Carbon storage and DNA absorption in allophanic soils and paleosols

Andisols and andic paleosols dominated by the nanocrystalline mineral allophane sequester large amounts of carbon (C), attributable mainly to its chemical bonding with charged hydroxyl groups on the surface of allophane together with its physical protection in nanopores within and between allophane nanoaggregates. C near-edge X-ray absorption fine structure (NEXAFS) spectra for a New Zealand Andisol (Tirau series) showed that the organic matter (OM) mainly comprises quinonic, aromatic, aliphatic, and carboxylic C. In different buried horizons from several other Andisols, C contents varied but the C species were similar, attributable to pedogenic processes operating during developmental upbuilding, downward leaching, or both. The presence of OM in natural allophanic soils weakened the adsorption of DNA on clay; an adsorption isotherm experiment involving humic acid (HA) showed that HA-free synthetic allophane adsorbed seven times more DNA than HA-rich synthetic allophane. Phosphorus X-ray absorption near-edge structure (XANES) spectra for salmonsperm DNA and DNA-clay complexes indicated that DNA was bound to the allophane clay through the phosphate group, but it is not clear if DNA was chemically bound to the surface of the allophane or to OM, or both. We plan more experiments to investigate interactions among DNA, allophane (natural and synthetic), and OM. Because DNA shows a high affinity to allophane, we are studying the potential to reconstruct late Quaternary palaeoenvironments by attempting to extract and characterise ancient DNA from allophanic paleosol

Kinase inhibit region of SOCS3 attenuates IL6-induced proliferation and astrocytic differentiation of neural stem cells via cross talk between signaling pathways

Aims: Efficiency of neural stem cells (NSCs) therapy for brain injury is restricted by astrogliosis around the damaged region, in which JAK2/STAT3 signaling plays a key role. The SOCS3 that can directly inhibit JAK/STAT3 pathway. Here, we investigated the effects of a fusion peptide that combined kinase inhibitory region (KIR) of SOCS3 and virus trans-activator of transcription (TAT) on biological behavior of cultured NSCs under inflammatory conditions. Methods: NSCs were isolated from embryonic brain of SD rats, TAT-KIR was synthesized, and penetration rate was evaluated by flow cytometry (FACS). CCK8, immunostaining, and FACS were used to detected of TAT-KIR on the proliferation of NSCs. The expressions of GFAP and β tubulin III positive cells induced by IL6 with/without TAT-KIR were examined by immunostaining and Western blotting to observe the NSCs differentiation, and the effect of TAT-KIR on signaling cross talk was observed by Western blotting. Results: Penetration rate of TAT-KIR into primary cultured NSCs was up to 94%. TAT-KIR did not affect the growth and viability of NSCs. It significantly reduced the NSCs proliferation that enhanced by IL-6 stimulation via blocking the cell cycle progression from the G0/G1 to S phase. In addition, TAT-KIR attenuated astrocytic differentiation and kept high level of neuronal differentiation derived from IL-6-induced NSCs. The fate of NSCs differentiation under inflammatory conditions was affected by TAT-KIR, which was associated with synchronous inhibition of STAT3 and AKT, while promoting JNK expression. Conclusion: TAT-KIR mimetic of SOCS3 could be a promising approach for brain repair via regulating the biological behaviors of exogenous NSCs

The Weak Gravity Conjecture and the Viscosity Bound with Six-Derivative Corrections

The weak gravity conjecture and the shear viscosity to entropy density bound place constraints on low energy effective field theories that may help to distinguish which theories can be UV completed. Recently, there have been suggestions of a possible correlation between the two constraints. In some interesting cases, the behavior was precisely such that the conjectures were mutually exclusive. Motivated by these works, we study the mass to charge and shear viscosity to entropy density ratios for charged AdS5 black branes, which are holographically dual to four-dimensional CFTs at finite temperature. We study a family of four-derivative and six-derivative perturbative corrections to these backgrounds. We identify the region in parameter space where the two constraints are satisfied and in particular find that the inclusion of the next-to-leading perturbative correction introduces wider possibilities for the satisfaction of both constraints.Comment: 24 pages, 6 figures, v2: published version, refs added, minor clarificatio

Pathological behaviour of the scalar graviton in Ho\v{r}ava-Lifshitz gravity

We confirm the recent claims that, in the infrared limit of Ho\v{r}ava-Lifshitz gravity, the scalar graviton becomes a ghost if the sound speed squared is positive on the flat de Sitter and Minkowski background. In order to avoid the ghost and tame the instability, the sound speed squared should be negative and very small, which means that the flow parameter $\lambda$ should be very close to its General Relativity (GR) value. We calculate the cubic interactions for the scalar graviton which are shown to have a similar structure with those of the curvature perturbation in k-inflation models. The higher order interactions become increasing important for a smaller sound speed squared, that is, when the theory approaches GR. This invalidates any linearized analysis and any predictability is lost in this limit as quantum corrections are not controllable. This pathological behaviour of the scalar graviton casts doubt on the validity of the projectable version of the theory.Comment: 7 pages, references added; v3: Typos corrected, minor changes to text and precise determination of the strong coupling scale. Replaced to match published version

Provably scale-covariant networks from oriented quasi quadrature measures in cascade

This article presents a continuous model for hierarchical networks based on a combination of mathematically derived models of receptive fields and biologically inspired computations. Based on a functional model of complex cells in terms of an oriented quasi quadrature combination of first- and second-order directional Gaussian derivatives, we couple such primitive computations in cascade over combinatorial expansions over image orientations. Scale-space properties of the computational primitives are analysed and it is shown that the resulting representation allows for provable scale and rotation covariance. A prototype application to texture analysis is developed and it is demonstrated that a simplified mean-reduced representation of the resulting QuasiQuadNet leads to promising experimental results on three texture datasets.Comment: 12 pages, 3 figures, 1 tabl

