bluuebunny/crossref_metadata_2025 huggingface dataset:
Repeated elevational transitions in hemoglobin function during the evolution of Andean hummingbirds
Authors: Projecto-Garcia Joana , Natarajan Chandrasekhar , Moriyama Hideaki , Weber Roy E. , Fago Angela , Cheviron Zachary A. , Dudley Robert , McGuire Jimmy A. , Witt Christopher C. , Storz Jay F.
Published: December 2013

Significance

Hummingbirds have exceedingly high oxygen demands because of their elevated rates of aerobic metabolism, and yet they thrive in high-altitude environments in the Andes where oxygen is scarce. Here we report the finding that when hummingbird species colonized new elevational zones, evolutionary changes in the respiratory properties of hemoglobin were repeatedly mediated by the same amino acid replacements. Specifically, ancestral sequence reconstruction and protein engineering experiments revealed that parallel adaptation of hemoglobin function in multiple species is attributable to repeated amino acid replacements at a single pair of interacting sites. This striking parallelism at the molecular level suggests a surprising degree of reproducibility and predictability in adaptive protein evolution.
Coevolutionary signals across protein lineages help capture multiple protein conformations
Authors: Morcos Faruck , Jana Biman , Hwa Terence , Onuchic José N.
Published: December 2013

Significance

We show that directly coupled evolutionary residue pairs provide a distinct footprint of conformational diversity in protein families. This is revealed as competing residue contacts unique to distinct configurations of proteins with multiple conformations. We demonstrate that combining this information with physical models of proteins is sufficient to uncover conformational diversity for several protein families. We discovered that such directly coupled residues not only allow us to accurately transition between apo and holo conformations but also help to uncover intermediate states that are not easily accessible to experimental or other computational methods. This enhanced sampling of the functional conformational space of proteins may have broad implications in protein structure determination and the design of ligands that can trap intermediate states.
Stoichiometry for activation of neuronal α7 nicotinic receptors
Authors: Andersen Natalia , Corradi Jeremías , Sine Steven M. , Bouzat Cecilia
Published: December 2013

Significance

Nicotinic α7 receptors are neurotransmitter-gated ion channels that participate in cognitive, cytoprotective, and anti-inflammatory processes and have emerged as targets for neurological disorders and therapeutic drugs. They are associated with extrasynaptic volume transmission where they are exposed to low ACh concentrations and thus function with partial occupancy of their five identical binding sites. By generating α7 receptors with different numbers of functional ACh binding sites and measuring open-channel lifetimes of individual receptors, we find that occupancy of one site produces a maximal response and that the additional sites enhance agonist sensitivity. Thus, ACh occupancy of only one of five sites in α7 produces a maximal response, adapting it to extrasynaptic volume transmission in neuronal and nonneuronal cells.
Formation of highly porous aerosol particles by atmospheric freeze-drying in ice clouds
Authors: Adler Gabriela , Koop Thomas , Haspel Carynelisa , Taraniuk Ilya , Moise Tamar , Koren Ilan , Heiblum Reuven H. , Rudich Yinon
Published: December 2013

Significance

Aerosols cycling through clouds affect particle morphological and chemical properties, thus modifying aerosol effects on cloud microphysics and climate. Previous studies have focused on aerosol processing in warm clouds via aqueous-phase reactions. Here we investigate the physical modifications of aerosols following processing within ice clouds using a unique laboratory setup that simulates ice cloud processes. The processed particles have a porous structure due to phase separation upon freezing, subsequent glass transition, and ice sublimation. Such modified aerosols can be better ice and cloud condensation nuclei and scatter less light. These changes have implications for aerosol–cloud interactions and optical properties of aerosols in the vicinity of clouds.
Relaxin-3/RXFP3 system regulates alcohol-seeking
Authors: Ryan Philip J. , Kastman Hanna E. , Krstew Elena V. , Rosengren K. Johan , Hossain Mohammed Akhter , Churilov Leonid , Wade John D. , Gundlach Andrew L. , Lawrence Andrew J.
Published: December 2013

Significance

Relapse and hazardous drinking represent the most difficult clinical problems in treating patients with alcohol use disorders. Increasing our understanding of the brain circuits and chemicals that regulate alcohol intake and relapse offers the potential for more targeted therapeutic approaches to assist in relapse prevention. Using a rat model of alcohol use and alcohol-seeking, we provide the first evidence that a neuropeptide, namely relaxin-3, acts upon specific receptors (relaxin family peptide 3) within the brain to regulate alcohol self-administration and relapse-like behavior. In the case of relapse-like alcohol-seeking, this system appears particularly involved in stress-mediated relapse via actions within a brain region called the bed nucleus of the stria terminalis.
Role for regulated phosphatase activity in generating mitotic oscillations in
Xenopus
cell-free extracts
Authors: Zhang Tongli , Tyson John J. , Novák Béla
Published: December 2013

