage IIIc in the CRT group and CT group were 29.0 and 23.0 months, respectively (P = 0.049), and those of the median DFSs were 21.2 and 15.1 months, respectively (P = 0.015). There was no significant difference in main adverse events between two groups. Collectively, adjuvant chemoradiotherapy in gastric cancer patients with D2 resection was well tolerated. For Stage IIIc patients, the addition of adjuvant chemoradiotherapy was associated with a significant benefit in both OS and DFS.
Quantitative diagnosis of HER2 protein expressing breast cancer by single‐particle quantum dot imaging
Authors: Miyashita Minoru , Gonda Kohsuke , Tada Hiroshi , Watanabe Mika , Kitamura Narufumi , Kamei Takashi , Sasano Hironobu , Ishida Takanori , Ohuchi Noriaki
Published: September 2016

Overexpression of HER2 is one of the major causes of breast cancer, and therefore precise diagnosis of its protein expression level is important. However, current methods estimating the HER2‐expression level are insufficient due to problem with the lack of quantification. This might result in a gap between diagnostics and therapeutics targeting HER2. Therefore, a new effective diagnostic method is needed. We developed a new immunohistochemical (IHC) technique with quantum dots (QD)‐conjugated trastuzumab using single‐particle imaging to quantitatively measure the HER2 expression level. Tissues from 37 breast cancer patients with available detailed clinical information were tested by IHC with QDs (IHC‐QD) and the correlation with IHC with 3,3′‐diaminobenzidine (DAB), fluorescence in situ hybridization (FISH), and IHC‐QD was examined. The number of QD‐conjugated trastuzumab particles binding specifically to a cancer cell was precisely calculated as the IHC‐QD score. The IHC‐QD score in 37 cases was correlated proportionally with the score of HER2 gene copy number as assessed by FISH (R = 0.83). When HER2 positivity was judged to be positive, the IHC‐QD score with our cut‐off level was exactly concordant with the FISH score with a cut‐off value of 2.0. Furthermore, IHC‐QDs score and time to progression (TTP) of trastuzumab therapy were well correlated in HER2‐positive cases (R = 0.69). Conversely, the correlation between FISH score and TTP was not observed. We developed a precisely quantitative IHC method using trastuzumab‐conjugated QDs and single‐particle imaging analysis and propose the possibility of using IHC‐QDs score as a predictive factor for trastuzumab therapy.
Officials discourage preschool suspensions, encourage mental health consultations
Authors: Knopf Alison
Published: September 2016

Last month, National Public Radio reported this fact: thousands of children are suspended or expelled from preschool every year, mainly because of behavior problems. This is pre‐kindergarten — and it's public school. How many are suspended or expelled from private preschool or day care is not even known.
Nitrogen Dioxide Catalyzed Oxidative Thiocyanation of Arenes with Ambient Air as the Terminal Oxidant
Authors: Ren Yun‐Lai , Wang Wenhui , Zhao Bo , Tian Xinzhe , Zhao Shuang , Wang Jianji , Li Fuwei
Published: September 2016

NO2 is an effective catalyst for the oxidative thiocyanation of arenes. This unique catalyst is inexpensive and separated easily from the final products because of its low boiling point. The mild reaction conditions allow a series of arenes and thiophenes to be thiocyanated smoothly in moderate to high yields. A preliminary mechanistic investigation suggests that the present reaction may proceed through a radical pathway.
Ionic Liquid–Silicotungstic Acid Composites as Efficient and Recyclable Catalysts for the Selective Esterification of Glycerol with Lauric Acid to Monolaurin
Authors: Han Xiaoxiang , Zhang Xiaofang , Zhu Guangqi , Liang Juanjuan , Cao Xianghui , Kan Renjun , Hung Chin‐Te , Liu Li‐Li , Liu Shang‐Bin
Published: September 2016

