bluuebunny/crossref_metadata_2025 huggingface dataset:
Reproductive traits of the pompano, Trachinotus ovatus (Linnaeus, 1758), in the north-western Mediterranean
Authors: Villegas-Hernández Harold , Muñoz Marta , Lloret Josep
Published: August 2015

This study describes for the first time the reproductive traits of the warm-water pompano, Trachinotus ovatus. Specimens were sampled from landings by artisanal fishing vessels in the NW Mediterranean. Monthly collections, from July 2010 through to September 2012, yielded 226 individuals (118 females and 108 males). The size at 50% maturity (L50) was estimated at 30.9 and 29.1 cm TL for females and males, respectively. Specific reproductive traits, such as oocyte size-frequency distributions, presence of recent post-ovulatory follicles along with oocytes in the final phases of gonadal development, and massive atresia in post-spawning individuals, indicated that pompanos are multiple batch spawners with asynchronous oocyte development and indeterminate fecundity. Monthly variations in the gonadosomatic index and in the phases of gonadal development indicated July and August as the spawning season. There were also noticeable inter-annual variations in spawning phenology, mean diameters of the oocytes, relative batch fecundity and eggs quality, all of which corresponded to changes in sea surface temperatures. This study enhances our understanding of the need for research into the reproduction of warm-water species, which are currently expanding into the increasingly warmer waters of the world's more northerly seas and oceans.
Can metabotyping help deliver the promise of personalised nutrition?
Authors: O'Donovan Clare B. , Walsh Marianne C. , Gibney Michael J. , Gibney Eileen R. , Brennan Lorraine
Published: August 2015

Over a decade since the completion of the human genome sequence, the promise of personalised nutrition available to all has yet to become a reality. While the definition was originally very gene-focused, in recent years, a model of personalised nutrition has emerged with the incorporation of dietary, phenotypic and genotypic information at various levels. Developing on from the idea of personalised nutrition, the concept of targeted nutrition has evolved which refers to the delivery of tailored dietary advice at a group level rather than at an individual level. Central to this concept is metabotyping or metabolic phenotyping, which is the ability to group similar individuals together based on their metabolic or phenotypic profiles. Applications of the metabotyping concept extend from the nutrition to the medical literature. While there are many examples of the metabotype approach, there is a dearth in the literature with regard to the development of tailored interventions for groups of individuals. This review will first explore the effectiveness of personalised nutrition in motivating behaviour change and secondly, examine potential novel ways for the delivery of personalised advice at a population level through a metabotyping approach. Based on recent findings from our work, we will demonstrate a novel strategy for the delivery of tailored dietary advice at a group level using this concept. In general, there is a strong emerging evidence to support the effectiveness of personalised nutrition; future work should ascertain if targeted nutrition can motivate behaviour change in a similar manner.
ISAAK RUBIN: HISTORIAN OF ECONOMIC THOUGHT DURING THE STALINIZATION OF SOCIAL SCIENCES IN SOVIET RUSSIA
Authors: Boldyrev Ivan , Kragh Martin
Published: August 2015

Research within the history of economic thought has focused only little on the development of economics under dictatorship. This paper attempts to show how a country with a relatively large and internationally established community of social scientists in the 1920s, the Soviet Union, was subjected to repression. We tell this story through the case of Isaak Il’ich Rubin, a prominent Russian economist and historian of economic thought, who in the late 1920s was denounced by rival scholars and repressed by the political system. By focusing not only on his life and work, but also on that of his opponents and institutional clashes, we show how the decline of a social science tradition in Russia and the USSR as well as the Stalinization of Soviet social sciences emerged as a process over time. We analyze the complex interplay of ideas, scholars, and their institutional context, and conclude that subsequent repression was arbitrary, suggesting that no clear survival or career strategy existed in the Stalinist system, due to a situation of fundamental uncertainty.
Who Plays the Tune in “Body and Soul”? A Performance History Using Recorded Sources
Authors: BOWEN JOSÉ ANTONIO
Published: August 2015

This essay explores the multiple histories, traditions, and authorities present in more than 200 recorded performances of “Body and Soul.” The early recordings (dozens of them from 1930 alone) demonstrate both enormous variety and distinct British and American performance patterns, but few of these innovations survive beyond 1940. Coleman Hawkins's version from 1939, and not the original sheet music or early performance history, set a standard key (D-flat—even for singers!) and a slower standard tempo (quarter = 90, although later it became even slower). Charlie Parker and others in the 1940s, however, were influenced by the Chu Berry and Roy Eldridge recording of 1938, which introduced a “jump” chorus widely reproduced for two decades. Billie Holiday determined which set of lyrics would be sung, but not the form in which they would occur. John Coltrane and McCoy Tyner's new modal approach in 1960 created both direct imitators and also a new tradition of trying to neutralize the harmonic complexity of the tune, which Hawkins had so carefully exploited. This study asks whether a more African and less European model of jazz tunes might reveal a less fixed and more complex notion of a musical work that includes orally preserved and recorded innovations and performance traditions. This research also explores how the record itself, as a physical object, has become an authority.
Refining the pathway of carbide insertion into the nitrogenase M-cluster
Authors: Wiig Jared A. , Hu Yilin , Ribbe Markus W.
Published: August 2015

