bluuebunny/crossref_metadata_2025 huggingface dataset:
Ex Vivo Expansion of Human outgrowth Endothelial Cells Leads to IL-8-Mediated Replicative Senescence and Impaired Vasoreparative Function
Authors: Medina Reinhold J. , O'Neill Christina L. , O'Doherty T. Michelle , Chambers Sarah E.J. , Guduric-Fuchs Jasenka , Neisen Jessica , Waugh David J. , Simpson David A. , Stitt Alan W.
Published: April 2013

Harnessing outgrowth endothelial cells (OECs) for vasoreparative therapy and tissue engineering requires efficient ex vivo expansion. How such expansion impacts on OEC function is largely unknown. In this study, we show that OECs become permanently cell-cycle arrested after ex vivo expansion, which is associated with enlarged cell size, β-galactosidase activity, DNA damage, tumor suppressor pathway activation, and significant transcriptome changes. These senescence hallmarks were coupled with low telomerase activity and telomere shortening, indicating replicative senescence. OEC senescence limited their regenerative potential by impairing vasoreparative properties in vitro and in vivo. Integrated transcriptome-proteome analysis identified inflammatory signaling pathways as major mechanistic components of the OEC senescence program. In particular, IL8 was an important facilitator of this senescence; depletion of IL8 in OECs significantly extended ex vivo lifespan, delayed replicative senescence, and enhanced function. While the ability to expand OEC numbers prior to autologous or allogeneic therapy remains a useful property, their replicative senescence and associated impairment of vasorepair needs to be considered. This study also suggests that modulation of the senescence-associated secretory phenotype could be used to optimize OEC therapy.
Understanding Structure Formation in Organolithium Compounds: An Experimental and Quantum‐Chemical Approach
Authors: Götz Kathrin , Gessner Viktoria H. , Unkelbach Christian , Kaupp Martin , Strohmann Carsten
Published: April 2013

As the reactivity of organolithium compounds is strongly connected with the structure of the involved species, the structural knowledge is a prerequisite for the understanding of reaction mechanisms. Using the example of methyllithium, we address particularly the issues of stabilizing non‐classical interactions in organolithium aggregates and the relations between disaggregation and polarity, using a combination of X‐ray structure analysis and quantum‐chemical methods. The structure analyses of a series of MeLi adducts, among them the diethyl ether adduct (MeLi·Et2O)4, exhibit varying arrangements of the α‐hydrogen atoms relative to lithium. α‐Hydrogen orientations differ even when changing the stereochemistry of the ligand in dimeric adducts. Computations confirm only weak stabilizing effects of agostic Li–H interactions, which compete with other aspects of the spatial situation in the formed aggregates. NPA and QTAIM analyses on different aggregates (e.g. monomer, dimer, tetramer, extended crystal environment) with different co‐ligands reveal a complicated relation between the degree of aggregation and Li–C bond polarity but a more clearcut dependence on the lithium coordination number.
Dietary approach to hypertension based on low glycaemic index and principles of DASH (Dietary Approaches to Stop Hypertension): a randomised trial in a primary care service
Authors: Lima Sílvia Tereza Rodrigues Moreira , da Silva Nalin de Souza Bárbara , França Ana Karina Teixeira , Filho Natalino Salgado , Sichieri Rosely
Published: April 2013

Hypertension is one of the leading causes of morbidity and mortality in Brazil. Diet may play an important role in reducing blood pressure (BP), as has been shown for diets high in fruits, vegetables and low-fat dairy products and low in salt (Dietary Approaches to Stop Hypertension (DASH)-Na). A low-glycaemic index Brazilian diet combined with the principles of the DASH-Na diet was evaluated in a randomised study of 206 individuals who were followed for 6 months. In the control group (CG), counselling was based on standard care and mainly focused on salt intake reduction. An intention-to-treat analysis showed that, after 6 months, systolic BP was reduced by 14·4 mmHg and diastolic BP by 9·7 mmHg in the experimental group (EG), compared with 6·7 and 4·6 mmHg, respectively, in the CG. After adjusting for body weight, BP at baseline and age, these changes were 12·1 and 7·9 mmHg, respectively. Urinary Na excretion was also reduced by 43·4 mEq/24 h in the EG. Food intake was modified accordingly during the intervention with an increase in the consumption of vegetables (2·97–5·85 frequency of consumption measured in three non-consecutive days), fruits (4·09–7·18), beans (1·94–3·13) and fish (1·80–2·74) by the EG. The present study showed the feasibility of a Brazilian dietary approach to treating hypertension by reducing urinary Na excretion and BP, changes that may have a great impact on public health and promote the benefits of controlling hypertension.
Dietary electrolyte balance affects the nutrient digestibility and maintenance energy expenditure of Nile tilapia
Authors: Saravanan S. , Geurden I. , Orozco Z. G. A. , Kaushik S. J. , Verreth J. A. J. , Schrama J. W.
Published: April 2013

