bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA sequences and chromosome structure
Authors: Southern Edwin M.
Published: April 2013

In this review evidence for the possible relationship between higher order chromosome structure and the distribution of tandem and dispersed repeated sequences in DNA has been examined. Evidence from studies of chromosome diminution in lower eukaryotes suggests that simple sequence DNAs may have a germ-line function and, in mammals, changes in simple sequence methylation, associated with changes in chromosome condensation, support the idea that the centromeric and telomeric heterochromatin may have a function in germ-line cells. For the major families of dispersed repeats, the weight of available evidence suggests that if they do play a role in chromosome organization, it is not an important one. Cytosine methylation is suggested as a candidate for a role in organizing the chromatin. Long-range patterns of methylation in vertebrates, the relationship of this to gene structure, and the association of changes in methylation with gene activity accord with current evidence linking specific nuclear structures to defined points in coding regions.
c-myc gene activation and chromosomal translocation
Authors: Rabbitts T. H. , Baer R. , Davis M. , Forster A. , Rabbitts P. H. , Malcolm S.
Published: April 2013

Burkitt’s lymphoma cells are characterized by the presence of specific chromosomal translocation bringing the immunoglobulin and the c-myc proto-oncogenes into the proximity of each other. Different translocations involve each of the three immunoglobulin loci but the breakpoint with respect to the c-myc gene is shown to be very variable. In t8/14 the breakpoint occurs upstream from the c-myc gene whilst in the variant lymphomas it occurs downstream from the gene. Possible ways in which the translocation affects the c-myc gene are discussed.
Escherichia coli rimM and yjeQ null strains accumulate immature 30S subunits of similar structure and protein complement
Authors: Leong Vivian , Kent Meredith , Jomaa Ahmad , Ortega Joaquin
Published: April 2013

Assembly of the Escherichia coli 30S ribosomal subunits proceeds through multiple parallel pathways. The protein factors RimM, YjeQ, RbfA, and Era work in conjunction to assist at the late stages of the maturation process of the small subunit. However, it is unclear how the functional interplay between these factors occurs in the context of multiple parallel pathways. To understand how these factors work together, we have characterized the immature 30S subunits that accumulate in ΔrimM cells and compared them with immature 30S subunits from a ΔyjeQ strain. The cryo-EM maps obtained from these particles showed that the densities representing helices 44 and 45 in the rRNA were partially missing, suggesting mobility of these motifs. These 30S subunits were also partially depleted in all tertiary ribosomal proteins, particularly those binding in the head domain. Using image classification, we identified four subpopulations of ΔrimM immature 30S subunits differing in the amount of missing density for helices 44 and 45, as well as the amount of density existing in these maps for the underrepresented proteins. The structural defects found in these immature subunits resembled those of the 30S subunits that accumulate in the ΔyjeQ strain. These findings are consistent with an “early convergency model” in which multiple parallel assembly pathways of the 30S subunit converge into a late assembly intermediate, as opposed to the mature state. Functionally related factors will bind to this intermediate to catalyze the last steps of maturation leading to the mature 30S subunit.
Increasing the Adsorption Capacity of Barley Husk by Plasma Stream Influence
Authors: Шайхиев  , Shaykhiev I. , Степанова  , Stepanova S. , Кондаленко  , Kondalenko O. , Абдуллин  , Abdullin I.
Published: April 2013

It is shown that at impact on a barley husk surface by plasma stream in waterproof mode a change of modified material surface occurs in comparison with initial material at the expense of protrusive fragments smoothing from 700–800 to 350–500 nanometers. The highest ratio of cleaning water from oil and the smallest water absorption is observed when using the sample № 22b processed in a propane-butane mix. Optimum parameters are found: working chamber pressure P = 26,6 Pas, current on anode Ia = 0,6 A, voltage on anode Ua = 2,5 kV, plasma-supporting gas consumption Q = 0,06 g/s, time t = 600 s. It is established that oil removal ratio when using the processed samples made not less than 99,8 %.
Risk Concepts in Human Life and Activity
Authors: Федорец  , Fedorets Aleksandr
Published: April 2013

Analysis of risk as a concept from the point of view of its influence on human activity purposes is carried out in this article. The concepts of risk connected with desire to get the benefit and to evade from damage are considered. Yang risk and Yin risk concepts are entered, need of their joint account in the risk analysis is proved. The analysis of Uncertainty and Freedom concepts within a context of risk analysis is carried out. For risks in which two and more parties of interpersonal or social relations manifest their interest, it is shown that in this case each of the parties, pursuing its own aims, analyzes its risks and manages them. These risks don’t coincide in the same way as don’t coincide the parties’ interests therefore each party risks are subject for separate analysis, assessment and management. The concepts of «professional risk» as risk which owner is the worker as the holder of professional competences, « enterprise risk» which owner is the employer and «social risk» which owner is the government are entered and defined as separate elements of «occupational risk» — general complex «worker’s life and health risk», caused by enterprise production activity.
Demography and Morbidity in Russian Regions as Indicators of Territories’ Ecological Trouble
Authors: Барабаш  , Barabash A. , Левич  , Levich A. , Булгаков  , Bulgakov N. , Юзбеков
Published: April 2013

