Temporal Variation of NO2 and O3 in Rome (Italy) from Pandora and In Situ Measurements

To assess the best measures for the improvement of air quality, it is crucial to investigate in situ and columnar pollution levels. In this study, ground-based measurements of nitrogen dioxide (NO2) and ozone (O-3) collected in Rome (Italy) between 2017 and 2022 are analyzed. Pandora sun-spectrometers provided the time series of the NO2 vertical column density (VC-NO2), tropospheric column density (TC-NO2), near-surface concentration (SC-NO2), and the O-3 vertical column density (VC-O-3). In situ concentrations of NO2 and O-3 are provided by an urban background air quality station. The results show a clear reduction of NO2 over the years, thanks to the recent ecological transition policies, with marked seasonal variability, observable both by columnar and in situ data. Otherwise, O-3 does not show inter-annual variations, although a clear seasonal cycle is detectable. The results suggest that the variation of in situ O-3 is mainly imputable to photochemical reactions while, in the VC-O-3, it is triggered by the predominant contribution of stratospheric O-3. The outcomes highlight the importance of co-located in situ and columnar measurements in urban environments to investigate physical and chemical processes driving air pollution and to design tailored climate change adaptation strategies

Visceral Adipose Tissue Bioenergetics Varies According to Individuals' Obesity Class

Obesity is associated with complex adipose tissue energy metabolism remodeling. Whether AT metabolic reprogramming differs according to body mass index (BMI) and across different obesity classes is unknown. This study's purpose was to evaluate and compare bioenergetics and energy substrate preference of visceral adipose tissue (VAT) pertaining to individuals with obesity class 2 and class 3. VAT obtained from patients with obesity (n = 15) class 2 (n = 7; BMI 37.53 +/- 0.58 kg/m(2)) or class 3 (n = 8; BMI 47.79 +/- 1.52 kg/m(2)) was used to assess oxygen consumption rate (OCR) bioenergetics and mitochondrial substrate preferences. VAT of patients with obesity class 3 presented significantly higher non-mitochondrial oxygen consumption (p < 0.05). In VAT of patients with obesity class 2, inhibition of pyruvate and glutamine metabolism significantly decreased maximal respiration and spare respiratory capacity (p < 0.05), while pyruvate and fatty acid metabolism inhibition, which renders glutamine the only available substrate, increased the proton leak with a protective role against oxidative stress (p < 0.05). In conclusion, VAT bioenergetics of patients with obesity class 2 depicts a greater dependence on glucose/pyruvate and glutamine metabolism, suggesting that patients within this BMI range are more likely to be responsive to interventions based on energetic substrate modulation for obesity treatment

Chemodivergent Manganese-Catalyzed C–H Activation: Modular Synthesis of Fluorogenic Probes

Bioorthogonal diversification of peptides is generally dependent on impractical prefunctionalization methods. Here, the authors develop a manganese(I)-catalyzed C–H fluorescent labeling with BODIPY probes, which enables the development of activatable fluorophores to image cell function

Abnormal Brain Activation in Neurofibromatosis Type 1: A Link between Visual Processing and the Default Mode Network

Neurofibromatosis type 1 (NF1) is one of the most common single gene disorders affecting the human nervous system with a high incidence of cognitive deficits, particularly visuospatial. Nevertheless, neurophysiological alterations in low-level visual processing that could be relevant to explain the cognitive phenotype are poorly understood. Here we used functional magnetic resonance imaging (fMRI) to study early cortical visual pathways in children and adults with NF1. We employed two distinct stimulus types differing in contrast and spatial and temporal frequencies to evoke relatively different activation of the magnocellular (M) and parvocellular (P) pathways. Hemodynamic responses were investigated in retinotopically-defined regions V1, V2 and V3 and then over the acquired cortical volume. Relative to matched control subjects, patients with NF1 showed deficient activation of the low-level visual cortex to both stimulus types. Importantly, this finding was observed for children and adults with NF1, indicating that low-level visual processing deficits do not ameliorate with age. Moreover, only during M-biased stimulation patients with NF1 failed to deactivate or even activated anterior and posterior midline regions of the default mode network. The observation that the magnocellular visual pathway is impaired in NF1 in early visual processing and is specifically associated with a deficient deactivation of the default mode network may provide a neural explanation for high-order cognitive deficits present in NF1, particularly visuospatial and attentional. A link between magnocellular and default mode network processing may generalize to neuropsychiatric disorders where such deficits have been separately identified

Identification of Novel Human Damage Response Proteins Targeted through Yeast Orthology

