bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibitory mechanisms that generate centre and surround properties in ON and OFF brisk‐sustained ganglion cells in the rabbit retina
Authors: Buldyrev Ilya , Taylor W. Rowland 
Published: October 2012

Key points
ON and OFF cells in the retina are excited by increases and decreases in visual contrast, respectively. ON and OFF brisk‐sustained ganglion cells (BSGCs) have antagonistic ‘centre‐surround’ receptive fields; a visual stimulus that excites the centre is inhibitory in the surround. Such lateral inhibition enhances sensitivity to contrast borders.
This study provides the first detailed comparison of visually evoked, excitatory and inhibitory synaptic inputs driving the centres and surrounds of ON and OFF BSGCs.
GABAergic lateral inhibition suppresses excitatory inputs to BSGCs presynaptically, via GABAC receptors at ON BSGCS and GABAA and GABAC receptors at OFF BSGCs. Feed‐forward glycinergic inhibition, driven through the ON pathway, contributes to centre but not surround responses in both cell types.
Centre excitation is mediated by AMPA receptors in ON BSGCs, and NMDA and AMPA receptors in OFF BSGCs.
The results reveal mechanistic differences in homologous neural circuits that perform a similar neural computation in the visual system.
Abstract  Lateral inhibition produces the centre‐surround organization of retinal receptive fields, in which inhibition driven by the mean luminance enhances the sensitivity of ganglion cells to spatial and temporal contrast. Surround inhibition is generated in both synaptic layers; however, the synaptic mechanisms within the inner plexiform layer are not well characterized within specific classes of retinal ganglion cell. Here, we compared the synaptic circuits generating concentric centre‐surround receptive fields in ON and OFF brisk‐sustained ganglion cells (BSGCs) in the rabbit retina. We first characterized the synaptic inputs to the centre of ON BSGCs, for comparison with previous results from OFF BSGCs. Similar to wide‐field ganglion cells, the spatial extent of the excitatory centre and inhibitory surround was larger for the ON than the OFF BSGCs. The results indicate that the surrounds of ON and OFF BSGCs are generated in both the outer and the inner plexiform layers. The inner plexiform layer surround inhibition comprised GABAergic suppression of excitatory inputs from bipolar cells. However, ON and OFF BSGCs displayed notable differences. Surround suppression of excitatory inputs was weaker in ON than OFF BSGCs, and was mediated largely by GABAC receptors in ON BSGCs, and by both GABAA and GABAC receptors in OFF BSGCs. Large ON pathway‐mediated glycinergic inputs to ON and OFF BSGCs also showed surround suppression, while much smaller GABAergic inputs showed weak, if any, spatial tuning. Unlike OFF BSGCs, which receive strong glycinergic crossover inhibition from the ON pathway, the ON BSGCs do not receive crossover inhibition from the OFF pathway. We compare and discuss possible roles for glycinergic inhibition in the two cell types.
Contribution of Adenosine A
2B
Receptors in Clostridium difficile Intoxication and Infection
Authors: Warren Cirle A. , Li Yuesheng , Calabrese Gina M. , Freire Rosemayre S. , Zaja-Milatovic Snjezana , van Opstal Edward , Figler Robert A. , Linden Joel , Guerrant Richard L. 
Published: October 2012

ABSTRACT

Clostridium difficile
toxins A (TcdA) and B (TcdB) induce a pronounced systemic and intestinal inflammatory response. A
2B
adenosine receptors (A
2B
ARs) are the predominant adenosine receptors in the intestinal epithelium. We investigated whether A
2B
ARs are upregulated in human intestinal cells by TcdA or TcdB and whether blockade of A
2B
ARs can ameliorate
C. difficile
TcdA-induced enteritis and alter the outcome of
C. difficile
infection (CDI). Adenosine receptor subtype (A
1
, A
2A
, A
2B
, and A
3
) mRNAs were assayed in HCT-8 cells. Ileal loops from wild-type rabbits and mice and A
2B
AR
−/−
mice were treated with TcdA, with or without the selective A
2B
AR antagonist ATL692 or PSB1115. A murine model of CDI was used to determine the effect of A
2B
AR deletion or blockade with the orally available agent ATL801, on clinical outcome, histopathology and intestinal interleukin-6 (IL-6) expression from infection. TcdA and TcdB upregulated A
2B
AR gene expression in HCT-8 cells. ATL692 decreased TcdA-induced secretion and epithelial injury in rabbit ileum. Deletion of A
2B
ARs reduced secretion and histopathology in TcdA-challenged mouse ileum. Deletion or blockade of A
2B
ARs reduced histopathology, IL-6 expression, weight loss, diarrhea, and mortality in
C. difficile
-infected mice. A
2B
ARs mediate
C. difficile
toxin-induced enteritis and disease. Inhibition of A
2B
AR activation may be a potential strategy to limit morbidity and mortality from CDI.
The Vibrio cholerae trh Gene Is Coordinately Regulated
In Vitro
with Type III Secretion System Genes by VttR
A
/VttR
B
but Does Not Contribute to Caco2-BBE Cell Cytotoxicity
Authors: Miller Kelly A. , Hamilton Elaine , Dziejman Michelle 
Published: October 2012

