bluuebunny/crossref_metadata_2025 huggingface dataset:
Bisphenol A delays the perinatal chloride shift in cortical neurons by epigenetic effects on the
Kcc2
promoter
Authors: Yeo Michele , Berglund Ken , Hanna Michael , Guo Junjie U. , Kittur Jaya , Torres Maria D. , Abramowitz Joel , Busciglio Jorge , Gao Yuan , Birnbaumer Lutz , Liedtke Wolfgang B.
Published: February 2013

Bisphenol A (BPA) is a ubiquitous compound that is emerging as a possible toxicant during embryonic development. BPA has been shown to epigenetically affect the developing nervous system, but the molecular mechanisms are not clear. Here we demonstrate that BPA exposure in culture led to delay in the perinatal chloride shift caused by significant decrease in potassium chloride cotransporter 2 (
Kcc2
) mRNA expression in developing rat, mouse, and human cortical neurons. Neuronal chloride increased correspondingly. Treatment with epigenetic compounds decitabine and trichostatin A rescued the BPA effects as did knockdown of histone deacetylase 1 and combined knockdown histone deacetylase 1 and 2. Furthermore, BPA evoked increase in tangential interneuron migration and increased chloride in migrating neurons. Interestingly, BPA exerted its effect in a sexually dimorphic manner, with a more accentuated effect in females than males. By chromatin immunoprecipitation, we found a significant increase in binding of methyl-CpG binding protein 2 to the “cytosine-phosphate-guanine shores” of the
Kcc2
promoter, and decrease in binding of acetylated histone H3K9 surrounding the transcriptional start site. Methyl-CpG binding protein 2-expressing neurons were more abundant resulting from BPA exposure. The sexually dimorphic effect of BPA on
Kcc2
expression was also demonstrated in cortical neurons cultured from the offspring of BPA-fed mouse dams. In these neurons and in cortical slices, decitabine was found to rescue the effect of BPA on
Kcc2
expression. Overall, our results indicate that BPA can disrupt
Kcc2
gene expression through epigenetic mechanisms. Beyond increase in basic understanding, our findings have relevance for identifying unique neurodevelopmental toxicity mechanisms of BPA, which could possibly play a role in pathogenesis of human neurodevelopmental disorders.
Transketolase reaction under credible prebiotic conditions
Authors: Breslow Ronald , Appayee Chandrakumar
Published: February 2013

A transketolase reaction was catalyzed by cyanide ion under prebiotic conditions instead of its modern catalyst, thiamine pyrophosphate (TPP). Cyanide ion converted fructose plus glyceraldehyde to erythrose plus xylulose, the same products as are formed in modern biochemistry (but without the phosphate groups on the sugars). Cyanide was actually a better catalyst than was TPP in simple solution, where there is a negligible concentration of the C-2 anion of TPP, but of course not with an enzyme in modern biology. The cyanide ion was probably not toxic on prebiotic earth, but only when the oxygen atmosphere developed and iron porphyrin species were needed, which cyanide poisons. Thus, catalyses by TPP that are so important in modern biochemistry in the Calvin cycle for photosynthesis and the gluconic acid pathway for glucose oxidation, among other processes, were probably initially performed instead by cyanide ion until its toxicity with metalloproteins became a problem and primitive enzymes were present to work with TPP, or most likely its primitive precursors.
RETRACTED: Somatic hypermutation maintains antibody thermodynamic stability during affinity maturation
Authors: Wang Feng , Sen Shiladitya , Zhang Yong , Ahmad Insha , Zhu Xueyong , Wilson Ian A. , Smider Vaughn V. , Magliery Thomas J. , Schultz Peter G.
Published: February 2013

Somatic hypermutation and clonal selection lead to B cells expressing high-affinity antibodies. Here we show that somatic mutations not only play a critical role in antigen binding, they also affect the thermodynamic stability of the antibody molecule. Somatic mutations directly involved in antigen recognition by antibody 93F3, which binds a relatively small hapten, reduce the melting temperature compared with its germ-line precursor by up to 9 °C. The destabilizing effects of these mutations are compensated by additional somatic mutations located on surface loops distal to the antigen binding site. Similarly, somatic mutations enhance both the affinity and thermodynamic stability of antibody OKT3, which binds the large protein antigen CD3. Analysis of the crystal structures of 93F3 and OKT3 indicates that these somatic mutations modulate antibody stability primarily through the interface of the heavy and light chain variable domains. The historical view of antibody maturation has been that somatic hypermutation and subsequent clonal selection increase antigen–antibody specificity and binding energy. Our results suggest that this process also optimizes protein stability, and that many peripheral mutations that were considered to be neutral are required to offset deleterious effects of mutations that increase affinity. Thus, the immunological evolution of antibodies recapitulates on a much shorter timescale the natural evolution of enzymes in which function and thermodynamic stability are simultaneously enhanced through mutation and selection.
Free energy landscape for the binding process of Huperzine A to acetylcholinesterase
Authors: Bai Fang , Xu Yechun , Chen Jing , Liu Qiufeng , Gu Junfeng , Wang Xicheng , Ma Jianpeng , Li Honglin , Onuchic José N. , Jiang Hualiang
Published: February 2013

Drug-target residence time (
t
= 1/
k
off
, where
k
off
is the dissociation rate constant) has become an important index in discovering better- or best-in-class drugs. However, little effort has been dedicated to developing computational methods that can accurately predict this kinetic parameter or related parameters,
k
off
and activation free energy of dissociation (

