Enantiopure ethyl 2,3-dibromopropionate: Enantioselective synthesis vs preparative HPLC enantioseparation of racemate on multigram scale

Racemic ethyl 2,3-dibromopropionate, commercially available at low price, is a key intermediate used in the synthesis of several heterocycle fragments, which are present in many biologically active compounds. Surprisingly, the enantiomers are not commercially available and have never been described in the literature. In this work, we undertook two different strategies to obtain these enantiomers, which are enantioselective synthesis and preparative HPLC enantioseparation of commercially available racemate on multigram scale. The first strategy has proved inadequate because racemization occurred during the synthesis (ee ≈ 9-50%). Conversely, the second strategy produced a very good enantioseparation of commercially available racemate (ee > 99.5% for both enantiomers) on multigram scale.     

Quantified 123I-Thyroid Scan based classification of hyperthyroidism

The original thyroid scan (TS) was widely used to identify typical imaging patterns, suggesting the widely accepted main following clinical diagnoses: Grave's disease, Toxic adenoma, [hetero]-nodular goiters and thyroiditis. With the diffusion of sensitive TSH assays, considerable advances in the comprehension of the molecular mechanisms of hormonosynthesis, and new quantification possibilities especially using ¹²³I, the TS is a textbook of molecular imaging. The image can be finely quantified with, not only as regards the Uptake (¹²³IUp) and related parameters but also, the quantification of the spatial targeting leading to a Spatial Target Index (STI). Using this new molecular ¹²³I-TS, TSH values, and when required, correlation to Multiparametric Ultrasounds (MPUS), we generated a basic classification system of hyperthyroidism, with well-defined indexed criteria (C11-1 to C17-3), that allows reporting 24 distinct etiologies. Selected criteria involve TS and contrast patterns, precocious ¹²³IUp (p¹²³IUp), maximal TSH-dependent physiological Uptake, lobar concentration, Uptake and concentration ratios, STI, ^99mTc-MIBI TS and correlative MPUS. This approach allows to identify 4 subtypes of Graves’ disease, including hyperplastic, nodular and common GD variants entangled with Hashimoto's struma, 4 subtypes of Thyroid Functional Autonomy, including Disseminated Functional Autonomy, that cannot be diagnosed with other conventional procedures. Criteria C14-1 to C17-3 report on hyperthyroidism and iodine overload, factitia, main thyroiditis presentations and rare central or tumoral etiologies of hyperthyroidism. This classification, based on ¹²³I-TS molecular imaging, leads to unprecedented diagnostic finesse and paves the way for a personalized theranostic approach in thyroid pathology. Further development towards artificial intelligence networks is under study.     

The Chimonanthus salicifolius genome provides insight into magnoliid evolution and flavonoid biosynthesis

Chimonanthus salicifolius, a member of the Calycanthaceae of magnoliids, is one of the most famous medicinal plants in Eastern China. Here, we report a chromosome‐level genome assembly of C. salicifolius, comprising 820.1 Mb of genomic sequence with a contig N50 of 2.3 Mb and containing 36 651 annotated protein‐coding genes. Phylogenetic analyses revealed that magnoliids were sister to the eudicots. Two rounds of ancient whole‐genome duplication were inferred in the C. salicifolious genome. One is shared by Calycanthaceae after its divergence with Lauraceae, and the other is in the ancestry of Magnoliales and Laurales. Notably, long genes with > 20 kb in length were much more prevalent in the magnoliid genomes compared with other angiosperms, which could be caused by the length expansion of introns inserted by transposon elements. Homologous genes within the flavonoid pathway for C. salicifolius were identified, and correlation of the gene expression and the contents of flavonoid metabolites revealed potential critical genes involved in flavonoids biosynthesis. This study not only provides an additional whole‐genome sequence from the magnoliids, but also opens the door to functional genomic research and molecular breeding of C. salicifolius.     