Problems of environment quality assessment and methodical questions of ecological data analysis are considered in this article. The assessment and analysis of use of Insitu-technology of environment quality control are given. The establishment method of local environmental standards is considered. Recommendations on Insitu-technology application are offered according to results of work. Demography and morbidity indicators in Russian regions and standards of ecological factors are considered.
Learning by Doing and the Locus of Innovative Capability in Biotechnology Research
Authors: Jain Amit
Published: April 2013

Innovative capability, the knowledge a firm uses to innovate, is an input into and an output of the process of innovation. In this paper, I put forward the notion that innovative capability, similar to experience in production, accumulates by learning by doing and that innovation is characterized by a learning curve. Using patent data from 20,886 scientists working in 611 biotechnology firms in the U.S. and Canadian biotechnology industry from 1970 to 2007, I estimate a learning curve in innovation and determine the loci of innovative capability. Although knowledge stocks in the different loci accumulate over time in day-to-day firm activities, empirical results suggest that the individual is the primary repository of innovative capability and that experience working together in teams has a secondary influence on productivity. Contrary to prior learning curve research, accumulated firm experience has no direct effect on productivity. However, when individuals possess relevant domain knowledge and have experience working together, they benefit from knowledge spillovers within the firm. This suggests that knowledge stocks in the different loci are complementary to one another and that the comingling of these disparate bins of knowledge is an important facet of innovative capability.
Decomposing Uncertainty and Its Effects on Imitation in Firm Exit Decisions
Authors: Gaba Vibha , Terlaak Ann
Published: April 2013

This study examines the effects of different uncertainty types on interorganizational imitation in firm exit decisions. We draw on herding models to conceptualize exit decisions as being based on a firm’s private information, which the firm updates with information inferred from observing the actions of others. We posit that different types of uncertainty differentially affect this observational learning process; in particular, we propose that certain uncertainty types attenuate (rather than foster) observational learning and subsequent imitation. We test this theory using a 29-year panel data set on the exit of private venture capital firms. Our results indicate that observational learning does influence imitation in firm exit decisions, and they also suggest that a common belief—that uncertainty enhances imitation—does not apply to all types of uncertainty. Specifically, we find that uncertainty fosters imitation only when it is idiosyncratic to the firm; uncertainties that are common to all firms, in contrast, actually reduce reliance on observational learning. By decomposing uncertainty into different types and explicating their effects on imitation, we demonstrate that this relationship is more nuanced than previously assumed and, in addition, highlight the role of deliberate information processing in imitation.
Prophylaxis of Thromboembolic Events in Patients with Nephrotic Syndrome
Authors: Pincus Kathleen J , Hynicka Lauren M
Published: April 2013

OBJECTIVE

To review published literature regarding use of strategies to prevent thrombotic events in patients with nephrotic syndrome (NS).

DATA SOURCES

The MEDLINE/PubMed, EMBASE, and Cochrane databases were queried from 1980 to December 2012 for articles in English using the search terms nephrotic syndrome, thrombosis, thromboembolism, anticoagulation, warfarin, heparin, low-molecular-weight heparin, enoxaparin, dalteparin, tinzaparin, statin, atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin, aspirin, direct thrombin inhibitor, rivaroxaban, argatroban, lepirudin, bivalirudin, dabigatran, factor Xa inhibitor, fondaparinux, rivaroxaban, clopidogrel, ticlopidine, and prasugrel.

STUDY SELECTION AND DATA EXTRACTION

All relevant original studies, meta-analyses, systematic reviews, guidelines, and review articles were assessed for inclusion. References from pertinent articles were examined for additional content not found during the initial search.

DATA SYNTHESIS

NS leads to multiple complications, including hypercoagulability. A small prospective cohort study used enoxaparin for primary prophylaxis and demonstrated successful prevention of thrombotic events with minimal adverse events. Additional information has come in the form of decision analyses, which show potential decreased morbidity and mortality when primary prophylaxis for thrombotic events is used; however, all data have numerous limitations. Other strategies for thrombus prevention, including statins and antiplatelet agents, also have been investigated.

CONCLUSIONS

When patients with NS are admitted to the hospital, develop an acute medical illness, or acquire an additional thrombotic events risk factor such as surgery, active malignancy, or pregnancy, consideration for primary pharmacologic prophylaxis with appropriately dosed low-molecular-weight heparin or other indicated anticoagulant should include the potential for increased thrombotic events risk in this patient population. Consideration may also be given to the use of primary pharmacologic prophylaxis with low-molecular-weight heparin or oral vitamin K antagonist in patients with membranous nephropathy once the albumin level drops below 2.0–2.5 g/dL. Short-term use of pharmacologic prophylaxis during the first 6 months following diagnosis warrants further investigation.
The Emerging Role of Tiotropium for Patients with Asthma
Authors: Bollmeier Suzanne Gielow , Lee Shin-Yu
Published: April 2013

OBJECTIVE

To review clinical data on the use of the long-acting anticholinergic agent tiotropium in patients with asthma.

