[Application of copy number variation sequencing combined with short tandem repeat in analysis of abortion and prenatal diagnosis].

OBJECTIVE: To explore the cause of abortion and strategy of prenatal diagnosis for pregnant women with high risk for chromosomal abnormalities by using copy number variation sequencing (CNV-seq) and short tandem repeats (STR) analysis. METHODS: A total of 36 samples were collected, including amniotic fluid, abortion tissue, whole blood, chorionic villi and umbilical cord blood. CNV-seq and STR analysis were carried out to detect microdeletions, microduplications, chromosomal aneuploidies, mosaicisms and triploidies. RESULTS: Among all samples, 1 was detected with 4p15.1p16.3 and 14q11.1q22.1 duplication, 1 was detected with 19p13.3 deletion, 8 were detected with chromosomal aneuploidies, 4 were detected with mosaicisms, two were detected with triploidies. No definite pathogenic CNVs were detected in 20 samples, which yielded a positive detection rate of 44.44%. CONCLUSION: As a high-throughput detection method, CNV-seq has the advantages of rapidity, simplicity and high accuracy. It may suit prenatal diagnosis and analysis of abortion factors in combination with STR analysis.

4H-Thieno[3,2-c]chromene based inhibitors of Notum Pectinacetylesterase.

A group of small molecule thienochromenes inhibitors of Notum Pectinacetylesterase are described. We developed SAR on three series based on carbon, oxygen and sulfur replacement of the 5-position. In each series, highly potent Notum Pectinacetylesterase inhibitors were identified.

III. Identification of novel CXCR3 chemokine receptor antagonists with a pyrazinyl-piperazinyl-piperidine scaffold.

The SAR of a novel pyrazinyl-piperazinyl-piperidine scaffold with CXCR3 receptor antagonist activity was explored. Optimization of the DMPK profile and reduction of hERG inhibition is described. Compound 16e with single-digit CXCR3 affinity, good rat PK and hERG profiles has been identified as a lead for further study.

Disclosing the distinct interfacial behaviors of structurally and configurationally diverse triazologlycolipids.

1- or 6-Triazologluco- and galactolipid derivatives bearing a lipid chain length of 16 carbons were efficiently constructed via click chemistry. The differentiation in their surface pressure-molecular area (π-A) isotherms first implies that these structurally and configurationally diverse amphiphiles adopt different distribution manner at air-water interfaces. The Langmuir-Blodgett (LB) films of the synthesized glycoconjugates on mica surface were subsequently prepared and visualized via atomic force microscopy (AFM), which exhibited diverse topographies and possess different contact angles with water. These data further suggest that the structural variation as well as epimeric identity of triazologlycolipids may result in their distinct interfacial behaviors at the air-solid interface. Furthermore, the addition of increasing amounts of 1-triazologalactolipid 2 to poly-diacetylene (PDA) was determined to impact the π-A isotherm of the latter, prompting us to further fabricate new colorimetrically detectable mixed-type vesicles containing triazologlycolipids for biochemical studies.

[Coupling anaerobic baffled reactor and membrane-aerated biofilm reactor].

Based on the consistent anaerobic status of outer layer of membrane-aerated biofilm reactor (MABR) and internal anaerobic baffled reactor (ABR), MABR and ABR were started up separately. The aerating membrane module was installed into a compartment of anaerobic baffled bioreactor to form the Hybrid MAB-ABR (HMABR). After the installation of membrane module, total COD and VFA concentrations in the HMABR effluent were deceased by 59.5% and 68.1% respectively, with increased nitrogenous pollutant remove efficiency by 83.5%, at influent COD concentration of 1600 mg/L and NH4+ -N concentration of 80 mg/L. When organic loading rate was increased by 50%, the effluent COD concentration was still below the level of 60 mg/L, indicating its good capability of counteracting influent organic loading fluctuation. Due to the decreased COD concentration and increased nitrate concentration in the third compartment after installing the membrane module, the biogas volume and methane contents in the third compartment were decreased, resulting in the steady and excellent effluent quality. In this hybrid process, the improved simultaneous removal of carbon and nitrogen for high-strength nitrogenous organic pollutants was realized in a single reactor.

SEPPA: a computational server for spatial epitope prediction of protein antigens.

In recent years, a lot of efforts have been made in conformational epitope prediction as antigen proteins usually bind antibodies with an assembly of sequentially discontinuous and structurally compact surface residues. Currently, only a few methods for spatial epitope prediction are available with focus on single residue propensity scales or continual segments clustering. In the method of SEPPA, a concept of 'unit patch of residue triangle' was introduced to better describe the local spatial context in protein surface. Besides that, SEPPA incorporated clustering coefficient to describe the spatial compactness of surface residues. Validated by independent testing datasets, SEPPA gave an average AUC value over 0.742 and produced a successful pick-up rate of 96.64%. Comparing with peers, SEPPA shows significant improvement over other popular methods like CEP, DiscoTope and BEpro. In addition, the threshold scores for certain accuracy, sensitivity and specificity are provided online to give the confidence level of the spatial epitope identification. The web server can be accessed at http://lifecenter.sgst.cn/seppa/index.php. Batch query is supported.

