bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermodynamics of combined-cycle electric power plants
Authors: Leff Harvey S.
Published: May 2012

Published data imply an average thermal efficiency of about 0.34 for U.S. electricity generating plants. With clever use of thermodynamics and technology, modern gas and steam turbines can be coupled, to effect dramatic efficiency increases. These combined-cycle power plants now reach thermal efficiencies in excess of 0.60. It is shown how the laws of thermodynamics make this possible.
Experiencing conceptual change about teaching: A case study from astronomy
Authors: Bailey Janelle M. , Nagamine Kentaro
Published: May 2012

Understanding faculty motivations for and barriers to change is an important component of facilitating instructional reform efforts to improve student learning. This case study describes the process of adoption of learner-centered instructional strategies by an astronomy faculty member, Ken, as viewed through the lens of conceptual change. Specifically, we applied the Cognitive Reconstruction of Knowledge Model (CRKM) to understand why Ken was willing to change his instructional strategies, what barriers to and supports for change existed, and how he and his students were impacted by this change. Ken’s statements and actions represented characteristics consistent with the CRKM. Notably, dissatisfaction, considered the primary motivator in many conceptual change models, was not of high importance in this case. Upon implementing learner-centered strategies, Ken’s students performed better on a measure of knowledge about stellar properties, which served to reinforce his motivation to continue with learner-centered methods.
Oersted Medal Address 2012: Narrative and Witz in Physics
Authors: Holbrow Charles H.
Published: May 2012

Physics is the syntax and grammar of science; it is the rules. Therefore, you must learn physics to write, speak, or do good science. But knowing the rules of physics won’t make you a good physicist or a good physics teacher any more than knowing grammar will make you a good writer. To bring physics alive you need strong narratives and interesting content. I will describe three examples: A course—“The Physics of Living in Space”; a textbook—Modern Introductory Physics; and a project—Astronomy’s Discoveries and Physics Education. I will also show examples of what I mean by “Witz” and why it is important in physics.
Thermal Inactivation of Infectious Hepatitis E Virus in Experimentally Contaminated Food
Authors: Barnaud Elodie , Rogée Sophie , Garry Pascal , Rose Nicolas , Pavio Nicole
Published: May 2012

Hepatitis E virus (HEV) infection of zoonotic origin is an emerging concern in industrialized countries. In the past few years, several cases of zoonotic hepatitis E have been identified and the consumption of food products derived from pork liver have been associated with clusters of human cases. More specifically, raw or undercooked pork products have been incriminated. Few data on the effect of heating on HEV inactivation in food products are available. In the present study, the various times and temperatures that are used during industrial processing of pork products were applied to experimentally contaminated food preparations. After treatment, the presence of residual infectious virus particles was investigated using real-time reverse transcription-PCR and an
in vivo
experimental model in pigs. Results show that heating the food to an internal temperature of 71°C for 20 min is necessary to completely inactivate HEV. These results are very important for determining processing methods to ensure food safety in regard to food-borne hepatitis E.
Development of an Efficient
In Vivo
System (P
junc
-TpaseIS

1223

) for Random Transposon Mutagenesis of Lactobacillus casei
Authors: Licandro-Seraut Hélène , Brinster Sophie , van de Guchte Maarten , Scornec Hélène , Maguin Emmanuelle , Sansonetti Philippe , Cavin Jean-François , Serror Pascale
Published: May 2012

The random transposon mutagenesis system P
junc
-TpaseIS

1223

is composed of plasmids pVI129, expressing IS
1223
transposase, and pVI110, a suicide transposon plasmid carrying the P
junc
sequence, the substrate of the IS
1223
transposase. This system is particularly efficient in
Lactobacillus casei
, as more than 10,000 stable, random mutants were routinely obtained via electroporation.
Genome Sequence of Thermotolerant Bacillus methanolicus: Features and Regulation Related to Methylotrophy and Production of
l
-Lysine and
l
-Glutamate from Methanol
Authors: Heggeset Tonje M. B. , Krog Anne , Balzer Simone , Wentzel Alexander , Ellingsen Trond E. , Brautaset Trygve
Published: May 2012

Bacillus methanolicus
can utilize methanol as its sole carbon and energy source, and the scientific interest in this thermotolerant bacterium has focused largely on exploring its potential as a biocatalyst for the conversion of methanol into
l
-lysine and
l
-glutamate. We present here the genome sequences of the important
B. methanolicus
model strain MGA3 (ATCC 53907) and the alternative wild-type strain PB1 (NCIMB13113). The physiological diversity of these two strains was demonstrated by a comparative fed-batch methanol cultivation displaying highly different methanol consumption and respiration profiles, as well as major differences in their
l
-glutamate production levels (406 mmol liter
−1
and 11 mmol liter
−1
, respectively). Both genomes are small (ca 3.4 Mbp) compared to those of other related bacilli, and MGA3 has two plasmids (pBM19 and pBM69), while PB1 has only one (pBM20). In particular, we focus here on genes representing biochemical pathways for methanol oxidation and concomitant formaldehyde assimilation and dissimilation, the important phosphoenol pyruvate/pyruvate anaplerotic node, the tricarboxylic acid cycle including the glyoxylate pathway, and the biosynthetic pathways for
l
-lysine and
l
-glutamate. Several unique findings were made, including the discovery of three different methanol dehydrogenase genes in each of the two
B. methanolicus
strains, and the genomic analyses were accompanied by gene expression studies. Our results provide new insight into a number of peculiar physiological and metabolic traits of
B. methanolicus
and open up possibilities for system-level metabolic engineering of this bacterium for the production of amino acids and other useful compounds from methanol.
Comparative Genomic Analyses of 17 Clinical Isolates of Gardnerella vaginalis Provide Evidence of Multiple Genetically Isolated Clades Consistent with Subspeciation into Genovars
Authors: Ahmed Azad , Earl Josh , Retchless Adam , Hillier Sharon L. , Rabe Lorna K. , Cherpes Thomas L. , Powell Evan , Janto Benjamin , Eutsey Rory , Hiller N. Luisa , Boissy Robert , Dahlgren Margaret E. , Hall Barry G. , Costerton J. William , Post J. Christopher , Hu Fen Z. , Ehrlich Garth D.
Published: May 2012