Acid–base disturbances caused by environmental factors and physiological events including feeding have been well documented in several fish species, but little is known about the impact of dietary electrolyte balance (dEB). In the present study, we investigated the effect of feeding diets differing in dEB ( − 100, 200, 500 or 800 mEq/kg diet) on the growth, nutrient digestibility and energy balance of Nile tilapia. After 5 weeks on the test diet, the growth of the fish was linearly affected by the dEB levels (P< 0·001), with the lowest growth being observed in the fish fed the 800 dEB diet. The apparent digestibility coefficient (ADC) of fat was unaffected by dEB, whereas the ADC of DM and protein were curvilinearly related to the dEB levels, being lowest and highest in the 200 and 800 dEB diets, respectively. Stomach chyme pH at 3 h after feeding was linearly related to the dEB levels (P< 0·05). At the same time, blood pH of the heart (P< 0·05) and caudal vein (P< 0·01) was curvilinearly related to the dEB levels, suggesting the influence of dEB on postprandial metabolic alkalosis. Consequently, maintenance energy expenditure (MEm) was curvilinearly related to the dEB levels (P< 0·001), being 54 % higher in the 800 dEB group (88 kJ/kg0·8per d) than in the 200 dEB group (57 kJ/kg0·8per d). These results suggest that varying dEB levels in a diet have both positive and negative effects on fish. On the one hand, they improve nutrient digestibility; on the other hand, they challenge the acid–base homeostasis (pH) of fish, causing an increase in MEm, and thereby reduce the energy required for growth.
The economies of pedagogy: Xenophon's wifely didactics
Authors: Too Yun Lee
Published: April 2013

Xenophon'sOeconomicusis a work which has recently prompted a number of widely divergent responses. A predominant reading offers that the work is a testimony to Greek misogyny in the classical period: the husband Ischomachus takes a young, inexperienced wife, who is accordingly and following custom tamed andinstructedto manage the space within the οἶχος. Another interpretation regards Xenophon and Ischomachus as better-than-average Greek men with respect to women's standing in society, or even as proto-feminist. In this treatment of the dialogue, the fact that the husband allows the wife herownspace – the home (as distinct from the farm outdoors) – and teaches her herownactivities – housework and the management of the household slaves – demonstrates a considerable degree of respect for the wife and for woman's worth, while Socrates' exclamation that the wife has a ‘masculine intellect (ἀνδϱιχὴν διάνοιαν)’ (10.1) is to be taken as proof of the Xenophontic wife's authority. There are further variations which qualify these interpretations: either the husband is regarded as echoing Socratic sympathy towards women while continuing to insist that the wife be a domestic; or the husband, despite being a misogynist, is seen as granting the wife some degree of autonomy.
The Mycenaean palatial economy: Making the most of the gaps in the evidence
Authors: Halstead Paul
Published: April 2013

It has long been recognised that the Linear B archives from the Mycenaean palaces of Late Bronze Age Greece document ‘a massive redistributive operation, in which all personnel and all activities, all movements of both persons and goods … were administratively fixed’. Goods, land and services were transferred within the extensive territory of each palace without the equivalences of value between commodities which are a prerequisite of market exchange. The transactions recorded in the Linear B archives are thus unambiguously ‘redistributive’, an Aegean variant of a form of exchange widespread in the ancient civilisations, and as such have attracted the interest both of economic historians and of prehistorians concerned with the development of complex society. The term ‘redistribution’ embraces a range of possible forms, however, and in the case of the Mycenaean palaces poses a number of questions.
Seductions of art: Encolpius and Eumolpus in a Neronian picture gallery
Authors: Elsner John
Published: April 2013

The age of Nero is universally considered – even by its more circumspect modern historians – to be a zenith of decadence. This view is not simply the invention of modern writers. It is one point on which the ancient sources, not only historians from Tacitus to Cassius Dio, but also biographers such as Suetonius and poets like Martial, are agreed. One problem with the almost monotonous tale of vice, sexual and gastronomic excess, cruelty and murder, by which Nero's reign has been characterised, is that this is a story written by the winners in the turmoil which followed Nero's fall. It is hardly, in other words, an objective or unbiased account.
Claudian's methods of borrowing in ‘De Raptu Proserpinae’
Authors: Clarke A. K.
Published: April 2013

The literary sources upon which Claudian drew for De Raptu Proserpinae were recognized early. A great number were noted by Parrhasius in his edition of the poem (1500), and others by the editors of the sixteenth and seventeenth centuries, particularly Heinsius. The eighteenth-century editors of Claudian had less work to do in this field. Gesner's edition (1759) made an important contribution to the study of Claudian, but the value of his commentary, both on the De Raptu and on the other poems, lay in judicious observation rather than discovery. Birt's edition in M.G.H. (1892) assembled the material in a valuable form, yet with the omission of some significant parallels and the addition of some which are slight and even questionable. Our task now is not so much to discover the sources of Claudian's language as to examine his use of them, and in attempting this we have two advantages. We have a better knowledge than our predecessors of Claudian's milieu and of classical culture at the end of the fourth century A.D.; and we have not been accustomed to regard poetry as necessarily less original because it is a grouping of associations.
Some passages in Statius
Authors: Williams R. D.
Published: April 2013

(i) Th. x, 935–9.

Stat tamen, extremumque in sidera versus anhelat,pectoraque invisis obicit fumantia muris,937 ne caderet: sed membra virum terrena relinquunt,exuiturque animus: paulum si tardius artuscessissent, potuit fulmen sperare secundum.

