Real-time estimation of the effective reproduction number of COVID-19 from behavioral data

Monitoring the effective reproduction number R_t R t of a rapidly unfolding pandemic in real-time is key to successful mitigation and prevention strategies. However, existing methods based on case numbers, hospital admissions or fatalities suffer from multiple measurement biases and temporal lags due to high test positivity rates or delays in symptom development or administrative reporting. Alternative methods such as web search and social media tracking are less directly indicating epidemic prevalence over time. We instead record age-stratified anonymous contact matrices at a daily resolution using a longitudinal online-offline survey in Hungary during the first two waves of the COVID-19 pandemic. This approach is innovative, cheap, and provides information in near real-time for estimating R_t R t at a daily resolution. Moreover, it allows to complement traditional surveillance systems by signaling periods when official monitoring infrastructures are unreliable due to observational biases

Presynaptic Nicotinic α7 and Non-α7 Receptors Stimulate Endogenous GABA Release from Rat Hippocampal Synaptosomes through Two Mechanisms of Action

BACKGROUND: Although converging evidence has suggested that nicotinic acetylcholine receptors (nAChR) play a role in the modulation of GABA release in rat hippocampus, the specific involvement of different nAChR subtypes at presynaptic level is still a matter of debate. In the present work we investigated, using selective α7 and α4β2 nAChR agonists, the presence of different nAChR subtypes on hippocampal GABA nerve endings to assess to what extent and through which mechanisms they stimulate endogenous GABA release. METHODOLOGY/FINDINGS: All agonists elicited GABA overflow. Choline (Ch)-evoked GABA overflow was dependent to external Ca(2+), but unaltered in the presence of Cd(2+), tetrodotoxin (TTX), dihydro-β-erythroidine (DHβE) and 1-(4,4-Diphenyl-3-butenyl)-3-piperidinecarboxylic acid hydrochloride SKF 89976A. The effect of Ch was blocked by methyllycaconitine (MLA), α-bungarotoxin (α-BTX), dantrolene, thapsigargin and xestospongin C, suggesting that GABA release might be triggered by Ca(2+) entry into synaptosomes through the α7 nAChR channel with the involvement of calcium from intracellular stores. Additionally, 5-Iodo-A-85380 dihydrochloride (5IA85380) elicited GABA overflow, which was Ca(2+) dependent, blocked by Cd(2+), and significantly inhibited by TTX and DHβE, but unaffected by MLA, SKF 89976A, thapsigargin and xestospongin C and dantrolene. These findings confirm the involvement of α4β2 nAChR in 5IA85380-induced GABA release that seems to occur following membrane depolarization and opening calcium channels. CONCLUSIONS/SIGNIFICANCE: Rat hippocampal synaptosomes possess both α7 and α4β2 nAChR subtypes, which can modulate GABA release via two distinct mechanisms of action. The finding that GABA release evoked by the mixture of sub-maximal concentration of 5IA85380 plus sub-threshold concentrations of Ch was significantly larger than that elicited by the sum of the effects of the two agonists is compatible with the possibility that they coexist on the same nerve terminals. These findings would provide the basis for possible selective pharmacological strategies to treat neuronal disorders that involve the dysfunction of hippocampal cholinergic system

Participant Reactions to Two-Way Immersion (TWI) Programs

The purpose of this study was to elicit participant reactions to two-way immersion (TWI) programs in the United States of America. A large number of recent studies have focused on instructor views and perspectives of two-way immersion programs, so this study aimed to gain insight from students who are, or who have, participated in TWI programs throughout North America. One hundred fifty-one TWI schools throughout the United States were contacted and asked to participate in this study. Two similar surveys were developed, one for current TWI students, and another for former TWI students. Students from these two groups were asked to fill out a confidential online survey that addressed specific linguistic skills, abilities, and preferences, as well as connection to the cultures of the target language. Forty-eight percent of the survey respondents were native speakers of English, and the remaining 52% were non-native speakers of English. The number of respondents to the former student survey was so low that the data were inconclusive, and, therefore, will not be included in this study. Since the survey was conducted online, the data were stored in a comma-delimited format for further evaluation. The data were then tallied and analyzed for common themes