Carbide insertion plays a pivotal role in the biosynthesis of M-cluster, the cofactor of nitrogenase. Previously, we proposed a carbide insertion pathway involving methyltransfer from SAM to a FeS precursor and hydrogen abstraction from this methyl group that initiates the radical-based precursor maturation. Here we demonstrate that the methyl group is transferred to a precursor-associated sulfur before hydrogen abstraction, thereby refining the initial steps of the carbide insertion pathway.
Splenic red pulp macrophages are intrinsically superparamagnetic and contaminate magnetic cell isolates
Authors: Franken Lars , Klein Marika , Spasova Marina , Elsukova Anna , Wiedwald Ulf , Welz Meike , Knolle Percy , Farle Michael , Limmer Andreas , Kurts Christian
Published: August 2015

A main function of splenic red pulp macrophages is the degradation of damaged or aged erythrocytes. Here we show that these macrophages accumulate ferrimagnetic iron oxides that render them intrinsically superparamagnetic. Consequently, these cells routinely contaminate splenic cell isolates obtained with the use of MCS, a technique that has been widely used in immunological research for decades. These contaminations can profoundly alter experimental results. In mice deficient for the transcription factor SpiC, which lack red pulp macrophages, liver Kupffer cells take over the task of erythrocyte degradation and become superparamagnetic. We describe a simple additional magnetic separation step that avoids this problem and substantially improves purity of magnetic cell isolates from the spleen.
Functional genomics indicate that schizophrenia may be an adult vascular-ischemic disorder
Authors: Moises H W , Wollschläger D , Binder H
Published: August 2015

In search for the elusive schizophrenia pathway, candidate genes for the disorder from a discovery sample were localized within the energy-delivering and ischemia protection pathway. To test the adult vascular-ischemic (AVIH) and the competing neurodevelopmental hypothesis (NDH), functional genomic analyses of practically all available schizophrenia-associated genes from candidate gene, genome-wide association and postmortem expression studies were performed. Our results indicate a significant overrepresentation of genes involved in vascular function (P<0.001), vasoregulation (that is, perivascular (P<0.001) and shear stress (P<0.01), cerebral ischemia (P<0.001), neurodevelopment (P<0.001) and postischemic repair (P<0.001) among schizophrenia-associated genes from genetic association studies. These findings support both the NDH and the AVIH. The genes from postmortem studies showed an upregulation of vascular-ischemic genes (P=0.020) combined with downregulated synaptic (P=0.005) genes, and ND/repair (P=0.003) genes. Evidence for the AVIH and the NDH is critically discussed. We conclude that schizophrenia is probably a mild adult vascular-ischemic and postischemic repair disorder. Adult postischemic repair involves ND genes for adult neurogenesis, synaptic plasticity, glutamate and increased long-term potentiation of excitatory neurotransmission (i-LTP). Schizophrenia might be caused by the cerebral analog of microvascular angina.
Fundamentals, achievements and challenges in the electrochemical sensing of pathogens
Authors: Monzó Javier , Insua Ignacio , Fernandez-Trillo Francisco , Rodriguez Paramaconi
Published: August 2015

Electrochemical sensors are powerful tools widely used in industrial, environmental and medical applications.
Determination of melamine and malachite green by surface-enhanced Raman scattering spectroscopy using starch-coated silver nanoparticles as substrates
Authors: Zhao Ying , Tian Yuan , Ma Pinyi , Yu Aimin , Zhang Hanqi , Chen Yanhua
Published: August 2015

Schematic illustration of the starch-coated AgNP SERS measurement for determining analytes.
An amperometric microbial biosensor for the determination of vitamin B12
Authors: Ovalle M. , Arroyo E. , Stoytcheva M. , Zlatev R. , Enriquez L. , Olivas A.
Published: August 2015

In this study we describe a sensitive amperometric microbial biosensor that is fast, economic, reliable, and can compete with the existing proposed methods for vitamin B12determination.
A low-cost microcontrolled photometer with one color recognition sensor for selective detection of Pb2+ using gold nanoparticles
Authors: de L. M. de Morais Camilo , Carvalho Julyana C. , Sant'Anna Celso , Eugênio Mateus , Gasparotto Luiz H. S. , Lima Kássio M. G.
Published: August 2015

The present work describes a microcontrolled photometer based on light-emitting-diodes (LEDs) for detection of Pb2+ using gold nanoparticles (AuNPs).
Copper catalyzed sequential arylation−oxidative dimerization of o-haloanilides: synthesis of dimeric HPI alkaloids
Authors: Shen Xianfu , Zhou Yongyun , Xi Yongkai , Zhao Jingfeng , Zhang Hongbin
Published: August 2015

A copper catalyzed sequential arylation−oxidative dimerization reaction was developed as the key step for the synthesis of hexahydropyrroloindole alkaloids.
Optofluidic laser array based on stable high-Q Fabry–Pérot microcavities
Authors: Wang Wenjie , Zhou Chunhua , Zhang Tingting , Chen Jingdong , Liu Shaoding , Fan Xudong
Published: August 2015

High-Q FP optofluidic laser array.
Conducting polymer nanofibers with controlled diameters synthesized in hexagonal mesophases
Authors: Ghosh Srabanti , Ramos Laurence , Remita Samy , Dazzi Alexandre , Deniset-Besseau Ariane , Beaunier Patricia , Goubard Fabrice , Aubert Pierre-Henri , Remita Hynd
Published: August 2015

