bluuebunny/crossref_metadata_2025 huggingface dataset:
M
elioribacter
Authors: Kublanov Ilya V. , Podosokorskaya Olga A.
Published: June 2018

Me.li.o.ri.bac'ter. L. masc. adj.
melior
superior, good; N.L. masc. n.
bacter
rod; N.L. masc. n.
Melioribacter
superior rod.

Ignavibacteriae / Ignavibacteria / Ignavibacteriales / Melioribacteraceae / Melioribacter

The genus
Melioribacter
was classified as a member of the family
Melioribacteraceae
, order
Ignavibacteriales
, class
Ignavibacteria
, and phylum
Ignavibacteriae
.
M. roseus
is the only cultivated representative of the genus and family and the second member of the phylum known so far.
M. roseus
is characterized as nonspore‐forming, motile rods with a Gram‐negative cell wall that tend to form rosettes and biofilms. It is a moderately thermophilic, slightly alkaliphilic, and slightly halotolerant microorganism. It grows either by fermentation or aerobic or anaerobic respiration using amorphous Fe(III) oxide (ferrihydrite), arsenate, or nitrite as electron acceptor. It is able to utilize acetate, proteinaceous substrates, or various sugars, including polysaccharides.
M. roseus
was isolated from a microbial mat, developing under the flow of hot water, emerging from a 2,775‐m‐deep well, located in the Tomsk region of Western Siberia, Russia.

DNA G + C content (mol%)
: 41 (calculated
in silico
from the complete genome sequence).

Type species
:
Melioribacter roseus
Podosokorskaya, Kadnikov, Gavrilov, Mardanov, Merkel, Karnachuk, Ravin, Bonch‐Osmolovskaya and Kublanov 2013b, 3132
VP
(Effective publication: Podosokorskaya, Kadnikov, Gavrilov, Mardanov, Merkel, Karnachuk, Ravin, Bonch‐Osmolovskaya and Kublanov 2013c, 1765)
C
hthonomonadales
Authors: Stott Matthew B. , Lee Kevin C.‐Y. , Morgan Xochitl C. , Carere Carlo R.
Published: June 2018

Chtho.no.mo.na.da'les. N.L. fem. pl. n.
Chthonomonadales
the order of the genus
Chthonomonas
.

Armatimonadetes / Chthonomonadetes / Chthonomonadales

The order
Chthonomonadales
was circumscribed for this volume on a phylogenetic basis via comparative 16S rRNA gene sequence analysis of a single isolated representative and uncultured representatives from multiple terrestrial and aquatic habitats; the order contains the family
Chthonomonadaceae
.

Type genus
:
Chthonomonas
Lee, Dunfield, Morgan, Crowe, Houghton, Vyssotski, Ryan, Lagutin, McDonald and Stott 2011, 2487
VP
.
C
aldisericales
Authors: Mori Koji
Published: June 2018

Cal.di.se.ri.ca'les. N.L. neut. pl. n.
Caldisericales
the order of the genus
Caldisericum
.

Caldiserica / Caldisericia / Caldisericales

Cells are multicellular filamentous with outer envelopes. Gram stain‐negative. Nonmotile. No spore formation. Anaerobic, chemoheterotrophic growth using thiosulfate, sulfite, and elemental sulfur as electron acceptors. Optimal growth at neutral pH, under thermophilic, nonhalophilic conditions. The major cellular fatty acid is C
17
:0
iso.
I
gnavibacteriales
Authors: Iino Takao
Published: June 2018

Ig.na.vi.bac.te.ri.a'les. N.L. neut. n.
Ignavibacterium
type genus of the order; ‐
ales
ending to denote an order; N.L. fem. pl. n.
Ignavibacteriales
the order of genus
Ignavibacterium
.

Ignavibacteriae / Ignavibacteria / Ignavibacteriales

The order
Ignavibacteriales
is a sole member of the class
Ignavibacteria
. The description of the order
Ignavibacteriales
is mainly defined based on the phylogenetic position of the 16S rRNA gene sequence. The description is similar to that for the family
Ignavibacteriaceae
. The order currently accommodates the families
Ignavibacteriaceae
and
Melioribacteraceae
.

DNA G + C content (mol%)
: 34–41.

Type genus
:
Ignavibacterium
Iino, Mori, Uchino, Nakagawa, Harayama and Suzuki 2010, 1380
VP
.
E
lusimicrobia
Authors: Brune Andreas
Published: June 2018

E.lu.si.mi.cro'bi.a. N.L. fem. pl. n.
Elusimicrobiales
type order of the phylum; dropping ending
‐ales
and inserting
‐a
to denote a phylum; N.L. fem. pl. n.
Elusimicrobia
the phylum of
Elusimicrobiales
.

Elusimicrobia

The phylum
Elusimicrobia
contains two classes,
Elusimicrobia
and
Endomicrobia
, each of which contains only a single cultured representative.
Elusimicrobium minutum
and
Endomicrobium proavitum
are obligate anaerobes with a purely fermentative metabolism and have relatively small genomes. Both are pleomorphic ultramicrobacteria that substantially differ in cell size between the growth phase and the stationary phase. A considerable amount of information is available also on uncultured members of the genus
Endomicrobium
(
Candidatus
Endomicrobium). While the members of these genera occur exclusively in the intestinal tracts of insects, the phylum
Elusimicrobia
also comprises numerous lineages of uncultured bacteria that have been detected in 16S rRNA‐based surveys of other, mostly anoxic habitats.

DNA G + C content (mol%)
: 35.2–39.9 (genome sequence).

