bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intermolecular π‐Electron Perturbations Generate Extrinsic Visible Contributions to Eumelanin Black Chromophore in Model Polymers with Interrupted Interring Conjugation
Authors: Ascione Laura , Pezzella Alessandro , Ambrogi Veronica , Carfagna Cosimo , d'Ischia Marco 
Published: September 2012

AbstractThe key structural factors underlying the unique black chromophore of eumelanin biopolymers have so far defied elucidation. Capitalizing on the ability of 1% polyvinylalcohol (PVA) to prevent pigment precipitation during melanogenesis in vitro, we have investigated the visible chromophore properties of soluble eumelanin‐like polymers produced by biomimetic oxidation of 5,6‐dihydroxyindole (DHI) and 5,6‐dihydroxyindole‐2‐carboxylic (DHICA) in 1% PVA‐containing buffer at pH 7. Upon dilution DHI‐eumelanin solutions exhibited almost linear visible absorbance changes, whereas DHICA‐eumelanin displayed a remarkable deviation from linearity in simple buffer, but not in PVA‐containing buffer. It is suggested that in DHICA polymers, exhibiting repeated interruptions of interring conjugation due to lack of planar conformations, the black chromophore is not due to an overlap of static entities defined intrinsically by the conjugation length across the carbon frame, but results largely from aggregation‐related intermolecular perturbations of the π‐electron systems which are extrinsic in character.
Late Aptian long‐lived glacio‐eustatic lowstand recorded on the Arabian Plate
Authors: Maurer Florian , van Buchem Frans S.P. , Eberli Gregor P. , Pierson Bernard J. , Raven Madeleine J. , Larsen Poul‐Henrik , Al‐Husseini Moujahed I. , Vincent Benoit 
Published: September 2012

Terra Nova, 25, 87–94, 2013AbstractCompelling physical evidence for a Late Aptian lowstand with an amplitude of at least 50 m is presented in subsurface seismic and core data from the Arabian Plate. Biostratigraphic dating indicates that the fall and rise bracketing this lowstand were rapid, and that the lowstand lasted for around 5 ma with distinctly cyclic sedimentation at the 0.4–0.5 ma scale (eccentricity band). A glacio‐eustatic mechanism is invoked as the most likely cause, which is supported by cooling indicated in oxygen isotope shifts and by evidence for a global expression of this lowstand from a number of locations at the mid and high latitudes. Hence, the Late Aptian data presented here document the longest Cretaceous sea‐level lowstand, interpreted as the longest cooling phase during the Cretaceous greenhouse.
Were ancient granitoid compositions influenced by contemporaneous atmospheric and hydrosphere oxidation states?
Authors: Jagoutz Oliver 
Published: September 2012

Terra Nova, 00, 1–7, 2012AbstractA feedback loop between subducted oceanic plate composition, subduction zone processes, arc magma chemistry, and the newly formed continental crust composition links to atmospheric and hydrosphere oxidation conditions through the low temperature weathering mechanisms of seafloor basalts. Sea‐floor weathering and the Na/K of the altered oceanic crust strongly depends on f(O2) conditions during alteration, that changed with earth history. The rise of oxygen at ∼2600–2400 Ma triggered associated changes in f(O2) seafloor alteration conditions providing a possible explanation for the observed change from the Na‐rich tonalite‐trondhjemite‐granodiorite (TTG) rocks in the Archean to the K‐rich granodiorite‐granite (GG) granitoids in post‐Archean times.
Design of chimeric expression elements that confer high‐level gene activity in chromoplasts
Authors: Caroca Rodrigo , Howell Katharine A. , Hasse Claudia , Ruf Stephanie , Bock Ralph 
Published: September 2012

SummaryNon‐green plastids, such as chromoplasts, generally have much lower activity of gene expression than chloroplasts in photosynthetically active tissues. Suppression of plastid genes in non‐green tissues occurs through a complex interplay of transcriptional and translational control, with the contribution of regulation of transcript abundance versus translational activity being highly variable between genes. Here, we have investigated whether the low expression of the plastid genome in chromoplasts results from inherent limitations in gene expression capacity, or can be overcome by designing appropriate combinations of promoters and translation initiation signals in the 5′ untranslated region (5′–UTR). We constructed chimeric expression elements that combine promoters and 5′–UTRs from plastid genes, which are suppressed during chloroplast‐to‐chromoplast conversion in Solanum lycopersicum (tomato) fruit ripening, either just at the translational level or just at the level of mRNA accumulation. These chimeric expression elements were introduced into the tomato plastid genome by stable chloroplast transformation. We report the identification of promoter‐UTR combinations that confer high‐level gene expression in chromoplasts of ripe tomato fruits, resulting in the accumulation of reporter protein GFP to up to 1% of total cellular protein. Our work demonstrates that non‐green plastids are capable of expressing genes to high levels. Moreover, the chimeric cis‐elements for chromoplasts developed here are widely applicable in basic and applied research using transplastomic methods.
Genetic and pharmacological modulation of giant depolarizing potentials in the neonatal hippocampus associates with increased seizure susceptibility
Authors: Vargas Ernesto , Petrou Steven , Reid Christopher A. 
Published: September 2012

