bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Diguanylate Cyclase SadC Is a Central Player in Gac/Rsm-Mediated Biofilm Formation in Pseudomonas aeruginosa
Authors: Moscoso Joana A. , Jaeger Tina , Valentini Martina , Hui Kailyn , Jenal Urs , Filloux Alain 
Published: September 2014

ABSTRACT

Pseudomonas aeruginosa
is a Gram-negative opportunistic human pathogen and a threat for immunocompromised and cystic fibrosis patients. It is responsible for acute and chronic infections and can switch between these lifestyles upon taking an informed decision involving complex regulatory networks. The RetS/LadS/Gac/Rsm network and the cyclic-di-GMP (c-di-GMP) signaling pathways are both central to this phenomenon redirecting the
P. aeruginosa
population toward a biofilm mode of growth, which is associated with chronic infections. While these two pathways were traditionally studied independently from each other, we recently showed that cellular levels of c-di-GMP are increased in the hyperbiofilm
retS
mutant. Here, we have formally established the link between the two networks by showing that the SadC diguanylate cyclase is central to the Gac/Rsm-associated phenotypes, notably, biofilm formation. Importantly, SadC is involved in the signaling that converges onto the RsmA translational repressor either via RetS/LadS or via HptB/HsbR. Although the level of expression of the
sadC
gene does not seem to be impacted by the regulatory cascade, the production of the SadC protein is tightly repressed by RsmA. This adds to the growing complexity of the signaling network associated with c-di-GMP in
P. aeruginosa
. While this organism possesses more than 40 c-di-GMP-related enzymes, it remains unclear how signaling specificity is maintained within the c-di-GMP network. The finding that SadC but no other diguanylate cyclase is related to the formation of biofilm governed by the Gac/Rsm pathway further contributes to understanding of this insulation mechanism.
The effects of random breath testing and lowering the minimum legal drinking age on traffic fatalities in Australian states
Authors: Jiang Heng , Livingston Michael , Manton Elizabeth 
Published: September 2014

ObjectiveThis study aims to apply time series analysis techniques to examine the effects of random breath testing (RBT) on three age-specific traffic fatalities in four Australian states while considering the effects of lowering the minimum legal drinking age (MLDA).MethodsLong-term time series of age-specific traffic crash deaths in four Australian states were used to analyse the impact of RBT implementation while considering the population growth, increase in motor vehicle registrations and the effects of lowering the MLDA.ResultsThe results of intervention analysis indicate that RBT has substantially reduced traffic fatalities in all four states since it was introduced, particularly among the 17-year-olds to 20-year-olds and 21-year-olds to 30-year-olds. New South Wales received the biggest total net effect from RBT implementation on traffic deaths. By contrast, RBT produced only a modest reduction in traffic fatalities among 30-year-olds to 39-year-olds. Lowering the MLDA was associated with significant increases in traffic fatalities among 17-year-olds to 39-year-olds in Queensland and Western Australia.ConclusionsControlling for the declining trend in traffic fatalities, the effects of changes in the MLDA law, the implementation of RBT has generated a huge effect, preventing an estimated 5279 traffic crash deaths in four Australian states. This provides further evidence that the implementation of RBT and increases in the MLDA are effective policies for reducing traffic fatalities.
P3-factorization of triangulated Cartesian product of complete graphs
Authors: Tamil Elakkiya A. , Muthusamy A. 
Published: September 2014

Partition of G into edge-disjoint H-factors is called an H-factorization of G. Shehzad Afzal and Clemens Brand have factorized graphs into factors which are isomorphic to triangulated Cartesian product of two subgraphs. Also they have discussed properties of triangulated Cartesian product of more than two graphs. In this paper, we show that the necessary conditions mn ≡ 0 (mod 3), m, n are odd and 3(mn + m + n - 3) ≡ 0 (mod 8) are sufficient for the existence of a P3-factorization of Km⧅ Kn, where ⧅ denotes triangulated Cartesian product of graphs, if one of the following holds:(i) m ≡ 9 (mod 12), n = 5, 13 and 17,(ii) m ≡ 9 (mod 12), ns, s > 1, n = 5, 13 and 17,(iii) m ≡ 9 (mod 12), n = psqtfor all s, t ≥ 1, where p = 5, 13 and q = 13, 17, p ≠ q,(iv) m ≡ 9 (mod 12), n ≡ 9 (mod 12).
Potential of MODFLOW to Model Hydrological Interactions in a Semikarst Floodplain of the Ozark Border Forest in the Central United States
Authors: Chinnasamy Pennan , Hubbart Jason A. 
Published: September 2014

