空间 、 身体 、女权: 中国都市女性写作

Chinese women have been continuous hits in mass media throughout the past decade. While names such as Mian Mian and Wei Hui have caught the attention of readers with their fin de siècle decadent writings, or , “genital writingd” as labeled by some critics, Mu Zimei, Zhuying Qingtong and Sister Lotus have excited netizens with their online sex diaries, hawking details of one-night stands, nude self-portraits, and pictures of flirtatious gestures respectively, which have caused far greater disturbances in China.On top of investigating whether these writers have bravely subverted the sexual hierarchy and avenged traditionally oppressed Chinese women or if they have willingly commercialized and objectified the female body, this article pays special attention to the notion of privacy and its relationship to the rise of the modern city and examines the complexity of privacy and publicity intruding upon one another in literary space. It proposes that contemporary Chinese literature has experienced a metamorphosis from an invasion of the private space by public space, specifically Maoist discourse, during the revolutionary periods to an intrusion of the public space by private space with the help of the Internet in capitalistic-communist China. This article also suggests that what the bad girl writers and bloggers have done would have been a revolution to celebrate the renaissance of the hidden and suppressed body in the traditionally male-orientated Chinese culture and a new representation of feminine consciousness of Chinese women. However, the body, intentionally used as the selling point of the works, has been objectified, marketized, and thus turned into a production of capitalist consumerism. As a result, instead of discovering the feminine consciousness, the female body serves to signify a re-entrapment of femininity by male chauvinism

HC-030031, a TRPA1 selective antagonist, attenuates inflammatory- and neuropathy-induced mechanical hypersensitivity

<p>Abstract</p> <p>Background</p> <p>Safe and effective treatment for chronic inflammatory and neuropathic pain remains a key unmet medical need for many patients. The recent discovery and description of the transient receptor potential family of receptors including TRPV1 and TRPA1 has provided a number of potential new therapeutic targets for treating chronic pain. Recent reports have suggested that TRPA1 may play an important role in acute formalin and CFA induced pain. The current study was designed to further explore the therapeutic potential of pharmacological TRPA1 antagonism to treat inflammatory and neuropathic pain.</p> <p>Results</p> <p>The <it>in vitro </it>potencies of HC-030031 versus cinnamaldehyde or allyl isothiocyanate (AITC or Mustard oil)-induced TRPA1 activation were 4.9 ± 0.1 and 7.5 ± 0.2 μM respectively (IC₅₀). These findings were similar to the previously reported IC₅₀of 6.2 μM against AITC activation of TRPA1 <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>. In the rat, oral administration of HC-030031 reduced AITC-induced nocifensive behaviors at a dose of 100 mg/kg. Moreover, oral HC-030031 (100 mg/kg) significantly reversed mechanical hypersensitivity in the more chronic models of Complete Freunds Adjuvant (CFA)-induced inflammatory pain and the spinal nerve ligation model of neuropathic pain.</p> <p>Conclusion</p> <p>Using oral administration of the selective TRPA1 antagonist HC-030031, our results demonstrated that TRPA1 plays an important role in the mechanisms responsible for mechanical hypersensitivity observed in inflammatory and neuropathic pain models. These findings suggested that TRPA1 antagonism may be a suitable new approach for the development of a potent and selective therapeutic agent to treat both inflammatory and neuropathic pain.</p

HC-030031, a TRPA1 selective antagonist, attenuates inflammatory- and neuropathy-induced mechanical hypersensitivity

<p>Abstract</p> <p>Background</p> <p>Safe and effective treatment for chronic inflammatory and neuropathic pain remains a key unmet medical need for many patients. The recent discovery and description of the transient receptor potential family of receptors including TRPV1 and TRPA1 has provided a number of potential new therapeutic targets for treating chronic pain. Recent reports have suggested that TRPA1 may play an important role in acute formalin and CFA induced pain. The current study was designed to further explore the therapeutic potential of pharmacological TRPA1 antagonism to treat inflammatory and neuropathic pain.</p> <p>Results</p> <p>The <it>in vitro </it>potencies of HC-030031 versus cinnamaldehyde or allyl isothiocyanate (AITC or Mustard oil)-induced TRPA1 activation were 4.9 ± 0.1 and 7.5 ± 0.2 μM respectively (IC₅₀). These findings were similar to the previously reported IC₅₀of 6.2 μM against AITC activation of TRPA1 <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>. In the rat, oral administration of HC-030031 reduced AITC-induced nocifensive behaviors at a dose of 100 mg/kg. Moreover, oral HC-030031 (100 mg/kg) significantly reversed mechanical hypersensitivity in the more chronic models of Complete Freunds Adjuvant (CFA)-induced inflammatory pain and the spinal nerve ligation model of neuropathic pain.</p> <p>Conclusion</p> <p>Using oral administration of the selective TRPA1 antagonist HC-030031, our results demonstrated that TRPA1 plays an important role in the mechanisms responsible for mechanical hypersensitivity observed in inflammatory and neuropathic pain models. These findings suggested that TRPA1 antagonism may be a suitable new approach for the development of a potent and selective therapeutic agent to treat both inflammatory and neuropathic pain.</p

