Coronavirus Disease 2019 (COVID-19) is believed to have emerged in Wuhan, China in late December 2019 and began rapidly spreading around the globe throughout the spring months of 2020. As COVID-19 ...proliferated across the United States, Asian Americans reported a surge in racially motivated hate crimes involving physical violence and harassment. Throughout history, pandemic-related health crises have been associated with the stigmatization and “othering” of people of Asian descent. Asian Americans have experienced verbal and physical violence motivated by individual-level racism and xenophobia from the time they arrived in America in the late 1700s up until the present day. At the institutional level, the state has often implicitly reinforced, encouraged, and perpetuated this violence through bigoted rhetoric and exclusionary policies. COVID-19 has enabled the spread of racism and created national insecurity, fear of foreigners, and general xenophobia, which may be related to the increase in anti-Asian hate crimes during the pandemic. We examine how these crimes – situated in historically entrenched and intersecting individual-level and institutional-level racism and xenophobia – have operated to “other” Asian Americans and reproduce inequality.
Abstract
In females, ovarian estradiol (E2) exerts both negative and positive feedback regulation on the neural circuits governing reproductive hormone secretion, but the cellular and molecular ...mechanisms underlying this remain poorly understood. In rodents, estrogen receptor α–expressing kisspeptin neurons in the hypothalamic anteroventral periventricular region (AVPV) are prime candidates to mediate E2 positive feedback induction of preovulatory gonadotropin-releasing hormone and luteinizing hormone (LH) surges. E2 stimulates AVPV Kiss1 expression, but the full extent of estrogen effects in these neurons is unknown; whether E2 stimulates or inhibits other genes in AVPV Kiss1 cells has not been determined. Indeed, understanding of the function(s) of AVPV kisspeptin cells is limited, in part, by minimal knowledge of their overall molecular phenotype, as only a few genes are currently known to be co-expressed in AVPV Kiss1 cells. To provide a more detailed profiling of co-expressed genes in AVPV Kiss1 cells, including receptors and other signaling factors, and test how these genes respond to E2, we selectively isolated actively translated mRNAs from AVPV Kiss1 cells of female mice and performed RNA sequencing (RNA-seq). This identified >13 000 mRNAs co-expressed in AVPV Kiss1 cells, including multiple receptor and ligand transcripts positively or negatively regulated by E2. We also performed RNAscope to validate co-expression of several transcripts identified by RNA-seq, including Pdyn (prodynorphin), Penk (proenkephalin), Vgf (VGF), and Cartpt (CART), in female AVPV Kiss1 cells. Given the important role of AVPV kisspeptin cells in positive feedback, E2 effects on identified genes may relate to the LH surge mechanism and/or other physiological processes involving these cells.
Women in the United States are more likely to be killed by an intimate partner than anyone else, and prior, severe domestic violence (DV) is typically involved in such intimate partner homicides ...(IPH). Black women experience disproportionately high rates of DV and IPHs, severe injury, and abuse with weapons. Distinct patterns of escalating DV are associated with impending risk of re-victimization and lethal violence. One of the most common predictors associated with formal DV help-seeking is severity of physical violence. The current study uses semi-structured interviews with 11 severe abuse survivors to answer the following research questions: (1) How do women experiencing severe abuse make sense of DV resources across the course of their abusive relationships? (2) How do women experiencing severe abuse make sense of services when fear of death/homicide risk is present? Approximately 91% of the sample is comprised of women of color (WOC) survivors. Results demonstrate that WOC survivors navigated complex journeys toward formal DV help-seeking that involved resisting help-seeking when the abuse still felt manageable; delaying help-seeking to protect themselves from escalating violence; and hastening help-seeking when breaking points were reached and the risk of death felt tangible. DV resources took on a different meaning in participants’ lives as abuse became more severe across the abuse lifecourse, and in relation to life circumstances and patterns of abuse, and personal perceptions of homicide risk. WOC participants also often experienced multiple structural barriers to formal help-seeking and waited until the violence was severe and/or life-threatening to make first contact, which highlights the necessity of immediate risk assessment with responsive service offerings that address the link between DV and poverty, as well as regular follow-up and ongoing support.
