bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and neurocognitive outcome in symptomatic isovaleric acidemia
Authors: Grünert Sarah C , Wendel Udo , Lindner Martin , Leichsenring Michael , Schwab K Otfried , Vockley Jerry , Lehnert Willy , Ensenauer Regina
Published: January 2012

Background

Despite its first description over 40 years ago, knowledge of the clinical course of isovaleric acidemia (IVA), a disorder predisposing to severe acidotic episodes during catabolic stress, is still anecdotal. We aimed to investigate the phenotypic presentation and factors determining the neurological and neurocognitive outcomes of patients diagnosed with IVA following clinical manifestation.

Methods

Retrospective data on 21 children and adults with symptomatic IVA diagnosed from 1976 to 1999 were analyzed for outcome determinants including age at diagnosis and number of catabolic episodes. Sixteen of 21 patients were evaluated cross-sectionally focusing on the neurological and neurocognitive status. Additionally, 155 cases of patients with IVA published in the international literature were reviewed and analyzed for outcome parameters including mortality.

Results

57% of study patients (12/21) were diagnosed within the first weeks of life and 43% (9/21) in childhood. An acute metabolic attack was the main cause of diagnostic work-up. 44% of investigated study patients (7/16) showed mild motor dysfunction and only 19% (3/16) had cognitive deficits. No other organ complications were found. The patients' intelligence quotient was not related to the number of catabolic episodes but was inversely related to age at diagnosis. In published cases, mortality was high (33%) if associated with neonatal diagnosis, following manifestation at an average age of 7 days.

Conclusions

Within the group of "classical" organic acidurias, IVA appears to be exceptional considering its milder neuropathologic implications. The potential to avoid neonatal mortality and to improve neurologic and cognitive outcome under early treatment reinforces IVA to be qualified for newborn screening.
Serum TSH and Risk of Papillary Thyroid Cancer in Nodular Thyroid Disease
Authors: Fiore Emilio , Vitti Paolo
Published: January 2012

Context:

TSH is the main factor involved in the control of proliferation of thyrocytes. Recently, a strong relationship between serum TSH and risk of thyroid malignancy has been reported.

Objectives:

The aim was to review published papers about the relationship between serum TSH and frequency of differentiated thyroid cancer.

Evidence Acquisition:

PubMed was used to identify studies focused on the relationship between TSH and differentiated thyroid cancer.

Evidence Synthesis:

In patients with nodular thyroid disease, the risk of thyroid malignancy increases with serum TSH, and even within normal ranges, higher TSH values are associated with a higher frequency and more advanced stage of thyroid cancer. The likelihood of papillary thyroid carcinoma is reduced when TSH is lower, as in thyroid autonomy, and increased when TSH is higher, as in thyroid autoimmunity. Treatment with l-thyroxine (LT4), which reduces serum TSH, is associated with significantly lower risk of developing clinically detectable thyroid cancer.

Conclusions:

TSH plays a key role in the development of clinically detectable thyroid cancer, and LT4 treatment reduces the risk of thyroid malignancy in patients with nodular thyroid disease. According to the guidelines of the main scientific societies, LT4 therapy is not currently recommended for the treatment of patients with nodular goiter. Even if the available data are not sufficient to advise LT4 treatment in all patients with nodular goiter with the aim of reducing the risk of papillary thyroid carcinoma, we propose that this indication should be reconsidered, taking into account recent evidence reported in the literature.
Virtue, Identity, and Agency
Authors: Herdt Jennifer A.
Published: January 2012

Despite a vibrant revival of the ethics of virtue, now spanning several decades, the discourse of virtue in later medieval and early modern thought and the distinctive forms this reflection takes across varying genres and social settings have been insufficiently integrated into narratives of the history of virtue ethics. The aim of this special issue is to remedy this lack by bringing together philosophical, theological, historical, and literary studies of virtue and the virtues in key thinkers, texts, and sociocultural contexts from the thirteenth through the seventeenth centuries. Varied as these essays are, common preoccupations emerge: with the dependent or independent character of virtuous agency, with the problems posed by self-love in both individual and collective manifestations, and with identifying the social conditions for the discernment and cultivation of the virtues. Even if the pagan discourse of virtue had been adopted by Christianity in its earliest centuries, both medieval and early modern European thinkers continued to wrestle with the interface between divine formation and social formation and their implications for the character of human moral agency.
Jesus in the Moral Theology of Thomas Aquinas
Authors: Wawrykow Joseph
Published: January 2012

That virtue is important in the ethics of Aquinas is generally acknowledged. So too is the fundamentally theological cast of Aquinas’s virtue ethics. In his reflections on the ethical life, Aquinas is especially concerned with the good willing and doing, made possible by virtue, that brings a person to the God who has established God as the beatifying end of the human person; and, the virtues that are most conducive to that life with God are, radically, the gift of God, due to divine initiative. Although less immediately obvious, Aquinas’s virtue ethics is also thoroughly Christocentric: it is in relation to Christ, who is model and savior, that a human being receives and grows in the virtues, and so moves closer to the beatifying end that is God. This article examines the Christological dimensions of the virtue ethics of Aquinas, suggesting along the way the implications for a modern engagement with that ethics.
Heroic Virtue in Blessed Raymond of Capua’s Life of Catherine of Siena
Authors: Astell Ann W.
Published: January 2012