Gardnerella vaginalis
is associated with a spectrum of clinical conditions, suggesting high degrees of genetic heterogeneity among stains. Seventeen
G. vaginalis
isolates were subjected to a battery of comparative genomic analyses to determine their level of relatedness. For each measure, the degree of difference among the
G. vaginalis
strains was the highest observed among 23 pathogenic bacterial species for which at least eight genomes are available. Genome sizes ranged from 1.491 to 1.716 Mb; GC contents ranged from 41.18% to 43.40%; and the core genome, consisting of only 746 genes, makes up only 51.6% of each strain's genome on average and accounts for only 27% of the species supragenome. Neighbor-grouping analyses, using both distributed gene possession data and core gene allelic data, each identified two major sets of strains, each of which is composed of two groups. Each of the four groups has its own characteristic genome size, GC ratio, and greatly expanded core gene content, making the genomic diversity of each group within the range for other bacterial species. To test whether these 4 groups corresponded to genetically isolated clades, we inferred the phylogeny of each distributed gene that was present in at least two strains and absent in at least two strains; this analysis identified frequent homologous recombination within groups but not between groups or sets.
G. vaginalis
appears to include four nonrecombining groups/clades of organisms with distinct gene pools and genomic properties, which may confer distinct ecological properties. Consequently, it may be appropriate to treat these four groups as separate species.
CcpA-Dependent Carbohydrate Catabolite Repression Regulates Galactose Metabolism in Streptococcus oligofermentans
Authors: Cai Jun , Tong Huichun , Qi Fengxia , Dong Xiuzhu
Published: May 2012

Streptococcus oligofermentans
is an oral commensal that inhibits the growth of the caries pathogen
Streptococcus mutans
by producing copious amounts of H
2
O
2
and that grows faster than
S. mutans
on galactose. In this study, we identified a novel eight-gene galactose (
gal
) operon in
S. oligofermentans
that was comprised of
lacABCD
,
lacX
, and three genes encoding a galactose-specific transporter. Disruption of
lacA
caused more growth reduction on galactose than mutation of
galK
, a gene in the Leloir pathway, indicating that the principal role of this operon is in galactose metabolism. Diauxic growth was observed in cultures containing glucose and galactose, and a luciferase reporter fusion to the putative
gal
promoter demonstrated 12-fold repression of the operon expression by glucose but was induced by galactose, suggesting a carbon catabolite repression (CCR) control in galactose utilization. Interestingly, none of the single-gene mutations in the well-known CCR regulators
ccpA
and
manL
affected diauxic growth, although the operon expression was upregulated in these mutants in glucose. A double mutation of
ccpA
and
manL
eliminated glucose repression of galactose utilization, suggesting that these genes have parallel functions in regulating
gal
operon expression and mediating CCR. Electrophoretic mobility shift assays demonstrated binding of CcpA to the putative catabolite response element motif in the promoter regions of the
gal
operon and
manL
, suggesting that CcpA regulates CCR through direct regulation of the transcription of the
gal
operon and
manL
. This provides the first example of oral streptococci using two parallel CcpA-dependent CCR pathways in controlling carbohydrate metabolism.
Ligand-Binding Properties and Conformational Dynamics of Autolysin Repeat Domains in Staphylococcal Cell Wall Recognition
Authors: Zoll Sebastian , Schlag Martin , Shkumatov Alexander V. , Rautenberg Maren , Svergun Dmitri I. , Götz Friedrich , Stehle Thilo
Published: May 2012

The bifunctional major autolysin Atl plays a key role in staphylococcal cell separation. Processing of Atl yields catalytically active amidase (AM) and glucosaminidase (GL) domains that are each fused to repeating units. The two repeats of AM (R1 and R2) target the enzyme to the septum, where it cleaves murein between dividing cells. We have determined the crystal structure of R2, which reveals that each repeat folds into two half-open β-barrel subunits. We further demonstrate that lipoteichoic acid serves as a receptor for the repeats and that this interaction depends on conserved surfaces in each subunit. Small-angle X-ray scattering of the mature amidase reveals the presence of flexible linkers separating the AM, R1, and R2 units. Different levels of flexibility for each linker provide mechanistic insights into the conformational dynamics of the full-length protein and the roles of its components in cell wall association and catalysis. Our analysis supports a model in which the repeats direct the catalytic AM domain to the septum, where it can optimally perform the final step of cell division.
Development of Competence for Genetic Transformation of
Streptococcus mutans
in a Chemically Defined Medium
Authors: Desai Kunal , Mashburn-Warren Lauren , Federle Michael J. , Morrison Donald A.
Published: May 2012