Conducting poly(diphenylbutadiyne) (PDPB) nanofibers with controlled diameters (5 to 25 nm) and relatively high conductivity were synthesized in soft templates using UV and gamma irradiation.
d-Isonucleotide (isoNA) incorporation around cleavage site of passenger strand promotes the vibration of Ago2-PAZ domain and enhances in vitro potency of siRNA
Authors: Huang Ye , Tian Miao , Zhang Yichao , Sheng Gang , Chen Zhuo , Ma Yuan , Chen Yue , Peng Yihong , Zhao Yi-Lei , Wang Yanli , Zhang Lihe , Yang Zhenjun
Published: August 2015

Isonucleotide modification around the cleavage site of the passenger strand affects the in vitro potency of modified siRNAs by altering the motion pattern of the Ago2-PAZ domain.
Rod–coil type miktoarm star copolymers consisting of polyfluorene and polylactide: precise synthesis and structure–morphology relationship
Authors: Saito Kengo , Isono Takuya , Sun Han-Sheng , Kakuchi Toyoji , Chen Wen-Chang , Satoh Toshifumi
Published: August 2015

Rod–coil type miktoarm star copolymers consisting of PF and PLA have been precisely synthesized for investigating the effect of macromolecular architecture on self-assembled nanostructures.
Flexible carbon nanofiber sponges for highly efficient and recyclable oil absorption
Authors: Ge Xiang , Yang Wei , Wang Jitong , Long Donghui , Ling Licheng , Qiao Wenming
Published: August 2015

Carbon nanofiber sponges composed of three-dimensional networks have been prepared though chemical vapor deposition. Such sponges exhibit controllable bulk density, admirable mechanical flexibility and high oil absorption capacity.
Tailoring the surface of liquid crystal droplets with chitosan/surfactant complexes for the selective detection of bile acids in biological fluids
Authors: Bera Tanmay , Deng Jinan , Fang Jiyu
Published: August 2015

The surface of 5CB droplets dispersed in aqueous solution is tailored by the adsorption of CHI/SC14S complexes at the 5CB/aqueous interface. The CHI/SC14S complex-coated 5CB droplets can be used as an optical probe to detect CA in biological fluids without dilution.
Electrocatalytic cycle of P450 cytochromes: the protective and stimulating roles of antioxidants
Authors: Shumyantseva V. V. , Makhova A. A. , Bulko T. V. , Kuzikov A. V. , Shich E. V. , Kukes V. , Archakov A. I.
Published: August 2015

This study reports the investigation of the catalytic activity of isolated cytochromes from the cytochrome P450 superfamily. Electrochemically driven CYP reactions may have practical relevance, providing a useful tool for drug assay studies.
A urinary metabolomics study of the metabolic dysfunction and the regulation effect of citalopram in rats exposed to chronic unpredictable mild stress
Authors: Yu Xinyu , Luo Jia , Chen Lijun , Zhang Chengxiang , Zhang Rutan , Hu Qi , Qiao Shanlei , Li Lei
Published: August 2015

This is the first attempt to combine the exploration of biomarkers of depression and evaluating the effect of citalopram by a metabolomics method, and then use the method to access the depression status according to the changed metabolome.
Recent advances in biological applications of cage metal complexes
Authors: Voloshin Yan Z. , Novikov Valentin V. , Nelyubina Yulia V.
Published: August 2015

This review highlights advances in biochemical and medical applications of cage metal complexes (clathrochelates) and related polyhedral compounds.
Correlation between surface chemistry, gasochromism and field emission properties of tungsten oxide nanowire thin films when exposed to atomic oxygen
Authors: Zhao C. X. , Deng S. Z. , Xu N. S. , Chen Jun
Published: August 2015

Effects of atomic oxygen exposure on gasochromism, chemical state and field emission properties of W20O58 nanowires have been investigated. We attempt to unvelling the origin for better understanding of the observed field emission characteristics.
Ultrasensitive electrochemiluminescence aptasensor based on a graphene/polyaniline composite film modified electrode and CdS quantum dot coated platinum nanostructured networks as labels
Authors: Kong Qingkun , Li Meng , Ma Chao , Yang Hongmei , Ge Shenguang , Yan Mei , Yu Jinghua
Published: August 2015

A simple electrochemiluminescence (ECL) aptasensor for adenosine triphosphate (ATP) based on graphene/polyaniline (GR/PANI) composite films modified glassy carbon electrode (GCE) was successfully fabricated.
Single-micelle-templated synthesis of hollow silica nanospheres with tunable pore structures
Authors: Li Yingyu , Kruk Michal
Published: August 2015

Single-micelle-templated hollow silica nanospheres with inner diameter tunable from 16 to 44 nm were synthesized using Pluronic F108 surfactant and suitable micelle swelling agent through control of initial synthesis temperature.
A novel “turn-on” fluorogenic probe for sensing hypochlorous acid based on BODIPY
Authors: Wang Enze , Qiao Han , Zhou Yanmei , Pang Lanfang , Yu Fang , Zhang Junli , Ma Tongsen
Published: August 2015

A highly selective and sensitive fluorescent probe (Bodipy-Hy) for the detection of hypochlorous acid was designed and easily synthesized by the condensation reaction (CN) of BODIPY aldehyde (BODIPY-AL) and hydrazine hydrate.
A new concept for production of (3S,4R)-6-[(benzyloxycarbonyl)amino]-5,6-dideoxyhex-2-ulose, a precursor of d-fagomine
Authors: Sudar Martina , Findrik Zvjezdana , Vasić-Rački Đurđa , Soler Anna , Clapés Pere
Published: August 2015