Composed at a point of significant transition in the history of hagiography as a genre, due to changes in the canonization process, Raymond of Capua’s Life of Catherine of Siena (1395) endeavors to attest to her heroic virtue by using both traditional discourse and the new scholastic discourse. Raymond’s fidelity to Catherine’s own doctrine of the virtues puts his argument in tension with that of Saint Thomas Aquinas.
Language Goes on Holiday: English Allegorical Drama and the Virtue Tradition
Authors: Beckwith Sarah
Published: January 2012

This article explores the virtue tradition in the English theatrical tradition of morality theater and its fortunes on the professional stage. It explores questions of recognition in allegorical drama by examining “mankind” and “mercy” in the morality play Mankind, the appropriation of this tradition by the forces of commerce in The Three Ladies of London and The Three Lords and Ladies of London, and Jonson’s hilarious use of the tradition in The Devil Is An Ass. Ordinary language philosophy helps to reveal what is at stake in this verbal drama of recognition.
Luther’s Attack on Self-Love: The Failure of Pagan Virtue
Authors: Irwin Terence
Published: January 2012

Luther’s denials (in his Commentary on Romans) of the natural capacity to acquire moral virtues rest on three assumptions. (1) Virtue requires the pursuit of virtuous action for its own sake. (2) In the state of sin, human aims and motives are all controlled by self-love. (3) Insofar as aims and motives are controlled by self-love, they are sinful and contrary to the demands of morality. Any aspiration to virtue of character, therefore, is misguided, given the dominance of self-love in the state of sin. This selective endorsement of some eudaemonist and some anti-eudaemonist claims about virtue and motivation results in an unstable position. Luther does not vindicate his claim that everyone is naturally incapable of moral virtue, because everyone is naturally dominated by self-love.
The roles of FGF and MAP kinase signaling in the segregation of the epiblast and hypoblast cell lineages in bovine and human embryos
Authors: Kuijk Ewart W. , van Tol Leni T. A. , Van de Velde Hilde , Wubbolts Richard , Welling Maaike , Geijsen Niels , Roelen Bernard A. J.
Published: January 2012

At the blastocyst stage of mammalian pre-implantation development, three distinct cell lineages have formed: trophectoderm, hypoblast (primitive endoderm) and epiblast. The inability to derive embryonic stem (ES) cell lines in a variety of species suggests divergence between species in the cell signaling pathways involved in early lineage specification. In mouse, segregation of the primitive endoderm lineage from the pluripotent epiblast lineage depends on FGF/MAP kinase signaling, but it is unknown whether this is conserved between species. Here we examined segregation of the hypoblast and epiblast lineages in bovine and human embryos through modulation of FGF/MAP kinase signaling pathways in cultured embryos. Bovine embryos stimulated with FGF4 and heparin form inner cell masses (ICMs) composed entirely of hypoblast cells and no epiblast cells. Inhibition of MEK in bovine embryos results in ICMs with increased epiblast precursors and decreased hypoblast precursors. The hypoblast precursor population was not fully ablated upon MEK inhibition, indicating that other factors are involved in hypoblast differentiation. Surprisingly, inhibition of FGF signaling upstream of MEK had no effects on epiblast and hypoblast precursor numbers in bovine development, suggesting that GATA6 expression is not dependent on FGF signaling. By contrast, in human embryos, inhibition of MEK did not significantly alter epiblast or hypoblast precursor numbers despite the ability of the MEK inhibitor to potently inhibit ERK phosphorylation in human ES cells. These findings demonstrate intrinsic differences in early mammalian development in the role of the FGF/MAP kinase signaling pathways in governing hypoblast versus epiblast lineage choices.
Long-term nose-only cigarette smoke exposure induces emphysema and mild skeletal muscle dysfunction in mice
Authors: Rinaldi Manuela , Maes Karen , De Vleeschauwer Stéphanie , Thomas Debby , Verbeken Erik K. , Decramer Marc , Janssens Wim , Gayan-Ramirez Ghislaine N
Published: January 2012

Mouse models of chronic obstructive pulmonary disease (COPD) focus on airway inflammation and lung histology, but their use has been hampered by the lack of pulmonary function data in their assessment. Systemic effects such as muscle dysfunction are also poorly modeled in emphysematous mice. We aimed to develop a cigarette-smoke-induced emphysema mouse model in which serial lung function and muscular dysfunction could be assessed, allowing the disease to be monitored more appropriately. C57Bl6 mice were nose-only exposed to cigarette smoke or filtered air for 3-6 months. Lung function tests were repeated in the same mice after 3 and 6 months of cigarette smoke or air exposure and compared with lung histological changes. Contractile properties of skeletal muscles and muscle histology were also determined at similar time points in separate groups of mice. Serial lung function measurements documented hyperinflation after 3 and 6 months of cigarette smoke exposure, with a significant 31-37% increase in total lung capacity (TLC) and a significant 26-35% increase in compliance (Cchord) when compared with animals exposed to filtered air only (P<0.001 after 3 and after 6 months). These functional changes preceded the changes in mean linear intercept, which became only significant after 6 months of cigarette smoke exposure and which correlated very well with TLC (r=0.74, P=0.004) and Cchord (r=0.79, P=0.001). After 6 months of cigarette smoke exposure, a significant fiber-type shift from IIa to IIx/b was also observed in the soleus muscle (P<0.05), whereas a 20% reduction of force was present at high stimulation frequencies (80 Hz; P=0.09). The extensor digitorum longus (EDL) muscle was not affected by cigarette smoke exposure. These serial pulmonary function variables are sensitive outcomes to detect emphysema progression in a nose-only cigarette-smoke-exposed animal model of COPD. In this model, muscular changes became apparent only after 6 months, particularly in muscles with a mixed fiber-type composition.
BCS1L gene mutation presenting with GRACILE-like syndrome and complex III deficiency
Authors: Lynn Adrienne M , King Richard I , Mackay Richard J , Florkowski Chris M , Wilson Callum J
Published: January 2012

