bluuebunny/crossref_metadata_2025 huggingface dataset:
HSF-1 activates the ubiquitin proteasome system to promote non-apoptotic developmental cell death in C. elegans
Authors: Kinet Maxime J , Malin Jennifer A , Abraham Mary C , Blum Elyse S , Silverman Melanie R , Lu Yun , Shaham Shai
Published: March 2016

Apoptosis is a prominent metazoan cell death form. Yet, mutations in apoptosis regulators cause only minor defects in vertebrate development, suggesting that another developmental cell death mechanism exists. While some non-apoptotic programs have been molecularly characterized, none appear to control developmental cell culling. Linker-cell-type death (LCD) is a morphologically conserved non-apoptotic cell death process operating in Caenorhabditis elegans and vertebrate development, and is therefore a compelling candidate process complementing apoptosis. However, the details of LCD execution are not known. Here we delineate a molecular-genetic pathway governing LCD in C. elegans. Redundant activities of antagonistic Wnt signals, a temporal control pathway, and mitogen-activated protein kinase kinase signaling control heat shock factor 1 (HSF-1), a conserved stress-activated transcription factor. Rather than protecting cells, HSF-1 promotes their demise by activating components of the ubiquitin proteasome system, including the E2 ligase LET-70/UBE2D2 functioning with E3 components CUL-3, RBX-1, BTBD-2, and SIAH-1. Our studies uncover design similarities between LCD and developmental apoptosis, and provide testable predictions for analyzing LCD in vertebrates.
Degradation of Gadd45 mRNA by nonsense-mediated decay is essential for viability
Authors: Nelson Jonathan O , Moore Kristin A , Chapin Alex , Hollien Julie , Metzstein Mark M
Published: March 2016

The nonsense-mediated mRNA decay (NMD) pathway functions to degrade both abnormal and wild-type mRNAs. NMD is essential for viability in most organisms, but the molecular basis for this requirement is unknown. Here we show that a single, conserved NMD target, the mRNA coding for the stress response factor growth arrest and DNA-damage inducible 45 (GADD45) can account for lethality in Drosophila lacking core NMD genes. Moreover, depletion of Gadd45 in mammalian cells rescues the cell survival defects associated with NMD knockdown. Our findings demonstrate that degradation of Gadd45 mRNA is the essential NMD function and, surprisingly, that the surveillance of abnormal mRNAs by this pathway is not necessarily required for viability.
Phase diagram and polarization of stable phases of (Ga1−
xInx)2O3
Authors: Maccioni Maria Barbara , Fiorentini Vincenzo
Published: March 2016

The full phase diagram of (Ga1−

x
In
x
)2O3 is obtained theoretically. The phases competing for the ground state are monoclinic β (low x), hexagonal (x ∼ 0.5), and bixbyite (large x). Three disconnected mixing regions interlace with two distinct phase-separation regions, and at x ∼ 0.5, the coexistence of hexagonal and β alloys with phase-separated binary components is expected. We also explore the permanent polarization of the phases, but none of them are polar. On the other hand, we find that ε-Ga2O3, which was stabilized in recent experiments, is pyroelectric with a large polarization and piezoelectric coupling, and could be used to produce high-density electron gases at interfaces.
Emerging Radiometals forPETImaging
Authors: Nedrow Jessie R. , Anderson Carolyn J.
Published: March 2016

Radiopharmaceuticals are drugs containing a radionuclide and are utilized for diagnosis, monitoring, and/or treatment of diseases. This article focuses on the development of emerging radiometal‐based imaging agents for positron emission tomography (PET), as well as new developments in F‐18‐labeled agents via aluminum fluoride chemistry. The incorporation of radiometals through chelation is typically simpler than the common multistep reactions to incorporate F‐18 into molecules, and radiometal‐conjugates generally require minimal if any purification. Widely studied PET radiometals (e.g., gallium‐68, copper‐64, zirconium‐89, yttrium‐86, and rubidium‐82) can be readily produced and have desirable decay properties for PET imaging. However, there are several emerging radiometals with desirable properties for PET imaging (e.g., scandium‐44, multiple isotopes of copper, terbium‐182, gallium‐66, and cobalt‐55) with unique properties (e.g., a range of half‐lives) that provide additional opportunities for PET imaging and allow for the developmental of new and unique PET radiopharmaceuticals.
Nanocarrier‐Mediated Codelivery of Small Molecular Drugs and siRNA to Enhance Chondrogenic Differentiation and Suppress Hypertrophy of Human Mesenchymal Stem Cells
Authors: Xu Jianbin , Li Jinming , Lin Sien , Wu Tianyi , Huang Heqin , Zhang Kunyu , Sun Yuxin , Yeung Kelvin W. K. , Li Gang , Bian Liming
Published: March 2016