Abstract
Riparian shallow groundwater and nutrient movement is important for aquatic and forest ecosystem health. Understanding stream water (SW)–shallow groundwater (GW) interactions is necessary for proper management of floodplain biodiversity, but it is particularly confounding in underrepresented semikarst hydrogeological systems. The Modular Three-Dimensional Finite-Difference Ground-Water Flow Model (MODFLOW) was used to simulate shallow groundwater flow and nutrient transport processes in a second-growth Ozark border forest for the 2011 water year. MODFLOW provided approximations of hydrologic head that were statistically comparable to observed data (Nash–Sutcliffe = 0.47, r2 = 0.77, root-mean-square error = 0.61 cm, and mean difference = 0.46 cm). Average annual flow estimates indicated that 82% of the reach length was a losing stream, while the remaining 18% was gaining. The reach lost more water to the GW during summer (2405 m3 day−1) relative to fall (2184 m3 day−1), spring (2102 m3 day−1), and winter (1549 m3 day−1) seasons. Model results showed that the shallow aquifer had the highest nitrate loading during the winter season (707 kg day−1). A Particle-Tracking Model for MODFLOW (MODPATH) revealed significant spatial variations between piezometer sites (p = 0.089) in subsurface flow path and travel time, ranging from 213 m and 3.6 yr to 197 m and 11.6 yr. The current study approach is novel with regard to the use of transient flow conditions (as opposed to steady state conditions) in underrepresented semikarst geological systems of the U.S. Midwest. This study emphasizes the significance of semikarst geology in regulating SW–GW hydrologic and nutrient interactions and provides baseline information and modeling predictions that will facilitate future studies and management plans.
Effect of Observation Network Design on Meteorological Forecasts of Asian Dust Events
Authors: Yang Eun-Gyeong , Kim Hyun Mee , Kim JinWoong , Kay Jun Kyung 
Published: September 2014

Abstract
To improve the prediction of Asian dust events on the Korean Peninsula, meteorological fields must be accurately predicted because dust transport models require them as input. Accurate meteorological forecasts could be obtained by integrating accurate initial conditions obtained from data assimilation processes in numerical weather prediction. In data assimilation, selecting the appropriate observation location is important to ensure that the initial conditions represent the surrounding meteorological flow. To investigate the effect of observation network configuration on meteorological forecasts during Asian dust events on the Korean Peninsula, observing system simulation experiments using several simulated and real observation networks were tested with the Weather Research and Forecasting modeling system for 11 Asian dust events affecting the Korean Peninsula during a recent 6-yr period. First, the characteristics of randomly fixed and adaptively selected observation networks were investigated with various observation densities. The adaptive observation strategy could reduce forecast errors more efficiently than the fixed observation strategy. For both the fixed and adaptive observation strategies, the mean forecast error reduction rates increased as the number of assimilated observations and the distance between observation sites increased up to 300 km. Second, the effects of redistributing the real observation sites and adding observation sites to the real observation network based on the adaptive observation strategy were investigated. Adding adaptive observation sites to the real observation network in statistically sensitive regions improved the forecast performance more than redistributing real observation sites did. The strategy of adding adaptive observation sites is used to suggest the optimal meteorological observation network for meteorological forecasts of Asian dust transport events on the Korean Peninsula.
Polyclonal versus monoclonal immunoglobulin-free light chains quantification
Authors: Di Noto Giuseppe , Cimpoies Elena , Dossi Alessandra , Paolini Lucia , Radeghieri Annalisa , Caimi Luigi , Ricotta Doris 
Published: September 2014