ABSTRACT

Numerous virulence factors have been associated with pathogenic non-O1/non-O139 serogroup strains of
Vibrio cholerae
. Among them are the
t
hermostable
d
irect
h
emolysin (TDH) and the
T
DH-
r
elated
h
emolysin (TRH), which share amino acid similarities to the TDH and TRH proteins of
Vibrio parahaemolyticus
, where they have been shown to contribute to pathogenesis. Although TDH and TRH homologs can be encoded on extrachromosomal elements in
V. cholerae
, type III secretion system (T3SS)-positive strains, such as AM-19226, carry a copy of
trh
within the T3SS genomic island. Transcriptional fusion analysis showed that in strain AM-19226,
trh
expression is regulated in a bile-dependent manner by a family of transmembrane transcriptional regulators that includes VttR
A
, VttR
B
, and ToxR. Genes encoding T3SS structural components are expressed under similar conditions, suggesting that within the T3SS genomic island, genes encoding proteins unrelated to the T3SS and loci involved in T3SS synthesis are coregulated. Despite similar
in vitro
expression patterns, however, TRH is not required for AM-19226 to colonize the infant mouse intestine, nor does it contribute to bile-mediated cytotoxicity when strain AM-19226 is cocultured with the mammalian cell line Caco2-BBE. Instead, we found that a functional T3SS is essential for AM-19226 to induce bile-mediated cytotoxicity
in vitro
. Collectively, the results are consistent with a more minor role for the
V. cholerae
TRH in T3SS-positive strains compared to the functions attributed to the
V. parahaemolyticus
TDH and TRH proteins.
Rethinking Biosafety in Research on Potential Pandemic Pathogens
Authors: Lipsitch Marc , Bloom Barry R. 
Published: October 2012

ABSTRACT
If accidentally released, mammalian-transmissible influenza A/H5N1 viruses could pose a greater threat to public health than possibly any other infectious agent currently under study in laboratories, because of such viruses’ likely combination of transmissibility and virulence to humans. We advocate explicit risk-benefit assessments before work on such pathogens is permitted or funded, improvement of biosafety practices and enforcement, and harmonization of criteria for permitting such experiments across government agencies, as well as internationally. Such potential pandemic pathogens, as they have been called, jeopardize not only laboratory workers and their contacts, but also the wider population, who should be involved in assessments of when such risks are acceptable in the service of scientific knowledge that may itself bear major public health benefits.
Tianeptine in combination with monoamine oxidase inhibitors for major depressive disorder
Authors: Tobe Edward H 
Published: October 2012

Major depressive disorder may respond to monotherapy with monoamine oxidase inhibitors (MAOIs) or tianeptine. Literature search showed no reports of MAOIs combined with tianeptine. The method included was clinical case history. A 59-year-old woman had partial improvement of depression with the MAOI tranylcypromine combined with topiramate, trazodone and ziprasidone. The patient had further improvement of depression symptoms after addition of tianeptine. No adverse events were evident. The combination of MAIOs and tianeptine may be effective for refractory major depressive disorder.
TRIM59, a novel multiple cancer biomarker for immunohistochemical detection of tumorigenesis
Authors: Khatamianfar Vida , Valiyeva Fatma , Rennie Paul S , Lu Wei-yang , Yang Burton B , Bauman Glenn S , Moussa Madeleine , Xuan Jim W 
Published: October 2012

