Pseudogap temperature as a Widom line in doped Mott insulators

The pseudogap refers to an enigmatic state of matter with unusual physical properties found below a characteristic temperature $T^*$ in hole-doped high-temperature superconductors. Determining $T^*$ is critical for understanding this state. Here we study the simplest model of correlated electron systems, the Hubbard model, with cluster dynamical mean-field theory to find out whether the pseudogap can occur solely because of strong coupling physics and short nonlocal correlations. We find that the pseudogap characteristic temperature $T^*$ is a sharp crossover between different dynamical regimes along a line of thermodynamic anomalies that appears above a first-order phase transition, the Widom line. The Widom line emanating from the critical endpoint of a first-order transition is thus the organizing principle for the pseudogap phase diagram of the cuprates. No additional broken symmetry is necessary to explain the phenomenon. Broken symmetry states appear in the pseudogap and not the other way around.Comment: 6 pages, 4 figures and supplementary information; published versio

Inhibition of I kappa B Kinase Attenuates the Organ Injury and Dysfunction Associated with Hemorrhagic Shock

R Sordi is supported by the program Science without Borders, CAPES Foundation, Ministry of Education of Brazil, Brasilia/DF, Brazil; NSA Patel is, in part, supported by the Bart’s and The LondonCharity (753/1722). The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union′s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement n° 608765, from the William Harvey Research Foundation and University of Turin (Ricerca Locale ex-60%). This work contributes to the Organ Protection research theme of the Barts Centre for Trauma Sciences, supported by the Barts and The London Charity (Award 753/1722) and forms part of the research themes contributing to the translational research portfolio of Barts and the London Cardiovascular Biomedical Research Unit, which is supported and funded by the National Institute of Health Researc

The quorum-sensing molecules farnesol/homoserine lactone and dodecanol operate via distinct modes of action in Candida albicans

Living as a commensal, Candida albicans must adapt and respond to environmental cues generated by the mammalian host and by microbes comprising the natural flora. These signals have opposing effects on C. albicans, with host cues promoting the yeast-to-hyphal transition and bacteria-derived quorum-sensing molecules inhibiting hyphal development. Hyphal development is regulated through modulation of the cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway, and it has been postulated that quorum-sensing molecules can affect filamentation by inhibiting the cAMP pathway. Here, we show that both farnesol and 3-oxo-C12-homoserine lactone, a quorum-sensing molecule secreted by Pseudomonas aeruginosa, block hyphal development by affecting cAMP signaling; they both directly inhibited the activity of the Candida adenylyl cyclase, Cyr1p. In contrast, the 12-carbon alcohol dodecanol appeared to modulate hyphal development and the cAMP signaling pathway without directly affecting the activity of Cyr1p. Instead, we show that dodecanol exerted its effects through a mechanism involving the C. albicans hyphal repressor, Sfl1p. Deletion of SFL1 did not affect the response to farnesol but did interfere with the response to dodecanol. Therefore, quorum sensing in C. albicans is mediated via multiple mechanisms of action. Interestingly, our experiments raise the possibility that the Burkholderia cenocepacia diffusible signal factor, BDSF, also mediates its effects via Sfl1p, suggesting that dodecanol's mode of action, but not farnesol or 3-oxo-C12-homoserine lactone, may be used by other quorum-sensing molecules

Desempenho de frangos de corte (22 a 42 dias) alimentados com dietas peletizadas contendo glicerina bruta.

A maior parte das rações produzidas para frangos de corte no Brasil são peletizadas. Como benefício deste processamento observa-se melhora na digestibilidade dos nutrientes, redução de contaminações por patógenos, bem como melhorias nas condições de transporte. Existem muitos aditivos umectantes que podem ser utilizados para melhorar o processo de peletização, contudo a glicerina além de ser um umectante eficiente (1) é um alimento energético que tem grande potencial de produção no país. Assim sendo, objetivou-se avaliar o desempenho de frangos de corte na fase final (22 a 42 dias) alimentados com rações peletizadas ou fareladas com a inclusão de níveis crescentes de glicerina bruta