The exemplary search capabilities of flying insects have established them as one of the most diverse taxa on Earth. However, we still lack the fundamental ability to quantify, represent, and predict ...trajectories under natural contexts to understand search and its applications. For example, flying insects have evolved in complex multimodal three-dimensional (3D) environments, but we do not yet understand which features of the natural world are used to locate distant objects. Here, we independently and dynamically manipulate 3D objects, airflow fields, and odor plumes in virtual reality over large spatial and temporal scales. We demonstrate that flies make use of features such as foreground segmentation, perspective, motion parallax, and integration of multiple modalities to navigate to objects in a complex 3D landscape while in flight. We first show that tethered flying insects of multiple species navigate to virtual 3D objects. Using the apple fly Rhagoletis pomonella, we then measure their reactive distance to objects and show that these flies use perspective and local parallax cues to distinguish and navigate to virtual objects of different sizes and distances. We also show that apple flies can orient in the absence of optic flow by using only directional airflow cues, and require simultaneous odor and directional airflow input for plume following to a host volatile blend. The elucidation of these features unlocks the opportunity to quantify parameters underlying insect behavior such as reactive space, optimal foraging, and dispersal, as well as develop strategies for pest management, pollination, robotics, and search algorithms.
Adolescents who experience prior victimization such as child abuse within the home and experience low self-esteem/depression are at higher risk of repetitive bullying victimization when compared to ...those without such experiences. Recent scholarship has explored growth trajectories of bullying during adolescent development; however, relatively little is known about distinct trajectory patterns of bullying victimization across adolescent development. The current study identifies unobserved subgroups thus capturing the heterogeneity in developmental pathways in bullying victimization.
The current study uniquely utilized a multitheoretical approach to help explain the phenomenon of bullying victimization among a national sample of 2,190 youth in South Korea from 2010 to 2016. Theories tested include the integrated approach of target congruence, lifestyle and routine activities theories (LRAT), and the state dependence and population heterogeneity perspectives. To conduct this analysis, we performed a three-step latent class growth analysis.
The study revealed three distinct trajectory groups. Korean adolescents who had higher levels of low self-esteem demonstrated greater odds of belonging to both the early-onset and decreasing and increasing and late peak groups. Those who had low-self-esteem and were depressed demonstrated greater odds of belonging to the early-onset and decreasing group. Prior experience of child abuse for the early-onset and decreasing group was fully mediated by the measures of target congruence and lifestyles.
The current study contributes to research on developmental victimization by demonstrating the utility of integrating target congruence variables with lifestyle-routine activity concepts in explaining heterogeneity.
Calorie restriction (CR) extends lifespan and has been shown to reduce age-related diseases including cancer, diabetes, and cardiovascular and neurodegenerative diseases in experimental models. ...Recent translational studies have tested the potential of CR or CR mimetics as adjuvant therapies to enhance the efficacy of chemotherapy, radiation therapy, and novel immunotherapies. Chronic CR is challenging to employ in cancer patients, and therefore intermittent fasting, CR mimetic drugs, or alternative diets (such as a ketogenic diet), may be more suitable. Intermittent fasting has been shown to enhance treatment with both chemotherapy and radiation therapy. CR and fasting elicit different responses in normal and cancer cells, and reduce certain side effects of cytotoxic therapy. Findings from preclinical studies of CR mimetic drugs and other dietary interventions, such as the ketogenic diet, are promising for improving the efficacy of anticancer therapies and reducing the side effects of cytotoxic treatments. Current and future clinical studies will inform on which cancers, and at which stage of the cancer process, CR, fasting, or CR mimetic regimens will prove most effective.
This paper elucidates some of the controlling factors governing soil desiccation. The desiccation tests were conducted on three materials -- clay, potato starch and milled quartz sand -- all three ...featuring similar fracture energy. Two controlling factors were identified in desiccation cracking, regardless of the material. The first is the tensile stress and strain energy development within the material when the material is restrained against shrinkage. The second factor is that the exact positions of crack initiations will be controlled by the flaws and/or pores within the material. If the material has particles giving relatively large and uniform pore sizes with high moisture diffusivity leading to high shrinkage energy prior to cracking, then the fracture energy balance indicates that cracking can occur in near hexagonal patterns with 1208 crack initiations, which occur predominantly simultaneously.