Streptococcus mutan
s develops competence for genetic transformation in response to regulatory circuits that sense at least two peptide pheromones. One peptide, known as CSP, is sensed by a two-component signal transduction system through a membrane receptor, ComD. The other, derived from the primary translation product ComS, is thought to be sensed by an intracellular receptor, ComR, after uptake by oligopeptide permease. To allow study of this process in a medium that does not itself contain peptides, development of competence was examined in the chemically defined medium (CDM) described by van de Rijn and Kessler (Infect. Immun.
27:
444, 1980). We confirmed a previous report that in this medium
comS
mutants of strain UA159 respond to a synthetic peptide comprising the seven C-terminal residues of ComS (ComS
11-17
) by increasing expression of the alternative sigma factor SigX, which in turn allows expression of competence effector genes. This response provided the basis for a bioassay for the ComS pheromone in the 100 to 1,000 nM range. It was further observed that
comS
+
(but not
comS
mutant) cultures developed a high level of competence in the late log and transition phases of growth in this CDM without the introduction of any synthetic stimulatory peptide. This endogenous competence development was accompanied by extracellular release of one or more signals that complemented a
comS
mutation at levels equivalent to 1 μM synthetic ComS
11-17
.
DprB Facilitates Inter- and Intragenomic Recombination in Helicobacter pylori
Authors: Zhang Xue-Song , Blaser Martin J.
Published: May 2012

For naturally competent microorganisms, such as
Helicobacter pylori
, the steps that permit recombination of exogenous DNA are not fully understood. Immediately downstream of an
H. pylori
gene (
dprA
) that facilitates high-frequency natural transformation is HP0334 (
dprB
), annotated to be a putative Holliday junction resolvase (HJR). We showed that the HP0334 (
dprB
) gene product facilitates high-frequency natural transformation. We determined the physiologic roles of DprB by genetic analyses. DprB controls
in vitro
growth, survival after exposure to UV or fluoroquinolones, and intragenomic recombination.
dprB ruvC
double deletion dramatically decreases both homologous and homeologous transformation and survival after exposure to DNA-damaging agents. Moreover, the DprB protein binds to synthetic Holliday junction structures rather than double-stranded or single-stranded DNA. These results demonstrate that the
dprB
product plays important roles affecting inter- and intragenomic recombination. We provide evidence that the two putative
H. pylori
HJRs (DprB and RuvC) have overlapping but distinct functions involving intergenomic (primarily DprB) and intragenomic (primarily RuvC) recombination.
Secretion Genes as Determinants of Bacillus anthracis Chain Length
Authors: Nguyen-Mau Sao-Mai , Oh So-Young , Kern Valerie J. , Missiakas Dominique M. , Schneewind Olaf
Published: May 2012

Bacillus anthracis
grows in chains of rod-shaped cells, a trait that contributes to its escape from phagocytic clearance in host tissues. Using a genetic approach to search for determinants of
B. anthracis
chain length, we identified mutants with insertional lesions in
secA2
. All isolated
secA2
mutants exhibited an exaggerated chain length, whereas the dimensions of individual cells were not changed. Complementation studies revealed that
slaP
(
S
-
l
ayer
a
ssembly
p
rotein), a gene immediately downstream of
secA2
on the
B. anthracis
chromosome, is also a determinant of chain length. Both
secA2
and
slaP
are required for the efficient secretion of Sap and EA1 (Eag), the two S-layer proteins of
B. anthracis
, but not for the secretion of S-layer-associated proteins or of other secreted products. S-layer assembly via
secA2
and
slaP
contributes to the proper positioning of BslO, the S-layer-associated protein, and murein hydrolase, which cleaves septal peptidoglycan to separate chains of bacilli. SlaP was found to be both soluble in the bacterial cytoplasm and associated with the membrane. The purification of soluble SlaP from
B. anthracis
-cleared lysates did not reveal a specific ligand, and the membrane association of SlaP was not dependent on SecA2, Sap, or EA1. We propose that SecA2 and SlaP promote the efficient secretion of S-layer proteins by modifying the general secretory pathway of
B. anthracis
to transport large amounts of Sap and EA1.
Degradation of 2,3-Dihydroxybenzoate by a Novel
meta
-Cleavage Pathway
Authors: Marín Macarena , Plumeier Iris , Pieper Dietmar H.
Published: May 2012