Background The clinical usefulness of the serum-free light chain assays has expanded since their first description, and further applications other than plasma cell dyscrasia are emerging. Currently, we have the ability to perform the measurements with two certified methods: the Freelite™ assay (The Binding Site Ltd, Birmingham, UK) and the new N Latex free-light chain assay (Siemens, Germany). In the present study, we investigated the impact of free light chain concentrations and structures on their quantification, performed with both tests. Methods A total of 524 serum samples from 497 patients from our routine laboratory were analysed with the Freelite™ and the N Latex free light chain assay. The results were compared in two subgroups: with or without monoclonal component. Twenty-four samples were subsequently investigated for the presence of dimeric and monomeric free light chain with sodium dodecyl sulphate polyacrylamide gel electrophoresis and densitometric quantification. Results Methods comparison showed that the Pearson rank correlation coefficients were 0.90 for polyclonal k and 0.91 for polyclonal λ free light chain. Conversely for monoclonal immunoglobulins, the Pearson rank correlation coefficient was lower with 0.82 for kM >500 mg/L and 0.56 for λM >500 mg/L. Furthermore, densitometric quantification of the involved monoclonal free light chains showed that both assays do not reflect the Coomassie-stained protein mass. Conclusion Samples containing high amounts of a single pathologic free light chain may not be considered like a sample containing a sum of different polyclonal free light chains. Indeed, free light chain dimerization leads to different scatter efficiency of macromolecular complexes.
Patients with longstanding primary antiphospholipid syndrome: retrospective analysis of organ damage and mortality
Authors: Dall’Ara F , Reggia R , Taraborelli M , Andreoli L , Taglietti M , Frassi M , Franceschini F , Tincani A 
Published: September 2014

Objective To assess the prevalence of disease- and therapy-related complications and of the organ damage after a follow-up of 15 years or more in patients with primary antiphospholipid syndrome (PAPS). Methods Medical records of patients prospectively followed in our centre for at least 15 years were retrospectively reviewed. Results Thirty-five Caucasian patients (33 female, two male) with diagnosis of PAPS followed from 1984 to 2013 with a mean age at onset of 32 years (SD 8.17) and a median follow-up of 20.5 years (range 15–30) were included. The occurrence of systemic autoimmune disease was observed in 14% of patients. Haemorrhagic, infective and neoplastic events were recorded in 34%, 6% and 9% respectively. Organ damage was present in 20% of patients at the end of the follow-up (17% neurological and 3% renal) and was significantly associated with the occurrence of thrombotic events ( p: 0.027), particularly arterial ( p < 0.001). A 48-year-old patient died from sepsis. Conclusion During long-term follow-up of PAPS systemic autoimmunity is not unexpected. Organ damage progresses in a significant proportion of patients especially if they have suffered previous arterial events. Our study clearly shows the possible evolution of the disease and of organ damage, suggesting that optimal therapy and optimal prophylaxis of each PAPS patient should be carefully identified and strictly applied.
Children born to SLE and APS mothers
Authors: Nalli C , Iodice A , Andreoli L , Lojacono A , Motta M , Fazzi E , Tincani A 
Published: September 2014

Background Systemic lupus erythematosus (SLE) and antiphospholipid antibody syndrome (APS) are autoimmune diseases that affect women of childbearing age. Pregnancies in these patients carry several complications such as prematurity. Maternal IgG antiphospholipid antibodies (aPL) can cross the placenta but they don’t generally cause any neonatal thrombotic event. Because of the incompleteness of the fetal blood-brain barrier, aPL could theoretically reach the fetal brain. Whether this can have an effect on brain development is still under investigation. Some studies performed in children of patients with SLE and/or APS showed an increased number of learning disabilities without impairment in intelligence level. Objectives The objectives of this article are to evaluate the neurodevelopment outcome in 30 children (median age 9 years) born to mothers with SLE and/or APS with IgG anti-beta2-glycoprotein I during the third trimester of pregnancy and found positive for the same antibodies at birth. Methods A neurological physical exam was performed in all children. We submitted some questionnaires to the mothers: the Child Behavior CheckList (CBCL) and a homemade set of questions obtained by a team composed of rheumatologists and pediatric neurologists. Intellectual functioning was determined by the Wechsler scale for corrected age. Results In all children neurological physical exam and intelligence levels were found to be normal but mild behavior disorders and history of neurological manifestations were shown in three children. Conclusions Offspring of patients with SLE and/or APS are generally healthy. We and others observed the occurrence of minor neurological disorders that might be related to maternal disease or to prematurity. The limited number of the available data on this sensitive issue supports the need for further studies.
Immunomodulatory effects of Ziziphora tenuior L. extract on the dendritic cells
Authors: Azadmehr Abbas , latifi Robabeh , Mosalla Sahar , Hajiaghaee Reza , Shahnazi Mojtaba 
Published: September 2014

Abstract

Background

Ziziphora tenuior L. (Kakuti in Persian) is used in traditional medicine for treatment of gastrointestinal disorders as carminative and analgesic plant. The other usages of this plant are included treatment of diarrhea and nausea. Therefore in the present study we evaluated the immunomodulatory effects of the ethanolic extract of this plant on the dendritic cells (DCs).

