bluuebunny/crossref_metadata_2025_split huggingface dataset:
A physiological view of the central and peripheral mechanisms that regulate the release of catecholamines at the adrenal medulla
Authors: De Diego A. M. G. , Gandía L. , García A. G. 
Published: July 2010

AbstractHere we review the tight neural control of the differential secretion into the circulation, of the adrenal medullary hormones adrenaline and noradrenaline. One or the other catecholamines are differentially released on various stress conditions. This is specifically controlled by central nervous system nuclei at the cortex, hypothalamus and spinal cord. Different firing patterns of splanchnic nerves and nicotinic or muscarinic receptors cause the selective release of noradrenaline or adrenaline, to adapt the body to the ‘fight or flight’ reaction, or during severe hypoglycaemia, haemorrhage, cold, acute myocardial infarction or other severe stressful conflicts. Endogenously acetylcholine (ACh) released at the splanchnic nerve‐chromaffin cell synapse, acting on muscarinic and nicotinic receptors, causes membrane depolarization and action potentials (AP) in chromaffin cells. These changes vary with the animal species, the cell preparation (intact bisected adrenal, adrenal slices, or isolated fresh or cultured cells) or the recording technique (intracellular microelectrodes, patch‐clamp, perforated‐patch, cell‐attached). Conflicting results leave many open questions concerning the actions of ACh on chromaffin cell excitability. The use of adrenal slices and field electrical stimulation will surely provide new insights into these mechanisms. Chromaffin cells have been thoroughly used as models to study the relationship between Ca2+entry, cytosolic Ca2+signals, exocytosis and endocytosis, using patch‐clamp and amperometric techniques. Cells have been stimulated with single depolarizing pulses (DPs), DP trains and with simulated AP waveforms. These approaches have provided useful information but we have no data on APs generated by pulsatile secretory quanta of ACh, trying to mimic the intermittent and repetitive splanchnic nerve discharge of the neurotransmitter. We present some recent experiments using ultrashort ACh pulses (25 ms), that cause non‐desensitizing repetitive APs with each ACh pulse, at low ACh concentrations (30 μm). Ultrashort pulses of a high ACh concentration (1000 μm) causes a single AP followed by a prolonged depolarization. It could be interesting trying to correlate these ‘patterns of splanchnic nerve discharge’ with Ca2+signals and exocytosis. This, together with the use of adrenal slices and transmural electrical stimulation of splanchnic nerves will provide new physiologically sound data on the regulation of adrenal medullary secretion.
Secretory granule behaviour adjacent to the plasma membrane before and during exocytosis: total internal reflection fluorescence microscopy studies
Authors: Holz R. W. , Axelrod D. 
Published: July 2010

AbstractOur current notions of different granule pools, granule interaction with the plasma membrane, and ultimately granule and plasma membrane soluble N‐ethylmaleimide‐sensitive‐factor attachement protein (SNARE) interactions, result largely from inferences based upon biochemical alterations of secretion kinetics. Another view of events comes from studies using total internal reflection fluorescence microscopy (TIRFM) to investigate granule behaviour immediately adjacent to the plasma membrane. The motions of secretory (chromaffin) granules in bovine chromaffin cells visualized by TIRFM are highly restricted, as if granules are caged or tethered. These small motions are regulated by ATP and Ca2+, two factors that increase priming of the secretory response. There is no evidence that granules decrease their motion immediately before secretion. To the contrary, there is a tendency for granules to increase their motions and travel within a few hundred milliseconds of fusion. Hence, the notion of a long‐lived docked state as a prelude to fusion does not encompass the physical reality of molecular scale motions, multiple tethering states and significant travel immediately preceding the exocytotic event. Increased travel may increase the probability of granules interacting productively with the plasma membrane constituents, thereby, increasing the probability of fusion.
Risk factors for incident open‐angle glaucoma: a population‐based 20‐year follow‐up study
Authors: Ekström Curt 
Published: July 2010

