Spectral Asymmetry Induces a Re-Entrant Quantum Hall Effect in a Topological Insulator.

The band inversion of topological materials in three spatial dimensions is intimately connected to the parity anomaly of 2D massless Dirac fermions, known from quantum field theory. At finite magnetic fields, the parity anomaly reveals itself as a non-zero spectral asymmetry, i.e., an imbalance between the number of conduction and valence band Landau levels, due to the unpaired zero Landau level. This work reports the realization of this 2D Dirac physics at a single surface of the 3D topological insulator (Hg,Mn)Te. An unconventional re-entrant sequence of quantized Hall plateaus in the measured Hall resistance can be directly related to the occurrence of spectral asymmetry in a single topological surface state. The effect should be observable in any topological insulator where the transport is dominated by a single Dirac surface state.

Development of a flow cytometry-based plating-free system for strain engineering in industrial fungi.

Recent technical advances regarding filamentous fungi have accelerated the engineering of fungal-based production and benefited basic science. However, challenges still remain and limit the speed of fungal applications. For example, high-throughput technologies tailored to filamentous fungi are not yet commonly available for genetic modification. The currently used fungal genetic manipulations are time-consuming and laborious. Here, we developed a flow cytometry-based plating-free system to directly screen and isolate the transformed protoplasts in industrial fungi Myceliophthora thermophila and Aspergillus niger. This system combines genetic engineering via the 2A peptide and the CRISPR-Cas9 system, strain screening by flow cytometry, and direct sorting of colonies for deep-well-plate incubation and phenotypic analysis while avoiding culturing transformed protoplasts in plates, colony picking, conidiation, and cultivation. As a proof of concept, we successfully applied this system to generate the glucoamylase-hyperproducing strains MtYM6 and AnLM3 in M. thermophila and A. niger, respectively. Notably, the protein secretion level and enzyme activities in MtYM6 were 17.3- and 25.1-fold higher than in the host strain. Overall, these findings suggest that the flow cytometry-based plating-free system can be a convenient and efficient tool for strain engineering in fungal biotechnology. We expect this system to facilitate improvements of filamentous fungal strains for industrial applications. KEY POINTS: • Development of a flow cytometry-based plating-free (FCPF) system is presented. • Application of FCPF system in M. thermophila and A. niger for glucoamylase platform. • Hyper-produced strains MtYM6 and AnLM3 for glucoamylase production are generated.

Genetic Architecture Underlying Nascent Speciation-The Evolution of Eurasian Pigs under Domestication.

Speciation is a process whereby the evolution of reproductive barriers leads to isolated species. Although many studies have addressed large-effect genetic footprints in the advanced stages of speciation, the genetics of reproductive isolation in nascent stage of speciation remains unclear. Here, we show that pig domestication offers an interesting model for studying the early stages of speciation in great details. Pig breeds have not evolved the large X-effect of hybrid incompatibility commonly observed between "good species." Instead, deleterious epistatic interactions among multiple autosomal loci are common. These weak Dobzhansky-Muller incompatibilities confer partial hybrid inviability with sex biases in crosses between European and East Asian domestic pigs. The genomic incompatibility is enriched in pathways for angiogenesis, androgen receptor signaling and immunity, with an observation of many highly differentiated cis-regulatory variants. Our study suggests that partial hybrid inviability caused by pervasive but weak interactions among autosomal loci may be a hallmark of nascent speciation in mammals.

Magnetotransport properties near the Dirac point of Dirac semimetal Cd3As2 nanowires.

Three-dimensional (3D) Dirac semimetals are featured by 3D linear energy-momentum dispersion relation, which have been proposed to be a desirable system to study Dirac fermions in 3D space and Weyl fermions in solid-state materials. Significantly, to reveal exotic transport properties of Dirac semimetals, the Fermi level should be close to the Dirac point, around which the linear dispersion is retained. Here we report the magnetotransport properties near the Dirac point in Cd3As2 nanowires, manifesting the evolution of band structure under magnetic field. Ambipolar field effect is observed with the Dirac point at V g = 3.9 V. Under high magnetic field, there is a resistivity dip in transfer curve at the Dirac point, which is caused by the Zeeman splitting enhanced density of state around the Dirac point. Furthermore, the low carrier density in the nanowires makes it feasible to enter into the quantum limit regime, resulting in the quantum linear magnetoresistance being observed even at room temperature. Besides, the dramatic reduction of bulk conductivity due to the low carrier density, together with a large surface to volume ratio of the nanowire, collectively help to reveal the Shubnikov-de Haas oscillations from the surface states. Our studies on transport properties around the Dirac point therefore provide deep insights into the emerging exotic physics of Dirac and Weyl fermions.