一株稀有海洋真菌Stachybotrys longispora FG216的De Novo测序及基因组学分析

【背景】长孢葡萄穗霉菌(Stachybotrys longispora) FG216是一株稀有海洋真菌,其次生代谢产物FGFC1具有纤溶活性。进行S. longispora FG216的基因组序列分析,将充实和促进海洋微生物功能基因和次生代谢产物合成生物学的基础研究和应用研究。【目的】解析S. longispora FG216的基因组序列,分析基因组生物功能和同源相似性关系,分析次生代谢产物纤溶活性化合物FGFC1的相关基因。【方法】基于Illumina HiSeq高通量测序平台对S. longispora FG216菌株进行De Novo测序,使用SSPACE、Augustus等软件进行组装、编码基因预测、基因功能注释、物种共线性分析以及预测FGFC1次生代谢产物合成基因簇。【结果】S. longispora FG216的基因组测序总长度为45622830bp,共得到605个Scaffold,GC含量为51.31%,注释预测得到13329个编码基因和169个非编码RNA。基因组测序数据提交至国家微生物科学数据中心(编号为NMDC60016264),其中13 053、8 422、8 460、7 714和2 847个基因分别能够在NR、KEGG、KOG、GO和CAZy数据库匹配到注释信息。比较基因组学分析发现,Stachybotrys具有保守性,核心基因占基因家族总数目的71.44%,S. longispora FG216与S. chlorohalonata IBT 40285的相似性最高;同时,预测得到101个次生代谢产物合成基因簇,其中18个基因簇与已知的化合物相匹配。通过antiSMASH预测,Cluster57是编码合成FGFC1母核结构异吲哚啉酮的基因簇,与S.chlorohalonataIBT40285中的基因簇相似度为40%。【结论】海洋稀有真菌S.longisporaFG216的基因组信息已上传至国家微生物科学数据中心公开使用,为Stachybotrys种属的研究提供了重要的参考意义,同时发现了S. longispora FG216次生代谢产物纤溶活性化合物FGFC1母核部分编码基因是Cluster 57。     

Origins and Long-Term Patterns of Copy-Number Variation in Rhesus Macaques

Mutations play a key role in the development of disease in an individual and the evolution of traits within species. Recent work in humans and other primates has clarified the origins and patterns of single-nucleotide variants, showing that most arise in the father’s germline during spermatogenesis. It remains unknown whether larger mutations, such as deletions and duplications of hundreds or thousands of nucleotides, follow similar patterns. Such mutations lead to copy-number variation (CNV) within and between species, and can have profound effects by deleting or duplicating genes. Here, we analyze patterns of CNV mutations in 32 rhesus macaque individuals from 14 parent–offspring trios. We find the rate of CNV mutations per generation is low (less than one per genome) and we observe no correlation between parental age and the number of CNVs that are passed on to offspring. We also examine segregating CNVs within the rhesus macaque sample and compare them to a similar data set from humans, finding that both species have far more segregating deletions than duplications. We contrast this with long-term patterns of gene copy-number evolution between 17 mammals, where the proportion of deletions that become fixed along the macaque lineage is much smaller than the proportion of segregating deletions. These results suggest purifying selection acting on deletions, such that the majority of them are removed from the population over time. Rhesus macaques are an important biomedical model organism, so these results will aid in our understanding of this species and the disease models it supports.     

A new discovery of Neanderthal settlements in Turkey: Sürmecik open-air campsite in Western Anatolia

Western Anatolia is the poorest region in terms of Turkey's Palaeolithic finds. In the past years, only a few Palaeolithic artefacts were known from the surface in the provinces of İzmir, Manisa, Kütahya and Afyonkarahisar in western Anatolia. After the fossil Homo erectus skull fragment was found in the travertine deposits in Kocabaş (Denizli) in 2002, the importance of the region more increased. After this important discovery, Dr. Kadriye Özçelik started a Palaeolithic survey in Denizli and found a large number of chipped stone tools from the Lower and Middle Palaeolithic periods. Nevertheless, the last important Palaeolithic discovery in the region was made in Sürmecik (Banaz-Uşak) in 2015. This is an open-air campsite belonging to the Middle Palaeolithic period. Here is also a mining area where a mining operation is conducted. The chipped stone artefacts of the Sürmecik Palaeolithic open-air campsite come from a clay layer between hematite and limonite deposits under a travertine layer of about 4.5–5 meters in thickness. Faunal remains represent mostly by equids species. All stages of Mousterian culture are clearly visible in this open-air campsite. Sürmecik is the richest middle Palaeolithic open-air campsite in Turkey. The 83,002 lithic pieces were collected in the excavations carried out in 2016 and 2017. It is thought that the lithic assemblage will exceed 100,000 with the ongoing studies. The group of bifacial leaf points in this collection is seen in Turkey for the first time. Four master thesis studies started on the lithic material of Sürmecik. It is planned to take some samples for dating analysis along with ongoing studies.     

Dwellings and workspaces at Strandvägen, 5600–5000 cal. BC

This paper describes identified workspaces and the manufacture of slotted bone points at the Late Mesolithic settlement Strandvägen in Motala, in eastern central Sweden. Several dwellings were documented, Dwelling 1 being typically round-oval in shape 9 × 5.5 meters, with a floor area covering 49.5 m². Radiocarbon dates fall between approximately 5600-5200 cal BC. A combined archaeological record, with lithics and bone artefacts as well as analyses of the osteological assemblage has shown that slotted bone tools with mounted lithic inserts have been produced adjacent of the dwelling. The spatial distribution of bone flakes, microblades, processed resin and slotted artefacts testify to a clearly and delimited craft area near the shoreline of the river Motala Ström. Analyses of the finds, e.g. birch bark resin and prepared bone preforms by direct percussion, also help in reconstructing the stages of manufacturing composite projectile points in this part of Eurasia.