5,772 research outputs found
Combined SIRT3 and SIRT5 deletion is associated with inner retinal dysfunction in a mouse model of type 1 diabetes
Abstract Diabetic retinopathy (DR) is a major cause of blindness in working adults in the industrialized world. In addition to vision loss caused by macular edema and pathological angiogenesis, DR patients often exhibit neuronal dysfunction on electrophysiological testing, suggesting that there may be an independent neuronal phase of disease that precedes vascular disease. Given the tremendous metabolic requirements of the retina and photoreceptors in particular, we hypothesized that derangements in metabolic regulation may accelerate retinal dysfunction in diabetes. As such, we induced hyperglycemia with streptozotocin in mice with monoallelic Nampt deletion from rod photoreceptors, mice lacking SIRT3, and mice lacking SIRT5 and tested multiple components of retinal function with electroretinography. None of these mice exhibited accelerated retinal dysfunction after induction of hyperglycemia, consistent with normal-appearing retinal morphology in hyperglycemic Sirt3 −/− or Sirt5 −/− mice. However, mice lacking both SIRT3 and SIRT5 (Sirt3 −/− Sirt5 −/− mice) exhibited significant evidence of inner retinal dysfunction after induction of hyperglycemia compared to hyperglycemic littermate controls, although this dysfunction was not accompanied by gross morphological changes in the retina. These results suggest that SIRT3 and SIRT5 may be involved in regulating neuronal dysfunction in DR and provide a foundation for future studies investigating sirtuin-based therapies
Epidemiology and Immune Pathogenesis of Viral Sepsis
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis can be caused by a broad range of pathogens; however, bacterial infections represent the majority of sepsis cases. Up to 42% of sepsis presentations are culture negative, suggesting a non-bacterial cause. Despite this, diagnosis of viral sepsis remains very rare. Almost any virus can cause sepsis in vulnerable patients (e.g., neonates, infants, and other immunosuppressed groups). The prevalence of viral sepsis is not known, nor is there enough information to make an accurate estimate. The initial standard of care for all cases of sepsis, even those that are subsequently proven to be culture negative, is the immediate use of broad-spectrum antibiotics. In the absence of definite diagnostic criteria for viral sepsis, or at least to exclude bacterial sepsis, this inevitably leads to unnecessary antimicrobial use, with associated consequences for antimicrobial resistance, effects on the host microbiome and excess healthcare costs. It is important to understand non-bacterial causes of sepsis so that inappropriate treatment can be minimised, and appropriate treatments can be developed to improve outcomes. In this review, we summarise what is known about viral sepsis, its most common causes, and how the immune responses to severe viral infections can contribute to sepsis. We also discuss strategies to improve our understanding of viral sepsis, and ways we can integrate this new information into effective treatment
Genome wide association mapping in <i>Arabidopsis thaliana</i> identifies novel genes involved in linking allyl glucosinolate to altered biomass and defense
A key limitation in modern biology is the ability to rapidly identify genes underlying newly identified complex phenotypes. Genome wide association studies (GWAS) have become an increasingly important approach for dissecting natural variation by associating phenotypes with genotypes at a genome wide level. Recent work is showing that the Arabidopsis thaliana defense metabolite, allyl glucosinolate (GSL), may provide direct feedback regulation, linking defense metabolism outputs to the growth, and defense responses of the plant. However, there is still a need to identify genes that underlie this process. To start developing a deeper understanding of the mechanism(s) that modulate the ability of exogenous allyl GSL to alter growth and defense, we measured changes in plant biomass and defense metabolites in a collection of natural 96 A. thaliana accessions fed with 50 μM of allyl GSL. Exogenous allyl GSL was introduced exclusively to the roots and the compound transported to the leaf leading to a wide range of heritable effects upon plant biomass and endogenous GSL accumulation. Using natural variation we conducted GWAS to identify a number of new genes which potentially control allyl responses in various plant processes. This is one of the first instances in which this approach has been successfully utilized to begin dissecting a novel phenotype to the underlying molecular/polygenic basis
Implications of SU(2) symmetry on the dynamics of population difference in the two-component atomic vapor
We present an exact many body solution for the dynamics of the population
difference induced by an rf-field in the two-component atomic cloud
characterized by equal scattering lengths. This situation is very close to the
actual JILA experiments with the two-component Rb vapor. We show that no
