Chemical approach to generating long-term self-renewing pMN progenitors from human embryonic stem cells

Spinal cord impairment involving motor neuron degeneration and demyelination can cause life-long disabilities, but effective clinical interventions for restoring neurological functions have yet been developed. In early spinal cord development, neural progenitors in the pMN (‘progenitors of motor neurons’) domain, defined by the expression of oligodendrocyte transcription factor 2 (OLIG2), in ventral spinal cord first generate motor neurons and then switch the fate to produce myelin-forming oligodendrocytes. Given their differentiation potential, pMN progenitors could be a valuable cell source for cell therapy in relevant neurological conditions such as spinal cord injury. However, fast generation and expansion of pMN progenitors in vitro while conserving their differentiation potential has so far been technically challenging. In this study, based on the chemical screening, we have developed a new recipe for efficient induction of pMN progenitors from human embryonic stem cells. More importantly, these OLIG2+ pMN progenitors can be stably maintained for multiple passages without losing their ability to produce spinal motor neurons and oligodendrocytes rapidly. Our results suggest that these self-renewing pMN progenitors could potentially be useful as a renewable source of cell transplants for spinal cord injury and demyelinating disorders

Topological Electronic Structure and Its Temperature Evolution in Antiferromagnetic Topological Insulator MnBi2Te4

Topological quantum materials coupled with magnetism can provide a platform for realizing rich exotic physical phenomena, including quantum anomalous Hall effect, axion electrodynamics and Majorana fermions. However, these unusual effects typically require extreme experimental conditions such as ultralow temperature or sophisticate material growth and fabrication. Recently, new intrinsic magnetic topological insulators were proposed in MnBi2Te4-family compounds - on which rich topological effects could be realized under much relaxed experimental conditions. However, despite the exciting progresses, the detailed electronic structures observed in this family of compounds remain controversial up to date. Here, combining the use of synchrotron and laser light sources, we carried out comprehensive and high resolution angle-resolved photoemission spectroscopy studies on MnBi2Te4, and clearly identified its topological electronic structures including the characteristic gapless topological surface states. In addition, the temperature evolution of the energy bands clearly reveals their interplay with the magnetic phase transition by showing interesting differences for the bulk and surface states, respectively. The identification of the detailed electronic structures of MnBi2Te4 will not only help understand its exotic properties, but also pave the way for the design and realization of novel phenomena and applications.Comment: 18 pages, 4 figur

The histone H3K9 methyltransferase SUV39H links SIRT1 repression to myocardial infarction

Myocardial infarction (MI) dampens heart function and poses a great health risk. The class III deacetylase sirtuin 1 (SIRT1) is known to confer cardioprotection. SIRT1 expression is downregulated in the heart by a number of stress stimuli that collectively drive the pathogenesis of MI, although the underlying mechanism remains largely obscure. Here we show that in primary rat neonatal ventricular myocytes (NRVMs), ischaemic or oxidative stress leads to a rapid upregulation of SUV39H, the mammalian histone H3K9 methyltransferase, paralleling SIRT1 downregulation. Compared to wild-type littermates, SUV39H knockout mice are protected from MI. Likewise, suppression of SUV39H activity with chaetocin attenuates cardiac injury following MI. Mechanistically, SUV39H cooperates with heterochromatin protein 1 gamma (HP1γ) to catalyse H3K9 trimethylation on the SIRT1 promoter and represses SIRT1 transcription. SUV39H augments intracellular ROS levels in a SIRT1-dependent manner. Our data identify a previously unrecognized role for SUV39H linking SIRT1 trans-repression to myocardial infarction

Identification of an intraocular microbiota

The current dogma in ophthalmology and vision research presumes the intraocular environment to be sterile. However, recent evidence of intestinal bacterial translocation into the bloodstream and many other internal organs including the eyes, found in healthy and diseased animal models, suggests that the intraocular cavity may also be inhabited by a microbial community. Here, we tested intraocular samples from over 1000 human eyes. Using quantitative PCR, negative staining transmission electron microscopy, direct culture, and high-throughput sequencing technologies, we demonstrated the presence of intraocular bacteria. The possibility that the microbiome from these low-biomass communities could be a contamination from other tissues and reagents was carefully evaluated and excluded. We also provide preliminary evidence that a disease-specific microbial signature characterized the intraocular environment of patients with age-related macular degeneration and glaucoma, suggesting that either spontaneous or pathogenic bacterial translocation may be associated with these common sight-threatening conditions. Furthermore, we revealed the presence of an intraocular microbiome in normal eyes from non-human mammals and demonstrated that this varied across species (rat, rabbit, pig, and macaque) and was established after birth. These findings represent the first-ever evidence of intraocular microbiota in humans

Measurement of the branching fractions of psi(2S) -> 3(pi+pi-) and J/psi -> 2(pi+pi-)

Using data samples collected at sqrt(s) = 3.686GeV and 3.650GeV by the BESII detector at the BEPC, the branching fraction of psi(2S) -> 3(pi+pi-) is measured to be [4.83 +- 0.38(stat) +- 0.69(syst)] x 10^-4, and the relative branching fraction of J/psi -> 2(pi+pi-) to that of J/psi -> mu+mu- is measured to be [5.86 +- 0.19(stat) +- 0.39(syst)]% via psi(2S) -> (pi+pi-)J/psi, J/psi -> 2(pi+pi-). The electromagnetic form factor of 3(pi+pi-) is determined to be 0.21 +- 0.02 and 0.20 +- 0.01 at sqrt(s) = 3.686GeV and 3.650GeV, respectively.Comment: 17pages, 7 figures, submitted to Phys. Rev.

A Unified Approach to the Classical Statistical Analysis of Small Signals

We give a classical confidence belt construction which unifies the treatment of upper confidence limits for null results and two-sided confidence intervals for non-null results. The unified treatment solves a problem (apparently not previously recognized) that the choice of upper limit or two-sided intervals leads to intervals which are not confidence intervals if the choice is based on the data. We apply the construction to two related problems which have recently been a battle-ground between classical and Bayesian statistics: Poisson processes with background, and Gaussian errors with a bounded physical region. In contrast with the usual classical construction for upper limits, our construction avoids unphysical confidence intervals. In contrast with some popular Bayesian intervals, our intervals eliminate conservatism (frequentist coverage greater than the stated confidence) in the Gaussian case and reduce it to a level dictated by discreteness in the Poisson case. We generalize the method in order to apply it to analysis of experiments searching for neutrino oscillations. We show that this technique both gives correct coverage and is powerful, while other classical techniques that have been used by neutrino oscillation search experiments fail one or both of these criteria.Comment: 40 pages, 15 figures. Changes 15-Dec-99 to agree more closely with published version. A few small changes, plus the two substantive changes we made in proof back in 1998: 1) The definition of "sensitivity" in Sec. V(C). It was inconsistent with our actual definition in Sec. VI. 2) "Note added in proof" at end of the Conclusio