The clinical presentation of a neonate with GRACILE-like syndrome, complex III deficiency and BCS1L mutations is discussed. This case is compared and contrasted with the original Finnish reports of GRACILE syndrome and other cases with a similar phenotype. This case confirms the pathogenicity of the BCS1L gene mutation c.166C>T, and provides support for the pathogenicity of a sequence variation, c.−588T>A, previously reported.
An energetically beneficial leader–linker interaction abolishes ligand-binding cooperativity in glycine riboswitches
Authors: Sherman Eileen M. , Esquiaqui Jackie , Elsayed Galal , Ye Jing-Dong
Published: January 2012

Comprised of two aptamers connected by a short nucleotide linker, the glycine riboswitch was the first example of naturally occurring RNA elements reported to bind small organic molecules cooperatively. Earlier works have shown binding of glycine to the second aptamer allows tertiary interactions to be made between the two aptamers, which facilitates binding of a separate glycine molecule to the first aptamer, leading to glycine-binding cooperativity. Prompted by a distinctive protection pattern in the linker region of a minimal glycine riboswitch construct, we have identified a highly conserved (>90%) leader–linker duplex involving leader nucleotides upstream of the previously reported consensus glycine riboswitch sequences. In >50% of the glycine riboswitches, the leader–linker interaction forms a kink-turn motif. Characterization of three glycine ribsowitches showed that the leader–linker interaction improved the glycine-binding affinities by 4.5- to 86-fold. In-line probing and native gel assays with two aptamers in trans suggested synergistic action between glycine-binding and interaptamer interaction during global folding of the glycine riboswitch. Mutational analysis showed that there appeared to be no ligand-binding cooperativity in the glycine riboswitch when the leader–linker interaction is present, and the previously measured cooperativity is simply an artifact of a truncated construct missing the leader sequence.
The Jobseeker Assessment of Employability: Preliminary Evidence
Authors: Bull Gregory J.
Published: January 2012

This study reports the results of a preliminary study to develop a measure of employability for use in vocational rehabilitation settings. The instrument was piloted on 20 volunteer jobseeker participants then modified and trialled with a further 73 jobseeker participants. The partial credit Rasch model was applied to determine if the items formed a unidimensional construct. A 22-item Job Seeker Assessment of Employability scale resulted. The data support a developmental model of vocational rehabilitation that depicts jobseeker employability on a continuum.
Barriers to Physical Activity in Individuals with Spinal Cord Injury: A Western Australian Study
Authors: Roberton Terri , Bucks Romola S. , Skinner Timothy C. , Allison Gary T. , Dunlop Sarah A.
Published: January 2012

This study examined barriers to physical activity reported individuals with spinal cord injury (SCI) and the degree to which these barriers differed across varying degrees of independence. Participants were 65 individuals recruited from the Western Australian Spinal Cord Injury database. Data on physical activity participation and perceived barriers to physical activity participation were collected using a cross-sectional survey and analysed using independent samples t-tests. We found that, regardless of level of ambulation or ability to transfer, few participants reported being physically active. While there were no significant differences in the amount of barriers reported by individuals with different levels of independence, the type of barriers reported varied across groups.
Rehabilitation Judgments With Incomplete Information: A Case Study
Authors: Athanasou James A
Published: January 2012

This case study outlines the accuracy of a rehabilitation counsellor in judgments of the quality of life of actual cases comprising accident victims. Up to seven cues of information relating to health, energy, daily activities, self, personal relations, money and living conditions were provided to the counsellor. He/she had to decide whether the clients considered their own quality of life to be poor or good. The counsellor was consistent in his/her judgments (test–retest reliability = .79). The counsellor was accurate in 60% of cases, but this is only marginally better than an automatic decision that every accident victim is dissatisfied with his/her quality of life. The judgment accuracy was suboptimal. It was influenced by a reliance (93%) on satisfaction with personal relationships, whereas basic issues such as money for everyday living were more important in predicting quality of life. It did not appear that increasing the amount of information led to an increase in accuracy. The correlation between accuracy and the number of cues was very low (-.160).
Construction and Validation of a Supervisor Principle Ethics Scale
Authors: Schultz Jared C.
Published: January 2012

