bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatiotemporal dynamics of neocortical excitation and inhibition during human sleep
Authors: Peyrache Adrien , Dehghani Nima , Eskandar Emad N. , Madsen Joseph R. , Anderson William S. , Donoghue Jacob A. , Hochberg Leigh R. , Halgren Eric , Cash Sydney S. , Destexhe Alain
Published: January 2012

Intracranial recording is an important diagnostic method routinely used in a number of neurological monitoring scenarios. In recent years, advancements in such recordings have been extended to include unit activity of an ensemble of neurons. However, a detailed functional characterization of excitatory and inhibitory cells has not been attempted in human neocortex, particularly during the sleep state. Here, we report that such feature discrimination is possible from high-density recordings in the neocortex by using 2D multielectrode arrays. Successful separation of regular-spiking neurons (or bursting cells) from fast-spiking cells resulted in well-defined clusters that each showed unique intrinsic firing properties. The high density of the array, which allowed recording from a large number of cells (up to 90), helped us to identify apparent monosynaptic connections, confirming the excitatory and inhibitory nature of regular-spiking and fast-spiking cells, thus categorized as putative pyramidal cells and interneurons, respectively. Finally, we investigated the dynamics of correlations within each class. A marked exponential decay with distance was observed in the case of excitatory but not for inhibitory cells. Although the amplitude of that decline depended on the timescale at which the correlations were computed, the spatial constant did not. Furthermore, this spatial constant is compatible with the typical size of human columnar organization. These findings provide a detailed characterization of neuronal activity, functional connectivity at the microcircuit level, and the interplay of excitation and inhibition in the human neocortex.
Nematode sperm maturation triggered by protease involves sperm-secreted serine protease inhibitor (Serpin)
Authors: Zhao Yanmei , Sun Wei , Zhang Pan , Chi Hao , Zhang Mei-Jun , Song Chun-Qing , Ma Xuan , Shang Yunlong , Wang Bin , Hu Youqiao , Hao Zhiqi , Hühmer Andreas F. , Meng Fanxia , L'Hernault Steven W. , He Si-Min , Dong Meng-Qiu , Miao Long
Published: January 2012

Spermiogenesis is a series of poorly understood morphological, physiological and biochemical processes that occur during the transition of immotile spermatids into motile, fertilization-competent spermatozoa. Here, we identified a Serpin (serine protease inhibitor) family protein (As_SRP-1) that is secreted from spermatids during nematode
Ascaris suum
spermiogenesis (also called sperm activation) and we showed that As_SRP-1 has two major functions. First, As_SRP-1 functions
in cis
to support major sperm protein (MSP)-based cytoskeletal assembly in the spermatid that releases it, thereby facilitating sperm motility acquisition. Second, As_SRP-1 released from an activated sperm inhibits,
in trans
, the activation of surrounding spermatids by inhibiting vas deferens-derived As_TRY-5, a trypsin-like serine protease necessary for sperm activation. Because vesicular exocytosis is necessary to create fertilization-competent sperm in many animal species, components released during this process might be more important modulators of the physiology and behavior of surrounding sperm than was previously appreciated.
Quantitative, directional measurement of electric field heterogeneity in the active site of ketosteroid isomerase
Authors: Fafarman Aaron T. , Sigala Paul A. , Schwans Jason P. , Fenn Timothy D. , Herschlag Daniel , Boxer Steven G.
Published: January 2012

Understanding the electrostatic forces and features within highly heterogeneous, anisotropic, and chemically complex enzyme active sites and their connection to biological catalysis remains a longstanding challenge, in part due to the paucity of incisive experimental probes of electrostatic properties within proteins. To quantitatively assess the landscape of electrostatic fields at discrete locations and orientations within an enzyme active site, we have incorporated site-specific thiocyanate vibrational probes into multiple positions within bacterial ketosteroid isomerase. A battery of X-ray crystallographic, vibrational Stark spectroscopy, and NMR studies revealed electrostatic field heterogeneity of 8 MV/cm between active site probe locations and widely differing sensitivities of discrete probes to common electrostatic perturbations from mutation, ligand binding, and pH changes. Electrostatic calculations based on active site ionization states assigned by literature precedent and computational pK
a
prediction were unable to quantitatively account for the observed vibrational band shifts. However, electrostatic models of the D40N mutant gave qualitative agreement with the observed vibrational effects when an unusual ionization of an active site tyrosine with a pK
a
near 7 was included. UV-absorbance and
13
C NMR experiments confirmed the presence of a tyrosinate in the active site, in agreement with electrostatic models. This work provides the most direct measure of the heterogeneous and anisotropic nature of the electrostatic environment within an enzyme active site, and these measurements provide incisive benchmarks for further developing accurate computational models and a foundation for future tests of electrostatics in enzymatic catalysis.
Striatum processes reward differently in adolescents versus adults
Authors: Sturman David A. , Moghaddam Bita
Published: January 2012