The synthesis of glycerol monolaurate (GML) by the esterification of glycerol (GL) with lauric acid (LA) over a series of propyl sulfonic acid‐functionalized ionic liquids (SAFILs)‐modified silicotungstic acid (STA; H4SiW12O40) composite catalysts has been investigated. The synthesized organic–inorganic hybrid catalysts were characterized by different physicochemical techniques. In particular, their acidic properties were studied by solid‐state 31P magic angle spinning (MAS) NMR spectroscopy by using adsorbed trimethylphosphine oxide (TMPO) as a probe. The effects of key reaction parameters, such as glycerol/lauric acid molar ratio, amount of catalyst, reaction time, and reaction temperature on LA conversion and GML product yield were elucidated and optimized with response surface methodology (RSM). The N,N‐dimethyl(benzyl)ammonium propyl sulfobetaine (DMBPS)‐modified STA [DMBPSH]H3SiW12O40 exhibited the optimal catalytic activity and was exploited for process optimization. A highest GML yield of 79.1 % was achieved with the optimized reaction conditions. The high catalytic activity of these hybrid catalysts were attributed to strong acidity, low transport resistance, and their “pseudoliquid” characteristics. A kinetic study was made based on a second‐order irreversible model of the esterification reaction, which resulted in an activation energy of 39.49 kJ mol−1 for [DMBPSH]H3SiW12O40 under optimized reaction conditions.
Magnesium Storage Performance and Surface Film Formation Behavior of Tin Anode Material
Authors: Nguyen Dan‐Thien , Tran Xuan Minh , Kang Joonsup , Song Seung‐Wan
Published: September 2016

Electrochemical cycling performance of microsize bulk and thin film Sn electrodes up to 50 cycles in Mg half‐cell configuration, as well as Mg diffusivity and interfacial reaction behavior in a phenylmagnesium chloride (PhMgCl)/THF electrolyte are studied. The bulk Sn electrode delivers capacities of 321–289 mAh g−1 with capacity retention of 90 % and coulombic efficiencies higher than 99 % over 30 cycles, and thus demonstrates the potential of Sn anodes. The Sn film electrode shows good cycling ability. Surface analysis by XPS reveals that the surface of cycled electrodes is composed of a mixture of various inorganic salts of Sn and Mg formed by interfacial reactions between Sn and PhMgCl, and organic functionality produced by decomposition of THF, indicating surface film formation. The Mg2+ diffusivity of Sn is on the order of 10−11 cm2 s−1, which is four orders of magnitude lower than the Li+ diffusivity of Sn in Li‐ion batteries. Advanced material design for enhanced electronic conductivity and control of the interfacial chemistry for formation of a surface protective film are believed to be the keys to overcome such sluggish kinetics, increase the capacity, and improve the cycling performance.
Back‐Illuminated Si‐Based Photoanode with Nickel Cobalt Oxide Catalytic Protection Layer
Authors: Bae Dowon , Mei Bastian , Frydendal Rasmus , Pedersen Thomas , Seger Brian , Hansen Ole , Vesborg Peter C. K. , Chorkendorff Ib
Published: September 2016

The front cover artwork is provided by Ib Chorkendorff, Dowon Bae, and co‐workers at the Technical University of Denmark (Denmark). The image highlights a time‐dependent improvement in the water oxidation reaction of a back‐side illuminated c‐Si‐based photoanode protected by a co‐sputtered thin film of NiCoOX with iron incorporation. Read the full text of the Article at 10.1002/celc.201500554.
Bioluminophore and Flavin Mononucleotide Fluorescence Quenching of Bacterial Bioluminescence—A Theoretical Study
Authors: Luo Yanling , Liu Ya‐Jun
Published: September 2016