Psychometric properties on a newly developed Supervisor Principle Ethics Scale (SPES) are reported. The SPES was created to measure supervisees' perceptions of supervisors' use of ethical principles (Autonomy, Beneficence/Nonmaleficence, Justice, Veracity, Fidelity). Participants were vocational rehabilitation counsellors with a state agency in the United States (US) (Males = 38, Females = 49). They completed the SPES and the Supervisory Working Alliance-Trainee Form (Efstation, Patton, & Kardash, 1990). The five factors of the SPES were significantly correlated with the Supervisory Working Alliance-Trainee Form (SWAI-T), suggesting evidence of construct validity. Potential uses for the SPES in research and training activities are discussed.
Cytosolic Calcium Coordinates Mitochondrial Energy Metabolism with Presynaptic Activity
Authors: Chouhan Amit K. , Ivannikov Maxim V. , Lu Zhongmin , Sugimori Mutsuyuki , Llinas Rodolfo R. , Macleod Gregory T.
Published: January 2012

Most neurons fire in bursts, imposing episodic energy demands, but how these demands are coordinated with oxidative phosphorylation is still unknown. Here, using fluorescence imaging techniques on presynaptic termini ofDrosophilamotor neurons (MNs), we show that mitochondrial matrix pH (pHm), inner membrane potential (Δψm), and NAD(P)H levels ([NAD(P)H]m) increase within seconds of nerve stimulation. The elevations of pHm, Δψm, and [NAD(P)H]mindicate an increased capacity for ATP production. Elevations in pHmwere blocked by manipulations that blocked mitochondrial Ca2+uptake, including replacement of extracellular Ca2+with Sr2+and application of either tetraphenylphosphonium chloride or KB-R7943, indicating that it is Ca2+that stimulates presynaptic mitochondrial energy metabolism. To place this phenomenon within the context of endogenous neuronal activity, the firing rates of a number of individually identified MNs were determined during fictive locomotion. Surprisingly, although endogenous firing rates are significantly different, there was little difference in presynaptic cytosolic Ca2+levels ([Ca2+]c) between MNs when each fires at its endogenous rate. The average [Ca2+]clevel (329 ± 11 nm) was slightly above the average Ca2+affinity of the mitochondria (281 ± 13 nm). In summary, we show that when MNs fire at endogenous rates, [Ca2+]cis driven into a range where mitochondria rapidly acquire Ca2+. As we also show that Ca2+stimulates presynaptic mitochondrial energy metabolism, we conclude that [Ca2+]clevels play an integral role in coordinating mitochondrial energy metabolism with presynaptic activity inDrosophilaMNs.
Wandering Neuronal Migration in the Postnatal Vertebrate Forebrain
Authors: Scott Benjamin B. , Gardner Timothy , Ji Ni , Fee Michale S. , Lois Carlos
Published: January 2012

Most non-mammalian vertebrate species add new neurons to existing brain circuits throughout life, a process thought to be essential for tissue maintenance, repair, and learning. How these new neurons migrate through the mature brain and which cues trigger their integration within a functioning circuit is not known. To address these questions, we used two-photon microscopy to image the addition of genetically labeled newly generated neurons into the brain of juvenile zebra finches. Time-lapsein vivoimaging revealed that the majority of migratory new neurons exhibited a multipolar morphology and moved in a nonlinear manner for hundreds of micrometers. Young neurons did not use radial glia or blood vessels as a migratory scaffold; instead, cells extended several motile processes in different directions and moved by somal translocation along an existing process. Neurons were observed migrating for ∼2 weeks after labeling injection. New neurons were observed to integrate in close proximity to the soma of mature neurons, a behavior that may explain the emergence of clusters of neuronal cell bodies in the adult songbird brain. These results provide direct,in vivoevidence for a wandering form of neuronal migration involved in the addition of new neurons in the postnatal brain.
Retromer Binds the FANSHY Sorting Motif in SorLA to Regulate Amyloid Precursor Protein Sorting and Processing
Authors: Fjorback Anja W. , Seaman Matthew , Gustafsen Camilla , Mehmedbasic Arnela , Gokool Suzanne , Wu Chengbiao , Militz Daniel , Schmidt Vanessa , Madsen Peder , Nyengaard Jens R. , Willnow Thomas E. , Christensen Erik Ilsø , Mobley William B. , Nykjær Anders , Andersen Olav M.
Published: January 2012

sorLA is a sorting receptor for amyloid precursor protein (APP) genetically linked to Alzheimer's disease (AD). Retromer, an adaptor complex in the endosome-to-Golgi retrieval pathway, has been implicated in APP transport because retromer deficiency leads to aberrant APP sorting and processing and levels of retromer proteins are altered in AD. Here we report that sorLA and retromer functionally interact in neurons to control trafficking and amyloidogenic processing of APP. We have identified a sequence (FANSHY) in the cytoplasmic domain of sorLA that is recognized by the VPS26 subunit of the retromer complex. Accordingly, we characterized the interaction between the retromer complex and sorLA and determined the role of retromer on sorLA-dependent sorting and processing of APP. Mutations in the VPS26 binding site resulted in receptor redistribution to the endosomal network, similar to the situation seen in cells with VPS26 knockdown. The sorLA mutant retained APP-binding activity but, as opposed to the wild-type receptor, misdirected APP into a distinct non-Golgi compartment, resulting in increased amyloid processing. In conclusion, our data provide a molecular link between reduced retromer expression and increased amyloidogenesis as seen in patients with sporadic AD.
Causal Interactions in Attention Networks Predict Behavioral Performance
Authors: Wen Xiaotong , Yao Li , Liu Yijun , Ding Mingzhou
Published: January 2012

