Effect of Lactobacillus acidophilus supernatants on body weight and leptin expression in rats

<p>Abstract</p> <p>Background</p> <p><it>Lactobacillus </it>extracts and supernatants have been used as probiotics in human and veterinary medicine for their ability to enhance wound healing and immunity. Previous data from our laboratory demonstrated that <it>Lactobacillus </it>supernatant (LS) stimulated wound healing, angiogenesis and proliferation of embryonic cells after topical application. This current study shows that LS after its administration into the cerebral ventricles of male rats exerts systemic effects.</p> <p>Methods</p> <p>The right lateral cerebral ventricle of young male rats was accessed through intracerebroventricular cannulation (ICV) under anesthesia and aseptic conditions. One group of control rats received saline solution, a second control group received 0.8 M lactic acid solution (to control for acidity of LS), and a third group received LS. The animals were sacrificed 12, 24, 48, 96 and 120 hours after the injection. Selected tissues were collected, fixed in 10% buffered formalin and used for immunohistochemistry and <it>in situ </it>hybridization. Other tissues were frozen and extracted for immunoblotting</p> <p>Results</p> <p>LS-injected animals had a slight decrease in body weight when compared to their initial weight and to both control groups. Using immunohistochemistry and <it>in situ </it>hybridization leptin expression was studied in multiple brain sections and peripheral adipose tissue of control and LS-injected rats. Strong cytoplasmic stain was observed by both techniques in neurons of the cerebral cortex, thalamus, hypothalamus, hippocampus and, to lesser degree, in the cells of the choroid plexus in the LS-injected rats. Control animals demonstrated much less intense staining in neurons located in the same regions using immunohistochemistry and almost no staining with <it>in situ </it>hybridization technique. Adipose tissue exhibited slight presence of leptin in LS-treated animals. In contrast no immunohistochemical staining for GM-CSF and TNFα was observed in brains from control and treated rats. Western blotting showed mild increase in leptin and leptin receptors in intestines and retroperitoneal adipose tissues of LS-injected rats.</p> <p>Conclusion</p> <p>This study demonstrates that direct administration of LS into rat CNS leads to a decrease in body weight of rats and an increase in the expression of leptin in specific areas of the brain and retroperitoneal adipose tissue.</p

Copy number polymorphisms near SLC2A9 are associated with serum uric acid concentrations

BACKGROUND: Hyperuricemia is associated with multiple diseases, including gout, cardiovascular disease, and renal disease. Serum urate is highly heritable, yet association studies of single nucleotide polymorphisms (SNPs) and serum uric acid explain a small fraction of the heritability. Whether copy number polymorphisms (CNPs) contribute to uric acid levels is unknown. RESULTS: We assessed copy number on a genome-wide scale among 8,411 individuals of European ancestry (EA) who participated in the Atherosclerosis Risk in Communities (ARIC) study. CNPs upstream of the urate transporter SLC2A9 on chromosome 4p16.1 are associated with uric acid ([Formula: see text] , p=3.19×10(-23)). Effect sizes, expressed as the percentage change in uric acid per deleted copy, are most pronounced among women ((3.97)4.93(5.87) [ (2.5)50(97.5) denoting percentiles], p=4.57×10(-23)) and independent of previously reported SNPs in SLC2A9 as assessed by SNP and CNP regression models and the phasing SNP and CNP haplotypes ([Formula: see text]). Our finding is replicated in the Framingham Heart Study (FHS), where the effect size estimated from 4,089 women is comparable to ARIC in direction and magnitude ((1.41)4.70(7.88), p=5.46×10(-03)). CONCLUSIONS: This is the first study to characterize CNPs in ARIC and the first genome-wide analysis of CNPs and uric acid. Our findings suggests a novel, non-coding regulatory mechanism for SLC2A9-mediated modulation of serum uric acid, and detail a bioinformatic approach for assessing the contribution of CNPs to heritable traits in large population-based studies where technical sources of variation are substantial

Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group

Bush the transnationalist: a reappraisal of the unilateralist impulse in US foreign policy, 2001-2009

This article challenges the common characterisation of George W. Bush’s foreign policy as “unilateral.” It argues that the Bush administration developed a new post-9/11 understanding of terrorism as a transnational, networked phenomenon shaped by the forces of globalisation. This led to a new strategic emphasis on bi- and multilateral security co-operation and counterterrorism operations, especially outside of Afghanistan and Iraq, driven by the perceived need to counter a transnational security challenge present in multiple locations. This (flawed) attempt to engage with transnational security challenges supplemented the existing internationalist pillar of the Bush administration’s foreign policy. Highlighting the transnational realm of international relations and the ways in which the Bush administration was able to co-opt other states to tackle perceived transnational challenges also shows the high importance the administration attached to concerted action even as it frequented eschewed institutional multilateralism