Adolescents often respond differently than adults to the same salient motivating contexts, such as peer interactions and pleasurable stimuli. Delineating the neural processing differences of adolescents is critical to understanding this phenomenon, as well as the bases of serious behavioral and psychiatric vulnerabilities, such as drug abuse, mood disorders, and schizophrenia. We believe that age-related changes in the ways salient stimuli are processed in key brain regions could underlie the unique predilections and vulnerabilities of adolescence. Because motivated behavior is the central issue, it is critical that age-related comparisons of brain activity be undertaken during motivational contexts. We compared single-unit activity and local field potentials in the nucleus accumbens (NAc) and dorsal striatum (DS) of adolescent and adult rats during a reward-motivated instrumental task. These regions are involved in motivated learning, reward processing, and action selection. We report adolescent neural processing differences in the DS, a region generally associated more with learning than reward processing in adults. Specifically, adolescents, but not adults, had a large proportion of neurons in the DS that activated in anticipation of reward. More similar response patterns were observed in NAc of the two age groups. DS single-unit activity differences were found despite similar local field potential oscillations. This study demonstrates that in adolescents, a region critically involved in learning and habit formation is highly responsive to reward. It thus suggests a mechanism for how rewards might shape adolescent behavior differently, and for their increased vulnerabilities to affective disorders.
Differential regulation of the activity of deleted in liver cancer 1 (DLC1) by tensins controls cell migration and transformation
Authors: Cao Xuan , Voss Courtney , Zhao Bing , Kaneko Tomonori , Li Shawn Shun-Cheng
Published: January 2012

The epithelial growth factor receptor plays an important role in cell migration and cancer metastasis, but the underlying molecular mechanism is not fully understood. We show here that differential regulation of the rhodopsin-GTPase-activating (Rho-GAP) activity of deleted in liver cancer 1 (DLC1) by tensin3 and COOH-terminal tensin-like protein (cten) controls EGF-driven cell migration and transformation. Tensin3 binds DLC1 through its actin-binding domain, a region that is missing in cten, and thereby releases an autoinhibitory interaction between the sterile alpha motif and Rho-GAP domains of DLC1. Consequently, tensin3, but not cten, promotes the activation of DLC1, which, in turn, leads to inactivation of RhoA and decreased cell migration. Depletion of endogenous tensin3, but not cten, augmented the formation of actin stress fibers and focal adhesions and enhanced cell motility. These effects were, however, ablated by an inhibitor of the Rho-associated protein kinase. Importantly, activation of DLC1 by tensin3 or its actin-binding domain drastically reduced the anchorage-independent growth of transformed cells. Our study therefore links dynamic regulation of tensin family members by EGF to Rho-GAP through DLC1 and suggests that the tensin-DLC1-RhoA signaling axis plays an important role in tumorigenesis and cancer metastasis, and may be explored for cancer intervention.
β-Bulge triggers route-switching on the functional landscape of interleukin-1β
Authors: Capraro Dominique T. , Roy Melinda , Onuchic José N. , Gosavi Shachi , Jennings Patricia A.
Published: January 2012

Proteins fold into three-dimensional structures in a funneled energy landscape. This landscape is also used for functional activity. Frustration in this landscape can arise from the competing evolutionary pressures of biological function and reliable folding. Thus, the ensemble of partially folded states can populate multiple routes on this journey to the native state. Although protein folding kinetics experiments have shown the presence of such routes for several proteins, there has been sparse information about the structural diversity of these routes. In addition, why a given protein populates a particular route more often than another protein of similar structure and sequence is not clear. Whereas multiple routes are observed in theoretical studies on the folding of interleukin-1β (IL-1β), experimental results indicate one dominant route where the central portion of the protein folds first, and is then followed by closure of the barrel in this β-trefoil fold. Here we show, using a combination of computation and experiment, that the presence of functionally important regions like the β-bulge in the signaling protein IL-1β strongly influences the choice of folding routes. By deleting the β-bulge, we directly observe the presence of route-switching. This route-switching provides a direct link between route selection and the folding and functional landscapes of a protein.
Polar growth in the Alphaproteobacterial order Rhizobiales
Authors: Brown Pamela J. B. , de Pedro Miguel A. , Kysela David T. , Van der Henst Charles , Kim Jinwoo , De Bolle Xavier , Fuqua Clay , Brun Yves V.
Published: January 2012

Elongation of many rod-shaped bacteria occurs by peptidoglycan synthesis at discrete foci along the sidewall of the cells. However, within the Rhizobiales, there are many budding bacteria, in which new cell growth is constrained to a specific region. The phylogeny of the Rhizobiales indicates that this mode of zonal growth may be ancestral. We demonstrate that the rod-shaped bacterium
Agrobacterium tumefaciens
grows unidirectionally from the new pole generated after cell division and has an atypical peptidoglycan composition. Polar growth occurs under all conditions tested, including when cells are attached to a plant root and under conditions that induce virulence. Finally, we show that polar growth also occurs in the closely related bacteria
Sinorhizobium meliloti
,
Brucella abortus
, and
Ochrobactrum anthropi
. We find that unipolar growth is an ancestral and conserved trait among the Rhizobiales, which includes important mutualists and pathogens of plants and animals.
Evolution of CpG island promoter function underlies changes in KChIP2 potassium channel subunit gene expression in mammalian heart
Authors: Yan Qinghong , Masson Rajeev , Ren Yi , Rosati Barbara , McKinnon David
Published: January 2012

