Mutations in the proline-rich transmembrane protein 2 (PRRT2) are associated with paroxysmal kinesigenic dyskinesia (PKD) and several other paroxysmal neurological diseases, but the PRRT2 function and pathogenic mechanisms remain largely obscure. Here we show that PRRT2 is a presynaptic protein that interacts with components of the SNARE complex and downregulates its formation. Loss-of-function mutant mice showed PKD-like phenotypes triggered by generalized seizures, hyperthermia, or optogenetic stimulation of the cerebellum. Mutant mice with specific PRRT2 deletion in cerebellar granule cells (GCs) recapitulate the behavioral phenotypes seen in Prrt2-null mice. Furthermore, recording made in cerebellar slices showed that optogenetic stimulation of GCs results in transient elevation followed by suppression of Purkinje cell firing. The anticonvulsant drug carbamazepine used in PKD treatment also relieved PKD-like behaviors in mutant mice. Together, our findings identify PRRT2 as a novel regulator of the SNARE complex and provide a circuit mechanism underlying the PRRT2-related behaviors.

FOXP3+ Regulatory T (Treg) cells play a key role in the maintenance of immune homeostasis and tolerance. Disruption of Foxp3 expression results in the generation of instable Treg cells and acquisition of effector T-cell-like function. Here we report that the E3 deubiquitinase USP21 prevents the depletion of FOXP3 at the protein level and restricts the generation of T-helper-1-like Treg cells. Mice depleted of Usp21 specifically in Treg cells display immune disorders characterized by spontaneous T-cell activation and excessive T-helper type 1 (Th1) skewing of Treg cells into Th1-like Treg cells. USP21 stabilizes FOXP3 protein by mediating its deubiquitination and maintains the expression of Treg signature genes. Our results demonstrate how USP21 prevents FOXP3 protein depletion and controls Treg lineage stability in vivo.

Selective hydrogenation of 5-hydroxymethylfurfural (HMF) has potential application in high quality biofuels.Herein, the catalytic hydrodeoxygenation (HDO) of HMF to 2,5-dimethylfuran (DMF) was investigated using bi-functional Ru-MoO x /C catalyst prepared by initial wetness impregnation. The high dispersion and electronic transfer between Ru and MoO x were demonstrated by a series of characterization techniques.During this HDO process, the synergy effect between metallic Ru and acidic MoO x species in the RuMoO x /C catalyst plays an essential role in obtaining maximized target product DMF (79.4%) via effective aldehyde group hydrogenation by Ru followed by dehydration over MoO x . This work also elucidated that DMF production proceeded through two distinct pathways: the 2,5-hydroxymethyl furan intermediate was preferable by the aldehyde group hydrogenation of HMF over the Ru-MoO x /C catalyst. Over MoO x / C catalyst, comparatively, 5-methyl furfural was the key intermediate by direct hydrogenolysis of the hydroxyl group in HMF. This kind of catalyst is stable for the first two runs by maintaining the target product yield. After the third run, the catalyst showed deactivation gradually but could be almost completely recovered after regeneration by H 2 reduction.

Here we present a facile one-pot method to prepare high-quality CdTe nanocrystals in aqueous phase. In contrast to the use of oxygen-sensitive NaHTe or H2Te as Te source in the current synthetic methods, we employ more stable sodium tellurite as the Te source for preparing highly luminescent CdTe nanocrystals in aqueous solution. By selecting mercaptosuccinic acid (MSA) as capping agent and providing the borate-citrate acid buffering solution, CdTe nanocrystals with high quantum yield (QY >70% at pH range 5.0–8.0) can be conveniently prepared by this method. The influence of parameters such as the pH value of the precursor solution and the molar ratio of Cd2+ to Na2TeO3 on the QY of CdTe nanocrystals was systematically investigated in our experiments. Under optimal conditions, the QY of CdTe nanocrystals is even high up to 83%. The biological application of luminescent MSA-CdTe to HEK 293 cell imaging was also illustrated.

The new melokhanines A-J (1-10) and 22 known (11-32) alkaloids were isolated from the twigs and leaves of Melodinus khasianus. The new compounds and their absolute configurations were elucidated by extensive analysis of spectroscopic, X-ray diffraction, and computational data. Melokhanine A (1), composed of a hydroxyindolinone linked to an octahydrofuro[2,3-b]pyridine moiety, is an unprecedented monoterpenoid indole alkaloid. Melokhanines B-H (2-8) possess a new 6/5/5/6/6 pentacyclic indole alkaloid skeleton. Alkaloids 1-16, 25-27, 31, and 32 showed the best antibacterial activity against Pseudomonas aeruginosa (MIC range 2-22 μM). Among the seven dermatophytes tested, compound 1 showed significant inhibitory activity against Microsporum canis, M. ferrugineum, and Trichophyton ajelloi (MIC range 38-150 μM), i.e., half the efficacy of the positive control, griseofulvin.

No abstract

No abstract

No abstract