Results

Ziziphora tenuior L. extract significantly (p = 0.002) increased the level of surface expression of CD40 as an important co-stimulatory marker on DCs compared to the control. However this extract did not change CD86 and MHC-II molecules, so it could promote DCs phenotypic maturation. Treatment of DCs with the extract resulted in slightly increased of the production of (IL-12); however, this change was not significant. In addition, the ability of treated DCs to stimulate allogenic T cells proliferation and cytokines secretion was examined in the co-cuture of these cells with T cells in mixed lymphocyte reaction (MLR). Z. tenuior L. at the 100 μg/ml concentration inhibited the proliferation of allogenic T cells and also significantly (P < 0.001) increased the level of IL-10. Moreover, the extract at 10–100 μg/ml concentration caused slightly increase in IFN-γ production and decreased IL-4 cytokines but these changes were not significant.

Conclusions
These findings indicated that Z. tenuior L. extract can modulate immune response by induction of CD40 expression on DCs and cytokine production; whereas it can inhibit T cell stimulating activity of DCs in high concentration. These findings possibly in part explain the traditional use of this plant in treatment of immune-mediated disorders. However future studies are needed.
Does the Thyroid-Stimulating Hormone Measured Concurrently With First Trimester Biochemical Screening Tests Predict Adverse Pregnancy Outcomes Occurring After 20 Weeks Gestation?
Authors: Ong Gregory S. Y. , Hadlow Narelle C. , Brown Suzanne J. , Lim Ee Mun , Walsh John P. 
Published: September 2014

Context:
Maternal hypothyroidism in early pregnancy is associated with adverse outcomes, but not consistently across studies. First trimester screening for chromosomal anomalies is routine in many centers and provides an opportunity to test thyroid function.

Objective:
To determine if thyroid function tests performed with first trimester screening predicts adverse pregnancy outcomes.

Design, Participants and Setting:
A cohort study of 2411 women in Western Australia with singleton pregnancies attending first trimester screening between 9 and 14 weeks gestation.

Outcome Measures:
We evaluated the association between TSH, free T4, free T3, thyroid antibodies, free beta human chorionic gonadotrophin (β-hCG) and pregnancy associated plasma protein A (PAPP-A) with a composite of adverse pregnancy events as the primary outcome. Secondary outcomes included placenta previa, placental abruption, pre-eclampsia, pregnancy loss after 20 weeks gestation, threatened preterm labor, preterm birth, small size for gestational age, neonatal death, and birth defects.

Results:
TSH exceeded the 97.5th percentile for the first trimester (2.15 mU/L) in 133 (5.5%) women, including 22 (1%) with TSH above the nonpregnant reference range (4 mU/L) and 5 (0.2%) above 10 mU/L. Adverse outcomes occurred in 327 women (15%). TSH and free T4 did not differ significantly between women with or without adverse pregnancy events. On the multivariate analysis, neither maternal TSH &gt;2.15 mU/L nor TSH as a continuous variable predicted primary or secondary outcomes.

Conclusion:
Testing maternal TSH as part of first trimester screening does not predict adverse pregnancy outcomes. This may be because in the community setting, mainly mild abnormalities in thyroid function are detected.
Exogenous Kisspeptin Administration as a Probe of GnRH Neuronal Function in Patients With Idiopathic Hypogonadotropic Hypogonadism
Authors: Chan Yee-Ming , Lippincott Margaret F. , Butler James P. , Sidhoum Valerie F. , Li Cindy X. , Plummer Lacey , Seminara Stephanie B. 
Published: September 2014

Context:
Idiopathic hypogonadotropic hypogonadism (IHH) results from defective synthesis, secretion, or action of GnRH. Kisspeptin is a potent stimulus for GnRH secretion.

Objective:
We probed the functional capacity of the GnRH neuronal network in patients with IHH.

Participants:
Eleven subjects with congenital IHH (9 men and 2 women) and one male subject who underwent reversal of IHH were studied. Six of the twelve subjects had an identified genetic cause of their IHH: KAL1 (n = 1), FGFR1 (n = 3), PROKR2 (n = 1), GNRHR (n = 1).

Intervention:
Subjects underwent q10 min blood sampling to measure GnRH-induced LH secretion at baseline and in response to intravenous boluses of kisspeptin (0.24 nmol/kg) and GnRH (75 ng/kg) both pre- and post-six days of treatment with exogenous GnRH (25 ng/kg sc every 2 h).

