bluuebunny/crossref_metadata_2025_split huggingface dataset:
LINC
Complexes and Their Role in Human Disease
Authors: Calvi Alessandra , Burke Brian 
Published: August 2015

Abstract

In most metazoan cell types, the nucleus occupies a clearly defined region of the cytoplasm. For instance in epithelial cells, it is commonly positioned close to the basal membrane, whereas in skeletal muscle fibres, the majority of nuclei are uniformly distributed adjacent to the plasma membrane. A few muscle cell nuclei, however, cluster beneath the postsynaptic membrane. In certain cell types, the nucleus may be repositioned according to cell cycle phase or cell activity. Each of these situations requires that nuclei be physically coupled to the cytoskeleton. This is accomplished in large part by
LINC
(linker of the nucleoskeleton and cytoskeleton) complexes. These structures consist of inner nuclear membrane
SUN
(Sad1p‐UNC‐84)‐domain proteins that function as transluminal tethers for outer nuclear membrane
KASH
‐domain proteins. Together,
SUN–KASH
pairs function as links in a molecular chain that couples cytoskeletal elements, including motor proteins, to nuclear components. In addition to having obligate roles in nuclear positioning and chromatin organisation,
LINC
complexes may also function in mechanotransduction. The fact that a number of human diseases have been associated with
LINC
complex defects indicates that in many cell types these represent essential structures at the interface between the nucleus and cytoplasm.

Key Concepts

The nuclear envelope forms the interface between the nucleus and cytoplasm. Its most prominent features are the inner and outer nuclear membranes (INM and ONM) separated by a narrow (∼50 nm) gap, the perinuclear space (PNS).

SUN domain proteins of the INM function as transluminal tethers for KASH domain proteins in the ONM.

The nucleoplasmic domain of SUN proteins provides binding sites for both chromatin proteins and components of the nuclear lamina.

KASH domain proteins represent attachment sites at the nuclear envelope for a variety of cytoskeletal elements, including motor proteins.

SUN–KASH pairs, which span both nuclear membranes, are known as LINC (linker of the nucleoskeleton and cytoskeleton) complexes and mechanically couple nuclear structures to the cytoskeleton.

LINC complexes have essential roles in nuclear migration and positioning in multiple cell types.

During meiosis, LINC complexes have an essential role in telomere‐led chromosome movement, a process that facilitates homologous chromosome pairing and synapsis.

LINC complexes are thought to mediate the transmission of mechanical signals to the nucleus: mechanotransduction.
Alkylations of Arylboronic Acids including Difluoroethylation/Trifluoroethylation via Nickel‐Catalyzed Suzuki Cross‐Coupling Reaction
Authors: Zhang Xiaofei , Yang Chunhao 
Published: August 2015

AbstractAn efficient alkylation method of functionalized alkyl halides under mild nickel‐catalyzed C(sp3)C(sp2) Suzuki cross‐coupling conditions is described. The features of this approach are excellent functional group compatibility, low cost nickel catalyst, and the use of a mild base. This is also the first successful example of the nickel‐catalyzed direct 2,2‐difluoroethylation or 2,2,2‐trifluoroethylation of aryl‐/heteroarylboronic acids.magnified image
Stereocontrolled Synthesis of Difunctionalized Azetidinones and β2, 3‐Amino Acid Derivatives from Cyclodienes by Ring‐Opening and Cross‐Metathesis Reactions
Authors: Kardos Márton , Kiss Loránd , Fülöp Ferenc 
Published: August 2015

AbstractA stereocontrolled approach to highly functionalized 3,4‐disubstituted azetidin‐2‐ones and β2, 3‐amino acid derivatives from readily available cycloalkadienes was achieved. The syntheses involved 1,3‐dipolar cycloaddition of chlorosulfonyl isocyanate, followed by ring‐opening metathesis of the unsaturated bi‐ or tricyclic β‐lactams, and cross‐metathesis of the resulting divinyl‐substituted azetidinones. The substituted lactams were subsequently transformed by heteroring‐opening into the corresponding functionalized acyclic β2, 3‐amino acid derivatives.
Macrocyclic Weakly Coordinating Anions
Authors: Landskron Kai 
Published: August 2015

