Sirt1 Deletion Leads to Enhanced Inflammation and Aggravates Endotoxin-Induced Acute Kidney Injury

Bacterial endotoxin has been known to induce excessive inflammatory responses and acute kidney injury. In the present study, we used a mouse model of endotoxemia to investigate the role of Sirt1 in inflammatory kidney injury. We examined molecular and cellular responses in inducible Sirt1 knockout (Sirt1-/-) mice and wild type littermates (Sirt1+/+) in lipopolysaccharide (LPS)-induced kidney injury. Our studies demonstrated that Sirt1 deletion caused aggravated kidney injury, which was associated with increased inflammatory responses including elevated pro-inflammatory cytokine production, and increased ICAM-1 and VCAM-1 expression. Inflammatory signaling such as STAT3/ERK phosphorylation and NF-κB activation was markedly elevated in kidney tissues of Sirt1 knockout mice after LPS challenge. The results indicate that Sirt1 is protective against LPS-induced acute kidney injury by suppressing kidney inflammation and down-regulating inflammatory signaling

The structure of HI in galactic disks: Simulations vs observations

We generate synthetic HI Galactic plane surveys from spiral galaxy simulations which include stellar feedback processes. Compared to a model without feedback we find an increased scale height of HI emission (in better agreement with observations) and more realistic spatial structure (including supernova blown bubbles). The synthetic data show HI self-absorption with a morphology similar to that seen in observations. The density and temperature of the material responsible for HI self-absorption is consistent with observationally determined values, and is found to be only weakly dependent on absorption strength and star formation efficiency.Comment: 12 pages, 7 figures. Accepted for publication in MNRA

4-[(4-Benzyl­oxybenzyl­idene)amino]-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one

In the title mol­ecule, C25H23N3O2, two terminal phenyl rings are twisted by 50.20 (6) and 71.26 (5)° from the mean plane (r.m.s. deviation = 0.032 Å) of the central benzyl­idene–amino–pyrazolone fragment. The N atoms of the pyrazole ring have a pyramidal environment, the sums of the valence angles around them being 353.5 (2) and 347.3 (2)°. The crystal structure is stabilized by C—H⋯O interactions

4-(3-Carb­oxy-1-ethyl-6-fluoro-4-oxo-1,4-dihydro-7-quinol­yl)-1-methyl­piper­azin­ium picrate

The pefloxacinium cation of the title salt, C17H21FN3O3 +·C6H2N3O7 −, is composed of an essentially planar quinoline ring system [maximum deviation = 0.021 (2) Å] and a piperazine ring, which adopts a chair conformation. In the picrate anion, the two O atoms of one of the o-NO2 groups are disordered over two positions, with an occupancy ratio of 0.56 (4):0.44 (4). In the crystal structure, cations and anions are connected by inter­molecular N—H⋯O, O—H⋯O, C—H⋯O and C—H⋯F hydrogen bonds, forming a three-dimensional network. In addition, π–π inter­actions between the pyridine rings and between the benzene rings of the anions, with centroid–centroid distances of 3.6103 (12) and 3.5298 (11) Å, respectively, are observed

Globalization of Diabetes: The role of diet, lifestyle, and genes

Type 2 diabetes is a global public health crisis that threatens the economies of all nations, particularly developing countries. Fueled by rapid urbanization, nutrition transition, and increasingly sedentary lifestyles, the epidemic has grown in parallel with the worldwide rise in obesity. Asia's large population and rapid economic development have made it an epicenter of the epidemic. Asian populations tend to develop diabetes at younger ages and lower BMI levels than Caucasians. Several factors contribute to accelerated diabetes epidemic in Asians, including the “normal-weight metabolically obese” phenotype; high prevalence of smoking and heavy alcohol use; high intake of refined carbohydrates (e.g., white rice); and dramatically decreased physical activity levels. Poor nutrition in utero and in early life combined with overnutrition in later life may also play a role in Asia's diabetes epidemic. Recent advances in genome-wide association studies have contributed substantially to our understanding of diabetes pathophysiology, but currently identified genetic loci are insufficient to explain ethnic differences in diabetes risk. Nonetheless, interactions between Westernized diet and lifestyle and genetic background may accelerate the growth of diabetes in the context of rapid nutrition transition. Epidemiologic studies and randomized clinical trials show that type 2 diabetes is largely preventable through diet and lifestyle modifications. Translating these findings into practice, however, requires fundamental changes in public policies, the food and built environments, and health systems. To curb the escalating diabetes epidemic, primary prevention through promotion of a healthy diet and lifestyle should be a global public policy priority

Unravelling the importance of the eukaryotic and bacterial communities and their relationship with Legionella spp. ecology in cooling towers: a complex network

ABSTRACT: Background Cooling towers are a major source of large community-associated outbreaks of Legionnaires’ disease, a severe pneumonia. This disease is contracted when inhaling aerosols that are contaminated with bacteria from the genus Legionella, most importantly Legionella pneumophila. How cooling towers support the growth of this bacterium is still not well understood. As Legionella species are intracellular parasites of protozoa, it is assumed that protozoan community in cooling towers play an important role in Legionella ecology and outbreaks. However, the exact mechanism of how the eukaryotic community contributes to Legionella ecology is still unclear. Therefore, we used 18S rRNA gene amplicon sequencing to characterize the eukaryotic communities of 18 different cooling towers. The data from the eukaryotic community was then analysed with the bacterial community of the same towers in order to understand how each community could affect Legionella spp. ecology in cooling towers. Results We identified several microbial groups in the cooling tower ecosystem associated with Legionella spp. that suggest the presence of a microbial loop in these systems. Dissolved organic carbon was shown to be a major factor in shaping the eukaryotic community and may be an important factor for Legionella ecology. Network analysis, based on co-occurrence, revealed that Legionella was correlated with a number of different organisms. Out of these, the bacterial genus Brevundimonas and the ciliate class Oligohymenophorea were shown, through in vitro experiments, to stimulate the growth of L. pneumophila through direct and indirect mechanisms. Conclusion Our results suggest that Legionella ecology depends on the host community, including ciliates and on several groups of organisms that contribute to its survival and growth in the cooling tower ecosystem. These findings further support the idea that some cooling tower microbiomes may promote the survival and growth of Legionella better than others