Variation in calanoid copepod resting egg abundance among lakes with different acidification histories

Abstract The maintenance of species and genetic diversity within zooplankton egg banks may be crucial to the re-establishment of zooplankton communities following historical disturbance, such as anthropogenic acidification which globally caused widespread damage to ecological communities. Despite this, no other study has described basic characteristics of zooplankton egg banks among lakes with different acidification histories, such as variation in resting egg concentration. Theoretically, habitats with frequent periods of harsh environmental conditions are expected to select for resting egg production or prolonged dormancy in zooplankton, which would increase the size of the resting egg bank in lake sediments. In this study, we compared abundances of viable and inviable calanoid copepod resting eggs among three freshwater lakes with different acidification histories. While Swan Lake underwent major chemical and biological changes from acid and metal deposition, Teardrop and Bat lakes were relatively unaffected by historical acidification and had comparatively constant, but different pH over time. We also tested the effect of age on the viability of resting eggs. As predicted, higher numbers of viable resting eggs were found in recent sediments from acid-recovering Swan Lake compared to study lakes with relatively temporally constant environments (Teardrop and Bat lakes) when the total number of eggs was held as a covariate. We detected this result in spite of similar pelagic abundances of Leptodiaptomus minutus, the dominant species in zooplankton communities of these lakes. This pattern did not necessarily hold for inviable egg concentrations since these eggs were more abundant in both Swan and Bat lakes compared to Teardrop Lake in older sediments (1939-1951, 1800s). Within study lakes, the abundance of viable resting eggs declined with increased egg age. Further study is required to test mechanisms underlying these patterns

Allergen Delivery Inhibitors: A Rationale for Targeting Sentinel Innate Immune Signaling of Group 1 House Dust Mite Allergens through Structure-Based Protease Inhibitor Design

Diverse evidence from epidemiologic surveys and investigations into the molecular basis of allergenicity have revealed that a small cadre of “initiator” allergens promote the development of allergic diseases, such as asthma, allergic rhinitis, and atopic dermatitis. Pre-eminent among these initiators are the group 1 allergens from house dust mites (HDM). In mites, group 1 allergens function as cysteine peptidase digestive enzymes to which humans are exposed by inhalation of HDM fecal pellets. Their protease nature confers the ability to activate high gain signaling mechanisms which promote innate immune responses, leading to the persistence of allergic sensitization. An important feature of this process is that the initiator drives responses both to itself and to unrelated allergens lacking these properties through a process of collateral priming. The clinical significance of group 1 HDM allergens in disease, their serodominance as allergens, and their IgE-independent bioactivities in innate immunity make these allergens interesting therapeutic targets in the design of new small-molecule interventions in allergic disease. The attraction of this new approach is that it offers a powerful, root-cause-level intervention from which beneficial effects can be anticipated by interference in a wide range of effector pathways associated with these complex diseases. This review addresses the general background to HDM allergens and the validation of group 1 as putative targets. We then discuss structure-based drug design of the first-in-class representatives of allergen delivery inhibitors aimed at neutralizing the proteolytic effects of HDM group 1 allergens, which are essential to the development and maintenance of allergic diseases

Loss of LAMP5 Interneurons Drives Neuronal Network Dysfunction in Alzheimer’s Disease

In Alzheimer\u27s disease (AD), where amyloid-β (Aβ) and tau deposits in the brain, hyperexcitation of neuronal networks is an underlying disease mechanism, but its cause remains unclear. Here, we used the Collaborative Cross (CC) forward genetics mouse platform to identify modifier genes of neuronal hyperexcitation. We found LAMP5 as a novel regulator of hyperexcitation in mice, critical for the survival of distinct interneuron populations. Interestingly, synaptic LAMP5 was lost in AD brains and LAMP5 interneurons degenerated in different AD mouse models. Genetic reduction of LAMP5 augmented functional deficits and neuronal network hypersynchronicity in both Aβ- and tau-driven AD mouse models. To this end, our work defines the first specific function of LAMP5 interneurons in neuronal network hyperexcitation in AD and dementia with tau pathology

Heterogeneous Nuclear Ribonucleoprotein K Is Overexpressed in Acute Myeloid Leukemia and Causes Myeloproliferation in Mice via Altered

