Prevalence of COVID-19 vaccine reactogenicity among Bangladeshi physicians.

Increased COVID-19 vaccine hesitancy presents a major hurdle in global efforts to contain the COVID-19 pandemic. This study was designed to estimate the prevalence of adverse events after the first dose of the Covishield (AstraZeneca) vaccine among physicians in Bangladesh. A cross-sectional study was conducted using an online questionnaire for physicians (n = 916) in Bangladesh. Physicians who received at least one dose of the COVID-19 vaccine were included. The study was carried out from April 12 to May 31, 2021. More than 58% of respondents (n = 533) reported one or more adverse events. Soreness of the injected arm (71.9%), tiredness (56.1%), fever (54.4%), soreness of muscles (48.4%), headache (41.5%) and sleeping more than usual (26.8%) were the most commonly reported adverse events. Most vaccine-related reactogenicities were reported by the younger cohorts (<45 years). The majority of respondents reported severity of reactogenicity as "mild," experienced on the day of vaccination, and lasting for 1-3 days. The most common reactogenicity was pain at the injection site; the second most common was tiredness. Almost half (49.2%) of the physicians took acetaminophen (paracetamol) to minimize the effects of vaccine reactogenicity. Multivariate logistic regression analyses showed that physicians with diabetes and hypertension (OR = 2.729 95% CI: 1.282-5.089) and asthma with other comorbidities (OR = 1.885 95% CI: 1.001-3.551) had a significantly higher risk of vaccine-related reactogenicities than physicians without comorbidities. Further safety studies with larger cohorts are required to monitor vaccine safety and provide assurance to potential vaccine recipients.

Nanosized titanium dioxide elevates toxicity of cationic metals species for Daphnia - have aging and natural organic matter an unexpected impact?

In aquatic ecosystems, nanosized titanium dioxide particles (nTiO2) likely interact with natural organic matter (NOM) and may alter the ecotoxicity of co-occurring metals. The magnitude of changes in toxicity may be modulated by the duration of interactions (i.e. aging) between these factors. As those interactions are hardly addressed in literature, the present study aimed at assessing the impact of aging durations (0, 1, 3 and 6 days) on metals with mainly cationic (silver (Ag), cadmium (Cd)) or anionic (arsenic (As)) toxic ions in combination with three nTiO2 levels (0.0, 0.6 and 3.0 mg/L) and two NOM levels (0 versus 8 mg TOC/L). The interaction of these factors was additionally investigated for two aging scenarios: in one scenario nTiO2 were aged together with one of the metals, while in other scenario metals were added to aged nTiO2. Subsequently, their combined acute effects on Daphnia magna were assessed. The results uncovered that nTiO2 elevate the toxicity of metals with mainly cationic species (i.e. Ag+ and Cd2+) with the effect size depending on their valence electron. Contrary, nTiO2 have no impact on the metal with mainly anionic species (i.e. HAsO42-). Furthermore, NOM reduced metal toxicity only for Ag and aging duration had a limited impact on the test outcome suggesting that relevant interactions between metal and nTiO2 occur rather quick (below 24 h). These findings suggest that the charge of metals' most toxic species is the determining factor for its interaction with nanoparticles and the resulting ecotoxicological effect assessment.

The Coding and Small Non-coding Hippocampal Synaptic RNAome.

Neurons are highly compartmentalized cells that depend on local protein synthesis. Messenger RNAs (mRNAs) have thus been detected in neuronal dendrites, and more recently in the pre- and postsynaptic compartments as well. Other RNA species such as microRNAs have also been described at synapses where they are believed to control mRNA availability for local translation. A combined dataset analyzing the synaptic coding and non-coding RNAome via next-generation sequencing approaches is, however, still lacking. Here, we isolate synaptosomes from the hippocampus of young wild-type mice and provide the coding and non-coding synaptic RNAome. These data are complemented by a novel approach for analyzing the synaptic RNAome from primary hippocampal neurons grown in microfluidic chambers. Our data show that synaptic microRNAs control almost the entire synaptic mRNAome, and we identified several hub microRNAs. By combining the in vivo synaptosomal data with our novel microfluidic chamber system, our findings also support the hypothesis that part of the synaptic microRNAome may be supplied to neurons via astrocytes. Moreover, the microfluidic system is suitable for studying the dynamics of the synaptic RNAome in response to stimulation. In conclusion, our data provide a valuable resource and point to several important targets for further research.

Functional Divergence of Mammalian TFAP2a and TFAP2b Transcription Factors for Bidirectional Sleep Control.

Sleep is a conserved behavioral state. Invertebrates typically show quiet sleep, whereas in mammals, sleep consists of periods of nonrapid-eye-movement sleep (NREMS) and REM sleep (REMS). We previously found that the transcription factor AP-2 promotes sleep in Caenorhabditiselegans and Drosophila In mammals, several paralogous AP-2 transcription factors exist. Sleep-controlling genes are often conserved. However, little is known about how sleep genes evolved from controlling simpler types of sleep to govern complex mammalian sleep. Here, we studied the roles of Tfap2a and Tfap2b in sleep control in mice. Consistent with our results from C. elegans and Drosophila, the AP-2 transcription factors Tfap2a and Tfap2b also control sleep in mice. Surprisingly, however, the two AP-2 paralogs play contrary roles in sleep control. Tfap2a reduction of function causes stronger delta and theta power in both baseline and homeostasis analysis, thus indicating increased sleep quality, but did not affect sleep quantity. By contrast, Tfap2b reduction of function decreased NREM sleep time specifically during the dark phase, reduced NREMS and REMS power, and caused a weaker response to sleep deprivation. Consistent with the observed signatures of decreased sleep quality, stress resistance and memory were impaired in Tfap2b mutant animals. Also, the circadian period was slightly shortened. Taken together, AP-2 transcription factors control sleep behavior also in mice, but the role of the AP-2 genes functionally diversified to allow for a bidirectional control of sleep quality. Divergence of AP-2 transcription factors might perhaps have supported the evolution of more complex types of sleep.

Alpha-synuclein deregulates the expression of COL4A2 and impairs ER-Golgi function.

Alpha-synuclein (aSyn) is the major protein component of Lewy bodies and Lewy neurites, the typical pathological hallmarks in Parkinson's disease (PD) and Dementia with Lewy bodies. aSyn is capable of inducing transcriptional deregulation, but the precise effect of specific aSyn mutants associated with familial forms of PD, remains unclear. Here, we used transgenic mice overexpressing human wild-type (WT) or A30P aSyn to compare the transcriptional profiles of the two animal models. We found that A30P aSyn promotes strong transcriptional deregulation and increases DNA binding. Interestingly, COL4A2, a major component of basement membranes, was found to be upregulated in both A30P aSyn transgenic mice and in dopaminergic neurons expressing A30P aSyn, suggesting a crucial role for collagen related genes in aSyn-induced toxicity. Finally, we observed that A30P aSyn alters Golgi morphology and increases the susceptibility to endoplasmic reticulum (ER) stress in dopaminergic cells. In total, our findings provide novel insight into the putative role of aSyn on transcription and on the molecular mechanisms involved, thereby opening novel avenues for future therapeutic interventions in PD and other synucleinopathies.