937 Nec PQr Nee BLMNCfbWDS Turon. Brux. 5337 Nee (Ne sscr.) Tol.

The last part of book x of the Thebaid describes the grandiose defiance of Capaneus. He grows weary of dealing death below the walls of Thebes, and climbs to the height of the battlements, where he towers above the city and terrifies it with his huge shadow. He taunts the gods and Jupiter himself to do battle for Thebes against him, and when Jupiter in anger darkens the sky and lightning begins to flash, he cries

His, ait, in Thebas, his iam decet ignibus uti,hinc renovare faces, lassamque accendere quercum. (925–6.)
Thucydides, II, 45, 2
Authors: Lacey W. K.
Published: April 2013

Thucydides 11, 45, 2. , .

It would be imprudent for a commentator on this famous passage who wishes to suggest that its importance for an understanding of the position of women in Athens is greatly exaggerated to offer more dian a tentative view of its significance, and die remarks below should be taken in this light.
Aspects of the Social Thought of Dio Chrysostom and of the Stoics
Authors: Brunt P. A.
Published: April 2013

On re-reading Dio of Prusa's Euboicus, I formed the impression that his ideas on manual labour and on the respectability of occupations open to the poor are somewhat different from those conventionally adopted by Greeks and Romans of the upper class, to which Dio belonged. Part 1 of this paper discusses these ideas in the Euboicus and in some related works of Dio. It will inter alia afford some conjectural support to von Arnim's hypothesis that the Euboicus was delivered at Rome. Probably Dio's attitude was influenced by his experience in exile, when he had known what it was to be poor and had even propounded Cynic opinions. But the Euboicus is a work of his old age (VII. 1), and his conduct after his restoration to his home in A.D. 96 was conspicuously non-Cynic. If then we find some indication that he was also indebted to some previous theorizing on appropriate occupations for the free poor, we need not think of a Cynic model; indeed we should not, for the Cynics were little given to the kind of casuistry involved. In Part I some evidence will be found that Dio was also influenced by Stoic teaching, and in Part II it will be argued that his discussion of the way in which the poor could decently earn their living goes back to Stoic works on practical morality of the kind illustrated by Panaetius' treatise On Appropriate Action; however, Dio's ideas are not those of the Middle Stoa and more probably derive from Cleanthes or Chrysippus. In this connection I take Cicero, de officiis 1. 150 f., to represent the views of Panaetius, and as I have found that this interpretation can be contested, I have tried to justify it in the Appendix.
Androtion and the Four Hundred
Authors: Andrewes A.
Published: April 2013

This paper should have had a longer and more explanatory title. I am not overmuch concerned with the interesting general question of the influence exerted by the Atthis of Androtion on subsequent accounts, primarily of course on that of the Aristotelian Athenaion Politeia: the specific problem I wish to discuss is the use of documents in these chapters of AP, and the possibility that they were transmitted by Androtion. Jacoby in his introduction to that author (n. 86) treats it as ‘fairly certain’ that ‘A. supplied the documents for the reform of the constitution in 412/1 B.C. (AP 29–33) in detail and evidently with approval as a kind of model constitution’. He was not alone in this opinion, which needs examination. The argument is necessarily speculative, a weighing of probabilities, and the only statement for which I claim certainty is that Wilamowitz was wrong in one detail.

In the first excitement of the publication of AP some eminent scholars, headed by Wilamowitz and Köhler, acclaimed the data found in AP as authentic documents which could be used to ‘correct’ Thucydides. The counter-attack by Ed. Meyer concentrated on the argument that official documents are not the best guide to what actually happens in a revolution: that is, Meyer still accepted the documents as authentic, but he upheld the narrative of Thucydides against them. To the best of my knowledge it was not till 1907 that the question was raised, by Judeich, whether any authentic documents would have survived the restoration of democracy.
Notes on the text of Catullus
Authors: Nisbet R. G. M.
Published: April 2013

The text of Catullus is notoriously corrupt, and though much has been healed, something remains to be done. An article may still be useful if it encourages scepticism and speculation. I have found Baehrens the best commentator for this particular purpose; for information about the manuscripts I rely on Mynors. The text printed is that of V where I wish to discuss it, but it is sometimes silently altered where I do not. Textual variants are mentioned only where they are relevant to the argument.
On Lucan
Authors: Bailey D. R. Shackleton
Published: April 2013

1. 151-7 qualiter expressum ventis per nubila fulmenaetheris impulsi sonitu mundique fragoreemicuit rupitque diem populosque paventesterruit obliqua praestringens lumina flamma:in sua templa furit, nullaque exire vetantemateria magnamque cadens magnamque revertensdat stragem late sparsosque recolligit ignes.