Cartilage loss is a leading cause of disability among adults, and effective therapy remains elusive. Human mesenchymal stem cells (hMSCs), which have demonstrated self‐renewal and multipotential differentiation, are a promising cell source for cartilage repair. However, the hypertrophic differentiation of the chondrogenically induced MSCs and resulting tissue calcification hinders the clinical translation of MSCs for cartilage repair. Here, a multifunctional nanocarrier based on quantum dots (QDs) is developed to enhance chondrogenic differentiation and suppress hypertrophy of hMSCs simultaneously. Briefly, the QDs are modified with β‐cyclodextrin (β‐CD) and RGD peptide. The resulting nanocarrier is capable of carrying hydrophobic small molecules such as kartogenin in the hydrophobic pockets of conjugated β‐CD to induce chondrogenic differentiation of hMSCs. Meanwhile, via electrostatic interaction the conjugated RGD peptides bind the cargo siRNA targeting Runx2, which is a key regulator of hMSC hypertrophy. Furthermore, due to the excellent photostability of QDs, hMSCs labeled with the nanocarrier can be tracked for up to 14 d after implantation in nude mice. Overall, this work demonstrates the potential of our nanocarrier for inducing and maintaining the chondrogenic phenotype and tracking hMSCs in vivo.
Donor–Acceptor Poly(3‐hexylthiophene)‐block‐Pendent Poly(isoindigo) with Dual Roles of Charge Transporting and Storage Layer for High‐Performance Transistor‐Type Memory Applications
Authors: Wang Jau‐Tzeng , Takashima Shoichi , Wu Hung‐Chin , Chiu Yu‐Cheng , Chen Yougen , Isono Takuya , Kakuchi Toyoji , Satoh Toshifumi , Chen Wen‐Chang
Published: March 2016

Field‐effect transistor memories usually require one additional charge storage layer between the gate contact and organic semiconductor channel. To avoid such complication, new donor–acceptor rod–coil diblock copolymers (P3HT44‐b‐Pison) of poly(3‐hexylthiophene) (P3HT)‐block‐poly(pendent isoindigo) (Piso) are designed, which exhibit high performance transistor memory characteristics without additional charge storage layer. The P3HT and Piso blocks are acted as the charge transporting and storage elements, respectively. The prepared P3HT44‐b‐Pison can be self‐assembled into fibrillar‐like nanostructures after the thermal annealing process, confirmed by atomic force microscopy and grazing‐incidence X‐ray diffraction. The lowest‐unoccupied molecular orbital levels of the studied polymers are significantly lowered as the block length of Piso increases, leading to a stronger electron affinity as well as charge storage capability. The field‐effect transistors (FETs) fabricated from P3HT44‐b‐Pison possess p‐type mobilities up to 4.56 × 10−2 cm2 V−1 s−1, similar to that of the regioregular P3HT. More interestingly, the FET memory devices fabricated from P3HT44‐b‐Pison exhibit a memory window ranging from 26 to 79 V by manipulating the block length of Piso, and showed stable long‐term data endurance. The results suggest that the FET characteristics and data storage capability can be effectively tuned simultaneously through donor/acceptor ratio and thin film morphology in the block copolymer system.
Synthesis of Planar Chiral Shvo Catalysts for Asymmetric Transfer Hydrogenation
Authors: Dou Xiaowei , Hayashi Tamio
Published: March 2016

A new type of planar chiral Shvo catalysts, where the chirality is based solely on different substitution flanking the CO function, was prepared and used for transfer hydrogenation of imines and ketones. The reduction of ketimines represented by N‐(1‐phenylethylidene)aniline and prochiral ketones such as phenyl trifluoromethyl ketone with 2‐propanol was efficiently catalyzed by 0.5 mol% of the chiral Shvo catalyst to give high yields of the corresponding reduction products with the enantioselectivities in the range 45% to 64% ee.

magnified image
Organocatalytic Enantioselective Conjugate Addition of Malonic Acid Half Thioesters to Coumarin‐3‐carboxylic Acids Using N‐Heteroarenesulfonyl Cinchona Alkaloid Amides
Authors: Nakamura Shuichi , Toda Ayaka , Sano Masahide , Hatanaka Tsubasa , Funahashi Yasuhiro
Published: March 2016

We disclose herein an efficient enantioselective conjugate addition reaction between coumarin‐3‐carboxylic acids and malonic acid half thioesters (MAHTs). The reaction was catalyzed by N‐heteroarenesulfonyl Cinchona alkaloid amides to afford double‐decarboxylative conjugate addition products in good yield with high enantioselectivity. The reaction of various coumarin‐3‐carboxylic acids with MAHTs gave products in high yield with high enantioselectivity.

magnified image
Nondisruptive Dissolution of Hyperpolarized 129Xe into Viscous Aqueous and Organic Liquid Crystalline Environments
Authors: Truxal Ashley E. , Slack Clancy C. , Gomes Muller D. , Vassiliou Christophoros C. , Wemmer David E. , Pines Alexander
Published: March 2016

Studies of hyperpolarized xenon‐129 (hp‐129Xe) in media such as liquid crystals and cell suspensions are in demand for applications ranging from biomedical imaging to materials engineering but have been hindered by the inability to bubble Xe through the desired media as a result of viscosity or perturbations caused by bubbles. Herein a device is reported that can be reliably used to dissolve hp‐129Xe into viscous aqueous and organic samples without bubbling. This method is robust, requires small sample volumes (<60 μL), is compatible with existing NMR hardware, and is made from readily available materials. Experiments show that Xe can be introduced into viscous and aligned media without disrupting molecular order. We detected dissolved xenon in an aqueous liquid crystal that is disrupted by the shear forces of bubbling, and we observed liquid‐crystal phase transitions in (MBBA). This tool allows an entirely new class of samples to be investigated by hyperpolarized‐gas NMR spectroscopy.
A Stable Heterocyclic Amino(phosphanylidene‐σ4‐phosphorane) Germylene
Authors: Del Rio Natalia , Baceiredo Antoine , Saffon‐Merceron Nathalie , Hashizume Daisuke , Lutters Dennis , Müller Thomas , Kato Tsuyoshi
Published: March 2016

