Quantum computing of molecular magnet Mn12_{12}

Quantum computation in molecular magnets is studied by solving the time-dependent Schr\"{o}dinger equation numerically. Following Leuenberger and Loss (Nature (London) 410, 789(2001)), an external oscillating magnetic field is applied to populate and manipulate the spin coherent states in molecular magnet Mn$_{12}$. The conditions to realize parallel recording and reading data bases of Grover algorithsm in molecular magnets are discussed in details. It is found that an accurate duration time of magnetic pulse as well as the amplitudes are required to design the device of quantum computing.Comment: 3 pages, 1 figur

Tissue-specific Genome Editing in vivo by MicroRNA-repressible Anti-CRISPR Proteins [preprint]

CRISPR-Cas systems are bacterial adaptive immune pathways that have revolutionized biotechnology and biomedical applications. Despite the potential for human therapeutic development, there are many hurdles that must be overcome before its use in clinical settings. Some clinical safety concerns arise from persistent activity of Cas9 after the desired editing is complete, or from editing activity in unintended cell types or tissues upon in vivo delivery [e.g. by adeno-associated viruses (AAV)]. Although tissue-specific promoters and serotypes with tissue tropisms can be used, suitably compact promoters are not always available for desired cell types, and AAV tissue tropisms are not absolute. To reinforce tissue-specific editing, we exploited anti-CRISPR proteins (Acrs), which are proteins evolved as countermeasures against CRISPR immunity. To inhibit Cas9 in all ancillary tissues without compromising editing in the target tissue, we established a flexible platform in which an Acr transgene is repressed by endogenous, tissue-specific microRNAs (miRNAs). We demonstrate that miRNAs regulate the expression of an Acr transgene bearing miRNA-binding sites in its 3’ UTR, and control subsequent genome editing outcomes in a cell-type specific manner. We also show that the strategy is applicable to multiple Cas9 orthologs and their respective Acrs. Furthermore, we demonstrate that in vivo delivery of Cas9 and Acrs that are targeted for repression by liver-specific miR-122 allow editing in the liver while Acrs devoid of miRNA regulation prevent Cas9 activity. This strategy provides additional safeguards against off-tissue genome editing by confining Cas9 activity to selected cell types

Theory for high spin systems with orbital degeneracy

High-spin systems with orbital degeneracy are studied in the large spin limit. In the absence of Hund's coupling, the classical spin model is mapped onto disconnected orbital systems with spins up and down, respectively. The ground state of the isotropic model is an orbital valence bond state where each bond is an orbital singlet with parallel spins, and neighbouring bonds interact antiferromagnetically. The possible relevance to the transition metal oxides are discussed.Comment: 4 page, three figures, to appear in Phys. Rev. Let

Theoretical Evidence for the Berry-Phase Mechanism of Anomalous Hall Transport: First-principles Studies on CuCr2_2Se4−x_{4-x}Brx_x

To justify the origin of anomalous Hall effect (AHE), it is highly desirable to have the system parameters tuned continuously. By quantitative calculations, we show that the doping dependent sign reversal in CuCr$_{2}$Se$_{4-x}$Br$_{x}$, observed but not understood, is nothing but direct evidence for the Berry-Phase mechanism of AHE. The systematic calculations well explain the experiment data for the whole doping range where the impurity scattering rates is changed by several orders with Br substitution. Further sign change is also predicted, which may be tested by future experiments.Comment: 4 page

Tissue-restricted genome editing in vivo specified by microRNA-repressible anti-CRISPR proteins

CRISPR-Cas systems are bacterial adaptive immune pathways that have revolutionized biotechnology and biomedical applications. Despite the potential for human therapeutic development, there are many hurdles that must be overcome before its use in clinical settings. Some clinical safety concerns arise from editing activity in unintended cell types or tissues upon in vivo delivery (e.g., by adeno-associated virus (AAV) vectors). Although tissue-specific promoters and serotypes with tissue tropisms can be used, suitably compact promoters are not always available for desired cell types, and AAV tissue tropism specificities are not absolute. To reinforce tissue-specific editing, we exploited anti-CRISPR proteins (Acrs) that have evolved as natural countermeasures against CRISPR immunity. To inhibit Cas9 in all ancillary tissues without compromising editing in the target tissue, we established a flexible platform in which an Acr transgene is repressed by endogenous, tissue-specific microRNAs (miRNAs). We demonstrate that miRNAs regulate the expression of an Acr transgene bearing miRNA-binding sites in its 3\u27-UTR and control subsequent genome editing outcomes in a cell-type specific manner. We also show that the strategy is applicable to multiple Cas9 orthologs and their respective anti-CRISPRs. Furthermore, we validate this approach in vivo by demonstrating that AAV9 delivery of Nme2Cas9, along with an AcrIIC3 Nme construct that is targeted for repression by liver-specific miR-122, allows editing in the liver while repressing editing in an unintended tissue (heart muscle) in adult mice. This strategy provides safeguards against off-tissue genome editing by confining Cas9 activity to selected cell types

Reproductive traits and mandibular gland pheromone of anarchistic honey bee workers Apis mellifera occurring in China