). In this paper, energy landscape theory that has been developed to understand protein folding and function is extended to develop a generally applicable computational framework that is able to construct a complete ligand-target binding free energy landscape. This enables both the binding affinity and the binding kinetics to be accurately estimated. We applied this method to simulate the binding event of the anti-Alzheimer’s disease drug (−)−Huperzine A to its target acetylcholinesterase (AChE). The computational results are in excellent agreement with our concurrent experimental measurements. All of the predicted values of binding free energy and activation free energies of association and dissociation deviate from the experimental data only by less than 1 kcal/mol. The method also provides atomic resolution information for the (−)−Huperzine A binding pathway, which may be useful in designing more potent AChE inhibitors. We expect this methodology to be widely applicable to drug discovery and development.
Habitat Use and Separation among Congeneric Darter Species
Authors: Pratt Anne E. , Lauer Thomas E.
Published: February 2013

Five darter species (Greenside DarterEtheostoma blennioides, Rainbow DarterE. caeruleum, Fantail DarterE. flabellare, Johnny DarterE. nigrum, and Orangethroat DarterE. spectabile) were collected from seven streams and rivers in two Indiana watersheds to determine patterns of microhabitat selection with respect to depth, water velocity (flow), and substrate size. Heterogeneous habitats create a variety of niche dimensions, promoting the coexistence of congeneric species. Greenside and Rainbow darters were most commonly found among intermediate substrate sizes (cobble + boulder) and in locations with higher velocities and deeper water. Fantail and Orangethroat darters associated with intermediate to large substrate sizes (cobble + bedrock) were found in shallower water with lower velocities. Fantail Darters were only observed in the Whitewater River watershed. In contrast, Johnny Darters were observed only within the White River watershed among small substrate sizes (silt + sand), moderate velocities, and deeper water. Based on nonmetric multidimensional scaling and multinomial logistic regression, substrate size was the most important variable in characterizing microhabitat selection. Ultimately, habitats produced patterns of segregation and coexistence among these five darters in Indiana streams. Although ecological patterns of microhabitat use are additionally influenced by competition, morphology, and life history traits, heterogeneous habitat features within ecosystems appear to be structuring fish assemblages.
Comprehension of Marked Pronouns in Spanish and English: Object Anaphors Cross-Linguistically
Authors: Taylor Ryan C. , Stowe Laurie A. , Redeker Gisela , Hoeks John C. J.
Published: February 2013

Previous research on pronoun resolution has identified several individual factors that are deemed to be important for resolving reference. In this paper, we argue that of these factors, as tested here, plausibility is the most important, but interacts with form markedness and structural parallelism. We investigated how listeners resolved object pronouns that were ambiguous in the sense of having more than one possible antecedent. We manipulated the form of the anaphoric expression in terms of accentuation (English: Experiments 1a and 2a) and morphology (Spanish: Experiments 1b and 2b). We looked at sentences where both antecedents were equally plausible, or where only one of the antecedents was plausible. Listeners generally resolved toward the (parallel) grammatical object of the previous clause. When the pronouns were marked due to accentuation (English) or use of specific morphology (Spanish), preference switched to the alternative antecedent, the grammatical subject of the previous clause. In contrast, when one of the two antecedents was a much more plausible antecedent than the other, antecedent choice was almost wholly dictated by plausibility, although reference form prominence did significantly attenuate the strength of the preference.
Sequential actin-based pushing forces drive meiosis I chromosome migration and symmetry breaking in oocytes
Authors: Yi Kexi , Rubinstein Boris , Unruh Jay R. , Guo Fengli , Slaughter Brian D. , Li Rong
Published: February 2013

Polar body extrusion during oocyte maturation is critically dependent on asymmetric positioning of the meiotic spindle, which is established through migration of the meiosis I (MI) spindle/chromosomes from the oocyte interior to a subcortical location. In this study, we show that MI chromosome migration is biphasic and driven by consecutive actin-based pushing forces regulated by two actin nucleators, Fmn2, a formin family protein, and the Arp2/3 complex. Fmn2 was recruited to endoplasmic reticulum structures surrounding the MI spindle, where it nucleated actin filaments to initiate an initially slow and poorly directed motion of the spindle away from the cell center. A fast and highly directed second migration phase was driven by actin-mediated cytoplasmic streaming and occurred as the chromosomes reach a sufficient proximity to the cortex to activate the Arp2/3 complex. We propose that decisive symmetry breaking in mouse oocytes results from Fmn2-mediated perturbation of spindle position and the positive feedback loop between chromosome signal-induced Arp2/3 activation and Arp2/3-orchestrated cytoplasmic streaming that transports the chromosomes.
Monoclonal IgG antibodies generated from joint-derived B cells of RA patients have a strong bias toward citrullinated autoantigen recognition
Authors: Amara Khaled , Steen Johanna , Murray Fiona , Morbach Henner , Fernandez-Rodriguez Blanca M. , Joshua Vijay , Engström Marianne , Snir Omri , Israelsson Lena , Catrina Anca I. , Wardemann Hedda , Corti Davide , Meffre Eric , Klareskog Lars , Malmström Vivianne
Published: February 2013

