Example of Disulfide Conformational Change in the Solid State: Preparation, Optical Properties, and X-ray Studies of a Cystamine-Based Iodoplombate Hybrid

A novel cystamine-based hybrid, namely, α-[NH3(CH2)2SS(CH2)2NH3PbI6]·2H3O (1a), was prepared under solvothermal conditions. Interestingly, 1a, which is built up from isolated PbI6 octahedra, can be easily changed into its polymorph, namely, β-[NH3(CH2)2S–S(CH2)2NH3PbI6]·2H3O (1b) only by heating it up to 45 °C. According to the results of X-ray diffraction analyses, the polymorphic phenomenon of 1a and 1b results from a conformational change in the helical diprotonated cystamine cation in the solid state. Both 1a and 1b crystallized in the orthorhombic Pna21 space group. The reversibility of this transformation is proved by single-crystal X-ray diffraction and second harmonic generation measurements

L'hyperméthylation de DOK1 n'a pas d'effet sur son niveau d'expression dans les tumeurs ovariennes : corrélation du niveau d'expression de DOK1 avec la survie des patientes du cancer ovarien

Les bases moléculaires de l’initiation et de la progression du cancer ovarien épithélial (COE) sont pauvrement comprises. Un élément pathogénique clé dans le cancer est l’inactivation de gènes suppresseurs de tumeurs, fréquemment due à l’hyperméthylation de leur région promotrice. Dans ce contexte, nous avons utilisé une approche épigénomique pour trouver des gènes hyperméthylés dans le COE. Nous avons employé un agent déméthylant, 5-aza-dC, pour réactiver les gènes hyperméthylés dans quatre lignées cellulaires du COE (SKOV3, OVCAR3, TOV112 et TOV21). Nous avons trouvé plusieurs cibles potentielles d’hyperméthylation qui pourraient jouer un rôle fonctionnel dans la suppression tumorale, l’apoptose ou la réparation de l’ADN. Nous avons évalué leur statut de méthylation par MSP (methylation-specific PCR) et BSP (bisulfite-sequencing PCR) avec des échantillons normaux et tumoraux et deux lignées cellulaires du COE. Parmi ces cibles, le gène DOK1 a démontré une évidence de méthylation de la région promotrice des échantillons tumoraux comparativement à celle de ceux qui sont normaux. Des clones surexprimant et d’autres sous-exprimant DOK1 ont été construits et validés. Son rôle potentiel dans la prolifération cellulaire, dans la sensibilité au taxol et au cisplatin, et dans le cycle cellulaire a été évalué par des études fonctionnelles et une légère implication a été détectée dans ces fonctions. Les changements d’expressions globales reliés à l’expression de ce gène ont également été analysés par la technologie de micropuces de l’ADN. Nos données montrent que DOK1 est touché par une hyperméthylation de sa région promotrice potentielle dans les tumeurs du COE. Par contre, cette hyperméthylation ne semble pas influencer son niveau d'expression. Au contraire, son expression augmente dans le cancer ovarien. Cette augmentation serait reliée à une diminution des risques de progression du COE. Cette observation confirme le rôle potentiel de suppresseur de tumeur de DOK1 dans le COE.The molecular basis of the epithelial ovarian cancer (EOC) initiation and progression are still poorly understood. A key pathogenic element in cancer is the inactivation of tumours suppressor genes, frequently due to the hypermethylation of their promoter sequence. In this context, we used an epigenomic approach to identify hypermethylated genes in the EOC. We used the demethylating agent, 5-aza-dC, to reactivate hypermethylated genes in four cells lines of EOC (SKOV3, OVCAR3, TOV112 and TOV21). We identified several targets genes potentially hypermethylated that could play a functional role in ovarian tumorigenesis suppression, apoptosis or DNA repair. We evaluated their methylation status by MSP (methylation-specific PCR) and BSP (bisulfite-sequencing PCR) within normal and tumoral ovarian samples and in two EOC cells lines. Among these targets, the DOK1 gene showed an evidence of methylation of the promoter region in the tumour samples compared to the normal ones. Clones over-expressing and others under-expressing DOK1 were built and validated. The potential role of this gene in cellular proliferation, sensitivity to taxol and cisplatin, and in the cell cycle was evaluated by functional studies and a little implication of the DOK1 gene was detected in these functions. The global expression changes connected to the expression of the DOK1 gene were also analyzed by the microarray genomics technology. Our data show that DOK1 is affected by hypermethylation of its potential promoter region in EOC tumors. This hypermethylation do seems not to influence its expression levels. On the contrary, its expression level increases in ovarian cancer. This increase would be connected to a reduction in the risks of progression of the COE. Moreover, this observation confirms the potential role of DOK1 as tumor suppressor in EOC

Accuracy and Effectiveness of an Orchestration Tool on Instructors\u27 Interventions and Groups\u27 Collaboration

This paper presents the development of a novel orchestration tool that predicts collaborative problem-solving (CPS) behaviors of undergraduate engineering groups and investigates the use of that tool by instructors. We explore the impact of receiving real-time, machine-learning, model-based prompts on 1) instructors\u27 orchestration strategies, which are strategies instructors use to manage and facilitate collaborative activities, and 2) groups\u27 participation, including how groups are engaged in CPS activities. The orchestration tool is a dashboard that notifies instructors of–and advises them on–monitoring and intervening with groups who may need collaborative support and guidance. We describe the accuracy of the models in predicting CPS behaviors and of instructors in identifying these behaviors in the classroom. We then describe how real-time prompts from models can affect instructors\u27 orchestration strategies and students\u27 participation. Our findings show that there is variability in the accuracy of our machine learning models and that instructors are better at identifying predictive behaviors as compared to the models. Instructors in this context engaged in orchestration strategies, like monitoring and probing when using the orchestration tool, and groups of students were largely talking while on-task across classes. We triangulate across data sources to examine the effectiveness of the orchestration tool in the classroom and share pedagogical and technical implications for the field