Type order
:
Elusimicrobiales
Geissinger, Herlemann, Mörschel, Maier and Brune 2010, 469
VP
(Effective publication: Geissinger, Herlemann, Mörschel, Maier and Brune 2009, 2839).
Efficient and Enantioselective Rhodium(I)‐Catalyzed Arylation of α‐Ketoesters: Synthesis of (S)‐Flutriafol
Authors: Chang Chiung‐An , Uang Tsung‐Ying , Jian Jia‐Hong , Zhou Meng‐Yi , Chen Ming‐Liang , Kuo Ting‐Shen , Wu Ping‐Yu , Wu Hsyueh‐Liang
Published: June 2018

An enantioselective addition of arylboronic acids and α‐ketoesters promoted by a Rhodium(I)‐chiral diene catalyst is reported. The transformation proceeds regioselectively in the presence of as low as 0.5 mol% of the catalyst generated in situ from a Rhodium(I) salt and diene L1, which is a bicyclo[2.2.1] ligand scaffold bearing 2,5 dinaphthyl substituents, to afford tertiary chiral α‐hydroxy esters with high stereoselectivities (90–99% ee's) and in 50–>99% yields. The method provides an expeditious and enantioselective synthesis of (S)‐flutriafol.

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Enantioselective Construction of Vicinal Sulfur‐containing Tetrasubstituted Stereocenters via Organocatalyzed Mannich‐Type Addition of Rhodanines to Isatin Imines
Authors: Huang Qiuhong , Zhang Lili , Cheng Yuyu , Li Pengfei , Li Wenjun
Published: June 2018

The catalyzed enantioselective nucleophilic addition of rhodanines has been established by employing isatin‐derived imines as suitable partners under chiral squaramide catalysis. By using this strategy, the resulting 3‐substituted 3‐amino‐2‐oxindoles featuring both rhodanine and vicinal sulfur‐containing tetrasubstituted stereocenters structural motifs were obtained in high yields with excellent enantioselectivities and diastereoselectivities.

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Palladium‐Catalyzed Solvent‐Dependent Divergent Synthesis of Benzylformamides
Authors: Wu Fu‐Peng , Peng Jin‐Bao , Qi Xinxin , Ying Jun , Wu Xiao‐Feng
Published: June 2018

A palladium‐catalyzed carbonylative cascade procedure for the synthesis of benzylformamides from aryl halides has been developed. The properties of the solvent chosen play a decisive role on the selectivity of the outcomes. Non‐coordinative solvent facilitates the coordination and insertion of CO to the amino‐palladium intermediate which then provides the formamides products. While the use of coordinative solvent leads to the formation of amines. A series of functional groups, including ester, ketone, nitro and cyano, were well tolerated under our conditions. The corresponding benzylformamides products were prepared in moderate to good yields without further optimization.

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Pd‐Catalyzed Decarboxylative Asymmetric Protonation of Sterically Hindered α‐Aryl Lactones and Dihydrocoumarins
Authors: James Jinju , Akula Ramulu , Guiry Patrick J.
Published: June 2018

Pd‐catalyzed decarboxylative asymmetric protonation (DAP) has been developed for sterically hindered α‐aryl lactone and dihydrocoumarin substrates. Optimization studies were conducted using δ‐lactone‐ and dihydrocoumarin‐derived α‐aryl, β‐oxo‐allyl esters with 2,4,6‐trimethoxyphenyl as the aryl substituent. In the absence of a chiral P,N‐ligand, (1R,2S)‐(−)ephedrine, a cheap and readily available chiral proton donor, induced enantioselectivities of up to 92% ee and 88% ee with lactone and dihydrocoumarin substrates, respectively. Bulky aryl groups containing di‐ortho substitutions and naphthyl groups gave the highest enantioselectivities of up to 92% and 86%, respectively. A stereochemical rationale is proposed to explain the preferred sense of asymmetric induction.

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An industrial‐scale synthesis of biodegradable soluble in organic solvents butyric–acetic chitin copolyesters
Authors: Draczynski Zbigniew , Bogun Maciej , Sujka Witold , Kolesinska Beata
Published: June 2018

The article presents the results of study related to upscaling chitin esterification reaction to the industrial scale. The obtained results allowed for creation of a product which can later be used in manufacturing biologically active dressing materials. The implementation of the laboratory scale showed that there is a possibility of upscaling the procedure to make it suitable for the needs of industry. Problems and risks associated with the transition to an industrial scale, such as process temperature control, time of the reaction and the method of isolation of product (emptying the industrial reactor from the reaction mixture), have been presented and discussed. The results of the tests showed the interdependence between the stages of production process, both in laboratory and in industrial scale. The realization of the presented project enabled solving the problems arising both from the preparation to the synthesis, carrying out the process itself, and obtaining the final product. An important factor in this case was to obtain the same physicochemical properties of the final product on both laboratory and industrial scale. The tests of biodegradation of butyric–acetic chitin copolyester in fresh human plasma and blood serum confirmed that two enzymatic degradation processes occur due to the presence of the enzymes in these body fluids. At the same time, enzymatic hydrolysis of ester bonds and enzymatic hydrolysis of the glycoside bonds of the main polysaccharide chain take place.
3D printed self‐expandable vascular stents from biodegradable shape memory polymer
Authors: Jia Han , Gu Shu‐Ying , Chang Kun
Published: June 2018

Considering the high in‐stent restenosis and stent thrombosis rate of stent implantation with balloon angioplasty, self‐expandable biodegradable vascular stent was prepared by 3D printing from shape memory polylactide (PLA). The printed stent could be compressed into a temporary shape with thinner diameter easy for implantation. The compressed stent had excellent shape fixity and could maintain its temporary shape at room temperature for storage. However, it could self‐expand to its initial shape after being implanted due to the heat triggering of shape memory polylactide. The longitudinal contraction or radical expansion under its working condition was carried out by finite element analysis. The combination of self‐expansion of biodegradable shape memory PLA with personalized designing of 3D printing provides the vascular stent a future solution for cardiovascular disease treatment.
Elucidating Self‐Assembling Peptide Aggregation via Morphoscanner: A New Tool for Protein‐Peptide Structural Characterization
Authors: Saracino Gloria A. A. , Fontana Federico , Jekhmane Shehrazade , Silva João Medeiros , Weingarth Markus , Gelain Fabrizio
Published: June 2018

