X连锁精神发育迟滞相关基因JARID1C研究进展

JARID1C基因属于X连锁精神发育迟滞相关基因之一, 其表达产物影响大脑神经系统中相关基因的转录和表达, 并可能与人类认知能力密切相关。对JARID1C基因功能的研究有助于理解该基因在精神发育迟滞形成和人类认知能力发展中的分子作用, 也能为精神发育迟滞的临床诊断和防治提供参考。文章对JARID1C基因的定位、分离、转录产物的生理功能及其认知功能做一综述, 并对以后的研究工作进行了展望。     

Temporal Coherence of Chlorophyll a during a Spring Phytoplankton Bloom in Xiangxi Bay of Three‐Gorges Reservoir,China

Algal bloom phenomenon was defined as “the rapid growth of one or more phytoplankton species which leads to a rapid increase in the biomass of phytoplankton”, yet most estimates of temporal coherence are based on yearly or monthly sampling frequencies and little is known of how synchrony varies among phytoplankton or of the causes of temporal coherence during spring algal bloom. In this study, data of chlorophyll a and related environmental parameters were weekly gathered at 15 sampling sites in Xiangxi Bay of Three‐Gorges Reservoir (TGR, China) to evaluate patterns of temporal coherence for phytoplankton during spring bloom and test if spatial heterogeneity of nutrient and inorganic suspended particles within a single ecosystem influences synchrony of spring phytoplankton dynamics. There is a clear spatial and temporal variation in chlorophyll a across Xiangxi Bay. The degree of temporal coherence for chlorophyll a between pairs of sites located in Xiangxi Bay ranged from –0.367 to 0.952 with mean and median values of 0.349 and 0.321, respectively. Low levels of temporal coherence were often detected among the three stretches of the bay (Down reach, middle reach and upper reach), while high levels of temporal coherence were often found within the same reach of the bay. The relative difference of DIN between pair sites was the strong predictor of temporal coherence for chlorophyll a in down and middle reach of the bay, while the relative difference in Anorganic Suspended Solids was the important factor regulating temporal coherence in middle and upper reach. Contrary to many studies, these results illustrate that, in a small geographic area (a single reservoir bay of approximately 25 km), spatial heterogeneity influence synchrony of phytoplankton dynamics during spring bloom and local processes may override the effects of regional processes or dispersal. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Interaction between hesperetin and human serum albumin revealed by spectroscopic methods

Hesperetin (5,7,3'-trihydroxyl-4'-methoxyl-flavanone) is an important bioactive compound in Chinese traditional medicine and has multiple biological and pharmacological activities. The interaction of hesperetin with human serum albumin (HSA) has been investigated by UV absorption, fluorescence and Fourier transformed infrared spectrometry. Fluorescence results showed that one molecule of protein combined with one molecule of drug at the molar ratio of drug to HSA ranging from 0.3 to 7 and the binding affinity (K(A)) was 8.11x10(4) M(-1). The primary binding site was most likely located on subdomain IIA. The binding ability of the drug to protein decreased from pH 6.4 to 8.4 in the drug to protein molar ratio of 1. Combining the curve-fitting results of infrared amide I band in D2O and H2O phosphate buffers, the alterations of protein secondary structure after drug complexation were estimated. With increasing the drug concentration, the percentage of protein alpha-helix structure decreased gradually. The reduction of protein alpha-helix structure reached about 7-9% after the protein interacted with hesperetin in D2O and H2O buffer solution at pH 7.4 when the drug to protein molar ratio was 10. This indicated a partial unfolding of HSA in the presence of the drug. From the results of UV absorption, fluorescence and Fourier transformed infrared spectrometry, the binding mode was discussed. The main mechanism of protein fluorescence quenching was a static quenching process and the hydroxyl groups of the drug in its neutral part played an important role in the binding process.     

Modeling the two‐locus architecture of divergent pollinator adaptation: how variation in SAD paralogs affects fitness and evolutionary divergence in sexually deceptive orchids

Divergent selection by pollinators can bring about strong reproductive isolation via changes at few genes of large effect. This has recently been demonstrated in sexually deceptive orchids, where studies (1) quantified the strength of reproductive isolation in the field; (2) identified genes that appear to be causal for reproductive isolation; and (3) demonstrated selection by analysis of natural variation in gene sequence and expression. In a group of closely related Ophrys orchids, specific floral scent components, namely n‐alkenes, are the key floral traits that control specific pollinator attraction by chemical mimicry of insect sex pheromones. The genetic basis of species‐specific differences in alkene production mainly lies in two biosynthetic genes encoding stearoyl–acyl carrier protein desaturases (SAD) that are associated with floral scent variation and reproductive isolation between closely related species, and evolve under pollinator‐mediated selection. However, the implications of this genetic architecture of key floral traits on the evolutionary processes of pollinator adaptation and speciation in this plant group remain unclear. Here, we expand on these recent findings to model scenarios of adaptive evolutionary change at SAD2 and SAD5, their effects on plant fitness (i.e., offspring number), and the dynamics of speciation. Our model suggests that the two‐locus architecture of reproductive isolation allows for rapid sympatric speciation by pollinator shift; however, the likelihood of such pollinator‐mediated speciation is asymmetric between the two orchid species O. sphegodes and O. exaltata due to different fitness effects of their predominant SAD2 and SAD5 alleles. Our study not only provides insight into pollinator adaptation and speciation mechanisms of sexually deceptive orchids but also demonstrates the power of applying a modeling approach to the study of pollinator‐driven ecological speciation.     