Bacterial bioluminescence with continuous glow has been applied to the fields of environmental toxin monitoring, drug screening, and in vivo imaging. Nonetheless, the chemical form of the bacterial bioluminophore is still a bone of contention. Flavin mononucleotide (FMN), one of the light‐emitting products, and 4a‐hydroxy‐5‐hydro flavin mononucleotide (HFOH), an intermediate of the chemical reactions, have both been assumed candidates for the light emitter because they have similar molecular structures and fluorescence wavelengths. The latter is preferred in experiments and was assigned in our previous density functional study. HFOH displays weak fluorescence in solutions, but exhibits strong bioluminescence in the bacterial luciferase. FMN shows the opposite behavior; its fluorescence is quenched when it is bound to the luciferase. This is the first example of flavin fluorescence quenching observed in bioluminescent systems and is merely an observation, both the quenching mechanism and quencher are still unclear. Based on theoretical analysis of high‐level quantum mechanics (QM), combined QM and molecular mechanics (QM/MM), and molecular dynamics (MD), this paper confirms that HFOH in its first singlet excited state is the bioluminophore of bacterial bioluminescence. More importantly, the computational results indicate that Tyr110 in the luciferase quenches the FMN fluorescence via an electron‐transfer mechanism.
Traceless Rhodium‐Catalyzed Hydroacylation Using Alkyl Aldehydes: The Enantioselective Synthesis of β‐Aryl Ketones
Authors: Bouisseau Anaïs , Gao Ming , Willis Michael C.
Published: September 2016

A one‐pot three‐step sequence involving Rh‐catalyzed alkene hydroacylation, sulfide elimination and Rh‐catalyzed aryl boronic acid conjugate addition gave products of traceless chelation‐controlled hydroacylation employing alkyl aldehydes. The stereodefined β‐aryl ketones were obtained in good yields with excellent control of enantioselectivity. Good variation of all three reaction components is possible.
Lewis Acid Accelerated Aryl Ether Bond Cleavage with Nickel: Orders of Magnitude Rate Enhancement Using AlMe3
Authors: Kelley Paul , Edouard Guy A. , Lin Sibo , Agapie Theodor
Published: September 2016

Study of the kinetics of intramolecular aryl ether C−O bond cleavage by Ni was facilitated by access to a family of metal complexes supported by diphosphines with pendant aryl‐methyl ethers. The nature of the aryl substituents was found to have little effect on the rate of cleavage. In contrast, soluble Lewis acidic additives accelerate the aryl ether cleavage dramatically. The effect of AlMe3 was studied in detail, and showed an increase in rate by several orders of magnitude. Low temperature NMR spectroscopy studies demonstrate quantitative coordination of ether to Al. From the Lewis acid‐bound precursor, the activation parameters for ether cleavage are significantly lower. These findings provide a mechanistic basis for milder catalyst design for the activation of strong bonds.
Visible‐Light‐Promoted Metal‐Free Aerobic Oxidation of Primary Amines to Acids and Lactones
Authors: Cheng Xiaokai , Yang Bo , Hu Xingen , Xu Qing , Lu Zhan
Published: September 2016

A unique metal‐free aerobic oxidation of primary amines via visible light photocatalytic double carbon–carbon bonds cleavage and multi carbon–hydrogen bonds oxidation was observed. Aerobic oxidation of primary amines could be controlled to afford acids by using dioxane with 18 W CFL, and lactones by using DMF with 8 W green LEDs, respectively. A plausible mechanism was proposed based on control experiments. This observation showed direct evidences for the fragmentation in the aerobic oxidation of aliphatic primary amines.
Young investigator challenge: The morphologic analysis of noninvasive follicular thyroid neoplasm with papillary‐like nuclear features on liquid‐based cytology: Some insights into their identification
Authors: Bizzarro Tommaso , Martini Maurizio , Capodimonti Sara , Straccia Patrizia , Lombardi Celestino Pio , Pontecorvi Alfredo , Larocca Luigi Maria , Rossi Esther Diana
Published: September 2016

BACKGROUND

Noninvasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP) represents a challenge for the diagnosis and management of thyroid carcinoma. Some authors have proposed histological criteria that are able to distinguish NIFTPs from invasive follicular variant of papillary thyroid carcinoma (I‐FVPTC). Hence, NIFTPs may have repercussions in the diagnostic categories on fine‐needle aspiration. In the current study, the authors evaluated the criteria for NIFTPs on liquid‐based cytology samples.