Lesion and functional brain imaging studies have suggested that there are two anatomically nonoverlapping attention networks. The dorsal frontoparietal network controls goal-oriented top-down deployment of attention; the ventral frontoparietal network mediates stimulus-driven bottom-up attentional reorienting. The interaction between the two networks and its functional significance has been considered in the past but no direct test has been carried out. We addressed this problem by recording fMRI data from human subjects performing a trial-by-trial cued visual spatial attention task in which the subject had to respond to target stimuli in the attended hemifield and ignore all stimuli in the unattended hemifield. Correlating Granger causal influences between regions of interest with behavioral performance, we report two main results. First, stronger Granger causal influences from the dorsal attention network (DAN) to the ventral attention network (VAN), i.e., DAN→VAN, are generally associated with enhanced performance, with right intraparietal sulcus (IPS), left IPS, and right frontal eye field being the main sources of behavior-enhancing influences. Second, stronger Granger causal influences from VAN to DAN, i.e., VAN→DAN, are generally associated with degraded performance, with right temporal-parietal junction being the main sources of behavior-degrading influences. These results support the hypothesis that signals from DAN to VAN suppress and filter out unimportant distracter information, whereas signals from VAN to DAN break the attentional set maintained by the dorsal attention network to enable attentional reorienting.
Stress-Induced Activation of the Dynorphin/κ-Opioid Receptor System in the Amygdala Potentiates Nicotine Conditioned Place Preference
Authors: Smith Jeffrey S. , Schindler Abigail G. , Martinelli Emma , Gustin Richard M. , Bruchas Michael R. , Chavkin Charles
Published: January 2012

Many smokers describe the anxiolytic and stress-reducing effects of nicotine, the primary addictive component of tobacco, as a principal motivation for continued drug use. Recent evidence suggests that activation of the stress circuits, including the dynorphin/κ-opioid receptor system, modulates the rewarding effects of addictive drugs. In the present study, we find that nicotine produced dose-dependent conditioned place preference (CPP) in mice. κ-Receptor activation, either by repeated forced swim stress or U50,488 (5 or 10 mg/kg, i.p.) administration, significantly potentiated the magnitude of nicotine CPP. The increase in nicotine CPP was blocked by the κ-receptor antagonist norbinaltorphimine (norBNI) either systemically (10 mg/kg, i.p.) or by local injection in the amygdala (2.5 μg) without affecting nicotine reward in the absence of stress. U50,488 (5 mg/kg, i.p.) produced anxiety-like behaviors in the elevated-plus maze and novel object exploration assays, and the anxiety-like behaviors were attenuated both by systemic nicotine (0.5 mg/kg, s.c.) and local injection of norBNI into the amygdala. Local norBNI injection in the ventral posterior thalamic nucleus (an adjacent brain region) did not block the potentiation of nicotine CPP or the anxiogenic-like effects of κ-receptor activation. These results suggest that the rewarding effects of nicotine may include a reduction in the stress-induced anxiety responses caused by activation of the dynorphin/κ-opioid system. Together, these data implicate the amygdala as a key region modulating the appetitive properties of nicotine, and suggest that κ-opioid antagonists may be useful therapeutic tools to reduce stress-induced nicotine craving.
Time of Day Regulates Subcellular Trafficking, Tripartite Synaptic Localization, and Polyadenylation of the Astrocytic Fabp7 mRNA
Authors: Gerstner Jason R. , Vanderheyden William M. , LaVaute Timothy , Westmark Cara J. , Rouhana Labib , Pack Allan I. , Wickens Marv , Landry Charles F.
Published: January 2012

The astrocyte brain fatty acid binding protein (Fabp7) has previously been shown to have a coordinated diurnal regulation of mRNA and protein throughout mouse brain, and an age-dependent decline in protein expression within synaptoneurosomal fractions. Mechanisms that control time-of-day changes in expression and trafficking Fabp7 to the perisynaptic process are not known. In this study, we confirmed an enrichment of Fabp7 mRNA and protein in the astrocytic perisynaptic compartment, and observed a diurnal change in the intracellular distribution of Fabp7 mRNA in molecular layers of hippocampus. Northern blotting revealed a coordinated time-of-day-dependent oscillation for the Fabp7 mRNA poly(A) tail throughout murine brain. Cytoplasmic polyadenylation element-binding protein 1 (CPEB1) regulates subcellular trafficking and translation of synaptic plasticity-related mRNAs. Here we show that Fabp7 mRNA coimmunoprecipitated with CPEB1 from primary mouse astrocyte extracts, and its 3′UTR contains phylogenetically conserved cytoplasmic polyadenylation elements (CPEs) capable of regulating translation of reporter mRNAs duringXenopusoocyte maturation. Given that Fabp7 expression is confined to astrocytes and neural progenitors in adult mouse brain, the synchronized cycling pattern of Fabp7 mRNA is a novel discovery among known CPE-regulated transcripts. These results implicate circadian, sleep, and/or metabolic control of CPEB-mediated subcellular trafficking and localized translation of Fabp7 mRNA in the tripartite synapse of mammalian brain.
The Head of the Table: Marking the “Front” of An Object Is Tightly Linked with Selection
Authors: Xu Yangqing , Franconeri Steven L.
Published: January 2012

