Self-assembled guanine ribbons as wide-bandgap semiconductors

We present a first principle study about the stability and the electronic properties of a new biomolecular solid-state material, obtained by the self-assembling of guanine (G) molecules. We consider hydrogen-bonded planar ribbons in isolated and stacked configurations. These aggregates present electronic properties similar to inorganic wide-bandgap semiconductors. The formation of Bloch-type orbitals is observed along the stacking direction, while it is negligible in the ribbon plane. Global band-like conduction may be affected by a dipole-field which spontaneously arises along the ribbon axis. Our results indicate that G-ribbon assemblies are promising materials for biomolecular nanodevices, consistently with recent experimental results.Comment: 7 pages, 3 figures, to be published in Physica

Inhibition of \u3cem\u3eCandida albicans\u3c/em\u3e and Mixed Salivary Bacterial Biofilms on Antimicrobial Loaded Phosphated Poly(methyl methacrylate)

Biofilms play a crucial role in the development of Candida-associated denture stomatitis. Inhibition of microbial adhesion to poly(methyl methacrylate) (PMMA) and phosphate containing PMMA has been examined in this work. C. albicans and mixed salivary microbial biofilms were compared on naked and salivary pre-conditioned PMMA surfaces in the presence or absence of antimicrobials (Cetylpyridinium chloride [CPC], KSL-W, Histatin 5 [His 5]). Polymers with varying amounts of phosphate (0–25%) were tested using four C. albicans oral isolates as well as mixed salivary bacteria and 24 h biofilms were assessed for metabolic activity and confirmed using Live/Dead staining and confocal microscopy. Biofilm metabolism was reduced as phosphate density increased (15%: p = 0.004; 25%: p = 0.001). Loading of CPC on 15% phosphated disks showed a substantial decrease (p = 0.001) in biofilm metabolism in the presence or absence of a salivary pellicle. Salivary pellicle on uncharged PMMA enhanced the antimicrobial activity of CPC only. CPC also demonstrated remarkable antimicrobial activity on mixed salivary bacterial biofilms under different conditions displaying the potent efficacy of CPC (350 µg/mL) when combined with an artificial protein pellicle (Biotene half strength)

Urinary ATP and visualization of intracellular bacteria: a superior diagnostic marker for recurrent UTI in renal transplant recipients?

Renal transplant recipients (RTR) are highly susceptible to urinary tract infections (UTIs) with over 50% of patients having at least one UTI within the first year. Yet it is generally acknowledged that there is considerable insensitivity and inaccuracy in routine urinalysis when screening for UTIs. Thus a large number of transplant patients with genuine urine infections may go undiagnosed and develop chronic recalcitrant infections, which can be associated with graft loss and morbidity. Given a recent study demonstrating ATP is released by urothelial cells in response to bacteria exposure, possibly acting at metabotropic P2Y receptors mediating a proinflammatory response, we have investigated alternative, and possibly more appropriate, urinalysis techniques in a cohort of RTRs.Mid-stream urine (MSU) samples were collected from 53 outpatient RTRs. Conventional leukocyte esterase and nitrite dipstick tests, and microscopic pyuria counts (in 1 ?l), ATP concentration measurements, and identification of intracellular bacteria in shed urothelial cells, were performed on fresh unspun samples and compared to ‘gold-standard’ bacterial culture results.Of the 53 RTRs, 22% were deemed to have a UTI by ‘gold-standard’ conventional bacteria culture, whereas 87%, 8% and 4% showed evidence of UTIs according to leukocyte esterase dipstick, nitrite dipstick, and a combination of both dipsticks, respectively. Intracellular bacteria were visualized in shed urothelial cells of 44% of RTRs, however only 1 of the 23 RTRs (44%) was deemed to have a UTI by conventional bacteria culture. A significant association of the ‘gold-standard’ test with urinary ATP concentration combined with visualization of intracellular bacteria in shed urothelial cells was determined using the Fisher’s exact test.It is apparent that standard bedside tests for UTIs give variable results and that seemingly quiescent bacteria in urothelial cells are very common in RTRs and may represent a focus of subclinical infection. Furthermore, our results suggest urinary ATP concentration combined with detection of intracellular bacteria in shed urinary epithelial cells may be a sensitive means by which to detect ‘occult’ infection in RTRs

APE1, the DNA base excision repair protein, regulates the removal of platinum adducts in sensory neuronal cultures by NER

Peripheral neuropathy is one of the major side effects of treatment with the anticancer drug, cisplatin. One proposed mechanism for this neurotoxicity is the formation of platinum adducts in sensory neurons that could contribute to DNA damage. Although this damage is largely repaired by nuclear excision repair (NER), our previous findings suggest that augmenting the base excision repair pathway (BER) by overexpressing the repair protein APE1 protects sensory neurons from cisplatin-induced neurotoxicity. The question remains whether APE1 contributes to the ability of the NER pathway to repair platinum-damage in neuronal cells. To examine this, we manipulated APE1 expression in sensory neuronal cultures and measured Pt-removal after exposure to cisplatin. When neuronal cultures were treated with increasing concentrations of cisplatin for two or three hours, there was a concentration-dependent increase in Pt-damage that peaked at four hours and returned to near baseline levels after 24h. In cultures where APE1 expression was reduced by ∼ 80% using siRNA directed at APE1, there was a significant inhibition of Pt-removal over eight hours which was reversed by overexpressing APE1 using a lentiviral construct for human wtAPE1. Overexpressing a mutant APE1 (C65 APE1), which only has DNA repair activity, but not its other significant redox-signaling function, mimicked the effects of wtAPE1. Overexpressing DNA repair activity mutant APE1 (226 + 177APE1), with only redox activity was ineffective suggesting it is the DNA repair function of APE1 and not its redox-signaling, that restores the Pt-damage removal. Together, these data provide the first evidence that a critical BER enzyme, APE1, helps regulate the NER pathway in the repair of cisplatin damage in sensory neurons

Analysis of the Local and Systemic Cytokine Response Profiles in Patients with Community-Acquired Pneumonia. Relationship with Disease Severity and Outcomes.