Objectives and designWe identified a novel TRIM59 gene, as an early signal transducer in two (SV40Tag and Ras) oncogene pathways in murine prostate cancer (CaP) models. We explore its clinical applications as a multitumour marker detecting early tumorigenesis by immunohistochemistry (IHC).Setting and participants88 CaP patients were from a tissue microarray (TMA) of radical prostatectomy specimen, 42 patients from a 35 multiple tumour TMA, 75 patients with renal cell carcinoma (RCC) and 92 patients from eight different tumour groups (breast, lung, parotid, gastrointestinal, female genital tract, bladder, kidney and prostate cancer).ResultsTRIM59 upregulation specifically in tumour area was determined by IHC in 291 cases of 37 tumour types. To demonstrate that TRIM59 upregulation is ‘tumour-specific’, we characterised a significant correlation of TRIM59 IHC signals with tumorigenesis and progression, while in control and normal area, TRIM59 IHC signal was all negative or significantly low. TRIM59 protein upregulation in prostate and kidney cancers was detectable in both intensity and extent in early tumorigenesis of prostate intraepithelial neoplasia (p<0.05) and grade 1 of RCC (p<0.05), and stopped until high grades cancer. The results of the correlation in these two large cohorts of tumour types confirmed and repeated murine CaP model studies. Enhanced TRIM59 expression was identified in most of the 37 different tumours, while the highest intensities were in lung, breast, liver, skin, tongue and mouth (squamous cell cancer) and endometrial cancers. Multiple tumour upregulation was further confirmed by comparing relative scores of TRIM59 IHC signals in eight tumours with a larger patient population; and by a mouse whole-mount embryo (14.5 days post conception) test on the origin of TRIM59 upregulation in epithelial cells.ConclusionsTRIM59 may be used a novel multiple tumour marker for immunohistochemical detecting early tumorigenesis and could direct a novel strategy for molecular-targeted diagnosis and therapy of cancer.
Impacts of early smoking initiation: long-term trends of lung cancer mortality and smoking initiation from repeated cross-sectional surveys in Great Britain
Authors: Funatogawa Ikuko , Funatogawa Takashi , Yano Eiji 
Published: October 2012

ObjectiveTo show long-term trends of smoking initiation in Great Britain including unanalysed data and assess the impact of early smoking initiation on the lung cancer mortality in later ages focusing on birth cohorts.DesignReanalysis of repeated cross-sectional surveys conducted 13 times during 1965–1987.SettingGreat Britain.ParticipantsMen and women aged 16 years and over in each survey.Primary outcome measuresSmoking initiation for 1898–1969 birth cohorts and lung cancer mortality in 1950–2009.ResultsIn men, 1900–1925 birth cohorts showed high smoking initiation (>32%, >50% and >80% at 15, 17 and 29 years old, respectively). Correspondingly, the lung cancer mortality in these cohorts exceeded 1 per 1000 at a young age (50–54 years old). In women, smoking initiation increased clearly from the 1898 cohort to the 1925 cohort (2% to 12%, 4% to 24%, and 13% to 54% at 15, 17 and 29 years old, respectively). Correspondingly, the age at which the mortality exceeded 1 per 1000 became younger (75–79 to 60–64 years old). In both men and women, short-term decreases in initiation were seen from the late-1920s cohorts. Correspondingly, lung cancer mortality decreased. In women, initiation increased again after the mid-1930s cohorts, and mortality increased after they became 60–64 years old.ConclusionsClear relationships between smoking initiation and lung cancer mortality across birth cohorts were observed. Countries with rapid increases in initiation in teens should not underestimate the risk in the distant future. Because of the long time lags within cohorts compared with rapid changes in smoking habits across cohorts, age-specific measures focusing on birth cohorts should be monitored.
Tectonostratigraphic evolution of the Upper Cretaceous–Cenozoic central Anatolian basins: an integrated study of diachronous ocean basin closure and continental collision
Authors: Nairn Steven P. , Robertson Alastair H. F. , Ünlügenç Ulvi Can , Tasli Kemal , İnan Nurdan 
Published: October 2012

