A yeast's eye view of mammalian reproduction: cross-species gene co-expression in meiotic prophase

Background  

Meiotic prophase is a critical stage in sexual reproduction. Aberrant chromosome recombination during this stage is a leading cause of human miscarriages and birth defects. However, due to the experimental intractability of mammalian gonads, only a very limited number of meiotic genes have been characterized. Here we aim to identify novel meiotic genes important in human reproduction through computational mining of cross-species and cross-sex time-series expression data from budding yeast, mouse postnatal testis, mouse embryonic ovary, and human fetal ovary.     

The reaction of cytochromes c and c2 with the Rhodospirillum rubrum reaction center involves the heme crevice domain

In order to define the interaction domain on Rhodospirillum rubrum cytochrome c2 for the photosynthetic reaction center, positively charged lysine amino groups on cytochrome c2 were modified to form negatively charged carboxydinitrophenyl lysines. The reaction mixture was separated into six different fractions by ion exchange chromatography on carboxymethylcellulose and sulfopropyl-Sepharose. Peptide mapping studies indicated that fraction A consisted of a mixture of singly labeled derivatives modified at lysines 58, 81, and 109 on the back of cytochrome c2. Fractions C1, C2, C3, and C4 were found to be mixtures of singly labeled derivatives modified at lysines 9, 13, 75, 86, and 88 on the front of cytochrome c2 surrounding the heme crevice. The photooxidation of the carboxydinitrophenyl-cytochrome c2 derivatives by reaction centers purified from R. rubrum was measured following excitation with a laser pulse. The second-order rate constant of fraction A modified at backside lysines was found to be 2.3 X 10(7) M-1 s-1, nearly the same as that of native cytochrome c2, 2.6 X 10(7) M-1 s-1. However, the rate constants of fractions C1-C4 were found to be 6 to 12-fold smaller than that of native cytochrome c2. These results indicate that lysines surrounding the heme crevice of cytochrome c2 are involved in electrostatic interactions with carboxylate groups at the binding site of the reaction center. The reaction rates of horse heart cytochrome c derivatives modified at single lysine amino groups with trifluoroacetyl or trifluoromethylphenylcarbamoyl were also measured. Modification of lysines 8, 13, 25, 27, 72, 79, or 87 surrounding the heme crevice was found to significantly lower the rate of reaction, while modification of lysines in other regions had no effect. This indicates that the reaction of horse heart cytochrome c with the reaction center also involves the heme crevice domain.     

Linkage map of seven polymorphic markers on rat Chromosome 18

A genetic linkage map of seven polymorphic markers was created with F₂ intercross progeny of F344/N and LEW/N rats and assigned to rat Chromosome (Chr) 18. Five of the markers described were defined by simple sequence length polymorphisms (SSLPs) associated with five genes: transthyretin (TTR), trypsin inhibitor-like protein (TILP), 2 adrenergic receptor (ADRB2), olfactory neuron-specific G protein (OLF), and gap junction protein (GJA1). One marker was defined by a restriction fragment length polymorphism (RFLP) detected with a probe for the human colony stimulating factor 1 receptor (CSF1R) gene. The D18N1R locus was defined by an anonymous DNA fragment amplified by the randomly amplified polymorphic DNA (RAPD) technique with a single short primer. These seven DNA loci formed a single genetic linkage group 30.4 cM in length with the following order: TTR-6.8 cM-D18N1R-9.1 cM-TILP-4.3 cM-CSF1R-0 cM-ADRB2-10.2 cM-OLF-0 cM-GJA1. The five SSLP markers were highly polymorphic. In a total of 13 inbred rat strains analyzed (F344/ N, LEW/N, LOU/MN, WBB1/N, WBB2/N, MR/N, MNR/N, ACI/N, SHR/N, WKY/N, BN/SsN, BUF/N, and LER/N), three to six alleles were detected for each marker. Remarkable linkage conservation was detected between the region of rat Chr 18 mapped and a region of mouse Chr 18. However, genes associated with these markers have been mapped to three different human chromosomes (Chrs 5, 6, and 18). The markers described here should be useful for genetic mapping studies and genetic monitoring of inbred rat strains.     

视黄酸和亚硒酸钠对肝癌细胞某些表型逆转的加和作用

 人肝癌细胞株SMMC-7721经1μmol/L视黄酸和或2.5μmol/L亚硒酸钠处理后,膜上纤维连接蛋白沉着量逐日上升,且较相应天数的对照组细胞增加,而甲胎蛋白分泌量和~3H-TdR参入率被明显抑制。视黄酸和亚硒酸钠同时处理的联合组作用强度接近于两者单独使用时作用强度的加和。对以上结果和视黄酸及亚硒酸钠使肝癌细胞接触抑制恢复及表型逆转的关系作了讨论。     

Circulating exosome‐derived bona fide long non‐coding RNAs predicting the occurrence and metastasis of hepatocellular carcinoma

Although the diagnosis and therapy approach developed, techniques for the early diagnosis of HCC remain insufficient which results in poor prognosis of patients. The traditional biomarker AFP, however, has been proved with low specificity. Circulating exosomal ncRNAs revealed different profiles reflecting the characteristics of tumour. In this study, we mainly focused on circulating exosomal ncRNAs which might be the fingerprint for HCC, especially for the diagnosis or metastasis prediction. A high throughput lncRNA microarray in exosomes extracted from cell‐free plasma was applied. The risk score analysis was employed to screen the potential exosome‐derived lncRNAs in two independent sets based on different clinical parameters in 200 paired HCC patients. After a multi‐stage validation, we finally revealed three lncRNAs, ENSG00000248932.1, ENST00000440688.1 and ENST00000457302.2, increased in HCC comparing with the both chronic hepatitis (CH) patients and cancer‐free controls. ROC curve revealed a higher sensitivity and specificity in predicting the occurrence of HCC from cancer‐free controls and CH patients with the area under curve (AUC) of 0.905 and 0.879 by combining AFP. The three lncRNA panel combined with AFP also indicted a fingerprint function in predicting the metastasis of HCC with the AUC of 0.870. In conclusion, ENSG00000248932.1, ENST00000440688.1 and ENST00000457302.2 might be the potential biomarker for the tumorigenesis prediction from CH patients or healthy controls and may also be applied for dynamic monitoring the metastasis of HCC.     