Antibodies targeting citrullinated proteins (ACPAs [anticitrullinated protein antibodies]) are commonly found in patients with rheumatoid arthritis (RA), strongly associate with distinct HLA-DR alleles, and predict a more aggressive disease course as compared with seronegative patients. Still, many features of these antibodies, including their site of production and the extent of MHC class II–driven T cell help, remain unclarified. To address these questions, we have used a single B cell–based cloning technology to isolate and express immunoglobulin (Ig) genes from joint-derived B cells of active RA patients. We found ∼25% of synovial IgG-expressing B cells to be specific for citrullinated autoantigens in the investigated ACPA+ RA patients, whereas such antibodies were not found in ACPA− patients. The citrulline-reactive monoclonal antibodies did not react with the unmodified arginine peptides, yet several reacted with more than one citrullinated antigen. A role for active antigen selection of the citrulline-reactive synovial B cells was supported by the strong bias toward amino acid replacement mutations in ACPA+ antibodies and by their loss of reactivity to citrullinated autoantigens when somatic mutations were reverted to the corresponding germline sequences.
The degrees of categorical theories with recursive models
Authors: Andrews Uri
Published: February 2013

We show that even for categorical theories, recursiveness of the models guarantees no information regarding the complexity of the theory. In particular, we show that every tt-degree reducible to

0

(
ω
)

0^{(\omega )}

contains both

ℵ
1

\aleph _1

-categorical and

ℵ
0

\aleph _0

-categorical theories in finite languages, all of whose countable models have recursive presentations.
Naturality of symmetric imprimitivity theorems
Authors: an Huef Astrid , Kaliszewski S. , Raeburn Iain , Williams Dana
Published: February 2013

The first imprimitivity theorems identified the representations of groups or dynamical systems which are induced from representations of a subgroup. Symmetric imprimitivity theorems identify pairs of crossed products by different groups which are Morita equivalent and hence have the same representation theory. Here we consider commuting actions of groupsHHandKKon aC∗C^*-algebra which are saturated and proper as defined by Rieffel in 1990. Our main result says that the resulting Morita equivalence of crossed products is natural in the sense that it is compatible with homomorphisms and induction processes.
Galaxy pairs in the Local Group
Authors: Fattahi Azadeh , Navarro Julio F. , Starkenburg Else , Barber Christopher R. , McConnachie Alan W.
Published: February 2013

Current models of galaxy formation predict that galaxy pairs of comparable magnitudes should become increasingly rare with decreasing luminosity. This seems at odds with the relatively high frequency of pairings among dwarf galaxies in the Local Group. We use literature data to show that ∼30 per cent of all the satellites of the Milky Way and Andromeda galaxies brighter than MV = −8 are found in likely physical pairs of comparable luminosity. Besides the previously recognized pairings of the Magellanic Clouds and of NGC 147/NGC 185, other candidate pairs include the Ursa Minor and Draco dwarf spheroidals, as well as the And I/And III satellites of M31. These pairs are much closer than expected by chance if the radial and angular distributions of satellites were uncorrelated; in addition, they have very similar line-of-sight velocities and luminosities that differ by less than three magnitudes. In contrast, the same criteria pair fewer than 4 per cent of satellites in N-body/semi-analytic models that match the radial distribution and luminosity function of Local Group satellites. If confirmed in studies of larger samples, the high frequency of dwarf galaxy pairings may provide interesting clues to the formation of faint galaxies in the current cosmological paradigm.
Signature of outflows in strong Mg ii absorbers in quasar sightlines
Authors: Sharma Mahavir , Nath Biman B. , Chand Hum
Published: February 2013

We report a correlation between velocity offset (β = v/c) of strong Mg ii absorption systems and the bolometric luminosity (Lbol) of quasars in SDSS-DR7. We find that β shows a power-law increase with Lbol, with a slope ∼1/4. We find that such a relation of β with Lbol is expected for outflows driven by scattering of black hole radiation by dust grains, and which are launched from the innermost dust survival radius. Our results indicate that a significant fraction of the strong Mg ii absorbers, in the range of β = 0–0.4, may be associated with the quasars themselves.
A Rhamnose-Rich O-Antigen Mediates Adhesion, Virulence, and Host Colonization for the Xylem-Limited Phytopathogen Xylella fastidiosa
Authors: Clifford Jennifer C. , Rapicavoli Jeannette N. , Roper M. Caroline
Published: February 2013

Xylella fastidiosa is a gram-negative, xylem-limited bacterium that causes a lethal disease of grapevine called Pierce's disease. Lipopolysaccharide (LPS) composes approximately 75% of the outer membrane of gram-negative bacteria and, because it is largely displayed on the cell surface, it mediates interactions between the bacterial cell and its surrounding environment. LPS is composed of a conserved lipid A-core oligosaccharide component and a variable O-antigen portion. By targeting a key O-antigen biosynthetic gene, we demonstrate the contribution of the rhamnose-rich O-antigen to surface attachment, cell–cell aggregation, and biofilm maturation: critical steps for successful infection of the host xylem tissue. Moreover, we have demonstrated that a fully formed O-antigen moiety is an important virulence factor for Pierce's disease development in grape and that depletion of the O-antigen compromises its ability to colonize the host. It has long been speculated that cell-surface polysaccharides play a role in X. fastidiosa virulence and this study confirms that LPS is a major virulence factor for this important agricultural pathogen.
Citrus Huanglongbing: A Newly Relevant Disease Presents Unprecedented Challenges
Authors: Wang Nian , Trivedi Pankaj
Published: February 2013

