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Although gene expression divergence has long been postulated to be the primary driver of human evolution, identifying the genes and genetic variants underlying uniquely human traits has proven to be quite challenging. Theory suggests that cell-type-specific cis-regulatory variants may fuel evolutionary adaptation due to the specificity of their effects. These variants can precisely tune the expression of a single gene in a single cell-type, avoiding the potentially deleterious consequences of trans-acting changes and non-cell type-specific changes that can impact many genes and cell types, respectively. It has recently become possible to quantify human-specific cis-acting regulatory divergence by measuring allele-specific expression in human-chimpanzee hybrid cells--the product of fusing induced pluripotent stem (iPS) cells of each species in vitro. However, these cis-regulatory changes have only been explored in a limited number of cell types. Here, we quantify human-chimpanzee cis-regulatory divergence in gene expression and chromatin accessibility across six cell types, enabling the identification of highly cell-type-specific cis-regulatory changes. We find that cell-type-specific genes and regulatory elements evolve faster than those shared across cell types, suggesting an important role for genes with cell-type-specific expression in human evolution. Furthermore, we identify several instances of lineage-specific natural selection that may have played key roles in specific cell types, such as coordinated changes in the cis-regulation of dozens of genes involved in neuronal firing in motor neurons. Finally, using novel metrics and a machine learning model, we identify genetic variants that likely alter chromatin accessibility and transcription factor binding, leading to neuron-specific changes in the expression of the neurodevelopmentally important genes FABP7 and GAD1. Overall, our results demonstrate that integrative analysis of cis-regulatory divergence in chromatin accessibility and gene expression across cell types is a promising approach to identify the specific genes and genetic variants that make us human. [ABSTRACT FROM AUTHOR]

The article analyzes issues associated with Chinese literature as revealed by Wang Guowei, Cai Yuanpei and Lu Xun. Topics discusesd include importance of political enchantment as highlighted in traditional Chinese aesthetics, Lu Xun's analysis of Qu Yuan affirming critical relation of literature to morality; deploying language of bodily exercise, rigorous training, and physical and spiritual energy by Lu Xun; reconsidering literature as a service provider and a didactic by Lu Xun.

ATP-sensitive K+ (KATP) channels are expressed in gastrointestinal smooth muscles, and their activity is regulated by muscarinic receptor stimulation. However, the physiological significance and mechanisms of muscarinic regulation of KATP channels are not fully understood. We examined the effects of the KATP channel opener cromakalim and the KATP channel blocker glibenclamide on electrical activity of single mouse ileal myocytes and on mechanical activity in ileal segment preparations. To explore muscarinic regulation of KATP channel activity and its underlying mechanisms, the effect of carbachol (CCh) on cromakalim-induced KATP channel currents ( IKATP) was studied in myocytes of M2 or M3 muscarinic receptor-knockout (KO) and wild-type (WT) mice. Cromakalim (10 µM) induced membrane hyperpolarization in single myocytes and relaxation in segment preparations from WT mice, whereas glibenclamide (10 µM) caused membrane depolarization and contraction. CCh (100 µM) induced sustained suppression of IKATP in cells from both WT and M2KO mice. However, CCh had a minimal effect on IKATP in M3KO and M2/M3 double-KO cells. The Gq/11 inhibitor YM-254890 (10 μM) and PLC inhibitor U73122 (1 μM), but not the PKC inhibitor calphostin C (1 μM), markedly decreased CCh-induced suppression of IKATP in WT cells. These results indicated that KATP channels are constitutively active and contribute to the setting of resting membrane potential in mouse ileal smooth muscles. M3 receptors inhibit the activity of these channels via a Gq/11/PLC-dependent but PKC-independent pathways, thereby contributing to membrane depolarization and contraction of smooth muscles. NEW & NOTEWORTHY We systematically investigated the regulation of ATP-sensitive K+ channels by muscarinic receptors expressed on mouse ileal smooth muscles. We found that M3 receptors inhibit the activity of ATP-sensitive K+ channels via a Gq/11/PLC-dependent, but PKC-independent, pathway. This muscarinic suppression of ATP-sensitive K+ channels contributes to membrane depolarization and contraction of smooth muscles. [ABSTRACT FROM AUTHOR]

The article looks into the role of the modern chinese novel in democracy and world literature. Topics include liberal humanism in relation to the Chinese Revolution, the May Fourth Enlightenment legacy of the Lu Xun Academy in China, and the concept of socialist humanism. It also examines how national autonomy influenced the people against imperialism and feudalism in the country.

The article discusses various reports published within the issue, including an investigation of the dialectical nature of unevenness in post-socialist China by Haomin Gong, the recourse in 1990s China by Rebecca Karl, and the withdrawal of authors from the Chinese Writers' Association by Haiyan Lee.

This article focuses on the diasporic phenomenon in a political community. Diaspora is associated with population movement, advances in communications technology, expansion of world markets and flows of capital and labour. It argues that the nation-state is an important factor in giving diasporics a sense of identity and community. The rise of a professional class and the boom in the Asian-Pacific economy have obscured the issue of rights rooted in nationally defined citizenship. The political community derives its power from history, traditions and cultural memory.

Ruptures of the social fabrics accompany China's rapid pace of development and its integration into the global market, severing the connection between cultural memory and history. Increasingly abstracted into economic, administrative, and exchange processes, the matrix of meaning and values that used to connect individuals to society and the past to the present has lost its self-evidence and cohesive power. In the emergent society of consumption and mass media the older Marxian notion of history as social and political practice is receding from public purview and China's past is being dissolved into spectacles. The 1980s critique of the grand narrative was taken over by the liberal-consumerist erasure of history under the spell of global capital. Cultural production has exhibited a downturn to the immediate and the everyday, to consumptive practices and frivolous pleasure. In opposition to this there arose a striving for renewed engagement with history, an intensified attempt to seek possibilities in the past for understanding and responding to swift changes. Wang Anyi's fiction epitomizes a serious engagement with history. This essay focuses on the mythical motif in Wang's fiction that draws on memory, associated with legend, folklore, and tradition, to critique the accelerative thrust of modern history. The novel Reality and Fiction (Jishi yu xugou) represents a poignant attempt to invoke a primordial history steeped in myth. The short story 'Marriage of the Fairies' ('Tianxian pei') illustrates the way memory can be a strong resource that binds a group into a community under the exigency of change as well as a critique of modernity. [ABSTRACT FROM AUTHOR]

Analyzes how geographical and historical differences influenced the circulation of capital. Notions about nostalgia; Controversies concerning real and abstract labor; Comment on the book 'Song of Unending Sorrow,' by Wang Anyi; Historical mutations of commodity.

Focuses on the availability of books on the tradition of Chinese cultural heritage in a local library in East Brunswick, New Jersey. Accounts of harrowing experiences of living in contemporary China; Formation of a genre of semiqutobiography; Impact of the September 11 terrorist attacks on the military memorabilia of the books.