Observation of D+ → K(+)η(') and search for CP violation in D+ → π(+)η(') decays

We report the first observation of the doubly Cabibbo-suppressed decays D(+)→K(+)η((')) using a 791 fb(-1) data sample collected with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider. The ratio of the branching fractions of doubly Cabibbo-suppressed relative to singly Cabibbo-suppressed D(+)→π(+)η((')) decays are B(D(+)→K(+)η)/B(D(+)→π(+)η)=(3.06±0.43±0.14)% and B(D(+)→K(+)η')/B(D(+)→π(+)η')=(3.77±0.39±0.10)%. From these, we find that the relative final-state phase difference between the tree and annihilation amplitudes in D(+) decays, δ(TA), is (72±9)° or (288±9)°. We also report the most precise measurements of CP asymmetries to date: A(CP)(D(+)→π(+)η)=(+1.74±1.13±0.19)% and A(CP)(D(+)→π(+)η')=(-0.12±1.12±0.17)%.     

Viscosity scaling for the glassy phase of protein folding

Although commendable progress has been made in the understanding of the physics of protein folding, a key unresolved issue is whether Kramers' diffusion model of chemical reactions is generally applicable to activated barrier crossing events during folding. To examine the solvent viscosity effect on the folding transition of native-like trapped intermediates, laser flash photolysis has been used to measure the microsecond folding kinetics of a natively folded state of CO-liganded ferrocytochrome c (M-state) in the 1-250 cP range of glycerol viscosity at pH 7.0, 20 degrees C. The single rate coefficient for the folding of the M-state to the native state of the protein (i.e., the M --> N folding process) decreases initially when the solvent viscosity is low (<10 cP), but saturates at higher viscosity, indicating that Kramers model is not general enough for scaling the viscosity dependence of post-transition folding involving glassy dynamics. Analysis based on the Grote-Hynes idea of time dependent friction in conjunction with defect diffusion dynamics can account for the observed non-Kramers scaling.     

Effect of peptide-based captopril analogues on angiotensin converting enzyme activity and peroxynitrite-mediated tyrosine nitration

Angiotensin converting enzyme (ACE) regulates the blood pressure by converting angiotensin I to angiotensin II and bradykinin to bradykinin 1-7. These two reactions elevate the blood pressure as angiotensin II and bradykinin are vasoconstrictory and vasodilatory hormones, respectively. Therefore, inhibition of ACE is an important strategy for the treatment of hypertension. The natural substrates of ACE, i.e., angiotensin II and bradykinin, contain a Pro-Phe motif near the site of hydrolysis. Therefore, there may be a Pro-Phe binding pocket at the active site of ACE, which may facilitate the substrate binding. In view of this, we have synthesized a series of thiol- and selenol-containing dipeptides and captopril analogues and studied their ACE inhibition activities. This study reveals that both the selenol or thiol moiety and proline residues are essential for ACE inhibition. Although the introduction of a Phe residue to captopril and its selenium analogue considerably reduces the inhibitory effect, there appears to be a Phe binding pocket at the active site of ACE.     

Temperature responsive phosphorescent small unilamellar vesicles

Self-assembled lipid vesicles with embedded amphiphilic terbium(III) complexes show a strong temperature dependence of their phosphorescence intensity and lifetime in the physiological range.     

Stereoselective synthesis of novel annulated thiopyrano indole derivatives from simple oxindole via intramolecular 1,3-dipolar cycloaddition reactions of nitrone and nitrile oxide

Synthesis of some novel isoxazolidine/dihydroisoxazole annulated thiopyrano[2,3-b]indole derivatives from simple oxindole via 1,3-dipolar cycloaddition reaction involving nitrone and nitrile oxide as 1,3-dipole is reported.     

Evidence for direct CP violation in B±→ηh± and observation of B0→ηK0

We report measurements of the branching fractions and CP asymmetries for B(±)→ηh(±) (h=K or π) and the observation of the decay B(0)→ηK(0) from the final data sample of 772×10(6) B ?B pairs collected with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider. The measured branching fractions are B(B(±)→ηK(±))=(2.12±0.23±0.11)×10(-6), B(B(±)→ηπ(±))=(4.07±0.26±0.21)×10(-6), and B(B(0)→ηK(0))=(1.27(-0.29)(+0.33)±0.08)×10(-6), where the last decay is observed for the first time with a significance of 5.4 standard deviations (σ). We also find evidence for CP violation in the charged B modes, A(CP)(B(±)→ηK(±))=-0.38±0.11±0.01 and A(CP)(B(±)→ηπ(±))=-0.19±0.06±0.01 with significances of 3.8 σ and 3.0 σ, respectively. For all measurements, the first and second uncertainties are statistical and systematic, respectively.     