2,3-Dihydroxybenzoate is the precursor in the biosynthesis of several siderophores and an important plant secondary metabolite that, in bacteria, can be degraded via
meta
-cleavage of the aromatic ring. The
dhb
cluster of
Pseudomonas reinekei
MT1 encodes a chimeric
meta
-cleavage pathway involved in the catabolism of 2,3-dihydroxybenzoate. While the first two enzymes, DhbA and DhbB, are phylogenetically related to those involved in 2,3-dihydroxy-
p
-cumate degradation, the subsequent steps are catalyzed by enzymes related to those involved in catechol degradation (DhbCDEFGH). Characterization of kinetic properties of DhbA extradiol dioxygenase identified 2,3-dihydroxybenzoate as the preferred substrate. Deletion of the encoding gene impedes growth of
P. reinekei
MT1 on 2,3-dihydroxybenzoate. DhbA catalyzes 3,4-dioxygenation with 2-hydroxy-3-carboxymuconate as the product, which is then decarboxylated by DhbB to 2-hydroxymuconic semialdehyde. This compound is then subject to dehydrogenation and further degraded to citrate cycle intermediates. Transcriptional analysis revealed genes of the
dhB
gene cluster to be highly expressed during growth with 2,3-dihydroxybenzoate, whereas a downstream-localized gene encoding 2-hydroxymuconic semialdehyde hydrolase, dispensable for 2,3-dihydroxybenzoate metabolism but crucial for 2,3-dihydroxy-
p
-cumate degradation, was only marginally expressed. This is the first report describing a gene cluster encoding enzymes for the degradation of 2,3-dihydroxybenzoate.
Two Surfaces of a Conserved Interdomain Linker Differentially Affect Output from the RST Sensing Module of the Bacillus subtilis Stressosome
Authors: Gaidenko Tatiana A. , Bie Xiaomei , Baldwin Enoch P. , Price Chester W.
Published: May 2012

The stressosome is a 1.8-MDa cytoplasmic complex that conveys environmental signals to the σ
B
stress factor of
Bacillus subtilis
. A functionally irreducible complex contains multiple copies of three proteins: the RsbRA coantagonist, RsbS antagonist, and RsbT serine-threonine kinase. Homologues of these proteins are coencoded in different genome contexts in diverse bacteria, forming a versatile sensing and transmission module called RST after its common constituents. However, the signaling pathway within the stressosome itself is not well defined. The N-terminal, nonheme globin domains of RsbRA project from the stressosome and are presumed to channel sensory input to the C-terminal STAS domains that form the complex core. A conserved, 13-residue α-helical linker connects these domains. We probed the
in vivo
role of the linker using alanine scanning mutagenesis, assaying stressosome output in
B. subtilis
via a σ
B
-dependent reporter fusion. Substitutions at four conserved residues increased output 4- to 30-fold in unstressed cells, whereas substitutions at four nonconserved residues significantly decreased output. The periodicity of these effects supports a model in which RsbRA functions as a dimer
in vivo
, with the linkers forming parallel paired helices via a conserved interface. The periodicity further suggests that the opposite, nonconserved faces make additional contacts important for efficient stressosome operation. These results establish that the linker influences stressosome output under steady-state conditions. However, the stress response phenotypes of representative linker substitutions provide less support for the notion that the N-terminal globin domain senses acute environmental challenge and transmits this information via the linker helix.
Selenium-Dependent Biogenesis of Formate Dehydrogenase in
Campylobacter jejuni
Is Controlled by the
fdhTU
Accessory Genes
Authors: Shaw Frances L. , Mulholland Francis , Le Gall Gwénaëlle , Porcelli Ida , Hart Dave J. , Pearson Bruce M. , van Vliet Arnoud H. M.
Published: May 2012

The food-borne bacterial pathogen
Campylobacter jejuni
efficiently utilizes organic acids such as lactate and formate for energy production. Formate is rapidly metabolized via the activity of the multisubunit formate dehydrogenase (FDH) enzyme, of which the FdhA subunit is predicted to contain a selenocysteine (SeC) amino acid. In this study we investigated the function of the
cj1500
and
cj1501
genes of
C. jejuni
, demonstrate that they are involved in selenium-controlled production of FDH, and propose the names
fdhT
and
fdhU
, respectively. Insertional inactivation of
fdhT
or
fdhU
in
C. jejuni
resulted in the absence of FdhA and FdhB protein expression, reduced
fdhABC
RNA levels, the absence of FDH enzyme activity, and the lack of formate utilization, as assessed by
1
H nuclear magnetic resonance. The
fdhABC
genes are transcribed from a single promoter located two genes upstream of
fdhA
, and the decrease in
fdhABC
RNA levels in the
fdhU
mutant is mediated at the posttranscriptional level. FDH activity and the ability to utilize formate were restored by genetic complementation with
fdhU
and by supplementation of the growth media with selenium dioxide. Disruption of SeC synthesis by inactivation of the
selA
and
selB
genes also resulted in the absence of FDH activity, which could not be restored by selenium supplementation. Comparative genomic analysis suggests a link between the presence of
selA
and
fdhTU
orthologs and the predicted presence of SeC in FdhA. The
fdhTU
genes encode accessory proteins required for FDH expression and activity in
C. jejuni
, possibly by contributing to acquisition or utilization of selenium.
Consent to tissue banking for research: qualitative study and recommendations
Authors: Soto Carmen , Tarrant Carolyn , Pritchard-Jones Kathy , Dixon-Woods Mary
Published: May 2012

Objective

To explore how families of children with cancer experience giving consent for tissue banking and to produce recommendations on good practice.

Design

79 participants from 42 families (41 mothers, 18 fathers, 20 children and young people with cancer) took part in semistructured interviews to explore their experiences of being approached for consent to tissue banking.

Setting

Tertiary care facilities for childhood cancer.

Results

Families are generally supportive of tissue banking, although they report that it may be difficult for them to consider all the implications when asked for consent. They typically do not want detailed information when consent is sought close to diagnosis, preferring to see tissue banking as part of routine practice. Families often recognise that their consent may not be fully informed, but are content to give consent based on their understanding at the time. Some may want a chance to go over the information and revisit their decision when things have settled.