Genome-wide study refines the quantitative trait locus for number of ribs in a Large White × Minzhu intercross pig population and reveals a new candidate gene.

In China, sparerib is one of the most valuable parts of the pork carcass. As a result, candidate gene mining for number of ribs has become an interesting study focus. To examine the genetic basis for this major trait, we genotyped 596 individuals from an F2 Large White × Minzhu intercross pig population using the PorcineSNP60 Genotyping BeadChip. The genome-wide association study identified a locus for number of ribs in a 2.38-Mb region on Sus scrofa chromosome 7 (SSC7 of Sus scrofa genome assembly, Sscrofa10.2). We identified the top significant SNP ASGA0035536, which explained 16.51 % of the phenotypic variance. A previously reported candidate causal mutation (g.19034 A>C) in vertebrae development-associated gene VRTN explained 8.79 % of the phenotypic variation on number of ribs and had a much lower effect than ASGA0035536. Haplotype sharing analysis in F1 boars localized the rib number QTL to a 951-kb interval on SSC7. This interval encompassed 17 annotated genes in Sscrofa10.2, including the previously reported VRTN candidate gene. Of the 17 candidate genes, LTBP2, which encodes a latent transforming growth factor beta binding protein, was previously reported to indirectly regulate the activity of growth differentiation factor Gdf11, which has been shown to increase the number of ribs in knock-out mice. Thus, we propose LTBP2 as a good new candidate gene for number of ribs in the pig population. This finding advances our understanding of the genetic architecture of rib number in pigs.

Two-Carrier Transport Induced Hall Anomaly and Large Tunable Magnetoresistance in Dirac Semimetal Cd3As2 Nanoplates.

Cd3As2 is a model material of Dirac semimetal with a linear dispersion relation along all three directions in the momentum space. The unique band structure of Cd3As2 is made with both Dirac and topological properties. It can be driven into a Weyl semimetal by symmetry breaking or a topological insulator by enhancing the spin-orbit coupling. Here we report the temperature and gate voltage-dependent magnetotransport properties of Cd3As2 nanoplates with Fermi level near the Dirac point. The Hall anomaly demonstrates the two-carrier transport accompanied by a transition from n-type to p-type conduction with decreasing temperature. The carrier-type transition is explained by considering the temperature-dependent spin-orbit coupling. The magnetoresistance exhibits a large nonsaturating value up to 2000% at high temperatures, which is ascribed to the electron-hole compensation in the system. Our results are valuable for understanding the experimental observations related to the two-carrier transport in Dirac/Weyl semimetals, such as Na3Bi, ZrTe5, TaAs, NbAs, and HfTe5.

Aharonov-Bohm oscillations in Dirac semimetal Cd3As2 nanowires.

Three-dimensional Dirac semimetals, three-dimensional analogues of graphene, are unusual quantum materials with massless Dirac fermions, which can be further converted to Weyl fermions by breaking time reversal or inversion symmetry. Topological surface states with Fermi arcs are predicted on the surface and have been observed by angle-resolved photoemission spectroscopy experiments. Although the exotic transport properties of the bulk Dirac cones have been demonstrated, it is still a challenge to reveal the surface states via transport measurements due to the highly conductive bulk states. Here, we show Aharonov-Bohm oscillations in individual single-crystal Cd3As2 nanowires with low carrier concentration and large surface-to-volume ratio, providing transport evidence of the surface state in three-dimensional Dirac semimetals. Moreover, the quantum transport can be modulated by tuning the Fermi level using a gate voltage, enabling a deeper understanding of the rich physics residing in Dirac semimetals.

Mensenchymal stem cells can delay radiation-induced crypt death: impact on intestinal CD44(+) fragments.

Intestinal stem cells are primitive cells found within the intestinal epithelium that play a central role in maintaining epithelial homeostasis through self-renewal and commitment into functional epithelial cells. Several markers are available to identify intestinal stem cells, such as Lgr5, CD24 and EphB2, which can be used to sort intestinal stem cells from mammalian gut. Here, we identify and isolate intestinal stem cells from C57BL/6 mice by using a cell surface antigen, CD44. In vitro, some CD44(+) crypt cells are capable of forming "villus-crypt"-like structures (organoids). A subset strongly positive for CD44 expresses high levels of intestinal stem-cell-related genes, including Lgr5, Bmi1, Hopx, Lrig1, Ascl2, Smoc2 and Rnf43. Cells from this subset are more capable of developing into organoids in vitro, compared with the subset weakly positive for CD44. However, the organoids are sensitive to ionizing irradiation. We investigate the specific roles of mesenchymal stem cells in protecting organoids against radiation-induced crypt death. When co-cultured with mesenchymal stem cells, the crypt domains of irradiated organoids possess more proliferative cells and fewer apoptotic cells than those not co-cultured with mesenchymal stem cells. Cd44v6 continues to be expressed in the crypt domains of irradiated organoids co-cultured with mesenchymal stem cells. Our results indicate specific roles of mesenchymal stem cells in delaying radiation-induced crypt death in vitro.

