Lifetime measurements of Triaxial Strongly Deformed bands in 163^{163}Tm

With the Doppler Shift Attenuation Method, quadrupole transition moments, $Q_t$, were determined for the two recently proposed Triaxial Strongly Deformed (TSD) bands in $^{163}$Tm. The measured $Q_t$ moments indicate that the deformation of these bands is larger than that of the yrast, signature partners. However, the measured values are smaller than those predicted by theory. This observation appears to be valid for TSD bands in several nuclei of the regionComment: 8 pages, 5 figures. Submitted to Physical Review

A Composite Chiral Pair of Rotational Bands in the odd-A Nucleus 135Nd

High-spin states in 135Nd were populated with the 110Pd(30Si,5n)135Nd reaction at a 30Si bombarding energy of 133 MeV. Two Delta(I)=1 bands with close excitation energies and the same parity were observed. These bands are directly linked by Delta(I)=1 and Delta(I)=2 transitions. The chiral nature of these two bands is confirmed by comparison with three-dimensional tilted axis cranking calculations. This is the first observation of a three-quasiparticle chiral structure and established the primarily geometric nature of this phenomenon.Comment: 10 pages, 5 figures (1 in color), 1 table, submitted to Physics Review Letters, written in REVTEX4 forma

Aberrant chromatin landscape following loss of the H3.3 chaperone Daxx in haematopoietic precursors leads to Pu.1-mediated neutrophilia and inflammation

Defective silencing of retrotransposable elements has been linked to inflammageing, cancer and autoimmune diseases. However, the underlying mechanisms are only partially understood. Here we implicate the histone H3.3 chaperone Daxx, a retrotransposable element repressor inactivated in myeloid leukaemia and other neoplasms, in protection from inflammatory disease. Loss of Daxx alters the chromatin landscape, H3.3 distribution and histone marks of haematopoietic progenitors, leading to engagement of a Pu.1-dependent transcriptional programme for myelopoiesis at the expense of B-cell differentiation. This causes neutrophilia and inflammation, predisposing mice to develop an autoinflammatory skin disease. While these molecular and phenotypic perturbations are in part reverted in animals lacking both Pu.1 and Daxx, haematopoietic progenitors in these mice show unique chromatin and transcriptome alterations, suggesting an interaction between these two pathways. Overall, our findings implicate retrotransposable element silencing in haematopoiesis and suggest a cross-talk between the H3.3 loading machinery and the pioneer transcription factor Pu.1

A glucose biosensor based on novel Lutetium bis-phthalocyanine incorporated silica-polyaniline conducting nanobeads

The facile preparation of highly sensitive electrochemical bioprobe based on lutetium 13 phthalocyanine incorporated silica nanoparticles (SiO2(LuPc2)) grafted with Poly(vinyl 14 alcohol-vinyl acetate) itaconic acid (PANI(PVIA)) doped polyaniline conducting nanobeads 15 (SiO2(LuPc2)PANI(PVIA)-CNB) is reported. The preparation of CNB involves two stages (i) 16 pristine synthesis of LuPc2 incorporated SiO2 and PANI(PVIA); (ii) covalent grafting of 17 PANI(PVIA) onto the surface of SiO2(LuPc2). The morphology and other physico-chemical 18 characteristics of CNB were investigated. The scanning electron microscopy images show 19 that the average particle size of SiO2(LuPc2)PANI(PVIA)-CNB was between 180-220 nm. 20 The amperometric measurements showed that the fabricated SiO2(LuPc2)PANI(PVIA)-21 CNB/GOx biosensor exhibited wide linear range (1-16 mM) detection of glucose with a low 22 detection limit of 0.1 mM. SiO2(LuPc2)PANI(PVIA)-CNB/GOx biosensor exhibited high 23 sensitivity (38.53 μA mM−1 cm−2) towards the detection of glucose under optimized 24 conditions. Besides, the real (juice and serum) sample analysis based on a standard addition 25 method and direct detection method showed high precision for measuring glucose at 26 SiO2(LuPc2)PANI(PVIA)-CNB/GOx biosensor. The SiO2(LuPc2)PANI(PVIA)-CNB/GOx 27 biosensor stored under refrigerated condition over a period of 45 days retains ~ 96.4 % 28 glucose response current

The role of autophagy in the cross-talk between epithelial-mesenchymal transitioned tumor cells and cancer stem-like cells

Epithelial-mesenchymal transition (EMT) and cancer stem-like cells (CSC) are becoming highly relevant targets in anticancer drug discovery. A large body of evidence suggests that epithelial-mesenchymal transitioned tumor cells (EMT tumor cells) and CSCs have similar functions. There is also an overlap regarding the stimuli that can induce the generation of EMT tumor cells and CSCs. Moreover, direct evidence has been brought that EMT can give rise to CSCs. It is unclear however, whether EMT tumor cells should be considered CSCs or if they have to undergo further changes. In this article we summarize available evidence suggesting that, indeed, additional programs must be engaged and we propose that macroautophagy (hereafter, autophagy) represents a key trait distinguishing CSCs from EMT tumor cells. Thus, CSCs have often been reported to be in an autophagic state and blockade of autophagy inhibits CSCs. On the other hand, there is ample evidence showing that EMT and autophagy are distinct events. CSCs, however, represent, by themselves, a heterogeneous population. Thus, CSCs have been distinguished in predominantly noncycling and cycling CSCs, the latter representing CSCs that self-renew and replenish the pool of differentiated tumor cells. We now suggest that the non-cycling CSC subpopulation is in an autophagic state. We propose also two models to explain the relationship between EMT tumor cells and these two major CSC subpopulations: a branching model in which EMT tumor cells can give rise to cycling or non-cycling CSCs, respectively, and a hierarchical model in which EMT tumor cells are first induced to become autophagic CSCs and, subsequently, cycling CSCs. Finally, we address the therapeutic consequences of these insights

Synthesis of γ-, δ-, and ε-Lactams by Asymmetric Transfer Hydrogenation of N-(tert-Butylsulfinyl)iminoesters

Highly enantiomerically enriched γ- and δ-lactams have been prepared by a simple and very efficient procedure that involves the asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)iminoesters followed by desulfinylation of the nitrogen atom and spontaneous cyclization to the desired lactams during the basic workup procedure. Five- and six-membered ring lactams bearing aromatic, heteroaromatic, and aliphatic substituents have been obtained in very high yields and ee’s up to >99%. A slight modification of the procedure also allowed the preparation of ε-lactams in good yields and very high enantioselectivities. Both enantiomers of the final lactams could be prepared with equal efficiency by changing the absolute configuration of the sulfinyl chiral auxiliary

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era