Self‐assembling and molecular folding are ubiquitous in Nature: they drive the organization of systems ranging from living creatures to DNA molecules. Elucidating the complex dynamics underlying these phenomena is of crucial importance. However, a tool for the analysis of the various phenomena involved in protein/peptide aggregation is still missing. Here, an innovative software is developed and validated for the identification and visualization of b‐structuring and b‐sheet formation in both simulated systems and crystal structures of proteins and peptides. The novel software suite, dubbed Morphoscanner, is designed to identify and intuitively represent b‐structuring and b‐sheet formation during molecular dynamics trajectories, paying attention to temporary strand‐strand alignment, suboligomer formation and evolution of local order. Self‐assembling peptides (SAPs) constitute a promising class of biomaterials and an interesting model to study the spontaneous assembly of molecular systems in vitro. With the help of coarse‐grained molecular dynamics the self‐assembling of diverse SAPs is simulated into molten aggregates. When applied to these systems, Morphoscanner highlights different b‐structuring schemes and kinetics related to SAP sequences. It is demonstrated that Morphoscanner is a novel versatile tool designed to probe the aggregation dynamics of self‐assembling systems, adaptable to the analysis of differently coarsened simulations of a variety of biomolecules.
Immunotherapy for pancreatic cancer: Barriers and breakthroughs
Authors: Torphy Robert J. , Zhu Yuwen , Schulick Richard D.
Published: June 2018

Immunotherapy is a rapidly growing field and represents a paradigm shift in the treatment of malignancies as it offers a new therapeutic approach beyond surgery, conventional chemotherapy, and radiation treatment. Targeting immune checkpoints, such as cytotoxic T‐lymphocyte‐associated antigen 4 and programmed death 1/programmed death ligand 1 has had immense clinical success resulting in sustained treatment response for a subset of patients with certain malignancies such as melanoma, non‐small‐cell lung cancer, urothelial carcinoma, squamous cell carcinoma of the head and neck, renal cell cancer, hepatocellular cancer, and metastatic colorectal cancer. Importantly, there has been limited success in the use of immunotherapy in the treatment of pancreatic cancer. Investigation into the complex tumor microenvironment of pancreatic cancer that is composed of immune cells, stromal cells, and extracellular matrix proteins has begun to shed light on important attributes of this microenvironment that act as barriers to the effective use of immunotherapy. In this review, we will discuss the progress that has been made in treating pancreatic cancer with immunotherapy, the barriers that have limited treatment success, and breakthroughs with combination treatments that hold promise for the future.
Metal‐organic gels of simple chemicals and their high efficacy in removing arsenic(V) in water
Authors: Gao Zhiliang , Sui Jianfei , Xie Xiaolin , Li Xiaoyu , Song Shuo , Zhang Hongshu , Hu Yuanyuan , Hong Yue , Wang Xiaolin , Cui Jiwei , Hao Jingcheng
Published: June 2018

Metal‐organic gels (MOGs) have emerged as a class of functional materials that show great potential applications in the field of catalysis, energy storage, template synthesis, and environmental technology. The construction of functional MOGs and the control of functionality are still challenging due to complicated chemicals or routes involved in previous works. Here we report a series of tunable multifunctional MOGs by directly gelating between Fe3+ and simple chemicals, propanedioic acid (H2PA), succinic acid (H2SA), glutaric acid (H2GA), and fumaric acid (H2FA) in ethanol. The obtained MOGs exhibit self‐healing property and good conductivity, and were used for high efficacy removal of arsenic (As) in water. The ease, low cost, and scalability of the assembly process combined with multifunctionality make these MOGs be potentially applied in the fields of energy storage and sewage disposal. © 2018 American Institute of Chemical Engineers AIChE J, 64: 3719–3727, 2018
Detection and quantification of vitamins in microliter volumes of biological samples by LC‐MS for clinical screening
Authors: Khaksari Maryam , Mazzoleni Lynn R. , Ruan Chunhai , Song Peng , Hershey Neil D. , Kennedy Robert T. , Burns Mark A. , Minerick Adrienne R.
Published: June 2018

A method for simultaneous determination of water‐soluble vitamins B1, B2, B3 (nicotinamide), B5, B6 (pyridoxamine), B9 and fat‐soluble vitamins E (α‐tocopherol) and K1 in tears, and B1, B2, B3, B5, B6, B9, A (retinol), and E in blood serum is described. Liquid chromatography‐mass spectrometry (LC‐MS) was used with a ternary mobile phase of water and acetonitrile containing 0.1% formic acid and methanol containing 5 mM ammonium formate. Vitamins were quantified using an internal standard method. Using 25 μL injection volumes, the limits of detection were in the range of 0.066‐5.3 ng in tear, and 0.087‐1.1 ng in serum with linear responses for all vitamins. Intra‐ and inter‐day precision and recoveries were satisfactory. This is the first study to demonstrate simultaneous vitamin detections in microliters of biological samples which has distinct advantages in many diagnostic applications with limited available fluids (e.g., tears; elderly anemic blood) or sampling small subjects (e.g., rodents). © 2018 American Institute of Chemical Engineers AIChE J, 64: 3709–3718, 2018
Clinical characteristics and prognostic factors of sinonasal undifferentiated carcinoma: a multicenter study
Authors: de Bonnecaze Guillaume , Verillaud Benjamin , Chaltiel Leonor , Fierens Sylvestre , Chapelier Mark , Rumeau Cécile , Malard Olivier , Gavid Marie , Dufour Xavier , Righini Christian , Uro‐coste Emmanuelle , Rives Michel , Bach Christine , Baujat Bertrand , Janot François , de Gabory Ludovic , Vergez Sebastien
Published: June 2018

Background

Sinonasal undifferentiated carcinoma (SNUC) is a very rare entity with a poor prognosis. Due to the lack of studies on the subject, evidence is lacking concerning its management.