DATA SOURCES

A literature search was performed via EMBASE and MEDLINE (1966-November 2012). The search was limited to human data published in the English language. Search terms included asthma, tiotropium, and long-acting anticholinergics.

STUDY SELECTION AND DATA EXTRACTION

Relevant information related to the use of tiotropium in patients with asthma was reviewed. Randomized controlled trials and open-label trials were included. The references of published articles identified in the search were also examined for additional studies appropriate to include in the review. Data were prioritized if they originated from human studies, especially if derived from randomized, placebo-controlled trials. Trials and case reports involving the use of long-acting anticholinergic tiotropium in asthma patients were included; conversely, trials involving ipratropium were not.

DATA SYNTHESIS

Two large randomized controlled trials support the safety and efficacy of adding tiotropium to the treatment regimen of select patients with poorly controlled asthma already receiving combination high-dose glucocorticosteroid/long-acting β-agonist (LABA) therapy. Pharmacogenomic studies have shown that patients with polymorphisms of the β2-adrenoreceptor ( ADRB2; 16 Arg/Arg and 16 Arg/Gly) are particularly responsive to treatment with tiotropium. Smaller studies indicate that the advantages may be most pronounced in patients with a predominance of sputum neutrophils and that tiotropium can assist with decreasing the inhaled corticosteroid (ICS) dose. An increased risk of cardiovascular events was not identified.

CONCLUSIONS

Tiotropium should be considered in patients with asthma who remain symptomatic while receiving high-dose ICS and LABA therapy. Specifically, patients with high sputum neutrophil levels or with 16 Arg/Arg or 16 Arg/Gly polymorphism of the ADRB2 gene appear to respond best.
Intravenous Lipid Emulsion to Reverse Acute Drug Toxicity in Pediatric Patients
Authors: Presley Joseph D , Chyka Peter A
Published: April 2013

OBJECTIVE

To identify and summarize published cases in which intravenous lipid emulsion was used to treat pediatric patients with acute drug toxicities.

DATA SOURCES

PubMed, SCOPUS, and EMBASE were searched up to December 2012 for relevant publications using the terms fat emulsion, lipid emulsion, Intralipid, Liposyn, Medialipide, Medialipid, lipid rescue, ILE, IVLE, IFE, IVFE, or lipid and intoxication, overdose, poisoning, toxicity, resuscitation, antidote, and rescue that were limited to reports in humans aged 18 years or younger.

STUDY SELECTION AND DATA EXTRACTION

A publication was included if an intravenous lipid emulsion was used to treat acute-onset drug toxicity as reported in prospective or retrospective observational studies, case reports, and abstracts for patients aged 18 years or younger.

DATA SYNTHESIS

Fourteen case reports were identified in which intravenous lipid emulsion was used to treat toxicities due to local anesthetics and other medications (amitriptyline, diltiazem, bupropion, dosulepin, lamotrigine, quetiapine, and verapamil). Thirteen cases demonstrated a beneficial response in reversing systemic toxicity; 1 of these patients developed hypertriglyceridemia and pancreatitis. The dosage regimens used in this series were dissimilar.

CONCLUSIONS

There is an increasing interest in use of intravenous lipid emulsions to treat life-threatening toxicity from several lipophilic drugs in adults and children. Although most of the literature describes adult cases, intravenous lipid emulsion has been used in neonates and adolescents, with generally positive outcomes. Given the life-threatening, sometimes near-death situations in which an intravenous lipid emulsion is typically used after conventional resuscitation is unsuccessful and the dramatic positive response to this therapy in most published cases, its use likely will continue. Continued reporting of pediatric cases will guide the optimal use and safety profile of intravenous lipid emulsion for the emergent reversal of drug toxicity.
Chronic Pain: Lost Inhibition?
Authors: Henderson Luke A. , Peck Chris C. , Petersen Esben T. , Rae Caroline D. , Youssef Andrew M. , Reeves Jenna M. , Wilcox Sophie L. , Akhter Rahena , Murray Greg M. , Gustin Sylvia M.
Published: April 2013

Human brain imaging has revealed that acute pain results from activation of a network of brain regions, including the somatosensory, insular, prefrontal, and cingulate cortices. In contrast, many investigations report little or no alteration in brain activity associated with chronic pain, particularly neuropathic pain. It has been hypothesized that neuropathic pain results from misinterpretation of thalamocortical activity, and recent evidence has revealed altered thalamocortical rhythm in individuals with neuropathic pain. Indeed, it was suggested nearly four decades ago that neuropathic pain may be maintained by a discrete central generator, possibly within the thalamus. In this investigation, we used multiple brain imaging techniques to explore central changes in subjects with neuropathic pain of the trigeminal nerve resulting in most cases (20 of 23) from a surgical event. Individuals with chronic neuropathic pain displayed significant somatosensory thalamus volume loss (voxel-based morphometry) which was associated with decreased thalamic reticular nucleus and primary somatosensory cortex activity (quantitative arterial spin labeling). Furthermore, thalamic inhibitory neurotransmitter content was significantly reduced (magnetic resonance spectroscopy), which was significantly correlated to the degree of functional connectivity between the somatosensory thalamus and cortical regions including the primary and secondary somatosensory cortices, anterior insula, and cerebellar cortex. These data suggest that chronic neuropathic pain is associated with altered thalamic anatomy and activity, which may result in disturbed thalamocortical circuits. This disturbed thalamocortical activity may result in the constant perception of pain.
Multiple Sources of Striatal Inhibition Are Differentially Affected in Huntington's Disease Mouse Models
Authors: Cepeda Carlos , Galvan Laurie , Holley Sandra M. , Rao Shilpa P. , André Véronique M. , Botelho Elian P. , Chen Jane Y. , Watson Joseph B. , Deisseroth Karl , Levine Michael S.
Published: April 2013