Of the rival interpretations of templa in 155, ‘temples’ and ‘quarters of the sky’ Housman espoused the latter; but he did not explain sua, which Weise explained as ‘loca aut regna, in quibus oritur et quasi habitat et regnat fulmen’ (‘the quarter of the sky whence it came’ Haskins). Such in fact seems the only possible interpretation, given the chosen sense of templa, despite Duff's ‘it rushes to its appointed quarter of the sky’ or Bourgery's ‘elle fond sur les lieux qu'elle consacre.’ But why should Lucan tell us this (Weise's ‘habitat et regnat’ is only his own embroidery), and so spoil his sequel? How a Roman reader would understand templa should be obvious to anyone who has read Pease's note on Cic. Div. 1.19 ipse suos quondam tumulos aut templa petivit/et Capitolinis iniecit sedibus ignis.
Titi Livi Lib. XCI
Authors: Ogilvie R. M.
Published: April 2013

 tamen insequenti ipso pervigilante in eodem loco alia excitata turris prima luce miraculo hostibus fuit. Simul et oppidi turris quae maximum propugnaculum fuerat, subrutis fundamentis, dehiscere ingentibus rimis et tum [xvi litt.] ṭọ [iii litt.] igni coepit; incendiique simul et ruinae metu territi Contrebienses de muro trepidi refugerunt; et ut legati mitterentur ad dedendam urbem ab universa multitudine conclamatum est. Eadem virtus quae irritaverat oppugnantem victorem placabiliorem fecit. Obsidibus acceptis pecuniae modicam exegit summam armaque omnia ademit. Transfugas liberos vivos ad se adduci iussit; fugitivos, quorum maior multitudo erat, ipsis imperavit ut interficerent. Iugulatos de muro deiecerunt.

Cum magna iactura militum quattuor et quadraginta diebus Contrebia expugnata, relictoque ibi L. Insteio [xvi litt.] ipse ad Hiberum flumen copias reduxit. Ibi hibernaculis secundum oppidum quod Castra Aelia vocatur aedificatis ipse in castris manebat; interdiu conventum sociarum civitatium in oppido agebat. Arma ut fierent pro copiis cuiusque populi per totam provinciam edixerat; quibus inspectis referre vetera arma milites iussit, quae aut itineribus crebris aut oppu [c. xxx litt.] facta erant, novaque iis per centuriones divisit. Equitatum quoque novis instruxit armis, vestimentaque praeparata ante divisa, et stipendium datum.
History and revelation in Vergil's underworld
Authors: Feeney D. C.
Published: April 2013

Vergil's parade of heroes, a panegyric that becomes a threnody, is an odd blend. It is framed by an elaborate quasi-philosophical eschatology, whose relation to the parade is problematical. Much of the passage puts itself forward as high panegyric, yet certain sections are at variance with that tendency. The lament for Marcellus (868-86) is most commonly remarked upon; other passages are equally, or more, anomalous. Still, the massive self-assurance of the picture of the underworld has its own imposing conviction, so that although the disparateness of the contributing elements has been documented often enough, few have felt the need to dispute the question of whether the blend coheres as a single statement. One noteworthy reader of Vergil was, however, compelled to give minute attention to the implications of the historical vision in Book 6. Incidentally throughout the Bellum Ciuile, but especially in his own sixth book, with the vision of hell called forth by the agency of the witch Erictho, Lucan provides a provocative reading of Aeneid 6. His insights will be exploited in the discussion as a valuable stimulus to reflection and re-assessment; an appendix will give a more systematic account of his re-interpretation of Vergil.
Propertius 4.5, Ovid Amores 1.6 and Roman Comedy
Authors: Yardley J. C.
Published: April 2013

‘The absence of Roman comedy … from the influences which the [Augustan] poets like to name proves only that they were not creditable, not in fashion, not that they had made no contribution.’ So Jasper Griffin in his recent book on the Roman poets. Griffin observes that scholars have been deterred from postulating Roman comic influence on the Augustan poets merely by the ‘magisterial pronouncements of the great scholars’, and he amasses considerable circumstantial evidence to support his theory that the Augustan poets, and especially the elegists, were indeed indebted to Roman comedy. He observes, for example, that Cicero provides evidence for the continuing popularity of Roman drama; that (a very important point) Horace complains of the popularity of the Roman comedians whom ‘powerful Rome learns by heart’ (Epist.2.1.60-1); that the same poet, despite his denigration of Roman comedy, obviously knew and referred to it; that Roman comedy seems to be the source, or a source, for the ‘naughtiness’ of elegy and the rejection of traditional Roman values (with the comicamatoresdistressed by contemporarymoresand the elegists flouting them); that if the elegists do not acknowledge their debt to the Roman comic poets, then no more does Horace in theOdesacknowledge his manifest indebtedness to Hellenistic poetry, claiming instead to be following Sappho and Alcaeus.
The Athenian Embassy to Sparta in 371 B.C.
Authors: Mosley D. J.
Published: April 2013

Xenophon records that in 371 an embassy was sent from Athens to Sparta in order to negotiate a settlement. His account contains several peculiar features concerning both the procedure of the embassy and the personnel employed. To submit the historical writings of Xenophon to close and detailed scrutiny is often an unrewarding task, yet it is well to bear in mind that at the time of the events under discussion Xenophon, who had been exiled from Athens, was resident in the Peloponnese and he ought therefore to have been in a position to combine an understanding of the political workings of Athens with a knowledge of what went on in Sparta.