Objects in the world do not have a surface that can be objectively labeled the “front.” We impose this designation on one surface of an object according to several cues, including which surface is associated with the most task-relevant information or the direction of motion of an object. However, when these cues are competing, weak, or absent, we can also flexibly assign one surface as the front. One possibility is that this assignment is guided by the location of the “spotlight” of selection, where the selected region becomes the front. Here we used an electrophysiological correlate to show a direct temporal link between object structure assignments and the spatial locus of selection. We found that when human participants viewed a shape whose front and back surfaces were ambiguous, seeing a given surface as front was associated with selectively attending to that location. In Experiment 1, this pattern occurred during directed rapid (every 1 s) switches in structural percepts. In Experiment 2, this pattern occurred during spontaneous reversals, from 900 ms before to 600 ms after the reported percept. These results suggest that the distribution of selective attention might guide the organization of object structure.
Higher Binding of the Dopamine D3Receptor-Preferring Ligand [11C]-(+)-Propyl-Hexahydro-Naphtho-Oxazin in Methamphetamine Polydrug Users: A Positron Emission Tomography Study
Authors: Boileau Isabelle , Payer Doris , Houle Sylvain , Behzadi Arian , Rusjan Pablo M. , Tong Junchao , Wilkins Diana , Selby Peter , George Tony P. , Zack Martin , Furukawa Yoshiaki , McCluskey Tina , Wilson Alan A. , Kish Stephen J.
Published: January 2012

Positron emission tomography (PET) findings suggesting lower D2-type dopamine receptors and dopamine concentration in brains of stimulant users have prompted speculation that increasing dopamine signaling might help in drug treatment. However, this strategy needs to consider the possibility, based on animal and postmortem human data, that dopaminergic activity at the related D3receptor might, in contrast, be elevated and thereby contribute to drug-taking behavior. We tested the hypothesis that D3receptor binding is above normal in methamphetamine (MA) polydrug users, using PET and the D3-preferring ligand [11C]-(+)-propyl-hexahydro-naphtho-oxazin ([11C]-(+)-PHNO). Sixteen control subjects and 16 polydrug users reporting MA as their primary drug of abuse underwent PET scanning after [11C]-(+)-PHNO. Compared with control subjects, drug users had higher [11C]-(+)-PHNO binding in the D3-rich midbrain substantia nigra (SN; +46%;p< 0.02) and in the globus pallidus (+9%;p= 0.06) and ventral pallidum (+11%;p= 0.1), whereas binding was slightly lower in the D2-rich dorsal striatum (approximately −4%, NS; −12% in heavy users,p= 0.01) and related to drug-use severity. The [11C]-(+)-PHNO binding ratio in D3-rich SN versus D2-rich dorsal striatum was 55% higher in MA users (p= 0.004), with heavy but not moderate users having ratios significantly different from controls. [11C]-(+)-PHNO binding in SN was related to self-reported “drug wanting.” We conclude that the dopamine D3receptor, unlike the D2receptor, might be upregulated in brains of MA polydrug users, although lower dopamine levels in MA users could have contributed to the finding. Pharmacological studies are needed to establish whether normalization of D3receptor function could reduce vulnerability to relapse in stimulant abuse.
Transgenic Expression of Intraneuronal Aβ42But Not Aβ40Leads to Cellular Aβ Lesions, Degeneration, and Functional Impairment without Typical Alzheimer's Disease Pathology
Authors: Abramowski Dorothee , Rabe Sabine , Upadhaya Ajeet Rijal , Reichwald Julia , Danner Simone , Staab Dieter , Capetillo-Zarate Estibaliz , Yamaguchi Haruyasu , Saido Takaomi C. , Wiederhold Karl-Heinz , Thal Dietmar Rudolf , Staufenbiel Matthias
Published: January 2012

An early role of amyloid-β peptide (Aβ) aggregation in Alzheimer's disease pathogenesis is well established. However, the contribution of intracellular or extracellular forms of Aβ to the neurodegenerative process is a subject of considerable debate. We here describe transgenic mice expressing Aβ1–40(APP47) and Aβ1–42(APP48) with a cleaved signal sequence to insert both peptides during synthesis into the endoplasmic reticulum. Although lower in transgene mRNA, APP48 mice reach a higher brain Aβ concentration. The reduced solubility and increased aggregation of Aβ1–42may impair its degradation. APP48 mice develop intracellular Aβ lesions in dendrites and lysosomes. The hippocampal neuron number is reduced already at young age. The brain weight decreases during aging in conjunction with severe white matter atrophy. The mice show a motor impairment. Only very few Aβ1–40lesions are found in APP47 mice. Neither APP47 nor APP48 nor the bigenic mice develop extracellular amyloid plaques. While intracellular membrane expression of Aβ1–42in APP48 mice does not lead to the AD-typical lesions, Aβ aggregates develop within cells accompanied by considerable neurodegeneration.
Calcium Binding by Synaptotagmin's C2A Domain is an Essential Element of the Electrostatic Switch That Triggers Synchronous Synaptic Transmission
Authors: Striegel Amelia R. , Biela Laurie M. , Evans Chantell S. , Wang Zhao , Delehoy Jillian B. , Sutton R. Bryan , Chapman Edwin R. , Reist Noreen E.
Published: January 2012