Methods

A multicenter collaborative study was conducted to assess treatment strategy, oncological outcome, and prognostic factors.

Results

Definitive analyses focused on 54 patients with a majority of advanced stage; the 3‐year overall survival (OS) and 3‐year recurrence‐free survival (RFS) rates were, respectively, 62.4% and 47.8%. During the follow‐up, 18 patients (33.3%) died, 10 (18.5%) developed metastases, 7 had lymph‐node involvement (13%), and 12 (22.2%) showed recurrence or local progression. In univariate analyses, treatment modalities associated with improved RFS were induction chemotherapy (p = 0.02) and intensity‐modulated radiotherapy (p = 0.007). In the multivariate analyses, only induction chemotherapy (p = 0.047, hazard ratio [HR] = 0.39) was significantly associated with improved RFS.

Conclusion

Multimodal therapies including induction chemotherapy and intensity‐modulated radiotherapy may improve the prognosis of SNUC; surgery might improve local control. Further multicenter studies are required.
Total Synthesis Establishes the Biosynthetic Pathway to the Naphterpin and Marinone Natural Products
Authors: Murray Lauren A. M. , McKinnie Shaun M. K. , Pepper Henry P. , Erni Reto , Miles Zachary D. , Cruickshank Michelle C. , López‐Pérez Borja , Moore Bradley S. , George Jonathan H.
Published: June 2018

The naphterpins and marinones are naphthoquinone meroterpenoids with an unusual aromatic oxidation pattern that is biosynthesized from 1,3,6,8‐tetrahydroxynaphthalene (THN). We propose that cryptic halogenation of THN derivatives by vanadium‐dependent chloroperoxidase (VCPO) enzymes is key to this biosynthetic pathway, despite the absence of chlorine in these natural products. This speculation inspired a total synthesis to mimic the naphterpin/marinone biosynthetic pathway. In validation of this biogenetic hypothesis, two VCPOs were discovered that interconvert several of the proposed biosynthetic intermediates.
Enhanced HPLC‐MS/MS method for the quantitative determination of the co‐administered drugs ceftriaxone sodium and lidocaine hydrochloride in human plasma following an intramuscular injection and application to a pharmacokinetic study
Authors: Mohamed Dalia , Kamal Maha
Published: June 2018

A sensitive HPLC–MS/MS method was established for the quantification of ceftriaxone sodium (CFT) and lidocaine HCl (LDC) in human plasma utilizing cefixime (CFX) and tadalafil (TDA) as internal standards. The analytes were extracted from human plasma by protein precipitation using acetonitrile. Chromatographic separation was performed on Kinetex C18 (50.0 × 4.6 mm, 5 μm particle size) column with methanol–0.01 M ammonium acetate pH 6.4 (70: 30, v/v) as mobile phase. Multiple reaction monitoring involving the transitions 555.10 → 396.20, 235.20 → 86.00, 454.20 → 284.80 and 390.20 → 268.20 was utilized to quantify CFT, LDC, CFX and TDA, respectively, using a triple quadrupole mass spectrometer which was operated in positive ion mode. The method revealed linearity in the concentration range of 3.0–300.0 μg/mL for CFT and 3.0–300.0 ng/mL for LDC. The validation of the method was achieved in accordance to the US Food and Drug Administration guidelines. A pharmacokinetic study was performed on healthy Egyptian volunteers after intramuscular injection of sterile ceftriaxone sodium (1 g CFT dissolved in 3.5 mL of 1% LDC) after approval from the ethics committee. The pharmacokinetic parameters were: Cmax 141.15 ± 39.84 (μg/mL) and 55.02 ± 9.36 (ng/mL); tmax (h) 2.50 ± 0.50 and 1.5 ± 0.50; t½ (h) 7.30 ± 2.98 and 4.23 ± 1.96; and Kel (h−1) 0.10 ± 0.04 and 0.20 ± 0.13 for CFT and LDC, respectively.
The prestimulus default mode network state predicts cognitive task performance levels on a mental rotation task
Authors: Kamp Tabea , Sorger Bettina , Benjamins Caroline , Hausfeld Lars , Goebel Rainer
Published: June 2018

Background

Linking individual task performance to preceding, regional brain activation is an ongoing goal of neuroscientific research. Recently, it could be shown that the activation and connectivity within large‐scale brain networks prior to task onset influence performance levels. More specifically, prestimulus default mode network (DMN) effects have been linked to performance levels in sensory near‐threshold tasks, as well as cognitive tasks. However, it still remains uncertain how the DMN state preceding cognitive tasks affects performance levels when the period between task trials is long and flexible, allowing participants to engage in different cognitive states.

Methods

We here investigated whether the prestimulus activation and within‐network connectivity of the DMN are predictive of the correctness and speed of task performance levels on a cognitive (match‐to‐sample) mental rotation task, employing a sparse event‐related functional magnetic resonance imaging (fMRI) design.

Results

We found that prestimulus activation in the DMN predicted the speed of correct trials, with a higher amplitude preceding correct fast response trials compared to correct slow response trials. Moreover, we found higher connectivity within the DMN before incorrect trials compared to correct trials.