Abstract.Purpose: To study the effect of potential risk factors on the development of open‐angle glaucoma (OAG) in a population in which pseudoexfoliation (PEX) is a common finding.Methods:  In 1984–1986, a population‐based survey of 760 people aged 65–74 years was conducted in the municipality of Tierp, Sweden. From 1988 to 2006, a follow‐up study of the 530 people with normal visual fields has been in progress. To increase the cohort, 273 ophthalmic outpatients were enroled. Reliable visual fields were available for 679 people, representing 6 126 person‐years at risk. A time‐weighted mean intraocular pressure (IOP) for all visits was calculated.Results:  Sixty‐four subjects developed definite OAG, 29 of whom were exposed to PEX. Risk factors associated with OAG were higher age, a positive family history, increased IOP and PEX. The age‐standardized rate ratio (SRR) was 14.8 times (95% confidence interval [CI] 7.92–27.8) greater in subjects with mean IOP ≥20 mmHg than in those with mean IOP <20 mmHg. When subjects with IOP <20 mmHg at baseline were affected by PEX, the SRR increased 5.01‐fold (95% CI 1.97–12.8), compared with the unaffected group. However, when mean IOP at follow‐up was taken into account, there was no relationship between OAG and PEX as a distinct risk factor. Among participants in the population survey, 69% of all cases were attributable to a mean IOP ≥20 mmHg.Conclusion:  Increased IOP and PEX were serious risk factors for incident OAG. The effect of PEX was mediated by increased IOP.
Bifocals in children with Down syndrome (BiDS) – visual acuity, accommodation and early literacy skills
Authors: Nandakumar Krithika , Leat Susan J. 
Published: July 2010

Acta Ophthalmol. 2010: 88: e196–e204Abstract.Purpose:  Reduced accommodation is seen in children and young adults with Down syndrome (DS), yet providing bifocals has not become a routine clinical management. This study investigates the impact of bifocals on visual function, visual perceptual and early literacy skills in a group of school children with DS.Methods:  In this longitudinal study, each child was followed for 5 months with single‐vision (SV) lenses after which bifocals were prescribed if required, based on their accommodative response. Visual acuity (VA), accommodation, perceptual and literacy skills were measured after adaptation to bifocals and 5 months later. Educational progress and compliance with spectacle wear were assessed through school and parental reports.Results:  Fourteen children and young adults with DS participated in the study. Eighty‐five percent required bifocals with additions ranging from +1.00 D to +3.50 D. The mean near logMAR VA improved with bifocals (p = 0.007) compared to SV lenses. Repeated measures anova showed that there was more accurate focus (less accommodative lag) through the bifocals (p = 0.002), but no change in the accommodation exerted through the distance portion compared to SV lenses (p = 0.423). There was a main effect of time on sight words (p = 0.013), Word Identification (p = 0.047), Visual Closure (p = 0.006) and Visual Form Constancy (p = 0.001).Conclusion:  Bifocals provide clearer near vision in DS children with reduced accommodation. This is shown by improved VA and decreased lag of accommodation. The results indicate that the improvement in VA results in improved scores in early literacy skills. Better compliance with bifocals over SV lenses was seen.
Presence of Enteric Viruses in Source Waters for Drinking Water Production in the Netherlands
Authors: Lodder W. J. , van den Berg H. H. J. L. , Rutjes S. A. , de Roda Husman A. M. 
Published: July 2010

ABSTRACT
The quality of drinking water in the Netherlands has to comply with the Dutch Drinking Water Directive: less than one infection in 10,000 persons per year may occur due to consumption of unboiled drinking water. Since virus concentrations in drinking waters may be below the detection limit but entail a public health risk, the infection risk from drinking water consumption requires the assessment of the virus concentrations in source waters and of the removal efficiency of treatment processes. In this study, samples of source waters were taken during 4 years of regular sampling (1999 to 2002), and enteroviruses, reoviruses, somatic phages, and F-specific phages were detected in 75% (range, 0.0033 to 5.2 PFU/liter), 83% (0.0030 to 5.9 PFU/liter), 100% (1.1 to 114,156 PFU/liter), and 97% (0.12 to 14,403 PFU/liter), respectively, of 75 tested source water samples originating from 10 locations for drinking water production. By endpoint dilution reverse transcription-PCR (RT-PCR), 45% of the tested source water samples were positive for norovirus RNA (0.22 to 177 PCR-detectable units [PDU]/liter), and 48% were positive for rotavirus RNA (0.65 to 2,249 PDU/liter). Multiple viruses were regularly detected in the source water samples. A significant correlation between the concentrations of the two phages and those of the enteroviruses could be demonstrated. The virus concentrations varied greatly between 10 tested locations, and a seasonal effect was observed. Peak concentrations of pathogenic viruses occur in source waters used for drinking water production. If seasonal and short-term fluctuations coincide with less efficient or failing treatment, an unacceptable public health risk from exposure to this drinking water may occur.
Enhanced Production and Secretion of Heterologous Proteins by the Filamentous Fungus
Aspergillus oryzae
via Disruption of Vacuolar Protein Sorting Receptor Gene
Aovps10
Authors: Yoon Jaewoo , Aishan Tuerxun , Maruyama Jun-ichi , Kitamoto Katsuhiko 
Published: July 2010