Scaling of cardiac electrophysiology with body mass requires large changes in the ventricular action potential duration and heart rate in mammals. These changes in cellular electrophysiological function are produced by systematic and coordinated changes in the expression of multiple ion channel and transporter genes. Expression of one important potassium current, the transient outward current (
I
to
), changes significantly during mammalian evolution. Changes in
I
to
expression are determined, in part, by variation in the expression of an obligatory auxiliary subunit encoded by the KChIP2 gene. The KChIP2 gene is expressed in both cardiac myocytes and neurons and transcription in both cell types is initiated from the same CpG island promoter. Species-dependent variation of KChIP2 expression in heart is mediated by the evolution of the
cis
-regulatory function of this gene. Surprisingly, the major locus of evolutionary change for KChIP2 gene expression in heart lies within the CpG island core promoter. The results demonstrate that CpG island promoters are not simply permissive for gene expression but can also contribute to tissue-selective expression and, as such, can function as an important locus for the evolution of
cis
-regulatory function. More generally, evolution of the
cis
-regulatory function of voltage-gated ion channel genes appears to be an effective and efficient way to modify channel expression levels to optimize electrophysiological function.
Exceptionally preserved crustaceans from western Canada reveal a cryptic Cambrian radiation
Authors: Harvey Thomas H. P. , Vélez Maria I. , Butterfield Nicholas J.
Published: January 2012

The early history of crustaceans is obscured by strong biases in fossil preservation, but a previously overlooked taphonomic mode yields important complementary insights. Here we describe diverse crustacean appendages of Middle and Late Cambrian age from shallow-marine mudstones of the Deadwood Formation in western Canada. The fossils occur as flattened and fragmentary carbonaceous cuticles but provide a suite of phylogenetic and ecological data by virtue of their detailed preservation. In addition to an unprecedented range of complex, largely articulated filtering limbs, we identify at least four distinct types of mandible. Together, these fossils provide the earliest evidence for crown-group branchiopods and total-group copepods and ostracods, extending the respective ranges of these clades back from the Devonian, Pennsylvanian, and Ordovician. Detailed similarities with living forms demonstrate the early origins and subsequent conservation of various complex food-handling adaptations, including a directional mandibular asymmetry that has persisted through half a billion years of evolution. At the same time, the Deadwood fossils indicate profound secular changes in crustacean ecology in terms of body size and environmental distribution. The earliest radiation of crustaceans is largely cryptic in the fossil record, but “small carbonaceous fossils” reveal organisms of surprisingly modern aspect operating in an unfamiliar biosphere.
Experimental evolution of multicellularity
Authors: Ratcliff William C. , Denison R. Ford , Borrello Mark , Travisano Michael
Published: January 2012

Multicellularity was one of the most significant innovations in the history of life, but its initial evolution remains poorly understood. Using experimental evolution, we show that key steps in this transition could have occurred quickly. We subjected the unicellular yeast
Saccharomyces cerevisiae
to an environment in which we expected multicellularity to be adaptive. We observed the rapid evolution of clustering genotypes that display a novel multicellular life history characterized by reproduction via multicellular propagules, a juvenile phase, and determinate growth. The multicellular clusters are uniclonal, minimizing within-cluster genetic conflicts of interest. Simple among-cell division of labor rapidly evolved. Early multicellular strains were composed of physiologically similar cells, but these subsequently evolved higher rates of programmed cell death (apoptosis), an adaptation that increases propagule production. These results show that key aspects of multicellular complexity, a subject of central importance to biology, can readily evolve from unicellular eukaryotes.
Distinct energy metabolism of auditory and vestibular sensory epithelia revealed by quantitative mass spectrometry using MS2 intensity
Authors: Spinelli Kateri J. , Klimek John E. , Wilmarth Phillip A. , Shin Jung-Bum , Choi Dongseok , David Larry L. , Gillespie Peter G.
Published: January 2012

Measuring the abundance of many proteins over a broad dynamic range requires accurate quantitation. We show empirically that, in MS experiments, relative quantitation using summed dissociation-product ion-current intensities is accurate, albeit variable from protein to protein, and outperforms spectral counting. By applying intensities to quantify proteins in two complex but related tissues, chick auditory and vestibular sensory epithelia, we find that glycolytic enzymes are enriched threefold in auditory epithelia, whereas enzymes responsible for oxidative phosphorylation are increased at least fourfold in vestibular epithelia. This striking difference in relative use of the two ATP-production pathways likely reflects the isolation of the auditory epithelium from its blood supply, necessary to prevent heartbeat-induced mechanical disruptions. The global view of protein expression afforded by label-free quantitation with a wide dynamic range reveals molecular specialization at a tissue or cellular level.
Assembly of reconfigurable one-dimensional colloidal superlattices due to a synergy of fundamental nanoscale forces
Authors: Young Kaylie L. , Jones Matthew R. , Zhang Jian , Macfarlane Robert J. , Esquivel-Sirvent Raul , Nap Rikkert J. , Wu Jinsong , Schatz George C. , Lee Byeongdu , Mirkin Chad A.
Published: January 2012