AbstractHerein, the concept of macrocyclic weakly coordinating anions (M‐WCAs) is introduced. Synthetic methodologies are described how to access M‐WCAs by thermodynamically controlled self‐assembly in high yields, in particular through condensation and alkyne metathesis reactions. The anticipated properties and applications of M‐WCAs in solid state and in solution are discussed, specifically for gas storage and separation, homogeneous and heterogeneous catalysis, and as liquid and solid electrolytes.
Engineering of Energy Levels for Fully Conjugated D‐A Block CopolymersviaTuning the Ratios of Donor P3HT and Acceptor PNDIT
Authors: Wang Shifan , Guo Yan , Yang Jie , Tao Youtian , Huang Wei 
Published: August 2015

AbstractFully conjugated donor‐acceptor (D‐A) block copolymers, P3HT‐b‐PNDIT, containing p‐type poly(3‐hexylthiophene) (P3HT) and n‐type poly(naphthalene bismide) (PNDIT) segments are synthesized in a one‐pot reaction via Stille coupling polycondensation. Various D‐A block copolymers with low polydispersities (1.42–1.56) are obtained through further separation via preparative GPC. The structural and molecular features of block copolymers are verified by1H NMR, FTIR spectra, UV‐Vis absorption, differential scanning calorimetry (DSC) and cyclic voltammetry (CV). It is found that optical and electrochemical properties of D‐A block copolymers are strongly dependent on the combination ratio of the donor P3HT and acceptor PNDIT segment. By reducing the acceptor block lengths, the highest occupied molecular orbital (HOMO) energy levels of D‐A block copolymers sequentially rise, leading to the sequential decrease of energy gaps. To the best of our knowledge, this is the first report on engineering the energy levels of fully conjugated D‐A block copolymers by tuning donor and acceptor chain lengths. More?over, compared to D/A polymer blends, the all‐conjugated D‐A block copolymer films show significant fine structures and much smoother film morphologies.
Tocopherols in the Prevention and Treatment of Atherosclerosis and Related Cardiovascular Disease
Authors: Mathur Pankaj , Ding Zufeng , Saldeen Tom , Mehta Jawahar L. 
Published: August 2015

ABSTRACTOxidants/antioxidants play an important role in cellular homeostasis. The human body has endogenous molecules that work as antioxidants, such as glutathione, superoxide dismutase, peroxidases, and catalase. Exogenous substances in the diet, such as β‐carotene, ascorbate, and vitamin E, are vital antioxidants. Of these, vitamin E is likely the most important antioxidant in the human diet, and many studies have been performed to elucidate its role in health and disease. Vitamin E is a family of several compounds, of which α‐tocopherol is the most widely known analog. α‐Tocopherol exhibits antioxidative property in vitro and inhibits oxidation of low‐density lipoprotein cholesterol. In addition, α‐tocopherol shows anti‐inflammatory activity and modulates expression of proteins involved in the uptake, transport, and degradation of atherogenic lipids. Though α‐tocopherol exhibits important antioxidant, anti‐inflammatory, and antiatherogenic features in vitro, α‐tocopherol supplements have failed to consistently reduce atherosclerosis‐related events in human trials. The conflicting results have led to reconsideration of the importance previously given to α‐tocopherol and led to interest in other members of vitamin E family, especially γ‐tocopherol, which exerts a much more potent antioxidant, anti‐inflammatory, and cardioprotective effect than α‐tocopherol. This reconsideration has been backed by solid laboratory and clinical research. We suggest that the absence of γ‐tocopherol in traditional preparations may be one reason for the lack of consistent salutary effects of vitamin E preparations in clinical trials. This review summarizes our current understanding of tocopherols as antioxidant molecules and emerging evidence of an important role of γ‐tocopherol in the pathophysiology of atherosclerosis‐related cardiovascular disease.
The expression of tubb2b undergoes a developmental transition in murine cortical neurons
Authors: Breuss Martin , Morandell Jasmin , Nimpf Simon , Gstrein Thomas , Lauwers Mattias , Hochstoeger Tobias , Braun Andreas , Chan Kelvin , Sánchez Guajardo Edmundo R. , Zhang Lijuan , Suplata Marek , Heinze Katrin G. , Elsayad Kareem , Keays David A. 
Published: August 2015