Key points
Our earlier work established that seizure susceptibility in the GABAAγ2R43Q epilepsy mouse may be in part due to the developmental consequences of impaired GABA­A receptor function.
Giant depolarizing potentials (GDP) are brain network activity that involve GABA transmission, and they are thought to be important for the wiring of the developing brain.
The GABAAγ2R43Q epilepsy mutation may have an impact on this function.
To test this, we measured GPD events in a mouse model with the human mutation and showed a significantly lower frequency of these events.
We also reduced GDPs using a drug called bumetanide and showed an increased seizure susceptibility.
Our data suggest that both genetic and pharmacological reductions in GDP expression can increase the likelihood of having a seizure when exposed to heat.
Abstract  The expression of Na+–K+–2Cl− cotransporter (NKCC1) is responsible for high intracellular Cl− resulting in the excitatory action of GABAA receptor activation in the developing brain. Giant depolarizing potentials (GDPs) are spontaneous network oscillations that involve GABAA receptors and are thought to be important in establishing neuronal circuit wiring. Earlier work established that seizure susceptibility in the GABAAγ2R43Q epilepsy mouse is impacted by developmental consequences of impaired GABAA receptor function. We investigated the potential mechanism of the developmental influence by recording GDPs in the CA3 pyramidal neurons from brain slices of the neonatal GABAAγ2R43Q mouse. Interestingly, the number of GPDs was significantly lower in slices from mutant mouse compared with wild‐type control, suggesting an involvement in setting seizure susceptibility. To test this idea we blocked NKCC1 with bumetanide in neonatal mice and reduced the number of GDPs to a level similar to that seen in the mutant mice. We found that neonatal treatment with bumetanide resulted in a similar level of susceptibility to thermally induced seizures as described for the GABAAγ2R43Q mouse. These results provide evidence that a human GABAA receptor epilepsy mutation exerts a developmental influence by modulating the number of GDPs. It also draws attention to the potential risk of early treatment with bumetanide.
Features of proximal and distal excitatory synaptic inputs to layer V neurons of the rat medial entorhinal cortex
Authors: Medinilla Virginia , Johnson Oralee , Gasparini Sonia 
Published: September 2012

Key points
Layer V principal neurons of the entorhinal cortex receive the hippocampal output on their proximal and basal dendrites and send their axons to cortical areas, playing a fundamental role in memory processing.
The apical dendrites of these neurons are rich in spines and extend to the entorhinal superficial layers, in the proximity of axons from cortical neurons, which could make synapses onto these spines.
We stimulated afferent fibres in the superficial layers and recorded depolarizing responses in entorhinal layer V neurons, indicating that they receive excitatory inputs onto their distal dendrites.
The responses were completely blocked by glutamatergic receptor antagonists; stimulation of distal afferents could initiate dendritic spikes, which propagated to the soma to generate an action potential.
These results show that the distal dendrites of entorhinal layer V neurons have access to information that could affect the integration of the input from the hippocampus.
Abstract  The entorhinal cortex (EC) has a fundamental function in transferring information between the hippocampus and the neocortex. EC layer V principal neurons are the main recipients of the hippocampal output and send processed information to the neocortex, likely playing an important role in memory processing and consolidation. Most of these neurons have apical dendrites that extend to the superficial layers and are rich in spines, which could be the targets of excitatory inputs from fibres innervating that region. We have used electrical stimulation of afferent fibres coupled with whole‐cell patch‐clamp somatic recordings to study the features of distal excitatory inputs and compare them with those of proximal ones. The amplitude of putative unitary excitatory responses was ∼1.5 times larger for distal compared with proximal inputs. The responses were purely glutamatergic, as they were abolished by a combination of AMPA and NMDA glutamatergic receptor antagonists. Blockade of Ih by 4‐ethylphenylamino‐1,2‐dimethyl‐6‐methylaminopyrimidinium chloride (ZD7288) increased temporal summation; the increase was comparable for proximal and distal inputs. Proximal inputs initiated a somatic spike more reliably than distal ones; in some instances, somatic action potentials triggered by distal stimulation were preceded by dendritic spikes that fully propagated to the soma. Altogether, our results show that medial layer V entorhinal neurons receive excitatory synapses at distal dendritic locations, which gives them access to information encoded by inputs to the superficial layers as well as the deep layers. These findings are fundamentally relevant to understanding the role of the EC in the formation and consolidation of episodic memory.
A key circulatory defence against asphyxia in infancy – the heart of the matter!
Authors: Cohen Gary , Katz‐Salamon Miriam , Malcolm Girvan 
Published: September 2012