A novel cascade reaction combining three enzymes in one pot for the production of aldol adduct (3S,4R)-6-[(benzyloxycarbonyl)amino]-5,6-dideoxyhex-2-ulose was studied and 79% yield on aldol adduct was achieved in the batch reactor.
Control of cerium oxidation state through metal complex secondary structures
Authors: Levin Jessica R. , Dorfner Walter L. , Carroll Patrick J. , Schelter Eric J.
Published: August 2015

A series of alkali metal cerium diphenylhydrazido complexes, Mx(py)y[Ce(PhNNPh)4], M = Li, Na, and K, x = 4 (Li and Na) or 5 (K), and y = 4 (Li), 8 (Na), or 7 (K), were synthesized to probe how a secondary coordination sphere would modulate electronic structures at a cerium cation.
Spatiotemporal activation of molecules within cells using silica nanoparticles responsive to blue-green light
Authors: Amamoto Takaki , Hirata Tomoya , Takahashi Hironori , Kamiya Mako , Urano Yasuteru , Santa Tomofumi , Kato Masaru
Published: August 2015

Vehicle-nanoparticles that release cargo molecule at the cytoplasm of live cells by blue-green light has been developed.
The neural circadian system of mammals
Authors: Piggins Hugh D. , Guilding Clare
Published: August 2015

Humans and other mammals exhibit a remarkable array of cyclical changes in physiology and behaviour. These are often synchronized to the changing environmental light–dark cycle and persist in constant conditions. Such circadian rhythms are controlled by an endogenous clock, located in the suprachiasmatic nuclei of the hypothalamus. This structure and its cells have unique properties, and some of these are reviewed to highlight how this central clock controls and sculpts our daily activities.
Molecular parasitology in the 21st Century
Authors: Docampo Roberto
Published: August 2015

Protist parasites cause important human and animal diseases, and because of their early divergence from other eukaryotes they possess structural and biochemical characteristics not found in other cells. The completion of the genome projects of most human protist parasites and the development of novel molecular tools for their study guarantee a rapid progress in understanding how they invade, modify and survive within their hosts. The ultimate goal of these studies will be the identification of targets for the design of drugs, diagnostics and vaccines. In addition, the accessibility of some of these parasites to multiple genetic manipulations has converted them into model systems in cell and molecular biology studies that could lead to the understanding of basic biological processes, as well as their evolution and pathogenesis. In the present chapter we discuss the biochemical and molecular peculiarities of these parasites and the molecular tools available for their study.
African trypanosomes: the genome and adaptations for immune evasion
Authors: Rudenko Gloria
Published: August 2015

The African trypanosome Trypanosoma brucei is a flagellated unicellular parasite transmitted by tsetse flies that causes African sleeping sickness in sub-Saharan Africa. Trypanosomes are highly adapted for life in the hostile environment of the mammalian bloodstream, and have various adaptations to their cell biology that facilitate immune evasion. These include a specialized morphology, with most nutrient uptake occurring in the privileged location of the flagellar pocket. In addition, trypanosomes show extremely high rates of recycling of a protective VSG (variant surface glycoprotein) coat, whereby host antibodies are stripped off of the VSG before it is re-used. VSG recycling therefore functions as a mechanism for cleaning the VSG coat, allowing trypanosomes to survive in low titres of anti-VSG antibodies. Lastly, T. brucei has developed an extremely sophisticated strategy of antigenic variation of its VSG coat allowing it to evade host antibodies. A single trypanosome has more than 1500 VSG genes, most of which are located in extensive silent arrays. Strikingly, most of these silent VSGs are pseudogenes, and we are still in the process of trying to understand how non-intact VSGs are recombined to produce genes encoding functional coats. Only one VSG is expressed at a time from one of approximately 15 telomeric VSG ES (expression site) transcription units. It is becoming increasingly clear that chromatin remodelling must play a critical role in ES control. Hopefully, a better understanding of these unique trypanosome adaptations will eventually allow us to disrupt their ability to multiply in the mammalian bloodstream.
Malaria drug resistance: new observations and developments
Authors: Sá Juliana M. , Chong Jason L. , Wellems Thomas E.
Published: August 2015

Drug-resistant micro-organisms became widespread in the 20th Century, often with devastating consequences, in response to widespread use of natural and synthetic drugs against infectious diseases. Antimalarial resistance provides one of the earliest examples, following the introduction of new medicines that filled important needs for prophylaxis and treatment around the globe. In the present chapter, we offer a brief synopsis of major antimalarial developments from two natural remedies, the qinghaosu and cinchona bark infusions, and of synthetic drugs inspired by the active components of these remedies. We review some contributions that early efficacy studies of antimalarial treatment brought to clinical pharmacology, including convincing documentation of atebrine-resistant malaria in the 1940s, prior to the launching of what soon became first-choice antimalarials, chloroquine and amodiaquine. Finally, we discuss some new observations on the molecular genetics of drug resistance, including delayed parasite clearances that have been increasingly observed in response to artemisinin derivatives in regions of South-East Asia.
A new detector for fully automatic peptide synthesis
Authors: FOX JOHN E.
Published: August 2015

Summary

A new method of monitoring the rate of reactions in solidphase peptide synthesis is described. A conductivity detector in the reaction cell (patent applied for) enables the deprotection, washing and subsequent coupling stages to be examined in detail. The half-lives of the reactions can be calculated and hence the optimum reaction times can be predicted. Difficult sequences are sensed and appropriate action taken completely automatically.
Perfused heart studies to investigate lipid metabolism
Authors: Evans R. D. , Bennett M.J. , Hauton D.
Published: August 2015

