Leptogenesis and low energy CP phases with two heavy neutrinos

An attractive explanation for non-zero neutrino masses and small matter antimatter asymmetry of the present Universe lies in "leptogenesis". At present the {\it size} of the lepton asymmetry is precisely known, while the {\it sign} is not known yet. In this work we determine the sign of this asymmetry in the framework of two right handed neutrino models by relating the leptogenesis phase(s) with the low energy CP violating phases appearing in the leptonic mixing matrix. It is shown that the knowledge of low energy lepton number violating re-phasing invariants can indeed determine the sign of the present matter antimatter asymmetry of the Universe and hence indirectly probing the light physical neutrinos to be Majorana type.Comment: 26 pages (revtex), 8 eps figures, Typos corrected and one reference is added, Section VI is expanded, Two new figures are added, Journal version, To appear in PR

Bounds on neutrino masses from leptogenesis in type-II see-saw models

The presence of the triplet $\Delta_{L}$ in left-right symmetric theories leads to type-II see-saw mechanism for the neutrino masses. In these models, assuming a normal mass hierarchy for the heavy Majorana neutrinos, we derive a lower bound on the mass of the lightest of heavy Majorana neutrino from the leptogenesis constraint. From this bound we establish a consistent picture for the hierarchy of heavy Majorana neutrinos in a class of left right symmetric models in which we identify the neutrino Dirac mass matrix with that of Fritzsch type charged lepton mass matrix. It is shown that these values are compatible with the current neutrino oscillation data.Comment: minor typos corrected, references added, match with published versio

4-(4-Methoxy­phen­yl)-1-phenyl­pyridine-2,6(1H,3H)-dione

In the title compound, C18H15NO3, the pyridine-2,6-dione ring adopts an envelope conformation. The phenyl ring lies approximately perpendicular to the mean plane of the pyridine-2,6-dione ring [dihedral angle = 81.5 (1)°], while the methoxy­phenyl ring is tilted to the same plane by a dihedral angle of 34.8 (1)°. Inter­molecular C—H⋯O inter­actions link the mol­ecules into chains along [100]

3-(4-Methoxy­phen­yl)pent-2-ene-1,5-dioic acid

In the title compound, C12H12O5, mol­ecules are linked into anti­parallel hydrogen-bonded sheets through inversion dimers generated via two O—H⋯O hydrogen bonds. Using the R 2 2(8) motif as a building block, hydrogen-bonded chains of a C 2 2(8) superstructure are then generated

Effect of post harvest treatments and harvesting stage on vase life and flower quality of cut Oriental lily

An investigation was carried out to study the effect of post harvest treatments and harvesting stage on vase life and flower quality of cut Oriental lily cv. Avocado. The results showed that highest vase life (15.83 days) and vase solution uptake (49.17 ml) was recorded with sucrose (2%) + 5-SSA (200ppm), whereas maximum flower diameter (15.17 cm) was recorded in vase solution containing sucrose (2%) + 5-SSA (100ppm). Earliest opening of florets (4.42 days) reported under sucrose (2%) + 5-SSA (200ppm). Effect of treatments was found non-significant in respect to opening of florets. Harvesting at green bud stage exhibited extended vase life (14.33 days) and higher vase solution uptake (40.43 ml), whereas maximum flower diameter (14.25 cm) recorded at 75% colour development stage. Based on the results it is concluded that 5-SSA could be an inexpensive and potential chemical for delaying senescence and for extending the keeping quality of cut liliums commercially

AMBRA1 is able to induce mitophagy via LC3 binding, regardless of PARKIN and p62/SQSTM1

Damaged mitochondria are eliminated by mitophagy, a selective form of autophagy whose dysfunction associates with neurodegenerative diseases. PINK1, PARKIN and p62/SQTMS1 have been shown to regulate mitophagy, leaving hitherto ill-defined the contribution by key players in 'general' autophagy. In basal conditions, a pool of AMBRA1 - an upstream autophagy regulator and a PARKIN interactor - is present at the mitochondria, where its pro-autophagic activity is inhibited by Bcl-2. Here we show that, upon mitophagy induction, AMBRA1 binds the autophagosome adapter LC3 through a LIR (LC3 interacting region) motif, this interaction being crucial for regulating both canonical PARKIN-dependent and -independent mitochondrial clearance. Moreover, forcing AMBRA1 localization to the outer mitochondrial membrane unleashes a massive PARKIN- and p62-independent but LC3-dependent mitophagy. These results highlight a novel role for AMBRA1 as a powerful mitophagy regulator, through both canonical or noncanonical pathways

INVESTIGATION ON THE PRODUCTION OF L-GLUTAMINASE FROM PSEUDOMONAS STUTZERI STRAIN UNDER SOLID STATE FERMENTATION USING VARIOUS AGRO RESIDUES

Solid state fermentation was carried out for the production of L-glutaminase by Pseudomonas stutzeri PIMS6 using different agro residues including green gram husk, Bengal gram husk, cattle feed, wheat bran and groundnut oil cake as solid substrates. L-glutaminase has received significant attention in recent years owing to its potential applications in medicine as an anticancer agent, as an efficient anti-retroviral agent and as a biosensor. In food industries it is used as a flavor and aroma enhancing agent. The maximum yield (55.24 U/gds) of L-glutaminase by Pseudomomonas stutzeri PIMS6 was obtained using cattle feed at 75% initial moisture content, initial pH 8.0, supplemented with glucose (1.0%), ammonium sulphate (1.0%),  inoculated with 5% of inoculum and incubated at 37°C for 96 h. Both physico-chemical and nutritional parameters played a significant role in the production of the enzyme L-glutaminase.Keywords: L-glutaminase, Pseudomonas stutzeri PIMS6, Cattle feed, Solid state fermentation