Conclusions

Families' views can inform practical recommendations for optimising the experience of consent for tissue banking. Current guidelines for obtaining consent should be revisited to take account of families' preferences.
Managing patient deterioration: assessing teamwork and individual performance
Authors: Cooper Simon , Cant Robyn , Porter Jo , Missen Karen , Sparkes Louise , McConnell-Henry Tracy , Endacott Ruth
Published: May 2012

Objective

To assess the ability of rural Australian nurse teams to manage deteriorating patients.

Methods

This quasi-experimental design used pre- and post-intervention assessments and observation to evaluate nurses' simulated clinical performance. Registered nurses (n=44) from two hospital wards completed a formative knowledge assessment and three team-based video recorded scenarios (Objective Structured Clinical Examinations (OSCE)). Trained patient actors simulated deteriorating patients. Skill performance and situation awareness were measured and team performance was rated using the Team Emergency Assessment Measure.

Results

Knowledge in relation to patient deterioration management varied (mean 63%, range 27–100%) with a median score of 64%. Younger nurses with a greater number of working hours scored the highest (p=0.001). OSCE performance was generally low with a mean performance of 54%, but performance was maintained despite the increasing complexity of the scenarios. Situation awareness was generally low (median 50%, mean 47%, range 17–83%, SD 14.03) with significantly higher levels in younger participants (r=−0.346, p=0.021). Teamwork ratings averaged 57% with significant associations between the subscales (Leadership, Teamwork and Task Management) (p<0.006), the global rating scale (p<0.001) and two of the OSCE measures (p<0.049). Feedback from participants following the programme indicated significant improvements in knowledge, confidence and competence (p<0.001).

Conclusion

Despite a satisfactory knowledge base, the application of knowledge was low with notable performance deficits in these demanding and stressful situations. The identification and management of patient deterioration needs to be taught in professional development programmes incorporating high fidelity simulation techniques. The Team Emergency assessment tool proved to be a valid measure of team performance in patient deterioration scenarios.
Implementation of a patient selection protocol for intra-arterial therapy increases treatment rates in patients with acute ischemic stroke
Authors: Rost Natalia S , Smith Eric E , Nogueira Raul G , Fitzpatrick Kaitlin M , Yoo Albert J , Hirsch Joshua A , Schwamm Lee H
Published: May 2012

Background

Strategies for patient selection for intra-arterial therapy (IAT) in acute ischemic stroke (AIS) are highly variable. The degree of protocol adoption and treatment rates associated with implementation of a service-wide patient selection IAT protocol were assessed.

Methods

All patients with AIS prospectively recorded in our stroke database from January 2007 to June 2009 were reviewed. The IAT patient selection protocol was implemented in March 2008. Patients were defined as likely to benefit (LTB) from IAT if they had brain imaging completed within 6 h from last known well time, NIH Stroke Scale score ≥8, infarct volume ≤100 ml and evidence of proximal artery occlusion.

Results

Of 1348 subjects identified, 118 (8.7%) met the criteria for LTB and 62 (52%) underwent IAT. There was a significant increase in rates of IAT among LTB patients after protocol implementation (61% vs 40%, p<0.02). In LTB patients, factors associated with IAT were stroke duration (OR 0.78, 95% CI 0.6 to 0.9 per hour), arrival within later calendar months during study period (OR 1.1, 95% CI 1.02 to 1.2 per month), intravenous tissue plasminogen activator (OR 0.6, 95% CI 0.4 to 0.9) and age (OR 0.98, 95% CI 0.95 to 1.02 per year). After multivariable adjustment, only stroke duration (OR 0.65, 95% CI 0.5 to 0.8 per hour) remained an independent predictor of IAT.

Conclusions

Most patients with AIS did not meet our criteria for LTB and only 52% of those defined as LTB received IAT. Protocol adoption increased the use of IAT over time; however, further exploration of factors associated with the reasons for non-treatment and the impact of IAT on outcomes is necessary.
Critical-Period Plasticity in the Visual Cortex
Authors: Levelt Christiaan N. , Hübener Mark
Published: May 2012

In many regions of the developing brain, neuronal circuits undergo defined phases of enhanced plasticity, termed critical periods. Work in the rodent visual cortex has led to important insights into the cellular and molecular mechanisms regulating the timing of the critical period. Although there is little doubt that the maturation of specific inhibitory circuits plays a key role in the opening of the critical period in the visual cortex, it is less clear what puts an end to it. In this review, we describe the established mechanisms and point out where more experimental work is needed. We also show that plasticity in the visual cortex is present well before, and long after, the peak of the critical period.
Attractor Dynamics of Spatially Correlated Neural Activity in the Limbic System
Authors: Knierim James J. , Zhang Kechen
Published: May 2012

Attractor networks are a popular computational construct used to model different brain systems. These networks allow elegant computations that are thought to represent a number of aspects of brain function. Although there is good reason to believe that the brain displays attractor dynamics, it has proven difficult to test experimentally whether any particular attractor architecture resides in any particular brain circuit. We review models and experimental evidence for three systems in the rat brain that are presumed to be components of the rat's navigational and memory system. Head-direction cells have been modeled as a ring attractor, grid cells as a plane attractor, and place cells both as a plane attractor and as a point attractor. Whereas the models have proven to be extremely useful conceptual tools, the experimental evidence in their favor, although intriguing, is still mostly circumstantial.
Decision-Related Activity in Sensory Neurons: Correlations Among Neurons and with Behavior
Authors: Nienborg Hendrikje , R. Cohen Marlene , Cumming Bruce G.
Published: May 2012