The isolated perfused heart preparation is an invaluable model for investigating metabolism in a variety of physiological and pathological states. It avoids confounding systemic factors (e.g. endocrine, metabolic and work load changes) and permits simultaneous measurement of mechanical function. The ability to measure arteriovenous concentration differences across the myocardium and the coronary flow rate, together with the use of radiolabelled substrates, permits assessment of substrate assimilation and disposition of most potential energetic substrates. In the case of lipids, metabolism of non-esterified fatty acids has been extensively investigated in the perfused rat heart, but fatty acids may also be derived from circulating triacylglycerols (TAG) in lipoproteins [chylomicrons, very-low-density-lipoprotein (VLDL)]. TAG requires initial hydrolysis by the endothelial enzyme lipoprotein lipase and hence an intact heart preparation is vital to maintain tissue structural integrity. Chylomicron-TAG utilization and fate (oxidation, tissue-lipid deposition) in isolated working hearts has been studied using chylomicrons obtained from thoracic-duct catheters. However, lack of availability of sufficient quantities of VLDL has hindered examination of their cardiac utilization; the recent development of a technique to produce large quantities of radiolabelled rat VLDL has facilitated these studies and established that VLDL-TAG is an important metabolic substrate for working heart. Results relating to myocardial utilization of VLDL-TAG under varying physiological (lactation) and pathological (endotoxinaemia) conditions will be presented. The putative role of VLDL as a regulator of cardiac lipid metabolism will also be discussed.
NMR spectroscopy and imaging of the neonatal brain
Authors: Cooper C. E. , Wyatt J. S.
Published: August 2015

Magnetic resonance spectroscopy and imaging provide unique information about the brain to the biochemist and the clinician. In particular, the ability to image metabolites other than water and to get detailed information about dynamic cellular processes (such as blood flow, blood oxygenation and cell swelling) is leading to many new insights into brain function and dysfunction. This review describes the use of old and new NMR techniques which demonstrate that mitochondrial dysfunction plays an important role in the cell death that occurs following an hypoxic-ischaemic insult to the neonatal brain.
Hepatocyte couplets
Authors: Coleman R. , Roma M. G.
Published: August 2015

Hepatocyte couplets, by retaining functional and morphological polarity similar to that of hepatocytes in situ, are a valuable in vitro model to study mechanisms of bile secretion, cholestasis and hepatocellular injury. They have been useful in studies of the hormonal control of bile formation and are suitable for morphological studies. The availability of periportal- and perivenous-enriched couplet populations now allows a zonal perspective. Their contribution to our understanding of regulatory aspects of hepatobiliary dysfunction due to toxicological or cholestatic insult, as well as its reversion by using hepatoprotective agents, is still at an early stage. The next few years should see further exiting contributions to our understanding of hepatobiliary function and dysfunction.
Lipid metabolism in peroxisomes: enzymology, functions and dysfunctions of the fatty acid α- and β-oxidation systems in humans
Authors: Wanders R. J. A. , van Grunsven E. G. , Jansen G. A.
Published: August 2015

Peroxisomes are subcellular organelles present in virtually all eukaryotic cells catalysing a number of indispensable functions in cellular metabolism. The importance of peroxisomes in man is stressed by the existence of an expanding group of genetic diseases in which there is an impairment in one or more peroxisomal functions. One of the major functions of peroxisomes concerns their role in lipid metabolism, which includes: (i) fatty acid β-oxidation; (ii) ether phospholipid synthesis; (iii) fatty acid α-oxidation; and (iv) isoprenoid biosynthesis. In this paper, we review the current state of knowledge concerning the peroxisomal fatty acid α- and β-oxidation systems with particular emphasis on the enzymes involved and the various disorders of fatty acid oxidation in peroxisomes. We also pay attention to the fact that some of the metabolites that accumulate as the result of a defect in peroxisomal α- and/or β-oxidation are activators of members of the family of nuclear receptors, including peroxisome-proliferator-act-ivated receptor α.
Mitochondria and cell death
Authors: Halestrap A. P. , Doran E. , Gillespie J. P. , O'Toole A.
Published: August 2015

Mitochondria play a central role in both apoptosis and necrosis through the opening of the mitochondrial permeability transition pore (MPTP). This is thought to be formed through a Ca2+-triggered conformational change of the adenine nucleotide translocase (ANT) bound to matrix cyclophilin-D and we have now demonstrated this directly by reconstitution of the pure components. Opening of the MPTP causes swelling and uncoupling of mitochondria which, unrestrained, leads to necrosis. In ischaemia/reperfusion injury of the heart we have shown MPTP opening directly. Recovery of hearts correlates with subsequent closure, and agents that prevent opening or enhance closure protect from injury. Transient MPTP opening may also be involved in apoptosis by initially causing swelling and rupture of the outer membrane to release cytochrome c (cyt c), which then activates the caspase cascade and sets apoptosis in motion. Subsequent MPTP closure allows ATP levels to be maintained, ensuring that cell death remains apoptotic rather than necrotic. Apoptosis in the hippocampus that occurs after a hypoglycaemic or ischaemic insult is triggered by this means. Other apoptotic stimuli such as cytokines or removal of growth factors also involve mitochondrial cyt c release, but here there is controversy over whether the MPTP is involved. In many cases cyt c release is seen without any mitochondrial depolarization, suggesting that the MPTP does not open. Recent data of our own and others have revealed a specific outer-membrane cyt c-release pathway involving porin that does not release other intermembrane proteins such as adenylate kinase. This is opened by pro-apototic members of the Bcl-2 family such as BAX and prevented by anti-apoptotic members such as Bcl-xL. Our own data suggest that this pathway may interact directly with the ANT in the inner membrane at contact sites.
Role of hormone-controlled T-cell cytokines in the maintenance of pregnancy
Authors: Piccinni M.-P. , Maggi E. , Romagnani S.
Published: August 2015