A new stable heterocyclic germylene, in which the divalent germanium atom lies between a nitrogen atom and a phosphanylidene phosphorane group, was synthesized. Experimental and theoretical studies revealed the peculiar effect of phosphanylidene phosphorane substituent, which is a stronger π‐donor towards germanium than an amino group is. Because of the weak phosphorus–germanium π‐bond, this new germylene compound shows an enhanced reactivity compared to classical N‐heterocyclic germylenes.
Asymmetric Brønsted Acid Catalyzed Substitution of Diaryl Methanols with Thiols and Alcohols for the Synthesis of Chiral Thioethers and Ethers
Authors: Chatupheeraphat Adisak , Liao Hsuan‐Hung , Mader Steffen , Sako Makoto , Sasai Hiroaki , Atodiresei Iuliana , Rueping Magnus
Published: March 2016

An enantioselective addition of thiols and alcohols to aza‐ortho‐quinone methides, starting from diaryl methanols, was developed. The asymmetric additions occur under mild reaction conditions in the presence of chiral phosphoric acids and furnish the corresponding adducts with excellent yields and enantioselectivities.
Moenomycin Biosynthesis: Structure and Mechanism of Action of the Prenyltransferase MoeN5
Authors: Zhang Lilan , Chen Chun‐Chi , Ko Tzu‐Ping , Huang Jian‐Wen , Zheng Yingying , Liu Weidong , Wang Iren , Malwal Satish R. , Feng Xinxin , Wang Ke , Huang Chun‐Hsiang , Hsu Shang‐Te Danny , Wang Andrew H.‐J. , Oldfield Eric , Guo Rey‐Ting
Published: March 2016

The structure of MoeN5, a unique prenyltransferase involved in the biosynthesis of the antibiotic moenomycin, is reported. MoeN5 catalyzes the reaction of geranyl diphosphate (GPP) with the cis‐farnesyl group in phosphoglycolipid 5 to form the (C25) moenocinyl‐sidechain‐containing lipid 7. GPP binds to an allylic site (S1) and aligns well with known S1 inhibitors. Alkyl glycosides, glycolipids, can bind to both S1 and a second site, S2. Long sidechains in S2 are “bent” and co‐locate with the homoallylic substrate isopentenyl diphosphate in other prenyltransferases. These observations support a MoeN5 mechanism in which 5 binds to S2 with its C6–C11 group poised to attack C1 in GPP to form the moenocinyl sidechain, with the more distal regions of 5 aligning with the distal glucose in decyl maltoside. The results are of general interest because they provide the first structures of MoeN5 and a structural basis for its mechanism of action, results that will facilitate the design of new antibiotics.
Chemoenzymatic epoxidation of Karanja oil: an alternative to chemical epoxidation?
Authors: Bajwa Arjun S. , Sathaye Sadhana , Kulkarni Vaishali M. , Patwardhan Anand V.
Published: March 2016

In light of increasing concern about diminishing fossil fuel reserve, a lot of research is being focussed on the production of chemicals using renewable feedstock. Vegetable oils provide this valuable renewable feedstock as they offer a large number of possibilities. One of the interesting possibilities offered is epoxidized vegetable oil, which can be used as a plasticizer, polyvinyl chloride stabilizer, diluent, etc. Hence, a chemoenzymatic method for epoxidation of Karanja oil was investigated. The enzyme reusability, the important criteria for commercial exploitation of the technique, was also investigated. Three commercially available immobilized lipase enzymes were screened and Novozyme 435 was found to be best for chemoenzymatic epoxidation of Karanja oil. The study revealed that epoxide conversion of 80% (equivalent to chemical methods) was obtained at room temperature in the absence of any side reactions. Maximum epoxide conversion was obtained in 8–9 h at 30 °C as compared with 6 h for conventional methods at 80 °C. The reaction could also be carried out in the absence of any solvent to an extent of 56% oxirane conversion. The catalyst was found to be strongly affected by temperature and H2O2 and denatured after repeated runs, showing a maximal reusability of four runs. The enzymatic method is beyond doubt a cleaner and greener technology compared with conventional method. The advantages of energy efficiency along with 100% selectivity make it a method for the future. Copyright © 2016 Curtin University of Technology and John Wiley & Sons, Ltd.
Combined experimental and numerical kinetic characterization of NR vulcanized with sulfur, N‐terbutyl, 2‐benzothiazylsulfenamide, and N,N‐diphenylguanidine
Authors: Milani G. , Hanel T. , Donetti R. , Milani F.
Published: March 2016

A comprehensive experimental and numerical analysis aimed at investigating the rheometer behavior of Natural Rubber (NR) vulcanized with sulfur and two accelerators [N,N‐diphenylguanidine (DPG) and N‐terbutyl, 2‐benzothiazylsulfenamide (TBBS)] is presented. To fit experimental data, the general reaction scheme proposed by Han and co‐workers for vulcanized sulfur NR is re‐adapted and suitably modified, taking into account DPG and TBBS single contributions. An ad hoc interactive software based on GUI technology is utilized to fit experimental data, allowing estimating kinetic constants also by unexperienced users. Chain reactions initiated by the formation of macrocompounds responsible for the formation of the instable crosslinked polymer are accounted for. In the presence of two accelerators, reactions are assumed to proceed in parallel, making the hypothesis of negligible interactions, being their concentrations rather similar. From the kinetic scheme adopted, a closed form solution is found for the crosslinking density, with the only limitation that the induction period is excluded from computations. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43519.
Thermomechanical properties and water uptake capacity of soy protein‐based bioplastics processed by injection molding
Authors: Fernández‐Espada Lucía , Bengoechea Carlos , Cordobés Felipe , Guerrero Antonio
Published: March 2016