We report that triangular gold nanoprisms in the presence of attractive depletion forces and repulsive electrostatic forces assemble into equilibrium one-dimensional lamellar crystals in solution with interparticle spacings greater than four times the thickness of the nanoprisms. Experimental and theoretical studies reveal that the anomalously large
d
spacings of the lamellar superlattices are due to a balance between depletion and electrostatic interactions, both of which arise from the surfactant cetyltrimethylammonium bromide. The effects of surfactant concentration, temperature, ionic strength of the solution, and prism edge length on the lattice parameters have been investigated and provide a variety of tools for in situ modulation of these colloidal superstructures. Additionally, we demonstrate a purification procedure based on our observations that can be used to efficiently separate triangular nanoprisms from spherical nanoparticles formed concomitantly during their synthesis.
Genome-wide siRNA screen for mediators of NF-κB activation
Authors: Gewurz Benjamin E. , Towfic Fadi , Mar Jessica C. , Shinners Nicholas P. , Takasaki Kaoru , Zhao Bo , Cahir-McFarland Ellen D. , Quackenbush John , Xavier Ramnik J. , Kieff Elliott
Published: January 2012

Although canonical NFκB is frequently critical for cell proliferation, survival, or differentiation, NFκB hyperactivation can cause malignant, inflammatory, or autoimmune disorders. Despite intensive study, mammalian NFκB pathway loss-of-function RNAi analyses have been limited to specific protein classes. We therefore undertook a human genome-wide siRNA screen for novel NFκB activation pathway components. Using an Epstein Barr virus latent membrane protein (LMP1) mutant, the transcriptional effects of which are canonical NFκB-dependent, we identified 155 proteins significantly and substantially important for NFκB activation in HEK293 cells. These proteins included many kinases, phosphatases, ubiquitin ligases, and deubiquinating enzymes not previously known to be important for NFκB activation. Relevance to other canonical NFκB pathways was extended by finding that 118 of the 155 LMP1 NF-κB activation pathway components were similarly important for IL-1β–, and 79 for TNFα–mediated NFκB activation in the same cells. MAP3K8, PIM3, and six other enzymes were uniquely relevant to LMP1-mediated NFκB activation. Most novel pathway components functioned upstream of IκB kinase complex (IKK) activation. Robust siRNA knockdown effects were confirmed for all mRNAs or proteins tested. Although multiple ZC3H-family proteins negatively regulate NFκB, ZC3H13 and ZC3H18 were activation pathway components. ZC3H13 was critical for LMP1, TNFα, and IL-1β NFκB-dependent transcription, but not for IKK activation, whereas ZC3H18 was critical for IKK activation. Down-modulators of LMP1 mediated NFκB activation were also identified. These experiments identify multiple targets to inhibit or stimulate LMP1-, IL-1β–, or TNFα–mediated canonical NFκB activation.
Cooperative effects of aminopeptidase N (CD13) expressed by nonmalignant and cancer cells within the tumor microenvironment
Authors: Guzman-Rojas Liliana , Rangel Roberto , Salameh Ahmad , Edwards Julianna K. , Dondossola Eleonora , Kim Yun-Gon , Saghatelian Alan , Giordano Ricardo J. , Kolonin Mikhail G. , Staquicini Fernanda I. , Koivunen Erkki , Sidman Richard L. , Arap Wadih , Pasqualini Renata
Published: January 2012

Processes that promote cancer progression such as angiogenesis require a functional interplay between malignant and nonmalignant cells in the tumor microenvironment. The metalloprotease aminopeptidase N (APN; CD13) is often overexpressed in tumor cells and has been implicated in angiogenesis and cancer progression. Our previous studies of APN-null mice revealed impaired neoangiogenesis in model systems without cancer cells and suggested the hypothesis that APN expressed by nonmalignant cells might promote tumor growth. We tested this hypothesis by comparing the effects of APN deficiency in allografted malignant (tumor) and nonmalignant (host) cells on tumor growth and metastasis in APN-null mice. In two independent tumor graft models, APN activity in both the tumors and the host cells cooperate to promote tumor vascularization and growth. Loss of APN expression by the host and/or the malignant cells also impaired lung metastasis in experimental mouse models. Thus, cooperation in APN expression by both cancer cells and nonmalignant stromal cells within the tumor microenvironment promotes angiogenesis, tumor growth, and metastasis.
1st Asia-Pacific Transport Working Group (APTWG) Meeting
Authors: Ida K. , Dong J.Q. , Kikuchi M. , Kwon J.M. , Diamond P.H.
Published: January 2012

This conference report summarizes the contributions to, and discussions at, the 1st Asia-Pacific Transport Working Group Meeting held in Toki, Japan, on 14–17 June 2011. The topics of the meeting were organized under four main headings: momentum transport, non-locality in transport, edge turbulence and L–H transition and 3D effects on transport physics. The events which initiated this meeting are also described in this report.
Weak approximation for low degree Del Pezzo surfaces
Authors: Xu Chenyang
Published: January 2012

Let

K
=

Func

(
C
)

K=\textrm {Func}(C)

be the function field of a smooth curve

C
C

. For every Del Pezzo surface

S

/

K

S/K

which is an appropriately generic, weak approximation for

S
S

holds at every place of

K
K

, i.e., for every closed point

c
c

of

C
C

. This combines earlier work in (arXiv:0810.2597) with an analysis of weak approximation near boundary points of the parameter spaces for Del Pezzo surfaces of degrees 1 and 2.
SNP calling using genotype model selection on high-throughput sequencing data
Authors: You Na , Murillo Gabriel , Su Xiaoquan , Zeng Xiaowei , Xu Jian , Ning Kang , Zhang Shoudong , Zhu Jiankang , Cui Xinping
Published: January 2012

Motivation: A review of the available single nucleotide polymorphism (SNP) calling procedures for Illumina high-throughput sequencing (HTS) platform data reveals that most rely mainly on base-calling and mapping qualities as sources of error when calling SNPs. Thus, errors not involved in base-calling or alignment, such as those in genomic sample preparation, are not accounted for.