Significance

A long-standing puzzle in the cell-cycle field is how it can be that the anaphase-promoting complex/cyclosome (APC/C) gets activated only when cyclin-dependent kinase 1 (Cdk1) activity reaches a very high level in metaphase but stays active even after Cdk1 activity drops to much lower levels as cells exit mitosis. In this manuscript, we propose that the regulation of a protein phosphatase 2A (PP2A:B55δ) by Greatwall kinase might provide a solution to this puzzle. Our proposal is consistent with what is already known about the regulation of Cdk1 and PP2A:B55δ in frog eggs, and it leads to testable predictions.
Optical control of an ion channel gate
Authors: Lemoine Damien , Habermacher Chloé , Martz Adeline , Méry Pierre-François , Bouquier Nathalie , Diverchy Fanny , Taly Antoine , Rassendren François , Specht Alexandre , Grutter Thomas
Published: December 2013

Significance

Engineered light-sensitive ion channels offer the opportunity to govern electrical activity of neurons. To date, developed strategies have relied on specific actions on either ligand-binding or permeation pathways. Here we developed a unique and versatile method, in which the gating machinery of an ATP-activated channel (purinergic P2X receptor) was reprogrammed to respond to light. We found that channels covalently modified by azobenzene-containing reagents at the transmembrane segments could be reversibly turned on and off by light, without the need of the natural ligand (here ATP). We demonstrate photocontrol of neuronal activity by a light-gated P2X receptor, in which the natural sensitivity to ATP was genetically removed. These light-gated P2X receptors represent valuable tools for investigating their physiological functions.
Codon 104 variation of
p53
gene provides adaptive apoptotic responses to extreme environments in mammals of the Tibet plateau
Authors: Zhao Yang , Ren Ji-Long , Wang Ming-Yang , Zhang Sheng-Ting , Liu Yu , Li Min , Cao Yi-Bin , Zu Hu-Yue , Chen Xiao-Cheng , Wu Chung-I , Nevo Eviatar , Chen Xue-Qun , Du Ji-Zeng
Published: December 2013

Significance

This work explores the environmental correlates of variations in codon 104 of the
p53
gene in three mammalian species: two subterranean mammals, highland- and lowland-dwelling wild zokors (
Myospalax baileyi
and
Myospalax cansus
, respectively), and one highland-dwelling aboveground species, the root vole (
Microtus oeconomus
). In
Microtus oeconomus
the codon 104E variation in
p53
suppresses apoptotic gene reactivation and cell apoptosis. In contrast, in
M
.
baileyi
the codon104N variation is responsible for the transactivation of apoptotic genes under three environmental stresses—hypoxia, hypercapnia (acidic stress, high CO
2
), and cold temperature—that characterize its ecological niche in the Tibet plateau. We conclude that p53 in nature is adapted in structure and function in accordance with specific ecological stresses.
Genome-block expression-assisted association studies discover malaria resistance genes in
Anopheles gambiae
Authors: Li Jun , Wang Xiaohong , Zhang Genwei , Githure John I. , Yan Guiyun , James Anthony A.
Published: December 2013

Significance

We developed an approach to fine-map large genomic regions that play important roles for malaria parasite resistance in the vector mosquito,
Anopheles gambiae
. Direct-association studies in wild mosquitoes from malaria-endemic areas in Africa identified three mutations in three genes that are associated significantly with
Plasmodium falciparum
infection. We confirmed the involvement of these genes in parasite infection by silencing them. The discovered genes will help us understand interactions between the mosquitoes and parasites. The identified single-nucleotide polymorphisms could be used to develop a malaria risk-assessment tool and may help eliminate parasite-susceptible mosquitoes.
Deconstructing complexin function in activating and clamping Ca
2+
-triggered exocytosis by comparing knockout and knockdown phenotypes
Authors: Yang Xiaofei , Cao Peng , Südhof Thomas C.
Published: December 2013

Significance

Complexin, a presynaptic protein that avidly binds to assembled SNARE complexes, is known to activate Ca
2+
-triggered exocytosis of synaptic vesicles. However, the function of complexin in priming the readily releasable pool of vesicles and in clamping spontaneous exocytosis remained debatable because knockout and knockdown approaches produced different results. Here, in a direct comparison of these approaches, we find that complexin-deficient neurons invariably exhibited a decrease in vesicle priming, but that their spontaneous release phenotype depended on the developmental history and type of neuron. Viewed together, our data suggest that complexin generally functions in priming and Ca
2+
triggering of exocytosis, and additionally, dependent on the developmental context, contributes to the control of spontaneous exocytosis.
Couple Bargaining or Socio-Economic Status?
Authors: Baizán Pau , Domínguez Marta , González María José
Published: December 2013

The quality of time dedicated to child care has potentially positive effects on children's life chances. However, the determinants of parental time allocation to child care remain largely unexplored. We assess two main explanations for differences among parents in the amount of time spent with children. The first, based on the relative resources hypothesis, links variation in time spent with children to the relative attributes (occupation, education or income) of one partner with the other. The second, derived from the social status hypothesis, suggests that variation in time spent with children can be attributed to the relative social position of the couple (i.e. higher status couples spend more time with children regardless of within-couple difference). To investigate these questions, we use a sample of parents living in a partnership with children younger than 10 years old from the 2002 to 2003 Spanish Time Use Survey (STUS) (n = 7438). We find little support for the ‘relative resources hypothesis’, although it has some explanatory power on supervisory and routine activities performed with children. Instead, consistent with the ‘social status hypothesis’, we find that time spent on child care is attributable to the social position of the couple, regardless of between-parent differences in income or education. The ‘social status hypothesis’ is especially relevant for explaining the time that parents devote to activities that have a higher potential for the development of the child's cognitive and social capabilities.
Effects of Stimulus Order on Discrimination Processes in Comparative and Equality Judgements: Data and Models
Authors: Dyjas Oliver , Ulrich Rolf
Published: December 2013