We read that Callias the son of Hipponicus, Autocles the son of Strombichides, Demostratus the son of Aristophon, Aristocles, Cephisodotus, Melanopus and Lycaethus, seven names in all, were sent as envoys, and further that the popular orator Callistratus was also present in Sparta. Included in the account are three speeches which at first sight are discordant and which Xenophon attributes to Callias, Autocles and Callistratus.
Chronic bullying victimization across school transitions: The role of genetic and environmental influences
Authors: Bowes Lucy , Maughan Barbara , Ball Harriet , Shakoor Sania , Ouellet-Morin Isabelle , Caspi Avshalom , Moffitt Terrie E. , Arseneault Louise
Published: April 2013

We investigated the antecedents and consequences of chronic victimization by bullies across a school transition using a genetically sensitive longitudinal design. Data were from the Environmental Risk Longitudinal Twin Study (E-Risk), an epidemiological cohort of 2,232 children. We used mothers' and children's reports of bullying victimization during primary school and early secondary school. Children who experienced frequent victimization at both time points were classed as “chronic victims” and were found to have an increased risk for mental health problems and academic difficulties compared to children who were bullied only in primary school, children bullied for the first time in secondary school, and never-bullied children. Biometric analyses revealed that stability in victimization over this period was influenced primarily by genetic and shared environmental factors. Regression analyses showed that children's early characteristics such as preexistent adjustment difficulties and IQ predicted chronic versus transitory victimization. Family risk factors for chronic victimization included socioeconomic disadvantage, low maternal warmth, and maltreatment. Our results suggest that bullying intervention programs should consider the role of the victims' behaviors and family background in increasing vulnerability to chronic victimization. Our study highlights the importance of widening antibullying interventions to include families to reduce the likelihood of children entering a pathway toward chronic victimization.
Codevelopment of externalizing and internalizing symptoms in middle to late childhood: Sex, baseline respiratory sinus arrhythmia, and respiratory sinus arrhythmia reactivity as predictors
Authors: Hinnant J. Benjamin , El-Sheikh Mona
Published: April 2013

We investigated the roles of sex and respiratory sinus arrhythmia (RSA), an index of autonomic parasympathetic nervous system activity, as predictors of codeveloping externalizing and internalizing symptoms in middle childhood. We expected that sex, baseline RSA (RSA-B), and RSA reactivity (RSA-R) to two types of tasks would interact to differentiate co-occurring trajectories of symptoms. We tested these hypotheses by combining longitudinal data from two independent samples (n = 390; 210 girls, 180 boys) with repeated measures at ages 8, 9, 10, and 11. RSA-R was measured in response to a socially stressful and frustrating stressor. Indicators of growth in externalizing and internalizing symptoms were derived from multiple domain growth models and used in person-centered growth mixture analyses. Three groups of externalizing and internalizing trajectories were found. Profile membership was predicted by several two-way interactions among sex, RSA-B, or RSA-R but was not predicted by three-way interactions. Children with low RSA-B and strong RSA withdrawal, girls with low RSA-B, and girls with strong RSA withdrawal were more likely to be on a developmental trajectory of low externalizing symptoms and moderately elevated internalizing symptoms. Membership in the high externalizing and high internalizing trajectory was predicted by weak RSA withdrawal for boys and strong RSA withdrawal for girls. The type of stressor task also played a role in predicting probability of profile membership. Results are discussed in the context of developmental psychobiology and implications for the codevelopment of psychopathology symptoms in childhood.
Effects of early maternal distress and parenting on the development of children's self-regulation and externalizing behavior
Authors: Choe Daniel Ewon , Olson Sheryl L. , Sameroff Arnold J.
Published: April 2013

Emotional distress experienced by mothers increases young children's risk of externalizing problems through suboptimal parenting and child self-regulation. An integrative structural equation model tested hypotheses that mothers’ parenting (i.e., low levels of inductive discipline and maternal warmth) would mediate adverse effects of early maternal distress on child effortful control, which in turn would mediate effects of maternal parenting on child externalizing behavior. This longitudinal study spanning ages 3, 6, and 10 included 241 children, mothers, and a subset of teachers. The hypothesized model was partially supported. Elevated maternal distress was associated with less inductive discipline and maternal warmth, which in turn were associated with less effortful control at age 3 but not at age 6. Inductive discipline and maternal warmth mediated adverse effects of maternal distress on children's effortful control. Less effortful control at ages 3 and 6 predicted smaller relative decreases in externalizing behavior at 6 and 10, respectively. Effortful control mediated effects of inductive discipline, but not maternal warmth, on externalizing behavior. Findings suggest elevated maternal distress increases children's risk of externalizing problems by compromising early parenting and child self-regulation.
Gene × Environment effects of serotonin transporter, dopamine receptor D4, and monoamine oxidase A genes with contextual and parenting risk factors on symptoms of oppositional defiant disorder, anxiety, and depression in a community sample of 4-year-old children
Authors: Lavigne John V. , Herzing Laura B. K. , Cook Edwin H. , Lebailly Susan A. , Gouze Karen R. , Hopkins Joyce , Bryant Fred B.
Published: April 2013

Genetic factors can play a key role in the multiple level of analyses approach to understanding the development of child psychopathology. The present study examined gene–environment correlations and Gene × Environment interactions for polymorphisms of three target genes, the serotonin transporter gene, the D4 dopamine receptor gene, and the monoamine oxidase A gene in relation to symptoms of anxiety, depression, and oppositional behavior. Saliva samples were collected from 175 non-Hispanic White, 4-year-old children. Psychosocial risk factors included socioeconomic status, life stress, caretaker depression, parental support, hostility, and scaffolding skills. In comparison with the short forms (s/s, s/l) of the serotonin transporter linked polymorphic repeat, the long form (l/l) was associated with greater increases in symptoms of oppositional defiant disorder in interaction with family stress and with greater increases in symptoms of child depression and anxiety in interaction with caretaker depression, family conflict, and socioeconomic status. In boys, low-activity monoamine oxidase A gene was associated with increases in child anxiety and depression in interaction with caretaker depression, hostility, family conflict, and family stress. The results highlight the important of gene–environment interplay in the development of symptoms of child psychopathology in young children.
A Brief History of Wine in Spain
Authors: Estreicher Stefan K.
Published: April 2013

