Magnetic and defect probes of the SmB6_6 surface state

The impact of non-magnetic and magnetic impurities on topological insulators is a central problem concerning their fundamental physics and possible novel spintronics and quantum computing applications. SmB$_6$, predicted to be a topological Kondo insulator, is considered a benchmark material. Using a spin-polarized tip in scanning tunneling spectroscopy destroys the signature peak of the topological surface state, revealing its spin texture. Further, combining local STS with macroscopic transport measurements on SmB$_6$ containing different substitutions enables us to investigate the effect of impurities. The surface states around impurities are locally suppressed with different length scales depending on their magnetic properties and, for sufficiently high impurity level, globally destroyed. Our study points directly to the topological nature of SmB$_6$, and unveils, microscopically and macroscopically, how impurities -- magnetic or non-magnetic -- affect topological surface states

Acetylation-induced TDP-43 pathology is suppressed by an HSF1-dependent chaperone program

TDP-43 pathology marks a spectrum of multisystem proteinopathies including amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and sporadic inclusion body myositis. Surprisingly, it has been challenging to recapitulate this pathology, highlighting an incomplete understanding of TDP-43 regulatory mechanisms. Here we provide evidence supporting TDP-43 acetylation as a trigger for disease pathology. Using cultured cells and mouse skeletal muscle, we show that TDP-43 acetylation-mimics promote TDP-43 phosphorylation and ubiquitination, perturb mitochondria, and initiate degenerative inflammatory responses that resemble sporadic inclusion body myositis pathology. Analysis of functionally linked amyotrophic lateral sclerosis proteins revealed recruitment of p62, ubiquilin-2, and optineurin to TDP-43 aggregates. We demonstrate that TDP-43 acetylation-mimic pathology is potently suppressed by an HSF1-dependent mechanism that disaggregates TDP-43. Our study illustrates bidirectional TDP-43 processing in which TDP-43 aggregation is targeted by a coordinated chaperone response. Thus, activation or restoration of refolding mechanisms may alleviate TDP-43 aggregation in tissues that are uniquely susceptible to TDP-43 proteinopathies.TDP-43 aggregation is linked to various diseases including amyotrophic lateral sclerosis. Here the authors show that acetylation of the protein triggers TDP-43 pathology in cultured cells and mouse skeletal muscle, which can be cleared through an HSF1-dependent chaperone mechanism that disaggregates the protein

Intrinsic Tau Acetylation Is Coupled to Auto-Proteolytic Tau Fragmentation

Tau proteins are abnormally aggregated in a range of neurodegenerative tauopathies including Alzheimer’s disease (AD). Recently, tau has emerged as an extensively post-translationally modified protein, among which lysine acetylation is critical for normal tau function and its pathological aggregation. Here, we demonstrate that tau isoforms have different propensities to undergo lysine acetylation, with auto-acetylation occurring more prominently within the lysine-rich microtubule-binding repeats. Unexpectedly, we identified a unique intrinsic property of tau in which auto-acetylation induces proteolytic tau cleavage, thereby generating distinct N- and C-terminal tau fragments. Supporting a catalytic reaction-based mechanism, mapping and mutagenesis studies showed that tau cysteines, which are required for acetyl group transfer, are also essential for auto-proteolytic tau processing. Further mass spectrometry analysis identified the C-terminal 2nd and 4th microtubule binding repeats as potential sites of auto-cleavage. The identification of acetylation-mediated auto-proteolysis provides a new biochemical mechanism for tau self-regulation and warrants further investigation into whether auto-catalytic functions of tau are implicated in AD and other tauopathies

Diaqua­bis(9-oxo-4,5-diaza­fluoren-3-olato-κ2 N 4,O 3)cadmium(II)

The title compound, [Cd(C11H5N2O2)2(H2O)2], is a mononuclear complex consisting of a CdII atom, two 3-hydr­oxy-4,5-diaza­fluoren-9-one ligands and two coordinated water mol­ecules. The CdII atom, lying on a twofold axis, displays a distorted octa­hedral coordintion. Adjacent mol­ecules are linked by O—H⋯O hydrogen bonds and π–π inter­actions [centroid–centroid distance = 3.84 (1) Å], leading to a one-dimensional chain. Weak C—H⋯O hydrogen bonds connect the chains into a two-dimensional supra­molecular structure

A Dual Pathogenic Mechanism Links Tau Acetylation to Sporadic Tauopathy

Tau acetylation has recently emerged as a dominant post-translational modification (PTM) in Alzheimer’s disease (AD) and related tauopathies. Mass spectrometry studies indicate that tau acetylation sites cluster within the microtubule (MT)-binding region (MTBR), suggesting acetylation could regulate both normal and pathological tau functions. Here, we combined biochemical and cell-based approaches to uncover a dual pathogenic mechanism mediated by tau acetylation. We show that acetylation specifically at residues K280/K281 impairs tau-mediated MT stabilization, and enhances the formation of fibrillar tau aggregates, highlighting both loss and gain of tau function. Full-length acetylation-mimic tau showed increased propensity to undergo seed-dependent aggregation, revealing a potential role for tau acetylation in the propagation of tau pathology. We also demonstrate that methylene blue, a reported tau aggregation inhibitor, modulates tau acetylation, a novel mechanism of action for this class of compounds. Our study identifies a potential “two-hit” mechanism in which tau acetylation disengages tau from MTs and also promotes tau aggregation. Thus, therapeutic approaches to limit tau K280/K281 acetylation could simultaneously restore MT stability and ameliorate tau pathology in AD and related tauopathies

A data analysis method for isochronous mass spectrometry using two time-of-flight detectors at CSRe

The concept of isochronous mass spectrometry (IMS) applying two time-of-flight (TOF) detectors originated many years ago at GSI. However, the corresponding method for data analysis has never been discussed in detail. Recently, two TOF detectors have been installed at CSRe and the new working mode of the ring is under test. In this paper, a data analysis method for this mode is introduced and tested with a series of simulations. The results show that the new IMS method can significantly improve mass resolving power via the additional velocity information of stored ions. This improvement is especially important for nuclides with Lorentz factor $\gamma$-value far away from the transition point $\gamma _t$ of the storage ring CSRe.Comment: published in Chinese Physics C Vol. 39, No. 10 (2015) 10620

A Redescription of the Ichnospecies Koreanaornis Anhuiensis (Aves) from the Lower Cretaceous Qiuzhuang Formation at Mingguang City, Anhui Province, China

The Cretaceous bird trackway originally labeled Aquatilavipes anhuiensis, in 1994, had previously been examined, photographed and replicated, but never described or illustrated in detail. However, it has been part of a widening discussion about the distribution of Aquatilavipes and Koreanaornis in China (and Korea). Here we illustrate and formally describe the holotype in detail and assign it to Koreanaornis (Koreanaornis anhuiensis) as informally proposed by previous authors. We also demonstrate that most authenticated reports of Koreanaornis, including the Anhui occurrence, are from the Lower Cretaceous, not from the Upper Cretaceous as previously reported