intrinsic decoherence exists for , provided the exact SU(2) symmetry
holds. This contrasts with finite dissipation of the normal modes even in the
presence of the SU(2) symmetry. The intrinsic decoherence for \ may
occur as long as deviations from the exact SU(2) symmetry are taken into
account. Such decoherence, however, should be characterized by very long times
governed by the smallness of the deviations from the symmetry. We suggest
testing the evolution of by conducting echo-type experiments.Comment: 5 RevTex pages, no figures, typos correcte
Aligned electrospun nanofibers specify the direction of dorsal root ganglia neurite growth
Nerve injury, a significant cause of disability, may be treated more effectively using nerve guidance channels containing longitudinally aligned fibers. Aligned, electrospun nanofibers direct the neurite growth of immortalized neural stem cells, demonstrating potential for directing regenerating neurites. However, no study of neurite guidance on these fibers has yet been performed with primary neurons. Here, we examined neurites from dorsal root ganglia explants on electrospun poly- L -lactate nanofibers of high, intermediate, and random alignment. On aligned fibers, neurites grew radially outward from the ganglia and turned to follow the fibers upon contact. Neurite guidance was robust, with neurites never leaving the fibers to grow on the surrounding cover slip. To compare the alignment of neurites to that of the nanofiber substrates, Fourier methods were used to quantify the alignment. Neurite alignment, however striking, was inferior to fiber alignment on all but the randomly aligned fibers. Neurites on highly aligned substrates were 20 and 16% longer than neurites on random and intermediate fibers, respectively. Schwann cells on fibers assumed a very narrow morphology compared to those on the surrounding coverslip. The robust neurite guidance demonstrated here is a significant step toward the use of aligned, electrospun nanofibers for nerve regeneration. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/57401/1/31285_ftp.pd
Noncontact Diffuse Optical Assessment of Blood Flow Changes in Head and Neck Free Tissue Transfer Flaps
Knowledge of tissue blood flow (BF) changes after free tissue transfer may enable surgeons to predict the failure of flap thrombosis at an early stage. This study used our recently developed noncontact diffuse correlation spectroscopy to monitor dynamic BF changes in free flaps without getting in contact with the targeted tissue. Eight free flaps were elevated in patients with head and neck cancer; one of the flaps failed. Multiple BF measurements probing the transferred tissue were performed during and post the surgical operation. Postoperative BF values were normalized to the intraoperative baselines (assigning “1”) for the calculation of relative BF change (rBF). The rBF changes over the seven successful flaps were 1.89±0.15, 2.26±0.13, and 2.43±0.13 (mean±standard error), respectively, on postoperative days 2, 4, and 7. These postoperative values were significantly higher than the intraoperative baseline values (
Loss of stearoyl-CoA desaturase 2 disrupts inflammatory response in macrophages
Macrophages are innate immune cells that patrol tissues and are the first responders to detect infection. They orchestrate the host immune response in eliminating invading pathogens and the subsequent transition from inflammation to tissue repair. Macrophage dysfunction contributes to age-related pathologies, including low-grade inflammation in advanced age that is termed inflammaging. Our laboratory has previously identified that macrophage expression of a fatty acid desaturase, stearoyl-CoA desaturase 2 (SCD2), declines with age. Herein, we delineate the precise cellular effects of SCD2 deficiency in murine macrophages. We found that deletion o
Migration of dissolved organic carbon in biochars and biochar-mineral complexes
The objective of this work was to determine the contribution of dissolved organic carbon (DOC) from a biochar mineral complex (BMC), so as to better understand the interactions between DOC, biochar, clay, and minerals during thermal treatment, and the effects of BMC on amended soils. The BMC was prepared by heating a mixture of a H3PO4-treated saligna biochar from Acacia saligna, clays, other minerals, and chicken manure. The BMC was applied to a sandy loam soil in Western Australia, where wheat was grown. Liquid chromatography-organic carbon detection (LC-OCD) tests were carried out on water extracts from the untreated biochar, the BMC, the BMC-amended soil, and on a control soil to measure the DOC concentration. LC-OCD tests provide a fingerprint of the DOC, which allows the fractions of DOC to be determined. Thermal processing enhanced the reaction of the A. saligna biochar with manure, clays and minerals, and affected the distribution of the DOC fractions. Notably, the process leads to immobilization of hydrophobic DOC and to an increase in the concentration of low-molecular-weight neutrals in the BMC. The application of the BMC to soil increases the DOC in the amended soil, especially the biopolymer fraction
- …