ABSTRACTThe development of the mammalian brain requires the generation, migration, and differentiation of neurons, cellular processes that are dependent on a dynamic microtubule cytoskeleton. Mutations in tubulin genes, which encode for the structural subunits of microtubules, cause detrimental neurological disorders known as the tubulinopathies. The disease spectra associated with different tubulin genes are overlapping but distinct, an observation believed to reflect functional specification of this multigene family. Perturbation of the β‐tubulin TUBB2B is known to cause polymicrogyria, pachygyria, microcephaly, and axon guidance defects. Here we provide a detailed analysis of the expression pattern of its murine homolog Tubb2b. The generation and characterization of BAC‐transgenic eGFP reporter mouse lines has revealed that it is highly expressed in progenitors and postmitotic neurons during cortical development. This contrasts with the 8‐week‐old cortex, in which Tubb2b expression is restricted to macroglia, and expression is almost completely absent in mature neurons. This developmental transition in neurons is mirrored in the adult hippocampus and the cerebellum but is not a universal feature of Tubb2b; its expression persists in a population of postmitotic neurons in the 8‐week‐old retina. We propose that the dynamic spatial and temporal expression of Tubb2b reflects specific functional requirements of the microtubule cytoskeleton. J. Comp. Neurol. 523:2161–2186, 2015. © 2015 Wiley Periodicals, Inc.
SymS: a symmetrical scheduler to improve multi‐threaded program performance on NUMA systems
Authors: Zhu Liang , Jin Hai , Liao Xiaofei 
Published: August 2015

SummaryThe nonuniform memory access (NUMA) architecture has been used extensively in data centers. Most of the previous works used single‐threaded multiprogrammed workloads to study the performance of NUMA systems, which mainly focus on two classes of problems: resource contention and data locality. However, when running multi‐threaded programs on NUMA systems, the critical thread of these programs significantly influences the system performance and brings new challenges that are different from those in a single‐threaded situation. In particular, an additional scheduling scheme is desired to avoid the performance degradation caused by the critical thread of multi‐threaded programs running on NUMA systems. This work presents a scheduler, Symmetrical Scheduler, which successfully solves the lagging problem by balancing the number of the costly remote shared data accesses for threads on NUMA systems. To the best of our knowledge, little work has been conducted to examine the performance impacted by the critical thread of multi‐threaded programs on NUMA systems. By running the PARSEC benchmark on such systems, our methodology can improve the program performance by a factor of 6% on average and achieve maximally 25.3% improvement compared with Linux kernel scheduling mechanism. Copyright © 2015 John Wiley & Sons, Ltd.
Mapping cell populations in flow cytometry data for cross‐sample comparison using the Friedman–Rafsky test statistic as a distance measure
Authors: Hsiao Chiaowen , Liu Mengya , Stanton Rick , McGee Monnie , Qian Yu , Scheuermann Richard H. 
Published: August 2015

AbstractFlow cytometry (FCM) is a fluorescence‐based single‐cell experimental technology that is routinely applied in biomedical research for identifying cellular biomarkers of normal physiological responses and abnormal disease states. While many computational methods have been developed that focus on identifying cell populations in individual FCM samples, very few have addressed how the identified cell populations can be matched across samples for comparative analysis. This article presents FlowMap‐FR, a novel method for cell population mapping across FCM samples. FlowMap‐FR is based on the Friedman–Rafsky nonparametric test statistic (FR statistic), which quantifies the equivalence of multivariate distributions. As applied to FCM data by FlowMap‐FR, the FR statistic objectively quantifies the similarity between cell populations based on the shapes, sizes, and positions of fluorescence data distributions in the multidimensional feature space. To test and evaluate the performance of FlowMap‐FR, we simulated the kinds of biological and technical sample variations that are commonly observed in FCM data. The results show that FlowMap‐FR is able to effectively identify equivalent cell populations between samples under scenarios of proportion differences and modest position shifts. As a statistical test, FlowMap‐FR can be used to determine whether the expression of a cellular marker is statistically different between two cell populations, suggesting candidates for new cellular phenotypes by providing an objective statistical measure. In addition, FlowMap‐FR can indicate situations in which inappropriate splitting or merging of cell populations has occurred during gating procedures. We compared the FR statistic with the symmetric version of Kullback–Leibler divergence measure used in a previous population matching method with both simulated and real data. The FR statistic outperforms the symmetric version of KL‐distance in distinguishing equivalent from nonequivalent cell populations. FlowMap‐FR was also employed as a distance metric to match cell populations delineated by manual gating across 30 FCM samples from a benchmark FlowCAP data set. An F‐measure of 0.88 was obtained, indicating high precision and recall of the FR‐based population matching results. FlowMap‐FR has been implemented as a standalone R/Bioconductor package so that it can be easily incorporated into current FCM data analytical workflows. © 2015 International Society for Advancement of Cytometry
Tracking changes in life‐history traits related to unnecessary virulence in a plant‐parasitic nematode
Authors: Castagnone‐Sereno Philippe , Mulet Karine , Iachia Cathy 
Published: August 2015