Human CD4 T helper lymphocytes can be subdivided into at least three distinct functional subsets on the basis of their cytokine secretion profiles. One type of CD4+ lymphocyte, T helper 1 (Th1), produces interferon (IFN)-γ and tumour necrosis factor β, a second type (Th2) produces interleukin (IL)-4 and IL-5 and a third type (Th0) produces both Th1 and Th2 cytokines. The apparent paradox that embryos are not rejected by the maternal immune system despite the presence of paternal MHC histocompatibility antigens has been explained in mice by a Th2 switch at the level of the materno-fetal interface. We showed that some hormones enhanced during pregnancy can affect the development of Th1 and Th2 responses. Indeed, we found that progesterone promotes the production of IL-4 and IL-5, whereas relaxin promotes the production of IFN-γ by T-cells. In addition, we showed that leukaemia inhibitory factor (LIF), which is essential for embryo implantation, associates with Th2 cells and is upregulated by IL-4 and progesterone. We also showed that LIF is down-regulated by Th1 inducers [IL-12, IFN-γ and IFN-α]. Further-more, we found a decreased production of LIF, IL-4 and IL-10 by decidual T-cells in women with unexplained recurrent abortions in comparison with women with normal gestation at the moment of voluntary abortion. The decreased production of LIF, IL-4 and IL-10 was not found in peripheral-blood T-cells. These results suggest that the local production of LIF and/or Th2 cytokines may contribute to the maintenance of pregnancy.
Immunosenescence: potential causes and strategies for reversal
Authors: Aspinall R. , Andrew D.
Published: August 2015

Age-related deterioration in immune function has been recognized in many species. In humans the clinical manifestation of such immune dysfunction is age-related increases in the susceptibility to certain infections and in the incidence of some autoimmune disease and certain cancers. Laboratory investigations reveal age-related changes in the peripheral T cell pool, in the predominant phenotype, cytokine production profiles, signalling function and in replicative ability following stimulus with antigen, mitogens or anti-CD3 antibody. These changes in the properties of peripheral T cells are thought to be causally linked to an age-associated involution in the thymus. Our analysis reveals that thymic involution is due to a change in the thymic microenvironment linked to a reduction in the level of available interleukin 7. Treatment with interleukin 7 leads to a reversal of thymic atrophy with increased thymopoiesis. This provides the potential to reverse the immune dysfunction seen in the peripheral T cell pool by replacing old cells with new output generated in the thymus. Problems to overcome in order for such an experimental therapy to be successful require careful analysis in order to provide an optimal strategy to ensure that new T cell emigrants from the thymus have a broad range of specificities and are able to enter the peripheral T cell pool.
Origins and evolution of AIDS viruses: estimating the time-scale
Authors: Sharp P. M. , Bailes E. , Gao F. , Beer B. E. , Hirsch V. M. , Hahn B. H.
Published: August 2015

The primate lentiviruses comprise SIV strains from various host species, as well as two viruses, HIV-1 and HIV-2, that cause AIDS in humans. The origins of HIV-1 and HIV-2 have been traced to cross-species transmissions from chimpanzees and sooty mangabey monkeys respectively. Two approaches have been taken to estimate the time-scale of the evolution of these viruses. Certain groups of SIV strains appear to have evolved in a host-dependent manner, implying a time-scale of many thousands or even millions of years. In stark contrast, molecular clock calculations have previously been used to estimate a time-scale of only tens or hundreds of years. Those calculations largely ignored heterogeneity of evolutionary rates across different sites within sequences. In fact, the distribution of rates at different sites seems extremely skewed in HIV-1, and so the time-depth of the primate lentivirus evolutionary tree may have been underestimated by at least a factor of ten. However, these date estimates still seem to be far too recent to be consistent with host-dependent evolution.
Post-genomic views of a ‘unique’ metabolism in the eukaryotic flagellum
Authors: Ginger M.L.
Published: August 2015

This short review summarizes recent advances in our understanding of energy metabolism within the eukaryotic flagellum. Using the example of adenylate kinase, we discuss how a requirement to target metabolic enzymes into the flagellum results in the presence of genes encoding novel isoforms of ubiquitous enzymes within flagellate eukaryotes.
Insulin and cholesterol pathways in neuronal function, memory and neurodegeneration
Authors: Nelson T.J. , Alkon D.L.
Published: August 2015