ABSTRACT

Filamentous fungi have received attention as hosts for heterologous protein production because of their high secretion capability and eukaryotic posttranslational modifications. However, despite these positive attributes, a bottleneck in posttranscriptional processing limits protein yields. The vacuolar protein sorting gene
VPS10
encodes a sorting receptor for the recognition and delivery of several yeast vacuolar proteins. Although it can also target recombinant and aberrant proteins for vacuolar degradation, there is limited knowledge of the effect of its disruption on heterologous protein production. In this study, cDNA encoding AoVps10 from the filamentous fungus
Aspergillus oryzae
was cloned and sequenced. Microscopic observation of the transformant expressing AoVps10 fused with enhanced green fluorescent protein showed that the fusion protein localized at the Golgi and prevacuolar compartments. Moreover, disruption of the
Aovps10
gene resulted in missorting and secretion of vacuolar carboxypeptidase AoCpyA into the medium, indicating that AoVps10 is required for sorting of vacuolar proteins to vacuoles. To investigate the extracellular production levels of heterologous proteins, Δ
Aovps10
mutants expressing either bovine chymosin (CHY) or human lysozyme (HLY) were constructed. Interestingly, the Δ
Aovps10
mutation increased the maximum extracellular production levels of CHY and HLY by 3- and 2.2-fold, respectively. Western blot analysis of extracellular heterologous proteins also demonstrated an improvement in productivity. These results suggest that AoVps10 plays a role in the regulation of heterologous protein secretion in
A. oryzae
and may be involved in the vacuolar protein degradation through the Golgi apparatus.
Molecular Characterization of GrlA, a Specific Positive Regulator of
ler
Expression in Enteropathogenic
Escherichia coli
Authors: Jiménez Rafael , Cruz-Migoni Sara B. , Huerta-Saquero Alejandro , Bustamante Víctor H. , Puente José L. 
Published: July 2010

ABSTRACT

Enteropathogenic
Escherichia coli
(EPEC) infections are characterized by the formation of attaching and effacing (A/E) lesions on the surfaces of infected epithelial cells. The genes required for the formation of A/E lesions are located within the locus of enterocyte effacement (LEE). Ler is the key regulatory factor controlling the expression of LEE genes. Expression of the
ler
gene is positively regulated by GrlA, which is encoded by the LEE. Here, we analyze the mechanism by which GrlA positively regulates
ler
expression and show that in the absence of H-NS, GrlA is no longer essential for
ler
activation, further confirming that GrlA acts in part as an H-NS antagonist on the
ler
promoter. Single-amino-acid mutants were constructed to test the functional significance of the putative helix-turn-helix (HTH) DNA binding motif found in the N-terminal half of GrlA, as well as at the C-terminal domain of the protein. Several mutations within the HTH motif, but not all, completely abolished GrlA activity, as well as specific binding to its target sequence downstream from position −54 in the
ler
regulatory region. Some of these mutants, albeit inactive, were still able to interact with the negative regulator GrlR, indicating that loss of activity was not a consequence of protein misfolding. Additional residues in the vicinity of the HTH domain, as well as at the end of the protein, were also shown to be important for GrlA activity as a transcriptional regulator, but not for its interaction with GrlR. In summary, GrlA consists of at least two functional domains, one involved in transcriptional activation and DNA binding and the other in heterodimerization with GrlR.
Dual Two-Component Regulatory Systems Are Involved in Aromatic Compound Degradation in a Polychlorinated-Biphenyl Degrader,
Rhodococcus jostii
RHA1
Authors: Takeda Hisashi , Shimodaira Jun , Yukawa Kiyoshi , Hara Naho , Kasai Daisuke , Miyauchi Keisuke , Masai Eiji , Fukuda Masao 
Published: July 2010