International audienceAbstractIn honey bee colonies, workers, in particular of “anarchistic” lineages, can activate their ovaries and lay eggs, even in the presence of the queen. We identified three queenright colonies showing typical signs of worker reproduction. To characterize this new lineage, we extracted the mandibular gland and analyzed it using gas chromatography. The total amounts of the five main components of the mandibular gland, namely methyl p-hydroxyben-zoate (HOB), 9-oxo-2(E)-decenoic acid (9-ODA), (S)-9-hydroxy-(E)-2-decenoic acid (9-HDA), 10-HDA, and 10-hydroxyde-canoic acid (10-HDAA) were significantly higher in the mandibular gland profiles of workers with activated ovaries (AWs, 8.88 ± 1.71 μg) compared to workers with inactivated ovaries (IAWs, 4.00 ± 2.09 μg). Furthermore, the chemical profiles of IAWs were dominated by the “worker substances” 10-HDA (34.64 ± 8.19 %) and its precursor 10-HDAA (22.88 ± 4.95 %), while the chemical profiles in AWs were dominated by the precursor of the queen substance 9-HDA (40.04 ± 7.55 %). The ratios of two precursor substances 10-HDAA/9-HDA of IAWs were more worker like (>1.0) whereas AWs were more queen like (≤1.0). These results suggest that the mandibular pheromones of anarchistic workers resemble a more queen-like reproductive active profile and that these workers may represent a reversion to a more basal reproductive phenotype

Two-dimensional gapless spin liquids in frustrated SU(N) quantum magnets

A class of the symmetrically frustrated SU(N) models is constructed for quantum magnets based on the generators of SU(N) group. The total Hamiltonian lacks SU(N) symmtry. A mean field theory in the quasi-particle representation is developed for spin liquid states. Numerical solutions in two dimension indicate that the ground states are gapless and the quasi-particles are Dirac particles. The mechanism may be helpful in exploring the spin liquid phases in the spin-1 bilinear-biquadratic model and the spin-orbital model in higher dimensions.Comment: 9 pages, 3 figures, to appear in New Journal of Physic

Gegen Qinlian Decoction Treats Diarrhea in Piglets by Modulating Gut Microbiota and Short-Chain Fatty Acids

Gut microbiota and its metabolites, short-chain fatty acids (SCFAs), play important roles in diarrheal diseases. Gegen Qinlian decoction (GQD), a Chinese herb formula, has been widely used to treat infectious diarrhea for centuries. However, little is known about the mechanism underlying its efficacy and whether it is mediated by gut microbiota and SCFAs. In this study, the composition of gut microbiota from bacterial diarrheal piglets was assessed using 16S rRNA analysis. The concentrations of fecal SCFAs were determined using a gas chromatography-mass spectrometer (GC-MS). The expression of mucosal pro-inflammatory cytokines in the colon was ascertained. Results showed that GQD reverses the reduction in the richness of gut microbiota, changes its structure, and significantly increases the relative abundances of SCFA-producing bacteria, including Akkermansia, Bacteroides, Clostridium, Ruminococcus, and Phascolarctobacterium. Moreover, GQD increased the levels of fecal SCFAs, including acetic acid, propionic acid, and butyric acid. GQD thus attenuates diarrhea in piglets. Further, our results suggest that the SCFAs could help to attenuate mucosal pro-inflammatory responses following GQD treatment by inhibiting histone deacetylase and the NF-κB pathway. We thus suggseted that gut microbiota play an important role during diarrhea treatment, an effect may be promoted by the GQD-induced structural changes of the gut microbial community and production of SCFAs. The increased levels of SCFAs probably provide further help to attenuate mucosal inflammation and diarrhea. In conclusion, our study might provide evidence that GQD treats diarrhea maybe involved in modulating gut microbiota and increasing SCFA levels

HSP90/AXL/eIF4E-regulated unfolded protein response as an acquired vulnerability in drug-resistant KRAS-mutant lung cancer

Drug resistance and tumor heterogeneity are formidable challenges in cancer medicine, which is particularly relevant for KRAS-mutant cancers, the epitome of malignant tumors recalcitrant to targeted therapy efforts and first-line chemotherapy. In this study, we delineate that KRAS-mutant lung cancer cells resistant to pemetrexed (MTA) and anti-MEK drug trametinib acquire an exquisite dependency on endoplasmic reticulum (ER) stress signaling, rendering resistant cancer cells selectively susceptible to blockage of HSP90, the receptor tyrosine kinase AXL, the eukaryotic translation initiation factor 4E (eIF4E), and the unfolded protein response (UPR). Mechanistically, acquisition of drug resistance enables KRAS-mutant lung cancer cells to bypass canonical KRAS effectors but entail hyperactive AXL/eIF4E, increased protein turnover in the ER, and adaptive activation of an ER stress-relief UPR survival pathway whose integrity is maintained by HSP90. Notably, the unique dependency and sensitivity induced by drug resistance are applicable to KRAS-mutant lung cancer cells undergoing de novo intratumor heterogeneity. In line with these findings, HSP90 inhibitors synergistically enhance antitumor effects of MTA and trametinib, validating a rational combination strategy to treat KRAS-mutant lung cancer. Collectively, these results uncover collateral vulnerabilities co-occurring with drug resistance and tumor heterogeneity, informing novel therapeutic avenues for KRAS-mutant lung cancer

Suppression of Quantum Phase Interference in Molecular Magnets Fe₈ with Dipolar-Dipolar Interaction

Renormalized tunnel splitting with a finite distribution in the biaxial spin model for molecular magnets is obtained by taking into account the dipolar interaction of enviromental spins. Oscillation of the resonant tunnel splitting with a transverse magnetic field along the hard axis is smeared by the finite distribution which subsequently affects the quantum steps of hysteresis curve evaluated in terms of the modified Landau-Zener model of spin flipping induced by the sweeping field. We conclude that the dipolar-dipolar interaction drives decoherence of quantum tunnelling in molcular magnets Fe₈, which explains why the quenching points of tunnel spliting between odd and even resonant tunnelling predcited theoretically were not observed experimentally.Comment: 5 pages including 3 figure and 1 table. To appear in Physical Review