Evolutionary trajectories of two distinct avian influenza epidemics: Parallelisms and divergences

Influenza A virus can quickly acquire genetic mutations that may be associated with increased virulence, host switching or antigenic changes. To provide new insights into the evolutionary dynamics and the adaptive strategies of distinct avian influenza lineages in response to environmental and host factors, we compared two distinct avian influenza epidemics caused by the H7N1 and H7N3 subtypes that circulated under similar epidemiological conditions, including the same domestic species reared in the same densely populated poultry area for similar periods of time.The two strains appear to have experienced largely divergent evolution: the H7N1 viruses evolved into a highly pathogenic form, while the H7N3 did not. However, a more detailed molecular and evolutionary analysis revealed several common features: (i) the independent acquisition of 32 identical mutations throughout the entire genome; (ii) the evolution and persistence of two sole genetic groups with similar genetic characteristics; (iii) a comparable pattern of amino acid variability of the HA proteins during the low pathogenic epidemics; and (iv) similar rates of nucleotide substitutions. These findings suggest that the evolutionary trajectories of viruses with the same virulence level circulating in analogous epidemiological conditions may be similar. In addition, our deep sequencing analysis of 15 samples revealed that 17 of the 32 parallel mutations were already present at the beginning of the two epidemics, suggesting that fixation of these mutations may occur with different mechanisms, which may depend on the fitness gain provided by each mutation. This highlighted the difficulties in predicting the acquisition of mutations that can be correlated to viral adaptation to specific epidemiological conditions or to changes in virus virulence.     

The Clitoris—An Appraisal of its Reproductive Function During the Fertile Years: Why Was It,and Still Is,Overlooked in Accounts of Female Sexual Arousal

Stimulating the clitoris activates the brain to instigate changes in the female genital tract, namely, the enhancement of vaginal blood flow that increases vaginal luminal pO₂, vaginal transudate (lubrication) facilitating painless penile penetration and partial neutralization of the basal luminal acidic pH, vaginal tenting, and ballooning delaying sperm transport and allowing semen de-coagulation and capacitation (sperm activation) factors to act until arousal ends (often by orgasm induction). All these genital changes taken together are of major importance in facilitating the possibility of reproductive success (and thus gene propagation) no matter how or when the clitoris is stimulated—they reveal its overlooked reproductive function. Of course, also commensurate with these changes, is its activation of sexual pleasure. The clitoris thus has both procreative (reproductive) and recreative (pleasure) functions of equal importance. Clitoridectomy creates not only sexual disability but also a reproductive disability. Clin. Anat. 32:136–145, 2019. © 2019 Wiley Periodicals, Inc.     

芍药甘草汤的历史沿革与现代研究

芍药甘草汤最早见于张仲景《伤寒杂病论》,由白芍和甘草(炙)等比例配伍而成,具有养血敛阴、调和肝脾、缓急止痛之功效,用于血虚津伤和筋脉失濡所致的腿脚挛急、脘腹疼痛。被历代医家推崇并沿用至今,并且拓展出了应用范围。现代药理研究表明,芍药甘草汤具有显著的解痉、止痛、镇咳、平喘及抗炎等作用,用于治疗痉挛性疾病、疼痛性疾病、炎症性疾病、支气管哮喘及妇产科疾病等。笔者从芍药甘草汤的历史沿革与方义衍变、组方配伍分析、药理药效学研究、现代临床应用4个方面进行系统阐述,以期为该经典名方的现代研究开发提供理论依据和文献参考,并为其制剂的临床定位提供理论和实践支撑。     

Transposable elements shape the human proteome landscape via formation of cis‐acting upstream open reading frames

Transposons are major drivers of mammalian genome evolution. To obtain new insights into the contribution of transposons to the regulation of protein translation, we here examined how transposons affected the genesis and function of upstream open reading frames (uORFs), which serve as cis‐acting elements to regulate translation from annotated ORFs (anORFs) located downstream of the uORFs in eukaryotic mRNAs. Among 39,786 human uORFs, 3,992 had ATG trinucleotides of a transposon origin, termed “transposon‐derived upstream ATGs” or TuATGs. Luciferase reporter assays suggested that many TuATGs modulate translation from anORFs. Comparisons with transposon consensus sequences revealed that most TuATGs were generated by nucleotide substitutions in non‐ATG trinucleotides of integrated transposons. Among these non‐ATG trinucleotides, GTG and ACG were converted into TuATGs more frequently, indicating a CpG methylation‐mediated process of TuATG formation. Interestingly, it is likely that this process accelerated human‐specific upstream ATG formation within transposon sequences in 5′ untranslated regions after divergence between human and nonhuman primates. Methylation‐mediated TuATG formation seems to be ongoing in the modern human population and could alter the expression of disease‐related proteins. This study shows that transposons have potentially been shaping the human proteome landscape via cis‐acting uORF creation.     