Polymorphism of lead(ii) benzenethiolate: a noncentrosymmetric new allotropic form of Pb(SPh)2

Depending upon its conditions of crystallization, lead(II) benzenethiolate can exist in two forms: a low-temperature centrosymmetric phase α-Pb(SPh)2 which can be converted by heating into the noncentrosymmetric, 2nd order NLO strongly active and room temperature metastable β-Pb(SPh)2 phase, thus affording an example of transition towards noncentrosymmetry induced by a rise of temperature

Human Papillomavirus and Cardiovascular Disease

International audienc

Increased acetylcholinesterase expression in bumble bees during neonicotinoid-coated corn sowing

While honey bee exposure to systemic insecticides has received much attention, impacts on wild pollinators have not been as widely studied. Neonicotinoids have been shown to increase acetylcholinesterase (AChE) activity in honey bees at sublethal doses. High AChE levels may therefore act as a biomarker of exposure to neonicotinoids. This two-year study focused on establishing whether bumble bees living and foraging in agricultural areas using neonicotinoid crop protection show early biochemical signs of intoxication. Bumble bee colonies (Bombus impatiens) were placed in two different agricultural cropping areas: 1) control (≥3 km from fields planted with neonicotinoid-treated seeds) or 2) exposed (within 500 m of fields planted with neonicotinoid-treated seeds) and maintained for the duration of corn sowing. As determined by Real Time qPCR, AChE mRNA expression was initially significantly higher in bumble bees from exposed sites, then decreased throughout the planting season to reach a similar endpoint to that of bumble bees from control sites. These findings suggest that exposure to neonicotinoid seed coating particles during the planting season can alter bumble bee neuronal activity. To our knowledge, this is the first study to report in situ that bumble bees living in agricultural areas exhibit signs of neonicotinoid intoxication

Safe Discharge Home With Telemedicine of Patients Requiring Nasal Oxygen Therapy After COVID-19

Introduction: The COVID-19 pandemic created challenges to healthcare systems worldwide. To allow overwhelmed hospitals to focus on the most fragile and severely ill patients, new types of management had to be set up. During the pandemic, patients with COVID-19 from greater Paris area were monitored at home using a web-based remote system called COVIDOM™, using self-administered questionnaires, which triggered alerts to a regional control center. To ease hospital discharge and to prevent hospital from being overwhelmed, patients still requiring low-flow oxygen therapy discharged home were also included in this telemedicine solution. We aim to evaluate the safety of this original management. Methods: We conducted a retrospective multicenter cohort of patients discharged home from hospital after COVID-19 and still requiring nasal oxygen therapy, who were monitored by questionnaire and trained physicians using COVIDOM. During late follow-up, the status of the patients using a Euro-Qol (EQ-5D-5L) questionnaire, and the Medical Research Council (MRC) Dyspnea scale was collected. Results: From March 21st to June 21st 2020, 73 COVID-19 patients still receiving nasal oxygen at hospital discharge were included. Median [Inter-Quartile Range (IQR)] age was 62.0 [52.5–69.0] years, 64.4% were male. Altogether, risk factors were observed in 49/73 (67%) patients, mainly hypertension (35.6%), diabetes mellitus (15.1%) and active neoplasia (11.0%). Among the cohort, 26% of patients were previously managed in ICU. Oxygen therapy was required for a median [IQR] of 20 [16–31] days. No death or urgent unplanned hospitalization were observed during the COVIDOM telemonitoring. During the late follow-up evaluation (6 months after inclusion), the mean EQ-5D-5L questionnaire score was 7.0 ± 1.6, and the mean MRC dyspnea scale was 0.8 ± 1.0, indicating absence of dyspnea. Five patients have died from non-COVID causes. Conclusions: In this preliminary study, early discharge home of patients with severe COVID-19 disease who still required low-oxygen therapy seems to be safe

Investigating Postsynaptic Effects of a Drosophila Neuropeptide on Muscle Contraction

Supplementary figures for J Neurophysiol 131: 137–151, 2024. First published December 27, 2023; doi:10.1152/jn.00246.2023.Neuropeptides play key physiological roles by acting as transmitters or hormones that modulate chemical synapses, but distinguishing presynaptic and postsynaptic effects can be challenging. The Drosophila neuropeptide, DPKQDFMRFamide, was previously shown to enhance excitatory junctional potentials (EJPs) and muscle contraction by presynaptic and postsynaptic actions. Here, postsynaptic actions of the peptide were investigated by examining how it modulates effects of the excitatory neurotransmitter L-glutamate on muscles of 3rd instar larvae after removing the central nervous system. DPKQDFMRFamide enhanced glutamate-evoked contractions with at low concentrations (EC50 1.3 nM), consistent with its role as a neurohormone, and the combined effect of both substances was more than additive. Glutamate-evoked contractions were also enhanced when transmitter release was blocked in temperature-sensitive mutants. The peptide increased membrane depolarization in muscle cells when co-applied with glutamate, and its effects were blocked by nifedipine, an L-type channel blocker, indicating actions at the plasma membrane and involving calcium influx. DPKQDFMRFamide also enhanced contractions induced by caffeine in the absence of extracellular calcium, suggesting increased calcium release from the sarcoplasmic reticulum (SR) or effects downstream of calcium release from the SR. The peptide’s effects do not appear to involve calcium/calmodulin-dependent protein kinase II (CaMKII), previously shown to mediate presynaptic effects. The approach used here might be useful for examining postsynaptic effects of neurohormones and cotransmitters in other systems.NSERC 4629