Państwo, gospodarka, społeczeństwo w integrującej się Europie TOM 3

Ze wstępu: "1 maja 2004 przyniesie radykalną zmianą sytuacji dotychczasowych kandydatów do Unii Europejskiej. Z roli aplikanta i petenta przekształcą się we współdecydenta. Już dziś z przyszłymi członkami konsultuje się większość kwestii wymagających strategicznych decyzji. Przez ostatnie dziesięć lat wysiłek polityczny i intelektualny był skierowany na uzyskanie członkostwa Unii, a w ostatnim okresie negocjacji - na osiągnięcie najlepszych według polityków i ekonomistów warunków akcesji. 1 ten etap mamy już za sobą. Pora zacząć patrzeć przed siebie, lecz niejako petent, ale kraj współodpowiedzialny za dalsze funkcjonowanie i rozwój powiększonej Unii. Z tej perspektywy istotnajest analiza gospodarki europejskiej, z którąjuż dziś gospodarka państw kandydackich, także Polski, jest silnie powiązana. Wiedza na ten temat jest uboga i ograniczona do przeglądu bieżących wskaźników makroekonomicznych. Zarówno w ośrodkach rządowych, jak i pozarządowych dominuje podejście analizujące, co z konkretnego wydarzenia w innym kraju wynika dla gospodarki polskiej. Stanowczo nie wystarczy to do pełnienia odpowiedzialnej roli współdecydenta. Potrzebna jest pogłębiona wiedza na temat gospodarki europejskiej jako całości i poszczególnych krajów, a także najważniejszych partnerów handlowych i gospodarczych zjednoczonej Europy. Konieczne są pogłębione prace studialne dotyczące mechanizmów międzynarodowych, gdyż organy unijne będą się zajmować w najbliższych latach dalszym rozwojem europejskiego jednolitego Rynku, rywalizacją gospodarczą z USA i krajami azjatyckimi, liberalizacjąhandlu światowego."(...

The Pharmacological Effects of Phenylephrine are Indirect, Mediated by Noradrenaline Release from the Cytoplasm

Phenylephrine (PE) is a canonical α(1)-adrenoceptor-selective agonist. However, unexpected effects of PE have been observed in preclinical and clinical studies, that cannot be easily explained by its actions on α(1)-adrenoceptors. The probability of the involvement of α(2)- and β-adrenoceptors in the effect of PE has been raised. In addition, our earlier study observed that PE released noradrenaline (NA) in a [Ca(2+)](o)-independent manner. To elucidate this issue, we have investigated the effects of PE on [(3)H]NA release and α(1)-mediated smooth muscle contractions in the mouse vas deferens (MVD) as ex vivo preparation. The release experiments were designed to assess the effects of PE at the presynaptic terminal, whereas smooth muscle isometric contractions in response to electrical field stimulation were used to measure PE effect postsynaptically. Our results show that PE at concentrations between 0.3 and 30 µM significantly enhanced the resting release of [(3)H]NA in a [Ca(2+)](o)-independent manner. In addition, prazosin did not affect the release of NA evoked by PE. On the contrary, PE-evoked smooth muscle contractions were inhibited by prazosin administration indicating the α(1)-adrenoceptor-mediated effect. When the function of the NA transporter (NAT) was attenuated with nisoxetine, PE failed to release NA and the contractions were reduced by approximately 88%. The remaining part proved to be prazosin-sensitive. The present work supports the substantial indirect effect of PE which relays on the cytoplasmic release of NA, which might explain the reported side effects for PE

Sustained E2F-Dependent Transcription Is a Key Mechanism to Prevent Replication-Stress-Induced DNA Damage

Summary: Recent work established DNA replication stress as a crucial driver of genomic instability and a key event at the onset of cancer. Post-translational modifications play an important role in the cellular response to replication stress by regulating the activity of key components to prevent replication-stress-induced DNA damage. Here, we establish a far greater role for transcriptional control in determining the outcome of replication-stress-induced events than previously suspected. Sustained E2F-dependent transcription is both required and sufficient for many crucial checkpoint functions, including fork stalling, stabilization, and resolution. Importantly, we also find that, in the context of oncogene-induced replication stress, where increased E2F activity is thought to cause replication stress, E2F activity is required to limit levels of DNA damage. These data suggest a model in which cells experiencing oncogene-induced replication stress through deregulation of E2F-dependent transcription become addicted to E2F activity to cope with high levels of replication stress. : Bertoli et al. establish a far greater role for transcriptional control in determining the outcome of replication-stress-induced events than previously suspected. Their data predict a model in which cells that experience oncogene-induced replication stress become addicted to E2F-dependent transcription to cope with high levels of replication stress