The optimization of the processing conditions in the production of soy protein bioplastics by injection molding has been essential in order to develop materials with a great capacity to absorb water while displaying good mechanical properties. Using a 50/50 (wt/wt) soy protein/glycerol mixture, and 40 °C, 500 bar, and 70 °C as reference values for cylinder temperature, injection pressure, and mold temperature, respectively, the effect of those processing parameters over thermomechanical and hydrophilic properties was studied. Processing parameters did not show a great influence over the thermomechanical bending properties within temperatures ranging from −30 to 130 °C, as most samples displayed a similar response, independently of the parameter studied. On the other hand, when studying tensile and hydrophilic properties, the main effect corresponded to the cylinder and mold temperature values, as pressure did not exert a clear influence when increased from 300 to 900 bar. Samples with a lower water uptake were obtained when processed at higher temperature, as a result of crosslinking promotion. Moreover, a greater extensibility was observed when bioplastics are processed at high mold temperatures. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43524.
Improving flame retardancy and melt processability of polyethersulfone using low molecular weight additives
Authors: Owusu‐Nkwantabisah Silas , Staudt Claudia , Lesser Alan J.
Published: March 2016

The effect of a calcium stearate (CaSt2) additive on the melt processability and flame retardancy of polyethersulfone (PES) was studied. Measurements of the viscosity of PES and its composites showed a marked decrease in viscosity with increase in the fraction of CaSt2 additive. About 40% reduction in viscosity of PES was achieved with addition of 5 wt % CaSt2. By decreasing the viscosity, the CaSt2 additive enabled the melt extrusion of PES at lower temperatures up to 90 °C below that of conventional melt processing. The flammability was also investigated using a Pyrolysis Combustion Flow Calorimeter (PCFC). The CaSt2 additive resulted in tremendous improvement in the flame retardancy of PES as evident in the reduction of the heat release capacity (HRC) of the composites by up to 37%. Moreover, the peak of heat release rate (pHRR) of PES in the composites was up to 84% lower than in the neat polymer. The remarkable improvement in flame retardancy of PES was demonstrated to be related to the rapid charring of the composites and the in situ formation of calcium carbonate/calcium oxide upon decomposition of CaSt2. The CaSt2 additive was also found to enhance the flame retardancy of thermoplastics including polyamide‐6 and polypropylene (PP). © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43525.
The MYpop toolbox: Putting yeast stress responses in cellular context on single cell and population scales
Authors: Spiesser Thomas , Kühn Clemens , Krantz Marcus , Klipp Edda
Published: March 2016

Systems biology holds the promise to integrate multiple sources of information in order to build ever more complete models of cellular function. To do this, the field must overcome two significant challenges. First, the current strategy to model average cells must be replaced with population based models accounting for cell‐to‐cell variability. Second, models must be integrated with each other and with basic cellular function. This requires a core model of cellular physiology as well as a multiscale simulation platform to support large‐scale simulation of culture or tissues from single cells. Here, we present such a simulation platform with a core model of yeast physiology as scaffold to integrate and simulate SBML models. The software automates this integration helping users simulate their model of choice in context of the cell division cycle. We benchmark model merging, simulation and analysis by integrating a minimal model of osmotic stress into the core model and analyzing it. We characterize the effect of single cell differences on the dynamics of osmoadaptation, estimating when normal cell growth is resumed and obtaining an explanation for experimentally observed glycerol dynamics based on population dynamics. Hence, the platform can be used to reconcile single cell and population level data.
Concentrating membrane proteins using ultrafiltration without concentrating detergents
Authors: Feroz Hasin , Vandervelden Craig , Ikwuagwu Bon , Ferlez Bryan , Baker Carol S. , Lugar Daniel J. , Grzelakowski Mariusz , Golbeck John H. , Zydney Andrew L. , Kumar Manish
Published: March 2016

Membrane proteins (MPs) are of rapidly growing interest in the design of pharmaceutical products, novel sensors, and synthetic membranes. Ultrafiltration (UF) using commercially available centrifugal concentrators is typically employed for laboratory‐scale concentration of low‐yield MPs, but its use is accompanied by a concomitant increase in concentration of detergent micelles. We present a detailed analysis of the hydrodynamic processes that control detergent passage during ultrafiltration of MPs and propose methods to optimize detergent passage during protein concentration in larger‐scale membrane processes. Experiments were conducted using nonionic detergents, octyl‐β‐D glucoside (OG), and decyl‐β‐D maltoside (DM) with the bacterial water channel protein, Aquaporin Z (AqpZ) and the light driven chloride pump, halorhodopsin (HR), respectively. The observed sieving coefficient (So), a measure of detergent passage, was evaluated in both stirred cell and centrifugal systems. So for DM and OG increased with increasing filtrate flux and decreasing shear rates in the stirred cell, that is, with increasing concentration polarization (CP). Similar effects were observed during filtration of MP‐detergent (MPD) micelles. However, lower transmission was observed in the centrifugal system for both detergent and MPD systems. This is attributed to free convection‐induced shear and hence reduced CP along the membrane surface during centrifugal UF. Thus to concentrate MPs without retention of detergent, design of UF systems that promote CP is required. Biotechnol. Bioeng. 2016;113: 2122–2130. © 2016 Wiley Periodicals, Inc.
Optimization of biomolecule separation by combining microscale filtration and design‐of‐experiment methods
Authors: Kazemi Amir S. , Kawka Karina , Latulippe David R.
Published: March 2016