In Huntington's disease (HD) mouse models, spontaneous inhibitory synaptic activity is enhanced in a subpopulation of medium-sized spiny neurons (MSNs), which could dampen striatal output. We examined the potential source(s) of increased inhibition using electrophysiological and optogenetic methods to assess feedback and feedforward inhibition in two transgenic mouse models of HD. Single whole-cell patch-clamp recordings demonstrated that increased GABA synaptic activity impinges principally on indirect pathway MSNs. Dual patch recordings between MSNs demonstrated reduced connectivity between MSNs in HD mice. However, while connectivity was strictly unidirectional in controls, in HD mice bidirectional connectivity occurred. Other sources of increased GABA activity in MSNs also were identified. Dual patch recordings from fast spiking (FS) interneuron–MSN pairs demonstrated greater but variable amplitude responses in MSNs. In agreement, selective optogenetic stimulation of parvalbumin-expressing, FS interneurons induced significantly larger amplitude MSN responses in HD compared with control mice. While there were no differences in responses of MSNs evoked by activating single persistent low-threshold spiking (PLTS) interneurons in recorded pairs, these interneurons fired more action potentials in both HD models, providing another source for increased frequency of spontaneous GABA synaptic activity in MSNs. Selective optogenetic stimulation of somatostatin-expressing, PLTS interneurons did not reveal any significant differences in responses of MSNs in HD mice. These findings provide strong evidence that both feedforward and to a lesser extent feedback inhibition to MSNs in HD can potentially be sources for the increased GABA synaptic activity of indirect pathway MSNs.
Amelioration of Binge Eating by Nucleus Accumbens Shell Deep Brain Stimulation in Mice Involves D2 Receptor Modulation
Authors: Halpern Casey H. , Tekriwal Anand , Santollo Jessica , Keating Jeffrey G. , Wolf John A. , Daniels Derek , Bale Tracy L.
Published: April 2013

Hedonic overconsumption contributing to obesity involves altered activation within the mesolimbic dopamine system. Dysregulation of dopamine signaling in the nucleus accumbens shell (NAS) has been implicated in reward-seeking behaviors, such as binge eating, which contributes to treatment resistance in obesity (Wise, 2012). Direct modulation of the NAS with deep brain stimulation (DBS), a surgical procedure currently under investigation in humans for the treatment of major depression, obsessive–compulsive disorder, and addiction, may also be effective in ameliorating binge eating. Therefore, we examined the ability of DBS of the NAS to block this behavior in mice. c-Fos immunoreactivity was assessed as a marker of DBS-mediated neuronal activation. NAS DBS was found to reduce binge eating and increased c-Fos levels in this region. DBS of the dorsal striatum had no influence on this behavior, demonstrating anatomical specificity for this effect. The dopamine D2 receptor antagonist, raclopride, attenuated the action of DBS, whereas the D1 receptor antagonist, SCH-23390, was ineffective, suggesting that dopamine signaling involving D2 receptors underlies the effect of NAS DBS. To determine the potential translational relevance to the obese state, chronic NAS DBS was also examined in diet-induced obese mice and was found to acutely reduce caloric intake and induce weight loss. Together, these findings support the involvement of the mesolimbic dopamine pathways in the hedonic mechanisms contributing to obesity, and the efficacy of NAS DBS to modulate this system.
Disrupting Sensitization of Transient Receptor Potential Vanilloid Subtype 1 Inhibits Inflammatory Hyperalgesia
Authors: Fischer Michael J. M. , Btesh Joan , McNaughton Peter A.
Published: April 2013

Transient receptor potential vanilloid subtype 1 (TRPV1) is a heat-sensitive ion channel that plays a key role in enhanced pain sensation after inflammation, but directly blocking TRPV1 causes hyperthermia and decreased sensitivity to painful levels of heat in animals and humans. Here we explore an alternative analgesic strategy in which the modulation of TRPV1 is inhibited by antagonizing the interaction between TRPV1 and A kinase anchoring protein 79 (AKAP79), a scaffolding protein essential for positioning serine–threonine kinases adjacent to target phosphorylation sites. We first defined key residues in the domain in TRPV1 that interacts with AKAP79, and we then used this information to construct short peptides capable of preventing TRPV1–AKAP79 interaction. An effective peptide, when coupled to a TAT sequence conferring cell permeability, was found to be analgesic in three mouse models of inflammatory hyperalgesia. These results demonstrate the potential value of interfering with the interaction between TRPV1 and AKAP79 as a novel analgesic strategy.
Longitudinal Change in the Neural Bases of Adolescent Social Self-Evaluations: Effects of Age and Pubertal Development
Authors: Pfeifer Jennifer H. , Kahn Lauren E. , Merchant Junaid S. , Peake Shannon J. , Veroude Kim , Masten Carrie L. , Lieberman Matthew D. , Mazziotta John C. , Dapretto Mirella
Published: April 2013

