The antiferromagnetic (AFM) compound MnBi2Te4 is suggested to be the first realization of an AFM topological insulator. We report on inelastic neutron scattering studies of the magnetic interactions ...in MnBi2Te4 that possess ferromagnetic triangular layers with AFM interlayer coupling. The spin waves display a large spin gap and pairwise exchange interactions within the triangular layer are long ranged and frustrated by large next-nearest neighbor AFM exchange. The degree of frustration suggests proximity to a variety of magnetic phases, potentially including skyrmion phases, which could be accessed in chemically tuned compounds or upon the application of symmetry-breaking fields.
Noncoding RNA molecules (ncRNAs) have been implicated in numerous biological processes including transcriptional regulation and the modulation of protein function. Yet, in spite of the apparent ...abundance of ncRNA, little is known about the biological role of the projected thousands of ncRNA genes present in the human genome. To facilitate functional analysis of these RNAs, we have created an arrayed library of short hairpin RNAs (shRNAs) directed against 512 evolutionarily conserved putative ncRNAs and, via cell-based assays, we have begun to determine their roles in cellular pathways. Using this system, we have identified an ncRNA repressor of the nuclear factor of activated T cells (NFAT), which interacts with multiple proteins including members of the importin-beta superfamily and likely functions as a specific regulator of NFAT nuclear trafficking.
Magnetic kagome metals are a promising platform to develop unique quantum transport and optical phenomena caused by the interplay between topological electronic bands, strong correlations, and ...magnetic order. This interplay may result in exotic quasiparticles that describe the coupled electronic and spin excitations on the frustrated kagome lattice. Here, we observe novel elementary magnetic excitations within the ferromagnetic Mn kagome layers in TbMn
Sn
using inelastic neutron scattering. We observe sharp, collective acoustic magnons and identify flat-band magnons that are localized to a hexagonal plaquette due to the special geometry of the kagome layer. Surprisingly, we observe another type of elementary magnetic excitation; a chiral magnetic quasiparticle that is also localized on a hexagonal plaquette. The short lifetime of localized flat-band and chiral quasiparticles suggest that they are hybrid excitations that decay into electronic states.
Maintenance of a constant cell volume in response to extracellular or intracellular osmotic changes is critical for cellular homeostasis. Activation of a ubiquitous volume-regulated anion channel ...(VRAC) plays a key role in this process; however, its molecular identity in vertebrates remains unknown. Here, we used a cell-based fluorescence assay and performed a genome-wide RNAi screen to find components of VRAC. We identified SWELL1 (LRRC8A), a member of a four-transmembrane protein family with unknown function, as essential for hypotonicity-induced iodide influx. SWELL1 is localized to the plasma membrane, and its knockdown dramatically reduces endogenous VRAC currents and regulatory cell volume decrease in various cell types. Furthermore, point mutations in SWELL1 cause a significant change in VRAC anion selectivity, demonstrating that SWELL1 is an essential VRAC component. These findings enable further molecular characterization of the VRAC channel complex and genetic studies for understanding the function of VRAC in normal physiology and disease.
A hallmark of the phase diagrams of quantum materials is the existence of multiple electronic ordered states, which, in many cases, are not independent competing phases, but instead display a complex ...intertwinement. In this review, we focus on a particular realization of intertwined orders: a primary phase characterized by a multi-component order parameter and a fluctuation-driven vestigial phase characterized by a composite order parameter. This concept has been widely employed to elucidate nematicity in iron-based and cuprate superconductors. Here we present a group-theoretical framework that extends this notion to a variety of phases, providing a classification of vestigial orders of unconventional superconductors and density waves. Electronic states with scalar and vector chiral order, spin-nematic order, Ising-nematic order, time-reversal symmetry-breaking order, and algebraic vestigial order emerge from one underlying principle. The formalism provides a framework to understand the complexity of quantum materials based on symmetry, largely without resorting to microscopic models.
Abstract
Knowledge of magnetic symmetry is vital for exploiting nontrivial surface states of magnetic topological materials. EuIn
2
As
2
is an excellent example, as it is predicted to have collinear ...antiferromagnetic order where the magnetic moment direction determines either a topological-crystalline-insulator phase supporting axion electrodynamics or a higher-order-topological-insulator phase with chiral hinge states. Here, we use neutron diffraction, symmetry analysis, and density functional theory results to demonstrate that EuIn
2
As
2
actually exhibits low-symmetry helical antiferromagnetic order which makes it a stoichiometric magnetic topological-crystalline axion insulator protected by the combination of a 180
∘
rotation and time-reversal symmetries:
$${C}_{2}\times {\mathcal{T}}={2}^{\prime}$$
C
2
×
T
=
2
′
. Surfaces protected by
$${2}^{\prime}$$
2
′
are expected to have an exotic gapless Dirac cone which is unpinned to specific crystal momenta. All other surfaces have gapped Dirac cones and exhibit half-integer quantum anomalous Hall conductivity. We predict that the direction of a modest applied magnetic field of
μ
0
H
≈ 1 to 2 T can tune between gapless and gapped surface states.