Acute myeloid leukemia (AML) is driven by numerous molecular events that contribute to disease progression. Herein, we identify hnRNP K overexpression as a recurrent abnormality in AML that negatively correlates with patient survival. Overexpression of hnRNP K in murine fetal liver cells results in altered self-renewal and differentiation potential. Further, murine transplantation models reveal that hnRNP K overexpression results in myeloproliferation in vivo. Mechanistic studies expose a direct functional relationship between hnRNP K and RUNX1—a master transcriptional regulator of hematopoiesis often dysregulated in leukemia. Molecular analyses show that overexpression of hnRNP K results in an enrichment of an alternatively spliced isoform of RUNX1 lacking exon 4. Our work establishes hnRNP K’s oncogenic potential in influencing myelogenesis through its regulation of RUNX1 splicing and subsequent transcriptional activity

Overview of the Microbiome Among Nurses study (Micro-N) as an example of prospective characterization of the microbiome within cohort studies

A lack of prospective studies has been a major barrier for assessing the role of the microbiome in human health and disease on a population-wide scale. To address this significant knowledge gap, we have launched a large-scale collection targeting fecal and oral microbiome specimens from 20,000 women within the Nurses’ Health Study II cohort (the Microbiome Among Nurses study, or Micro-N). Leveraging the rich epidemiologic data that have been repeatedly collected from this cohort since 1989; the established biorepository of archived blood, urine, buccal cell, and tumor tissue specimens; the available genetic and biomarker data; the cohort’s ongoing follow-up; and the BIOM-Mass microbiome research platform, Micro-N furnishes unparalleled resources for future prospective studies to interrogate the interplay between host, environmental factors, and the microbiome in human health. These prospectively collected materials will provide much-needed evidence to infer causality in microbiome-associated outcomes, paving the way toward development of microbiota-targeted modulators, preventives, diagnostics and therapeutics. Here, we describe a generalizable, scalable and cost-effective platform used for stool and oral microbiome specimen and metadata collection in the Micro-N study as an example of how prospective studies of the microbiome may be carried out

Endogenous Levels of Circulating Androgens and Risk of Crohn's Disease and Ulcerative Colitis Among Women: A Nested Case–Control Study from the Nurses' Health Study Cohorts

Background: Androgens, which are known to be altered by exogenous hormone use, have recently been linked to alterations of the gut microbiome and mucosal immune function. No study has evaluated the association between circulating levels of androgens and risk of Crohn's disease (CD) and ulcerative colitis (UC). Methods: We conducted a nested case–control study of women enrolled in the Nurses' Health Study and Nurses' Health Study II who provided a blood specimen. Cases of CD and UC were each matched to 2 controls. Prediagnosis plasma levels of dehydroepiandrosterone sulfate, testosterone, and sex hormone–binding globulin were measured. We examined the association of each analyte with risk of CD or UC using conditional logistic regression models. Results: Compared with women in the lowest quintile of testosterone, the multivariable-adjusted odds ratios for CD were 0.86 (95% confidence interval, 0.39–1.90) for women in the second quintile, 0.49 (95% confidence interval, 0.21–1.15) for the third quartile, 0.22 (0.08–0.65) for the fourth quintile, and 0.39 (95% confidence interval, 0.16–0.99) for the highest quintile (Plinear trend = 0.004). In contrast, we did not observe a consistent association between prediagnostic testosterone and risk of UC (Plinear trend = 0.84). We also did not observe any association between plasma levels of sex hormone–binding globulin or dehydroepiandrosterone sulfate and risk of UC or CD (all Plinear trends > 0.10). Conclusions: Among women, prediagnostic circulating testosterone is associated with a lower risk of CD but not UC. Further studies to understand the biological mechanisms by which endogenous androgens may mediate the etiopathogenesis of CD are warranted

Stability and reproducibility of proteomic profiles measured with an aptamer-based platform

The feasibility of SOMAscan, a multiplex, high sensitivity proteomics platform, for use in studies using archived plasma samples has not yet been assessed. We quantified 1,305 proteins from plasma samples donated by 16 Nurses’ Health Study (NHS) participants, 40 NHSII participants, and 12 local volunteers. We assessed assay reproducibility using coefficients of variation (CV) from duplicate samples and intra-class correlation coefficients (ICC) and Spearman correlation coefficients (r) of samples processed (i.e., centrifuged and aliquoted into separate components) immediately, 24, and 48 hours after collection, as well as those of samples collected from the same individuals 1 year apart. CVs were <20% for 99% of proteins overall and <10% for 92% of proteins in heparin samples compared to 66% for EDTA samples. We observed ICC or Spearman r (comparing immediate vs. 24-hour delayed processing) ≥0.75 for 61% of proteins, with some variation by anticoagulant (56% for heparin and 70% for EDTA) and protein class (ranging from 49% among kinases to 83% among hormones). Within-person stability over 1 year was good (ICC or Spearman r ≥ 0.4) for 91% of proteins. These results demonstrate the feasibility of SOMAscan for analyses of archived plasma samples