ABSTRACT

A Gram-positive polychlorinated-biphenyl (PCB) degrader,
Rhodococcus jostii
RHA1, degrades PCBs by cometabolism with biphenyl. A two-component BphS1T1 system encoded by
bphS1
and
bphT1
(formerly
bphS
and
bphT
) is responsible for the transcription induction of the five gene clusters,
bphAaAbAcAdC1B1
,
etbAa1Ab1CbphD1
,
etbAa2Ab2AcD2
,
etbAdbphB2
, and
etbD1
, which constitute multiple enzyme systems for biphenyl/PCB degradation. The
bphS2
and
bphT2
genes, which encode BphS2 and BphT2, virtually identical to BphS1 (92%) and BphT1 (97%), respectively, were characterized. BphS2T2 induced the activation of the
bphAa
promoter in a host,
Rhodococcus erythropolis
IAM1399, in the presence of a variety of aromatics, including benzene, toluene, ethylbenzene, xylenes, isopropylbenzene, and chlorinated benzenes, as effectively as BphS1T1. The substrate spectrum of BphS2T2 was the same as that of BphS1T1, except for biphenyl, which is a substrate only for BphS1T1. BphS2T2 activated transcription from the five promoters of biphenyl/PCB degradation enzyme gene clusters as effectively as BphS1T1. The targeted disruptions of the
bphS1
,
bphS2
,
bphT1
, and
bphT2
genes indicated that all these genes are involved in the growth of RHA1 on aromatic compounds. The hybrid system with
bphS1
and
bphT2
and that with
bphS2
and
bphT1
were constructed, and both systems conducted induced activation of the
bphAa
promoter, indicating cross-communication. These results indicated that RHA1 employs not only multiple enzyme systems, but also dual regulatory systems for biphenyl/PCB degradation. Comparison of the sequences, including
bphS2T2
, with the
bphS1T1
-containing sequences and the corresponding sequences in other rhodococcal degraders suggests that
bphS2T2
might have originated from
bphS1T1
.
Functional Identification of theProteusmirabilisCore Lipopolysaccharide Biosynthesis Genes
Authors: Aquilini Eleonora , Azevedo Joana , Jimenez Natalia , Bouamama Lamiaa , Tomás Juan M. , Regué Miguel 
Published: July 2010

ABSTRACTIn this study, we report the identification of genes required for the biosynthesis of the core lipopolysaccharides (LPSs) of two strains ofProteusmirabilis. SinceP.mirabilisandKlebsiellapneumoniaeshare a core LPS carbohydrate backbone extending up to the second outer-core residue, the functions of the commonP.mirabilisgenes was elucidated by genetic complementation studies using well-defined mutants ofK.pneumoniae. The functions of strain-specific outer-core genes were identified by using as surrogate acceptors LPSs from two well-definedK.pneumoniaecore LPS mutants. This approach allowed the identification of two new heptosyltransferases (WamA and WamC), a galactosyltransferase (WamB), and anN-acetylglucosaminyltransferase (WamD). In both strains, most of these genes were found in the so-calledwaagene cluster, although one common core biosynthetic gene (wabO) was found outside this cluster.
BLUE OCEAN OR FAST-SECOND INNOVATION? A FOUR-BREAKTHROUGH MODEL TO EXPLAIN SUCCESSFUL MARKET DOMINATION
Authors: BUISSON BERNARD , SILBERZAHN PHILIPPE 
Published: July 2010

Innovation is widely recognized as a major driver of long-term corporate growth. Successful innovators who manage to dominate new markets enjoy Schumpeterian rents for their inventions. How then can a firm dominate a new market? Two streams of literature have proposed opposite answers to this question. The First Mover approach indicates that by setting up a strong differentiation strategy, companies are supposed to create a new area where profits abound. This approach is supported especially by Kim and Mauborgne (2004) who coined the term Blue Ocean to describe it. The Fast Second approach, defended by Markides and Geroski (2005), contends, on the contrary, that companies should not try to become pioneers, but should target the newly created market in second position, and colonize it. But neither Blue Ocean nor Fast Second are able to convincingly explain successful market domination. Our study of 24 innovation cases suggests that innovation which leads to market domination is instead achieved by using four kinds of breakthroughs, separately of simultaneously.
IMPROVING CUSTOMERS TARGETING WITH SHORT INTERVENTION TESTING
Authors: GOFMAN ALEX , MOSKOWITZ HOWARD R. 
Published: July 2010