Giant negative magnetoresistance induced by the chiral anomaly in individual Cd3As2 nanowires.

Dirac electronic materials beyond graphene and topological insulators have recently attracted considerable attention. Cd3As2 is a Dirac semimetal with linear dispersion along all three momentum directions and can be viewed as a three-dimensional analogue of graphene. By breaking of either time-reversal symmetry or spatial inversion symmetry, the Dirac semimetal is believed to transform into a Weyl semimetal with an exotic chiral anomaly effect, however the experimental evidence of the chiral anomaly is still missing in Cd3As2. Here we show a large negative magnetoresistance with magnitude of -63% at 60 K and -11% at 300 K in individual Cd3As2 nanowires. The negative magnetoresistance can be modulated by gate voltage and temperature through tuning the density of chiral states at the Fermi level and the inter-valley scatterings between Weyl nodes. The results give evidence of the chiral anomaly effect and are valuable for understanding the Weyl fermions in Dirac semimetals.

DNA methylation signatures of long intergenic noncoding RNAs in porcine adipose and muscle tissues.

Long intergenic noncoding RNAs (lincRNAs) are one of the major unexplored components of genomes. Here we re-analyzed a published methylated DNA immunoprecipitation sequencing (MeDIP-seq) dataset to characterize the DNA methylation pattern of pig lincRNA genes in adipose and muscle tissues. Our study showed that the methylation level of lincRNA genes was higher than that of mRNA genes, with similar trends observed in comparisons of the promoter, exon or intron regions. Different methylation pattern were observed across the transcription start sites (TSS) of lincRNA and protein-coding genes. Furthermore, an overlap was observed between many lincRNA genes and differentially methylated regions (DMRs) identified among different breeds of pigs, which show different fat contents, sexes and anatomic locations of tissues. We identify a lincRNA gene, linc-sscg3623, that displayed differential methylation levels in backfat between Min and Large White pigs at 60 and 120 days of age. We found that a demethylation process occurred between days 150 and 180 in the Min and Large White pigs, which was followed by remethylation between days 180 and 210. These results contribute to our understanding of the domestication of domestic animals and identify lincRNA genes involved in adipogenesis and muscle development.

Zeeman effect on surface electron transport in topological insulator Bi2Se3 nanoribbons.

Topological insulators have exotic surface states that are massless Dirac fermions, manifesting special magnetotransport properties, such as the Aharonov-Bohm effect, Shubnikov-de Haas oscillations, and weak antilocalization effects. In the surface Dirac cone, the band structures are typically closely related to the p-orbitals and possess helical orbital texture. Here we report on the tunability of the transport properties via the interaction between the magnetic field and the spin-orbital angular momentum of the surface states in individual Bi2Se3 nanoribbons. Because the surface states have a large Landé factor and helical spin-orbital texture, the in-plane magnetic field induced Zeeman energy will result in the deformation of the Dirac cone, which gives rise to spin polarization of the surface states. The spin-dependent scattering of the conducting electrons on the existing local magnetic moments produces a giant negative magnetoresistance. The negative magnetoresistance is robust with a ratio of -20% at 2 K and -0.5% at 300 K under 14 T. The results are valuable for possible orbital-electronics based on topological insulators.

A genome-wide association study of limb bone length using a Large White × Minzhu intercross population.