Insulin and cholesterol play important roles in basic metabolic processes in peripheral tissues. Both insulin and cholesterol can also act as signalling molecules in the central nervous system that participate in neuronal function, memory and neurodegenerative diseases. A high-cholesterol diet improves spatial memory in experimental animals. β-Amyloid, the toxic peptide in neurons of AD (Alzheimer's disease) patients, binds cholesterol and catalyses its oxidation to 7β-hydroxycholesterol, a highly toxic oxysterol that is a potent inhibitor of α-PKC (α-protein kinase C), an enzyme critical in memory consolidation and synaptic plasticity and implicated in AD. Oxidized cholesterol also can act as a second messenger for insulin. Oxidized low-density lipoprotein inhibits insulin-dependent phosphorylation of the signalling kinases ERK (extracellular-signal-regulated kinase) and PKB/Akt. In sporadic AD patients, insulin levels are decreased, suggesting links between AD and diabetes. Insulin signalling is also important in synaptic plasticity. Insulin receptors are up-regulated and undergo translocation after spatial learning. Insulin modulates the activity of excitatory and inhibitory receptors including the glutamate and γ-aminobutyric acid receptors and activates two biochemical pathways: the shc-ras-mitogen-activated protein kinase pathway and the PI3K (phosphoinositide 3-kinase)/PKC pathway, both of which are involved in memory processing. These findings point to a convergence at the biochemical level between pathways involved in AD and those important for normal memory.
Increased risk of Alzheimer's disease in Type II diabetes: insulin resistance of the brain or insulin-induced amyloid pathology?
Authors: Biessels G.J. , Kappelle L.J.
Published: August 2015

Type II diabetes mellitus (DM2) is associated with an increased risk of cognitive dysfunction and dementia. The increased risk of dementia concerns both Alzheimer's disease and vascular dementia. Although some uncertainty remains into the exact pathogenesis, several mechanisms through which DM2 may affect the brain have now been identified. First, factors related to the ‘metabolic syndrome’, a cluster of metabolic and vascular risk factors (e.g. dyslipidaemia and hypertension) that is closely linked to DM2, may be involved. A number of these risk factors are predictors of cerebrovascular disease, accelerated cognitive decline and dementia. Secondly, hyperglycaemia may be involved, through adverse effects of potentially ‘toxic’ glucose metabolites on the brain and its vasculature. Thirdly, insulin itself may be involved. Insulin can directly modulate synaptic plasticity and learning and memory, and disturbances in insulin signalling pathways in the periphery and in the brain have recently been implicated in Alzheimer's disease and brain aging. Insulin also regulates the metabolism of β-amyloid and tau, the building blocks of amyloid plaques and neurofibrillary tangles, the neuropathological hallmarks of Alzheimer's disease. In this paper, the evidence for the association between DM2 and dementia and for each of these underlying mechanisms will be reviewed, with emphasis on the role of insulin itself.
Adipose tissue changes in obesity
Authors: Coppack S.W.
Published: August 2015

This review gives a broad description of some of the changes in adipose tissue seen in obesity. There are multiple changes in adipose tissue in obesity: histological, neural and vascular, relating to lipid and carbo-hydrate metabolism and to adipose tissue's endocrine functions. Some may originate from a simple physical expansion of cell size and number. It is unclear which are the most important either in terms of intermediary metabolism or of contributing to the co-morbidities of obesity. Important questions for the future include the reversibility of obesity-related changes and indeed whether the changes differ between depots and species. Recent studies examining physiological regulation within adipose tissue demonstrate it to be relatively unresponsive to changes in everyday life.
Mouse models of PPAR-γ deficiency: dissecting PPAR-γ's role in metabolic homoeostasis
Authors: Gray S.L. , Dalla Nora E. , Vidal-Puig A.J.
Published: August 2015

The identification of humans with mutations in PPAR-γ (peroxisome-proliferator-activated receptor-γ) has underlined its importance in the pathogenesis of the metabolic syndrome. Genetically modified mice provide powerful tools to dissect the mechanisms by which PPAR-γ regulates metabolic processes. Ablation of PPAR-γ in vivo is lethal and thus dissection of PPAR-γ function using mouse models has relied on the development of tissue and isoform-specific ablation and mouse models of human mutations. These models exhibit phenotypes of partial PPAR-γ impairment and are useful to elucidate how PPAR-γ regulates specific metabolic processes. These murine models have confirmed the involvement of PPAR-γ in adipose tissue development, maintenance and distribution. The mechanism involved in PPAR-γ regulation of glucose homoeostasis is obscure as both agonism and partial impairment of PPAR-γ increase insulin sensitivity. While adipose tissue is likely to be the primary target for the insulin-sensitizing effects of PPAR-γ, some murine models suggest PPAR-γ expressed outside adipose tissue may also contribute actively to maintain glucose homoeostasis. Interestingly, mutations in PPAR-γ that cause severe insulin resistance in humans when expressed in mice do not result in insulin insensitivity. However, these murine models can recapitulate the effects in fuel partitioning, post-prandial lipid handling and vasculature dysfunction observed in humans. In summary, these murine models of PPAR-γ have provided useful in vivo systems to dissect the function of PPAR-γ, but additionally have revealed a picture of complexity. These models have confirmed a key role for PPAR-γ in the metabolic syndrome; however, they challenge the concept that insulin resistance is the main factor linking the clinical manifestations of the metabolic syndrome.
The role of cell-derived oligomers of Aβ in Alzheimer's disease and avenues for therapeutic intervention
Authors: Walsh D.M. , Klyubin I. , Shankar G.M. , Townsend M. , Fadeeva J.V. , Betts V. , Podlisny M.B. , Cleary J.P. , Ashe K.H. , Rowan M.J. , Selkoe D.J.
Published: August 2015