Half‐Heusler Thermoelectric Module with High Conversion Efficiency and High Power Density

Half‐Heusler (HH) compounds have shown great potential in waste heat recovery. Among them, p‐type NbFeSb and n‐type ZrNiSn based alloys have exhibited the best thermoelectric (TE) performance. However, TE devices based on NbFeSb‐based HH compounds are rarely studied. In this work, bulk volumes of p‐type (Nb_0.8Ta_0.2)_0.8Ti_0.2FeSb and n‐type Hf_0.5Zr_0.5NiSn_0.98Sb_0.02 compounds are successfully prepared with good phase purity, compositional homogeneity, and matchable TE performance. The peak zTs are higher than 1.0 at 973 K for Hf_0.5Zr_0.5NiSn_0.98Sb_0.02 and at 1200 K for (Nb_0.8Ta_0.2)_0.8Ti_0.2FeSb. Based on an optimal design by a full‐parameters 3D finite element model, a single stage TE module with 8 n‐p HH couples is assembled. A high conversion efficiency of 8.3% and high power density of 2.11 W cm^?2 are obtained when hot and cold side temperatures are 997 and 342 K, respectively. Compared to the previous TE module assembled by the same materials, the conversion efficiency is enhanced by 33%, while the power density is almost the same. Given the excellent mechanical robustness and thermal stability, matchable thermal expansion coefficient and TE properties of NbFeSb and ZrNiSn based HH alloys, this work demonstrates their great promise for power generation with both high conversion efficiency and high power density.     

Flexible chromosome painting based on multiplex PCR of oligonucleotides and its application for comparative chromosome analyses in Cucumis

Chromosome painting is a powerful technique for chromosome and genome studies. We developed a flexible chromosome painting technique based on multiplex PCR of a synthetic oligonucleotide (oligo) library in cucumber (Cucumis sativus L., 2n = 14). Each oligo in the library was associated with a universal as well as nested specific primers for amplification, which allow the generation of different probes from the same oligo library. We were also able to generate double‐stranded labelled oligos, which produced much stronger signals than single‐stranded labelled oligos, by amplification using fluorophore‐conjugated primer pairs. Oligos covering cucumber chromosome 1 (Chr1) and chromosome 4 (Chr4) consisting of eight segments were synthesized in one library. Different oligo probes generated from the library painted the corresponding chromosomes/segments unambiguously, especially on pachytene chromosomes. This technique was then applied to study the homoeologous relationships among cucumber, C. hystrix and C. melo chromosomes based on cross‐species chromosome painting using Chr4 probes. We demonstrated that the probe was feasible to detect interspecies chromosome homoeologous relationships and chromosomal rearrangement events. Based on its advantages and great convenience, we anticipate that this flexible oligo‐painting technique has great potential for the studies of the structure, organization, and evolution of chromosomes in any species with a sequenced genome.     

Therapeutic efficacy of novel memantine nitrate MN‐08 in animal models of Alzheimer’s disease

Alzheimer''s disease (AD) is a leading cause of dementia in elderly individuals and therapeutic options for AD are very limited. Over‐activation of N‐methyl‐D‐aspartate (NMDA) receptors, amyloid β (Aβ) aggregation, a decrease in cerebral blood flow (CBF), and downstream pathological events play important roles in the disease progression of AD. In the present study, MN‐08, a novel memantine nitrate, was found to inhibit Aβ accumulation, prevent neuronal and dendritic spine loss, and consequently attenuate cognitive deficits in 2‐month‐old APP/PS1 transgenic mice (for a 6‐month preventative course) and in the 8‐month‐old triple‐transgenic (3×Tg‐AD) mice (for a 4‐month therapeutic course). In vitro, MN‐08 could bind to and antagonize NMDA receptors, inhibit the calcium influx, and reverse the dysregulations of ERK and PI3K/Akt/GSK3β pathway, subsequently preventing glutamate‐induced neuronal loss. In addition, MN‐08 had favorable pharmacokinetics, blood‐brain barrier penetration, and safety profiles in rats and beagle dogs. These findings suggest that the novel memantine nitrate MN‐08 may be a useful therapeutic agent for AD.     

Endonasal Endoscopic Treatment of Recurrent Dacryocystitis

This report assessed clinical conditions leading to recurrent dacryocystitis and success rates of its treatment by endonasal endoscopic dacryocystorhinostomy. Forty-eight patients with recurrent dacryocystitis underwent endonasal endoscopic surgery and were followed up for at least 6 months. High bone windows, small bone window openings, small lacrimal sac stomas, scar tissues, and organic diseases of the nasal cavity led to fistula closure. Out of 48 patients, 45 (93.8 %) patients were cured by endonasal endoscopic surgery. Endonasal endoscopic dacryocystorhinostomy is beneficial for recurrent dacryocystitis.