Self-evaluations undergo significant transformation during early adolescence, developing in parallel with the heightened complexity of teenagers' social worlds. Intuitive theories of adolescent development, based in part on animal work, suggest that puberty is associated with neural-level changes that facilitate a “social reorientation” (Nelson et al., 2005). However, direct tests of this hypothesis using neuroimaging are limited in humans. This longitudinal fMRI study examined neurodevelopmental trajectories associated with puberty, self-evaluations, and the presumed social reorientation during the transition from childhood to adolescence. Participants (N= 27, mean age = 10.1 and 13.1 years at time points one and two, respectively) engaged in trait evaluations of two targets (the self and a familiar fictional other), across two domains of competence (social and academic). Responses in ventromedial PFC increased with both age and pubertal development during self-evaluations in the social domain, but not in the academic domain. These results suggest that changes in social self-evaluations are intimately connected with biology, not just peer contexts, and provide important empirical support for the relationship between neurodevelopment, puberty, and social functioning.
Nuclear Factor κB-Dependent Histone Acetylation is Specifically Involved in Persistent Forms of Memory
Authors: Federman Noel , de la Fuente Verónica , Zalcman Gisela , Corbi Nicoletta , Onori Annalisa , Passananti Claudio , Romano Arturo
Published: April 2013

Memory consolidation requires gene expression regulation by transcription factors, which eventually may induce chromatin modifications as histone acetylation. This mechanism is regulated by histone acetylases and deacetylases. It is not yet clear whether memory consolidation always recruits histone acetylation or it is only engaged in more persistent memories. To address this question, we used different strength of training for novel object recognition task in mice. Only strong training induced a long-lasting memory and an increase in hippocampal histone H3 acetylation. Histone acetylase inhibition in the hippocampus during consolidation impaired memory persistence, whereas histone deacetylase inhibition caused weak memory to persist. Nuclear factor κB (NF-κB) transcription factor inhibition impaired memory persistence and, concomitantly, reduced the general level of H3 acetylation. Accordingly, we found an important increase in H3 acetylation at a specific NF-κB-regulated promoter region of theCamk2dgene, which was reversed by NF-kB inhibition. These results show for the first time that histone acetylation is a specific molecular signature of enduring memories.
dCREB2-Mediated Enhancement of Memory Formation
Authors: Tubon Thomas C. , Zhang Jiabin , Friedman Eugenia L. , Jin Haining , Gonzales Erin D. , Zhou Hong , Drier Diana , Gerstner Jason R. , Paulson Emily A. , Fropf Robin , Yin Jerry C. P.
Published: April 2013

CREB-responsive transcription has an important role in adaptive responses in all cells and tissue. In the nervous system, it has an essential and well established role in long-term memory formation throughout a diverse set of organisms. Activation of this transcription factor correlates with long-term memory formation and disruption of its activity interferes with this process. Most convincingly, augmenting CREB activity in a number of different systems enhances memory formation. InDrosophila, a sequence rearrangement in the original transgene used to enhance memory formation has been a source of confusion. This rearrangement prematurely terminates translation of the full-length protein, leaving the identity of the “enhancing molecule” unclear. In this report, we show that a naturally occurring, downstream, in-frame initiation codon is used to make a dCREB2 protein off of both transgenic and chromosomal substrates. This protein is a transcriptional activator and is responsible for memory enhancement. A number of parameters can affect enhancement, including the short-lived activity of the activator protein, and the time-of-day when induction and behavioral training occur. Our results reaffirm that overexpression of a dCREB2 activator can enhance memory formation and illustrate the complexity of this behavioral enhancement.
Thalamocortical Long-Term Potentiation Becomes Gated after the Early Critical Period in the Auditory Cortex
Authors: Chun Sungkun , Bayazitov Ildar T. , Blundon Jay A. , Zakharenko Stanislav S.
Published: April 2013

Cortical maps in sensory cortices are plastic, changing in response to sensory experience. The cellular site of such plasticity is currently debated. Thalamocortical (TC) projections deliver sensory information to sensory cortices. TC synapses are currently dismissed as a locus of cortical map plasticity because TC synaptic plasticity is thought to be limited to neonates, whereas cortical map plasticity can be induced in both neonates and adults. However, in the auditory cortex (ACx) of adults, cortical map plasticity can be induced if animals attend to a sound or receive sounds paired with activation of cholinergic inputs from the nucleus basalis. We now show that, in the ACx, long-term potentiation (LTP), a major form of synaptic plasticity, is expressed at TC synapses in both young and mature mice but becomes gated with age. Using single-cell electrophysiology, two-photon glutamate uncaging, and optogenetics in TC slices containing the auditory thalamus and ACx, we show that TC LTP is expressed postsynaptically and depends on group I metabotropic glutamate receptors. TC LTP in mature ACx can be unmasked by cortical disinhibition combined with activation of cholinergic inputs from the nucleus basalis. Cholinergic inputs passing through the thalamic radiation activate M1muscarinic receptors on TC projections and sustain glutamate release at TC synapses via negative regulation of presynaptic adenosine signaling through A1adenosine receptors. These data indicate that TC LTP in the ACx persists throughout life and therefore can potentially contribute to experience-dependent cortical map plasticity in the ACx in both young and adult animals.
Principles of Multisensory Behavior
Authors: Otto Thomas U. , Dassy Brice , Mamassian Pascal
Published: April 2013