Metastases are the leading cause of mortality in patients with cancer. Metastasis formation requires cancer cells to adapt their cellular phenotype. However, how metabolism supports this adaptation ...of cancer cells is poorly defined. We use 2D versus 3D cultivation to induce a shift in the cellular phenotype of breast cancer cells. We discover that proline catabolism via proline dehydrogenase (Prodh) supports growth of breast cancer cells in 3D culture. Subsequently, we link proline catabolism to in vivo metastasis formation. In particular, we find that PRODH expression and proline catabolism is increased in metastases compared to primary breast cancers of patients and mice. Moreover, inhibiting Prodh is sufficient to impair formation of lung metastases in the orthotopic 4T1 and EMT6.5 mouse models, without adverse effects on healthy tissue and organ function. In conclusion, we discover that Prodh is a potential drug target for inhibiting metastasis formation.
Purpose To compare clinical outcomes of anterior cruciate ligament (ACL) reconstruction and investigate whether the clinical results of 4-strand hamstring tendon (HT) reconstruction are still ...inferior to that of the patellar tendon (PT). Methods We performed a comprehensive systematic review and meta-analysis of the English literature on PubMed, Scopus, Web of Science, and the Cochrane register for papers that compared clinical outcomes of PT versus HT for ACL reconstruction. Outcome measures analyzed included rate of rerupture, KT-1000, International Knee Documentation Committee grade, Lachman, pivot shift, Lysholm score, Tegner Activity Scale, anterior knee pain, and discomfort on kneeling. Results We included 19 studies from an initial 1,168 abstracts for the systematic review, and, eventually, 19 studies were included in the meta-analysis. The study population consisted of a total of 1784 patients. The average follow-up duration was 58.8 months. We found significant differences in favor of the HT technique in the domains of anterior knee pain, kneeling pain, and restriction in the range of active extension (“extension deficit”). We found no differences between the PT and HT technique in terms of rerupture rate. There were no clinically significant differences for the outcomes of Lysholm score and Tegner Activity Scale as well as the KT-1000 side-to-side at maximum manual force. Conclusions Contemporary 4-strand HT ACL reconstruction is comparable with the PT technique in terms of clinical stability and postoperative functional status across most parameters studied. The HT technique carries lower risk of postoperative complications such as anterior knee pain, kneeling discomfort, and extension deficit. Primary ACL reconstruction using the 4-strand HT technique achieves clinical results that are comparable with the PT technique with significantly less postoperative complications. Level of Evidence Level I, systemic review and meta-analysis of Level I studies.
High-throughput gene expression profiling has become an important tool for investigating transcriptional activity in a variety of biological samples. To date, the vast majority of these experiments ...have focused on specific biological processes and perturbations. Here, we have generated and analyzed gene expression from a set of samples spanning a broad range of biological conditions. Specifically, we profiled gene expression from 91 human and mouse samples across a diverse array of tissues, organs, and cell lines. Because these samples predominantly come from the normal physiological state in the human and mouse, this dataset represents a preliminary, but substantial, description of the normal mammalian transcriptome. We have used this dataset to illustrate methods of mining these data, and to reveal insights into molecular and physiological gene function, mechanisms of transcriptional regulation, disease etiology, and comparative genomics. Finally, to allow the scientific community to use this resource, we have built a free and publicly accessible website (http://expression.gnf.org) that integrates data visualization and curation of current gene annotations.
A high-throughput RNA interference (RNAi) screen targeting 542 genes of the human kinome was used to discover regulators of RNAi. Here we report that the proto-oncogene Akt-3/PKBγ (Akt3) ...phosphorylates Argonaute 2 (Ago2) at S387, which downregulates cleavage and upregulates translational repression of endogenous microRNA (miRNA)-targeted messenger RNAs (mRNAs). We further demonstrate that Akt3 coimmunoprecipitates with Ago2 and phosphorylation of Ago2 at S387 facilitates its interaction with GW182 and localization to cytoplasmic processing bodies (P bodies), where miRNA-targeted mRNAs are thought to be stored and degraded. Therefore, Akt3-mediated phosphorylation of Ago2 is a molecular switch between target mRNA cleavage and translational repression activities of Ago2.
► Akt3 interacts with and phosphorylates Ago2 at S387 ► Phosphorylation of Ago2 increases translational repression of pten and pdcd4 ► Phosphorylation of Ago2 decreases mRNA cleavage of the hoxb8 oncogene ► Akt3-mediated phosphorylation of Ago2 is an RNAi molecular switch
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