In typical discrimination experiments, participants are presented with a constant standard and a variable comparison stimulus and their task is to judge which of these two stimuli is larger (comparative judgement). In these experiments, discrimination sensitivity depends on the temporal order of these stimuli (Type B effect) and is usually higher when the standard precedes rather than follows the comparison. Here, we outline how two models of stimulus discrimination can account for the Type B effect, namely the weighted difference model (or basic Sensation Weighting model) and the Internal Reference Model. For both models, the predicted psychometric functions for comparative judgements as well as for equality judgements, in which participants indicate whether they perceived the two stimuli to be equal or not equal, are derived and it is shown that the models also predict a Type B effect for equality judgements. In the empirical part, the models’ predictions are evaluated. To this end, participants performed a duration discrimination task with comparative judgements and with equality judgements. In line with the models’ predictions, a Type B effect was observed for both judgement types. In addition, a time-order error, as indicated by shifts of the psychometric functions, and differences in response times were observed only for the equality judgement. Since both models entail distinct additional predictions, it seems worthwhile for future research to unite the two models into one conceptual framework.
Sip1 mediates an E-cadherin-to-N-cadherin switch during cranial neural crest EMT
Authors: Rogers Crystal D. , Saxena Ankur , Bronner Marianne E.
Published: December 2013

The neural crest, an embryonic stem cell population, initially resides within the dorsal neural tube but subsequently undergoes an epithelial-to-mesenchymal transition (EMT) to commence migration. Although neural crest and cancer EMTs are morphologically similar, little is known regarding conservation of their underlying molecular mechanisms. We report that Sip1, which is involved in cancer EMT, plays a critical role in promoting the neural crest cell transition to a mesenchymal state. Sip1 transcripts are expressed in premigratory/migrating crest cells. After Sip1 loss, the neural crest specifier gene FoxD3 was abnormally retained in the dorsal neuroepithelium, whereas Sox10, which is normally required for emigration, was diminished. Subsequently, clumps of adherent neural crest cells remained adjacent to the neural tube and aberrantly expressed E-cadherin while lacking N-cadherin. These findings demonstrate two distinct phases of neural crest EMT, detachment and mesenchymalization, with the latter involving a novel requirement for Sip1 in regulation of cadherin expression during completion of neural crest EMT.
The RNA-binding protein Fus directs translation of localized mRNAs in APC-RNP granules
Authors: Yasuda Kyota , Zhang Huaye , Loiselle David , Haystead Timothy , Macara Ian G. , Mili Stavroula
Published: December 2013

RNA localization pathways direct numerous mRNAs to distinct subcellular regions and affect many physiological processes. In one such pathway the tumor-suppressor protein adenomatous polyposis coli (APC) targets RNAs to cell protrusions, forming APC-containing ribonucleoprotein complexes (APC-RNPs). Here, we show that APC-RNPs associate with the RNA-binding protein Fus/TLS (fused in sarcoma/translocated in liposarcoma). Fus is not required for APC-RNP localization but is required for efficient translation of associated transcripts. Labeling of newly synthesized proteins revealed that Fus promotes translation preferentially within protrusions. Mutations in Fus cause amyotrophic lateral sclerosis (ALS) and the mutant protein forms inclusions that appear to correspond to stress granules. We show that overexpression or mutation of Fus results in formation of granules, which preferentially recruit APC-RNPs. Remarkably, these granules are not translationally silent. Instead, APC-RNP transcripts are translated within cytoplasmic Fus granules. These results unexpectedly show that translation can occur within stress-like granules. Importantly, they identify a new local function for cytoplasmic Fus with implications for ALS pathology.
The shelterin protein POT-1 anchors Caenorhabditis elegans telomeres through SUN-1 at the nuclear periphery
Authors: Ferreira Helder C. , Towbin Benjamin D. , Jegou Thibaud , Gasser Susan M.
Published: December 2013

Telomeres are specialized protein–DNA structures that protect chromosome ends. In budding yeast, telomeres form clusters at the nuclear periphery. By imaging telomeres in embryos of the metazoan Caenorhabditis elegans, we found that telomeres clustered only in strains that had activated an alternative telomere maintenance pathway (ALT). Moreover, as in yeast, the unclustered telomeres in wild-type embryos were located near the nuclear envelope (NE). This bias for perinuclear localization increased during embryogenesis and persisted in differentiated cells. Telomere position in early embryos required the NE protein SUN-1, the single-strand binding protein POT-1, and the small ubiquitin-like modifier (SUMO) ligase GEI-17. However, in postmitotic larval cells, none of these factors individually were required for telomere anchoring, which suggests that additional mechanisms anchor in late development. Importantly, targeted POT-1 was sufficient to anchor chromatin to the NE in a SUN-1–dependent manner, arguing that its effect at telomeres is direct. This high-resolution description of telomere position within C. elegans extends our understanding of telomere organization in eukaryotes.
Loss of centrioles causes chromosomal instability in vertebrate somatic cells
Authors: Sir Joo-Hee , Pütz Monika , Daly Owen , Morrison Ciaran G. , Dunning Mark , Kilmartin John V. , Gergely Fanni
Published: December 2013