Citrus huanglongbing (HLB) is one of the oldest citrus diseases and has been known for over a century. HLB is caused by ‘Candidatus Liberibacter’ spp. that are phloem-limited, fastidious α-proteobacteria and infect hosts in different Kingdoms (i.e., Animalia and Plantae). When compared with well-characterized, cultivatable plant-pathogenic Gram-negative bacteria, the interactions of uncultured insect-vectored plant-pathogenic bacteria, including ‘Ca. Liberibacter’ spp., with their hosts remain poorly understood. ‘Ca. Liberibacter’ spp. have been known to cause HLB, which has been rapidly spreading worldwide, resulting in dramatic economic losses. HLB presents an unprecedented challenge to citrus production. In this review, we focus on the most recent research on citrus, ‘Candidatus Liberibacter asiaticus’, and psyllid interactions, specifically considering the following topics: evolutionary relationships among ‘Ca. Liberibacter’ spp., genetic diversity, host range, genome analysis, transmission, virulence mechanisms, and the ecological importance of HLB. Currently, no efficient management strategy is available to control HLB, although some promising progress has been made. Further studies are needed to understand citrus, ‘Ca. L. asiaticus’, and psyllid interactions to design innovative management strategies. Although HLB has been problematic for over a century, we can only win the battle against HLB with a coordinated and deliberate effort by the citrus industry, citrus growers, researchers, legislatures, and governments.
The effect of raising and lowering tryptophan levels on human mood and social behaviour
Authors: Young Simon N.
Published: February 2013

Acute tryptophan depletion (ATD) studies indicate that low serotonin can lower mood and also increase aggression, although results vary somewhat between studies with similar participants. Lowering of mood after ATD is related to the susceptibility of the study participants to clinical depression, and some participants show no effect on mood. This indicates that low serotonin can contribute to lowered mood, but cannot—by itself—cause lowered mood, unless other unknown systems interact with serotonin to lower mood. Studies using tryptophan supplementation demonstrate that increased serotonin can decrease quarrelsomeness and increase agreeableness in everyday life. Social interactions that are more agreeable and less quarrelsome are associated with better mood. Thus, serotonin may have direct effects on mood, but may also be able to influence mood through changes in social behaviour. The increased agreeableness and decreased quarrelsomeness resulting from increases in serotonin will help foster congenial relations with others and should help to increase social support. As social support and social isolation have an important relationship with both physical and mental health, more research is needed on the implications of the ability of serotonin to modulate social behaviour for the regulation of mood, and for future physical and mental health.
Identifying serotonergic mechanisms underlying the corticolimbic response to threat in humans
Authors: Fisher Patrick M. , Hariri Ahmad R.
Published: February 2013

A corticolimbic circuit including the amygdala and medial prefrontal cortex (mPFC) plays an important role in regulating sensitivity to threat, which is heightened in mood and anxiety disorders. Serotonin is a potent neuromodulator of this circuit; however, specific serotonergic mechanisms mediating these effects are not fully understood. Recent studies have evaluated molecular mechanisms mediating the effects of serotonin signalling on corticolimbic circuit function using a multi-modal neuroimaging strategy incorporating positron emission tomography and blood oxygen level-dependent functional magnetic resonance imaging. This multi-modal neuroimaging strategy can be integrated with additional techniques including imaging genetics and pharmacological challenge paradigms to more clearly understand how serotonin signalling modulates neural pathways underlying sensitivity to threat. Integrating these methodological approaches offers novel opportunities to identify mechanisms through which serotonin signalling contributes to differences in brain function and behaviour, which in turn can illuminate factors that confer risk for illness and inform the development of more effective treatment strategies.
‘It's the way that you look at it’—a cognitive neuropsychological account of SSRI action in depression
Authors: Harmer Catherine J. , Cowen Philip J.
Published: February 2013

The fact that selective serotonin reuptake inhibitors (SSRIs) have antidepressant effects in some patients supports the notion that serotonin plays a role in the mode of action of antidepressant drugs. However, neither the way in which serotonin may alleviate depressed mood  nor the reason why several weeks needs to elapse before the full antidepressant effect of treatment is expressed  is known. Here, we propose a neuropsychological theory of SSRI antidepressant action based on the ability of SSRIs to produce positive biases in the processing of emotional information. Both behavioural and neuroimaging studies show that SSRI administration produces positive biases in attention, appraisal and memory from the earliest stages of treatment, well before the time that clinical improvement in mood becomes apparent. We suggest that the delay in the clinical effect of SSRIs can be explained by the time needed for this positive bias in implicit emotional processing to become apparent at a subjective, conscious level. This process is likely to involve the re-learning of emotional associations in a new, more positive emotional environment. This suggests intriguing links between the effect of SSRIs to promote synaptic plasticity and neurogenesis, and their ability to remediate negative emotional biases in depressed patients.
The neurobiology of depression—revisiting the serotonin hypothesis. II. Genetic, epigenetic and clinical studies
Authors: Albert Paul R. , Benkelfat Chawki
Published: February 2013