METHODS

The authors recorded all 61 liquid‐based cytology samples proved to be histological FVPTC between January 2013 and March 2016 and analyzed the architectural, cytoplasmic, and nuclear parameters. They compared them with a cohort of 40 PTC cases and 20 follicular adenoma cases.

RESULTS

The authors reported 37 NIFTP cases and 24 I‐FVPTC cases at histology. The cytological diagnoses of follicular nodules in the NIFTP cases were twice those found in the I‐FVPTC cases (54.1% vs 29.2%). The number of positive for malignancy cases among the NIFTPs were approximately half those of I‐FVPTC cases. When compared with I‐FVPTCs, 70% of the NIFTP cases demonstrated a nuclear size <20 μm (P = .025) and rarely exhibited grooves (13% vs 42%; P = .009). The authors found 100% of cases with wild‐type BRAF gene in NIFTP cases versus 38.4% in mutated I‐FVPTC cases (P = .046). The cytoplasmic features might help to discriminate NIFTPs from follicular adenomas but not from I‐FVPTCs (P>.05). A predominant microfollicular pattern was recognized in both NIFTPs and I‐FVPTCs (97.3% vs 100%).

CONCLUSIONS

The majority of NIFTPs appear to be devoid of nuclear pseudoinclusions and papillary structures, thereby allowing the inclusion in the follicular nodule cases. Nuclear size and microfollicular clusters may suggest the discrimination between NIFTPs and I‐FVPCs. Cancer Cytopathol 2016;124:699‐710. © 2016 American Cancer Society.
Chirality Controls Reaction‐Diffusion of Nanoparticles for Inhibiting Cancer Cells
Authors: Du Xuewen , Zhou Jie , Wang Jiaqing , Zhou Rong , Xu Bing
Published: September 2016

Reaction‐diffusion (RD) is the most important inherent feature of living organisms, but it has yet to be used for developing biofunctional nanoparticles (NPs). Here we show the use of chirality to control the RD of NPs for selective inhibition of cancer cells. We observe that l‐phosphotyrosine (l‐pY)‐decorated NPs (NP@l‐pYs) are innocuous to cells, but d‐pY‐decorated ones (NP@d‐pYs) selectively inhibit cancer cells. Our study shows that phosphatases, present in the culture and overexpressed on the cancer cells, dephosphorylate NP@l‐pYs much faster than NP@d‐pYs. Such a rate difference allows the NP@d‐pYs to be mainly dephosphorylated on cell surface, and thus adhere selectively on the cancer cells, resulting in poly(ADP‐ribose)polymerase (PARP)‐hyperactivation‐mediated cell death. Without phosphate groups or with premature dephosphorylation before reaching cancer cells (as in the case of NP@l‐pYs), the NPs are innocuous to cells. Moreover, NP@d‐pYs exhibit even more potent activity than cisplatin for inhibiting platinum‐resistant ovarian cancer cells (e.g., A2780‐cis). As the first example of chirality controlling a RD process of NPs for inhibiting cancer cells, this work illustrates a fundamentally new way to develop nanomedicine based on RD processes and nanoparticles.
Active‐Site Targeting Paramagnetic Probe for Matrix Metalloproteinases
Authors: Baldoneschi Veronica , Cerofolini Linda , Dragoni Elisa , Storai Andrea , Luchinat Claudio , Fragai Marco , Richichi Barbara , Nativi Cristina
Published: September 2016