Most animal cells contain a centrosome, which comprises a pair of centrioles surrounded by an ordered pericentriolar matrix (PCM). Although the role of this organelle in organizing the mitotic spindle poles is well established, its precise contribution to cell division and cell survival remains a subject of debate. By genetically ablating key components of centriole biogenesis in chicken DT40 B cells, we generated multiple cell lines that lack centrioles. PCM components accumulated in acentriolar microtubule (MT)-organizing centers but failed to adopt a higher-order structure, as shown by three-dimensional structured illumination microscopy. Cells without centrioles exhibited both a delay in bipolar spindle assembly and a high rate of chromosomal instability. Collectively, our results expose a vital role for centrosomes in establishing a mitotic spindle geometry that facilitates correct kinetochore–MT attachments. We propose that centrosomes are essential in organisms in which rapid segregation of a large number of chromosomes needs to be attained with fidelity.
Gata2 cis-element is required for hematopoietic stem cell generation in the mammalian embryo
Authors: Gao Xin , Johnson Kirby D. , Chang Yuan-I , Boyer Meghan E. , Dewey Colin N. , Zhang Jing , Bresnick Emery H.
Published: December 2013

The generation of hematopoietic stem cells (HSCs) from hemogenic endothelium within the aorta, gonad, mesonephros (AGM) region of the mammalian embryo is crucial for development of the adult hematopoietic system. We described a deletion of a Gata2 cis-element (+9.5) that depletes fetal liver HSCs, is lethal at E13–14 of embryogenesis, and is mutated in an immunodeficiency that progresses to myelodysplasia/leukemia. Here, we demonstrate that the +9.5 element enhances Gata2 expression and is required to generate long-term repopulating HSCs in the AGM. Deletion of the +9.5 element abrogated the capacity of hemogenic endothelium to generate HSC-containing clusters in the aorta. Genomic analyses indicated that the +9.5 element regulated a rich ensemble of genes that control hemogenic endothelium and HSCs, as well as genes not implicated in hematopoiesis. These results reveal a mechanism that controls stem cell emergence from hemogenic endothelium to establish the adult hematopoietic system.
NextClip: an analysis and read preparation tool for Nextera Long Mate Pair libraries
Authors: Leggett Richard M. , Clavijo Bernardo J. , Clissold Leah , Clark Matthew D. , Caccamo Mario
Published: December 2013

Summary: Illumina’s recently released Nextera Long Mate Pair (LMP) kit enables production of jumping libraries of up to 12 kb. The LMP libraries are an invaluable resource for carrying out complex assemblies and other downstream bioinformatics analyses such as the characterization of structural variants. However, LMP libraries are intrinsically noisy and to maximize their value, post-sequencing data analysis is required. Standardizing laboratory protocols and the selection of sequenced reads for downstream analysis are non-trivial tasks. NextClip is a tool for analyzing reads from LMP libraries, generating a comprehensive quality report and extracting good quality trimmed and deduplicated reads.

Availability and implementation: Source code, user guide and example data are available from https://github.com/richardmleggett/nextclip/.

Contact:  Richard.Leggett@tgac.ac.uk

Supplementary information:  Supplementary data are available at Bioinformatics online.
Market-driven considerations affecting the prospects of alternative road fuels
Authors: Freedman David
Published: December 2013

Without significant intervention, demand for crude oil could rise by a further 25% by 2035, stemming from its use for transportation, particularly road transport. Many technologies for alternative fuels and substitute transport energy carriers are being researched, but successful implementation of these technologies at scale will require attention to consumer-behavioural and policy challenges as well as adapting existing or introducing new commercial value chains. In particular, there will be new capital-intensive roles for which there are no obvious contenders as yet. The legacy of diverse urban planning and fuel taxation policies and varying degrees of consumer inertia will lead to different rates of adoption of different alternative technologies in regional markets. In the absence of technology that provides a compelling consumer proposition, substitution of crude demand in mature markets will be challenging, as will be channelling exponential growth from growing markets like China into less crude-intensive road transport solutions.
Oil and the world economy: some possible futures
Authors: Kumhof Michael , Muir Dirk
Published: December 2013

This paper, using a six-region dynamic stochastic general equilibrium model of the world economy, assesses the output and current account implications of permanent oil supply shocks hitting the world economy. For modest-sized shocks and conventional production technologies, the effects are modest. But for larger shocks, for elasticities of substitution that decline as oil usage is reduced to a minimum, and for production functions in which oil acts as a critical enabler of technologies, output growth could drop significantly. Also, oil prices could become so high that smooth adjustment, as assumed in the model, may become very difficult.
The implications of the declining energy return on investment of oil production
Authors: Murphy David J.
Published: December 2013