Results: A novel method of consensus and SNP calling, Genotype Model Selection (GeMS), is given which accounts for the errors that occur during the preparation of the genomic sample. Simulations and real data analyses indicate that GeMS has the best performance balance of sensitivity and positive predictive value among the tested SNP callers.

Availability: The GeMS package can be downloaded from https://sites.google.com/a/bioinformatics.ucr.edu/xinping-cui/home/software or http://computationalbioenergy.org/software.html

Contact:  xinping.cui@ucr.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
ReLA, a local alignment search tool for the identification of distal and proximal gene regulatory regions and their conserved transcription factor binding sites
Authors: González Santi , Montserrat-Sentís Bàrbara , Sánchez Friman , Puiggròs Montserrat , Blanco Enrique , Ramirez Alex , Torrents David
Published: January 2012

Motivation: The prediction and annotation of the genomic regions involved in gene expression has been largely explored. Most of the energy has been devoted to the development of approaches that detect transcription start sites, leaving the identification of regulatory regions and their functional transcription factor binding sites (TFBSs) largely unexplored and with important quantitative and qualitative methodological gaps.

Results: We have developed ReLA (for REgulatory region Local Alignment tool), a unique tool optimized with the Smith–Waterman algorithm that allows local searches of conserved TFBS clusters and the detection of regulatory regions proximal to genes and enhancer regions. ReLA's performance shows specificities of 81 and 50% when tested on experimentally validated proximal regulatory regions and enhancers, respectively.

Availability: The source code of ReLA's is freely available and can be remotely used through our web server under http://www.bsc.es/cg/rela.

Contact:  david.torrents@bsc.es

Supplementary information:  Supplementary data are available at Bioinformatics online.
CODEX: exploration of semantic changes between ontology versions
Authors: Hartung Michael , Gross Anika , Rahm Erhard
Published: January 2012

Summary: Life science ontologies substantially change over time to meet the requirements of their users and to include the newest domain knowledge. Thus, an important task is to know what has been modified between two versions of an ontology (diff). This diff should contain all performed changes as compact and understandable as possible. We present CODEX (Complex Ontology Diff Explorer), a tool that allows determining semantic changes between two versions of an ontology, which users can interactively analyze in multiple ways.

Availability and implementation: CODEX is available under http://www.izbi.de/codex and is supported by all major browsers. It is implemented in Java based on Google Web Toolkit technology. Additionally, users can access a web service interface to use the diff functionality in their applications and analyses.

Contact:  hartung@izbi.uni-leipzig.de
Optic Nerve Sheath Diameter Used as Ultrasonographic Assessment of the Incidence of Raised Intracranial Pressure in Preeclampsia
Authors: Dubost Clément , Le Gouez Agnès , Jouffroy Viridiana , Roger-Christoph Sandrine , Benhamou Dan , Mercier Frédéric J. , Geeraerts Thomas
Published: January 2012

Background

In some cases of severe preeclampsia/eclampsia, brain imaging displays signs compatible with raised intracranial pressure. We aimed to estimate the incidence of raised intracranial pressure in preeclampsia using ocular ultrasonography.

Methods

Optic nerve sheath diameter (ONSD) measurements were compared in 26 preeclamptic and 25 healthy pregnant women. For each optic nerve, two measurements were made (transverse plane and sagittal plane) using a 7.5 MHz ultrasound linear probe. Preeclamptic patients were followed-up until postpartum day 7.

Results

Median ONSD values were significantly greater in preeclamptic patients compared with healthy pregnant women at delivery (5.4 mm (95% CI: 5.2, 5.7) vs. 4.5 mm (95% CI: 4.3, 4.8), P < 0.0001). At delivery, 5/26 (19%) of preeclamptic patients had ONSD values above 5.8 mm (value associated in the literature with 95% risk of raised intracranial pressure) whereas none of the healthy pregnant group had such high ONSD values. In the preeclamptic group, ONSD decreased after the third postpartum day. ONSD values at day 7 were not significantly different from those obtained in the normal pregnancy group (P = 0.10).

Conclusion

In about 20% of preeclamptic patients, ONSD reaches values compatible with intracranial pressure above 20 mmHg. Further work is needed to confirm this incidence and to better understand the diagnostic and therapeutic usefulness of this easy-to-do monitoring technique.
Can Colonic Manometry Studies Be Done on the Day of Colonic Motility Catheter Placement?
Authors: Ammoury Rana F. , Emhardt John D. , Aitchison William B. , Horn Debra S. , Croffie Joseph M.
Published: January 2012

Background and Aims:

Colonic manometry has been used to assess colonic neuromuscular integrity in pediatric patients with severe constipation unresponsive to standard medical therapy and to tailor their treatment plans. There are presently no available standard protocols for conducting colonic manometry studies. The aim of the present study was to determine whether colonic manometry studies can be conducted on the same day the colonic motility catheters are placed and to compare the effects of inhaled sevoflurane versus intravenous propofol, used during catheter placement, on colonic motility.

