Making Gender Trouble: How Sex Education Subverts Compulsory Heteronormativity and Re- Imagines Judith Butler’s Gender Trouble

This paper approaches the internationally successful Netflix series Sex Education through Judith Butler’s Gender Trouble and investigates how the show – through its characters – imagines and constructs a realm of cultural possibility that exceeds the heteronormative matrix. This paper reads the representation of the characters Eric Effiong (Ncuti Gatwa) and Adam Groff (Connor Swindells) throughout the first season of Sex Education as an answer to questions Butler poses concerning identity and legibility. In doing so, this paper argues that the series subverts culturally constructed heteronormativity through the repetition of attributes which construct the heteronormative matrix. The show thus, through this repetition, destabilizes the attributes that – according to Butler – naturalize this exact matrix. This paper thus explores how Sex Education engages with Butler’s ideas and suggests how the realm of cultural possibility that Butler imagines might function

MOVILIDAD DE CAPITALES Y POLITICA MONETARIA EN COLOMBIA

En este documento se estima un modelo de los mercados financieros colombianos en el que se examinan: 1) El control de las autoridades sobre la tasa de interés; y 2) Los efectos de la política de "minidevaluaciones" sobre las expectativas de devaluación y la tasa interna de interés. Aparentemente, las autoridades poseen cierto control sobre la masa monetaria en el largo plazo, básicamente debido a la existencia del "control de cambios", pero gran parte de dicho control parece desvanecerse a medida que la demanda por activos tiende a ajustarse a su nivel deseado. La tasa esperada de devaluación no está ligada al ritmo de las "minidevaluaciones".POLITICA MONETARIA,

Various Insights into the Relationship between Love and Joy

In this open section, we have attempted to bring together the complexities and paradoxes entailed by the notions of love and joy. We have chosen different forms to express what love is, what it does, and what it can be. We have tried to capture the various ways in which love surfaces and attempted to connect it to its intricate joy without losing sight of the complexities of these notions

Absolute proteomic quantification reveals design principles of sperm flagellar chemosensation

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Troetschel, C., Hamzeh, H., Alvarez, L., Pascal, R., Lavryk, F., Boenigk, W., Koerschen, H. G., Mueller, A., Poetsch, A., Rennhack, A., Gui, L., Nicastro, D., Struenker, T., Seifert, R., & Kaupp, U. B. Absolute proteomic quantification reveals design principles of sperm flagellar chemosensation. Embo Journal, 39(4), (2020): e102723, doi:10.15252/embj.2019102723.Cilia serve as cellular antennae that translate sensory information into physiological responses. In the sperm flagellum, a single chemoattractant molecule can trigger a Ca2+ rise that controls motility. The mechanisms underlying such ultra‐sensitivity are ill‐defined. Here, we determine by mass spectrometry the copy number of nineteen chemosensory signaling proteins in sperm flagella from the sea urchin Arbacia punctulata. Proteins are up to 1,000‐fold more abundant than the free cellular messengers cAMP, cGMP, H+, and Ca2+. Opto‐chemical techniques show that high protein concentrations kinetically compartmentalize the flagellum: Within milliseconds, cGMP is relayed from the receptor guanylate cyclase to a cGMP‐gated channel that serves as a perfect chemo‐electrical transducer. cGMP is rapidly hydrolyzed, possibly via “substrate channeling” from the channel to the phosphodiesterase PDE5. The channel/PDE5 tandem encodes cGMP turnover rates rather than concentrations. The rate‐detection mechanism allows continuous stimulus sampling over a wide dynamic range. The textbook notion of signal amplification—few enzyme molecules process many messenger molecules—does not hold for sperm flagella. Instead, high protein concentrations ascertain messenger detection. Similar mechanisms may occur in other small compartments like primary cilia or dendritic spines.We thank Heike Krause for preparing the manuscript. Financial support by the Deutsche Forschungsgemeinschaft (DFG) via the priority program SPP 1726 “Microswimmers” and the Cluster of Excellence 1023 “ImmunoSensation” is gratefully acknowledged. We thank D. Stoddard for management of the UTSW cryo‐electron microscope facility, which is funded in part by a Cancer Prevention and Research Institute of Texas (CPRIT) Core Facility Award (RP170644). This study was supported by HHS|National Institutes of Health (NIH) grant R01 GM083122 and by CPRIT grant RR140082 to D. Nicastro

The ErbB2ΔEx16 splice variant is a major oncogenic driver in breast cancer that promotes a pro-metastatic tumor microenvironment.