Declining production from conventional oil resources has initiated a global transition to unconventional oil, such as tar sands. Unconventional oil is generally harder to extract than conventional oil and is expected to have a (much) lower energy return on (energy) investment (EROI). Recently, there has been a surge in publications estimating the EROI of a number of different sources of oil, and others relating EROI to long-term economic growth, profitability and oil prices. The following points seem clear from a review of the literature: (i) the EROI of global oil production is roughly 17 and declining, while that for the USA is 11 and declining; (ii) the EROI of ultra-deep-water oil and oil sands is below 10; (iii) the relation between the EROI and the price of oil is inverse and exponential; (iv) as EROI declines below 10, a point is reached when the relation between EROI and price becomes highly nonlinear; and (v) the minimum oil price needed to increase the oil supply in the near term is at levels consistent with levels that have induced past economic recessions. From these points, I conclude that, as the EROI of the average barrel of oil declines, long-term economic growth will become harder to achieve and come at an increasingly higher financial, energetic and environmental cost.
Synaptic plasticity in health and disease: introduction and overview
Authors: Bliss T. V. P. , Collingridge G. L. , Morris R. G. M.
Published: December 2013

We summarize the reviews and research papers submitted by speakers at a discussion meeting on Synaptic Plasticity in Health and Disease held at the Royal Society, London on 2–3 December 2013, and a subsequent satellite meeting convened at the Royal Society/Kavli Centre at Chicheley Hall on 4–5 December 2013. Together, these contributions give an overview of current research and controversies in a vibrant branch of neuroscience with important implications for the understanding of many forms of learning and memory, and a wide spectrum of neurological and cognitive disorders.
NMDA receptor-dependent long-term potentiation comprises a family of temporally overlapping forms of synaptic plasticity that are induced by different patterns of stimulation
Authors: Park Pojeong , Volianskis Arturas , Sanderson Thomas M. , Bortolotto Zuner A. , Jane David E. , Zhuo Min , Kaang Bong-Kiun , Collingridge Graham L.
Published: December 2013

N-methyl-d-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP) is extensively studied since it is believed to use the same molecular mechanisms that are required for many forms of learning and memory. Unfortunately, many controversies exist, not least the seemingly simple issue concerning the locus of expression of LTP. Here, we review our recent work and some of the extensive literature on this topic and present new data that collectively suggest that LTP can be explained, during its first few hours, by the coexistence of at least three mechanistically distinct processes that are all triggered by the synaptic activation of NMDARs.
Shank mutant mice as an animal model of autism
Authors: Yoo Juyoun , Bakes Joseph , Bradley Clarrisa , Collingridge Graham L. , Kaang Bong-Kiun
Published: December 2013

In this review, we focus on the role of the Shank family of proteins in autism. In recent years, autism research has been flourishing. With genetic, molecular, imaging and electrophysiological studies being supported by behavioural studies using animal models, there is real hope that we may soon understand the fundamental pathology of autism. There is also genuine potential to develop a molecular-level pharmacological treatment that may be able to deal with the most severe symptoms of autism, and clinical trials are already underway. The Shank family of proteins has been strongly implicated as a contributing factor in autism in certain individuals and sits at the core of the alleged autistic pathway. Here, we analyse studies that relate Shank to autism and discuss what light this sheds on the possible causes of autism.
GluA1 trafficking and metabotropic NMDA: addressing results from other laboratories inconsistent with ours
Authors: Nabavi Sadegh , Fox Rocky , Alfonso Stephanie , Aow Jonathan , Malinow Roberto
Published: December 2013

We have previously shown that when over-expressed in neurons, green fluorescent protein (GFP) tagged GluA1 (GluA1-GFP) delivery into synapses is dependent on plasticity. A recent study suggests that GluA1 over-expression leads to its incorporation into the synapse, in the absence of additional long-term potentiation-like manipulations. It is possible that a GFP tag was responsible for the difference. Using rectification index as a measure of synaptic delivery of GluA1, we found no difference in the synaptic delivery of GluA1-GFP versus untagged GluA1. We recently published a study showing that while D-APV blocks NMDAr-dependent long-term depression (LTD), MK-801 and 7-chloro kynurenate (7CK) fail to block LTD. We propose a metabotropic function for the NMDA receptor in LTD induction. In contrast to our observations, recent unpublished data suggest that the above antagonists are equally effective in blocking LTD. We noticed different methodology in their study. Here, we show that their methodology has complex effects on synaptic transmission. Therefore, it is not possible to conclude that 7CK is effective in blocking LTD from their type of experiment.
Neurotransmitter receptor and time dependence of the synaptic plasticity disrupting actions of Alzheimer's disease Aβ
in vivo
Authors: Klyubin Igor , Ondrejcak Tomas , Hayes Jennifer , Cullen William K. , Mably Alexandra J. , Walsh Dominic M. , Rowan Michael J.
Published: December 2013