The serotonin system originates from a small number of neurons (a few hundred thousand of the 100 billion in man) located in the midbrain raphe nuclei, that project widely throughout the central nervous system to influence a large array of inter-related biological functions, not least of which are circuits involved in mood and emotion. The serotonin hypothesis of depression has postulated that a reduction in serotonin leads to increased predisposition to depression. Indeed, it has become evident from therapeutic strategies that affect serotonin activity, that alterations in serotonin may not only predispose to depression, but also to aggressive behaviour, impulsivity, obsessive–compulsive behaviour and suicide. Many potential mechanisms known to alter the genes that regulate the serotonin system, including developmental epigenetic modifications, are presented, as additional evidence implicating the serotonin system. This second issue of two special issues of
Philosophical Transactions B
presents a series of reviews, perspectives and new findings that argue that the serotonin hypothesis remains an important idea that continues to guide research into the aetiology and treatment of depression.
Serotonin and beyond: therapeutics for major depression
Authors: Blier Pierre , El Mansari Mostafa
Published: February 2013

The serotonin (5-HT, 5-hydroxytryptamine) system has been implicated in the pathogenesis of major depressive disorder (MDD). The case for its contribution to the therapeutic efficacy of a wide variety of antidepressant treatments is, however, much stronger. All antidepressant strategies have been shown to enhance 5-HT transmission in the brain of laboratory animals. Catecholamines, norepinephrine (NE) and dopamine (DA) can also play a pivotal role in the mechanism of action of certain antidepressant strategies. The enhancement of 5-HT transmission by selective serotonin reuptake inhibitors, which leads to a dampening of the activity of NE and DA neurons, may account in part for the low remission rate achieved with these medications and/or the residuals symptoms after remission is achieved. The functional connectivity between the 5-HT, NE and DA systems can be used to understand the mechanism of action of a wide variety of augmentation strategies in treatment-resistant MDD. Proof-of-concept studies have shown that antidepressant medications with complementary mechanisms of action on monoaminergic systems can double the remission rate achieved in a trial of standard duration. Novel approaches are also being used to treat MDD, which also appear to involve the monoaminergic system(s) to a varying extent.
High-Frequency Thin-Film AlN-on-Diamond Lateral–Extensional Resonators
Authors: Fatemi Hediyeh , Zeng Hongjun , Carlisle John , Abdolvand Reza
Published: February 2013

In this paper, low-impedance lateral–extensional microresonators are fabricated on a stack of aluminum nitride (AlN) directly deposited on a polished ultrananocrystalline diamond (UNCD) film. The large acoustic velocity of UNCD is utilized to extend the frequency of such resonators beyond 1 GHz while the frequency-defining features are not reduced excessively. In order to promote the growth of a

$c$

-plane piezoelectric AlN film, the surface of the UNCD film is polished after deposition. Three different UNCD films with different Young's modulus values were prepared, and frequencies up to two times that of similar devices fabricated on silicon have been achieved. The finite-element analysis is employed to evaluate the effect of various physical parameters on the performance of the thin-film piezoelectric-on-substrate resonators in order to achieve very low motional resistance

$(R_{m})$

. Several resonators were designed with various lateral dimensions and different numbers of support tethers to evaluate the propositions. The lowest

$R_{m}$

 was measured from a multitethered 29th-order thin-film piezoelectric-on-diamond (TPoD) resonator (22

 $Omega$

) and

$fcdot Q$

 product of

$2.72 ast 10^{12}$

 at 888 MHz. The temperature coefficient of frequency of this TPoD resonator is measured to be

$-9.6 hbox{ppm}/^{circ} hbox{C}$

, which is much lower than that of the devices fabricated on silicon. Also, this device can withstand input powers up to

$+$

27 dBm, leading to a delivered power density per unit area of

$sim!!2.9 muhbox{W}/muhbox{m}^{2}$

.

$hfill$

[2012-0099]
Lethal drought leads to reduction in nonstructural carbohydrates in Norway spruce tree roots but not in the canopy
Authors: Hartmann Henrik , Ziegler Waldemar , Trumbore Susan
Published: February 2013

Heat waves and droughts are expected to increase in frequency and severity in many regions with future climate change, threatening the survival of a number of forest ecosystems. However, our understanding of the physiological processes and mechanisms underlying drought‐induced tree mortality is incomplete. Here, we present results on the physiological response of young Norway spruce trees exposed to lethal drought stress.

We applied three levels of drought treatment (control, drying–rewetting, complete drought) and monitored relevant physiological functions and processes of carbon and water relations at high temporal resolution until tree death occurred.

Only trees subjected to continuous drought died in our experiment. Trees subjected to drying–rewetting cycles consistently recovered in their ability to transport water, indicating that these trees do not suffer permanent damage to the hydraulic system. In all cases, drought reduced carbon assimilation, caused changes in carbon allocation and appeared to have severely reduced phloem functioning and carbon translocation. Structural growth was sacrificed for carbon investment in maintenance respiration and osmoprotection. Severe drought caused trees to rely on stored carbon reserves but, in contrast to above‐ground tissues, only root carbon pools were strongly reduced when trees died.