Multivariate analysis of the influence of peri-implant clinical parameters and local factors on radiographic bone loss in the posterior maxilla: a retrospective study on 277 dental implants

Objectives: The aim of the present study was to investigate whether peri-implant clinical parameters (modified plaque index (mPI), bleeding and/or suppuration on probing (B/SOP)) and local factors (type of prostheses, screw emergence, platform diameter, and abutment angulation) might contribute to the development of additional bone loss and peri-implantitis around dental implants. Materials and methods: Two hundred seventy-seven external hex connection implants placed in the posterior maxilla of 124 patients were retrospectively evaluated. They were divided into two groups: physiologic bone loss < 2 mm (PBL) or additional bone loss ≥ 2 mm (ABL). GEE logistic regression was applied to evaluate the influence of type of prostheses (implant-supported single crown (ISSC), fixed partial denture (ISFPD), and full denture (ISFD)) and clinical parameters (mPI and S/BOP) on bone loss. Results: Among the 277 implants, 159 (57.4%) presented PBL and 118 (42.6%) presented ABL. Within the ABL group, 20.6% implants were diagnosed with peri-implantitis. mPI significantly correlated with the type of prosthesis and the highest value of mPI (index = 3) was observed in ISFD (23.8%). Moreover, peri-implantitis was more frequently associated with ISFD (32.79%) than ISSC and ISFDP (13.79% and 13.48, respectively) Conclusions: ISFD in the posterior maxilla presented high rates of ABL and showed a higher prevalence of peri-implantitis. None of the local factors seemed to contribute to the development of these conditions. Further investigations are needed to prospectively support the results of the present study. Clinical relevance: Patients rehabilitated with ISFD should be carefully monitored and have more frequent maintenance visits to prevent or control peri-implant bone loss

Pharmacological Inhibition of FAK-Pyk2 Pathway Protects Against Organ Damage and Prolongs the Survival of Septic Mice

Sepsis and septic shock are associated with high mortality and are considered one of the major public health concerns. The onset of sepsis is known as a hyper-inflammatory state that contributes to organ failure and mortality. Recent findings suggest a potential role of two non-receptor protein tyrosine kinases, namely Focal adhesion kinase (FAK) and Proline-rich tyrosine kinase 2 (Pyk2), in the inflammation associated with endometriosis, cancer, atherosclerosis and asthma. Here we investigate the role of FAK-Pyk2 in the pathogenesis of sepsis and the potential beneficial effects of the pharmacological modulation of this pathway by administering the potent reversible dual inhibitor of FAK and Pyk2, PF562271 (PF271) in a murine model of cecal ligation and puncture (CLP)-induced sepsis. Five-month-old male C57BL/6 mice underwent CLP or Sham surgery and one hour after the surgical procedure, mice were randomly assigned to receive PF271 (25 mg/kg, s.c.) or vehicle. Twenty-four hours after surgery, organs and plasma were collected for analyses. In another group of mice, survival rate was assessed every 12 h over the subsequent 5 days. Experimental sepsis led to a systemic cytokine storm resulting in the formation of excessive amounts of both pro-inflammatory cytokines (TNF-α, IL-1β, IL-17 and IL-6) and the anti-inflammatory cytokine IL-10. The systemic inflammatory response was accompanied by high plasma levels of ALT, AST (liver injury), creatinine, (renal dysfunction) and lactate, as well as a high, clinical severity score. All parameters were attenuated following PF271 administration. Experimental sepsis induced an overactivation of FAK and Pyk2 in liver and kidney, which was associated to p38 MAPK activation, leading to increased expression/activation of several pro-inflammatory markers, including the NLRP3 inflammasome complex, the adhesion molecules ICAM-1, VCAM-1 and E-selectin and the enzyme NOS-2 and myeloperoxidase. Treatment with PF271 inhibited FAK-Pyk2 activation, thus blunting the inflammatory abnormalities orchestrated by sepsis. Finally, PF271 significantly prolonged the survival of mice subjected to CLP-sepsis. Taken together, our data show for the first time that the FAK-Pyk2 pathway contributes to sepsis-induced inflammation and organ injury/dysfunction and that the pharmacological modulation of this pathway may represents a new strategy for the treatment of sepsis