本草名词艾叶演变探析

艾作为一味中药,其名称最早出现在《诗经》中,其后又在本草古籍中称为艾蒿、灸草、蕲艾、黄草、医草、家艾、甜艾、草蓬、艾蓬、狼尾蒿子、香艾、野莲头、阿及艾、艾叶等等,其功用和主治也发生了变化,文章试就艾的发展演变进行探讨。     

舟山市3例发热伴血小板减少综合征的病原学与遗传特征

目的 对舟山市3例疑似发热伴血小板减少综合征(SFTS)病例进行病原学鉴定、确诊,并分析其遗传特征.方法 选用巢式RT-PCR测定新布尼亚病毒核酸及L、M、S3个特异性基因,并对基因扩增产物进行测序,测序结果与GenBank上公布的序列进行比对确认.用DNAStar软件构建进化树与序列距离表.用间接免疫荧光法测定患者恢复期和急性期血清新布尼亚病毒IgG抗体滴度.结果 3例SFTS患者急性期血清中均能检测到新布尼亚病毒的3个特异性基因片段,其中S基因核苷酸序列与舟山市同类基因核苷酸序列的同源性在94.4％～ 100.0％,患者恢复期血清病毒抗体滴度较急性期增高4倍以上.结论 经过病原学鉴定,3例临床疑似患者确诊为发热伴血小板减少综合征的新近感染病例.舟山市新布尼亚病毒的遗传特征比较稳定.     

Comparative anatomy of neonates of the three major mammalian groups (monotremes,marsupials, placentals) and implications for the ancestral mammalian neonate morphotype

The existing different modes of reproduction in monotremes, marsupials and placentals are the main source for our current understanding of the origin and evolution of the mammalian reproduction. The reproductive strategies and, in particular, the maturity states of the neonates differ remarkably between the three groups. Monotremes, for example, are the only extant mammals that lay eggs and incubate them for the last third of their embryonic development. In contrast, marsupials and placentals are viviparous and rely on intra‐uterine development of the neonates via choriovitelline (mainly marsupials) and chorioallantoic (mainly placentals) placentae. The maturity of a newborn is closely linked to the parental care strategy once the neonate is born. The varying developmental degrees of neonates are the main focus of this study. Monotremes and marsupials produce highly altricial and nearly embryonic offspring. Placental mammals always give birth to more developed newborns with the widest range from altricial to precocial. The ability of a newborn to survive and grow in the environment it was born in depends highly on the degree of maturation of vital organs at the time of birth. Here, the anatomy of four neonates of the three major extant mammalian groups is compared. The basis for this study is histological and ultrastructural serial sections of a hatchling of Ornithorhynchus anatinus (Monotremata), and neonates of Monodelphis domestica (Marsupialia), Mesocricetus auratus (altricial Placentalia) and Macroscelides proboscideus (precocial Placentalia). Special attention was given to the developmental stages of the organs skin, lung, liver and kidney, which are considered crucial for the maintenance of vital functions. The state of the organs of newborn monotremes and marsupials are found to be able to support a minimum of vital functions outside the uterus. They are sufficient to survive, but without capacities for additional energetic challenges. The organs of the altricial placental neonate are further developed, able to support the maintenance of vital functions and short‐term metabolic increase. The precocial placental newborn shows the most advanced state of organ development, to allow the maintenance of vital functions, stable thermoregulation and high energetic performance. The ancestral condition of a mammalian neonate is interpreted to be similar to the state of organ development found in the newborns of marsupials and monotremes. In comparison, the newborns of altricial and precocial placentals are derived from the ancestral state to a more mature developmental degree associated with advanced organ systems.     

Evidence of a conserved functional role for DNA methylation in termites

Many organisms are capable of developing distinct phenotypes from the same genotype. This developmental plasticity is particularly prevalent in insects, which can produce alternate adaptive forms in response to distinct environmental cues. The ability to develop divergent phenotypes from the same genotype often relies on epigenetic information, which affects gene function and is transmitted through cell divisions. One of the most important epigenetic marks, DNA methylation, has been lost in several insect lineages, yet its taxonomic distribution and functional conservation remain uninvestigated in many taxa. In the present study, we demonstrate that the signature of high levels of DNA methylation exists in the expressed genes of two termites, Reticulitermes flavipes and Coptotermes formosanus. Further, we show that DNA methylation is preferentially targeted to genes with ubiquitous expression among morphs. Functional associations of DNA methylation are also similar to those observed in other invertebrate taxa with functional DNA methylation systems. Finally, we demonstrate an association between DNA methylation and the long‐term evolutionary conservation of genes. Overall, our findings strongly suggest DNA methylation is present at particularly high levels in termites and may play similar roles to those found in other insects.