细胞重编程和移植技术用于帕金森病治疗的研究进展

帕金森病(Parkinson disease,PD)是一种复杂的中枢神经系统退行性疾病,主要病理特征为黑质致密部多巴胺神经元的进行性丧失.目前PD主要治疗手段包括药物和手术.但药物存在神经保护活性不足、缺乏对因治疗、晚期无药可用等问题,手术治疗风险较大.近年来,细胞重编程技术取得突破性进展,由重编程产生的诱导多能干细胞(induced pluripotent stem cells,iPSCs)、诱导多巴胺神经元(induced dopamine neurons,iDNs)和诱导神经干细胞(induced neural stem cells,i NSCs)可用于治疗PD.移植iPSCs分化而来的多巴胺能神经元、iDNs和iNSCs至相应脑区,可起到神经替代与修复作用,有效治疗PD.本文重点介绍细胞重编程的机制,总结iPSCs、iDNs和iNSCs治疗PD的优缺点,并阐述尚存在的挑战,探讨可能的解决方案.     

Modification of alternative splicing in bovine somatic cell nuclear transfer embryos using engineered CRISPR-Cas13d

Animal cloning can be achieved by somatic cell nuclear transfer(SCNT), but the resulting live birth rate is relatively low. We previously improved the efficiency of bovine SCNT by exogenous melatonin treatment or by overexpression of lysine-specific demethylase 4D(KDM4D) and 4E(KDM4E). In this study, we revealed abundant alternative splicing(AS) transitions during fertilization and embryonic genome activation, and demonstrated abnormal AS in bovine SCNT embryos compared with in vitro fertilized ...     

Quantitative Metaproteomics and Activity-based Protein Profiling of Patient Fecal Microbiome Identifies Host and Microbial Serine-type Endopeptidase Activity Associated With Ulcerative Colitis

The gut microbiota plays an important yet incompletely understood role in the induction and propagation of ulcerative colitis (UC). Organism-level efforts to identify UC-associated microbes have revealed the importance of community structure, but less is known about the molecular effectors of disease. We performed 16S rRNA gene sequencing in parallel with label-free data-dependent LC-MS/MS proteomics to characterize the stool microbiomes of healthy (n = 8) and UC (n = 10) patients. Comparisons of taxonomic composition between techniques revealed major differences in community structure partially attributable to the additional detection of host, fungal, viral, and food peptides by metaproteomics. Differential expression analysis of metaproteomic data identified 176 significantly enriched protein groups between healthy and UC patients. Gene ontology analysis revealed several enriched functions with serine-type endopeptidase activity overrepresented in UC patients. Using a biotinylated fluorophosphonate probe and streptavidin-based enrichment, we show that serine endopeptidases are active in patient fecal samples and that additional putative serine hydrolases are detectable by this approach compared with unenriched profiling. Finally, as metaproteomic databases expand, they are expected to asymptotically approach completeness. Using ComPIL and de novo peptide sequencing, we estimate the size of the probable peptide space unidentified (“dark peptidome”) by our large database approach to establish a rough benchmark for database sufficiency. Despite high variability inherent in patient samples, our analysis yielded a catalog of differentially enriched proteins between healthy and UC fecal proteomes. This catalog provides a clinically relevant jumping-off point for further molecular-level studies aimed at identifying the microbial underpinnings of UC.     

In-depth Profiling and Quantification of the Lysine Acetylome in Hepatocellular Carcinoma with a Trapped Ion Mobility Mass Spectrometer

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide with limited therapeutic options. Comprehensive investigation of protein posttranslational modifications in HCC is still limited. Lysine acetylation is one of the most common types of posttranslational modification involved in many cellular processes and plays crucial roles in the regulation of cancer. In this study, we analyzed the proteome and K-acetylome in eight pairs of HCC tumors and normal adjacent tissues using a timsTOF Pro instrument. As a result, we identified 9219 K-acetylation sites in 2625 proteins, of which 1003 sites exhibited differential acetylation levels between tumors and normal adjacent tissues. Interestingly, many novel tumor-specific K-acetylation sites were characterized, for example, filamin A (K865), filamin B (K697), and cofilin (K19), suggesting altered activities of these cytoskeleton-modulating molecules, which may contribute to tumor metastasis. In addition, we observed an overall suppression of protein K-acetylation in HCC tumors, especially for enzymes from various metabolic pathways, for example, glycolysis, tricarboxylic acid cycle, and fatty acid metabolism. Moreover, the expression of deacetylase sirtuin 2 (SIRT2) was upregulated in HCC tumors, and its role of deacetylation in HCC cells was further explored by examining the impact of SIRT2 overexpression on the proteome and K-acetylome in Huh7 HCC cells. SIRT2 overexpression reduced K-acetylation of proteins involved in a wide range of cellular processes, including energy metabolism. Furthermore, cellular assays showed that overexpression of SIRT2 in HCC cells inhibited both glycolysis and oxidative phosphorylation. Taken together, our findings provide valuable information to better understand the roles of K-acetylation in HCC and to treat this disease by correcting the aberrant acetylation patterns.     