Conclusion

These results indicate that pre‐existing activation and connectivity states within the DMN influence task performance on cognitive tasks, both effecting the correctness and speed of task execution. The findings support existing theories and empirical work on relating mind‐wandering and cognitive task performance to the DMN and expand these by establishing a relationship between the prestimulus DMN state and the speed of cognitive task performance.
Synthesis of 3‐Methylidene‐1‐tosyl‐2,3‐dihydroquinolin‐4(1H)‐ones as Potent Cytotoxic Agents
Authors: Koszuk Jacek , Bartosik Tomasz , Wojciechowski Jakub , Wolf Wojciech M. , Janecka Anna , Drogosz Joanna , Długosz Angelika , Krajewska Urszula , Mirowski Marek , Janecki Tomasz
Published: June 2018

An efficient synthetic strategy to 3‐methylidene‐2,3‐dihydroquinolin‐4(1H)‐ones variously substituted in position 2 has been developed. The title compounds were synthesized in the reaction sequence involving reaction of diethyl methylphosphonate with methyl 2‐(tosylamino)benzoate, condensation of thus formed diethyl 2‐oxo‐2‐(2‐N‐tosylphenyl)ethylphosphonate with various aldehydes followed by successful application of the obtained 3‐(diethoxyphosphoryl)‐1,2‐dihydroquinolin‐4‐ols as Horner–Wadsworth–Emmons reagents for the olefination of formaldehyde. Also, enantioselective approach to the target compounds has been evaluated using 3‐dimenthoxyphosphoryl group as a chiral auxiliary. Single X‐ray crystal analysis of (2S)‐3‐(dimenthoxyphosphoryl)‐2‐phenyl‐1‐tosyldihydroquinolin‐4‐ol revealed the presence of strong resonance‐assisted hydrogen bond (RAHB). The obtained 3‐methylidene‐2,3‐dihydroquinolin‐4(1H)‐ones were then tested for their cytotoxic activity against two leukemia cell lines NALM‐6 and HL‐60 and a breast cancer MCF‐7 cell line. All compounds showed very high cytotoxic activity with the IC50 values mostly below 1 μm in all three cancer cell lines. The selected analogs were also tested on human umbilical vein endothelial cells (HUVEC) and on human mammary gland/breast cells (MCF‐10A) to evaluate their influence on normal cells. Since one of the most serious problems in cancer chemotherapy is the development of drug resistance, the mRNA levels and activity of ABCB1 transporter considered to be the most important factor engaged in drug resistance, were evaluated in MCF‐7 cells treated with two selected analogs. Both compounds were strong ABCB1 transporter inhibitors that could prevent efflux of anticancer drugs from cancer cells.
Structure‐Based Design and Synthesis of Fluorene Derivatives as Novel RORγt Inverse Agonists
Authors: Gabr Moustafa T. , Abdel‐Raziq Mohammed S.
Published: June 2018

A new series of fluorene derivatives was designed and synthesized as novel retinoic acid receptor‐related orphan receptor gamma t (RORγt) inverse agonists utilizing a molecular hybridization approach. The new compounds 10 – 15 were evaluated for their RORγt activity using biochemical FRET and cellular reporter gene assays. Moreover, the inhibitory activity of the fluorene derivatives 10 – 15 in mouse Th17 cell differentiation assay was assessed. The hybrid compound 15 that combines both fluorene and arylsulfone moieties displayed promising RORγt activity with IC50 values of 68.6 and 99.5 nm in FRET and cellular assays, respectively. In addition, molecular modeling studies were employed to investigate potential binding mode of 15 to RORγt. These results render 15 a potential lead compound for development of therapeutics for Th17‐driven autoimmune diseases.
A Bioluminescent Ca2+ Indicator Based on a Topological Variant of GCaMP6s
Authors: Qian Yong , Rancic Vladimir , Wu Jiahui , Ballanyi Klaus , Campbell Robert E.
Published: June 2018

Fluorescent genetically encoded calcium ion indicators (GECIs) enable Ca2+ dynamics to be monitored in a diverse array of cell types and tissues. One drawback of green fluorescent GECIs, such as the widely used GCaMP6, is that the blue wavelengths of light used to excite the GECI also activate optogenetic actuators such as channelrhodopsins. Accordingly, it is particularly challenging simultaneously to use both optogenetic actuators and GECIs to both control and image cell signaling. Bioluminescence is an alternative imaging modality that circumvents this problem by avoiding the need for illumination for fluorescence excitation. Here, we report the development of a bioluminescent GECI, designated LUCI‐GECO1, based on efficient bioluminescent resonance energy transfer (BRET) between the NanoLuc luciferase and a topological variant of GCaMP6s. LUCI‐GECO1 is a sensitive ratiometric GECI that retains the highly optimized properties of GCaMP6s, as we demonstrate by imaging of chemically and optogenetically induced Ca2+ concentration changes in cultured cells and neurons.
PKG II inhibits PDGF‐BB triggered biological activities by phosphorylating PDGFRβ in gastric cancer cells
Authors: Wang Ying , Appiah‐Kubi Kwaku , Lan Ting , Wu Min , Pang Ji , Qian Hai , Tao Yan , Jiang Lu , Wu Yan , Chen Yongchang
Published: June 2018