Therapeutic effects of CXCR4+ subpopulation of transgene‐free induced cardiosphere‐derived cells on experimental myocardial infarction

ObjectivesMyocardial infarction (MI) is the most predominant type of cardiovascular diseases with high mortality and morbidity. Stem cell therapy, especially cardiac progenitor cell therapy, has been proposed as a promising approach for cardiac regeneration and MI treatment. Previously, we have successfully generated cardiac progenitor‐like cells, induced cardiosphere (iCS), via somatic reprogramming. However, the genome integration characteristic of virus‐based reprogramming approach hampered their therapeutic applications due to the risk of tumour formation. In the current study, we aim to establish a safer iCS generation strategy with transgene‐free approaches.Materials and MethodsFour transgene‐free approaches for somatic reprogramming, including episome, minicircle, self‐replicative RNA, and sendai virus, were compared, from the perspective of cardiac progenitor marker expression, iCS formation, and cardiac differentiation. The therapeutic effects were assessed in the mouse model of MI, from the perspective of survival rate, cardiac function, and structural alterations.ResultsThe self‐replicative RNA approach produced more iCS, which had cardiomyocyte differentiation ability and therapeutic effects on the mouse model of MI with comparable levels with endogenous cardiospheres and iCS generated with retrovirus. In addition, the CXCR4 (C‐X‐C chemokine receptor 4) positive subpopulation of iCS derived cells (iCSDC) delivered by intravenous injection was found to have similar therapeutic effects with intramyocardial injection on the mouse model of MI, representing a safer delivery approach.ConclusionThus, the optimized strategy for iCS generation is safer and has more therapeutic potentials.     

Identification,Design and Bio-Evaluation of Novel Hsp90 Inhibitors by Ligand-Based Virtual Screening

Heat shock protein 90 (Hsp90), whose inhibitors have shown promising activity in clinical trials, is an attractive anticancer target. In this work, we first explored the significant pharmacophore features needed for Hsp90 inhibitors by generating a 3D-QSAR pharmacophore model. It was then used to virtually screen the SPECS databases, identifying 17 hits. Compound S1 and S13 exhibited the most potent inhibitory activity against Hsp90, with IC₅₀ value 1.61±0.28 μM and 2.83±0.67 μM, respectively. Binding patterns analysis of the two compounds with Hsp90 revealed reasonable interaction modes. Further evaluation showed that the compounds exhibited good anti-proliferative effects against a series of cancer cell lines with high expression level of Hsp90. Meanwhile, S13 induced cell apoptosis in a dose-dependent manner in different cell lines. Based on the consideration of binding affinities, physicochemical properties and toxicities, 24 derivatives of S13 were designed, leading to the more promising compound S40, which deserves further optimization.     

Monitoring Hip and Elbow Dysplasia Achieved Modest Genetic Improvement of 74 Dog Breeds over 40 Years in USA

Hip (HD) and Elbow Dysplasia (ED) are two common complex developmental disorders of dogs. In order to decrease their prevalence and severity, the Orthopedic Foundation for Animals (OFA) has a voluntary registry of canine hip and elbow conformation certified by boarded radiologists. However, the voluntarily reports have been severely biased against exposing dogs with problems, especially at beginning period. Fluctuated by additional influential factors such as age, the published raw scores barely showed trends of improvement. In this study, we used multiple-trait mixed model to simultaneously adjust these factors and incorporate pedigree to derive Estimated Breeding Values (EBV). A total of 1,264,422 dogs from 74 breeds were evaluated for EBVs from 760,455 hip scores and 135,409 elbow scores. These EBVs have substantially recovered the reporting bias and the other influences. Clear and steady trends of genetic improvement were observed over the 40 years since 1970. The total genetic improvements were 16.4% and 1.1% of the phenotypic standard deviation for HD and ED, respectively. The incidences of dysplasia were 0.83% and 2.08%, and the heritabilities were estimated as 0.22 and 0.17 for hip and elbow scores, respectively. The genetic correlation between them was 0.12. We conclude that EBV is more effective than reporting raw phenotype. The weak genetic correlation suggested that selection based on hip scores would also slightly improve elbow scores but it is necessary to allocate effort toward improvement of elbow scores alone.