Our results indicate that drought‐induced changes in carbon allocation, use and transport differ between above‐ and below‐ground tissues in trees. While root death may have been caused by carbon depletion, this was definitely not the case in above‐ground tissues. Our findings indicate that mortality mechanisms are not defined at the organism level but rather within tree compartments.
“The Faith Society”? Quantifying Religious Belonging in Edwardian Britain, 1901–1914
Authors: Field Clive D.
Published: February 2013

Historians disagree about how the Edwardian era fits into the jigsaw of secularisation in Britain. Was it a time of religious crisis (Keith Robbins, Hugh McLeod) or a faith society (Callum Brown)? This article subjects the debate to quantitative scrutiny by examining the available statistics of church attendance and church membership/affiliation for 1901–1914. A mixed picture is reported, with elements of sacralisation and secularisation co‐existing. Although churchgoing was already in relative and absolute decline, one‐quarter of adults (disproportionately women) still worshipped on any given Sunday and two‐fifths at least monthly. Moreover, hardly anybody failed to be reached by a rite of passage conducted on religious premises. Only 1 per cent professed no faith and just over one‐half had some reasonably regular and meaningful relationship with organised religion in terms of church membership or adherence. For children, perhaps nine‐tenths attended Sunday school, however briefly.
Finding Antichrist: Apocalypticism in Nineteenth‐Century Catholic England and the Writings of Frederick Faber
Authors: Leighton Cadoc
Published: February 2013

The article discusses the apocalyptic beliefs of the nineteenth‐century English Oratorian and devotional writer, Frederick Faber, though initially providing a context among earlier and contemporary English Catholic apocalyptic writers. It proceeds, by means of a consideration of Faber's conscious de‐secularisation of language, to give an account of his identification of the elements of a transvalued contemporary popular concept of modernity as the signs of apocalyptic crisis. The article as a whole is intended to provide an aid to the perception and understanding of a pervasive apocalypticism in nineteenth‐century English‐speaking Catholicism.
Does method of birth make a difference to when women resume sex after childbirth?
Authors: McDonald EA , Brown SJ
Published: February 2013

Objective

To investigate the timing of resumption of vaginal sex and assess associations with method of birth, perineal trauma and other obstetric and social factors.

Design

Prospective pregnancy cohort study of nulliparous women.

Setting

Melbourne, Australia.

Sample

A total of 1507 nulliparous women recruited in early pregnancy (≤24 weeks).

Method

Women were recruited from six public hospitals. Data from hospital records and self‐administered questionnaires at recruitment and 3, 6 and 12 months postpartum were analysed using univariable and multivariable logistic regression.

Main outcome measure

Resumption of vaginal sex.

Results

Sexual activity was resumed earlier than vaginal sex, with 53% resuming sexual activity by 6 weeks postpartum, and 41% attempting vaginal sex. By 8 weeks a majority of women had attempted vaginal sex (65%), increasing to 78% by 12 weeks, and 94% by 6 months. Compared with women who had a spontaneous vaginal birth with an intact perineum, women who had a spontaneous vaginal birth with an episiotomy (adjusted odds ratio 3.43, 95% confidence interval 1.9–6.2) or sutured perineal tear (adjusted odds ratio 3.18, 95% confidence interval 2.1–4.9) were more likely not to have resumed vaginal sex by 6 weeks postpartum. Similarly, women who had an assisted vaginal birth or caesarean section had raised odds of delaying resumption of sex.

Conclusions

Most women having a first birth do not resume vaginal sex until later than 6 weeks postpartum. Women who have an operative vaginal birth, caesarean section or perineal tear or episiotomy appear to delay longer.
The Influence of Fetal Ethanol Exposure on Subsequent Development of the Cerebral Cortex as Revealed by Magnetic Resonance Imaging
Authors: Leigland Lindsey A. , Ford Matthew M. , Lerch Jason P. , Kroenke Christopher D.
Published: February 2013

Background

Fetal alcohol syndrome and related disorders (commonly referred to as fetal alcohol spectrum disorder, or FASD) cause significant hardships to the individuals affected. Previously, histological studies in animals have characterized developmental cerebral cortical abnormalities that result from prenatal ethanol (EtOH) exposure. Additionally, magnetic resonance imaging (MRI) studies have identified abnormalities associated with fetal EtOH exposure in the cerebral cortices of human children and adolescents. However, there is still a need to bridge the gap between human MRI studies and animal histological studies. The goal of the research presented here was to perform postmortem MRI experiments on rodents, during time periods relative to late human gestation through adulthood, to characterize anomalies associated with FASD throughout development. Additionally, by determining how histologically identified abnormalities are manifest in MRI measurements specifically during the critical early time points, neuroimaging‐based biomarkers of FASD can potentially be identified at much earlier ages in humans, thus reducing the impact of these disorders.

Methods

Cerebral cortical volume, thickness, and surface area were characterized by ex vivo MRI in Long‐Evans rat pups born from dams that were EtOH‐treated, maltose/dextrin‐treated, or untreated throughout gestation at 6 developmental time points (postnatal day [P] 0, P3, P6, P11, P19, and P60).

Results

Brain volume, isocortical volume, isocortical thickness, and isocortical surface area were all demonstrated to be reduced following prenatal exposure to EtOH. Significant differences among the treatment groups were observed throughout the range of time points studied, allowing for a comprehensive view of FASD influenced MRI outcomes throughout development. Isocortical surface area and isocortical thickness results contributed independent information important to interpreting effects of prenatal EtOH exposure on cerebral cortical development. Additionally, regional patterns in cortical thickness differences suggested primary sensory areas were particularly vulnerable to gestational EtOH exposure.

