Leber Hereditary Optic Neuropathy in a Boy with Fibrous Boney Dysplasia

Purpose:To report a case of Leber hereditary optic neuropathy combined with fibrous boney dysplasia. Methods: Case report. Results:A 16-year-old boy presented with painless vision loss in both eyes. He had a history of a right humerus fracture and right femoral fracture surgery after an uncomplicated fall.On examination in our clinic, his visual acuity was counting fingers at 20 cm OD and counting fingers at 40 cm OS.Both pupils reacted sluggishly to light.The findings on slit-lamp examination and funduscopy after pupillary dilation were all unremarkable. Computed tomography scans demonstrated fibrous dysplasia involving the right frontal, temporal, parietal, and occipital bones but no stenosis of either optic canal. His serum alkaline phosphatase was 522 U/L (reference range: 40-150 U/L). His vision showed no improvement after intravenous methylprednisolone pulse therapy.Finally,a 11778 mitochondrial DNA mutation was detected. He still had no visual recovery after treatment with oral coenzyme Q10,vitamin B1, and citicoline. Conclusion:Fibrous dysplasia of bone may be associated with Leber hereditary optic neuropathy,possibly due to the fact that it increases local oxygen consumption. (Eye Science 2013; 28:48-50)

T2T-YAO: A Telomere-to-telomere Assembled Diploid Reference Genome for Han Chinese

Since its initial release in 2001,the human reference genome has undergone continuous improvement in quality,and the recently released telomere-to-telomere(T2T)version-T2T-CHM13—reaches its highest level of continuity and accuracy after 20 years of effort by working on a simplified,nearly homozygous genome of a hydatidiform mole cell line.Here,to provide an authentic complete diploid human genome reference for the Han Chinese,the largest population in the world,we assembled the genome of a male Han Chinese individual,T2T-YAO,which includes T2T assemblies of all the 22+X+M and 22+Y chromosomes in both haploids.The quality of T2T-YAO is much better than those of all currently available diploid assemblies,and its haploid version,T2T-YAO-hp,generated by selecting the better assembly for each autosome,reaches the top quality of fewer than one error per 29.5 Mb,even higher than that of T2T-CHM13.Derived from an individual living in the aboriginal region of the Han population,T2T-YAO shows clear ancestry and potential genetic continuity from the ancient ancestors.Each haplotype of T2TYAO possesses330-Mb exclusive sequences,3100 unique genes,and tens of thousands of nucleotide and structural variations as compared with CHM13,highlighting the necessity of a population-stratified reference genome.The construction of T2T-YAO,an accurate and authentic representative of the Chinese population,would enable precise delineation of genomic variations and advance our understandings in the hereditability of diseases and phenotypes,especially within the context of the unique variations of the Chinese population.

Unraveling the drug distribution in brain enabled by MALDI MS imaging with laser-assisted chemical transfer

Accurate localization of central nervous system(CNS)drug distribution in the brain is quite challenging to matrix-assisted laser desorption/ionization(MALDI)mass spectrometry imaging(MSI),owing to the ionization competition/suppression of highly abundant endogenous biomolecules and MALDI matrix.Herein,we developed a highly efficient sample preparation technique,laser-assisted chemical transfer(LACT),to enhance the detection sensitivity of CNS drugs in brain tissues.A focused diode laser source transilluminated the tissue slide coated with α-cyano-4-hydroxycinnamic acid,an optimal matrix to highly absorb the laser radiation at 405 nm,and a very thin-layer chemical film mainly containing drug molecule was transferred to the acceptor glass slide.Subsequently,MALDI MSI was performed on the chemical film without additional sample treatment.One major advantage of LACT is to minimize ionization competition/suppression from the tissue itself by removing abundant endogenous lipid and protein components.The superior performance of LACT led to the successful visualization of regional distribution patterns of 16 CNS drugs in the mouse brain.Furthermore,the dynamic spatial changes of risperidone and its metabolite were visualized over a 24-h period.Also,the brain-to-plasma(B/P)ratio could be obtained according to MALDI MSI results,providing an alternative means to assess brain penetration in drug discovery.

An explanation to the high efficiency of m-THPC (tempor-fin) used in photodynamic therapy

Meso-tetrahydroxylphenyl chlorin (m-THPC) is one of the most efficient prospective sensitizers used in photodynamic therapy (PDT). ESR spectroscopy, fluorescence quenching experiments and cyclic voltammogram measurement were used to study its redox properties. The results showed that the ability of m-THPC generating su-peroxide radical anions was very strong, and the rate constant of m-THPC fluorescence quenching by oxygen kq (O2)=1.46×l010 mol-1 . s-1. The values of fluorescence quenching rate constant of m-THPC by some other electron acceptors, such as methyl viologen (MV2+) and anthraquinone (An), were also measured. And they were kq, (MV2+)=5.51×l09 mol-1 . s-1, kq (An)=7.81×l09 mol-1 .s-1. The oxidation potential of m-THPC was examined to be +0.62 V (vs. NHE) in acetonitrile. All these suggested that m-THPC should be a much stronger electron donor than photofrin, the currently used in clinical photodrug, and may react easily through electron transfer with biological matter to yield various

Timed-pNets： a communication behavioural semantic model for distributed systems

This paper presents an approach to build a communication behavioural semantic model for heterogeneous distributed systems that include synchronous and asynchronous communications. Since each node of such system has its own physical clock, it brings the challenges of correctly specifying the system time constraints. Based on the logical clocks proposed by Lamport, and CCSL proposed by Aoste team in INRIA, as well as pNets from Oasis team in INRIA, we develop timed-pNets to model communication behaviours for distributed systems. Timed-pNets are tree style hierarchical structures. Each node is associated with a timed specification which consists of a set of logical clocks and some relations on clocks. The leaves are represented by timed-pLTSs. Non-leaf nodes （called timed-pNets nodes） are synchronisation devices that synchronize the behaviours of subnets （these subnets can be leaves or non-leaf nodes）. Both timed-pLTSs and timed-pNets nodes can be translated to timed specifications. All these notions and methods are illustrated on a simple use-case of car insertion from the area of intelligent transportation systems （ITS）. In the end the TimeSquare tool is used to simulate and check the validity of our model.