Characterization of the androgen-dependent 22Kdalton glycoprotein from rat ventral prostate

Oxidation by molecular oxygen converted the 22Kdalton glycoprotein from rat ventral prostate into a 34K species and this reaction could be reversed by thiol reducing reagent. Measurement of the level of the 22Kdalton glycoprotein in prostatic cytosol by the radial immunodiffusion technique showed that changes in the 22Kdalton glycoprotein concentration in response to androgen withdrawal and replacement were slow in comparison to androgen regulated levels of mRNA coding for the protein. (3) Charcoal absorption steroid binding assays of the 22Kdalton glycoprotein revealed that the protein did not bind testosterone, estradiol, progesterone or corticosterone. These results indicate that the 22Kdalton glycoprotein is metabolically stable, not steroid-binding, and exists as an oligomer through disulfide crosslinking.     

湖南沅江鼎城段河蚬的性别组成与精子形态特征

本研究以湖南沅江鼎城段河蚬(Corbicula fluminea)为研究对象,在进一步验证该群体性别组成的基础上,分析壳长组成与性别比例之间关系,探讨该群体雄性、雌性和雌雄同体之间关系;同时以单鞭毛精子为参照,分析比较双鞭毛精子的形态特征,以期为我国河蚬的性别发生及生殖适应策略研究提供基础资料。结果显示：沅江鼎城段河蚬(n = 770)雄性、雌性和雌雄同体最小性成熟壳长分别为2.92 mm、5.66 mm和5.30 mm。697只性成熟河蚬中雄性、雌性和雌雄同体的比例近似1︰1︰6。雌雄同体的平均壳长[(22.55 ± 0.33)mm,n = 517]显著大于雄性[(20.44 ± 1.03)mm,n = 95]和雌性[(19.79 ± 0.99)mm,n = 85](P < 0.05),但雄性与雌性的平均壳长之间差异不显著(P > 0.05)。河蚬可以产生单鞭毛和双鞭毛两种类型的精子,单鞭毛精子头长范围4.93 ~ 21.79 μm,平均值(14.27 ± 0.82)μm(n = 30),双鞭毛精子头长范围10.29 ~ 22.04 μm,平均值(15.62 ± 0.62)μm(n = 26)。单、双鞭毛精子头长差异不显著(P > 0.05)。双鞭毛精子(n = 26)长尾的平均长度[(38.07 ± 1.44)μm]显著大于其短尾[(31.08 ± 1.60)μm]和单鞭毛精子(n = 30)尾部长度[(30.15 ± 1.75)μm](P < 0.01),但其短尾与单鞭毛精子的尾部平均长度之间无显著性差异(P > 0.05)。结果表明：湖南沅江鼎城段河蚬为雄性先熟,且可能存在雄性和(或)雌性向雌雄同体转换现象。河蚬具有单鞭毛型和双鞭毛型2种类型的精子,且双鞭毛精子的2个尾部不等长。同域共存河蚬的单鞭毛与双鞭毛精子在运动及受精能力方面的差异值得深入研究。     