Key points
A rise in heart rate boosts cardiac output and blood pressure, improves perfusion and oxygen delivery, and speeds recovery during an emergency.
Breathing efforts and lung inflation reflexively elevate heart rate during experimental asphyxia, and may rescue (‘auto resuscitate’) an animal from imminent death.
We analysed whether this mechanism elevates heart rate when a healthy, sleeping infant is confronted by mild, progressive asphyxia.
Term‐born infants aged 1–8 days rebreathed the expired gas for short periods to stimulate breathing and heart rate but not arousal from sleep.
We show that a rising CO2 level during asphyxia is much more strongly cardio‐acceleratory than either vigorous breathing efforts or lung inflation.
This excitatory action of CO2 on the heart develops soon after birth.
We suggest that (i) the hypercapnia during asphyxia helps raise heart rate; (ii) excitation by respiratory manoeuvres alone is relatively weak and short lived and may not produce the sustained heart rate rise needed to counteract circulatory depression.
Abstract  A resumption of, and escalation in, breathing efforts (hyperpnoea) reflexively accelerates heart rate (HR) and may facilitate cardiac and circulatory recovery from apnoea. We analysed whether this mechanism can produce a sustained rise in HR (tachycardia) when a sleeping infant is confronted by mild, rapidly worsening asphyxia, simulating apnoea. Twenty‐seven healthy term‐born infants aged 1–8 days rebreathed the expired gas for 90 s during quiet sleep to stimulate breathing and heart rate. To discriminate cardio‐excitatory effects of central respiratory drive, lung inflation, hypoxia, hypercapnia and asphyxia, we varied the inspired O2 level and compared temporal changes in response profiles as respiratory sensitivity to hypoxia and asphyxia ‘reset’ after birth. We demonstrate that asphyxia‐induced hyperpnoea and tachycardia strengthen dramatically over the first week with different time courses and via separate mechanisms. Cardiac excitation by hypercapnia improves first, followed by a slower improvement in respiratory hypoxic drive. A rise in CO2 consequently elicits stronger, longer lasting tachycardia than moderate increases in respiratory drive or lung expansion. We suggest that without a strong facilitating action of CO2 on the immature heart, respiratory manoeuvres may be unable to reflexively counteract strong vagal bradycardia. This may increase the vulnerability of some infants to apnoea – asphyxia.
Regulatory roles of the NMDA receptor GluN3A subunit in locomotion, pain perception and cognitive functions in adult mice
Authors: Mohamad Osama , Song Mingke , Wei Ling , Yu Shan Ping 
Published: September 2012

Key points
Adult glutamate NMDA receptor subunit 3A (GluN3A) knockout (KO) mice showed slow locomotor activity, motor deficits and increased pain sensation.
Hippocampal slices from juvenile and adult GluN3A KO mice showed greater long‐term potentiation compared with wild‐type slices.
Adult GluN3A KO mice showed enhanced abilities in learning and memory tasks.
GluN3A deletion resulted in increased expression and/or phosphorylation of Ca2+/calmodulin‐ dependent kinase II in the brain.
This is the first investigation showing that deletion of GluN3A in the embryonic stage has imperative impacts on multiple behaviours in adults.
Abstract  Since the discovery of the glutamate NMDA receptor subunit 3A (GluN3A), the functional role of this unique inhibitory subunit has been largely obscure. GluN3A expression is high in the neonatal brain but declines to a low level in the adult brain; it is thus commonly believed that GluN3A does not have a major functional impact in adulthood. Using wild‐type (WT) and GluN3A knockout (KO) mice, we show here that deletion of GluN3A affected multiple behavioural functions in adult animals. GluN3A KO mice showed impaired locomotor activity on a variety of motor function tests, and increased sensitivity to acute and sub‐acute inflammatory pain. GluN3A KO mice also showed enhanced recognition and spatial learning and memory functions. Hippocampal slices from juvenile and adult GluN3A KO mice showed greater long‐term potentiation (LTP) compared with WT slices. GluN3A deletion resulted in increased expression of Ca2+/calmodulin‐dependent kinase II (CaMKII) in the forebrain, and the phosphorylated CaMKII level upon LTP induction was significantly higher in the GluN3A KO hippocampus compared with WT controls. CaMKII inhibition abrogated the enhanced LTP in GluN3A KO slices. These data reveal for the first time that the presence of GluN3A may have profound impacts on several functional/behavioural activities in adult animals, and could be a therapeutic target for neurological disorders associated with NMDA receptor functions.
Virulent Bacteriophages Can Target O104:H4 Enteroaggregative Escherichia coli in the Mouse Intestine
Authors: Maura Damien , Galtier Matthieu , Le Bouguénec Chantal , Debarbieux Laurent 
Published: September 2012