No Interaction of Barrier-to-Autointegration Factor (BAF) with HIV-1 MA, Cone-Rod Homeobox (Crx) or MAN1-C in Absence of DNA

Barrier-to-autointegration factor is a cellular protein that protects retroviral DNA from autointegration. Its cellular role is not well understood, but genetic studies show that it is essential and depletion or knockout results in lethal nuclear defects. In addition to binding DNA, BAF interacts with the LEM domain, a domain shared among a family of lamin-associated polypeptides. BAF has also been reported to interact with several other viral and cellular proteins suggesting that these interactions may be functionally relevant. We find that, contrary to previous reports, BAF does not interact with HIV-1 MA, cone-rod homeobox (Crx) or MAN1-C. The reported interactions can be explained by indirect association through DNA binding and are unlikely to be biologically relevant. A mutation that causes a premature aging syndrome lies on the previously reported MAN1-C binding surface of BAF. The absence of direct binding of BAF to MAN1-C eliminates disruption of this interaction as the cause of the premature aging phenotype

A p53-independent role for the MDM2 antagonist Nutlin-3 in DNA damage response initiation.

BACKGROUND: The mammalian DNA-damage response (DDR) has evolved to protect genome stability and maximize cell survival following DNA-damage. One of the key regulators of the DDR is p53, itself tightly regulated by MDM2. Following double-strand DNA breaks (DSBs), mediators including ATM are recruited to the site of DNA-damage. Subsequent phosphorylation of p53 by ATM and ATM-induced CHK2 results in p53 stabilization, ultimately intensifying transcription of p53-responsive genes involved in DNA repair, cell-cycle checkpoint control and apoptosis. METHODS: In the current study, we investigated the stabilization and activation of p53 and associated DDR proteins in response to treatment of human colorectal cancer cells (HCT116p53+/+) with the MDM2 antagonist, Nutlin-3. RESULTS: Using immunoblotting, Nutlin-3 was observed to stabilize p53, and activate p53 target proteins. Unexpectedly, Nutlin-3 also mediated phosphorylation of p53 at key DNA-damage-specific serine residues (Ser15, 20 and 37). Furthermore, Nutlin-3 induced activation of CHK2 and ATM - proteins required for DNA-damage-dependent phosphorylation and activation of p53, and the phosphorylation of BRCA1 and H2AX - proteins known to be activated specifically in response to DNA damage. Indeed, using immunofluorescent labeling, Nutlin-3 was seen to induce formation of γH2AX foci, an early hallmark of the DDR. Moreover, Nutlin-3 induced phosphorylation of key DDR proteins, initiated cell cycle arrest and led to formation of γH2AX foci in cells lacking p53, whilst γH2AX foci were also noted in MDM2-deficient cells. CONCLUSION: To our knowledge, this is the first solid evidence showing a secondary role for Nutlin-3 as a DDR triggering agent, independent of p53 status, and unrelated to its role as an MDM2 antagonist

Cosmogenic neutron production at the Sudbury Neutrino Observatory

Neutrons produced in nuclear interactions initiated by cosmic-ray muons present an irreducible background to many rare-event searches, even in detectors located deep underground. Models for the production of these neutrons have been tested against previous experimental data, but the extrapolation to deeper sites is not well understood. Here we report results from an analysis of cosmogenically produced neutrons at the Sudbury Neutrino Observatory. A specific set of observables are presented, which can be used to benchmark the validity of geant4 physics models. In addition, the cosmogenic neutron yield, in units of 10-4 cm2/(g·μ), is measured to be 7.28±0.09(stat)-1.12+1.59(syst) in pure heavy water and 7.30±0.07(stat)-1.02+1.40(syst) in NaCl-loaded heavy water. These results provide unique insights into this potential background source for experiments at SNOLAB

Daratumumab plus bortezomib, cyclophosphamide, and dexamethasone in Asian patients with newly diagnosed AL amyloidosis: subgroup analysis of ANDROMEDA

Subcutaneous daratumumab plus bortezomib/cyclophosphamide/dexamethasone (VCd; D-VCd) improved outcomes versus VCd for patients with newly diagnosed immunoglobulin light-chain (AL) amyloidosis in the phase 3 ANDROMEDA study. We report a subgroup analysis of Asian patients (Japan; Korea; China) from ANDROMEDA. Among 388 randomized patients, 60 were Asian (D-VCd, n = 29; VCd, n = 31). At a median follow-up of 11.4 months, the overall hematologic complete response rate was higher for D-VCd versus VCd (58.6% vs. 9.7%; odds ratio, 13.2; 95% confidence interval [CI], 3.3–53.7; P < 0.0001). Six-month cardiac and renal response rates were higher with D-VCd versus VCd (cardiac, 46.7% vs. 4.8%; P = 0.0036; renal, 57.1% vs. 37.5%; P = 0.4684). Major organ deterioration progression-free survival (MOD-PFS) and major organ deterioration event-free survival (MOD-EFS) were improved with D-VCd versus VCd (MOD-PFS: hazard ratio [HR], 0.21; 95% CI, 0.06–0.75; P = 0.0079; MOD-EFS: HR, 0.16; 95% CI, 0.05–0.54; P = 0.0007). Twelve deaths occurred (D-VCd, n = 3; VCd, n = 9). Twenty-two patients had baseline serologies indicating prior hepatitis B virus (HBV) exposure; no patient experienced HBV reactivation. Although grade 3/4 cytopenia rates were higher than in the global safety population, the safety profile of D-VCd in Asian patients was generally consistent with the global study population, regardless of body weight. These results support D-VCd use in Asian patients with newly diagnosed AL amyloidosis. ClinicalTrials.gov Identifier: NCT03201965