Neurons in early sensory cortex show weak but systematic correlations with perceptual decisions when trained animals perform at psychophysical threshold. These correlations are observed across repeated presentations of identical stimuli and cannot be explained by variation in external factors. The relationship between the activity of individual sensory neurons and the animal's behavioral choice means that even neurons in early sensory cortex carry information about an upcoming decision. This relationship, termed choice probability, may reflect the effect of fluctuations in neuronal firing rate on the animal's decision, but it can also reflect modulation of sensory responses by cognitive factors, or network properties such as variability that is shared among populations of neurons. Here, we review recent work clarifying the relationship among fluctuations in the responses of individual neurons, correlated variability, and behavior in a variety of tasks and cortical areas. We also discuss the possibility that choice probability may in part reflect the influence of cognitive factors on sensory neurons and explore the situations in which choice probability can be used to make inferences about the role of particular sensory neurons in the decision-making process.
Compressed Sensing, Sparsity, and Dimensionality in Neuronal Information Processing and Data Analysis
Authors: Ganguli Surya , Sompolinsky Haim
Published: May 2012

The curse of dimensionality poses severe challenges to both technical and conceptual progress in neuroscience. In particular, it plagues our ability to acquire, process, and model high-dimensional data sets. Moreover, neural systems must cope with the challenge of processing data in high dimensions to learn and operate successfully within a complex world. We review recent mathematical advances that provide ways to combat dimensionality in specific situations. These advances shed light on two dual questions in neuroscience. First, how can we as neuroscientists rapidly acquire high-dimensional data from the brain and subsequently extract meaningful models from limited amounts of these data? And second, how do brains themselves process information in their intrinsically high-dimensional patterns of neural activity as well as learn meaningful, generalizable models of the external world from limited experience?
The Restless Engram: Consolidations Never End
Authors: Dudai Yadin
Published: May 2012

Memory consolidation is the hypothetical process in which an item in memory is transformed into a long-term form. It is commonly addressed at two complementary levels of description and analysis: the cellular/synaptic level (synaptic consolidation) and the brain systems level (systems consolidation). This article focuses on selected recent advances in consolidation research, including the reconsolidation of long-term memory items, the brain mechanisms of transformation of the content and of cue-dependency of memory items over time, as well as the role of rest and sleep in consolidating and shaping memories. Taken together, the picture that emerges is of dynamic engrams that are formed, modified, and remodified over time at the systems level by using synaptic consolidation mechanisms as subroutines. This implies that, contrary to interpretations that have dominated neuroscience for a while, but similar to long-standing cognitive concepts, consolidation of at least some items in long-term memory may never really come to an end.
Neural Basis of Reinforcement Learning and Decision Making
Authors: Lee Daeyeol , Seo Hyojung , Jung Min Whan
Published: May 2012

Reinforcement learning is an adaptive process in which an animal utilizes its previous experience to improve the outcomes of future choices. Computational theories of reinforcement learning play a central role in the newly emerging areas of neuroeconomics and decision neuroscience. In this framework, actions are chosen according to their value functions, which describe how much future reward is expected from each action. Value functions can be adjusted not only through reward and penalty, but also by the animal's knowledge of its current environment. Studies have revealed that a large proportion of the brain is involved in representing and updating value functions and using them to choose an action. However, how the nature of a behavioral task affects the neural mechanisms of reinforcement learning remains incompletely understood. Future studies should uncover the principles by which different computational elements of reinforcement learning are dynamically coordinated across the entire brain.
Social Control of the Brain
Authors: Fernald Russell D.
Published: May 2012

In the course of evolution, social behavior has been a strikingly potent selective force in shaping brains to control action. Physiological, cellular, and molecular processes reflect this evolutionary force, particularly in the regulation of reproductive behavior and its neural circuitry. Typically, experimental analysis is directed at how the brain controls behavior, but the brain is also changed by behavior over evolution, during development, and through its ongoing function. Understanding how the brain is influenced by behavior offers unusual experimental challenges. General principles governing the social regulation of the brain are most evident in the control of reproductive behavior. This is most likely because reproduction is arguably the most important event in an animal's life and has been a powerful and essential selective force over evolution. Here I describe the mechanisms through which behavior changes the brain in the service of reproduction using a teleost fish model system.
What Is the Brain-Cancer Connection?
Authors: Cao Lei , During Matthew J.
Published: May 2012

A focus of much cancer research is at the molecular and cellular levels. In contrast, the effects of social interactions and psychological state are less investigated, and considered by many a “soft” science. Yet several highly rigorous studies have begun to tease out biochemical pathways by which the brain can influence the development and growth of cancer. Previous reviews have discussed the concept of stress and cancer. Here, we discuss recent work showing environments that are more complex and challenging, but not stressful per se, and that have robust effects on peripheral cancer by activating a specific neuroendocrine brain-adipocyte axis. These enriched environments lead to activation of the sympathetic innervation of fat tissue, suppression of leptin, and a reduction in cancer proliferation by inducing hypothalamic BDNF expression. We summarize this work and discuss how these data integrate into the body of literature regarding stress, the environment, and cancer.
Dexamethasone blocks the systemic inflammation of alveolar hypoxia at several sites in the inflammatory cascade
Authors: Chao Jie , Viets Zachary , Donham Paula , Wood John G. , Gonzalez Norberto C.
Published: May 2012