There is considerable interest in developing microscale (i.e., high‐throughput) methods that enable multiple filtration experiments to be run in parallel with smaller sample amounts and thus reduce the overall required time and associated cost to run the filtration tests. Previous studies to date have focused on simply evaluating the filtration capacity, not the separation performance. In this work, the stirred‐well filtration (SWF) method was used in combination with design‐of‐experiment (DOE) methods to optimize the separation performance for three binary mixtures of bio‐molecules: protein–protein, protein‐polysaccharide, and protein‐DNA. Using the parallel based format of the SWF method, eight constant‐flux ultrafiltration experiments were conducted at once to study the effects of stirring conditions, permeate flux, and/or solution conditions (pH, ionic strength). Four separate filtration tests were conducted for each combination of process variables; in total, over 100 separate tests were conducted. The sieving coefficient and selectivity results are presented to match the DOE design format and enable a greater understanding of the effects of the different process variables that were studied. The method described herein can be used to rapidly determine the optimal combination of process factors that give the best separation performance for a range of membrane‐based separations applications and thus obviate the need to run a large number of traditional lab‐scale tests. Biotechnol. Bioeng. 2016;113: 2131–2139. © 2016 Wiley Periodicals, Inc.
Why should biochemistry students be introduced to molecular dynamics simulations—and how can we introduce them?
Authors: Elmore Donald E.
Published: March 2016

Molecular dynamics (MD) simulations play an increasingly important role in many aspects of biochemical research but are often not part of the biochemistry curricula at the undergraduate level. This article discusses the pedagogical value of exposing students to MD simulations and provides information to help instructors consider what software and hardware resources are necessary to successfully introduce these simulations into their courses. In addition, a brief review of the MD‐based activities in this issue and other sources are provided. © 2016 by The International Union of Biochemistry and Molecular Biology, 44:118–123, 2016.
The evolution of the Krebs cycle: A promising subject for meaningful learning of biochemistry
Authors: da Costa Caetano , Galembeck Eduardo
Published: March 2016

Evolution has been recognized as a key concept for biologists. To enhance comprehension and motivate biology undergraduates for the contents of central energetic metabolism, we addressed the Krebs cycle structure and functions in an evolutionary view. To this end, we created a study guide that contextualizes the emergence of the cyclic pathway, in light of the prokaryotic influence since the early anaerobic condition of the Earth to increase oxygen in the atmosphere. The study guide is composed of three interrelated sections: (1) a problem, designed to arouse curiosity, inform and motivate students, (2) a text about life evolution, including early microorganisms and the emergence of the Krebs cycle, and (3) questions for debate. The activity consisted on individual reading and peer discussion based on this written material, under the guidance of the instructors. The questions were designed to foster debate in an ever‐increasing level of complexity and to strengthen the main contextual aspects leading to emergence, evolving, and permanency of a complex metabolic pathway. Based on classroom observation, analysis of student's written responses, and individual interviews, we noticed they were engaged and motivated by the task, especially during group discussion. The whole experience suggests that the study guide was a stimulus to broaden the comprehension of the Krebs cycle, reinforcing the evolutionary approach as an important subject for learning purposes. © 2016 by The International Union of Biochemistry and Molecular Biology, 44:288–296, 2016.
A decade of human genome project conclusion: Scientific diffusion about our genome knowledge
Authors: Moraes Fernanda , Góes Andréa
Published: March 2016

The Human Genome Project (HGP) was initiated in 1990 and completed in 2003. It aimed to sequence the whole human genome. Although it represented an advance in understanding the human genome and its complexity, many questions remained unanswered. Other projects were launched in order to unravel the mysteries of our genome, including the ENCyclopedia of DNA Elements (ENCODE). This review aims to analyze the evolution of scientific knowledge related to both the HGP and ENCODE projects. Data were retrieved from scientific articles published in 1990–2014, a period comprising the development and the 10 years following the HGP completion. The fact that only 20,000 genes are protein and RNA‐coding is one of the most striking HGP results. A new concept about the organization of genome arose. The ENCODE project was initiated in 2003 and targeted to map the functional elements of the human genome. This project revealed that the human genome is pervasively transcribed. Therefore, it was determined that a large part of the non‐protein coding regions are functional. Finally, a more sophisticated view of chromatin structure emerged. The mechanistic functioning of the genome has been redrafted, revealing a much more complex picture. Besides, a gene‐centric conception of the organism has to be reviewed. A number of criticisms have emerged against the ENCODE project approaches, raising the question of whether non‐conserved but biochemically active regions are truly functional. Thus, HGP and ENCODE projects accomplished a great map of the human genome, but the data generated still requires further in depth analysis. © 2016 by The International Union of Biochemistry and Molecular Biology, 44:215–223, 2016.
Acrocyanosis revealing chronic lymphocytic leukemia
Authors: Lesesve Jean François
Published: March 2016

Key Clinical Message

Cold agglutinin disease arising in the context of chronic lymphocytic leukemia can misdiagnose a warm autoimmune hemolytic anemia.
Room‐Temperature Practical Copper‐Catalyzed Amination of Aryl Iodides
Authors: Deldaele Christopher , Evano Gwilherm
Published: March 2016

An efficient and highly practical procedure is reported for the Ullmann–Goldberg‐type copper‐catalyzed amination of aryl iodides. By using a combination of copper iodide and proline in the presence of an excess of an amine, a wide range of aryl iodides can be readily aminated at room temperature. The reaction proceeds well regardless of the electronic properties of the starting aryl iodide and the amination products can be obtained without the need for purification by column chromatography in most cases. Owing to its efficiency and the mildness of the reaction conditions, this amination could also be extended to the amination of complex aryl iodides at room temperature.
Iron‐Based Fischer–Tropsch Synthesis for the Efficient Conversion of Carbon Dioxide into Isoparaffins
Authors: Geng Shunshun , Jiang Feng , Xu Yuebing , Liu Xiaohao
Published: March 2016