耕作措施对土壤水热特性和微生物生物量碳的影响

通过山西寿阳设置的8a田间定位试验,比较了全量秸秆还田、免耕覆盖和常规耕作3种耕作措施下土壤含水量、温度及土壤微生物生物量碳变化.结果表明:免耕覆盖与全量还田处理显著提高土壤含水量,与常规耕作相比表层土壤体积含水量在玉米苗期、拔节期、灌浆期和成熟期分别高出18％、22％、29％、21％和3％、10％、12％、13％,具有保水保墒的作用.在苗期不同耕作措施对土壤温度的影响达到显著水平,5 cm处免耕覆盖、全量还田与常规耕作处理土壤温度依次为:18.12、18.76和19.44℃,免耕覆盖和全量还田处理平均温度比常规耕作分别低1.32℃和0.69℃.土壤微生物量碳在整个生育期动态变化是首先迅速上升在玉米生育高峰期(拔节期)达到最高峰,然后开始下降,成熟期趋于平缓.免耕覆盖与全量还田处理下玉米各生育期土壤表层微生物量碳显著高于常规耕作,在苗期、拔节期、灌浆期和成熟期分别比常规耕作高出70％、40％、85％和30％和10％、20％、15％和15％.土壤微生物量碳与土壤温度和土壤含水量相关和极相关.     

Complementary genetic and genomic approaches help characterize the linkage group I seed protein QTL in soybean

Background

Cotton fibers (produced by Gossypium species) are the premier natural fibers for textile production. The two tetraploid species, G. barbadense (Gb) and G. hirsutum (Gh), differ significantly in their fiber properties, the former having much longer, finer and stronger fibers that are highly prized. A better understanding of the genetics and underlying biological causes of these differences will aid further improvement of cotton quality through breeding and biotechnology. We evaluated an inter-specific Gh × Gb recombinant inbred line (RIL) population for fiber characteristics in 11 independent experiments under field and glasshouse conditions. Sites were located on 4 continents and 5 countries and some locations were analyzed over multiple years.

Results

The RIL population displayed a large variability for all major fiber traits. QTL analyses were performed on a per-site basis by composite interval mapping. Among the 651 putative QTLs (LOD > 2), 167 had a LOD exceeding permutation based thresholds. Coincidence in QTL location across data sets was assessed for the fiber trait categories strength, elongation, length, length uniformity, fineness/maturity, and color. A meta-analysis of more than a thousand putative QTLs was conducted with MetaQTL software to integrate QTL data from the RIL and 3 backcross populations (from the same parents) and to compare them with the literature. Although the global level of congruence across experiments and populations was generally moderate, the QTL clustering was possible for 30 trait x chromosome combinations (5 traits in 19 different chromosomes) where an effective co-localization of unidirectional (similar sign of additivity) QTLs from at least 5 different data sets was observed. Most consistent meta-clusters were identified for fiber color on chromosomes c6, c8 and c25, fineness on c15, and fiber length on c3.

Conclusions

Meta-analysis provided a reliable means of integrating phenotypic and genetic mapping data across multiple populations and environments for complex fiber traits. The consistent chromosomal regions contributing to fiber quality traits constitute good candidates for the further dissection of the genetic and genomic factors underlying important fiber characteristics, and for marker-assisted selection.     

Effects of dissolved organic matter from sewage sludge on the atrazine sorption by soils

The effects of dissolved organic matter (DOM), water soluble organic matter derived from sewage sludge, on the sorption of atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-trazine) by soils were studied using a batch equilibrium technique. Six paddy soils, chosen so as to have different organic carbon contents, were experimented in this investigation. Atrazine sorption isotherms on soils were described by the linear equation, and the distribution coefficients without DOM (Kd) or with DOM (Kd*) were obtained. Generally, the values of Kd*/Kd initially insoil-solution system form. Critical concentrations of DOM (DOMnp) were obtained where the value of Kd* was equal to Kd. The presence of DOM with concentrations lower than DOMnp promoted atrazine sorption on soils (Kd* ＞ Kd), whereas the presence of DOM with concentrations higher than DOMnp tended to inhibit atrazine sorption (Kd* ＜ Kd). Interestingly, DOMnp for tested soils was negatively correlated to the soil organic carbon content, and the maximum of Kd*/Kd (i.e.Kmax) correlated positively with the maximum of DOM sorption on soil (Xmax). Further investigations showed that the presence of hydrophobic fraction of DOM evidently promoted the atrazine sorption on soils, whereas the presence of hydrophilic DOM fraction obviously tended to inhibit the atrazine sorption. Interactions of soil surfaces with DOM and its fractions were suggested to be the major processes determining atrazine sorption on soils. The results of this work provide a reference to the agricultural use of organic amendment such as sewage sludge for improving the availability of atrazine in soils.