Alveolar hypoxia produces a rapid and widespread systemic inflammation in rats. The inflammation is initiated by the release into the circulation of monocyte chemoattractant protein-1 (MCP-1) from alveolar macrophages (AMO) activated by the low alveolar Po2. Circulating MCP-1 induces mast cell (MC) degranulation with renin release and activation of the local renin-angiotensin system, leading to microvascular leukocyte recruitment and increased vascular permeability. We investigated the effect of dexamethasone, a synthetic anti-inflammatory glucocorticoid, on the development of the systemic inflammation of alveolar hypoxia and its site(s) of action in the inflammatory cascade. The inflammatory steps investigated were the activation of primary cultures of AMO by hypoxia, the degranulation of MCs by MCP-1 in the mesentery microcirculation of rats, and the effect of angiotensin II (ANG II) on the leukocyte/endothelial interface of the mesentery microcirculation. Dexamethasone prevented the mesentery inflammation in conscious rats breathing 10% O2for 4 h by acting in all key steps of the inflammatory cascade. Dexamethasone: 1) blocked the hypoxia-induced AMO activation and the release of MCP-1 and abolished the increase in plasma MCP-1 of conscious, hypoxic rats; 2) prevented the MCP-1-induced degranulation of mesentery perivascular MCs and reduced the number of peritoneal MCs, and 3) blocked the leukocyte-endothelial adherence and the extravasation of albumin induced by topical ANG II in the mesentery. The effect at each site was sufficient to prevent the AMO-initiated inflammation of hypoxia. These results may explain the effectiveness of dexamethasone in the treatment of the systemic effects of alveolar hypoxia.
Nitrite anion stimulates ischemic arteriogenesis involving NO metabolism
Authors: Bir Shyamal C. , Pattillo Christopher B. , Pardue Sibile , Kolluru Gopi K. , Docherty John , Goyette Dave , Dvorsky Peter , Kevil Christopher G.
Published: May 2012

Nitric oxide (NO) is a potential regulator of ischemic vascular remodeling, and as such therapies augmenting its bioavailability may be useful for the treatment of ischemic tissue diseases. Here we examine the effect of administering the NO prodrug sodium nitrite on arteriogenesis activity during established tissue ischemia. Chronic hindlimb ischemia was induced by permanent unilateral femoral artery and vein ligation. Five days postligation; animals were randomized to control PBS or sodium nitrite (165 μg/kg) therapy twice daily. In situ vascular remodeling was measured longitudinally using SPY angiography and Microfil vascular casting. Delayed sodium nitrite therapy rapidly increased ischemic limb arterial vessel diameter and branching in a NO-dependent manner. SPY imaging angiography over time showed that nitrite therapy enhanced ischemic gracillis collateral vessel formation from the profunda femoris to the saphenous artery. Immunofluorescent staining of smooth muscle cell actin also confirmed that sodium nitrite therapy increased arteriogenesis in a NO-dependent manner. The NO prodrug sodium nitrite significantly increases arteriogenesis and reperfusion of established severe chronic tissue ischemia.
Na+/Ca2+ exchanger-1 protects against systolic failure in the Akitains2 model of diabetic cardiomyopathy via a CXCR4/NF-κB pathway
Authors: LaRocca Thomas J. , Fabris Frank , Chen Jiqiu , Benhayon Daniel , Zhang Shihong , McCollum LaTronya , Schecter Alison D. , Cheung Joseph Y. , Sobie Eric A. , Hajjar Roger J. , Lebeche Djamel
Published: May 2012

Diabetic cardiomyopathy is characterized, in part, by calcium handling imbalances associated with ventricular dysfunction. The cardiac Na+/Ca2+ exchanger 1 (NCX1) has been implicated as a compensatory mechanism in response to reduced contractility in the heart; however, its role in diabetic cardiomyopathy remains unknown. We aimed to fully characterize the Akitains2 murine model of type 1 diabetes through assessing cardiac function and NCX1 regulation. The CXCL12/CXCR4 chemokine axis is well described in its cardioprotective effects via progenitor cell recruitment postacute myocardial infarction; however, it also functions in regulating calcium dependent processes in the cardiac myocyte. We therefore investigated the potential impact of CXCR4 in diabetic cardiomyopathy. Cardiac performance in the Akitains2 mouse was monitored using echocardiography and in vivo pressure-volume analysis. The Akitains2 mouse is protected against ventricular systolic failure evident at both 5 and 12 mo of age. However, the preserved contractility was associated with a decreased sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a)/phospholamban ratio and increased NCX1 content. Direct myocardial injection of adenovirus encoding anti-sense NCX1 significantly decreased NCX1 expression and induced systolic failure in the Akitains2 mouse. CXCL12 and CXCR4 were both upregulated in the Akitains2 heart, along with an increase in IκB-α and NF-κB p65 phosphorylation. We demonstrated that CXCR4 activation upregulates NCX1 expression through a NF-κB-dependent signaling pathway in the cardiac myocyte. In conclusion, the Akitains2 type 1 diabetic model is protected against systolic failure due to increased NCX1 expression. In addition, our studies reveal a novel role of CXCR4 in the diabetic heart by regulating NCX1 expression via a NF-κB-dependent mechanism.
CD40 amplifies Fas-mediated apoptosis: a mechanism contributing to emphysema
Authors: Shigeta Ayako , Tada Yuji , Wang Ji-Yang , Ishizaki Shunsuke , Tsuyusaki Junichi , Yamauchi Keita , Kasahara Yasunori , Iesato Ken , Tanabe Nobuhiro , Takiguchi Yuichi , Sakamoto Akemi , Tokuhisa Takeshi , Shibuya Kazutoshi , Hiroshima Kenzo , West James , Tatsumi Koichiro
Published: May 2012