Methods:

Twenty patients, randomized to receive sevoflurane or propofol during catheter placement, underwent colonic manometry on the day of catheter placement as well as the day after. The total motility index (MI), change in MI in response to a meal and bisacodyl, and presence of high‐amplitude propagating contractions were compared between the 2 studies for each patient.

Results:

Ten patients were allocated to sevoflurane and 10 patients to propofol. A total of 8 (80%) patients in the sevoflurane group and 9 (90%) patients in the propofol group had no differences in their studies between days 1 and 2 when the tracings were interpreted manually for gross evidence of high‐amplitude propagating contractions and gastrocolonic reflex. Similarly, there was no change in the total MI between studies done on days 1 and 2 in either sevoflurane (978 ± 232 vs 978 ± 184; P = 0.99) or propofol (968 ± 200 vs 1078 ± 227; P = 0.29) group. When comparing change in MI in response to a meal or bisacodyl between the 2 days, there was no statistical difference noted in either group.

Conclusions:

Colonic manometry studies can be conducted as early as 4 hours following catheter placement with either propofol or sevoflurane used for anesthesia.
Snake modulates constriction in response to prey's heartbeat
Authors: Boback Scott M. , Hall Allison E. , McCann Katelyn J. , Hayes Amanda W. , Forrester Jeffrey S. , Zwemer Charles F.
Published: January 2012

Many species of snakes use constriction—the act of applying pressure via loops of their trunk—to subdue and kill their prey. Constriction is costly and snakes must therefore constrict their prey just long enough to ensure death. However, it remains unknown how snakes determine when their prey is dead. Here, we demonstrate that boas (
Boa constrictor
) have the remarkable ability to detect a heartbeat in their prey and, based on this signal, modify the pressure and duration of constriction accordingly. We monitored pressure generated by snakes as they struck and constricted warm cadaveric rats instrumented with a simulated heart. Snakes responded to the beating heart by constricting longer and with greater total pressure than when constricting rats with no heartbeat. When the heart was stopped midway through the constriction, snakes abandoned constriction shortly after the heartbeat ceased. Furthermore, snakes naive to live prey also responded to the simulated heart, suggesting that this behaviour is at least partly innate. These results are an example of how snakes integrate physiological cues from their prey to modulate a complex and ancient behavioural pattern.
Cooperation among germinating spores facilitates the growth of the fungus,
Neurospora crassa
Authors: Richard F. , Glass N. L. , Pringle A.
Published: January 2012

Fusions between individuals are a common feature of organisms with modular, indeterminate life forms, including plants, marine invertebrates and fungi. The consequences of fusion for an individual fungus are poorly understood. We used wild-type and fusion mutant strains of the genetic model
Neurospora crassa
to chronicle the fitness in two different laboratory habitats, and in each experiment started colonies from multiple different densities of asexual spores. On round Petri dishes, fusion enabled wild-type colonies to grow larger than mutant (
soft
) colonies; but in linear ‘race tubes’, the
soft
mutant always grew more quickly than the wild-type. Starting a colony with more spores always provided an advantage to a wild-type colony, but was more often neutral or a cost to the
soft
mutant. The ability to fuse does not provide a consistent advantage to wild-type colonies; net benefits are shaped by both habitat and initial spore densities.
Bioactive composite gradient coatings of nano-hydroxyapatite/polyamide66 fabricated on polyamide66 substrates
Authors: Huang Di , Zuo Yi , Li Jidong , Zou Qin , Zhang Li , Gong Mei , Wang Li , Li Limei , Li Yubao
Published: January 2012

Tightly bonding of bioactive coating is the first crucial need for orthopaedic implants. This study describes a novel and convenient technique to prepare bioactive coating with high adhesion on orthopaedic substitutes made of polymeric matrix. Here, a chemical corrosion method has been adopted to fabricate a coating on the surface of injection-moulded polyamide66 (PA66) substrates by corrosive nano-hydroxyapatite/polyamide66 (n-HA/PA66) composite slurry. Scanning electron microscopy observation shows that a porous chemical corrosion region presents between the coating and dense PA66 substrate. Energy-dispersive X-ray spectroscopy analysis indicates that the chemical corrosion region is mainly composed of PA66 matrix, and the coating layer is an n-HA-rich layer. Both the pore size and n-HA composition increase gradually from the polymeric substrate towards the coating surface. Mechanical testing shows the bonding strength can reach 13.7 ± 0.2 MPa, which is much higher than that fabricated on polymeric matrix by other coating methods. The gradual transition in coating structure and composition benefits for the interface bonding and for the surface bone-bonding bioactivity. Subsequent cell experiments corroborate n-HA-rich coating and a porous structure is benefitting for cell attachment and proliferation. The convenient coating method could be popularized and applied on similar polymer implants to produce a tightly and porous bioactive coating for bone tissue regeneration.
Fitness-maximizing foragers can use information about patch quality to decide how to search for and within patches: optimal Lévy walk searching patterns from optimal foraging theory
Authors: Reynolds A. M.
Published: January 2012