Previous studies revealed that type II cGMP‐dependent protein kinase G (PKG II) could inhibit the activation of epidermal growth factor receptor (EGFR) which is a widely investigated RTK. PDGFR belongs to family of receptor tyrosine kinases (RTKs) too. However, the effect of PKG II on PDGFR activation is not clear yet. This study investigated potential regulatory effect of PKG II on activation of PDGFRβ and the downstream signaling transductions in gastric cancer. The results from CCK8 assay and Transwell assay indicated that PDGF‐BB induced cell proliferation and migration. Activated PKG II reversed the above variations caused by PDGF‐BB. Immunoprecipitation and Western blotting results showed that PKG II combined with PDGFRβ and phosphorylated this receptor, and thereby inhibited PDGF‐BB induced activation of PDGFRβ, and MAPK/ERK and PI3K/Akt mediated signal transduction pathways. Based on the prediction by phosphorylation site software, Ser643 and Ser712 were mutated to alanine respectively which prevented phosphorylation at these sites. Mutation at Ser712 abolished the inhibitory function of PKG II on PDGFRβ activation but mutation of Ser643 had no such an effect, indicating that Ser712 was PKG II‐specific phosphorylating site of PDGFRβ. In conclusion, PKG II inhibited PDGFRβ activation in gastric cancer via phosphorylating Ser712 of this RTK.
LncRNA Gm5091 alleviates alcoholic hepatic fibrosis by sponging miR‐27b/23b/24 in mice
Authors: Zhou Bo , Yuan Wenwen , Li Xinping
Published: June 2018

The regulatory roles of lncRNAs in the development of alcoholic hepatic fibrosis (AHF) have not been revealed. Here, we found lncRNA Gm5091 was being downregulated in mouse hepatic stellate cells (HSCs) during AHF. Then, Gm5091 was, respectively, overexpressed and knocked down in alcohol‐treated primary HSCs. Our results showed that Gm5091 negatively regulated cell migration, ROS content, IL‐1β secretion, and expression of Collagen I and markers of HSC activation including α‐SMA and Desmin. Furthermore, bioinformatics analysis showed that Gm5091 sequence contained binding sites of miR‐27b, miR‐23b, and miR‐24, and we proved that miR‐27b/23b/24 all bound to Gm5091 by using RNA pull‐down assay. Full‐length Gm5091 could decrease the miR‐27b/23b/24 levels, but the truncated Gm5091 deleting the binding sites could not. Finally, we confirmed that full‐length Gm5091 could alleviate AHF in vivo, but the truncated Gm5091 could not. In conclusion, lncRNA Gm5091 alleviates mouse AHF by sponging miR‐27b/23b/24.
Insight of aroma in brown rice through chemical assessment of 2‐Acetyl‐1‐pyrroline (2AP) in aromatic germplasm of India
Authors: Peddamma Sathish Kumar , Ragichedu Praveen Kumar , Maddala Sekhar , Sanjeeva Rao Durbha , Lella Venkata Subba Rao , Konne Kalyan , Sripada Prabhakar , S Gopala Krishnan , Singh A. K. , Maganti Seshu Madhav
Published: June 2018

Background and objectives

Fragrance and flavor of aromatic rice are chief indicators for consumer acceptability. Aroma is evaluated by time‐consuming and labor‐intensive sensory or chemical methods. In this study, we aimed volatile profiles of aromatic rice germplasm.

Findings

Considering the volatile nature of aroma compounds, highly sensitive and robust gas chromatography mass spectrometry (GC‐MS) analysis is the best alternative and can accurately assess the volatile aromatic compounds. Aromatic (552) and nonaromatic (4) genotypes collected from 10 centers across the country were analyzed with GC‐MS. 2‐acetyl‐1‐pyrroline (2AP) was estimated in all the genotypes and 10 genotypes cultivated at four geographical indicator (GI) and five non‐GI centers. Full scan analysis was performed in genotypes with (22) and without (147) 2AP to identify and quantify other aroma compounds. Among the genotypes, 409 contain 2AP from 0.001 (UPRI93‐101) to 0.0478 (Jasmine Scented) ppm. The mean 2AP content was 0.009 ppm. Six more compounds were detected in full scan analysis. Of these, nonanal was highest followed by hexanal and four compounds (hydroxyl methyl furfural, indole, benzyl alcohol, and guaiacol) in similar concentration.

Conclusions

2‐acetyl‐1‐pyrroline was higher in varieties cultivated at GI locations and genotype response varied from 0.66 (IR 62873‐227‐1‐16) to 2.93 (Bindli) folds. Although seven compounds (2AP and six other aroma compounds) were found, at this stage, it is premature to assign one or more of these compounds as responsible for the desired aroma considering the specificity of olfactory receptors and their highly varying odor detection threshold for individual compounds.

Significance and novelty

This study is first in terms of number of genotypes used, identification of aromatic rice without 2AP, and assessing impact of GI on 2AP.
Recurrent pericarditis as an extra‐intestinal manifestation of ulcerative colitis in a 14‐year‐old girl
Authors: Van Gils Ann J. M. , van Gijlswijk Sandra , Taminiau Jan A. J. M. , Marchau Fabienne , Van De Vijver Els
Published: June 2018

Key Clinical Message

Pericarditis is a known complication of mesalazine in the treatment of ulcerative colitis. This case study illustrates that after diagnostic work‐up, pericarditis should not always be attributed to the use of mesalazine. It may be the presentation of an extra‐intestinal manifestation of ulcerative colitis. Restarting of mesalazine should be considered.
Expansion of the Substrate Specificity of Porcine Kidney D‐Amino Acid Oxidase for S‐Stereoselective Oxidation of 4‐Cl‐Benzhydrylamine
Authors: Yasukawa Kazuyuki , Motojima Fumihiro , Ono Atsushi , Asano Yasuhisa
Published: June 2018