Iron‐based Fischer–Tropsch (FT) synthesis in combination with hydroisomerization in the presence of zeolites for the synthesis of isoparaffins from CO2/H2 was conducted in a fixed‐bed reactor. Relative to supported iron catalysts, the precipitated one efficiently converted intermediate CO into hydrocarbons by supplying a high density of FT active sites on the catalyst surface. Removing water by interstage cooling and promoting the CO conversion step in the FT synthesis were effective approaches in achieving a high CO2 conversion, because of an increase in the driving force to the reaction equilibrium. Particle mixing of 92.6 Fe7.4 K with either 0.5 Pd/β or HZSM‐5 zeolite effectively hydroisomerized the resulting FT hydrocarbons into gasoline‐range isoparaffins. Particularly, HZSM‐5 displayed a higher isoparaffin selectivity at approximately 70 %, which resulted from easier hydrocracking and hydroisomerization of the olefinic FT primary products.
Flower‐like Cu2In2ZnS5 Nanosheets: A Novel Promising Photoelectrode for Water Splitting
Authors: Hong Tiantian , Liu Zhifeng , Zhang Jing , Li Guangmin , Liu Junqi , Zhang Xueqi , Lin Shaohua
Published: March 2016

This paper describes a promising photoelectrochemical electrode based on a flower‐like Cu2In2ZnS5 structure composed of nanosheets and its use as a photoelectrode for photoelectrochemical (PEC) water splitting for the first time. The detailed growth of Cu2In2ZnS5 was discussed. The morphology and microstructure were characterized in detail. PEC measurements showed that on the basis of the optimal hydrothermal time, flower‐like Cu2In2ZnS5 exhibited high photoelectrochemical activity, as the photocurrent density reached up to 2.00 mA cm−2. The remarkable PEC performance stems from crucial factors, including improved light absorption, an ideal band gap value, decoupling of the directions of light absorption and charge‐carrier collection, and large surface area. Our results indicate that the flower‐like Cu2In2ZnS5 structure composed of nanosheets has enormous potential in PEC water splitting.
Cobalt‐Catalyzed Cyclization of N‐Methoxy Benzamides with Alkynes using an Internal Oxidant through C−H/N−O Bond Activation
Authors: Sivakumar Ganesan , Vijeta Arjun , Jeganmohan Masilamani
Published: March 2016

The cyclization of substituted N‐methoxy benzamides with alkynes in the presence of an easily affordable cobalt complex and NaOAc provides isoquinolone derivatives in good to excellent yields. The cyclization reaction is compatible with a range of functional group‐substituted benzamides, as well as ester‐ and alcohol‐substituted alkynes. The cobalt complex [CoIIICp*(OR)2] (R=Me or Ac) serves as an efficient catalyst for the cyclization reaction. Later, isoquinolone derivatives were converted into 1‐chloro and 1‐bromo substituted isoquinoline derivatives in excellent yields in the presence of POCl3 or PBr3.
Design of 2D Porous Coordination Polymers Based on Metallacrown Units
Authors: Atzeri Corrado , Marchiò Luciano , Chow Chun Y. , Kampf Jeff W. , Pecoraro Vincent L. , Tegoni Matteo
Published: March 2016

A 12‐metallacrown‐4 (MC) complex was designed and employed as the building block in the synthesis of coordination polymers, one of which is the first permanently porous MC architecture. The connection of the four‐fold symmetric MC subunits by CuII nodes led to the formation of 2D layers of metallacrowns. Channels are present in the crystalline architecture, which exhibits permanent porosity manifested in N2 and CO2 uptake capacity.
A Cyclometalated Iridium(III) Complex Serves as a Phosphorescent Probe for Specific Mitochondrial Imaging in Living Cells
Authors: Wang Jinquan , Hou Xiaojuan , Jin Chengzhi , Chao Hui
Published: March 2016

A new cyclometalated iridium(III) complex [Ir(2‐pq)2(HPIP)]Cl (Ir1, 2‐pq=3‐phenylisoquinoline, HPIP=2‐(2‐hydroxyphenyl)imidazo[4,5‐f]1,10‐phenanthroline) was synthesized and applied to image mitochondria in living cells. Ir1 displayed excellent ability to selectively accumulate in mitochondria of live cells with no requirement of replacement of the culture medium. Due to Ir1 exhibiting better photostability than the commercially available mitochondrial trackers, this complex could be applicable for the imaging and tracking of the mitochondrial morphological changes over long periods of time. In addition, in vitro cytotoxicity investigation revealed that Ir1 showed negligible cytotoxicity at the concentrations employed. Based on these, Ir1 is suitable for organelle‐selective imaging in living cells.
Applications of DNA Nanotechnology in Synthesis and Assembly of Inorganic Nanomaterials
Authors: Ma Yurou , Yang Xiangdong , Wei Yurong , Yuan Quan
Published: March 2016

In addition to its inherited genetic function, DNA is one of the smartest and most flexible self‐assembling nanomaterials with programmable and predictable features, for which, more and more scientists combine DNA with nanomaterials and put them into designing, synthesizing and assembling. In this review, four modes of action of DNA molecules are introduced in a figurative and intuitive way, based on the four different roles it plays in synthesis and assembly of nanomaterials: (a) smart linkers to guide nanoparticle assembly, (b) 2D or 3D scaffold with well‐designed binding sites, (c) nucleation sites to directly facilitate Au/Pd/Ag/Cu nanowires, nanoparticles, nano‐ arrays and (d) serving as capping agents to prevent crystal growth, and control size and morphology. To be sure, this state‐of‐the‐art combination of functional DNA molecules and inorganic nanomaterials greatly encouraged step towards the development of analytical science, life science, environmental science, and other promising field they can address. DNA‐guided nanofabrication will eventually exceed expectations far beyond our scope in the near future.
An Efficient One‐pot Three‐component Process for Synthesis of Perfluoroalkylated Quinolizines
Authors: Shen Dandan , Xu Yanjie , He Dong , Han Jing , Chen Jie , Deng Hongmei , Shao Min , Zhang Hui , Cao Weiguo
Published: March 2016