The design and synthesis of the Ln3+ complexes of a DOTA‐containing (DOTA=1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid) inhibitor of matrix metalloproteinases are reported. The tight binding of the sulfonamide scaffold to the catalytic domain of the investigated matrix metalloproteinase is not impaired by the presence of the Ln3+‐DOTA moiety. The paramagnetic properties of the Ln3+ complex are exploited to obtain insights into the structural features of the ligand–protein interactions and to evaluate the influence of the linker length on the quality of the paramagnetic restraints.
Throughput and delay analysis of directional‐location aided routing protocol for vehicular ad hoc networks
Authors: Pandey Kavita , Raina Saurabh Kumar , Raw Ram Shringar , Singh Buddha
Published: September 2016

Vehicular ad hoc networks is an integral component of intelligent transportation systems and it is an important requisite for smarter cities. Network formation and deformation among the vehicles are very frequent because of the variation in speed. Furthermore, for safety applications, messages should not face any kind of delay or collision. Therefore, establishing communication between the vehicles becomes even more challenging. Position‐based routing protocols work productively in vehicular ad hoc networks. Only finding an efficient routing protocol does not solve our purport. We need to carefully examine the effect of media access control layer parameters additionally. In the event of collisions, a large number of nodes would be re‐transmitting rather than sending fresh packets. A node busy in sending the retransmitted packet is called a backlog node. With an increase in the number of collisions, number of backlog nodes also increases, which affects the delay and throughput. In this article, we present the mathematical modeling of delay and throughput with IEEE 802.11 distributed coordination function (at media access control layer) for directional‐location aided routing (D‐LAR) position based routing protocol. For performance evaluation, simulation has been done in realistic environment created with SUMO (traffic simulator) and NS‐2 (network simulator). Simulation results show the comparison between D‐LAR and location aided routing (LAR) on various metrics in terms of delay, packet delivery ratio, routing overhead, throughput, and collision probability. To validate the mathematical model, analytical results has been compared with simulation results. The results confirm that performance of D‐LAR is better than LAR in terms of increasing the throughput and reduction in routing overhead and delay.
Passive smoking increased risk of gestational diabetes mellitus independently and synergistically with prepregnancy obesity in Tianjin, China
Authors: Leng Junhong , Wang Peng , Shao Ping , Zhang Cuiping , Li Weiqin , Li Nan , Wang Leishen , Nan Hairong , Yu Zhijie , Hu Gang , Chan Juliana C.N. , Yang Xilin
Published: September 2016

Background

Passive smoking increased type 2 diabetes mellitus risk, but it is uncertain whether it also increased gestational diabetes mellitus (GDM) risk. We aimed to examine the association of passive smoking during pregnancy and its interaction with maternal obesity for GDM.

Methods

From 2010 to 2012, 12 786 Chinese women underwent a 50‐g 1‐hour glucose challenge test at 24 to 28 weeks of gestation and further underwent a 75‐g 2‐hour oral glucose tolerance test if the glucose challenge test result was ≥7.8 mmol/L. GDM was defined by the International Association of Diabetes and Pregnancy Study Group's cut points. Self‐reported passive smoking during pregnancy was collected by a questionnaire. Logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs). Additive interaction between maternal obesity and passive smoking was estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S). Significant RERI > 0, AP > 0, or S > 1 indicated additive interaction.

Results

A total of 8331 women (65.2%) were exposed to passive smoking during pregnancy. More women exposed to passive smoking developed GDM than nonexposed women (7.8% versus 6.3%, P = 0.002) with an adjusted OR of 1.29 (95%CI, 1.11 to 1.50). Compared with nonobesity and nonpassive smoking, prepregnancy obesity and passive smoking was associated with GDM risk with an adjusted OR of 3.09 (95%CI, 2.38‐4.02) with significant additive interaction (P < .05 for RERI and AP).