This paper describes the evolution of wine in Spain from Phoenician times to the present, within a historical context. Each of the six main sections deserves more careful analysis, but the broad overview given here could be of interest to the curious (and thirsty) reader.
Winckelmann and Antinous
Authors: Vout Caroline
Published: April 2013

The credit for inventing the scientific study of Greco-Roman sculpture still belongs to the German scholar, Johann Joachim Winckelmann. The reason for this, theGeschichte der Kunst des AlterthumsorHistory of the Art of Antiquity, was first published in Dresden in 1764 and supplemented in 1767 by theAnmerkungen über die Geschichte der Kunst des AlterthumsorFurther Remarks. So important was the project that Winckelmann was revising it when he was murdered a year later. This evolving version was published in Vienna in 1776. It is this amendedGeschichtethat formed the basis of influential French and Italian editions. These followed quickly, propelled perhaps by the interest generated by his murder. Though it was another hundred years before the text was translated into English, its impact has been extraordinary. Vestiges of the book are everywhere. Citations from the ‘final’ version permeate the literature. Even without opening it, we sense its influence on the field we call ‘Classical Art’.
Inhibitory Control Contributes to “Motor”- but not “Cognitive”- Impulsivity
Authors: Caswell Amy Jane , Morgan Michael John , Duka Theodora
Published: April 2013

Literature on impulsivity regularly claims inhibitory control deficits underlie impulsive behavior. The current study investigated whether taxing inhibitory control will increase reflection (decision making under conditions of uncertainty), temporal (delay of gratification), and motor impulsivity (behavioral disinhibition). Inhibitory control was challenged, via a random letter generation task presented during responding to three impulsivity measures: the Information Sampling Task (IST), Single Key Impulsivity Paradigm, and the Stop Signal Task (SST). Participants (n = 33) were assigned to the inhibitory control challenging (experimental) condition, or to a control condition in which inhibitory control was not challenged. The SST was affected by the inhibitory control challenge: participants in the experimental condition displayed increased motor impulsivity, evidenced in longer stop signal reaction times (SSRTs) compared to the control group. The manipulation did not affect reflection- or temporal- impulsivity measures. These data support the suggestion that the mechanisms underlying the motor subtype of impulsivity are dissociable from the temporal and reflection subtypes, and that engagement of inhibitory control is not necessary to prevent impulsive decision making.
Sensory Effects of Action Observation
Authors: Thomas Richard , Sink Jill , Haggard Patrick
Published: April 2013

Recent neurophysiological and behavioral studies suggest that the brain simulates the sensorimotor processing of observed actions. The relative contributions of sensory and motor simulation in this process remain unclear. Here, we use the well-established phenomenon of sensorimotor gating as a hallmark of motor representation. Perceived intensities of external stimuli are routinely suppressed during motor preparation and execution. Therefore, motor simulation should result in reduced perceptual intensity of sensory stimuli delivered during action observation. We obtained magnitude estimates for vibrotactile stimulation of the upper lip during observation of silent speech (lip-reading). Perceptual enhancement was consistently found across three experiments. The effect appeared to be specific to the observed action, somatotopically organized, and distinct from general attentional and response biases. We conclude that action observation produces perceptual enhancement. The experience of observing others’ actions may be driven more by sensory simulation than by motor simulation.
Mechanistic insights into small RNA recognition and modification by the HEN1 methyltransferase
Authors: Plotnikova Alexandra , Baranauskė Simona , Osipenko Aleksandr , Klimašauskas Saulius , Vilkaitis Giedrius
Published: April 2013

The HEN1 methyltransferase from Arabidopsis thaliana modifies the 3′-terminal nucleotides of small regulatory RNAs. Although it is one of the best characterized members of the 2′-O-methyltransferase family, many aspects of its interactions with the cofactor and substrate RNA remained unresolved. To better understand the substrate interactions and contributions of individual steps during HEN1 catalysis, we studied the binding and methylation kinetics of the enzyme using a series of unmethylated, hemimethylated and doubly methylated miRNA and siRNA substrates. The present study shows that HEN1 specifically binds double-stranded unmethylated or hemimethylated miR173/miR173* substrates with a subnanomolar affinity in a cofactor-dependent manner. Kinetic studies under single turnover and pre-steady state conditions in combination with isotope partitioning analysis showed that the binary HEN1–miRNA/miRNA* complex is catalytically competent; however, successive methylation of the two strands in a RNA duplex occurs in a non-processive (distributive) manner. We also find that the observed moderate methylation strand preference is largely exerted at the RNA-binding step and is fairly independent of the nature of the 3′-terminal nucleobase, but shows some dependency on proximal nucleotide mispairs. The results of the present study thus provide novel insights into the mechanism of RNA recognition and modification by a representative small RNA 2′-O-methyltransferase.
Reorganization of an intersubunit bridge induced by disparate 16S
ribosomal ambiguity
mutations mimics an EF-Tu-bound state
Authors: Fagan Crystal E. , Dunkle Jack A. , Maehigashi Tatsuya , Dang Mai N. , Devaraj Aishwarya , Miles Stacey J. , Qin Daoming , Fredrick Kurt , Dunham Christine M.
Published: April 2013