Amplification and overexpression of erbB2/neu proto-oncogene is observed in 20-30% human breast cancer and is inversely correlated with the survival of the patient. Despite this, somatic activating mutations within erbB2 in human breast cancers are rare. However, we have previously reported that a splice isoform of erbB2, containing an in-frame deletion of exon 16 (herein referred to as ErbB2ΔEx16), results in oncogenic activation of erbB2 because of constitutive dimerization of the ErbB2 receptor. Here, we demonstrate that the ErbB2ΔEx16 is a major oncogenic driver in breast cancer that constitutively signals from the cell surface. We further show that inducible expression of the ErbB2ΔEx16 variant in mammary gland of transgenic mice results in the rapid development of metastatic multifocal mammary tumors. Genetic and biochemical characterization of the ErbB2ΔEx16-derived mammary tumors exhibit several unique features that distinguish this model from the conventional ErbB2 ones expressing the erbB2 proto-oncogene in mammary epithelium. Unlike the wild-type ErbB2-derived tumors that express luminal keratins, ErbB2ΔEx16-derived tumors exhibit high degree of intratumoral heterogeneity co-expressing both basal and luminal keratins. Consistent with these distinct pathological features, the ErbB2ΔEx16 tumors exhibit distinct signaling and gene expression profiles that correlate with activation of number of key transcription factors implicated in breast cancer metastasis and cancer stem cell renewal

Pre-vocational therapy in mental health : clients' desired and achieved productivity status

Background: Knowledge about work-related occupational therapy in psychiatric inpatient and day hospital clients is limited. Aims: The aim of the study was to explore the desired and achieved productivity status in mental health service users participating in a pre-vocational therapy (PVT) intervention. Outcome variables were productivity status and achievement of desired productivity status at discharge, and change or persistence of productivity status between admission and discharge. Methods: This is a short-term prospective study based on observational data from health records (N = 98). Results: At admission, 53.2% of participants named a clear desired productivity status; 46.8% did not. Of the former, 76.9% expressed a desire for employment or education on the regular job market; 28.0% achieved their desired outcome at discharge, whereas 72.0% did not. Overall, 58.5% retained, established or increased productive activities, while 41.5% were not engaged in or had reduced productive activities at discharge. These two groups differed in socio-economic and social-security-related characteristics, treatment-related characteristics and psychiatric diagnosis. Conclusions and significance: Some, but not all kinds of clients in acute psychiatric inpatient and day hospital settings manage to take a first step towards productive activities during the first phase of treatment

ARRANJOS PRODUTIVOS LOCAIS: UMA ANÁLISE DO SETOR METAL-MECÂNICO NA REGIÃO DOS VALES DO RIO PARDO E TAQUARI

Este artigo buscou interpretar os objetivos e o andamento do presente projeto, considerando que assuntos relacionados a cooperação, desenvolvimento regional, vantagens competitivas têm se tornado cada vez mais importantes no âmbito nacional e internacional. Assim, analisou-se a prática do APL como forma de reorganizar a conjuntura atual, frente a esses grandes atores do mercado que impedem a inserção e/ou a sobrevivência de pequenas empresas

Coulomb explosion imaging of small polyatomic molecules with ultrashort x-ray pulses

Ultrashort x-ray pulses from free-electron lasers can efficiently charge up and trigger the full fragmentation of molecules. By coincident detection of up to five ions resulting from rapid Coulomb explosion of highly charged iodomethane, we show that the full three-dimensional equilibrium geometry of this prototypical polyatomic system can be determined from the measured ion momenta with the help of a charge buildup model. Supported by simulations of how the ion momenta would reflect specific changes in molecular bond lengths and angles, we demonstrate that Coulomb-explosion imaging with ultrashort x-ray pulses is a promising technique for recording movies of multidimensional nuclear wave packets, including hydrogen motions

Presenilin Is the Molecular Target of Acidic γ-Secretase Modulators in Living Cells

The intramembrane-cleaving protease γ-secretase catalyzes the last step in the generation of toxic amyloid-β (Aβ) peptides and is a principal therapeutic target in Alzheimer's disease. Both preclinical and clinical studies have demonstrated that inhibition of γ-secretase is associated with prohibitive side effects due to suppression of Notch processing and signaling. Potentially safer are γ-secretase modulators (GSMs), which are small molecules that selectively lower generation of the highly amyloidogenic Aβ42 peptides but spare Notch processing. GSMs with nanomolar potency and favorable pharmacological properties have been described, but the molecular mechanism of GSMs remains uncertain and both the substrate amyloid precursor protein (APP) and subunits of the γ-secretase complex have been proposed as the molecular target of GSMs. We have generated a potent photo-probe based on an acidic GSM that lowers Aβ42 generation with an IC50 of 290 nM in cellular assays. By combining in vivo photo-crosslinking with affinity purification, we demonstrated that this probe binds the N-terminal fragment of presenilin (PSEN), the catalytic subunit of the γ-secretase complex, in living cells. Labeling was not observed for APP or any of the other γ-secretase subunits. Binding was readily competed by structurally divergent acidic and non-acidic GSMs suggesting a shared mode of action. These findings indicate that potent acidic GSMs target presenilin to modulate the enzymatic activity of the γ-secretase complex