ABSTRACT

In vivo
bacteriophage targeting of enteroaggregative
Escherichia coli
(EAEC) was assessed using a mouse intestinal model of colonization with the O104:H4 55989Str strain and a cocktail of three virulent bacteriophages. The colonization model was shown to mimic asymptomatic intestinal carriage found in humans. The addition of the cocktail to drinking water for 24 h strongly decreased ileal and weakly decreased fecal 55989Str concentrations in a dose-dependent manner. These decreases in ileal and fecal bacterial concentrations were only transient, since 55989Str concentrations returned to their original levels 3 days later. These transient decreases were independent of the mouse microbiota, as similar results were obtained with axenic mice. We studied the infectivity of each bacteriophage in the ileal and fecal environments and found that 55989Str bacteria in the mouse ileum were permissive to all three bacteriophages, whereas those in the feces were permissive to only one bacteriophage. Our results provide the first demonstration that bacterial permissivity to infection with virulent bacteriophages is not uniform throughout the gut; this highlights the need for a detailed characterization of the interactions between bacteria and bacteriophages
in vivo
for the further development of phage therapy targeting intestinal pathogens found in the gut of asymptomatic human carriers.
Frequency, Spectrum, and Nonzero Fitness Costs of Resistance to Myxopyronin in Staphylococcus aureus
Authors: Srivastava Aashish , Degen David , Ebright Yon W. , Ebright Richard H. 
Published: September 2012

ABSTRACT

The antibiotic myxopyronin (Myx) functions by inhibiting bacterial RNA polymerase (RNAP). The binding site on RNAP for Myx—the RNAP “switch region SW1/SW2 subregion”—is different from the binding site on RNAP for the RNAP inhibitor currently used in broad-spectrum antibacterial therapy, rifampin (Rif). Here, we report the frequency, spectrum, and fitness costs of Myx resistance in
Staphylococcus aureus
. The resistance rate for Myx is 4 × 10
−8
to 7 × 10
−8
per generation, which is equal within error to the resistance rate for Rif (3 × 10
−8
to 10 × 10
−8
per generation). Substitutions conferring Myx resistance were obtained in the RNAP β subunit [six substitutions: V1080(1275)I, V1080(1275)L, E1084(1279)K, D1101(1296)E, S1127(1322)L, and S1127(1322)P] and the RNAP β′ subunit [five substitutions: K334(345)N, T925(917)K, T925(917)R, G1172(1354)C, and G1172(1354)D] (residues numbered as in
Staphylococcus aureus
RNAP and, in parentheses, as in
Escherichia coli
RNAP). Sites of substitutions conferring Myx resistance map to the RNAP switch region SW1/SW2 subregion and do not overlap the binding site on RNAP for Rif, and, correspondingly, Myx-resistant mutants exhibit no cross-resistance to Rif. All substitutions conferring Myx resistance exhibit significant fitness costs (4 to 15% per generation). In contrast, at least three substitutions conferring Rif resistance exhibit no fitness costs (≤0% per generation). The observation that all Myx-resistant mutants have significant fitness costs whereas at least three Rif-resistant mutants have no fitness costs, together with the previously established inverse correlation between fitness cost and clinical prevalence, suggests that Myx resistance is likely to have lower clinical prevalence than Rif resistance.
The Sequence-Activity Relationship between Metallo-β-Lactamases IMP-1, IMP-6, and IMP-25 Suggests an Evolutionary Adaptation to Meropenem Exposure
Authors: Liu Eleanor M. , Pegg Kevin M. , Oelschlaeger Peter 
Published: September 2012