The goals of this study were to investigate the relationship of systemic and local cytokine responses with time to clinical stability (TCS) in patients with community-acquired pneumonia (CAP) and to develop a model to integrate multiple cytokine data into “cytokine response profiles” based on local vs. systemic and pro- vs. anti-inflammatory cytokine patterns in order to better understand their relationships with measures of CAP severity and outcomes. Forty hospitalized patients enrolled through the Community Acquired Pneumonia Inflammatory Study Group (CAPISG) were analyzed. Based on the ranked distribution of the levels of eight different pro-inflammatory cytokines and chemokines (IL-1b, IL-6, IL-8, IL-12p40, IL-17A, IFNg, TNFa and CXCL10) in plasma and sputum on hospital admission, a “pro-inflammatory cytokine score (PICS)” was defined. PICS in plasma and sputum were plotted against each other and quadrants used to define profiles based on the four possible high/low combinations. A similar approach was used to contrast sputum PICS vs. anti-inflammatory cytokines (IL-1ra and IL-10). Some of the “profiles” thus defined were found to group patients with common etiologic characteristics and/or associate with similar measures of disease severity and/or clinical outcomes, suggesting the predictive value of the use of cytokine data in CAP patients

Predictions in SU(5) Supergravity Grand Unification with Proton Stability and Relic Density Constraints

It is shown that in the physically interesting domain of the parameter space of SU(5) supergravity GUT, the Higgs and the Z poles dominate the LSP annihilation. Here the naive analyses on thermal averaging breaks down and formulae are derived which give a rigorous treatment over the poles. These results are then used to show that there exist significant domains in the parameter space where the constraints of proton stability and cosmology are simultaneously satisfied. New upper limits on light particle masses are obtained.Comment: (An error in the reheating factor is corrected, strengthening the conclusions, i.e. the region in parameter space where the relic density constraints are satisfied is enlarged.

IL‐1β prevents ILC2 expansion, type 2 cytokine secretion, and mucus metaplasia in response to early‐life rhinovirus infection in mice

BackgroundEarly‐life wheezing‐associated respiratory infection with human rhinovirus (RV) is associated with asthma development. RV infection of 6‐day‐old immature mice causes mucous metaplasia and airway hyperresponsiveness which is associated with the expansion of IL‐13‐producing type 2 innate lymphoid cells (ILC2s) and dependent on IL‐25 and IL‐33. We examined regulation of this asthma‐like phenotype by IL‐1β.MethodsSix‐day‐old wild‐type or NRLP3−/− mice were inoculated with sham or RV‐A1B. Selected mice were treated with IL‐1 receptor antagonist (IL‐1RA), anti‐IL‐1β, or recombinant IL‐1β.ResultsRhinovirus infection induced Il25, Il33, Il4, Il5, Il13, muc5ac, and gob5 mRNA expression, ILC2 expansion, mucus metaplasia, and airway hyperresponsiveness. RV also induced lung mRNA and protein expression of pro‐IL‐1β and NLRP3 as well as cleavage of caspase‐1 and pro‐IL‐1β, indicating inflammasome priming and activation. Lung macrophages were a major source of IL‐1β. Inhibition of IL‐1β signaling with IL‐1RA, anti‐IL‐1β, or NLRP3 KO increased RV‐induced type 2 cytokine immune responses, ILC2 number, and mucus metaplasia, while decreasing IL‐17 mRNA expression. Treatment with IL‐1β had the opposite effect, decreasing IL‐25, IL‐33, and mucous metaplasia while increasing IL‐17 expression. IL‐1β and IL‐17 each suppressed Il25, Il33, and muc5ac mRNA expression in cultured airway epithelial cells. Finally, RV‐infected 6‐day‐old mice showed reduced IL‐1β mRNA and protein expression compared to mature mice.ConclusionMacrophage IL‐1β limits type 2 inflammation and mucous metaplasia following RV infection by suppressing epithelial cell innate cytokine expression. Reduced IL‐1β production in immature animals provides a mechanism permitting asthma development after early‐life viral infection.Early‐life rhinovirus infection increases epithelial expression of the innate cytokines IL‐25 and IL‐33, expands (type 2 innate lymphoid cells) ILC2s, and enhances development of an asthma‐like phenotype. Rhinovirus causes macrophage (NLR family, pyrin domain containing 3) NLRP3 inflammasome activation and bioactive IL‐1β production. IL‐1β production, which is deficient in immature mice, attenuates production of IL‐25 and IL‐33, thereby protecting against rhinovirus‐induced asthma development.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156197/3/all14241_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156197/2/all14241.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156197/1/all14241-sup-0001-FigS1.pd

Lepton-flavor violating decays as probes of quantum gravity?

Lepton flavor violating decays $Z \to \mu \tau$ and $J/\Psi, \Upsilon \to \mu \tau$ are considered. It is shown that these decays can reach sizeable magnitudes if some specific lepton-flavor violating 4-fermion operators are generated by low scale quantum gravity effects, or by some other new physics at a TeV scale.Comment: 18 pages, 1 figures, LaTeX, uses FEYNMAN package. New references adde