Conclusions

Structural MRI measurements were in accordance with previous histological studies performed in animal models of FASD. In addition to establishing a summary of MRI outcomes throughout development in FASD, this research suggests that MRI techniques are sufficiently sensitive to detect neuroanatomical effects of fetal EtOH exposure on development of the cerebral cortex during the period of time corresponding to late gestation in humans. Importantly, this research provides a link between animal histological data and human MRI data.
Effects of the feeding sequence of concentrate and forage and the feeding ratio of sake cake to grass hay on the characteristics and the entrapment effect of the ruminal mat in non‐lactating dairy cows
Authors: Izumi Kenichi
Published: February 2013

The effects of the feeding sequence of concentrate and forage, and of the feeding ratio of sake cake (SC) to grass hay (GH) on the ruminal mat characteristics and the entrapment effect for steamed flaked corn (SFC) by the mat were evaluated. Three non‐lactating, rumen‐cannulated Holstein cows were offered SC and GH using a ratio of 35:65 (SC35) or 65:35 (SC65). For SC35, SFC was fed at 1 h after or immediately before offering SC and GH, while for SC65, SFC was only fed at 1 h after. To estimate the degree of SFC entrapment in the ruminal mat, the location of SFC in the rumen and two types of mean retention time (MRT) were measured, that is, MRT for the SFC marker placed directly on the mat or taken orally. The ruminal mat was formed even when SC65 diet was consumed. The entrapment effect was not affected by the feeding sequence or the ratio. However, a more interesting finding is that the entrapment effect of the ruminal mat may not be as absolute as previously considered because of the large amount of SFC particles which precipitated at the bottom of the rumen 1 h after feeding.
Circulating N‐cadherin levels are a negative prognostic indicator in patients with multiple myeloma
Authors: Vandyke Kate , Chow Annie W.S. , Williams Sharon A. , To Luen B. , Zannettino Andrew C.W.
Published: February 2013

N‐cadherin (cadherin 2, type 1, N‐cadherin (neuronal); CDN2) is a homotypic adhesion molecule that is upregulated in breast, prostate and bladder cancer. Here we investigated the prognostic significance of upregulated N‐cadherin expression in multiple myeloma (MM). Our results indicate that N‐cadherin protein and gene expression is abnormally increased in trephine biopsies and CD38++/CD138+ plasma cells from MM patients, when compared with those of normal donors. In addition, levels of circulating N‐cadherin were elevated in a subset of patients with MM (n = 81; mean: 14·50 ng/ml, range: 0–146·78 ng/ml), relative to age‐matched controls (n = 27; mean: 2·66 ng/ml, range: 0–5·96 ng/ml), although this did not reach statistical significance. Notably, patients with abnormally high levels of N‐cadherin (>6 ng/ml) had decreased progression‐free survival (P = 0·036; hazard ratio: 1·94) and overall survival (P = 0·002; hazard ratio: 3·15), when compared with patients with normal N‐cadherin levels (≤6 ng/ml). Furthermore, multivariate analyses revealed that the combination of N‐cadherin levels and International Staging System (ISS) was a more powerful prognostic indicator than using ISS alone. Collectively, our studies demonstrate that circulating N‐cadherin levels are a viable prognostic marker for high‐risk MM patients.
Merkel cell polyomavirus large T antigen is detected in rare cases of nonmelanoma skin cancer
Authors: Mertz Kirsten D. , Paasinen Aino , Arnold Andreas , Baumann Michèle , Offner Felix , Willi Niels , Cathomas Gieri
Published: February 2013

Background

Studies of Merkel cell polyomavirus (MCPyV) in nonmelanoma skin cancers (NMSC) other than Merkel cell carcinoma (MCC) produced controversial results. Therefore, we studied the prevalence of MCPyV in basal cell carcinoma (BCC) and in squamous cell carcinoma (SCC).

Methods

Tissue specimens were analyzed for the presence of MCPyV DNA by conventional polymerase chain reaction (PCR). Expression of MCPyV large T protein was determined by immunohistochemistry.

Results

MCPyV DNA was frequently detected in skin cancers by PCR, in 36 of 88 BCCs, in 21 of 75 SCCs and in 10 of 47 normal skin samples. In BCC, a significant difference in the detection rate compared to normal skin was observed. In contrast, weak reactivity for MCPyV large T antigen was detected only sporadically in immunosuppressed patients (2 of 88 BCCs, 1 of 75 SCCs). Mutations of the large T antigen of MCPyV were more frequently observed in MCC than in BCC/SCC.

Conclusions

Our results suggest that the frequent detection of the MCPyV genome in NMSC by PCR reflects ubiquitous spread of the virus. However, the low immunohistochemical detection rate of MCPyV and the lack of MCC‐specific MCPyV mutations argue against an essential role of MCPyV in the development of skin cancers other than MCC.
Livedoid vasculopathy – current aspects of diagnosis and treatment of cutaneous infarction
Authors: Kerk Nina , Goerge Tobias
Published: February 2013