A facile multi‐component process for the synthesis of perfluoroalkylated quinolizine derivatives was achieved using various arylidenemalononitriles, pyridine, and methyl perfluoroalk‐2‐ynoates as starting materials. Moderate yields were obtained under mild condition. The structures of perfluoroalkylated quinolizine derivatives were characterized by means of 1H NMR, 13C NMR, 19F NMR, IR, LRMS and HRMS. Furthermore, the reaction mechanism was proposed.
Specific Electrochemiluminescence of Aptamer‐Functionalized Quantum Dots with Lysozyme and Hemin as Co‐Triggers
Authors: Ji Xubo , Yao Chuanguang , Wan Ying , Song Hongxin , Xin Peng , Cui Hongda , Zheng Chenyu , Deng Shengyuan
Published: March 2016

This work proposed a label‐free, cost‐effective and fairly sensitive electrogenerated chemiluminescence (ECL) strategy for the specific detection of lysozyme based on the hemin/G‐quadruplex hybrid. Gold nanoparticles were spread onto the chitosan thin‐film as substrate to adsorb thiolated captures: a hairpin‐structured DNA, integrating dual head‐tail connected functional domains: one aptamer sequence for lysozyme and the other for hemin (iron(III) proto‐porphyrin IX). In the presence of the both, the hairpin conformation unfolded and transformed into the hemin/G‐quadruplex motif, which quenched the ECL emission of underlaid quantum dots significantly via the consumption of dissolved oxygen as endogenous coreactant. This construction enabled a wide linear response to lysozyme, ranging from 20 pg·mL−1 to 5 µg·mL−1, with a detection limit as low as 4.95 pg·mL−1 (e.g. 9.4 pmol·L−1), demonstrating the prospective utilization of DNA technologies in bioanalysis.
Nucleophilic Trifluoromethylthiolation of Alkyl Chlorides, Bromides and Tosylates
Authors: Xu Chunfa , Chen Qingyun , Shen Qilong
Published: March 2016

A direct nucleophilic trifluoromethylthiolation of alkyl chlorides, bromides and tosylates with AgSCF3 was described. It was found that the presence of nBu4NI or a combination of nBu4NI/nBu4NBr significantly enhanced the reaction rates. The reaction conditions were mild, thus allowing the tolerance of a variety of functional groups.
Direct Perfluoroalkylthiolation of Few Chalcogenols
Authors: Glenadel Quentin , Billard Thierry
Published: March 2016

Trifluoromethanesulfenamide reagent can react with alcohols, in basic conditions, or with thiols, in catalytic acid conditions, to afford the corresponding trifluoromethanesulfenates or trifluoromethyldisulfides. The use of higher homologs of this reagent leads to synthesis of the nearly unknown perfluoroalkanesulfenates and perfluoroalkyldisulfides.
Copper‐Catalyzed Aerobic Oxidation of Azinylmethanes for Access to Trifluoromethylazinylols
Authors: Zheng Gang , Liu Hao , Wang Mang
Published: March 2016

A copper‐catalyzed oxygenation of methylazaarenes was found to occur in the absence of both ligand and additive, and has been successfully employed for the synthesis of trifluoromethylazinylketols. This synthetic strategy incorporates aerobic oxidation and a trifluoromethylation in one‐pot and provides a novel method for the trifluoromethylation of aliphatic CH bond.
Effect of N‐Terminal Acylation on the Activity of Myostatin Inhibitory Peptides
Authors: Takayama Kentaro , Nakamura Akari , Rentier Cédric , Mino Yusaku , Asari Tomo , Saga Yusuke , Taguchi Akihiro , Yakushiji Fumika , Hayashi Yoshio
Published: March 2016

Inhibition of myostatin, which negatively regulates skeletal muscle growth, is a promising strategy for the treatment of muscle atrophic disorders, such as muscular dystrophy, cachexia and sarcopenia. Recently, we identified peptide A (H‐WRQNTRYSRIEAIKIQILSKLRL‐NH2), the 23‐amino‐acid minimum myostatin inhibitory peptide derived from mouse myostatin prodomain, and highlighted the importance of its N‐terminal tryptophan residue for the effective inhibition. In this study, we synthesized a series of acylated peptide derivatives focused on the tryptophan residue to develop potent myostatin inhibitors. As a result of the investigation, a more potent derivative of peptide A was successfully identified in which the N‐terminal tryptophan residue is replaced with a 2‐naphthyloxyacetyl moiety to give an inhibitory peptide three times (1.19±0.11 μm) more potent than parent peptide A (3.53±0.25 μm). This peptide could prove useful as a new starting point for the development of improved inhibitory peptides.
Discovery of Non‐ATP‐Competitive Inhibitors of Polo‐like Kinase 1
Authors: Yun Taikangxiang , Qin Tan , Liu Ying , Lai Luhua
Published: March 2016