The combined use of multisensory signals is often beneficial. Based on neuronal recordings in the superior colliculus of cats, three basic rules were formulated to describe the effectiveness of multisensory signals: the enhancement of neuronal responses to multisensory compared with unisensory signals is largest when signals occur at the same location (“spatial rule”), when signals are presented at the same time (“temporal rule”), and when signals are rather weak (“principle of inverse effectiveness”). These rules are also considered with respect to multisensory benefits as observed with behavioral measures, but do they capture these benefits best? To uncover the principles that rule benefits in multisensory behavior, we here investigated the classical redundant signal effect (RSE; i.e., the speedup of response times in multisensory compared with unisensory conditions) in humans. Based on theoretical considerations using probability summation, we derived two alternative principles to explain the effect. First, the “principle of congruent effectiveness” states that the benefit in multisensory behavior (here the speedup of response times) is largest when behavioral performance in corresponding unisensory conditions is similar. Second, the “variability rule” states that the benefit is largest when performance in corresponding unisensory conditions is unreliable. We then tested these predictions in two experiments, in which we manipulated the relative onset and the physical strength of distinct audiovisual signals. Our results, which are based on a systematic analysis of response time distributions, show that the RSE follows these principles very well, thereby providing compelling evidence in favor of probability summation as the underlying combination rule.
MAPK Establishes a Molecular Context That Defines Effective Training Patterns for Long-Term Memory Formation
Authors: Philips Gary T. , Ye Xiaojing , Kopec Ashley M. , Carew Thomas J.
Published: April 2013

Although the importance of spaced training trials in the formation of long-term memory (LTM) is widely appreciated, surprisingly little is known about the molecular mechanisms that support interactions between individual trials. The intertrial dynamics of ERK/MAPK activation have recently been correlated with effective training patterns for LTM. However, whether and how MAPK is required to mediate intertrial interactions remains unknown. Using a novel two-trial training pattern which induces LTM inAplysia, we show that the first of two training trials recruits delayed protein synthesis-dependent nuclear MAPK activity that establishes a unique molecular context involving the recruitment of CREB kinase andApC/EBPand is an essential intertrial signaling mechanism for LTM induction. These findings provide the first demonstration of a requirement for MAPK in the intertrial interactions during memory formation and suggest that the kinetics of MAPK activation following individual experiences determines effective training intervals for LTM formation.
Infarct-Derived Chondroitin Sulfate Proteoglycans Prevent Sympathetic Reinnervation after Cardiac Ischemia-Reperfusion Injury
Authors: Gardner Ryan T. , Habecker Beth A.
Published: April 2013

Sympathetic nerves can regenerate after injury to reinnervate target tissues. Sympathetic regeneration is well documented after chronic cardiac ischemia, so we were surprised that the cardiac infarct remained denervated following ischemia-reperfusion (I-R). We used mice to ask if the lack of sympathetic regeneration into the scar was due to blockade by inhibitory extracellular matrix within the infarct. We found that chondroitin sulfate proteoglycans (CSPGs) were present in the infarct after I-R, but not after chronic ischemia, and that CSPGs caused inhibition of sympathetic axon outgrowthin vitro. Ventricle explants after I-R and chronic ischemia stimulated sympathetic axon outgrowth that was blocked by nerve growth factor antibodies. However, growth in I-R cocultures was asymmetrical, with axons growing toward the heart tissue consistently shorter than axons growing in other directions. Growth toward I-R explants was rescued by adding chondroitinase ABC to the cocultures, suggesting that I-R infarct-derived CSPGs prevented axon extension. Sympathetic ganglia lacking protein tyrosine phosphatase sigma (PTPRS) were not inhibited by CSPGs or I-R explantsin vitro, suggesting PTPRS is the major CSPG receptor in sympathetic neurons. To test directly if infarct-derived CSPGs prevented cardiac reinnervation, we performed I-R inptprs−/− andptprs+/− mice. Cardiac infarcts inptprs−/− mice were hyperinnervated, while infarcts inptprs+/− littermates were denervated, confirming that CSPGs prevent sympathetic reinnervation of the cardiac scar after I-R. This is the first example of CSPGs preventing sympathetic reinnervation of an autonomic target following injury, and may have important consequences for cardiac function and arrhythmia susceptibility after myocardial infarction.
Rap1 Signaling Prevents L-Type Calcium Channel-Dependent Neurotransmitter Release
Authors: Subramanian Jaichandar , Dye Louis , Morozov Alexei
Published: April 2013