AbstractEvaluating trade‐offs in life‐history traits of plant pathogens is essential to understand the evolution and epidemiology of diseases. In particular, virulence costs when the corresponding host resistance gene is lacking play a major role in the adaptive biology of pathogens and contribute to the maintenance of their genetic diversity. Here, we investigated whether life‐history traits directly linked to the establishment of plant–nematode interactions, that is, ability to locate and move toward the roots of the host plant, and to invade roots and develop into mature females, are affected in Meloidogyne incognita lines virulent against the tomato Mi‐1.2 resistance gene. Virulent and avirulent near‐isogenic lines only differing in their capacity to reproduce or not on resistant tomatoes were compared in single inoculation or pairwise competition experiments. Data highlighted (1) a global lack of trade‐off in traits associated with unnecessary virulence with respect to the nematode ability to successfully infest plant roots and (2) variability in these traits when the genetic background of the nematode is considered irrespective of its (a)virulence status. These data suggest that the variation detected here is independent from the adaptation of M. incognita to host resistance, but rather reflects some genetic polymorphism in this asexual organism.
Levosimendan improves exercise performance in patients with advanced chronic heart failure
Authors: Mushtaq Saima , Andreini Daniele , Farina Stefania , Salvioni Elisabetta , Pontone Gianluca , Sciomer Susanna , Volpato Valentina , Agostoni Piergiuseppe 
Published: August 2015

AbstractAimsCardiopulmonary exercise test (CPET) provides parameters such as peak VO2 and ventilation/CO2 production (VE/VCO2) slope, which are strong prognostic predictors in patients with stable advanced chronic heart failure (ADHF). The study aim was to evaluate the effects of the inodilator levosimendan on CPET in patients with ADHF under stable clinical conditions.Methods and resultsWe enrolled patients with ADHF (peak VO2 < 12 mL/min/kg) in a double‐blind, placebo‐controlled protocol. Patients were randomly assigned to i.v. infusion of placebo (500 mL 5% glucose; n = 19) or levosimendan (in 500 mL 5% glucose; n = 23). Before and 24 h after the end of the infusion, patients underwent determination of New York Heart Association class, B‐type natriuretic peptide (BNP), haemoglobin, serum creatinine, and blood urea nitrogen levels, as well as CPET, standard spirometry, and alveolar capillary gas diffusion. BNP showed no change with placebo (1042 ± 811 to 1043 ± 867 pg/mL), but it was decreased with levosimendan (1163 ± 897 to 509 ± 543 pg/mL, P < 0.001). No changes were observed for haemoglobin, creatinine, and blood urea nitrogen in either group. With levosimendan, a minor improvement was observed in spirometry measurements, but not in alveolar capillary gas diffusion. Peak VO2 showed a small, non‐significant increase with placebo (9.5 ± 1.7 to 10.0 ± 2.1 mL/kg/min, P = 0.12), and a greater increase with levosimendan (9.8 ± 1.7 to 11.0 ± 1.9 mL/kg/min, P < 0.005). The VE/VCO2 slope showed no change (44.0 ± 11 vs. 43.4 ± 10.3, P = 0.44), and a decrease (41.9 ± 10 vs. 36.6 ± 6.4, P < 0.001) in the placebo and in the levosimendan group, respectively.ConclusionLevosimendan treatment significantly improves peak VO2 and reduces VE/VCO2 slope and BNP in patients with ADHF.
Extended Threefold‐Symmetric Second‐Harmonic‐Generation Chromophores Based on 1,3,5‐Trisubstituted Benzene Complexes
Authors: Ziemann Elisabeth A. , Mietner J. Benedikt , Deffner Michael , Van Steerteghem Nick , Clays Koen , Herrmann Carmen , Heck Jürgen 
Published: August 2015