Livedoid vasculopathy is a rare, chronic, recurrent disease of the cutaneous microcirculation. Its typical clinical manifestation is a triad which consists of livedo racemosa of the skin, episodic painful ulcerations of the distal aspects of the legs and a healing process leaving small porcelain‐white scars called atrophie blanche. As an important result of recent research, livedoid vasculopathy has been defined as a coagulation disorder classified as a vasculopathy different from inflammatory vasculitis. This differentiation adds to the current pathophysiologic understanding and supports the therapeutic rationale with respect to the use of new systemic anticoagulants. The prevention of irreversible residual scarring and the improvement of patientsí quality of life are the main goals in treating cutaneous infarction and require early and consequent treatment. This article presents current knowledge on diagnosing this rare disease and offers practical guidance on its therapy.
Live‐cell analysis of plant reproduction: Live‐cell imaging, optical manipulation, and advanced microscopy technologies
Authors: Kurihara Daisuke , Hamamura Yuki , Higashiyama Tetsuya
Published: February 2013

Sexual reproduction ensures propagation of species and enhances genetic diversity within populations. In flowering plants, sexual reproduction requires complicated and multi‐step cell‐to‐cell communications among male and female cells. However, the confined nature of plant reproduction processes, which occur in the female reproductive organs and several cell layers of the pistil, limits our ability to observe these events in vivo. In this review, we discuss recent live‐cell imaging in in vitro systems and the optical manipulation techniques that are used to capture the dynamic mechanisms representing molecular and cellular communications in sexual plant reproduction.
Did support for economic and political reforms increase during the post‐communist transition, and if so, why?
Authors: Rovelli Riccardo , Zaiceva Anzelika
Published: February 2013

We study the dynamics of individual support for changes in the economic and political system, using a unique dataset for 12 transition economies over the period 1991–2004. We document that support for transition was initially lower in theCIScountries and that there has been a converging trend in the support for reforms between theCISand the Baltic and Central and Eastern European countries. We suggest several explanations for the initial divergence and the post‐98 convergence in support for transition between these three groups of countries, and show that economic growth, declining income inequality and improving quality of governance have contributed to increase the support for transition. In addition, we find that increased support for the market economy and democracy in theCISis accompanied by a larger increase in trust towards the political institutions. Our results also confirm the implications of Aghionet al. ()'s model of a negative correlation between trust and the demand for government regulation.
Detection efficiency and habitat use to inform inventory and monitoring efforts: juvenile coho salmon in the Knik River basin, Alaska
Authors: Sethi Suresh A. , Benolkin Elizabeth
Published: February 2013

Imperfect detection associated with sampling gear presents challenges for wildlife inventory and monitoring efforts. We examined occupancy dynamics and habitat use of juvenile coho salmon, Oncorhynchus kisutch, in shallow lake environments over a summer and early fall season in the Knik River area of south central Alaska using models which control for and estimate sampling gear detection efficiency. In addition, we present statements for the probability that observed absences at a survey site or from a survey area (a collection of sites) are true absences given some amount of sampling effort and analysts' beliefs about site occupancy and sampling gear detection efficiency which can be used to guide inventory and monitoring efforts for juvenile salmon or other wildlife and plant species. Occupancy modelling results demonstrate that minnow traps were effective at sampling juvenile coho in shallow lake environments, with a mean probability of detection across the study period of 0.68 (i.e., probability of detecting the presence of juvenile coho given that they are present at a trap site; SE = 0.03). Juvenile coho salmon migrated into shallow water lakes in late summer and early fall, presumably to seek out overwinter habitat. N‐mixture modelling examination of habitat use demonstrated that once in shallow lake environments, juvenile coho were widely distributed across a range of microhabitats, with some evidence for preference for shallower depths and warmer water temperatures.
Diagnostic potential of hepcidin testing in pediatrics
Authors: Cangemi Giuliana , Pistorio Angela , Miano Maurizio , Gattorno Marco , Acquila Maura , Bicocchi Maria Patrizia , Gastaldi Roberto , Riccardi Francesca , Gatti Cinzia , Fioredda Francesca , Calvillo Michaela , Melioli Giovanni , Martini Alberto , Dufour Carlo
Published: February 2013

Objectives

Hepcidin, a peptide hormone released by hepatocytes into circulation is the main regulator of dietary iron absorption and cellular iron release. Although commercial tests are available, assay harmonization for hepcidin has not been yet reached, making reference intervals and consequent clinical decisions still elusive for each assay and specific population. The aim of this study is to set up hepcidin measurement in pediatric age and to investigate its potential usefulness in the diagnosis and management of iron disorders in children.

Methods

Serum hepcidin was measured by using an automated commercial immunoassay. Reference values were obtained from 86 healthy children. Hepcidin was then evaluated in 52 children with diseases where this hormone was expected to be differently regulated.

Results

Hepcidin values were 43.6 ng/mL median; 32–52.7 1–3 q: in males and 36.4 ng/mL median; 28.5–45.7 1–3 q: in females (P = 0.039). Hepcidin was significantly higher in postpubertal normal females than in normal males. Hepcidin resulted up‐regulated in anemia of chronic disease of children affected by systemic Juvenile Idiopathic Arthritis and decreased after treatment with anakinra, an anti‐interleukin‐1 receptor antagonist. In iron deficiency anemia patients on oral iron supplementation and in β‐thalassemia subjects, hepcidin levels were similar to those found in healthy subjects.

Conclusions

This study sets up reference values for pediatric population and shows that in normal controls serum hepcidin react differently to puberty in females vs. males. In addition, it suggests that serum hepcidin may discriminate microcytic inflammatory anemia of Juvenile Idiopathic Arthritis from iron deficiency anemia. Overall these findings may represent a helpful tool for future studies tailored to understand the role of hepcidin in management of iron disorders in children.