The proposed consumer-driven innovation approach allows for the creation of individual communications with heterogeneous customers. It utilizes Rule Developing Experimentation (a modified conjoint analysis-based approach) to create a database of messages specific to the product and to segment consumers based on the patterns of individual utilities assigned to the different test elements. The paper introduces a new approach to identify a small subset of classification messages that allows for an actionable and parsimonious classification of any new population into pattern-based segments to achieve better targeting. The approach is demonstrated by a case study of identifying segment membership for better messages targeting prospective customers of a KIA car dealership.
Nerve growth factor promotes breast cancer angiogenesis by activating multiple pathways
Authors: Romon Rodrigue , Adriaenssens Eric , Lagadec Chann , Germain Emmanuelle , Hondermarck Hubert , Le Bourhis Xuefen 
Published: July 2010

Abstract

Background
Although several anti-angiogenic therapies have been approved in the treatment of cancer, the survival benefits of such therapies are relatively modest. Discovering new molecules and/or better understating signaling pathways of angiogenesis is therefore essential for therapeutic improvements. The objective of the present study was to determine the involvement of nerve growth factor (NGF) in breast cancer angiogenesis and the underlying molecular mechanisms.

Results
We showed that both recombinant NGF and NGF produced by breast cancer cells stimulated angiogenesis in Matrigel plugs in immunodeficient mice. NGF strongly increased invasion, cord formation and the monolayer permeability of endothelial cells. Moreover, NGF-stimulated invasion was under the control of its tyrosine kinase receptor (TrkA) and downstream signaling pathways such as PI3K and ERK, leading to the activation of matrix metalloprotease 2 and nitric oxide synthase. Interestingly, NGF increased the secretion of VEGF in both endothelial and breast cancer cells. Inhibition of VEGF, with a neutralizing antibody, reduced about half of NGF-induced endothelial cell invasion and angiogenesis in vivo.

Conclusions
Our findings provided direct evidence that NGF could be an important stimulator for breast cancer angiogenesis. Thus, NGF, as well as the activated signaling pathways, should be regarded as potential new targets for anti-angiogenic therapy against breast cancer.
TLX1 and NOTCH coregulate transcription in T cell acute lymphoblastic leukemia cells
Authors: Riz Irene , Hawley Teresa S , Luu Truong V , Lee Norman H , Hawley Robert G 
Published: July 2010

Abstract

Background
The homeobox gene TLX1 (for T-cell leukemia homeobox 1, previously known as HOX11) is inappropriately expressed in a major subgroup of T cell acute lymphoblastic leukemia (T-ALL) where it is strongly associated with activating NOTCH1 mutations. Despite the recognition that these genetic lesions cooperate in leukemogenesis, there have been no mechanistic studies addressing how TLX1 and NOTCH1 functionally interact to promote the leukemic phenotype.

Results
Global gene expression profiling after downregulation of TLX1 and inhibition of the NOTCH pathway in ALL-SIL cells revealed that TLX1 synergistically regulated more than 60% of the NOTCH-responsive genes. Structure-function analysis demonstrated that TLX1 binding to Groucho-related TLE corepressors was necessary for maximal transcriptional regulation of the NOTCH-responsive genes tested, implicating TLX1 modulation of the NOTCH-TLE regulatory network. Comparison of the dataset to publicly available biological databases indicated that the TLX1/NOTCH-coregulated genes are frequently targeted by MYC. Gain- and loss-of-function experiments confirmed that MYC was an essential mediator of TLX1/NOTCH transcriptional output and growth promotion in ALL-SIL cells, with TLX1 contributing to the NOTCH-MYC regulatory axis by posttranscriptional enhancement of MYC protein levels. Functional classification of the TLX1/NOTCH-coregulated targets also showed enrichment for genes associated with other human cancers as well as those involved in developmental processes. In particular, we found that TLX1, NOTCH and MYC coregulate CD1B and RAG1, characteristic markers of early cortical thymocytes, and that concerted downregulation of the TLX1 and NOTCH pathways resulted in their irreversible repression.

Conclusions
We found that TLX1 and NOTCH synergistically regulate transcription in T-ALL, at least in part via the sharing of a TLE corepressor and by augmenting expression of MYC. We conclude that the TLX1/NOTCH/MYC network is a central determinant promoting the growth and survival of TLX1+ T-ALL cells. In addition, the TLX1/NOTCH/MYC transcriptional network coregulates genes involved in T cell development, such as CD1 and RAG family members, and therefore may prescribe the early cortical stage of differentiation arrest characteristic of the TLX1 subgroup of T-ALL.