BACKGROUND: In pig, limb bone length influences ham yield and body height to a great extent and has important economic implications for pig industry. In this study, an intercross population was constructed between the indigenous Chinese Minzhu pig breed and the western commercial Large White pig breed to examine the genetic basis for variation in limb bone length. The aim of this study was to detect potential genetic variants associated with porcine limb bone length. METHODS: A total of 571 F2 individuals from a Large White and Minzhu intercross population were genotyped using the Illumina PorcineSNP60K Beadchip, and phenotyped for femur length (FL), humerus length (HL), hipbone length (HIPL), scapula length (SL), tibia length (TL), and ulna length (UL). A genome-wide association study was performed by applying the previously reported approach of genome-wide rapid association using mixed model and regression. Statistical significance of the associations was based on Bonferroni-corrected P-values. RESULTS: A total of 39 significant SNPs were mapped to a 11.93 Mb long region on pig chromosome 7 (SSC7). Linkage analysis of these significant SNPs revealed three haplotype blocks of 495 kb, 376 kb and 492 kb, respectively, in the 11.93 Mb region. Annotation based on the pig reference genome identified 15 genes that were located near or contained the significant SNPs in these linkage disequilibrium intervals. Conditioned analysis revealed that four SNPs, one on SSC2 and three on SSC4, showed significant associations with SL and HL, respectively. CONCLUSIONS: Analysis of the 15 annotated genes that were identified in these three haplotype blocks indicated that HMGA1 and PPARD, which are expressed in limbs and influence chondrocyte cell growth and differentiation, could be considered as relevant biological candidates for limb bone length in pig, with potential applications in breeding programs. Our results may also be useful for the study of the mechanisms that underlie human limb length and body height.

Genome-wide SNP scan in a porcine Large White×Minzhu intercross population reveals a locus influencing muscle mass on chromosome 2.

A high-density single nucleotide polymorphism (SNP) array containing 62 163 markers was employed for a genome-wide association study (GWAS) to identify variants associated with lean meat in ham (LMH, %) and lean meat percentage (LMP, %) within a porcine Large White×Minzhu intercross population. For each individual, LMH and LMP were measured after slaughter at the age of 240±7 days. A total of 557 F2 animals were genotyped. The GWAS revealed that 21 SNPs showed significant genome-wide or chromosome-wide associations with LMH and LMP by the Genome-wide Rapid Association using Mixed Model and Regression-Genomic Control approach. Nineteen significant genome-wide SNPs were mapped to the distal end of Sus Scrofa Chromosome (SSC) 2, where a major known gene responsible for muscle mass, IGF2 is located. A conditioned analysis, in which the genotype of the strongest associated SNP is included as a fixed effect in the model, showed that those significant SNPs on SSC2 were derived from a single quantitative trait locus. The two chromosome-wide association SNPs on SSC1 disappeared after conditioned analysis suggested the association signal is a false association derived from using a F2 population. The present result is expected to lead to novel insights into muscle mass in different pig breeds and lays a preliminary foundation for follow-up studies for identification of causal mutations for subsequent application in marker-assisted selection programs for improving muscle mass in pigs.

Photonic generation of arbitrarily phase-modulated microwave signals based on a single DDMZM.

We propose and demonstrate a compact and cost-effective photonic approach to generate arbitrarily phase-modulated microwave signals using a conventional dual-drive Mach-Zehnder modulator (DDMZM). One arm (arm1) of the DDMZM is driven by a sinusoidal microwave signal whose power is optimized to suppress the optical carrier, while the other arm (arm2) of the DDMZM is driven by a coding signal. In this way, the phase-modulated optical carrier from the arm2 and the sidebands from the arm1 are combined together at the output of the DDMZM. Binary phase-coded microwave pulses which are free from the baseband frequency components can be generated when the coding signal is a three-level signal. In this case, the precise π phase shift of the microwave signal is independent of the amplitude of the coding signal. Moreover, arbitrarily phase-modulated microwave signals can be generated when an optical bandpass filter is attached after the DDMZM to achieve optical single-sideband modulation. The proposed approach is theoretically analyzed and experimentally verified. The binary phase-coded microwave pulses, quaternary phase-coded microwave signal, and linearly frequency-chirped microwave signal are experimentally generated. The simulated and the experimental results agree very well with each other.

Photonic generation of background-free millimeter-wave ultra-wideband pulses based on a single dual-drive Mach-Zehnder modulator.

We propose a novel photonic approach for generating a background-free millimeter-wave (MMW) ultra-wideband (UWB) signal based on a conventional dual-drive Mach-Zehnder modulator (DMZM). One arm of the DMZM is driven by a local oscillator (LO) signal. The LO power is optimized to realize optical carrier suppressed modulation. The other arm is fed by a rectangular signal. The MMW UWB pulses are generated by truncating the continuous wave LO signal into a pulsed one in a photodetector (PD). The generated MMW UWB signal is background-free by eliminating the baseband frequency components because the optical power launched to the PD keeps constant all the time. The proposed method is theoretically analyzed and experimentally verified. The generated MMW UWB signal centered at a frequency of 26 GHz meets the Federal Communications Commission spectral mask very well.