Razvoj i optimizacija sustava za isporuku metoprolol sukcinata sa zadržavanjem u želucu

Metoprolol succinate (MS) gastroretentive (GR) controlled release system was formulated to increase gastric residence time leading to improved drug bioavailability. Box-Behnken model was followed using novel combinations of sodium alginate (SA), sodium carboxymethylcellulose (NaCMC), magnesium alumino metasilicate (MAS) as independent variables. Floating lag time (Flag), t25, t50, t75, diffusion exponent as dependent variables revealed that the amount of SA, NaCMC and MAS have a significant effect (p < 0.05) on t25, t50, t75 and Flag. MSGR tablets were prepared and evaluated for mass, thickness, hardness, friability, drug content and floating property. Tablets were studied for dissolution for 24 h and exhibited controlled release of MS with floating for 16 h. The release profile of the optimized batch MS01 fitted first-order kinetics (R2 = 0.9868, n = 0.543), indicating non-Fickian diffusion or anomalous transport by diffusion and swelling.U radu je opisan razvoj sustava za isporuku metoprolol sukcinata (MS) s kontroliranim oslobađanjem i produljenim vremenom zadržavanja u želucu (GR), u svrhu poboljšanja bioraspoloživosti. Primijenjen je Box-Behnkenov model, a kao zavisne varijable izabrane su nove kombinacije natrijevog alginata (SA), natrijeve soli karboksimetilceluloze (NaCMC) i magnezijevog aluminometasilikata (MAS). Vrijeme plutanja (Flag), t25, t50, t75 i difuzijski eksponent kao zavisne varijable otkrili su da količina SA, NaCMC i MAS ima značajan učinak (p < 0,05) na t25, t50, t75 i Flag. Pripravljenim tabletama određena je masa, debljina, tvrdoća, lomljivost, sadržaj ljekovite tvari i sposobnost plutanja. Oslobađanje MS praćeno je 24 h. Rezultati pokazuju da je oslobađanje kontrolirano, a vrijeme plutanja 16 h. Oslobađanje iz optimiranog pripravka MS01 slijedi kinetiku prvog reda (R2 = 0,9868, n = 0,543), što ukazuje na difuziju koja ne slijedi Fickov zakon već anomalni transport difuzijom i bubrenjem

Reversible Keap1 inhibitors are preferential pharmacological tools to modulate cellular mitophagy

Mitophagy orchestrates the autophagic degradation of dysfunctional mitochondria preventing their pathological accumulation and contributing to cellular homeostasis. We previously identified a novel chemical tool (hereafter referred to as PMI), which drives mitochondria into autophagy without collapsing their membrane potential (ΔΨm). PMI is an inhibitor of the protein-protein interaction (PPI) between the transcription factor Nrf2 and its negative regulator, Keap1 and is able to up-regulate the expression of autophagy-associated proteins, including p62/SQSTM1. Here we show that PMI promotes mitochondrial respiration, leading to a superoxide-dependent activation of mitophagy. Structurally distinct Keap1-Nrf2 PPI inhibitors promote mitochondrial turnover, while covalent Keap1 modifiers, including sulforaphane (SFN) and dimethyl fumarate (DMF), are unable to induce a similar response. Additionally, we demonstrate that SFN reverses the effects of PMI in co-treated cells by reducing the accumulation of p62 in mitochondria and subsequently limiting their autophagic degradation. This study highlights the unique features of Keap1-Nrf2 PPI inhibitors as inducers of mitophagy and their potential as pharmacological agents for the treatment of pathological conditions characterized by impaired mitochondrial quality control

Preconditioning Involves Selective Mitophagy Mediated by Parkin and p62/SQSTM1

Autophagy-dependent mitochondrial turnover in response to cellular stress is necessary for maintaining cellular homeostasis. However, the mechanisms that govern the selective targeting of damaged mitochondria are poorly understood. Parkin, an E3 ubiquitin ligase, has been shown to be essential for the selective clearance of damaged mitochondria. Parkin is expressed in the heart, yet its function has not been investigated in the context of cardioprotection. We previously reported that autophagy is required for cardioprotection by ischemic preconditioning (IPC). In the present study, we used simulated ischemia (sI) in vitro and IPC of hearts to investigate the role of Parkin in mediating cardioprotection ex vivo and in vivo. In HL-1 cells, sI induced Parkin translocation to mitochondria and mitochondrial elimination. IPC induced Parkin translocation to mitochondria in Langendorff-perfused rat hearts and in vivo in mice subjected to regional IPC. Mitochondrial depolarization with an uncoupling agent similarly induced Parkin translocation to mitochondria in cells and Langendorff-perfused rat hearts. Mitochondrial loss was blunted in Atg5-deficient cells, revealing the requirement for autophagy in mitochondrial elimination. Consistent with previous reports indicating a role for p62/SQSTM1 in mitophagy, we found that depletion of p62 attenuated mitophagy and exacerbated cell death in HL-1 cardiomyocytes subjected to sI. While wild type mice showed p62 translocation to mitochondria and an increase in ubiquitination, Parkin knockout mice exhibited attenuated IPC-induced p62 translocation to the mitochondria. Importantly, ablation of Parkin in mice abolished the cardioprotective effects of IPC. These results reveal for the first time the crucial role of Parkin and mitophagy in cardioprotection