Optimal foraging theory shows how fitness-maximizing foragers can use information about patch quality to decide how to search
within
patches. It is amply supported by empirical studies. Nonetheless, the theory largely ignores the fact that foragers may need to search
for
patches as well as for the targets within them. Here, using an exact but simple mathematical argument, it is shown how foragers can use information about patch quality to facilitate the execution of Lévy walk movement patterns with
μ
= 2 at inter-patch scales. These movement patterns are advantageous when searching
for
patches that are not depleted or rejected once visited but instead remain profitable. The analytical results are verified by the results of numerical simulations. The findings bring forth an innovative theoretical synthesis of searching for and within patches and, suggest that foragers' memories may be adaptive under spatially heterogeneous reward schedules.
Changes in kinematics and aerodynamics over a range of speeds inTadarida brasiliensis, the Brazilian free-tailed bat
Authors: Hubel Tatjana Y. , Hristov Nickolay I. , Swartz Sharon M. , Breuer Kenneth S.
Published: January 2012

To date, wake measurements using particle image velocimetry (PIV) of bats in flight have studied only three bat species, all fruit and nectar feeders. In this study, we present the first wake structure analysis for an insectivorous bat.Tadarida brasiliensis, the Brazilian free-tailed bat, is an aerial hunter that annually migrates long distances and also differs strikingly from the previously investigated species morphologically. We compare the aerodynamics ofT. brasiliensiswith those of other, frugivorous bats and with common swifts,Apus apus, a bird with wing morphology, kinematics and flight ecology similar to that of these bats. The comparison reveals that, for the range of speeds evaluated, the cyclical pattern of aerodynamic forces associated with a wingbeat shows more similarities betweenT. brasiliensisandA. apusthan betweenT. brasiliensisand other frugivorous bats.
Invertebrate learning and memory: Fifty years of olfactory conditioning of the proboscis extension response in honeybees
Authors: Giurfa Martin , Sandoz Jean-Christophe
Published: January 2012

The honeybeeApis melliferahas emerged as a robust and influential model for the study of classical conditioning, thanks to the existence of a powerful Pavlovian conditioning protocol, the olfactory conditioning of the proboscis extension response (PER). In 2011, the olfactory PER conditioning protocol celebrates 50 years since it was first introduced by Kimihisa Takeda in 1961. Here, we review its origins, developments, and perspectives in order to define future research avenues and necessary methodological and conceptual evolutions. We show that olfactory PER conditioning has become a versatile tool for the study of questions in extremely diverse fields in addition to the study of learning and memory and that it has allowed behavioral characterizations, not only of honeybees, but also of other insect species, for which the protocol was adapted. We celebrate, therefore, Takeda's original work and prompt colleagues to conceive and establish further robust behavioral tools for an accurate characterization of insect learning and memory at multiple levels of analysis.
Methylphenidate enhances extinction of contextual fear
Authors: Abraham Antony D. , Cunningham Christopher L. , Lattal K. Matthew
Published: January 2012

Methylphenidate (MPH, Ritalin) is a norepinephrine and dopamine transporter blocker that is widely used in humans for treatment of attention deficit disorder and narcolepsy. Although there is some evidence that targeted microinjections of MPH may enhance fear acquisition, little is known about the effect of MPH on fear extinction. Here, we show that MPH, administered before or immediately following extinction of contextual fear, will enhance extinction retention in C57BL/6 mice. Animals that received MPH (2.5–10 mg/kg) before an extinction session showed decreased freezing response during extinction, and the effect of the 10 mg/kg dose on freezing persisted to the next day. When MPH (2.5–40 mg/kg) was administered immediately following an extinction session, mice that received MPH showed dose-dependent decreases in freezing during subsequent tests. MPH administered immediately after a 3-min extinction session or 4 h following the first extinction session did not cause significant differences in freezing. Together, these findings demonstrate that MPH can enhance extinction of fear and that this effect is sensitive to dose, time of injection, and duration of the extinction session. Because MPH is widely used in clinical treatments, these experiments suggest that the drug could be used in combination with behavioral therapies for patients with fear disorders.
A New Type of Compartment, Defined by Plant-Specific Atg8-Interacting Proteins, Is Induced upon Exposure of Arabidopsis Plants to Carbon Starvation
Authors: Honig Arik , Avin-Wittenberg Tamar , Ufaz Shai , Galili Gad
Published: January 2012

Atg8 is a central protein in bulk starvation–induced autophagy, but it is also specifically associated with multiple protein targets under various physiological conditions to regulate their selective turnover by the autophagy machinery. Here, we describe two new closely related Arabidopsis thaliana Atg8-interacting proteins (ATI1 and ATI2) that are unique to plants. We show that under favorable growth conditions, ATI1 and ATI2 are partially associated with the endoplasmic reticulum (ER) membrane network, whereas upon exposure to carbon starvation, they become mainly associated with newly identified spherical compartments that dynamically move along the ER network. These compartments are morphologically distinct from previously reported spindle-shaped ER bodies and, in contrast to them, do not contain ER-lumenal markers possessing a C-terminal HDEL sequence. Organelle and autophagosome-specific markers show that the bodies containing ATI1 are distinct from Golgi, mitochondria, peroxisomes, and classical autophagosomes. The final destination of the ATI1 bodies is the central vacuole, indicating that they may operate in selective turnover of specific proteins. ATI1 and ATI2 gene expression is elevated during late seed maturation and desiccation. We further demonstrate that ATI1 overexpression or suppression of both ATI1 and ATI2, respectively, stimulate or inhibit seed germination in the presence of the germination-inhibiting hormone abscisic acid.
Safety and patient outcomes with lubiprostone for up to 52 weeks in patients with irritable bowel syndrome with constipation
Authors: Chey W. D. , Drossman D. A. , Johanson J. F. , Scott C. , Panas R. M. , Ueno R.
Published: January 2012

Background

Irritable bowel syndrome with constipation (IBS‐C) significantly decreases quality of life and the ability to perform daily living activities.