Kisspeptin, encoded by Kiss1, stimulates GnRH neurons to govern reproduction. In rodents, estrogen-sensitive kisspeptin neurons in the anterior ventral periventricular nucleus and neighboring ...periventricular nucleus are thought to mediate sex steroid-induced positive feedback induction of the preovulatory LH surge. These kisspeptin neurons coexpress estrogen and progesterone receptors and display enhanced neuronal activation during the LH surge. However, although estrogen regulation of kisspeptin neurons has been well studied, the role of progesterone signaling in regulating kisspeptin neurons is unknown. Here we tested whether progesterone action specifically in kisspeptin cells is essential for proper LH surge and fertility. We used Cre-lox technology to generate transgenic mice lacking progesterone receptors exclusively in kisspeptin cells (termed KissPRKOs). Male KissPRKOs displayed normal fertility and gonadotropin levels. In stark contrast, female KissPRKOs displayed earlier puberty onset and significant impairments in fertility, evidenced by fewer births and substantially reduced litter size. KissPRKOs also had fewer ovarian corpora lutea, suggesting impaired ovulation. To ascertain whether this reflects a defect in the ability to generate sex steroid-induced LH surges, females were exposed to an estradiol-positive feedback paradigm. Unlike control females, which displayed robust LH surges, KissPRKO females did not generate notable LH surges and expressed significantly blunted cfos induction in anterior ventral periventricular nucleus kisspeptin neurons, indicating that progesterone receptor signaling in kisspeptin neurons is required for normal kisspeptin neuronal activation and LH surges during positive feedback. Our novel findings demonstrate that progesterone signaling specifically in kisspeptin cells is essential for the positive feedback induction of normal LH surges, ovulation, and normal fertility in females.
Stress elicits activation of the hypothalamic-pituitary-adrenal axis, which leads to enhanced circulating glucocorticoids, as well as impaired gonadotropin secretion and ovarian cyclicity. Here, we ...tested the hypothesis that elevated, stress-levels of glucocorticoids disrupt ovarian cyclicity by interfering with the preovulatory sequence of endocrine events necessary for the LH surge. Ovarian cyclicity was monitored in female mice implanted with a cholesterol or corticosterone (Cort) pellet. Cort, but not cholesterol, arrested cyclicity in diestrus. Subsequent studies focused on the mechanism whereby Cort stalled the preovulatory sequence by assessing responsiveness to the positive feedback estradiol signal. Ovariectomized mice were treated with an LH surge-inducing estradiol implant, as well as Cort or cholesterol, and assessed several days later for LH levels on the evening of the anticipated surge. All cholesterol females showed a clear LH surge. At the time of the anticipated surge, LH levels were undetectable in Cort-treated females. In situ hybridization analyses the anteroventral periventricular nucleus revealed that Cort robustly suppressed the percentage of Kiss1 cells coexpressing cfos, as well as reduced the number of Kiss1 cells and amount of Kiss1 mRNA per cell, compared with expression in control brains. In addition, Cort blunted pituitary expression of the genes encoding the GnRH receptor and LHβ, indicating inhibition of gonadotropes during the blockage of the LH surge. Collectively, our findings support the hypothesis that physiological stress-levels of Cort disrupts ovarian cyclicity, in part, through disruption of positive feedback mechanisms at both the hypothalamic and pituitary levels which are necessary for generation of the preovulatory LH surge.
Understanding intra-articular biodistribution is imperative as candidate osteoarthritis (OA) drugs become increasingly site-specific. Cartilage has been identified as opportunistic for therapeutic ...intervention, but poses numerous barriers to drug delivery. To facilitate drug delivery to cartilage, nanoscale vehicles have been designed with different features that target the tissue's matrix. However, it is unclear if these targeting strategies are influenced by OA and the associated structural changes that occur in cartilage. The goal of this work was to study the effectiveness of different cartilage-targeting nanomaterials with respect to cartilage localization and retention, and to determine how these outcomes change in OA. To address these questions, a nanoparticle (NP) system was developed, and the formulation was tuned to possess three distinct cartilage-targeting strategies: (1) passive targeting cationic NPs for electrostatic attraction to cartilage, (2) active targeting NPs with binding peptides for collagen type II, and (3) untargeted neutrally-charged NPs. Ex vivo analyses with bovine cartilage explants demonstrated that targeting strategies significantly improved NP associations with both healthy and OA-like cartilage. In vivo studies with collagenase-induced OA in rats revealed that disease state influenced joint biodistribution for all three NP formulations. Importantly, the extent of cartilage accumulation for each NP system was affected by disease differently; with active NPs, but not passive NPs, cartilage accumulation was increased in OA relative to healthy knees. Together, this work suggests that NPs can be strategically designed for site-specific OA drug delivery, but the biodistribution of the NPs are influenced by the disease conditions into which they are delivered.
As emerging drugs for osteoarthritis are becoming increasingly site-specific, the need for targeted intra-articular drug delivery has evolved. To improve drug delivery to cartilage, targeting strategies for nanomaterials have been developed, but the manner in which these targeted systems accumulate at different sites within the joint remains poorly understood. Moreover, it is unclear how nanomaterial-tissue interactions change in osteoarthritic conditions, as tissue structure and composition change after disease onset. By understanding how nanomaterials distribute within healthy and disease joints, we can advance targeted drug delivery strategies and improve therapeutic outcomes for emerging drugs.
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