Many endogenous factors influence the time course and extent of the detrimental effects of amyloid β-protein (Aβ) on synaptic function. Here, we assessed the impact of varying endogenous glutamatergic and cholinergic transmission by pharmacological means on the disruption of plasticity at hippocampal CA3-to-CA1 synapses in the anaesthetized rat. NMDA receptors (NMDARs) are considered critical in mediating Aβ-induced inhibition of long-term potentiation (LTP). However, intracerebroventricular injection of Aβ
1–42
inhibited not only NMDAR-dependent LTP but also voltage-activated Ca
2+
-dependent LTP induced by strong conditioning stimulation during NMDAR blockade. On the other hand, another form of NMDAR-independent synaptic plasticity, endogenous acetylcholine-induced muscarinic receptor-dependent long-term enhancement, was not hindered by Aβ
1–42
. Interestingly, augmenting endogenous acetylcholine activation of nicotinic receptors prior to the injection of Aβ
1–42
prevented the inhibition of NMDAR-dependent LTP, whereas the same intervention when introduced after the infusion of Aβ was ineffective. We also examined the duration of action of Aβ, including water soluble Aβ from Alzheimer's disease (AD) brain. Remarkably, the inhibition of LTP induction caused by a single injection of sodium dodecyl sulfate-stable Aβ dimer-containing AD brain extract persisted for at least a week. These findings highlight the need to increase our understanding of non-NMDAR mechanisms and of developing novel means of overcoming, rather than just preventing, the deleterious synaptic actions of Aβ.
Untangling the two-way signalling route from synapses to the nucleus, and from the nucleus back to the synapses
Authors: Nonaka Mio , Fujii Hajime , Kim Ryang , Kawashima Takashi , Okuno Hiroyuki , Bito Haruhiko
Published: December 2013

During learning and memory, it has been suggested that the coordinated electrical activity of hippocampal neurons translates information about the external environment into internal neuronal representations, which then are stored initially within the hippocampus and subsequently into other areas of the brain. A widely held hypothesis posits that synaptic plasticity is a key feature that critically modulates the triggering and the maintenance of such representations, some of which are thought to persist over time as traces or tags. However, the molecular and cell biological basis for these traces and tags has remained elusive. Here, we review recent findings that help clarify some of the molecular and cellular mechanisms critical for these events, by untangling a two-way signalling crosstalk route between the synapses and the neuronal soma. In particular, a detailed interrogation of the soma-to-synapse delivery of immediate early gene product Arc/Arg3.1, whose induction is triggered by heightened synaptic activity in many brain areas, teases apart an unsuspected ‘inverse’ synaptic tagging mechanism that likely contributes to maintaining the contrast of synaptic weight between strengthened and weak synapses within an active ensemble.
Two sides to long-term potentiation: a view towards reconciliation
Authors: Padamsey Zahid , Emptage Nigel
Published: December 2013

Almost since the discovery of long-term potentiation (LTP) in the hippocampus, its locus of expression has been debated. Throughout the years, convincing evidence has accumulated to suggest that LTP can be supported either presynaptically, by an increase in transmitter release, or postsynaptically, by an increase in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor number. However, whereas postsynaptic enhancement appears to be consistently obtained across studies following LTP induction, presynaptic enhancement is not as reliably observed. Such discrepancies, along with the failure to convincingly identify a retrograde messenger required for presynaptic change, have led to the general view that LTP is mainly supported postsynaptically, and certainly, research within the field for the past decade has been heavily focused on the postsynaptic locus. Here, we argue that LTP can be expressed at either synaptic locus, but that pre- and postsynaptic forms of LTP are dissociable phenomena mediated by distinct mechanistic processes, which are sensitive to different patterns of neuronal activity. This view of LTP helps to reconcile discrepancies across the literature and may put to rest a decades-long debate.
Zif268
/
Egr1
gain of function facilitates hippocampal synaptic plasticity and long-term spatial recognition memory
Authors: Penke Zsuzsa , Morice Elise , Veyrac Alexandra , Gros Alexandra , Chagneau Carine , LeBlanc Pascale , Samson Nathalie , Baumgärtel Karsten , Mansuy Isabelle M. , Davis Sabrina , Laroche Serge
Published: December 2013

It is well established that
Zif268/Egr1
, a member of the
Egr
family of transcription factors, is critical for the consolidation of several forms of memory; however, it is as yet uncertain whether increasing expression of
Zif268
in neurons can facilitate memory formation. Here, we used an inducible transgenic mouse model to specifically induce
Zif268
overexpression in forebrain neurons and examined the effect on recognition memory and hippocampal synaptic transmission and plasticity. We found that
Zif268
overexpression during the establishment of memory for objects did not change the ability to form a long-term memory of objects, but enhanced the capacity to form a long-term memory of the spatial location of objects. This enhancement was paralleled by increased long-term potentiation in the dentate gyrus of the hippocampus and by increased activity-dependent expression of Zif268 and selected Zif268 target genes. These results provide novel evidence that transcriptional mechanisms engaging
Zif268
contribute to determining the strength of newly encoded memories.
Moderate AMPA receptor clustering on the nanoscale can efficiently potentiate synaptic current
Authors: Savtchenko Leonid P. , Rusakov Dmitri A.
Published: December 2013