Synaptotagmin is the major calcium sensor for fast synaptic transmission that requires the synchronous fusion of synaptic vesicles. Synaptotagmin contains two calcium-binding domains: C2A and C2B. Mutation of a positively charged residue (R233Q in rat) showed that Ca2+-dependent interactions between the C2A domain and membranes play a role in the electrostatic switch that initiates fusion. Surprisingly, aspartate-to-asparagine mutations in C2A that inhibit Ca2+binding support efficient synaptic transmission, suggesting that Ca2+binding by C2A is not required for triggering synchronous fusion. Based on a structural analysis, we generated a novel mutation of a single Ca2+-binding residue in C2A (D229E inDrosophila) that inhibited Ca2+binding but maintained the negative charge of the pocket. This C2A aspartate-to-glutamate mutation resulted in ∼80% decrease in synchronous transmitter release and a decrease in the apparent Ca2+affinity of release. Previous aspartate-to-asparagine mutations in C2A partially mimicked Ca2+binding by decreasing the negative charge of the pocket. We now show that the major function of Ca2+binding to C2A is to neutralize the negative charge of the pocket, thereby unleashing the fusion-stimulating activity of synaptotagmin. Our results demonstrate that Ca2+binding by C2A is a critical component of the electrostatic switch that triggers synchronous fusion. Thus, Ca2+binding by C2B is necessary and sufficient to regulate the precise timing required for coupling vesicle fusion to Ca2+influx, but Ca2+binding by both C2domains is required to flip the electrostatic switch that triggers efficient synchronous synaptic transmission.
Saccular-Specific Hair Cell Addition Correlates with Reproductive State-Dependent Changes in the Auditory Saccular Sensitivity of a Vocal Fish
Authors: Coffin Allison B. , Mohr Robert A. , Sisneros Joseph A.
Published: January 2012

The plainfin midshipman fish,Porichthys notatus, is a seasonal breeding teleost fish for which vocal–acoustic communication is essential for its reproductive success. Female midshipman use the saccule as the primary end organ for hearing to detect and locate “singing” males that produce multiharmonic advertisement calls during the summer breeding season. Previous work has shown that female auditory sensitivity changes seasonally with reproductive state; summer reproductive females become better suited than winter nonreproductive females to detect and encode the dominant higher harmonic components in the male's advertisement call, which are potentially critical for mate selection and localization. Here, we test the hypothesis that these seasonal changes in female auditory sensitivity are concurrent with seasonal increases in saccular hair cell receptors. We show that there is increased hair cell density in reproductive females and that this increase is not dependent on body size since similar changes in hair cell density were not found in the other inner ear end organs. We also observed an increase in the number of small, potentially immature saccular hair bundles in reproductive females. The seasonal increase in saccular hair cell density and smaller hair bundles in reproductive females was paralleled by a dramatic increase in the magnitude of the evoked saccular potentials and a corresponding decrease in the auditory thresholds recorded from the saccule. This demonstration of correlated seasonal plasticity of hair cell addition and auditory sensitivity may in part facilitate the adaptive auditory plasticity of this species to enhance mate detection and localization during breeding.
Looming Signals Reveal Synergistic Principles of Multisensory Integration
Authors: Cappe Céline , Thelen Antonia , Romei Vincenzo , Thut Gregor , Murray Micah M.
Published: January 2012

Multisensory interactions are a fundamental feature of brain organization. Principles governing multisensory processing have been established by varying stimulus location, timing and efficacy independently. Determining whether and how such principles operate when stimuli vary dynamically in their perceived distance (as when looming/receding) provides an assay for synergy among the above principles and also means for linking multisensory interactions between rudimentary stimuli with higher-order signals used for communication and motor planning. Human participants indicated movement of looming or receding versus static stimuli that were visual, auditory, or multisensory combinations while 160-channel EEG was recorded. Multivariate EEG analyses and distributed source estimations were performed. Nonlinear interactions between looming signals were observed at early poststimulus latencies (∼75 ms) in analyses of voltage waveforms, global field power, and source estimations. These looming-specific interactions positively correlated with reaction time facilitation, providing direct links between neural and performance metrics of multisensory integration. Statistical analyses of source estimations identified looming-specific interactions within the right claustrum/insula extending inferiorly into the amygdala and also within the bilateral cuneus extending into the inferior and lateral occipital cortices. Multisensory effects common to all conditions, regardless of perceived distance and congruity, followed (∼115 ms) and manifested as faster transition between temporally stable brain networks (vs summed responses to unisensory conditions). We demonstrate the early-latency, synergistic interplay between existing principles of multisensory interactions. Such findings change the manner in which to model multisensory interactions at neural and behavioral/perceptual levels. We also provide neurophysiologic backing for the notion that looming signals receive preferential treatment during perception.
Modified Aerosol Routes to Core-Shell Nano-Energetic Materials Synthesis
Authors: Feng Jingyu , Chowdhury Snehaunshu , Jian Guoqiang , Zachariah Michael R.
Published: January 2012