Photonic-assisted microwave phase shifter using a DMZM and an optical bandpass filter.

We propose and demonstrate a photonic-assisted wideband 360° microwave phase shifter based on a conventional dual-drive Mach-Zehnder modulator (DMZM) and an optical bandpass filter (OBPF). The two arms of the DMZM are driven by the fundamental microwave signal to be phase shifted and its frequency doubled component, respectively. The OBPF followed after the DMZM is used to remove the optical carrier and the sidebands at either side of the optical carrier. As a result, only two sidebands corresponding to the fundamental microwave signal and its frequency doubled component, respectively, are left. Moreover, the phase shift between the two sidebands can be continuously tunable by adjusting the bias voltage of the DMZM. This phase shift is mapped to the fundamental microwave signal which is recovered by beating the two sidebands in a photodetector (PD). The proposed approach is theoretically analyzed and experimentally verified.

High-mobility Bi2Se3 nanoplates manifesting quantum oscillations of surface states in the sidewalls.

Magnetotransport measurements of topological insulators are very important to reveal the exotic topological surface states for spintronic applications. However, the novel properties related to the surface Dirac fermions are usually accompanied by a large linear magnetoresistance under perpendicular magnetic field, which makes the identification of the surface states obscure. Here, we report prominent Shubnikov-de Haas (SdH) oscillations under an in-plane magnetic field, which are identified to originate from the surface states in the sidewalls of topological insulator Bi2Se3 nanoplates. Importantly, the SdH oscillations appear with a dramatically weakened magnetoresistance background, offering an easy path to probe the surface states directly when the coexistence of surface states and bulk conduction is inevitable. Moreover, under a perpendicular magnetic field, the oscillations in Hall conductivity have peak-to-valley amplitudes of 2 e(2)/h, giving confidence to achieve a quantum Hall effect in this system. A cross-section view of the nanoplate shows that the sidewall is (015) facet dominant and therefore forms a 58° angle with regard to the top/bottom surface instead of being perpendicular; this gives credit to the surface states' behavior as two-dimensional transport.

Widely tunable single-bandpass microwave photonic filter based on polarization processing of a nonsliced broadband optical source.

We propose a new scheme of microwave photonic filter (MPF) based on the polarization processing of a broadband optical source (BOS), which features single-bandpass response and a wide span of operation bandwidth. The BOS is orthogonally polarized by a polarization division multiplexing emulator (PDME) with a tunable time delay between the two polarization states and incident at ± 45° to one principle axis of a polarization modulator (PolM). The PDME cascades a PolM, and a polarizer realizes a microwave modulation making the phase of the carrier able to be tuned while ± 1st sidebands remain unchanged, which after propagating in a dispersive medium results in a tunable single-bandpass response in the RF domain. We experimentally verify the MPF. By adjusting the time delay and the optical spectrum bandwidth, the passband center frequency is continuously tuned from DC to 20 GHz and the 3 dB passband bandwidth changes while the optical spectrum bandwidth ranges from 1 to 4 nm.

LC3B-II deacetylation by histone deacetylase 6 is involved in serum-starvation-induced autophagic degradation.

Autophagy is a conserved mechanism for controlling the degradation of misfolded proteins and damaged organelles in eukaryotes and can be induced by nutrient withdrawal, including serum starvation. Although differential acetylation of autophagy-related proteins has been reported to be involved in autophagic flux, the regulation of acetylated microtubule-associated protein 1 light chain 3 (LC3) is incompletely understood. In this study, we found that the acetylation levels of phosphotidylethanolamine (PE)-conjugated LC3B (LC3B-II), which is a critical component of double-membrane autophagosome, were profoundly decreased in HeLa cells upon autophagy induction by serum starvation. Pretreatment with lysosomal inhibitor chloroquine did not attenuate such deacetylation. Under normal culture medium, we observed increased levels of acetylated LC3B-II in cells treated with tubacin, a specific inhibitor of histone deacetylase 6 (HDAC6). However, tubacin only partially suppressed serum-starvation-induced LC3B-II deacetylation, suggesting that HDAC6 is not the only deacetylase acting on LC3B-II during serum-starvation-induced autophagy. Interestingly, tubacin-induced increase in LC3B-II acetylation was associated with p62/SQSTM1 accumulation upon serum starvation. HDAC6 knockdown did not influence autophagosome formation but resulted in impaired degradation of p62/SQSTM1 during serum starvation. Collectively, our data indicated that LC3B-II deacetylation, which was partly mediated by HDAC6, is involved in autophagic degradation during serum starvation.