The prevailing view at present is that postsynaptic expression of the classical NMDA receptor-dependent long-term potentiation relies on an increase in the numbers of local AMPA receptors (AMPARs). This is thought to parallel an expansion of postsynaptic cell specializations, for instance dendritic spine heads, which accommodate synaptic receptor proteins. However, glutamate released into the synaptic cleft can normally activate only a hotspot of low-affinity AMPARs that occur in the vicinity of the release site. How the enlargement of the AMPAR pool is causally related to the potentiated AMPAR current remains therefore poorly understood. To understand possible scenarios of postsynaptic potentiation, here we explore a detailed Monte Carlo model of the typical small excitatory synapse. Simulations suggest that approximately 50% increase in the synaptic AMPAR current could be provided by expanding the existing AMPAR pool at the expense of 100–200% new AMPARs added at the same packing density. Alternatively, reducing the inter-receptor distances by only 30–35% could achieve a similar level of current potentiation without any changes in the receptor numbers. The NMDA receptor current also appears sensitive to the NMDA receptor crowding. Our observations provide a quantitative framework for understanding the ‘resource-efficient’ ways to enact use-dependent changes in the architecture of central synapses.
The synaptic plasticity and memory hypothesis: encoding, storage and persistence
Authors: Takeuchi Tomonori , Duszkiewicz Adrian J. , Morris Richard G. M.
Published: December 2013

The synaptic plasticity and memory hypothesis asserts that activity-dependent synaptic plasticity is induced at appropriate synapses during memory formation and is both necessary and sufficient for the encoding and trace storage of the type of memory mediated by the brain area in which it is observed. Criteria for establishing the necessity and sufficiency of such plasticity in mediating trace storage have been identified and are here reviewed in relation to new work using some of the diverse techniques of contemporary neuroscience. Evidence derived using optical imaging, molecular-genetic and optogenetic techniques in conjunction with appropriate behavioural analyses continues to offer support for the idea that changing the strength of connections between neurons is one of the major mechanisms by which engrams are stored in the brain.
Oropharyngeal and nasopharyngeal sampling for the detection of adolescent Streptococcus pneumoniae carriers
Authors: Principi Nicola , Terranova Leonardo , Zampiero Alberto , Manzoni Francesca , Senatore Laura , Rios Walter Peves , Esposito Susanna
Published: December 2013

Monitoring the dynamics of pneumococcal carriage makes it possible to evaluate the epidemiological characteristics of Streptococcus pneumoniae disease and the theoretical coverage offered by pneumococcal vaccines. It has been demonstrated that the nasopharyngeal (NP) sampling of respiratory secretions is superior to oropharyngeal (OP) sampling for identifying pneumococci carried by younger children, but adult data are conflicting and there are no published studies of adolescents. In order to compare the efficiency of OP and NP sampling in identifying and quantifying S. pneumoniae carriage in healthy adolescents, 2 swab samples were obtained from 530 adolescents aged 15–19 years, the first taken from the posterior pharyngeal wall through the mouth (OP) and the second through the nose (NP). Bacterial genomic DNA was tested for the autolysin-A-encoding gene (lytA) and wzg (cpsA) gene of S. pneumoniae in order to evaluate pneumococcal carrier status. All of the positive cases were serotyped. S. pneumoniae was identified in 35.8 % of the OP swabs and 3.5 % of the NP swabs (P<0.0001). The serotypes included in the 13-valent pneumococcal conjugate vaccine (PCV13) were found in all but two OP samples (98.9 %) and only 64.7 % of the NP samples (P<0.0001). The most frequently identified PCV13 serotype in both groups was 19F, followed by serotypes 5 and 9V. In conclusion, OP sampling appeared significantly more effective than NP sampling in identifying and characterizing pneumococcal carrier status in adolescents. This suggests that OP sampling should be used when evaluating the dynamics of pneumococcal carriage among adolescents and the theoretical coverage offered by PCV13.
A null model for Pearson coexpression networks
Authors: Gobbi Andrea , Jurman Giuseppe
Published: December 2013

Gene coexpression networks inferred by correlation from high-throughput profiling such as microarray data represent a simple but effective technique for discovering and interpreting linear gene relationships. In the last years several approach have been proposed to tackle the problem of deciding when the resulting correlation values are statistically significant. This is mostly crucial when the number of samples is small, yielding a non negligible chance that even high correlation values are due to random effects. Here we introduce a novel hard thresholding solution based on the assumption that a coexpression network inferred by randomly generated data is expected to be empty. The theoretical derivation of the new bound by geometrical methods is shown together with applications in onco- and neurogenomics.
Dichlorido{8-[2-(dimethylamino)ethylamino]quinoline-κ3
N,N′,N′′}zinc
Authors: Al-Sudani Abdul-Razak H.
Published: December 2013

In the title complex, [ZnCl2(C13H17N3)], the coordination sphere of the zinc cation is distorted square pyramidal. The three N atoms of the N,N′,N′′-tridentate 8-[2-(dimethylamino)ethylamino]quinoline ligand and one chloride ion constitute a considerably distorted square base. The apical site is occupied by another chloride ion. The distortion from the ideal square-pyramidal geometry is manifested by the N—Zn—N angle of 133.25 (11)°. Like most square-pyramidal metal complexes, the zinc cation is displaced towards the apical chloride ion. In the crystal, molecules are linked by N—H...Cl interactions. This leads to the formation of chains of molecules parallel to the b-axis direction.
(6-Chloropyridazin-3-yl)ferrocene
Authors: Shi Guo-Qing , Zhao Wen-En , Zhao Xiao-Hui , Hao Lu-Ye
Published: December 2013