Following the generic strategy of creating core-shell structured nanoparticles reported by our group previously [1] and exploring its applications, an aerosol route combined with iron carbonyl decomposition was developed to encapsulate strong oxidizer within mild oxidizer particles. This modified method enables the application of hygroscopic nano-energetic materials by stabilizing them within a water-insoluble shell. Fe2O3/I2O5 composite oxidizers have been created. Some of the results obtained from combustion tests show that the composite system significantly outperforms the single metal oxide (Fe2O3) system in both pressurization rate and peak pressure. The time-resolved mass spectrometry shows that a significant amount of O2 and I2 are released from the composite oxidizers. These preliminary results suggest a supplement to the previous strategy of obtaining the core-shell structured composite oxidizers and the method still needs to be further optimized.
Trends in lung cancer mortality in Brazil from the 1980s into the early 21st century: age-period-cohort analysis
Authors: Souza Mirian Carvalho de , Vasconcelos Ana Glória Godoi , Cruz Oswaldo Gonçalves
Published: January 2012

The aim of this study was to describe the pattern of trends in lung cancer mortality in Brazil and identify the effects of the factors age, period and cohort (APC) on mortality rates. A time series study was conducted using secondary population-based data. Lung cancer mortality rates by sex were calculated for the period 1980 to 2007. APC models were adjusted to identify the influence of age, period and cohort effects on rates. Lung cancer mortality rates are significantly higher among men. Specific rates for men over the age of 64 and for women of all ages are increasing. There was a greater increase of adjusted rates among women. With respect to the age effect, mortality risk increases with age starting with the earliest age groups. With regard to the cohort effect, there is a lesser risk of mortality among men born after 1950 and an increasing risk across all cohorts among women. The results regarding younger generations indicate that present trends are likely to continue. The cohort effect among women suggests an increasing trend in mortality rates, whereas a decrease in rates among men under the age of 65 suggests that this trend will continue. These trends reflect tobacco control measures adopted since 1986.
Stress Velopharyngeal Incompetence in Collegiate Trombone Players
Authors: Bennett Kassidy , Hoit Jeannette D.
Published: January 2012

Objectives

Symptoms of stress velopharyngeal incompetence (SVPI) have been reported by many wind instrument players. The current study was designed to determine (1) if symptoms of SVPI were accompanied by aeromechanical signs of SVPI and (2) if signs of SVPI differed across musical tasks.

Design

Participants were studied during a single recording session.

Setting

The study was conducted in a university laboratory.

Participants

Participants were 10 collegiate trombone players. They were separated into two groups: six who reported symptoms of SVPI and four who reported no symptoms.

Main Outcome Measure

Nasal pressure recorded during trombone playing was used to determine velopharyngeal status (open or closed).

Results

None of the participants exhibited an open velopharynx during trombone playing; however, all participants had positive nasal pressure (indicating an open velopharynx) immediately prior to sound onset on at least some of their breath groups. Two participants had positive nasal pressure prior to the vast majority of their productions and were given biofeedback and instruction to change this behavior.

Conclusions

Symptoms of SVPI do not necessarily indicate the presence of a velopharyngeal-nasal leak during wind instrument playing but may reflect awareness of air leaks immediately prior to sound production. Pre-sound velopharyngeal-nasal air leaks may be amenable to behavioral modification by biofeedback and instruction. Nasal pressure measurement (using a nasal cannula) provides a simple, yet powerful, way to identify SVPI.
Building facade failures
Authors: Beasley Kimball J
Published: January 2012

Building facades serve mainly to protect occupants and contents from the elements. Failure of the building envelope (i.e. walls, roof and windows) to function as intended usually has a significant impact on the serviceability of the building. Roofs and windows periodically fail and are replaced; however, the building facade is expected to endure the forces of nature for the service life of the building. The increasing complexity of modern buildings, combined with decreasing tolerance for undesirable performance of building systems, has resulted in an ever increasing frequency of building facade failures. This paper addresses common serviceability and performance problems associated with various types of building facades. Methods and tools useful for investigation of facade failures are discussed. The paper is not intended to be a comprehensive guide for the forensic investigator, but is offered as an aid to help recognise symptoms and evaluate conditions that underlie common building facade failures. The types of building facades and investigation methods discussed in this paper are primarily based on the author’s experience within the USA.
Perspectives on health and safety in construction and design
Authors: Emuze Fidelis , Smallwood John Julian
Published: January 2012

Although construction contributes a disproportionate number of injuries and fatalities across geographical boundaries, developing countries such as South Africa, perform worse in this regard than developed countries. Therefore, a range of interventions through legislation and industry initiatives have been introduced in order to improve construction health and safety (H&S) in South Africa. The Construction Regulations realised client and designer responsibility for H&S, in addition to contractor responsibility. For example, clients are required to provide the principal contractor with an H&S specification, and ensure that principal contractors have made adequate allowance for H&S, while designers are required to provide the client with all the relevant information about the design, and inform the contractor of any known or anticipated dangers or hazards. Research findings indicate that the Construction Regulations are perceived to have had an impact, in particular among project managers and contractors. Construction H&S performance is influenced by the H&S specification, and anecdotal evidence suggests that the medium-to-large principal contractors and subcontractors tend to address H&S to a greater degree than small contractors.