AbstractThe elongation of the π system of a donor–π–acceptor (D–π–A) chromophore has often proven to be beneficial for its nonlinear optical (NLO) activity. Against this background, different alkynyl protecting groups such as organosilyl and dicobalt hexacarbonyl functions were investigated with respect to their ability to enable the coordination of an electron‐withdrawing CpRu+ fragment (Cp = cyclopentadienyl) to a threefold ethynyl‐substituted benzene ring, acting as a potential 2D NLOphore, without undesired side reactions. In addition, the influence of the perpendicularly coordinated CpRu+ unit on the NLO properties was examined. The obtained organometallic triisopropylsilyl‐substituted benzene ruthenium complex and the multinuclear dicobalt hexacarbonyl protected ferrocene complex were fully characterized. Owing to the problems during the purification of the trimethylsilyl‐protected benzene ruthenium complex and the subsequent deprotection to the free alkyne complex, it was not possible to fully characterize those complexes. The introduction of the CpRu+ fragment was sensitive to the steric demands of the benzene substituents but beneficial for the generation of NLO activity. The first hyperpolarizabilities of the triisopropyl and dicobalt hexacarbonyl complexes were investigated by hyper‐Rayleigh scattering. The molecular structures were characterized by X‐ray crystallography and infrared (IR) spectroscopy. The structures and IR spectra were compared with Kohn–Sham density functional theory calculations.
Base‐Induced Cyclization of Propargyl ­Alkenylsulfones: A High‐Yielding Synthesis of 4,5‐Disubstituted 2H‐Thiopyran 1,1‐Dioxides
Authors: Hatial Ishita , Das Joyee , Ghosh Ananta K. , Basak Amit 
Published: August 2015

AbstractA convenient synthesis of 4,5‐disubstituted 2H‐thiopyran 1,1‐dioxides is reported through a base induced process starting from eneyne sulfones. Except for strongly electron‐withdrawing groups, the reaction tolerated a wide variety of substituents in the two aryl rings. This finding represents a major departure from the behaviour of the corresponding ethers. The reaction most probably proceeds through a 6π‐electrocyclization from an in‐situ‐generated 1,3,5‐trienyl sulfinate.
A Rapid Entry to Diverse γ‐Ylidenetetronate Derivatives through Regioselective ­Bromination of Tetronic Acid Derived γ‐Lactones and Metal‐Catalyzed Postfunctionalization
Authors: Chopin Nicolas , Yanai Hikaru , Iikawa Shinya , Pilet Guillaume , Bouillon Jean‐Philippe , Médebielle Maurice 
Published: August 2015

AbstractThe synthesis of a series of diverse methyl and benzyl γ‐ylidenetetronate derivatives was accomplished through the condensation of methyl and benzyl tetronates with (hetero)aryl aldehydes in a new two‐ or three‐step aldolisation/dehydration sequence. The bromination of methyl and benzyl γ‐ylidenetetronates occurred under mild conditions to provide the corresponding C‐3‐brominated γ‐unsaturated lactones. Di‐ and tribrominated γ‐lactones were prepared under slightly different conditions. Some brominated materials were employed in representative Stille, Suzuki–Miyaura, and Sonogashira cross‐coupling reactions to yield functionalized methyl and benzyl γ‐ylidenetetronate derivatives. Compounds that resulted from the Sonogashira cross‐coupling reactions were desilylated and converted into 1,2,3‐triazole derivatives through a copper(I)‐catalyzed 1,3‐dipolar cycloaddition reaction with benzyl azide.
Molecular screening of microbial communities for candidate indicators of multiple metal impacts in marine sediments from northern Australia
Authors: Cornall Alyssa , Rose Alea , Streten Claire , McGuinness Keith , Parry David , Gibb Karen 
Published: August 2015

Abstract

Coastal sediments accumulate metals from anthropogenic sources and as a consequence industry is required to monitor sediment health. The total concentration of a metal does not necessarily reflect its potential toxicity or biological impact, so biological assessment tools are useful for monitoring. Rapid biological assessment tools sensitive enough to detect relatively small increases in metal concentrations would provide early warning of future ecosystem impact. The authors investigated in situ populations of Archaea and Bacteria as potential tools for rapid biological assessment in sediment at 4 northern Australian coastal locations over 2 yr, in both wet and dry seasons. The 1 M HCl-extractable concentrations of metals in sediment were measured, and Archaeal and Bacterial community profiles were obtained by next-generation sequencing of sediment deoxyribonucleic acid (DNA). Species response curves were used to identify several taxonomic groups with potential as biological indicators of metal impact. Spatial variation, sediment grain size, water depth, and dissolved oxygen also correlated with microbial population shifts. Seasonal variation was less important than geographic location. Metal-challenge culture trials supported the identification of metal-resistant and -sensitive taxa. In situ Archaea and Bacteria are potentially sensitive indicators for changes in bioavailable concentrations of metals; however, the complexity of the system suggests it is important to identify metal-specific functional genes that may be informed by these sequencing surveys, and thus provide a useful addition to identity-based assays. Environ Toxicol Chem 2016;35:468–484. © 2015 SETAC