Studies in Saccharomyces cerevisiae show that many proteins influence cellular survival upon exposure to DNA damaging agents. We hypothesized that human orthologs of these S. cerevisiae proteins would also be required for cellular survival after treatment with DNA damaging agents. For this purpose, human homologs of S. cerevisiae proteins were identified and mapped onto the human protein-protein interaction network. The resulting human network was highly modular and a series of selection rules were implemented to identify 45 candidates for human toxicity-modulating proteins. The corresponding transcripts were targeted by RNA interference in human cells. The cell lines with depleted target expression were challenged with three DNA damaging agents: the alkylating agents MMS and 4-NQO, and the oxidizing agent t-BuOOH. A comparison of the survival revealed that the majority (74%) of proteins conferred either sensitivity or resistance. The identified human toxicity-modulating proteins represent a variety of biological functions: autophagy, chromatin modifications, RNA and protein metabolism, and telomere maintenance. Further studies revealed that MMS-induced autophagy increase the survival of cells treated with DNA damaging agents. In summary, we show that damage recovery proteins in humans can be identified through homology to S. cerevisiae and that many of the same pathways are represented among the toxicity modulators

Prevalence of pfmdr1, pfcrt, pfdhfr and pfdhps mutations associated with drug resistance, in Luanda, Angola

<p>Abstract</p> <p>Background</p> <p>Malaria is the infectious disease causing the highest morbidity and mortality in Angola and due to widespread chloroquine (CQ) resistance, the country has recently changed its first-line treatment recommendations for uncomplicated malaria, from CQ to artemisinin combination therapies (ACT) in adults, and sulphadoxine/pyrimethamine (S/P) in pregnant women. Loss of SP sensitivity is, however, progressing rapidly in Africa and, in this study, were investigated a number of molecular markers associated to CQ and S/P.</p> <p>Methods</p> <p>Blood samples were collected from 245 children with uncomplicated malaria, admitted at the Pediatric Hospital Dr. David Bernardino (HPDB), Angola, and the occurrence of mutations in <it>Plasmodium falciparum </it>was investigated in the <it>pfmdr1 </it>(N86Y) and <it>pfcrt </it>(K76T) genes, associated with CQ resistance, as well as in <it>pfdhfr </it>(C59R) and <it>pfdhps </it>(K540E), conferring SP resistance.</p> <p>Results</p> <p>The frequencies of <it>pfmdr1 </it>mutations in codon 86 were 28.6% N, 61.3% Y and 10.1% mixed infections (NY). The frequency of <it>pfcrt </it>mutations in codon 76 were 93.9% K, 5.7% T and 0.4% mixed infections (KT). For <it>pfdhfr </it>the results were in codon 59, 60.6% C, 20.6% R and 18.8% mixed infections (CR). Concerning <it>pfdhps</it>, 6.3% of the isolates were bearers of the mutation 540E and 5.4% mixed infections (K540E).</p> <p>Conclusion</p> <p>The results of this epidemiologic study showed high presence of CQ resistance markers while for SP a much lower prevalence was detected for the markers under study.</p

Neuroprotective function for ramified microglia in hippocampal excitotoxicity

<p>Abstract</p> <p>Background</p> <p>Most of the known functions of microglia, including neurotoxic and neuroprotective properties, are attributed to morphologically-activated microglia. Resting, ramified microglia are suggested to primarily monitor their environment including synapses. Here, we show an active protective role of ramified microglia in excitotoxicity-induced neurodegeneration.</p> <p>Methods</p> <p>Mouse organotypic hippocampal slice cultures were treated with <it>N</it>-methyl-D-aspartic acid (NMDA) to induce excitotoxic neuronal cell death. This procedure was performed in slices containing resting microglia or slices that were chemically or genetically depleted of their endogenous microglia.</p> <p>Results</p> <p>Treatment of mouse organotypic hippocampal slice cultures with 10-50 μM <it>N</it>-methyl-D-aspartic acid (NMDA) induced region-specific excitotoxic neuronal cell death with CA1 neurons being most vulnerable, whereas CA3 and DG neurons were affected less. Ablation of ramified microglia severely enhanced NMDA-induced neuronal cell death in the CA3 and DG region rendering them almost as sensitive as CA1 neurons. Replenishment of microglia-free slices with microglia restored the original resistance of CA3 and DG neurons towards NMDA.</p> <p>Conclusions</p> <p>Our data strongly suggest that ramified microglia not only screen their microenvironment but additionally protect hippocampal neurons under pathological conditions. Morphological activation of ramified microglia is thus not required to influence neuronal survival.</p