Results:
All subjects with abiding IHH failed to demonstrate a GnRH-induced LH response to exogenous kisspeptin. In contrast, the subject who achieved reversal of his hypogonadotropism demonstrated a robust response to kisspeptin.

Conclusions:
The functional capacity of the GnRH neuronal network in IHH patients is impaired, as evidenced by their inability to respond to the same dose of kisspeptin that effects a robust GnRH-induced LH response in healthy men and luteal-phase women. This impairment is observed across a range of genotypes, suggesting that it reflects a fundamental property of GnRH neuronal networks that have not been properly engaged during pubertal development. In contrast, a patient who had experienced reversal of his hypogonadotropism responded to exogenous kisspeptin.
Sex Hormone-Binding Globulin Gene Expression and Insulin Resistance
Authors: Winters Stephen J. , Gogineni Jyothi , Karegar Marjan , Scoggins Charles , Wunderlich Chris A. , Baumgartner Richard , Ghooray Dushan T. 
Published: September 2014

Context:
The plasma level of sex hormone binding globulin (SHBG), a glycoprotein produced by hepatocytes, is subject to genetic, hormonal, metabolic, and nutritional regulation, and is a marker for the development of the metabolic syndrome and diabetes.

Objective:
Because the mechanism for these associations is unclear, and no studies of SHBG gene expression in humans have been published, SHBG mRNA was measured in human liver samples and related to anthropometric data.

Setting:
Inpatients at a private, nonprofit, university-associated hospital were studied.

Participants:
Subjects were fifty five adult men and women undergoing hepatic resection as treatment for cancer.

Main Outcome Measures:
Main outcome measures were SHBG mRNA and serum SHBG levels.

Results:
SHBG mRNA was a strong predictor of serum SHBG with higher levels of the mRNA and protein in women than in men. The relationship between SHBG mRNA and circulating SHBG differed in males and females consistent with a sex difference in post-transcriptional regulation. A strong positive correlation was found between the level of the mRNA for the transcription factor HNF4α and SHBG mRNA. Insulin resistance (IR), assessed by homeostatis model assessment, was related inversely to SHBG mRNA and to HNF4α mRNA as well as to circulating SHBG levels. These mRNAs, as well as serum SHBG, were higher when the hepatic triglyceride concentration was low, and decreased with increasing body mass index but were unrelated to age.

Conclusions:
Fat accumulation in liver and IR are important determinants of SHBG gene expression and thereby circulating SHBG levels that are perhaps mediated through effects on the transcription factor HNF4α. These findings provide a potential mechanism to explain why low SHBG predicts the development of type 2 diabetes.
Expression of macrophage elastase (MMP12) in rat tail intervertebral disc and growth plate after asymmetric loading
Authors: Vasiliadis E. S. , Kaspiris A. , Grivas T. B. , Khaldi L. , Lamprou M. , Pneumaticos S. G. , Nikolopoulos K. , Korres D. S. , Papadimitriou E. 
Published: September 2014

Objectives The aim of this study was to examine whether asymmetric loading influences macrophage elastase (MMP12) expression in different parts of a rat tail intervertebral disc and growth plate and if MMP12 expression is correlated with the severity of the deformity. Methods A wedge deformity between the ninth and tenth tail vertebrae was produced with an Ilizarov-type mini external fixator in 45 female Wistar rats, matched for their age and weight. Three groups were created according to the degree of deformity (10°, 30° and 50°). A total of 30 discs and vertebrae were evaluated immunohistochemically for immunolocalisation of MMP12 expression, and 15 discs were analysed by western blot and zymography in order to detect pro- and active MMP12. Results No MMP12 expression was detected in the nucleus pulposus. Expression of MMP12 in the annulus progressively increased from group I to groups II and III, mainly at the concave side. Many growth plate chondrocytes expressed MMP12 in the control group, less in group I and rare in groups II and III. Changes in cell phenotype and reduction of cell number were observed, together with disorganisation of matrix microstructure similar to disc degeneration. ProMMP12 was detected at the area of 54 kDa and active MMP12 at 22 kDa. Conclusions Expression of MMP12 after application of asymmetric loading in a rat tail increased in the intervertebral disc but decreased in the growth plate and correlated with the degree of the deformity and the side of the wedged disc. Cite this article: Bone Joint Res 2014;3:273–9.