After four decades of research aimed at understanding tRNA selection on the ribosome, the mechanism by which
ribosomal ambiguity
(
ram
) mutations promote miscoding remains unclear. Here, we present two X-ray crystal structures of the
Thermus thermophilus
70S ribosome containing 16S rRNA
ram
mutations, G347U and G299A. Each of these mutations causes miscoding in vivo and stimulates elongation factor thermo unstable (EF-Tu)-dependent GTP hydrolysis in vitro. Mutation G299A is located near the interface of ribosomal proteins S4 and S5 on the solvent side of the subunit, whereas G347U is located 77 Å distant, at intersubunit bridge B8, close to where EF-Tu engages the ribosome. Despite these disparate locations, both mutations induce almost identical structural rearrangements that disrupt the B8 bridge—namely, the interaction of h8/h14 with L14 and L19. This conformation most closely resembles that seen upon EF-Tu⋅GTP⋅aminoacyl-tRNA binding to the 70S ribosome. These data provide evidence that disruption and/or distortion of B8 is an important aspect of GTPase activation. We propose that, by destabilizing B8, G299A and G347U reduce the energetic cost of attaining the GTPase-activated state and thereby decrease the stringency of decoding. This previously unappreciated role for B8 in controlling the decoding process may hold relevance for many other ribosomal mutations known to influence translational fidelity.
Blood meal-induced changes to antennal transcriptome profiles reveal shifts in odor sensitivities in
Anopheles gambiae
Authors: Rinker David C. , Pitts R. Jason , Zhou Xiaofan , Suh Eunho , Rokas Antonis , Zwiebel Laurence J.
Published: April 2013

Olfactory-driven behaviors are central to the lifecycle of the malaria vector mosquito
Anopheles gambiae
and are initiated by peripheral signaling in the antenna and other olfactory tissues. To continue gaining insight into the relationship between gene expression and olfaction, we have performed cohort comparisons of antennal transcript abundances at five time points after a blood meal, a key event in both reproduction and disease transmission cycles. We found that more than 5,000 transcripts displayed significant abundance differences, many of which were correlated by cluster analysis. Within the chemosensory gene families, we observed a general reduction in the level of chemosensory gene transcripts, although a subset of odorant receptors (AgOrs) was modestly enhanced in post–blood-fed samples. Integration of AgOr transcript abundance data with previously characterized AgOr excitatory odorant response profiles revealed potential changes in antennal odorant receptivity that coincided with the shift from host-seeking to oviposition behaviors in blood-fed female mosquitoes. Behavioral testing of ovipositing females to odorants highlighted by this synthetic analysis identified two unique, unitary oviposition cues for
An. gambiae,
2-propylphenol and 4-methylcyclohexanol. We posit that modest, yet cumulative, alterations of AgOr transcript levels modulate peripheral odor coding resulting in biologically relevant behavioral effects. Moreover, these results demonstrate that highly quantitative, RNAseq transcript abundance data can be successfully integrated with functional data to generate testable hypotheses.
Cofactor-dependent specificity of a DEAD-box protein
Authors: Young Crystal L. , Khoshnevis Sohail , Karbstein Katrin
Published: April 2013

DEAD-box proteins, a large class of RNA-dependent ATPases, regulate all aspects of gene expression and RNA metabolism. They can facilitate dissociation of RNA duplexes and remodeling of RNA–protein complexes, serve as ATP-dependent RNA-binding proteins, or even anneal duplexes. These proteins have highly conserved sequence elements that are contained within two RecA-like domains; consequently, their structures are nearly identical. Furthermore, crystal structures of DEAD-box proteins with bound RNA reveal interactions exclusively between the protein and the RNA backbone. Together, these findings suggest that DEAD-box proteins interact with their substrates in a nonspecific manner, which is confirmed in biochemical experiments. Nevertheless, this contrasts with the need to target these enzymes to specific substrates in vivo. Using the DEAD-box protein Rok1 and its cofactor Rrp5, which both function during maturation of the small ribosomal subunit, we show here that Rrp5 provides specificity to the otherwise nonspecific biochemical activities of the Rok1 DEAD-domain. This finding could reconcile the need for specific substrate binding of some DEAD-box proteins with their nonspecific binding surface and expands the potential roles of cofactors to specificity factors. Identification of helicase cofactors and their RNA substrates could therefore help define the undescribed roles of the 19 DEAD-box proteins that function in ribosome assembly.
Intervention in gene regulatory networks with maximal phenotype alteration
Authors: Yousefi Mohammadmahdi R. , Dougherty Edward R.
Published: April 2013

Motivation: A basic issue for translational genomics is to model gene interaction via gene regulatory networks (GRNs) and thereby provide an informatics environment to study the effects of intervention (say, via drugs) and to derive effective intervention strategies. Taking the view that the phenotype is characterized by the long-run behavior (steady-state distribution) of the network, we desire interventions to optimally move the probability mass from undesirable to desirable states Heretofore, two external control approaches have been taken to shift the steady-state mass of a GRN: (i) use a user-defined cost function for which desirable shift of the steady-state mass is a by-product and (ii) use heuristics to design a greedy algorithm. Neither approach provides an optimal control policy relative to long-run behavior.