Asthma Is a Risk Factor for Respiratory Exacerbations Without Increased Rate of Lung Function Decline:Five-Year Follow-up in Adult Smokers From the COPDGene Study

BACKGROUND: Previous investigations in adult smokers from the COPDGene Study have shown that early-life respiratory disease is associated with reduced lung function, COPD, and airway thickening. Using 5-year follow-up data, we assessed disease progression in subjects who had experienced early-life respiratory disease. We hypothesized that there are alternative pathways to reaching reduced FEV1 and that subjects who had childhood pneumonia, childhood asthma, or asthma-COPD overlap (ACO) would have less lung function decline than subjects without these conditions.METHODS: Subjects returning for 5-year follow-up were assessed. Childhood pneumonia was defined by self-reported pneumonia at &lt; 16 years. Childhood asthma was defined as self-reported asthma diagnosed by a health professional at &lt; 16 years. ACO was defined as subjects with COPD who self-reported asthma diagnosed by a health-professional at ≤ 40 years. Smokers with and those without these early-life respiratory diseases were compared on measures of disease progression.RESULTS: Follow-up data from 4,915 subjects were examined, including 407 subjects who had childhood pneumonia, 323 subjects who had childhood asthma, and 242 subjects with ACO. History of childhood asthma or ACO was associated with an increased exacerbation frequency (childhood asthma, P &lt; .001; ACO, P = .006) and odds of severe exacerbations (childhood asthma, OR, 1.41; ACO, OR, 1.42). A history of childhood pneumonia was associated with increased exacerbations of COPD (absolute difference [β], 0.17; P = .04). None of these early-life respiratory diseases were associated with an increased rate of lung function decline or progression on CT scans.CONCLUSIONS: Subjects who had early-life asthma are at increased risk of COPD developing and of having more active disease with more frequent and severe respiratory exacerbations without an increased rate of lung function decline over a 5-year period.TRIAL REGISTRY: ClinicalTrials.gov; No. NCT00608764; https://clinicaltrials.gov.</p

Aid on Demand: African Leaders and the Geography of China's Foreign Assistance

This article investigates whether China’s foreign aid is particularly prone to political capture by political leaders of aid-receiving countries. Specifically, we examine whether more Chinese aid is allocated to the political leaders’ birth regions and regions populated by the ethnic group to which the leader belongs, controlling for indicators of need and various fixed effects. We have collected data on 117 African leaders’ birthplaces and ethnic groups and geocoded 1,650 Chinese development finance projects across 3,097 physical locations committed to Africa over the 2000-2012 period. Our econometric results show that current political leaders’ birth regions receive substantially larger financial ows from China than other regions. On the contrary, when we replicate the analysis for the World Bank, our regressions with region-fixed effects show no evidence of such favoritism. For Chinese and World Bank aid alike, we also find no evidence that African leaders direct more aid to areas populated by groups who share their ethnicity, when controlling for region-fixed effects

Effects of irrigated parks on outdoor residential water use in a semi-arid city

We investigate whether public park amenities act as a substitute for outdoor water use by single-family residential (SFR) households in semi-arid Tucson, AZ, USA. Specifically we account for the effects of a park's proximity, size, and greenness (measured by NDVI), as well as the presence of a public swimming pool. SFR households with and without home pools are analyzed separately. We control for SFR property attributes, including house size, age, yard size and property NDVI. Results suggest that SFR outdoor water use is influenced by the conditions of all parks within an 8. km (5. mile) street distance. We also find significant differences between the "with" and "without" home pool groups. Households with pools used more outdoor water per square meter of house, per year of house age and per unit of NDVI. Households without pools appeared to reduce outdoor use in response to nearby small parks and increased park NDVI. "With pool" households had the opposite response: they appeared to increase outdoor water use in response to these variables. However, "with pool" households did reduce their outdoor water use in response to nearby public pools. Medium and large parks were associated with increased outdoor water use for both groups. We conclude that public green space and pools can substitute for private versions of these amenities, and if well designed, can contribute to water demand management and urban sustainability. This may be an avenue for addressing water supply shortages in semi-arid cities and other areas where populations are growing but water supplies are finite