Discovery and development of enzymes for the synthesis of chiral amines have been a hot topic for basic and applied aspects of biocatalysts. Based on our X‐ray crystallographic analyses of porcine kidney D‐amino acid oxidase (pkDAO) and its variants, we rationally designed a new variant that catalyzed the oxidation of (S)‐4‐Cl‐benzhydrylamine (CBHA) from pkDAO and obtained it by functional high‐throughput screening with colorimetric assay. The variant I230A/R283G was constructed from the variant R283G which had completely lost the activity for D‐amino acids, further gaining new activity toward (S)‐chiral amines with the bulky substituents. The variant enzyme (I230A/R283G) was characterized to have a catalytic efficiency of 1.85 s−1 for (S)‐CBHA, while that for (R)‐1‐phenylethylamine was diminished 10‐fold as compared with the Y228L/R283G variant. The variant was efficiently used for the synthesis of (R)‐CBHA in 96 % ee from racemic CBHA by the deracemization reaction in the presence of reducing agent such as NaBH4 in water. Furthermore, X‐ray crystallographic analysis of the new variant complexed with (S)‐CBHA, together with modelling study clearly showed the basis of understanding the structure‐activity relationship of pkDAO.
A Multiaddressable Dyad with Switchable Cyan/Magenta/Yellow Colors for Full‐Color Rewritable Paper
Authors: Qin Tianyou , Han Jiaqi , Geng Yue , Ju Le , Sheng Lan , Zhang Sean Xiao‐An
Published: June 2018

Reversible multicolor displays on solid media created from single‐molecule pigments are a long‐awaited goal. Herein, a new and simple molecular dyad, which can undergo switchable cyan (C), magenta (M), and yellow (Y) color changes in both solution and the solid state upon exposure to light, water/acid, and nucleophiles, has been designed and synthesized. The stimuli used herein can be applied independent of each other, which is beneficial for color changes without mutual interference. For comparison, mixtures of the two molecular switching motifs that form the basis of the dyad were also studied. The dyad greatly outperforms the corresponding mixed system with respect to reversible color switching on the paper substrate. Its potential for full‐color rewritable paper with excellent reversibility has been demonstrated. Legible multicolor prints, that is, high color contrast and resolution, good dispersion, and excellent reversibility, were achieved by using common water‐jet and light‐based printers. This work provides a very promising approach for the further development of full‐color switchable molecules, materials, and displays.
Ferrocene‐Functionalized Silsesquioxane‐Based Porous Polymer for Efficient Removal of Dyes and Heavy Metal Ions
Authors: Yang Xiaoru , Liu Hongzhi
Published: June 2018

A novel ferrocene‐linked organic–inorganic hybrid porous polymer has been successfully prepared by Friedel–Crafts reaction of octavinylsilsesquioxane and ferrocene. The relationship of structure/property was investigated by FTIR, NMR, XRD, Brunauer–Emmett–Teller (BET) etc. The obtained porous polymer exhibited a high surface area of 1015 m2 g−1 and a hierarchical pore structure. It could be applied to wastewater treatment with the absorption capacity of up to 1683 mg g−1 for Congo red (CR), 1083 mg g−1 for crystal violet (CV), 1003 mg g−1 for rhodamine B (RB), 441 mg g−1 for methylene blue (MB), 191 mg g−1 for Hg2+, and 328 mg g−1 for Pb2+. Remarkably, it could be easily regenerated and the removal efficiency remains almost constant even after six cycles.
Chemoselective Tyrosine Bioconjugation through Sulfate Click Reaction
Authors: Choi Eun Joung , Jung Dongwook , Kim Jong‐Seo , Lee Yan , Kim B. Moon
Published: June 2018

A novel and selective tyrosine functionalization strategy through SuFEx (sulfur fluoride exchange) chemistry is presented. In this approach, free tyrosine (Tyr) reacts selectively with aryl fluorosulfate in the presence of various nucleophilic amino acid residues in bio‐tolerable conditions. Chemoselectivity of this unique SuFEx reaction was confirmed in amino acid, peptide, and protein conjugations. The functions of peptides and proteins were well‐preserved as demonstrated from the Tyr‐specific modification of cell‐penetrating peptide and erythropoietin. This method is well‐suited for residue‐specific modification of native proteins, and thus would expand the versatility of bio‐conjugation in protein chemistry.
The de winter electrocardiogram pattern is a transient electrocardiographic phenomenon that presents at the early stage of ST‐segment elevation myocardial infarction
Authors: Xu Jing , Wang Aihua , Liu Li , Chen Zijun
Published: June 2018

Background

The de Winter electrocardiogram (EKG) pattern is a novel sign that indicates left anterior descending coronary artery (LAD) occlusion in patients with chest pain. This study aimed to assess the prevalence and clinical characteristics of patients with this pattern.

Hypothesis

The de Winter EKG pattern is an special anterior ST‐segment elevation myocardial infarction (STEMI) equivalents without obvious ST‐segment elevation.

Methods

This retrospective study included all patients with anterior myocardial infarction admitted between January 2011 and December 2017. Patients were categorized into two groups: those with the de Winter EKG pattern and those with typical STEMI.

Results

Of 441 patients, 15 (3.4%) with anterior myocardial infarction had the de Winter EKG pattern. Similar to those with typical STEMI, the majority of patients with the de Winter EKG pattern had ST‐segment elevation, pathologic Q wave, and absence of R wave at follow‐up. The median time from recognition of this pattern until its evolution was 114 minutes. The ST‐segment in leads V3R to V5R and leads V7 to V9 were normal or slightly depressed when a typical de Winter EKG pattern was noted in leads V1 to V6. The culprit lesion was mainly in the proximal LAD or the diagonal branch. Patients with this EKG pattern responded poorly to thrombolytic therapy.