Results: We use a linear programming approach to optimally shift the steady-state mass from undesirable to desirable states, i.e. optimization is directly based on the amount of shift and therefore must outperform previously proposed methods. Moreover, the same basic linear programming structure is used for both unconstrained and constrained optimization, where in the latter case, constraints on the optimization limit the amount of mass that may be shifted to ‘ambiguous’ states, these being states that are not directly undesirable relative to the pathology of interest but which bear some perceived risk. We apply the method to probabilistic Boolean networks, but the theory applies to any Markovian GRN.

Availability:  Supplementary materials, including the simulation results, MATLAB source code and description of suboptimal methods are available at http://gsp.tamu.edu/Publications/supplementary/yousefi13b.

Contact:  edward@ece.tamu.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
The Methylation of the PcMYB10 Promoter Is Associated with Green-Skinned Sport in Max Red Bartlett Pear
Authors: Wang Zhigang , Meng Dong , Wang Aide , Li Tianlai , Jiang Shuling , Cong Peihua , Li Tianzhong
Published: April 2013

Varieties of the European pear (Pyrus communis) can produce trees with both red- and green-skinned fruits, such as the Max Red Bartlett (MRB) variety, although little is known about the mechanism behind this differential pigmentation. In this study, we investigated the pigmentation of MRB and its green-skinned sport (MRB-G). The results suggest that a reduction in anthocyanin concentration causes the MRB-G sport. Transcript levels of PcUFGT (for UDP-glucose:flavonoid 3-O-glucosyltransferase), the key structural gene in anthocyanin biosynthesis, paralleled the change of anthocyanin concentration in both MRB and MRB-G fruit. We cloned the PcMYB10 gene, a transcription factor associated with the promoter of PcUFGT. An investigation of the 2-kb region upstream of the ATG translation start site of PcMYB10 showed the regions −604 to −911 bp and −1,218 to −1,649 bp to be highly methylated. A comparison of the PcMYB10 promoter methylation level between the MRB and MRB-G forms indicated a correlation between hypermethylation and the green-skin phenotype. An Agrobacterium tumefaciens infiltration assay was conducted on young MRB fruits by using a plasmid constructed to silence endogenous PcMYB10 via DNA methylation. The infiltrated fruits showed blocked anthocyanin biosynthesis, higher methylation of the PcMYB10 promoter, and lower expression of PcMYB10 and PcUFGT. We suggest that the methylation level of PcMYB10 is associated with the formation of the green-skinned sport in the MRB pear. The potential mechanism behind the regulation of anthocyanin biosynthesis is discussed.
Earnings management, institutional shareholdings, and performance of SEO firms
Authors: Yang Wen‐Ben , Hsu Junming , Yang Tung‐Hsiao
Published: April 2013

Purpose

The purpose of this paper is to investigate the interaction between earnings management and institutional shareholdings of firms conducting seasoned equity offerings (SEOs).

Design/methodology/approach

The authors work on three issues: first, whether earnings management of firms conducting seasoned equity offerings (SEOs) affects institutional investors' investment in their stocks; second, whether SEO firms' earnings management induces insider selling; and third, whether earnings management and changes in old and new institutional shareholdings around SEOs can jointly predict the long‐run post‐issue performance.

Findings

The results show that firms with aggressive earnings management attract more new institutions to buy their shares and induce heavy insider selling after SEOs, but perform worse in the long run. Firms with conservative earnings management and a significant increase in new institutional shareholdings after SEOs perform well.

Originality/value

These results reveal that issuers manage earnings aggressively to be better off in the short run by obtaining more funds, receiving new institutional investment, and possibly allowing their insiders to sell stocks at higher prices, but to make shareholders worse off in long run by reducing their wealth. The positive relation between new institutions' participation and issuers' performance implies that some of these institutions have private information about or can effectively monitor SEO firms.
Polarisation of the society: a possible outcome of the economic crisis?
Authors: Deli‐Gray Zsuzsa , Árva Lászlo , Matura Tamás
Published: April 2013

Purpose

This paper aims to evaluate the results of an empirical research whose objective was the analysis of the impact of the actual economic crisis on the expectations, preferences and attitudes of the Hungarian people towards the purchase of food and household items in retail stores.

Design/methodology/approach

A review of literature is followed by the description and evaluation of an empirical research. A sample of 1,000 people was randomly selected and data were collected by a pre‐tested questionnaire. By main component analyses 12 main components were identified and a k‐component cluster analysis was performed.

Findings

The findings of the empirical research show that people of the same country react entirely differently to the crisis from a behavioural point of view and that in Hungary the economic crisis resulted in the social polarisation of the citizens.

Research limitations/implications

The paper provides evidence for the social polarisation of the Hungarian people which has a serious impact on their purchases in retail stores and which makes the retail store managers rethink their actual strategy and positioning. As the crisis continues there is room for a longitudinal study in the country and for a comparative cross cultural study in the region.

Originality/value

The paper shows an original approach of analysing how the Hungarian people's purchases of food and household items changed after the break‐out of the economic crises by using behavioural and psychographic variables as the basis of evaluations.