The small GTPase Rap1 contributes to fear learning and cortico-amygdala plasticity by inhibiting glutamate release from cortical neurons, but mechanisms of this inhibition remain unknown. Conversely, L-type calcium channels (LTCCs) become involved in glutamate release after fear learning and LTP induction. Here, we show that Rap1 deletion in mouse primary cortical neurons increases synaptic vesicle exocytosis without altering endocytosis or vesicle pool size in an LTCC-dependent manner. We identify Erk1/2 as the downstream effector of Rap1 and show that its inhibition increases plasma membrane expression of LTCCs near presynaptic terminals. We propose that the Rap1 signaling enables plasticity and fear learning by regulating LTCCs at cortico-amygdala synapses.
Hyperglycemia downregulates Connexin36 in pancreatic islets via the upregulation of ICER-1/ICER-1γ
Authors: Haefliger Jacques-Antoine , Rohner-Jeanrenaud Françoise , Caille Dorothée , Charollais Anne , Meda Paolo , Allagnat Florent
Published: April 2013

Channels formed by the gap junction protein Connexin36 (CX36) contribute to the proper control of insulin secretion. We previously demonstrated that chronic exposure to glucose decreases Cx36 levels in insulin-secreting cells in vitro. Here, we investigated whether hyperglycemia also regulates Cx36 in vivo. Using a model of continuous glucose infusion in adult rats, we showed that prolonged (24–48 h) hyperglycemia reduced the Cx36 gene Gjd2 mRNA levels in pancreatic islets. Accordingly, prolonged exposure to high glucose concentrations also reduced the expression and function of Cx36 in the rat insulin-producing INS-1E cell line. The glucose effect was blocked after inhibition of the cAMP/PKA pathway and was associated with an overexpression of the inducible cAMP early repressor ICER-1/ICER-1γ, which binds to a functional cAMP-response element in the promoter of the Cx36 gene Gjd2. The involvement of this repressor was further demonstrated using an antisense strategy of ICER-1 inhibition, which prevented glucose-induced downregulation of Cx36. The data indicate that chronic exposure to glucose alters the in vivo expression of Cx36 by the insulin-producing β-cells through ICER-1/ICER-1γ overexpression. This mechanism may contribute to the reduced glucose sensitivity and altered insulin secretion, which contribute to the pathophysiology of diabetes.
Human and mouse embryonic development, metabolism and gene expression are altered by an ammonium gradient in vitro
Authors: Gardner D K , Hamilton R , McCallie B , Schoolcraft W B , Katz-Jaffe M G
Published: April 2013

Ammonium is generated in culture media by the spontaneous deamination of amino acids at 37 °C and through the metabolism of amino acids by human embryos. The appearance of ammonium is a time-dependent phenomenon and can compromise embryo physiology, development and viability. In this study, the effects of a gradient of ammonium on the development, metabolism and transcriptome of human and mouse embryos were investigated. Pronucleate oocytes were cultured in the presence of an ammonium gradient that mimicked the spontaneous deamination of Eagle's amino acids together with 1 mM glutamine. All embryos were cultured in sequential media G1/G2 at 5% O2, 6% CO2 and 89% N2. Human embryo metabolism was assessed through a non-invasive fluorometric analysis of pyruvate consumption. Transcriptome analysis was performed on the resultant blastocysts from both species using a microarray technology. Embryo development prior to compaction was negatively affected by the presence of low levels of ammonium in both species. Human embryo metabolism was significantly inhibited after just 24 and 48 h of culture. Transcriptome analysis of blastocysts from both species revealed significantly altered gene expression profiles, both decreased and increased. Functional annotation of the altered genes revealed the following over represented biological processes: metabolism, cell growth and/or maintenance, transcription, cell communication, transport, development and transcription regulation. These data emphasize the enhanced sensitivity of the cleavage-stage embryo to its environment and highlight the requirement to renew culture media at frequent intervals in order to alleviate the in vitro induced effects of ammonium build-up in the environment surrounding the embryo.
Live births from isolated primary/early secondary follicles following a multistep culture without organ culture in mice
Authors: Mochida Nahoko , Akatani-Hasegawa Akiko , Saka Kayo , Ogino Mai , Hosoda Yoko , Wada Ryu , Sawai Hideaki , Shibahara Hiroaki
Published: April 2013

Although the ovary has a large store of germ cells, most of them do not reach mature stages. If a culture system could be developed from early growing follicles to mature oocytes, it would be useful for biological research as well as for reproductive medicine. This study was conducted to establish a multistep culture system from isolated early growing follicles to mature oocytes using a mouse model. Early growing follicles with diameters of 60–95 μm corresponding to primary and early secondary follicles were isolated from 6-day-old mice and classified into three groups by diameter. These follicles contained oocytes with diameters of ∼45 μm and one or a few layered granulosa cells on the basal lamina. Embedding in collagen gel was followed by first-step culture. After 9-day culture, the growing follicles were transferred onto collagen-coated membrane in the second step. At day 17 of the culture series, the oocyte–granulosa cell complexes were subjected toin vitromaturation. Around 90% of the oocytes in follicles surviving at day 17 resumed second meiosis (metaphase II oocytes: 49.0–58.7%), regardless of the size when the follicle culture started. To assess developmental competence to live birth, the eggs were used for IVF and implantation in pseudopregnant mice. We successfully obtained two live offspring that produced next generations after puberty. We thus conclude that the culture system reported here was able to induce the growth of small follicles and the resultant mature oocytes were able to develop into normal mice.
Epididymosomes, prostasomes, and liposomes: their roles in mammalian male reproductive physiology
Authors: Sullivan Robert , Saez Fabrice
Published: April 2013