Aim

To demonstrate the long‐term safety, tolerability and patient outcomes of lubiprostone in patients with IBS‐C.

Methods

This extension study enrolled 522 IBS‐C patients who had completed one of two randomised phase 3 studies. All enrolled patients received open‐label lubiprostone orally for 36‐weeks (8 mcg, twice daily). The primary objective was the assessment of long‐term safety and tolerability, monitored via adverse events (AEs), laboratory parameters and vital signs. Additional outcome endpoints included monthly responder rates and patient evaluations of IBS‐C symptom severity and impact on quality of life.

Results

The evaluable safety population comprised of 520 patients; 476 of which had patient reported outcome data available. The overall safety profile of lubiprostone during this study was similar to that observed in the preceding phase 3 studies. The most common AEs were diarrhoea (11.0%), nausea (11.0%), urinary tract infection (9.0%), sinusitis (9.0%) and abdominal distention (5.8%). Diarrhoea and nausea were the most common treatment‐related AEs. No serious AEs were considered treatment‐related. Seventeen patients discontinued due to a treatment‐related AE, of which diarrhoea and nausea accounted for six (1.2%) and three (0.6%) respectively. For responder rates and patient‐evaluated parameters (n = 476), all groups experienced significant improvements from baseline, with initial improvements maintained throughout the study.

Conclusion

In patients with irritable bowel syndrome with constipation, lubiprostone 8 mcg twice daily was found to be safe and well tolerated over 9–13 months of treatment.
SNP‐based association mapping of the polled gene in divergent cattle breeds
Authors: Seichter D. , Russ I. , Rothammer S. , Eder J. , Förster M. , Medugorac I.
Published: January 2012

Naturally, hornless cattle are called polled. Although the POLL locus could be assigned to a c. 1.36‐Mb interval in the centromeric region of BTA1, the underlying genetic basis for the polled trait is still unknown. Here, an association mapping design was set up to refine the candidate region of the polled trait for subsequent high‐throughput sequencing. The case group comprised 101 homozygous polled animals from nine divergent cattle breeds, the majority represented by Galloway, Angus, Fleckvieh and Holstein Friesian. Additionally, this group included some polled individuals of Blonde d’Aquitaine, Charolais, Hereford, Jersey and Limousin breeds. The control group comprised horned Belgian Blue, Fleckvieh, Holstein Friesian and Illyrian Buša cattle. A genome‐wide scan using 49 163 SNPs was performed, which revealed one shared homozygous haplotype block consisting of nine neighbouring SNPs in all polled animals. This segment defines a 381‐kb interval on BTA1 that we consider to be the most likely location of the POLL mutation. Our results further demonstrate that the polled‐associated haplotype is also frequent in horned animals included in this study, and thus the haplotype as such cannot be used for population‐wide genetic testing. The actual trait‐associated haplotype may be revealed by using higher‐density SNP arrays. For the final identification of the causal mutation, we suggest high‐throughput sequencing of the entire candidate region, because the identification of functional candidate genes is difficult owing to the lack of a comparable model.
Trends of reporting of ‘serious’vs. ‘non‐serious’ adverse drug reactions over time: a study in the French PharmacoVigilance Database
Authors: Moulis Guillaume , Sommet Agnès , Durrieu Geneviève , Bagheri Haleh , Lapeyre‐Mestre Maryse , Montastruc Jean‐Louis ,   The French Association of PharmacoVigilance Centres
Published: January 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Several factors are known to influence spontaneous reporting of adverse drug reactions (ADRs). Among them, ‘seriousness’ of the reaction is one of the most important.

• However, evolution in the reporting of ‘serious’vs.‘non‐serious’ ADRs over time for the same drug remains unknown.

WHAT THIS STUDY ADDS

• Spontaneous reports mainly involve ‘non‐serious’ ADRs during the first years of marketing and ‘serious’ ADRs later, particularly for drugs with non‐hospital use.

AIM To investigate trends in spontaneous reporting to the French Pharmacovigilance system of ‘serious’ (SADRs) and ‘non‐serious’ (NSADRs) adverse drug reactions over time.

METHODS Annual SADR : NSADR ratios were calculated for each drug and their evolution tested with linear trend tests.

RESULTS Among the 39 new active substances commercialized in France in 2000, 16 had sufficient data to perform linear trend tests. An increasing linear relation was found for five widely prescribed drugs, a non‐significant increasing trend for eight others, i.e. drugs mostly used in hospitals.

CONCLUSION ADR reports mainly concern NSADRs during first years of marketing. Reports of SADRs are proportionally more frequent later.