Spark plasma sintering of TiyNb1-yCxN1-x monolithic ceramics obtained by mechanically induced self-sustaining reaction

Nanometer-sized titanium-niobium carbonitride powders (TiyNb1-yCxN1-x) with different Ti/Nb atomic ratios were obtained by a mechanically induced self-sustaining reaction, and sintered by spark plasma sintering technique at 1500 degrees C for 1 min in a vacuum atmosphere. Mechanical properties such as hardness and Young's modulus were determined by nanoindentation technique and friction and wear coefficients assessed by ball-on-disk testing using alumina ball in dry sliding conditions. The fracture surface and wear tracks of samples were examined by scanning electron microscopy. Results showed that it is possible to obtain dense monolithic ceramics from the solid solution (TiyNb1-yCxN1-x) with good mechanical properties and excellent wear resistance. The optimum values of nanomechanical properties were found for the Ti0.3Nb0.7C0.5N0.5 ceramic composition, which exhibited a high hardness over 26.0 GPa and Young's modulus around 400 GPa. Crown Copyright (C) 2012 Published by Elsevier B.V. All rights reserved.The authors would like to thank Dr. Emilio Rayon for performing the nanoindentation analysis in the Materials Technology institute (ITM) of the Polytechnic University of Valencia and to acknowledge the financial support received from Spanish Ministry of Science and Innovation for FPI grant (MAT2006-01783). This work was supported by the Spanish government under grant (MAT2010-17046), which is financed in part by the European Regional Development Fund of 2007-2013. E. Chicardi was supported by CSIC through a JAE-Pre grant, which is financed in part by the European Social Fund (ESF).Borrell Tomás, MA.; Salvador Moya, MD.; Garcia-Rocha, V.; Fernandez, A.; Chicardi, E.; Gotor, FJ. (2012). Spark plasma sintering of TiyNb1-yCxN1-x monolithic ceramics obtained by mechanically induced self-sustaining reaction. Materials Science and Engineering: A. 543:173-179. https://doi.org/10.1016/j.msea.2012.02.071S17317954

In Vitro Efficacy of Myxococcus fulvus ANSM068 to Biotransform Aflatoxin B1

Aflatoxin B1 (AFB1) is commonly found in cereals and animal feeds and causes a significant threat to the food industry and animal production. Several microbial isolates with high AFB1 transformation ability have been identified in our previous studies. The aim of this research was to characterize one of those isolates, Myxococcus fulvus ANSM068, and to explore its biotransformation mechanism. The bacterial isolate of M. fulvus ANSM068, isolated from deer feces, was able to transform AFB1 by 80.7% in liquid VY/2 medium after incubation at 30 °C for 72 h. The supernatant of the bacterial culture was more effective in transforming AFB1 as compared to the cells alone and the cell extract. The transformation activity was significantly reduced and eradicated after the culture supernatant was treated with proteinase K, proteinase K plus SDS and heating. Culture conditions, including nitrogen source, initial pH and incubation temperature were evaluated for an optimal AFB1 transformation. Liquid chromatography mass spectrometry (LCMS) analyses showed that AFB1 was transformed to a structurally different compound. Infrared analysis (IR) indicated that the lactone ring on the AFB1 molecule was modified by the culture supernatant. Chromatographies on DEAE-Ion exchange and Sephadex-Molecular sieve and SDS-PAGE electrophoresis were used to determine active components from the culture supernatant, indicating that enzyme(s) were responsible for the AFB1 biotransformation. This is the first report on AFB1 transformation by a strain of myxobacteria through enzymatic reaction(s)

Role of an Expanded Inositol Transporter Repertoire in Cryptococcus neoformans Sexual Reproduction and Virulence

Cryptococcus neoformans and Cryptococcus gattii are globally distributed human fungal pathogens and the leading causes of fungal meningitis. Recent studies reveal that myo-inositol is an important factor for fungal sexual reproduction. That C. neoformans can utilize myo-inositol as a sole carbon source and the existence of abundant inositol in the human central nervous system suggest that inositol is important for Cryptococcus development and virulence. In accord with this central importance of inositol, an expanded myo-inositol transporter (ITR) gene family has been identified in Cryptococcus. This gene family contains two phylogenetically distinct groups, with a total of 10 or more members in C. neoformans and at least six members in the sibling species C. gattii. These inositol transporter genes are differentially expressed under inositol-inducing conditions based on quantitative real-time PCR analyses. Expression of ITR genes in a Saccharomyces cerevisiae itr1 itr2 mutant lacking inositol transport can complement the slow-growth phenotype of this strain, confirming that ITR genes are bona fide inositol transporters. Gene mutagenesis studies reveal that the Itr1 and Itr1A transporters are important for myo-inositol stimulation of mating and that functional redundancies among the myo-inositol transporters likely exist. Deletion of the inositol 1-phosphate synthase gene INO1 in an itr1 or itr1a mutant background compromised virulence in a murine inhalation model, indicating the importance of inositol sensing and acquisition for fungal infectivity. Our study provides a platform for further understanding the roles of inositol in fungal physiology and virulence