Two‐polymerase mechanisms dictate error‐free and error‐prone translesion DNA synthesis in mammals

DNA replication across blocking lesions occurs by translesion DNA synthesis (TLS), involving a multitude of mutagenic DNA polymerases that operate to protect the mammalian genome. Using a quantitative TLS assay, we identified three main classes of TLS in human cells: two rapid and error‐free, and the third slow and error‐prone. A single gene, REV3L, encoding the catalytic subunit of DNA polymerase ζ (polζ), was found to have a pivotal role in TLS, being involved in TLS across all lesions examined, except for a TT cyclobutane dimer. Genetic epistasis siRNA analysis indicated that discrete two‐polymerase combinations with polζ dictate error‐prone or error‐free TLS across the same lesion. These results highlight the central role of polζ in both error‐prone and error‐free TLS in mammalian cells, and show that bypass of a single lesion may involve at least three different DNA polymerases, operating in different two‐polymerase combinations.     

Rice Lesion Mimic Gene Cloning and Association Analysis for Disease Resistance

Lesion mimic mutants refer to a class of mutants that naturally form necrotic lesions similar to allergic reactions on leaves in the absence of significant stress or damage and without being harmed by pathogens. Mutations in most lesion mimic genes, such as OsACL-A2 and OsSCYL2, can enhance mutants’ resistance to pathogens. Lesion mimic mutants are ideal materials for studying programmed cell death (PCD) and plant defense mechanisms. Studying the genes responsible for the rice disease-like phenotype is of great significance for understanding the disease resistance mechanism of rice. In this paper, the nomenclature, occurrence mechanism, genetic characteristics, regulatory pathways, and the research progress on the cloning and disease resistance of rice lesion mimic mutant genes were reviewed, in order to further analyze the various lesion mimic mutants of rice. The mechanism lays a theoretical foundation and provides a reference for rice breeding.     

水稻类病斑突变体的生理与遗传分析

从全基因组水平上筛选获得了10个籼稻和8个粳稻类病斑(lesion resembling disease,lrd27-44)突变体.从突变体性状受环境影响敏感程度可以分为环境钝感型和环境敏感型.从发育进程可以分为全生育期类病斑型,营养生长阶段起始类病斑型和生殖生长阶段起始类病斑型.病斑的光诱导表明病斑由受光信号激发的程序性细胞死亡引起,而不受损伤诱导.对其中4个突变体lrd32,lrd39,lrd40和lrd42的遗传分析结果表明,这些类病斑性状由1或2对隐性基因控制.两个突变体lrd37和lrd40表现出对白叶枯病菌的广谱抗病性,有关基因定位克隆正在进行中.     

左旋千金藤啶碱D_1激动-D_2 阻滞作用引起伏核双相放电活动的电生理研究(英文)

为确定左旋千金藤啶碱 (SPD)对中脑边缘DA神经系统的作用特性 ,本研究采用细胞外记录的电生理学方法 ,观察微电泳和尾静脉给药对 6 OHDA损毁及未损毁大鼠的伏核 (NAc)单位放电的影响。结果显示 :SPD累积给药 ( 0 0 2～ 2mg/kg,iv)可诱发NAc神经元双相放电特征 ,即小剂量抑制、大剂量兴奋。预先给予D2 受体拮抗剂spiperone ,SPD则仅产生兴奋效应 ,并被D1拮抗剂SCH 2 3390所翻转或阻断 ,提示SPD对NAc神经元放电有D1激动特性。另一方面 ,大剂量SPD完全翻转D2 激动剂LY 1715 5 5和D1/D2 混合型激动剂阿朴吗啡对NAc神经元的抑制作用 ,表明SPD还具有D2 受体的阻滞特性。与静脉给药不同 ,NAc内微电泳SPD ( 30mmol/L ,2 0～ 80nA)很难诱发该神经核的兴奋或抑制性放电 ,而微电泳D1激动剂SKF 38393能产生明显的放电抑制效应。然而 ,在 6 OHDA损毁大鼠 ,微电泳SPD可使绝大多数NAc神经元 ( 91% )放电抑制 ,并为D1阻滞剂SCH 2 3390所完全拮抗 ,而不受D2 阻滞剂spiperone的影响。以上结果表明 ,SPD对NAc神经元活动具有‘D2 阻滞 D1激动’的双重药理作用特性 ,后者与SPD作用于mPFC的D1受体有密切关系 ,这有利于治疗精神分裂症     