Conclusions

Passive smoking during pregnancy increased GDM risk in Chinese women independently and synergistically with prepregnancy obesity.
Glycemic control and safety in Chinese patients with type 2 diabetes mellitus who switched from premixed insulin to insulin glargine plus oral antidiabetics: a large, prospective, observational study
Authors: Zhang Bo , Zhao Jing , Yang Wenying ,   on behalf of the Lantus Registry Study Group
Published: September 2016

In some circumstances, the premixed insulin should be switched to alternative therapy. The effectiveness and the safety of switching from premixed insulin to insulin glargine plus oral antidiabetic drugs (OADs) in Chinese patients with type 2 diabetes mellitus (T2DM) have not been clarified and, hence, will be assessed in this study. Chinese patients with T2DM (2013 men and women aged 18–75 years) who had received premixed insulin ± OADs for ≥3 months with glycated hemoglobin (HbA1c) ≤ 10% were enrolled in a prospective, observational study conducted at 53 hospitals across China. At baseline and at the discretion of the physician, patients switched from premixed insulin to insulin glargine plus OADs. Changes in HbA1c, fasting plasma glucose (FPG), 2‐hour postprandial glucose (PPG), treatment satisfaction, and the incidence of hypoglycemia were assessed for 16 weeks. In total, 1850 patients completed the study. Mean HbA1c level for the group decreased significantly (from 7.8% ± 1.2% at week 1 to 7.0% ± 1.0% at week 16; P < .0001), and 55.2% of patients achieved HbA1c < 7% at week 16. Mean FPG and 2‐hour PPG decreased significantly (−1.4 ± 2.2 and −2.1 ± 3.9 mmol/L, respectively; both P < .0001), whereas patient satisfaction improved significantly. Adverse events were reported in 18.7% of patients. Chinese patients with T2DM who switched from premixed insulin to insulin glargine plus OADs achieved significantly improved glycemic control and treatment satisfaction with a low incidence of hypoglycemia. Patients who are most likely to achieve the HbA1c target less than 7% are younger, have shorter disease duration, and have lower baseline HbA1c and FPG levels.
Landscape composition and configuration in the central highlands of Ethiopia
Authors: Tolessa Terefe , Senbeta Feyera , Kidane Moges
Published: September 2016

Landscape dynamics are common phenomenon in the human‐dominated environments whereby it can be observed that the composition and configuration between landscape elements change over time. This dynamism brings about habitat loss and fragmentation that can greatly alter ecosystem services at patch, class, and landscape levels. We conducted a study to examine composition and configuration of forested landscape in the central highlands of Ethiopia using satellite images of over a period of four decades, and FRAGSTAT raster dataset was used to analyze fragmentation. Our result showed five land use/land cover (LULC) types in the study area. Cultivated land and settlement land increased at the expense of forestland, shrubland, and grassland. Fragmentation analysis showed the number of patches increased for all LULC types, indicating the level of fragmentation and interspersion. Juxtaposition increased for shrubland, grassland, and cultivated lands and decreased for settlement and forestland resulting in the fragmentation and isolation of patches. The study of LULC along with fragmentation at the landscape level can help improve our understanding of the pace at which conversion of landscape elements is happening and the impacts on ecosystem services as studies of LULC are courser in nature and would not show how each land use is reducing in size, proximity and shape among other things that determine ecosystem services. Such type of studies in rural landscapes are very vital to consider appropriate land management policies for the landscape level by taking into account the interaction between each element for sustainable development. We recommend land managers, conservationists, and land owners for observing the roles of each patch in the matrix to maximize the benefits than focusing on a single element.
Biomachining: Preservation of Acidithiobacillus ferrooxidans and treatment of the liquid residue
Authors: Díaz‐Tena Estíbaliz , Rojo Naiara , Gurtubay L. , Rodríguez‐Ezquerro Adrián , López de Lacalle Luis Norberto , Oyanguren Iñigo , Barbero Francisca , Elías Ana
Published: September 2016