Conclusions

We believe that the de Winter EKG pattern may be a sign of ischemia and presents at the early stage of STEMI rather than being an independent pattern. In patients with this pattern, a percutaneous coronary intervention rather than follow‐up and thrombolytic strategy should be performed.
On the use of machine learning techniques for the mechanical characterization of soft biological tissues
Authors: Cilla Myriam , Pérez‐Rey Ignacio , Martínez Miguel Angel , Peña Estefania , Martínez Javier
Published: June 2018

Motivated by the search for new strategies for fitting a material model, a new approach is explored in the present work. The use of numerical and complex algorithms based on machine learning techniques such as support vector machines for regression, bagged decision trees, and artificial neural networks is proposed for solving the parameter identification of constitutive laws for soft biological tissues. First, the mathematical tools were trained with analytical uniaxial data (circumferential and longitudinal directions) as inputs, and their corresponding material parameters of the Gasser, Ogden, and Holzapfel strain energy function as outputs. The train and test errors show great efficiency during the training process in finding correlations between inputs and outputs; besides, the correlation coefficients were very close to 1. Second, the tool was validated with unseen observations of analytical circumferential and longitudinal uniaxial data. The results show an excellent agreement between the prediction of the material parameters of the strain energy function and the analytical curves. Finally, data from real circumferential and longitudinal uniaxial tests on different cardiovascular tissues were fitted; thus, the material model of these tissues was predicted. We found that the method was able to consistently identify model parameters, and we believe that the use of these numerical tools could lead to an improvement in the characterization of soft biological tissues.
Root:shoot ratio in developing seedlings: How seedlings change their allocation in response to seed mass and ambient nutrient supply
Authors: Mašková Tereza , Herben Tomáš
Published: June 2018

Root:shoot (R:S) biomass partitioning is one of the keys to the plants' ability to compensate for limiting resources in the environment and thus to survive and succeed in competition. In adult plants, it can vary in response to many factors, such as nutrient availability in the soil or reserves in the roots from the previous season. The question remains whether, at the interspecific level, reserves in seeds can affect seedlings' R:S ratio in a similar way. Proper allocation to resource‐acquiring organs is enormously important for seedlings and is likely to determine their survival and further success. Therefore, we investigated the effect of seed mass on seedling R:S biomass partitioning and its interaction with nutrient supply in the substrate. We measured seedling biomass partitioning under two different nutrient treatments after 2, 4, 6, and 12 weeks for seventeen species differing in seed mass and covering. We used phylogenetically informed analysis to determine the independent influence of seed mass on seedling biomass partitioning. We found consistently lower R:S ratios in seedlings with higher seed mass. Expectedly, R:S was also lower with higher substrate nutrient supply, but substrate nutrient supply had a bigger effect on R:S ratio for species with higher seed mass. These findings point to the importance of seed reserves for the usage of soil resources. Generally, R:S ratio decreased over time and, similarly to the effect of substrate nutrients, R:S ratio decreased faster for large‐seeded species. We show that the seed mass determines the allocation patterns into new resource‐acquiring organs during seedling development. Large‐seeded species are more flexible in soil nutrient use. It is likely that faster development of shoots provides large‐seeded species with the key advantage in asymmetric above‐ground competition, and that this could constitute one of the selective factors for optimum seed mass.
Density‐dependent dispersal strategies in a cooperative breeder
Authors: Maag Nino , Cozzi Gabriele , Clutton‐Brock Tim , Ozgul Arpat
Published: June 2018

Dispersal is a key ecological process that influences the dynamics of spatially and socially structured populations and consists of three stages—emigration, transience, and settlement—and each stage is influenced by different social, individual, and environmental factors. Despite our appreciation of the complexity of the process, we lack a firm empirical understanding of the mechanisms underlying the different stages. Here, using data from 65 GPS‐collared dispersing female coalitions of the cooperatively breeding meerkat (Suricata suricatta), we present a comprehensive analysis of the effects of population density, mate availability, dispersing coalition size, and individual factors on each of the three stages of dispersal in a wild population. We expected a positive effect of density on dispersal due to increased kin competition at high densities. We further anticipated positive effects of mate availability, coalition size, and body condition on dispersal success. We observed increasing daily emigration and settlement probabilities at high population densities. In addition, we found that emigration and settlement probabilities also increased at low densities and were lowest at medium densities. Daily emigration and settlement probabilities increased with increasing female coalition size and in the presence of unrelated males. Furthermore, the time individuals spent in the transient stage increased with population density, whereas coalition size and presence of unrelated males decreased dispersal distance. The observed nonlinear relationship between dispersal and population density is likely due to limited benefits of cooperation at low population densities and increased kin competition at high densities. Our study provides empirical validation for the theoretical predictions that population density is an important factor driving the evolution of delayed dispersal and philopatry in cooperative breeders.
Nudging people with Type 2 diabetes towards better self‐management through personalized risk communication: A pilot randomized controlled trial in primary care
Authors: Rouyard Thomas , Leal Jose , Baskerville Richard , Velardo Carmelo , Salvi Dario , Gray Alastair
Published: June 2018

Objectives

To assess the feasibility in routine primary care consultation and investigate the effect on risk recall and self‐management of a new type of risk communication intervention based on behavioural economics (“nudge‐based”) for people with Type 2 diabetes mellitus (T2DM).

Methods

Forty adults with poorly controlled T2DM(HbA1c > 7.5%) were randomized to receive a personalized, nudge‐based risk communication intervention (n = 20) or standard care (n = 20). Risk recall and self‐management were evaluated at baseline and 12 weeks after the intervention.

Results

Both in terms of feasibility and acceptability, this new risk communication intervention was very satisfactory. Study retention rate after 12 weeks was very high (90%) and participants were highly satisfied with the intervention (4.4 out of 5 on theCOMRADEscale). Although not powered to identify significant between‐group effects, the intervention significantly improved risk recall after 12 weeks and intentions to make lifestyle changes (dietary behaviour) compared to standard care.

Conclusions

This pilot study provides the first evidence of the feasibility of implementing in primary care a nudge‐based risk communication intervention for people with T2DM. Based on the promising results observed, an adequately powered trial to determine the effectiveness of the intervention on long‐term self‐management is judged feasible. As a result of this feasibility study, some minor adaptations to the intervention and study methods that would help to facilitate a definitive trial are also reported.