Polo‐like kinase 1 (Plk1) is an evolutionarily conserved serine/threonine kinase, and its N‐terminal kinase domain (KD) controls cell signaling through phosphorylation. Inhibitors of Plk1 are potential anticancer drugs. Most known Plk1 KD inhibitors are ATP‐competitive compounds, which may suffer from low selectivity. In this study we discovered novel non‐ATP‐competitive Plk1 KD inhibitors by virtual screening and experimental studies. Potential binding sites in Plk1 KD were identified by using the protein binding site detection program Cavity. The identified site was subjected to molecular‐docking‐based virtual screening. The activities of top‐ranking compounds were evaluated by in vitro enzyme assay with full‐length Plk1 and direct binding assay with Plk1 KD. Several compounds showed inhibitory activity, and the most potent was found to be 3‐((2‐oxo‐2‐(thiophen‐2‐yl)ethyl)thio)‐6‐(pyridin‐3‐ylmethyl)‐1,2,4‐triazin‐5(4H)‐one (compound 4) with an IC50 value of 13.1±1.7 μm. Our work provides new insight into the design of kinase inhibitors that target non‐ATP binding sites.
Novel habitat use supports population maintenance in a reconfigured landscape
Authors: O'Bryan C. J. , Homyack J. A. , Baldwin R. F. , Kanno Y. , Harrison A.‐L.
Published: March 2016

Given the limited scope of unaltered, protected areas in most regions, understanding the contributions to imperiled species conservation by landscapes in which habitat elements have been reconfigured is critical. Commercial forestry has been a driver of altered structure and composition of forests and of distribution and character of aquatic systems. In eastern North America, extensive historical wetland drainage reconfigured hydrologic environments from low‐gradient wet flats and isolated wetlands to connected networks of linear ditches. Landscapes where both uplands and aquatic environments differ from historic conditions may affect most ecological aspects of semi‐aquatic species, including reptiles. Our objective was to determine if habitat selection and use decisions by spotted turtles (Clemmys guttata), a rare semi‐aquatic species, supported population maintenance in a reconfigured forest landscape in eastern North Carolina,USA. We captured 280 individuals and radiomarked 31 adults to examine habitat selection at multiple spatial scales with paired logistic regression, movements and home ranges with location data and utilization distributions (UDs), survival with a known‐fate model, and abundance with N‐mixture modeling. Across local and landscape scales, turtles selected features associated with ditches despite abundant, more natural aquatic depressions across the study area. Habitat metrics describing understory closure and substrate characteristics were important at local scales, and closed canopy forest and habitat heterogeneity was positively associated with activity areas at landscape‐scale spatial grains. Both movements and home ranges were centered on ditches, and turtles exploited ditches to access mates, nest sites, or uplands for estivation. In this highly reconfigured landscape, this species appeared to have sufficient behavioral plasticity to acquire key resources contributing to high survival and an abundant population. Isolation from road traffic and collection, both which negatively affect turtles elsewhere, was facilitated by limited public access. Our results suggest that conservation and management of rare species should not rely solely on habitat information gained from studies in more pristine areas because such results may not demonstrate the range in variation in behavior that might allow persistence in novel environments, absent key threats.
Non‐adherence to ivabradine and placebo and outcomes in chronic heart failure: an analysis from SHIFT
Authors: Böhm Michael , Lloyd Suzanne M. , Ford Ian , Borer Jeffrey S. , Ewen Sebastian , Laufs Ulrich , Mahfoud Felix , Lopez‐Sendon Jose , Ponikowski Piotr , Tavazzi Luigi , Swedberg Karl , Komajda Michel
Published: March 2016

Aims

In heart failure, non‐adherence increases events; in turn, the effect of hospitalization on adherence is incompletely understood. We explored the relationship of non‐adherence to outcomes, hospitalizations with non‐adherence, and the influence of non‐adherence on treatment effects of heart rate lowering with ivabradine.

Methods and results

In the randomized, controlled Systolic Heart failure treatment with the If‐inhibitor ivabradine Trial (SHIFT), we studied the effect of non‐adherence (n = 1287) compared with adherence (n = 5204) on cardiovascular outcomes. After adjustment, non‐adherence was associated with the primary composite endpoint of cardiovascular death and heart failure hospitalization (hazard ratio 3.47, 95% confidence interval 2.91–4.13, P < 0.0001). No interaction with the treatment groups of placebo or ivabradine (P for interaction 0.54) occurred. Similar results for cardiovascular death and heart failure hospitalization, as well as for cardiovascular hospitalization, heart failure death, and total death were observed. The effect of ivabradine was maintained in patients being adherent or becoming non‐adherent during the trial (P for interaction = 0.54). Patients with a previous hospitalization were more likely to become non‐adherent thereafter.

Conclusions

Non‐adherence identifies a group at particularly high cardiovascular event risk independent of treatment allocation. Non‐adherent patients in the ivabradine group maintain a treatment benefit. Patients with previous hospitalizations are more likely to become non‐adherent and represent a group of particularly high‐risk patients in whom special attention to stimulate adherence may be valuable.

Trial registration

ISRCTN70429960.
Palladium‐Catalyzed Aminocarbonylation of Aryl Halides with 2,4,6‐Trichloro‐1,3,5‐triazine/Formamide Mixed Reagent
Authors: Iranpoor Nasser , Panahi Farhad , Roozbin Fatemeh , Erfan Soodabeh , Rahimi Sajjad
Published: March 2016

In this work, the mixture of formamide and 2,4,6‐trichloro‐1,3,5‐triazine (cyanuric chloride or TCT) is introduced as a new amidating agent in Pd‐catalyzed aminocarbonylation of aryl halides. In the presence of a catalytic amount of palladium and TCT/formamide reagent, a range of aryl halides (X = Cl, Br, I) were converted into amides efficiently in N,N‐dimethylformamide at 120 °C.