Multiphoton infrared initiated thermal reactions of esters: pseudopericyclic eight-centered cis-elimination.

Multiphoton infrared absorption from a focused, pulsed CO(2) laser was used to initiate gas-phase thermal reactions of cis- and trans-3-penten-2-yl acetate. By varying the helium buffer gas pressure, it was possible to deduce the product distribution from the initial unimolecular reactions, separate from secondary reactions in a thermal cascade. Thus, trans-3-penten-2-yl acetate gives 54 +/- 5% of beta-elimination to give trans-1,3-pentadiene, 40 +/- 3% of [3,3]-sigmatropic rearrangement to give cis-3-penten-2-yl acetate and 6 +/- 4% of cis-1,3-pentadiene. Similar irradiation of cis-3-penten-2-yl acetate gives 45 +/- 1% of beta-elimination to give cis-1,3-pentadiene, 32 +/- 2% of [3,3]-sigmatropic rearrangement to give trans-3-penten-2-yl acetate and 23 +/- 2% of trans-1,3-pentadiene. The latter process is an eight-centered delta-elimination, which is argued to be a pseudopericyclic reaction. Although beta-eliminations have been suggested to be pericyclic, B3LYP/6-31G(d,p), MP2 and MP4 calculations suggest that both beta- and delta-eliminations, as well as [3,3]-sigmatropic rearrangements of esters are primarily pseudopericyclic in character, as judged by both geometrical, energetic and transition state aromaticity (NICS) criteria. Small distortions from the ideal pseudopericyclic geometries are argued to reflect small pericyclic contributions. It is further argued that when both pericyclic and pseudopericyclic orbital topologies are allowed and geometrically feasible, the calculated transition state may be the result of proportional mixing of the two states; this offers an explanation of the range of pseudopericyclic and pericyclic characters found in related reactions.

Exclusion of a transmembrane-type peptide from ordered-lipid domains (rafts) detected by fluorescence quenching: extension of quenching analysis to account for the effects of domain size and domain boundaries.

Sphingolipid/cholesterol-rich rafts are membrane domains thought to exist in the liquid-ordered state. To understand the rules governing the association of proteins with rafts, the behavior of a model membrane-inserted hydrophobic polypeptide (LW peptide, acetyl-K(2)W(2)L(8)AL(8)W(2)K(2)-amide) was examined. The distribution of LW peptide between coexisting ordered and disordered lipid domains was probed by measuring the amount of LW Trp fluorescence quenched by a nitroxide-labeled phospholipid that concentrated in disordered lipid domains. Strong quenching of the Trp fluorescence (relative to quenching in model membranes lacking domains) showed that LW peptide was concentrated in quencher-rich disordered domains and was largely excluded from ordered domains. Exclusion of LW peptide from the ordered domains was observed both in the absence and in the presence of 25-33 mol % cholesterol, indicating that the peptide is relatively excluded both from gel-state domains (which form in the absence of cholesterol) and from liquid-ordered-state domains (which form at high cholesterol concentrations). Because exclusion was also observed when ordered domains contained sphingomyelin in place of DPPC, or ergosterol in place of cholesterol, it appeared that this behavior was not strongly dependent on lipid structure. In both the absence and the presence of 25 mol % cholesterol, exclusion was also not strongly dependent upon the fraction of the bilayer in the form of ordered domains. To evaluate LW peptide behavior in more detail, an analysis of the effects of domain size and edges upon quenching was formulated. This analysis showed that quenching can be affected both by domain size and by whether a fluorescent molecule localized at domain edges. Its application to the quenching of LW peptide indicated that the peptide did not preferentially reside at the boundaries between ordered and disordered domains.

Chemoselectivity in the Reactions of Acetylketene and Acetimidoylketene: Confirmation of Theoretical Predictions.

Acetylketene (1) was generated by flash pyrolysis of 2,2,6-trimethyl-4H-1,3-dioxin-4-one (6). The selectivities of 1 toward a number of representative functional groups were measured for the first time in a series of competitive trapping reactions. The trend in reactivities toward 1 follows the general order amines > alcohols >> aldehydes approximately ketones and can be rationalized by considering both the nucleophilicity and the electrophilicity of the reacting species. Alcohols show significant selectivity based on steric hindrance, with MeOH approximately 1 degrees > 2 degrees > 3 degrees. These selectivities are consistent with the activation energies and the pseudopericyclic transition structure previously calculated for the addition of water to formylketene. The results, presented here, of ab initio transition structure calculations for the addition of ammonia to formylketene are qualitatively consistent with the experimental trends as well. N-Propylacetacetimidoylketene (2) was generated by the solution pyrolysis of tert-butyl N-propyl-3-amino-2-butenoate (9a) and showed similar selectivity toward alcohols as opposed to ketones and similar steric discrimination toward alcohols. This is again in agreement with previous ab initio calculations. Taken together, these experimental trends in the reactivities of both 1 and 2 toward a variety of reagents provide strong, although indirect support for the planar, pseudopericyclic transition structures for these reactions which are predicted by ab initio calculations.