Burgeoning evidence suggests that soluble oligomers of Aβ (amyloid β-protein) are the earliest effectors of synaptic compromise in Alzheimer's disease. Whereas most other investigators have employed synthetic Aβ peptides, we have taken advantage of a β-amyloid precursor protein-overexpressing cell line (referred to as 7PA2) that secretes sub-nanomolar levels of low-n oligomers of Aβ. These are composed of heterogeneous Aβ peptides that migrate on SDS/PAGE as dimers, trimers and tetramers. When injected into the lateral ventricle of rats in vivo, these soluble oligomers inhibit hippocampal long-term potentiation and alter the memory of a complex learned behaviour. Biochemical manipulation of 7PA2 medium including immunodepletion with Aβ-specific antibodies and fractionation by size-exclusion chromatography allowed us to unambiguously attribute these effects to low-n oligomers. Using this paradigm we have tested compounds directed at three prominent amyloid-based therapeutic targets: inhibition of the secretases responsible for Aβ production, inhibition of Aβ aggregation and immunization against Aβ. In each case, compounds capable of reducing oligomer production or antibodies that avidly bind Aβ oligomers also ameliorate the synaptotoxic effects of these natural, cell-derived oligomers.
Expression and activity of β-site amyloid precursor protein cleaving enzyme in Alzheimer's disease
Authors: Johnston J.A. , Liu W.W. , Todd S.A. , Coulson D.T.R. , Murphy S. , Irvine G.B. , Passmore A.P.
Published: August 2015

Several lines of evidence indicate that the Aβ peptide is involved at some level in the pathological process that results in the clinical symptoms of AD (Alzheimer's disease). The N-terminus of Aβ is generated by cleavage of the Met-Asp bond at position 671–672 of APP (amyloid precursor protein), catalysed by a proteolytic activity called β-secretase. Two ‘β-secretase’ proteases have been identified: BACE (β-site APP-cleaving enzyme) and BACE2. The cause of sporadic AD is currently unknown, but some studies have reported elevated BACE/β-secretase activity in brain regions affected by the disease. We have demonstrated that robust β-secretase activity is also detectable in platelets that contain APP and release Aβ. This review considers the current evidence for alterations in β-secretase activity, and/or alterations in BACE expression, in post-mortem brain tissue and platelets from individuals with AD.
Alternative mechanisms of initiating translation of mammalian mRNAs
Authors: Jackson R.J.
Published: August 2015

Of all the steps in mRNA translation, initiation is the one that differs most radically between prokaryotes and eukaryotes. Not only is there no equivalent of the prokaryotic Shine–Dalgarno rRNA–mRNA interaction, but also what requires only three initiation factor proteins (aggregate size ∼125 kDa) in eubacteria needs at least 28 different polypeptides (aggregate >1600 kDa) in mammalian cells, which is actually larger than the size of the 40 S ribosomal subunit. Translation of the overwhelming majority of mammalian mRNAs occurs by a scanning mechanism, in which the 40 S ribosomal subunit, primed for initiation by the binding of several initiation factors including the eIF2 (eukaryotic initiation factor 2)–GTP–MettRNAi complex, is loaded on the mRNA immediately downstream of the 5′-cap, and then scans the RNA in the 5′→3′ direction. On recognition of (usually) the first AUG triplet via base-pairing with the Met-tRNAi anticodon, scanning ceases, triggering GTP hydrolysis and release of eIF2–GDP. Finally, ribosomal subunit joining and the release of the other initiation factors completes the initiation process. This sketchy outline conceals the fact that the exact mechanism of scanning and the precise roles of the initiation factors remain enigmatic. However, the factor requirements for initiation site selection on some viral IRESs (internal ribosome entry sites/segments) are simpler, and investigations into these IRES-dependent mechanisms (particularly picornavirus, hepatitis C virus and insect dicistrovirus IRESs) have significantly enhanced our understanding of the standard scanning mechanism. This article surveys the various alternative mechanisms of initiation site selection on mammalian (and other eukaryotic) cellular and viral mRNAs, starting from the simplest (in terms of initiation factor requirements) and working towards the most complex, which paradoxically happens to be the reverse order of their discovery.
Formins and VASPs may co-operate in the formation of filopodia
Authors: Schirenbeck A. , Arasada R. , Bretschneider T. , Schleicher M. , Faix J.
Published: August 2015

Filopodia are finger-like cell protrusions composed of parallel arrays of actin filaments, which elongate through actin polymerization at their tips. These highly dynamic structures seem to be used by many cell types as sensing organs to explore environmental cues and have been implicated in cell motility as well as in cell–substrate adhesion. Formins are highly conserved multidomain proteins that play important roles in the nucleation of actin and the formation of linear actin filaments, yet their role in filopodia formation has remained poorly defined. The Dictyostelium diaphanous-related formin dDia2 is strongly enriched in filopodia tips. Genetic and biochemical analysis revealed that this protein is important for cell migration and cell adhesion, but most importantly for the formation of filopodia. Recently, we have identified the Dictyostelium VASP (vasodilator-stimulated phosphoprotein) orthologue as a binding partner of dDia2 and provide evidence for a co-operative role of both proteins in filopodia formation.
Takeover of host ribosomes by divergent IRES elements
Authors: Sarnow P. , Cevallos R.C. , Jan E.
Published: August 2015

The ribosome is the macromolecular machinery in the host cell for which all viruses have to compete. Early in infection, the viral mRNAs have to compete with the host for both the ribosomes and for the limited pool of eukaryotic initiation factors that are needed to facilitate the recruitment of ribosomes to both viral and cellular mRNAs. To circumvent this competition, certain viruses have evolved to recruit ribosomes to IRESs (internal ribosome entry sites), highly specialized RNA elements that are located at the 5′-end of the viral genomes. Here, we discuss how divergent IRES elements can recruit ribosomes and start protein synthesis with only a minimal set of eukaryotic translation initiation factors, and how this mode of translation initiation aids viral gene amplification during early onset of innate immune responses.