Screening of cosmological constant for De Sitter Universe in non-local gravity, phantom-divide crossing and finite-time future singularities

We investigate de Sitter solutions in non-local gravity as well as in non-local gravity with Lagrange constraint multiplier. We examine a condition to avoid a ghost and discuss a screening scenario for a cosmological constant in de Sitter solutions. Furthermore, we explicitly demonstrate that three types of the finite-time future singularities can occur in non-local gravity and explore their properties. In addition, we evaluate the effective equation of state for the universe and show that the late-time accelerating universe may be effectively the quintessence, cosmological constant or phantom-like phases. In particular, it is found that there is a case in which a crossing of the phantom divide from the non-phantom (quintessence) phase to the phantom one can be realized when a finite-time future singularity occurs. Moreover, it is demonstrated that the addition of an $R^2$ term can cure the finite-time future singularities in non-local gravity. It is also suggested that in the framework of non-local gravity, adding an $R^2$ term leads to possible unification of the early-time inflation with the late-time cosmic acceleration.Comment: 42 pages, no figure, version accepted for publication in General Relativity and Gravitatio

Neutron Majorana mass from exotic instantons

We show how a Majorana mass for the Neutron could result from non-perturbative quantum gravity effects peculiar to string theory. In particular, "exotic instantons" in un-oriented string compactifications with D-branes extending the (supersymmetric) standard model could indirectly produce an effective operator delta{m} n^t n+h.c. In a specific model with an extra vector-like pair of `quarks', acquiring a large mass proportional to the string mass scale (exponentially suppressed by a function of the string moduli fields), delta{m} can turn out to be as low as 10^{-24}-10^{-25} eV. The induced neutron-antineutron oscillations could take place with a time scale tau_{n\bar{n}} > 10^8 s, that could be tested by the next generation of experiments. On the other hand, proton decay and FCNC's are automatically strongly suppressed and are compatible with the current experimental limits. Depending on the number of brane intersections, the model may also lead to the generation of Majorana masses for R-handed neutrini. Our proposal could also suggest neutron-neutralino or neutron-axino oscillations, with implications in UCN, Dark Matter Direct Detection, UHECR and Neutron-Antineutron oscillations. This suggests to improve the limits on neutron-antineutron oscillations, as a possible test of string theory and quantum gravity.Comment: 35 pages, 11 figures. More comments on neutron-neutralino mixin

Phosphatidylinositol(4,5)bisphosphate coordinates actin-mediated mobilization and translocation of secretory vesicles to the plasma membrane of chromaffin cells

ORP5 and ORP8, members of the oxysterol-binding protein (OSBP)-related proteins (ORP) family, are endoplasmic reticulum membrane proteins implicated in lipid trafficking. ORP5 and ORP8 are reported to localize to endoplasmic reticulum-plasma membrane junctions via binding to phosphatidylinositol-4-phosphate (PtdIns(4)P), and act as a PtdIns(4)P/phosphatidylserine counter exchanger between the endoplasmic reticulum and plasma membrane. Here we provide evidence that the pleckstrin homology domain of ORP5/8 via PtdIns(4,5)P 2, and not PtdIns(4)P binding mediates the recruitment of ORP5/8 to endoplasmic reticulum-plasma membrane contact sites. The OSBP-related domain of ORP8 can extract and transport multiple phosphoinositides in vitro, and knocking down both ORP5 and ORP8 in cells increases the plasma membrane level of PtdIns(4,5)P 2 with little effect on PtdIns(4)P. Overall, our data show, for the first time, that phosphoinositides other than PtdIns(4)P can also serve as co-exchangers for the transport of cargo lipids by ORPs.ORP5/8 are endoplasmic reticulum (ER) membrane proteins implicated in lipid trafficking that localize to ER-plasma membrane (PM) contacts and maintain membrane homeostasis. Here the authors show that PtdIns(4,5)P 2 plays a critical role in the targeting and function of ORP5/8 at the PM

Proteomic Modeling for HIV-1 Infected Microglia-Astrocyte Crosstalk

Background: HIV-1-infected and immune competent brain mononuclear phagocytes (MP; macrophages and microglia) secrete cellular and viral toxins that affect neuronal damage during advanced disease. In contrast, astrocytes can affect disease by modulating the nervous system’s microenvironment. Interestingly, little is known how astrocytes communicate with MP to influence disease. Methods and Findings: MP-astrocyte crosstalk was investigated by a proteomic platform analysis using vesicular stomatitis virus pseudotyped HIV infected murine microglia. The microglial-astrocyte dialogue was significant and affected microglial cytoskeleton by modulation of cell death and migratory pathways. These were mediated, in part, through F-actin polymerization and filament formation. Astrocyte secretions attenuated HIV-1 infected microglia neurotoxicity and viral growth linked to the regulation of reactive oxygen species. Conclusions: These observations provide unique insights into glial crosstalk during disease by supporting astrocytemediated regulation of microglial function and its influence on the onset and progression of neuroAIDS. The results open new insights into previously undisclosed pathogenic mechanisms and open the potential for biomarker discovery an