Mammalian spermatozoa are unique cells in many ways, and the acquisition of their main function, i.e. fertilization capacity, is a multistep process starting in the male gonad and ending near the female egg for the few cells reaching this point. Owing to the unique character of this cell, the molecular pathways necessary to achieve its maturation also show some specific characteristics. One of the most striking specificities of the spermatozoon is that its DNA is highly compacted after the replacement of histones by protamines, making the classical processes of transcription and translation impossible. The sperm cells are thus totally dependent on their extracellular environment for their protection against oxidative stress, for example, or for the molecular changes occurring during the transit of the epididymis; the first organ in which post-testicular maturation takes place. The molecular mechanisms underlying sperm maturation are still largely unknown, but it has been shown in the past three decades that extracellular vesicles secreted by the male reproductive tract are involved in this process. This review will examine the roles played by two types of naturally occurring extracellular vesicles, epididymosomes and prostasomes, secreted by the epididymis and the prostate respectively. We will also describe how the use of artificial vesicles, liposomes, contributed to the study of male reproductive physiology.
Synthesis, Properties, and Applications of Hydrophilic Hollow Carbon Nanoparticles from C60 and its Soot
Authors: Kokubo Ken , Ueno Hiroshi , Nakamura Yuji , Yamakura Shizuka , Oshima Takumi
Published: April 2013

We have developed a facile synthetic method for highly water-soluble, hollow carbon nanoparticles with a diameter of ∼1 nm, as a so-called fullerenol. The method was extended to fullerene soot to obtain the corresponding hydrophilic carbon materials, and the products were subjected to IR and elemental analysis. Particle size analysis demonstrated the relatively high dispersion of particles with diameters of ∼70 nm, in water. The surface analysis using FE-SEM showed the difference in morphology between fullerene soot and activated carbon as well as between before and after hydrophilic treatment of the soot with hydrogen peroxide. Moreover, this hydrophilic fullerene soot exhibited high antioxidant activity as compared with fullerenol and C60.
Synergism in Binary (MWNT, SLG) Nano-carbons in Polymer Nano-composites: A Raman Study
Authors: Xu Peng , Loomis James , King Ben , Panchapakesan Balaji
Published: April 2013

Load transfer and mechanical strength of reinforced polymers are fundamental to developing advanced composites. This paper demonstrates enhanced load transfer and mechanical strength due to synergistic effects in binary mixtures of nano-carbon/polymer composites. Different compositional mixtures (always 1 wt. % total) of multi-wall carbon nanotubes (MWNTs) and single-layer graphene (SLG) were mixed in polydimethylsiloxane (PDMS), and effects on load transfer and mechanical strength were studied using Raman spectroscopy. Significant shifts in the G-bands were observed both in tension and compression for single as well binary nano-carbon counterparts in polymer composites. Small amounts of MWNT0.1 dispersed in SLG0.9/PDMS samples (subscripts represents weight percentage) reversed the sign of the Raman wavenumbers from positive to negative values demonstrating reversal of lattice stress. A wavenumber change from 10 cm-1 in compression (-10% strain) to 10 cm-1 in tension (50% strain), and an increase in elastic modulus of ∼103% was observed for MWNT0.1SLG0.9/PDMS with applied uniaxial tension. Presence of MWNTs in the matrix reduced the segmental polymeric chain length and provided limited extensibility to the chains. This in turn eliminated compressive deformation of SLG and significantly enhanced load transfer and mechanical strength of composites in tension. The orientation order of MWNT with application of uniaxial tensile strain directly affected the shift in Raman wavenumbers (2D band and G-band) and load transfer. It is observed that the cooperative behavior of binary nano-carbons in polymer composites resulted in enhanced load transfer and mechanical strength. Such binary compositions could be fundamental to developing advanced composites.
The Physical Essence of Mono-dispersed Nanometer Particle Surface Energy by Boundary bond Interaction
Authors: Su Lihong , Yin Xiaowei , Wan Caixia , Qiao Shengru
Published: April 2013

The surface energy quantifies the disruption of intermolecular bond that occurs when a surface is created. The paper discusses critical size dc of mono-dispersed nanometer particle by analyzing the change of interfacial surface energy. The traditional theory neglects that the mono-dispersed nanometer particle has quantum standing wave in its internal structure with a size below critical dc. During the preparation of mono-dispersed nanometer powder, the large surface energy is formed ont only by cutting surface bond but also by forming quantum standing wave that opposites to interfacial edge unsaturated bond on the nanometer partcile surface atom. The preparation process of nanometer material needs more energy than the size surpass dc material. The new theory can explain why the melting point of nanometer powder decreases and other phenomina of nanometer material.