Sensing of ammonia gas by undoped and aluminum-doped tin oxide nanoparticles by Raman spectroscopy

In this work, the statistical distribution functions for boson, fermions and their mixtures have been derived and it is found that distribution functions follow the symmetry features of \(\beta \) distribution. If occupation index is greater than unity, then it is easy in the present approach to visualise condensations in terms of intermediate values of mixing parameters. There are some applications of intermediate values of mixing parameters.     

A dynamical system approach to Bianchi III cosmology for Hu–Sawicki type <Emphasis Type="Italic">f</Emphasis>(<Emphasis Type="Italic">R</Emphasis>) gravity

The cosmological dynamics of spatially homogeneous but anisotropic Bianchi type-III space-time is investigated in presence of a perfect fluid within the framework of Hu–Sawicki model. We use the dynamical system approach to perform a detailed analysis of the cosmological behaviour of this model for the model parameters \(n=1, c_1=1\), determining all the fixed points, their stability and corresponding cosmological evolution. We have found stable fixed points with de Sitter solution along with unstable radiation like fixed points. We have identified a matter like point which act like an unstable spiral and when the initial conditions of a trajectory are very close to this point, it stabilizes at a stable accelerating point. Thus, in this model, the universe can naturally approach to a phase of accelerated expansion following a radiation or a matter dominated phase. It is also found that the isotropisation of this model is affected by the spatial curvature and that all the isotropic fixed points are found to be spatially flat.     

Progranulin is expressed within motor neurons and promotes neuronal cell survival

Background

Progranulin is a secreted high molecular weight growth factor bearing seven and one half copies of the cysteine-rich granulin-epithelin motif. While inappropriate over-expression of the progranulin gene has been associated with many cancers, haploinsufficiency leads to atrophy of the frontotemporal lobes and development of a form of dementia (frontotemporal lobar degeneration with ubiquitin positive inclusions, FTLD-U) associated with the formation of ubiquitinated inclusions. Recent reports indicate that progranulin has neurotrophic effects, which, if confirmed would make progranulin the only neuroprotective growth factor that has been associated genetically with a neurological disease in humans. Preliminary studies indicated high progranulin gene expression in spinal cord motor neurons. However, it is uncertain what the role of Progranulin is in normal or diseased motor neuron function. We have investigated progranulin gene expression and subcellular localization in cultured mouse embryonic motor neurons and examined the effect of progranulin over-expression and knockdown in the NSC-34 immortalized motor neuron cell line upon proliferation and survival.

Results

In situ hybridisation and immunohistochemical techniques revealed that the progranulin gene is highly expressed by motor neurons within the mouse spinal cord and in primary cultures of dissociated mouse embryonic spinal cord-dorsal root ganglia. Confocal microscopy coupled to immunocytochemistry together with the use of a progranulin-green fluorescent protein fusion construct revealed progranulin to be located within compartments of the secretory pathway including the Golgi apparatus. Stable transfection of the human progranulin gene into the NSC-34 motor neuron cell line stimulates the appearance of dendritic structures and provides sufficient trophic stimulus to survive serum deprivation for long periods (up to two months). This is mediated at least in part through an anti-apoptotic mechanism. Control cells, while expressing basal levels of progranulin do not survive in serum free conditions. Knockdown of progranulin expression using shRNA technology further reduced cell survival.

Conclusion

Neurons are among the most long-lived cells in the body and are subject to low levels of toxic challenges throughout life. We have demonstrated that progranulin is abundantly expressed in motor neurons and is cytoprotective over prolonged periods when over-expressed in a neuronal cell line. This work highlights the importance of progranulin as neuroprotective growth factor and may represent a therapeutic target for neurodegenerative diseases including motor neuron disease.     

A Comprehensive Review on the Techniques for Extraction of Bioactive Compounds from Medicinal Cannabis

Cannabis is well-known for its numerous therapeutic activities, as demonstrated in pre-clinical and clinical studies primarily due to its bioactive compounds. The Cannabis industry is rapidly growing; therefore, product development and extraction methods have become crucial aspects of Cannabis research. The evaluation of the current extraction methods implemented in the Cannabis industry and scientific literature to produce consistent, reliable, and potent medicinal Cannabis extracts is prudent. Furthermore, these processes must be subjected to higher levels of scientific stringency, as Cannabis has been increasingly used for various ailments, and the Cannabis industry is receiving acceptance in different countries. We comprehensively analysed the current literature and drew a critical summary of the extraction methods implemented thus far to recover bioactive compounds from medicinal Cannabis. Moreover, this review outlines the major bioactive compounds in Cannabis, discusses critical factors affecting extraction yields, and proposes future considerations for the effective extraction of bioactive compounds from Cannabis. Overall, research on medicinal marijuana is limited, with most reports on the industrial hemp variety of Cannabis or pure isolates. We also propose the development of sustainable Cannabis extraction methods through the implementation of mathematical prediction models in future studies.