The Confidence Database

Understanding how people rate their confidence is critical for the characterization of a wide range of perceptual, memory, motor and cognitive processes. To enable the continued exploration of these processes, we created a large database of confidence studies spanning a broad set of paradigms, participant populations and fields of study. The data from each study are structured in a common, easy-to-use format that can be easily imported and analysed using multiple software packages. Each dataset is accompanied by an explanation regarding the nature of the collected data. At the time of publication, the Confidence Database (which is available at https://osf.io/s46pr/) contained 145 datasets with data from more than 8,700 participants and almost 4 million trials. The database will remain open for new submissions indefinitely and is expected to continue to grow. Here we show the usefulness of this large collection of datasets in four different analyses that provide precise estimations of several foundational confidence-related effects

Targeting RNS/caveolin-1/MMP signaling cascades to protect against cerebral ischemia-reperfusion injuries: potential application for drug discovery

Reactive nitrogen species (RNS) play important roles in mediating cerebral ischemia-reperfusion injury. RNS activate multiple signaling pathways and participate in different cellular events in cerebral ischemia-reperfusion injury. Recent studies have indicated that caveolin-1 and matrix metalloproteinase (MMP) are important signaling molecules in the pathological process of ischemic brain injury. During cerebral ischemia-reperfusion, the production of nitric oxide (NO) and peroxynitrite (ONOO-), two representative RNS, down-regulates the expression of caveolin-1 (Cav-1) and, in turn, further activates nitric oxide synthase (NOS) to promote RNS generation. The increased RNS further induce MMP activation and mediate disruption of the blood-brain barrier (BBB), aggravating the brain damage in cerebral ischemia-reperfusion injury. Therefore, the feedback interaction among RNS/Cav-1/MMPs provides an amplified mechanism for aggravating ischemic brain damage during cerebral ischemia-reperfusion injury. Targeting the RNS/Cav-1/MMP pathway could be a promising therapeutic strategy for protecting against cerebral ischemia-reperfusion injury. In this mini-review article, we highlight the important role of the RNS/Cav-1/MMP signaling cascades in ischemic stroke injury and review the current progress of studies seeking therapeutic compounds targeting the RNS/Cav-1/MMP signaling cascades to attenuate cerebral ischemia-reperfusion injury. Several representative natural compounds, including calycosin-7-O-β-D-glucoside, baicalin, Momordica charantia polysaccharide (MCP), chlorogenic acid, lutein and lycopene, have shown potential for targeting the RNS/Cav-1/MMP signaling pathway to protect the brain in ischemic stroke. Therefore, the RNS/Cav-1/MMP pathway is an important therapeutic target in ischemic stroke treatment.published_or_final_versio

THE FACTORS INFLUENCING RENAL RECOVERY IN CARDIAC SURGERY ASSOCIATED ACUTE KIDNEY INJURY

Background. In-hospital mortality of cardiac surgery patients with AKI is 3-7 times higher than those without AKI. This prospective observational study was dedicated to evaluate a differential approach of applying continuous and intermittent modalities in CS-AKIpatients on the rate and grade of renalfunction recovery. Methods. One hundred and six adult cardiac surgery patients admitted hospital in 2008-2011 years, who had AKI and met inclusion criteria were allocated in CRRTorIRRTgroup. Results. Sixty eight cardiac surgery with AKI patients who needed RRT were discharged from hospital. Among them, recovery of renalfunction was observed in 54 patients (79,4%) and 14 patients (20,6%) remained RRT-depen- dant. Complete recovery of renalfunction was reached in 33 patients (48,5%), while partial was observed in 21 patients (30,9%). Univariate analysis showed that complete recovery of renalfunction in CS-AKI significantly associated with reducing of dopamine dose during thefirst day of RRT (p=0,01) and long-term use of dobutamine (p=0,009). Partial recovery was associated with early dobutamine withdrawal (p=0,005) and absence of MOT (p=0,016), while RRT- dependence at discharge was associated with absence of MOT (p=0,006) and escalation of dopamine dose on thefirst day of RRT (p=0,025). The rate of renal recovery was statistically significantly higher in patients with CS-AKI with MOFthan inpatients with CS-AKI without MOF. In univariate analysis RRT-dependance at discharge of patients with CS-AKI with MOF was statistically significantly associated with arising of dopamine dose during thefirst day of RRT (p=0,006) and no-use of dobutamine at RRT start (p=0,006). Partial recovery was associated with early withdrawal of dobutamine (p=0,038). Discussion. Frequency of renal recovery inpresented study was higher than in VA/NIHAcute Renal Failure Trial Network study because of differences inpatients'population and corresponds to otherstudies of CS-AKIpatients. Conclusions. Recovery of renalfunction in CS-AKI patients associated with decreasing dose of dopamine, prolonged use ofdobutamine, illness severity and does not associated with specific RRT modality