Biomachining has become a promising alternative to micromachining metal pieces, as it is considered more environmentally friendly than their physical and chemical machining counterparts. In this research work, two strategies that contribute to the development of this innovative technology and could promote its industrial implementation were investigated: preservation of biomachining microorganisms (Acidithiobacillus ferrooxidans) for their further use, and making valuable use of the liquid residue obtained following the biomachining process. Regarding the preservation method, freeze‐drying, freezing, and drying were tested to preserve biomachining bacteria, and the effect of different cryoprotectants, storage times, and temperatures was studied. Freezing at –80°C in Eppendorf cryovials using betaine as a cryoprotective agent reported the highest bacteria survival rate (40% of cell recovery) among the studied processes. The treatment of the liquid residue in two successive stages led to the precipitation of most of the total dissolved iron and divalent copper (99.9%). The by‐products obtained (iron and copper hydroxide) could be reused in several industrial applications, thereby enhancing the environmentally friendly nature of the biomachining process.
An optimized biotechnological system for the production of centellosides based on elicitation and bioconversion of Centella asiatica cell cultures
Authors: Hidalgo Diego , Steinmetz Virginie , Brossat Maude , Tournier‐Couturier Lucie , Cusido Rosa M. , Corchete Purificacion , Palazon Javier
Published: September 2016

Centella asiatica is a herbaceous plant of Asian traditional medicine. Besides wound healing, this plant is recommended for the treatment or care of various skin conditions such as dry skin, leprosy, varicose ulcers, eczema, and/or psoriasis. Triterpene saponins, known as centellosides, are the main metabolites associated with these beneficial effects. Considering the interest in these high value active compounds, there is a need to develop biosustainable and economically viable processes to produce them. Previous work using C. asiatica plant cell culture technology demonstrated the efficient conversion of amyrin derivatives into centellosides, opening a new way to access these biomolecules. The current study was aimed at increasing the production of centellosides in C. asiatica plant cell cultures. Herein, we report the application of a new elicitor, coronatine, combined with the addition of amyrin‐enriched resins as potential sustainable precursors in the centelloside pathway, for a positive synergistic effect on centelloside production. Our results show that coronatine is a powerful elicitor for increasing centelloside production and that treatments with sustainable natural sources of amyrins enhance centelloside yields. This process can be scaled up to an orbitally shaken CellBag, thereby increasing the capacity of the system for producing biomass and centellosides.
Nickel Network Derived from a Block Copolymer Template for MnO2 Electrodes as Dimensionally Stabilized Lithium‐Ion Battery Anodes
Authors: Tillmann Selina D. , Cekic‐Laskovic Isidora , Winter Martin , Loos Katja
Published: September 2016

To improve lithium‐ion batteries further, novel concepts for the reproducible preparation of highly structured bicontinuous battery electrodes are required. With this in mind, the main focus of this work is based on the block copolymer template‐directed synthesis of metal nanofoams suitable for the rational study and design of the final conductive matrix through molecular engineering of the starting polymer. As a proof of concept, diverse MnO2 electrodes with nickel foam as substrates are prepared and morphologically and structurally characterized by means of SEM, Raman spectroscopy, and XRD. To investigate the electrochemical properties of the prepared MnO2–nickel foam electrodes, cyclic voltammetry and galvanostatic cycling experiments, including C‐rate tests, are performed and the obtained results are discussed with respect to the deposition time. Compared with the reference, namely, bulk MnO2–nickel foil electrodes, superior electrochemical characteristics, particularly regarding C‐rate capability and long‐term cycling stability, are achieved, which is attributed to better dimensional stability of the composite electrode.
Advancing Lithium–Oxygen Battery Technology with an Iron–Nitrogen‐Doped Mesoporous Core–Shell Carbon Cathode Loaded with Ruthenium(IV) Oxide Nanoparticles
Authors: Zhou Ming , Li Chi‐Ying Vanessa , Chan Kwong‐Yu
Published: September 2016