Abstract
The Upper Cretaceous–Mid-Eocene Kırıkkale, Tuz Gölü, Haymana and Çankırı basins are bounded by the Pontide (Eurasian) continental margin to the north, the Niğde–Kırşehir microcontinent to the east and the Tauride–Anatolide continental unit to the south. The basins developed during northward subduction/collision of the İzmir–Ankara–Erzincan Ocean (‘northern Neotethys’) in the north and the inferred Inner Tauride Ocean in the south. Subduction of the İzmir–Ankara–Erzincan Ocean resulted in latest Cretaceous collision of the Niğde–Kırşehir microcontinent with the Pontide active margin and ophiolite emplacement. Some mid-ocean ridge-type oceanic crust remained to the SW and formed the basement of the Kırıkkale and Tuz Gölü basins. These basins are partially floored by an accretionary wedge to the west and by the Niğde–Kırşehir microcontinent to the east. Locally volcaniclastic, the sediment infill switched to terrigenous after latest Cretaceous. The Haymana Basin, further NW, developed as a forearc basin on the Mesozoic accretionary wedge and Pontide continental fragments. The Çankırı Basin also developed on an accretionary wedge, bounded by the Eurasian active margin to the north. An extensional setting prevailed during the latest Cretaceous related to subduction of remnant oceanic crust, followed by a switch to regional compression during Late Paleocene–Mid Eocene progressive and diachronous collision.
Risk of Heart Failure Complication During Hospitalization for Acute Myocardial Infarction in a Contemporary Population
Authors: Shah Ravi V. , Holmes DaJuanicia , Anderson Monique , Wang Tracy Y. , Kontos Michael C. , Wiviott Stephen D. , M. Scirica Benjamin 
Published: October 2012

Background—
Patients with acute myocardial infarction (MI) complicated by heart failure (HF) are subject to higher mortality during the index hospitalization. Early risk prediction and intervention may help prevent HF-related morbidity and mortality.

Methods and Results—

We examined 77 675 ST-elevation MI and 110 128 non-ST-elevation patients with MI without cardiogenic shock or HF at presentation treated at 609 hospitals in Acute Coronary Treatment and Intervention Outcomes Network Registry (ACTION) Registry-Get With The Guidelines between January 1, 2007, and March 31, 2011. Logistic regression identified patient characteristics associated with development of in-hospital HF. Overall, 3.8% of patients with MI developed in-hospital HF, which was associated with higher mortality in both ST-elevation MI and non-ST elevation MI. In multivariable logistic regression, left ventricular ejection fraction ≤30%, prior HF, diabetes mellitus, female sex, ST-elevation MI, and hypertension (all
P
<0.005) were independently associated with in-hospital HF. Patients who developed HF during non-ST-elevation MI were more likely to be medically managed without catheterization (30% versus 13% with HF,
P
<0.0001) or had longer delays to surgical or percutaneous revascularization. Patients with ST-elevation MI and HF were less likely to receive primary percutaneous coronary revascularization (84% versus 79% with HF,
P
<0.0001), and more likely to receive thrombolytic therapy (14% versus 11%;
P
=0.0001).

Conclusions—
Patients with MI who develop HF during hospitalization have a higher risk clinical profile and greater mortality, but may be less likely to receive revascularization in a timely fashion. Targeting these highest risk patients may improve outcome post-MI.
Premature Atrial Contractions in the General Population
Authors: Conen David , Adam Martin , Roche Frederic , Barthelemy Jean-Claude , Felber Dietrich Denise , Imboden Medea , Künzli Nino , von Eckardstein Arnold , Regenass Stephan , Hornemann Thorsten , Rochat Thierry , Gaspoz Jean-Michel , Probst-Hensch Nicole , Carballo David 
Published: October 2012

Background—
Premature atrial contractions (PACs) are independent predictors of atrial fibrillation, stroke, and death. However, little is known about PAC frequency in the general population and its association with other cardiovascular risk factors.

Methods and Results—

We performed a cross-sectional analysis among participants of the population-based Swiss cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA). 24-hour Holter electrocardiograms to assess PAC prevalence and frequency were performed in a random sample of 1742 participants aged ≥50 years. The median (interquartile range) number of PACs per hour was 0.8 (0.4–1.8), 1.1 (0.5–2.4), 1.4 (0.7–4.6), 2.3 (0.8–6.9), and 2.6 (1.2–6.5) among participants aged 50 to 55, 55 to 60, 60 to 65, 65 to 70, and ≥70 years, respectively (
P
<0.0001). Only 18 (1.0%) participants did not have at least 1 PAC during Holter monitoring. In multivariable negative binomial regression models, PAC frequency was significantly associated with age (risk ratio [RR] per SD 1.80;
P
<0.0001), height (RR per SD 1.52;
P
<0.0001), prevalent cardiovascular disease (RR 2.40;
P
<0.0001), log-transformed N-terminal pro B-type natriuretic peptides (RR per SD 1.27;
P
<0.0001), physical activity ≥2 hours per day (RR 0.69;
P
=0.002), and high-density lipoprotein cholesterol (RR per SD 0.80;
P
=0.0002). Hypertension and body mass index were not significantly related to PAC frequency.