The asymmetric unit of the title compound, [Fe(C5H5)(C9H6ClN2)], contains two independent molecules in which the cyclopentadienyl rings are almost parallel, making dihedral angles of 2.16 (4) and 2.71 (5), and the dihedral angles between the pyridazinyl and substituted cyclopentadienyl rings are 9.65 (5) and 11.53 (8)°. In the crystal, molecules are linked by C—H...N hydrogen bonds into chains along the c-axis direction.
Benzyltris[2-(dibenzylamino)ethyl]ammonium iodide
Authors: Bello Mollie J. , Brady Sarah E. , Zakharov Lev N. , Tyler David R.
Published: December 2013

In the title quaternary ammonium salt, C55H61N4
+·I−, all three N,N-dibenzylethanamine, –(CH2)2N(CH2C6H5)2, groups have different conformations. The N—C—C—N torsion angles are significantly different [89.86 (13), 162.61 (10) and 175.70 (10)°] and the dihedral angles between the phenyl rings in these groups are different as well [58.21 (4), 43.73 (4) and 76.72 (5)°]. In the crystal, the I− anions fill empty spaces between the bulky cations. The cations and anions are linked by weak C—H...I interactions, forming a chain along [110].
4-Methyl-N-(4-methylphenylsulfonyl)-N-[4-(4-methylphenyl)-1,3-thiazol-2-yl]benzenesulfonamide
Authors: Carballo Rubén M. , Hernández-Ortega Simón , Padilla-Montaño Nayely , Reyes-Martínez Reyna , Mirón-López Gumersindo
Published: December 2013

There are two independent molecules in the asymmetric unit of the title compound, C24H22N2O4S3. In each, the sulfonamide N atoms reveal nearly a trigonal-planar geometry with two S atoms of the O=S=O groups and one C atom of the thiazole ring; the angles around the N atoms are between 117.00 (13) and 123.86 (9)°. The methylphenylsulfonyl groups are in anti conformations, forming dihedral angles of 78.00 (7)/72.53 (5) and 77.09 (6)/71.50 (7)° with the trigonal S—N—S planes in the two molecules. The thiazole groups are rotated around the C—N bonds and are almost perpendicular to the S—N—S plane [dihedral angles of 78.00 (7)/72.53 (5) and 77.09 (6)/71.50 (7)°]. In the crystal, pairs of C—H...O interactions, with the O atoms of the sulfonamide groups as acceptors, link each of the independent molecules into inversion dimers.
Ethyl 6-methyl-2-oxo-4-[4-(1H-tetrazol-5-yl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate–dimethylformamide–water (2/1/1)
Authors: Ouyang Hua-Yong , Chang Yi-Qi , Zhao Lu
Published: December 2013

The asymmetric unit of the title compound, 2C15H16N6O3·C3H7NO·H2O, contains two independent ethyl 6-methyl-2-oxo-4-[4-(1H-tetrazol-5-yl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate molecules, in which the dihedral angles between the tetrazole and benzene rings are 20.54 (12) and 12.13 (12)°. An intramolecular C—H...O hydrogen bond occurs in each molecule. In the crystal, N—H...O, N—H...N, O—H...O and O—H...N hydrogen bonds, as well as weak C—H...O and C—H...N hydrogen bonds, link the molecules into a three-dimensional supramolecular architecture. π–π stacking is also observed between parallel tetrazole rings of adjacent molecules, the centroid–centroid distance being 3.482 (6) Å.
2,6-Bis(bromomethyl)pyridine
Authors: Cuzan Olesea , Straistari Tatiana , Turta Constantin , Réglier Marius
Published: December 2013

In the title molecule, C7H7Br2N, the C—Br vectors of the bromomethyl groups extend to opposite sides of the pyridine ring and are oriented nearly perpendicular to its plane. In the crystal, the molecules related by a c-glide-plane operation are arranged into stacks along the c axis, with centroid–centroid distances between neighboring aromatic rings of 3.778 (2) Å. A short Br...Br contact of 3.6025 (11) Å is observed within a pair of inversion-related molecules.
2-[(E)-2-(4-Ethoxyphenyl)ethenyl]-1-methylquinolinium 4-fluorobenzenesulfonate
Authors: Fun Hoong-Kun , Kobkeatthawin Thawanrat , Ruanwas Pumsak , Quah Ching Kheng , Chantrapromma Suchada
Published: December 2013

In the structure of the title salt, C20H20NO+·C6H4FO3S−, the 4-(ethoxyphenyl)ethenyl unit is disordered over two positions with a refined site-occupancy ratio of 0.610 (6):0.390 (6). The cation is nearly planar, the dihedral angle between the quinolinium and benzene rings being 6.7 (4) and 1.7 (7)° for the major and minor components, respectively. The ethoxy group is essentially coplanar with the benzene ring [C—O—C—Cmethy = 177.1 (8) and 177.8 (12)° for the major and minor components, respectively]. In the crystal, cations and anions are linked into chains along the b-axis direction by C—H...Osulfonyl weak interactions. These chains are further connected into sheets parallel to (001) by C—H...Osulfonyl weak interactions. The chains are also stacked along the a axis through π–π interactions involving the quinolinium and benzene rings [centroid–centroid distances = 3.636 (5) Å for the major component and 3.800 (9) Å for the minor component]. C—H...π interactions are also present.