Excessive apoptosis and prolonged inflammation of alveolar cells are associated with the pathogenesis of pulmonary emphysema. We aimed to determine whether CD40 affects alveolar epithelial cells and endothelial cells, with regard to evoking apoptosis and inflammation. Mice were repeatedly treated with agonistic-anti CD40 antibody (Ab), with or without agonistic-anti Fas Ab, and evaluated for apoptosis and inflammation in lungs. Human pulmonary microvascular endothelial cells and alveolar epithelial cells were treated with agonistic anti-CD40 Ab and/or anti-Fas Ab to see their direct effect on apoptosis and secretion of proinflammatory molecules in vitro. Furthermore, plasma soluble CD40 ligand (sCD40L) level was evaluated in patients with chronic obstructive pulmonary disease (COPD). In mice, inhaling agonistic anti-CD40 Ab induced moderate alveolar enlargement. CD40 stimulation, in combination with anti-Fas Ab, induced significant emphysematous changes and increased alveolar cell apoptosis. CD40 stimulation also enhanced IFN-γ-mediated emphysematous changes, not via apoptosis induction, but via inflammation with lymphocyte accumulation. In vitro, Fas-mediated apoptosis was enhanced by CD40 stimulation and IFN-γ in endothelial cells and by CD40 stimulation in epithelial cells. CD40 stimulation induced secretion of CCR5 ligands in endothelial cells, enhanced with IFN-γ. Plasma sCD40L levels were significantly increased in patients with COPD, inversely correlating to the percentage of forced expiratory volume in 1 s and positively correlating to low attenuation area score by CT scan, regardless of smoking history. Collectively CD40 plays a contributing role in the development of pulmonary emphysema by sensitizing Fas-mediated apoptosis in alveolar cells and increasing the secretion of proinflammatory chemokines.
Matrix Metalloproteinases and Minocycline: Therapeutic Avenues for Fragile X Syndrome
Authors: Siller Saul S. , Broadie Kendal
Published: May 2012

Fragile X syndrome (FXS) is the most common known genetic form of intellectual disability and autism spectrum disorders. FXS patients suffer a broad range of other neurological symptoms, including hyperactivity, disrupted circadian activity cycles, obsessive-compulsive behavior, and childhood seizures. The high incidence and devastating effects of this disease state make finding effective pharmacological treatments imperative. Recently, reports in both mouse andDrosophilaFXS disease models have indicated that the tetracycline derivative minocycline may hold great therapeutic promise for FXS patients. Both models strongly suggest that minocycline acts on the FXS disease state via inhibition of matrix metalloproteinases (MMPs), a class of zinc-dependent extracellular proteases important in tissue remodeling and cell-cell signaling. Recent FXS clinical trials indicate that minocycline may be effective in treating human patients. In this paper, we summarize the recent studies inDrosophilaand mouse FXS disease models and human FXS patients, which indicate that minocycline may be an effective FXS therapeutic treatment, and discuss the data forming the basis for the proposed minocycline mechanism of action as an MMP inhibitor.
Photocatalytic Degradation of Dichlorvos in Visible Light byMg2+-TiO2Nanocatalyst
Authors: Siva Rao T. , Segne Teshome Abdo , Susmitha T. , Balaram Kiran A. , Subrahmanyam C.
Published: May 2012

Photocatalytic activity of TiO2was studied by doping with magnesium (Mg2+-TiO2) with varying magnesium weight percentages ranging from 0.75–1.5 wt%. The doped and undoped samples were synthesized by sol-gel method and characterized by X-ray diffraction (XRD), N2adsorption-desorption (BET), X-ray photoelectron spectroscopy (XPS), UV-visible diffuse reflectance spectroscopy (DRS), and scanning electron microscopy (SEM). The XRD data has shown that anatase crystalline phase in Mg2+-TiO2catalysts, indicating that Mg2+ions did not influence the crystal patterns of TiO2. The presence of magnesium ions in TiO2matrix has been determined by XPS spectra. DRS spectra showed that there is a significant absorption shift towards the visible region for doped TiO2. The SEM images and BET results showed that doped catalyst has smaller particle size and highest surface area than undoped TiO2. The photocatalytic efficiency of the synthesized catalysts was investigated by the photocatalytic degradation of aqueous dichlorvos (DDVP) under visible light irradiation, and it was found that the Mg2+-doped catalysts have better catalytic activity than undoped TiO2. This can be attributed that there is a more efficient electron-hole creation in Mg2+-TiO2in visible light, contrary to undoped TiO2which can be excited only in UV irradiation. The effect of dopant concentration, pH of solution, dosage of catalysts, and initial pesticide concentration has been studied.