ABSTRACT
Metallo-β-lactamases are important determinants of antibacterial resistance. In this study, we investigate the sequence-activity relationship between the closely related enzymes IMP-1, IMP-6, and IMP-25. While IMP-1 is the more efficient enzyme across the overall spectrum of tested β-lactam antibacterial agents, IMP-6 and IMP-25 seem to have evolved to specifically inactivate the newer carbapenem meropenem. Molecular modeling indicates that the G235S mutation distinguishing IMP-25 from IMP-1 and IMP-6 may affect enzyme activity via Asn233.
The Two-Component System CprRS Senses Cationic Peptides and Triggers Adaptive Resistance in Pseudomonas aeruginosa Independently of ParRS
Authors: Fernández Lucía , Jenssen Håvard , Bains Manjeet , Wiegand Irith , Gooderham W. James , Hancock Robert E. W. 
Published: September 2012

ABSTRACT

Cationic antimicrobial peptides pass across the outer membrane by interacting with negatively charged lipopolysaccharide (LPS), leading to outer membrane permeabilization in a process termed self-promoted uptake. Resistance can be mediated by the addition of positively charged arabinosamine through the action of the
arnBCADTEF
operon. We recently described a series of two-component regulators that lead to the activation of the
arn
operon after recognizing environmental signals, including low-Mg
2+
(PhoPQ, PmrAB) or cationic (ParRS) peptides. However, some peptides did not activate the
arn
operon through ParRS. Here, we report the identification of a new two-component system, CprRS, which, upon exposure to a wide range of antimicrobial peptides, triggered the expression of the LPS modification operon. Thus, mutations in the
cprRS
operon blocked the induction of the
arn
operon in response to several antimicrobial peptides independently of ParRS but did not affect the response to low Mg
2+
. Distinct patterns of
arn
induction were identified. Thus, the responses to polymyxins were abrogated by either
parR
or
cprR
mutations, while responses to other peptides, including indolicidin, showed differential dependency on the CprRS and ParRS systems in a concentration-dependent manner. It was further demonstrated that, following exposure to inducing antimicrobial peptides,
cprRS
mutants did not become adaptively resistant to polymyxins as was observed for wild-type cells. Our microarray studies demonstrated that the CprRS system controlled a quite modest regulon, indicating that it was quite specific to adaptive peptide resistance. These findings provide greater insight into the complex regulation of LPS modification in
Pseudomonas aeruginosa
, which involves the participation of at least 4 two-component systems.
The Inactivation of Intrinsic Antibiotic Resistance Determinants Widens the Mutant Selection Window for Quinolones in Stenotrophomonas maltophilia
Authors: García-León Guillermo , Sánchez María B. , Martínez José L. 
Published: September 2012

ABSTRACT

We have determined that the mutational inactivation of the SmeDEF efflux pump and the SmQnr quinolone resistance protein widens the mutant selection windows for ofloxacin and ciprofloxacin of
Stenotrophomonas maltophilia
by reducing their MICs. Resistant mutants arising from a strain lacking SmeDEF and SmQnr presented levels of susceptibility similar to those of the wild-type strain. This indicates that inactivation of intrinsic resistance determinants might increase the chances for selecting resistant mutants at low antibiotic concentrations.
Expression of
STM4467
-Encoded Arginine Deiminase Controlled by the
STM4463
Regulator Contributes to Salmonella enterica Serovar Typhimurium Virulence
Authors: Choi Younho , Choi Jeongjoon , Groisman Eduardo A. , Kang Dong-Hyun , Shin Dongwoo , Ryu Sangryeol 
Published: September 2012

ABSTRACT

Arginine deiminase (ADI), carbamate kinase (CK), and ornithine transcarbamoylase (OTC) constitute the ADI system. In addition to metabolic functions, the ADI system has been implicated in the virulence of certain pathogens. The pathogenic intracellular bacterium
Salmonella enterica
serovar Typhimurium possesses the
STM4467
,
STM4466
, and
STM4465
genes, which are predicted to encode ADI, CK, and OTC, respectively. Here we report that the
STM4467
gene encodes an ADI and that ADI activity plays a role in the successful infection of a mammalian host by
S
. Typhimurium. An
STM4467
deletion mutant was defective for replication inside murine macrophages and was attenuated for virulence in mice. We determined that a regulatory protein encoded by the
STM4463
gene functions as an activator for
STM4467
expression. The expression of the ADI pathway genes was enhanced inside macrophages in a process that required STM4463. Lack of STM4463 impaired the ability of
S
. Typhimurium to replicate within macrophages. A mutant defective in
STM4467
-encoded ADI displayed normal production of nitric oxide by macrophages.