An iron‐nitrogen‐doped core–shell mesoporous carbon support loaded with a RuO2 catalyst was used as a Li–O2 cathode. Corrosion and degradation problems were avoided by doping carbon with iron and nitrogen. Well‐dispersed RuO2 in the hierarchical porous structure facilitated a reversible nanoscale solid‐phase reaction. At 2.0 A g−1 (on the basis of catalyst plus carbon support), a capacity of 10 Ah g−1 was demonstrated with a discharge potential of 2.4 V and a corresponding recharge potential of 3.6 V. On the other hand, at 1.0 A g−1, the discharge and recharge potentials are maintained at 2.5 V and 3.5 V, respectively, over 50 cycles.
Picturing the future‐conditional: montage and the global geographies of climate change
Authors: Mahony Martin
Published: September 2016

A growing body of work has explored the effects of visual imagery on shifting forms of environmental consciousness and politics. Circulating images of, for example, the ‘whole Earth’ have been ascribed agency in the emergence of new forms of planetary awareness and political globalism. This essay identifies a new form of global environmental image, in the shape of photographic montage depictions of future places transformed by the effects of climate change. Montage enables artists and designers to import the spatial formations of distant places into more familiar locations, in the process producing novel renderings of the interconnections of global environmental change. The future‐conditional – ‘if x, then y’ – has become a key register of scientific and artistic engagement with climate change, and practices of visual montage have offered means of reconciling the transformations of space and time in the imagination of putative futures. The essay situates such images within a longer lineage of depictions of the tropical and the ruined, and focuses on contemporary montage depictions of climate‐change‐induced migration. It argues that many of these ‘global montages’ problematically reinforce extant notions of geographical otherness. Yet montage, as a technique, also renders visible the choices, cuts, juxtapositions and arguments which lie behind any representation, thus offering the seed of a more reflexive mode of future‐conditional image‐making.
The politics of the anthropocene: a dialogue
Authors: Barry Andrew , Maslin Mark
Published: September 2016

This paper stages a dialogue between a human geographer and a physical geographer about the concept of the Anthropocene. The aim of the dialogue is not to arrive at an agreement about how the Anthropocene should be defined, but rather to open up the question of the politics of the concept and its definition. The dialogue revolves around three issues: (1) the politics of the debate about the geoscientific definition of the Anthropocene Epoch; (2) the relation between the geoscientific debate about the Anthropocene and the burgeoning literature on the Anthropocene in the social sciences and humanities, including human geography; (3) the relation between geoscientific and political concepts.
Correlations between macrophage polarizing cytokines, inflammatory mediators, osteoclast activity, and toll‐like receptors in tissues around aseptically loosened hip implants
Authors: Jämsen Eemeli , Kouri Vesa‐Petteri , Ainola Mari , Goodman Stuart B. , Nordström Dan C. , Eklund Kari K. , Pajarinen Jukka
Published: September 2016

Aseptic loosening and osteolysis of joint replacements are driven by macrophage‐mediated inflammatory reactions to implant‐derived wear debris, but many aspects of these events remain poorly characterized. To better understand the relationships among inflammatory and chemotactic mediators, macrophage phenotype and polarizing cytokines, osteoclast activity, and Toll‐like receptors (TLRs) in the pathogenesis of aseptic loosening, we determined how the relative expressions of these factors in the peri‐implant tissues correlate to each other and to the life span of the implants using Pearson correlation. The expression of pro‐inflammatory mediators and chemokines showed positive correlations among themselves, and with TLR4. Furthermore, M1‐polarizing IFN‐γ showed positive correlations with a number of pro‐inflammatory and chemotactic mediators, whereas M2‐polarizing IL‐4 showed no such association. IL‐8 expression significantly correlated with early time to revision. Similar trends were observed for TNF‐α, IFN‐γ, and CCL3, while the opposite was detected for IL‐4. However, none of the inflammatory mediators correlated with the markers of osteoclast activity or the RANKL/OPG ratio. The results highlight the importance of the inflammatory mediators, IFN‐γ and TLR4, in the pathogenesis of aseptic loosening; increased pro‐inflammatory status was associated with early time to revision, whereas IL‐4 correlated with longer implant survival. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 454–463, 2017.