感觉神经损伤后的变化及功能重建

切断家兔正中神经后,其支配区域的体感诱发电位消失,皮肤感觉神经末梢退变,正常轴浆转运中断。用桡神经浅支的尺侧分支与正中神经远端吻合后４周痛觉恢复,体感诱发电位重新出现,随修复后时间延长,该电位潜伏期缩短,波幅增高,在修复后３个月潜伏期接近正常,而波幅仅达正常值的１／２。与此同时,皮肤感觉神经末梢长出,辣根过氧化物酶逆行追踪显示,在原正中神经支配的前爪掌侧皮肤神经末梢与其胞体之间形成新的通路。本实验从功能与形态学上证明了损伤后感觉神经的功能重建。     

基于联邦深度学习的皮肤病智能诊断研究

近年来,基于人工智能的皮肤病智能诊断已经成为智慧医疗领域的热门课题。然而由于单一机构的数据有限,局部训练的神经网络难以满足医疗诊断服务的性能需求,从分散机构中收集数据的集中式学习又存在隐私泄漏的风险。基于上述挑战,本文提出一种基于联邦深度学习的皮肤病智能诊断算法。具体地,对比主流的集中式学习,为了在整合多方数据时防止隐私泄漏,本文引入了联邦学习。各客户端将本地模型发送到中心服务器进行聚合,中心服务器再将聚合得到的全局模型同步到各客户端,实现神经网络模型的训练。进一步,为了解决联邦学习中数据异构性的问题,本文在交叉熵损失的基础上增加了修正项,通过修正项限制本地模型和全局模型间的差异,增加模型对异构数据的关注度,从而减小数据异构对诊断结果的影响。实验结果表明,本文所提的皮肤病智能诊断算法与现有相关方案相比,诊断准确度提高了3%~4%,达到75.9%。     

Competition between the Plant-parasitic Nematodes Pratylenchus neglectus and Meloidogyne chitwoodi

In experiments on competition between Pratylenchus neglectus and Meloidogyne chitwoodi in barley, the species that parasitized the roots first inhibited penetration by the latter species. Prior presence of P. neglectus impeded the development of M. chitwoodi. Pratylenchus neglectus reduced egg production, final population levels, and reproductive index of M. chitwoodi. The reduction was linearly related to initial population densities of P. neglectus. Initial population densities of M. chitwoodi had no effect on final population levels of P. neglectus. Carbon assimilation by barley plants was reduced when either nematode species was present alone, but not when both were present together. Both nematode species assimilated lower amounts of carbon when present together than when present alone. A split-root experiment demonstrated that translocatable chemicals were not involved in the competition between the two species.     

Embryonic Barcoding of Equipotent Mammary Progenitors Functionally Identifies Breast Cancer Drivers

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Gross lesions in the Hubb octopus Octopus hubbsorum

A visible pathological condition located in the arms and mantle of the Hubb octopus Octopus hubbsorum from the Northeast Pacific waters is described for the first time. Histological sections confirmed later stages (fibrosis) of a chronic inflammatory condition of unknown aetiology.     

Factors predicting knee function in patients with meniscal lesions

The relationships between the magnitude of strength and muscle activation (EMG activity) deficits during maximal isokinetic knee movements and clinical and anthropometric factors (pain, effusion, type of meniscal lesion, degenerative changes, duration of symptoms and age) were studied in a group of 34 patients 5 days (5.3 ± 6.2 days) before arthroscopic meniscectomy. Moderate correlations were found between deficits in the area under the torque-angle curve (work) and the activation level in the agonist muscles during both the extension and flexion tests at 30° s⁻¹ and 180° s⁻¹ suggesting that the decrease in the isokinetic mechanical output is dependent on the reduced muscle activation. The severity of pain during tests was the best predictive clinical factor for the size of the work and EMG deficits but each of the tollowing factors: the presence of knee effusion and thigh atrophy, the type of meniscal lesion and the age of the patients, also had some predictive value for the magnitude of the deficits. In contrast, the duration of symptoms and the presence of osteo-articular degenerative changes were not related to the preoperative isokinetic knee performance. These results suggest that older patients (especially over 45 yr) with bucket-handle meniscal tears, knee effusion, thigh atrophy and severe pain on exertion, are most likely to have poor preoperative knee isokinetic performance. Since the magnitude of the pre- and postoperative knee deficits are correlated, it is important to identify patients at risk preoperatively so that optimal rehabilitation can be instituted.