Conclusions—
To our knowledge, this is the first study to assess risk factors for PAC frequency in the general population aged ≥50 years. PACs are common, and their frequency is independently associated with age, height, history of cardiovascular disease, natriuretic peptide levels, physical activity, and high-density lipoprotein cholesterol. The underlying mechanisms of these relationships need to be addressed in future studies.
House Price Fluctuations: The Role of Housing Wealth as Borrowing Collateral
Authors: Cooper Daniel 
Published: October 2012

AbstractRising house prices affect household spending by either loosening a household's lifetime budget constraint (pure wealth effect) or the household's borrowing constraint so that consumption rises toward the level implied by the consumption Euler equation (borrowing collateral effect). The empirical findings in this paper are consistent with house price appreciation affecting household spending through the borrowing collateral channel and not the pure wealth effect channel. The consumption of potentially borrowing constrained households increases between [dollar]0.06 and [dollar]0.18 per dollar increase in their housing equity, while the consumption of unconstrained households is little changed.
Immigrant Networks and Their Implications for Occupational Choice and Wages
Authors: Patel Krishna , Vella Francis 
Published: October 2012

Abstract
Occupational shares of various ethnic groups have grew tremendously in regional U.S. labor markets from 1980 to 2000. Using U.S. Census data, we examine the extent to which this growth is attributed to network effects by studying the relationship between the occupational choice of recently arrived immigrants with those of established immigrants from the same country, We find strong evidence of network effects. First, new arrivals are choosing the same occupations as their compatriots, a decision that is operating at the regional level. Second, individuals who choose the most common occupation of their compatriots enjoy a large and positive earnings effect.
The Effect of Rising Income Inequality on Taxation and Public Expenditures: Evidence from U.S. Municipalities and School Districts, 1970–2000
Authors: Boustan Leah , Ferreira Fernando , Winkler Hernan , Zolt Eric M. 
Published: October 2012

Abstract
The income distribution in many developed countries widened dramatically from 1970 to 2000. Some scholars argue that income inequality contributes to a host of social ills by undermining voters' willingness to support public expenditures. In contrast, we find that growing income inequality is associated with an expansion in government revenues and expenditures on a wide range of services in U.S. municipalities and school districts. Results are robust to a number of model specifications, including instrumental variables that address the endogeneity of the local income distribution. Our results are inconsistent with models predicting that heterogeneous societies provide lower levels of public goods.
Statistical and Physical Analysis of the Vertical Structure of Precipitation in the Mountainous West Region of the United States Using 11+ Years of Spaceborne Observations from TRMM Precipitation Radar
Authors: Cao Qing , Hong Yang , Gourley Jonathan J. , Qi Youcun , Zhang Jian , Wen Yixin , Kirstetter Pierre-Emmanuel 
Published: October 2012

AbstractThis study presents a statistical analysis of the vertical structure of precipitation measured by NASA–Japan Aerospace Exploration Agency’s (JAXA) Tropical Rainfall Measuring Mission (TRMM) precipitation radar (PR) in the region of southern California, Arizona, and western New Mexico, where the ground-based Next-Generation Radar (NEXRAD) network finds difficulties in accurately measuring surface precipitation because of beam blockages by complex terrain. This study has applied TRMM PR version-7 products 2A23 and 2A25 from 1 January 2000 to 26 October 2011. The seasonal, spatial, intensity-related, and type-related variabilities are characterized for the PR vertical profile of reflectivity (VPR) as well as the heights of storm, freezing level, and bright band. The intensification and weakening of reflectivity at low levels in the VPR are studied through fitting physically based VPR slopes. Major findings include the following: precipitation type is the most significant factor determining the characteristics of VPRs, the shape of VPRs also influences the intensity of surface rainfall rates, the characteristics of VPRs have a seasonal dependence with strong similarities between the spring and autumn months, and the spatial variation of VPR characteristics suggests that the underlying terrain has an impact on the vertical structure. The comprehensive statistical and physical analysis strengthens the understanding of the vertical structure of precipitation and advocates for the approach of VPR correction to improve surface precipitation estimation in complex terrain.