368 research outputs found

    Saffronizing California’s History Curriculum: Long Distance Hindu Nationalism In The United States

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    How U.S. public schools teach South Asian history has been a site of contestation since the 2000s. California’s solicitation of community input into its history curriculum has brought ideological clashes to the California Department of Education (CDE); these conflicts over South Asian history are an extension of struggles in India driven by rising Hindu nationalism, a widespread movement for a “Hindus-first” India that brutalizes subaltern groups and dissenters. This violence is often justified through manufactured histories demonizing Indian minorities and glorifying an ancient, Hindu civilization. This dissertation focused on the 2016-2017 controversy surrounding the CDE’s process to revise its history curriculum. U.S.-based Hindu nationalist groups, including the Hindu American Foundation and the Uberoi Foundation, took part in the process starting in 2014. In 2015, South Asia academics submitted to the CDE numerous challenges to the accuracy and political messaging of the histories supported by Hindu nationalist groups. In 2016, progressive and minority activists became involved, forming a coalition called South Asian Histories for All (SAHFA) to support the scholarly recommendations and to challenge sectarian narratives. This perspectival case study, authored by a SAHFA member, analyzes Hindu nationalist efforts to influence California’s history curriculum, through interviews with scholars and activists critical of Hindu nationalism and analyzing public documents. This study utilized three analytical frames to challenge sectarian histories. The first frame identified key groups on different sides of the controversy and the funding involved. Using tax returns and public documents, the first data chapter established the Hindu nationalist affiliations of several major groups participating in California’s history revision process and the resources mobilized in support of their versions of South Asian history. The second chapter analyzed the political messaging of the histories supported by Hindu nationalist groups, recognizing the groups targeted by the prejudices and hate energized by such narratives (e.g. as connected to caste, gender, and religion) and relating the political messages to events in India and to critical responses from progressive groups. The third discussed the mobilization strategies used by Hindu nationalist groups to insert their histories into California’s history curriculum, and the responses from non-Hindutva scholars and activists

    Hydrothermal–galvanic couple synthesis of directionally oriented BaTiO3 thin films on TiN-coated substrates

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    AbstractBaTiO3 films were synthesized on TiN-coated Si substrate below 100°C by a hydrothermal–galvanic couple technique in barium contained alkaline solutions. X-ray diffraction and electron backscatter diffraction results show that the BaTiO3 thin films were directionally oriented grown on the TiN/Si substrates, i.e., (111) BaTiO3 over (111) TiN. The surface morphologies revealed that BaTiO3 nucleated and grew over the TiN surface with a single layer. From kinetic analyses, the growth rates of BaTiO3 films prepared by the hydrothermal–galvanic couple technique were faster than a hydrothermal method. The galvanic effects were confirmed by investigating the induced currents and energies. The galvanic currents were generated and controlled by both the dissolution of TiN and the formation of BaTiO3. The output electric energies increased rapidly with the reaction time and leveled off at the full coverage of BaTiO3

    Structural and cognitive deficits in chronic carbon monoxide intoxication: a voxel-based morphometry study

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    BACKGROUND: Patients with carbon monoxide (CO) intoxication may develop ongoing neurological and psychiatric symptoms that ebb and flow, a condition often called delayed encephalopathy (DE). The association between morphologic changes in the brain and neuropsychological deficits in DE is poorly understood. METHODS: Magnetic resonance imaging and neuropsychological tests were conducted on 11 CO patients with DE, 11 patients without DE, and 15 age-, sex-, and education-matched healthy subjects. Differences in gray matter volume (GMV) between the subgroups were assessed and further correlated with diminished cognitive functioning. RESULTS: As a group, the patients had lower regional GMV compared to controls in the following regions: basal ganglia, left claustrum, right amygdala, left hippocampus, parietal lobes, and left frontal lobe. The reduced GMV in the bilateral basal ganglia, left post-central gyrus, and left hippocampus correlated with decreased perceptual organization and processing speed function. Those CO patients characterized by DE patients had a lower GMV in the left anterior cingulate and right amygdala, as well as lower levels of cognitive function, than the non-DE patients. CONCLUSIONS: Patients with CO intoxication in the chronic stage showed a worse cognitive and morphologic outcome, especially those with DE. This study provides additional evidence of gray matter structural abnormalities in the pathophysiology of DE in chronic CO intoxicated patients

    INSL6 Protective Effects in Heart Failure

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    Background The insulin/insulin‐like growth factor/relaxin family represents a group of structurally related but functionally diverse proteins. The family member relaxin‐2 has been evaluated in clinical trials for its efficacy in the treatment of acute heart failure. In this study, we assessed the role of insulin‐like peptide 6 (INSL6), another member of this protein family, in murine heart failure models using genetic loss‐of‐function and protein delivery methods. Methods and Results Insl6‐deficient and wild‐type (C57BL/6N) mice were administered angiotensin II or isoproterenol via continuous infusion with an osmotic pump or via intraperitoneal injection once a day, respectively, for 2 weeks. In both models, Insl6‐knockout mice exhibited greater cardiac systolic dysfunction and left ventricular dilatation. Cardiac dysfunction in the Insl6‐knockout mice was associated with more extensive cardiac fibrosis and greater expression of fibrosis‐associated genes. The continuous infusion of chemically synthesized INSL6 significantly attenuated left ventricular systolic dysfunction and cardiac fibrosis induced by isoproterenol infusion. Gene expression profiling suggests liver X receptor/retinoid X receptor signaling is activated in the isoproterenol‐challenged hearts treated with INSL6 protein. Conclusions Endogenous Insl6 protein inhibits cardiac systolic dysfunction and cardiac fibrosis in angiotensin II– and isoproterenol‐induced cardiac stress models. The administration of recombinant INSL6 protein could have utility for the treatment of heart failure and cardiac fibrosis

    Serotonin receptor HTR6-mediated mTORC1 signaling regulates dietary restriction-induced memory enhancement

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    Dietary restriction (DR; sometimes called calorie restriction) has profound beneficial effects on physiological, psychological, and behavioral outcomes in animals and in humans. We have explored the molecular mechanism of DR-induced memory enhancement and demonstrate that dietary tryptophan-a precursor amino acid for serotonin biosynthesis in the brain-and serotonin receptor 5-hydroxytryptamine receptor 6 (HTR6) are crucial in mediating this process. We show that HTR6 inactivation diminishes DR-induced neurological alterations, including reduced dendritic complexity, increased spine density, and enhanced long-term potentiation (LTP) in hippocampal neurons. Moreover, we find that HTR6-mediated mechanistic target of rapamycin complex 1 (mTORC1) signaling is involved in DR-induced memory improvement. Our results suggest that the HTR6-mediated mTORC1 pathway may function as a nutrient sensor in hippocampal neurons to couple memory performance to dietary intake

    Antitumor Agents. 280. Multidrug Resistance-Selective Desmosdumotin B Analogues

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    6,6,8-Triethyldesmosdumotin B (2) was discovered as a MDR–selective flavonoid with significant in vitro anticancer activity against a multi-drug resistant (MDR) cell line (KB-VIN) but without activity against the parent cells (KB). Additional 2-analogues were synthesized and evaluated to determine the effect of B-ring modifications on MDR-selectivity. Analogues with a B-ring Me (3) or Et (4) group had substantially increased MDR–selectivity. Three new disubstituted analogues, 35, 37 and 49, also had high collateral sensitivity (CS) indices of 273, 250 and 100, respectively. Furthermore, 2–4 also displayed MDR-selectivity in an MDR hepatoma-cell system. While 2–4 showed either no or very weak inhibition of cellular P-glycoprotein (P-gp) activity, they either activated or inhibited the actions of the first generation P-gp inhibitors verapamil or cyclosporin, respectively

    Unfolded Protein Response as a Compensatory Mechanism and Potential Therapeutic Target in PLN R14del Cardiomyopathy

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    BACKGROUND: Phospholamban (PLN) is a critical regulator of calcium cycling and contractility in the heart. The loss of arginine at position 14 in PLN (R14del) is associated with dilated cardiomyopathy with a high prevalence of ventricular arrhythmias. How the R14 deletion causes dilated cardiomyopathy is poorly understood, and there are no disease-specific therapies. METHODS: We used single-cell RNA sequencing to uncover PLN R14del disease mechanisms in human induced pluripotent stem cells (hiPSC-CMs). We used both 2-dimensional and 3-dimensional functional contractility assays to evaluate the impact of modulating disease-relevant pathways in PLN R14del hiPSC-CMs. RESULTS: Modeling of the PLN R14del cardiomyopathy with isogenic pairs of hiPSC-CMs recapitulated the contractile deficit associated with the disease in vitro. Single-cell RNA sequencing revealed the induction of the unfolded protein response (UPR) pathway in PLN R14del compared with isogenic control hiPSC-CMs. The activation of UPR was also evident in the hearts from PLN R14del patients. Silencing of each of the 3 main UPR signaling branches (IRE1, ATF6, or PERK) by siRNA exacerbated the contractile dysfunction of PLN R14del hiPSC-CMs. We explored the therapeutic potential of activating the UPR with a small molecule activator, BiP (binding immunoglobulin protein) inducer X. PLN R14del hiPSC-CMs treated with BiP protein inducer X showed a dose-dependent amelioration of the contractility deficit in both 2-dimensional cultures and 3-dimensional engineered heart tissues without affecting calcium homeostasis. CONCLUSIONS: Together, these findings suggest that the UPR exerts a protective effect in the setting of PLN R14del cardiomyopathy and that modulation of the UPR might be exploited therapeutically

    Antitumor agents 283. Further elaboration of Desmosdumotin C analogs as potent antitumor agents: Activation of spindle assembly checkpoint as possible mode of action

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    In our ongoing study of the desmosdumotin C (1) series, twelve new analogues, 21–32, mainly with structural modifications in ring-A, were prepared and evaluated for in vitro antiproliferative activity against several human tumor cell lines. Among them, the 4′-iodo-3,3,5-tripropyl-4-methoxy analogue (31) showed significant antiproliferative activity against multiple human tumor cell lines with ED50 values of 1.1–2.8 μM. Elongation of the C-3 and C-5 carbon chains reduced activity relative to propyl substituted analogues; however, activity was still better than that of natural compound 1. Among analogues with various ether groups on C-4, compounds with methyl (2) and propyl (26) ethers inhibited cell growth of multiple tumor cells lines, while 28 with an isobutyl ether showed selective antiproliferative activity against lung cancer A549 cells (ED50 1.7 μM). The gene expression profiles showed that 3 may modulate the spindle assembly checkpoint (SAC) and chromosome separation, and thus, arrest cells at the G2/M-phase
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