Observations of nitrogen isotope fractionation in deeply embedded protostars

(Abridged) The terrestrial planets, comets, and meteorites are significantly enriched in 15N compared to the Sun and Jupiter. While the solar and jovian nitrogen isotope ratio is believed to represent the composition of the protosolar nebula, a still unidentified process has caused 15N-enrichment in the solids. Several mechanisms have been proposed to explain the variations, including chemical fractionation. However, observational results that constrain the fractionation models are scarce. While there is evidence of 15N-enrichment in prestellar cores, it is unclear how the signature evolves into the protostellar phases. Our aim is to measure the 14N/15N ratio around three nearby, embedded low-to-intermediate-mass protostars. Isotopologues of HCN and HNC were used to probe the 14N/15N ratio. A selection of H13CN, HC15N, HN13C, and H15NC transitions was observed with the APEX telescope. The 14N/15N ratios were derived from the integrated intensities assuming a standard 12C/13C ratio. The assumption of optically thin emission was verified using radiative transfer modeling and hyperfine structure fitting. Two sources, IRAS 16293A and R CrA IRS7B, show 15N-enrichment by a factor of around 1.5-2.5 in both HCN and HNC with respect to the solar composition. Solar composition cannot be excluded for the third source, OMC-3 MMS6. Furthermore, there are indications of a trend toward increasing 14N/15N ratios with increasing outer envelope temperature. The enhanced 15N abundances in HCN and HNC found in two Class~0 sources (14N/15N of 160-290) and the tentative trend toward a temperature-dependent 14N/15N ratio are consistent with the chemical fractionation scenario, but 14N/15N ratios from additional tracers are indispensable for testing the models. Spatially resolved observations are needed to distinguish between chemical fractionation and isotope-selective photochemistry.Comment: Accepted for publication in Astronomy and Astrophysics. 16 pages, 13 figure

Boosting Adaptive Immunity: A New Role for PAFR Antagonists.

We have previously shown that the Platelet-Activating Factor Receptor (PAFR) engagement in murine macrophages and dendritic cells (DCs) promotes a tolerogenic phenotype reversed by PAFR-antagonists treatment in vitro. Here, we investigated whether a PAFR antagonist would modulate the immune response in vivo. Mice were subcutaneously injected with OVA or OVA with PAFR-antagonist WEB2170 on days 0 and 7. On day 14, OVA-specific IgG2a and IgG1 were measured in the serum. The presence of WEB2170 during immunization significantly increased IgG2a without affecting IgG1 levels. When WEB2170 was added to OVA in complete Freund's adjuvant, enhanced IgG2a but not IgG1 production was also observed, and CD4+ FoxP3+ T cell frequency in the spleen was reduced compared to mice immunized without the antagonist. Similar results were observed in PAFR-deficient mice, along with increased Tbet mRNA expression in the spleen. Additionally, bone marrow-derived DCs loaded with OVA were transferred into naïve mice and their splenocytes were co-cultured with fresh OVA-loaded DCs. CD4(+) T cell proliferation was higher in the group transferred with DCs treated with the PAFR-antagonist. We propose that the activation of PAFR by ligands present in the site of immunization is able to fine-tune the adaptive immune response

Reorganization of Active Surveillance of Acute Flaccid Paralysis (AFP) in Emilia-Romagna, Italy: a two-step Public Health intervention

BACKGROUND AND AIM OF THE WORK: The International Health Regulations Emergency Committee declared in 2014 that poliovirus circulation is a public health emergency of international concern. In 2017 and 2018 Italy was classified at intermediate risk of poliovirus reintroduction based on suboptimal poliovirus surveillance. Acute flaccid paralysis active surveillance is the gold standard in the polio eradication process. The aims of this study were to investigate the causes of reduced acute flaccid paralysis case reporting in Emilia-Romagna in the last few years (step 1) and to study a public health intervention to restore an adequate level of acute flaccid paralysis surveillance in that region (step 2). METHODS: In the first step a context analysis was performed by analysing the 2015-2017 Hospital Discharge Registers in Emilia-Romagna with the ICD-9-CM differential diagnosis codes for acute flaccid paralysis. Data from context analysis was then used to plan a new regional collaborative network of acute flaccid paralysis active surveillance. RESULTS: The active surveillance network was, at the end of the study, composed by 49 doctors from both hospital administrations and clinical wards from 4 University Hospitals and 7 Local Health Authorities throughout the Region. In 15 months, 7 acute flaccid paralysis cases have been reported; 85,7% received a full clinical and virological investigation and 83,3% completed the 60 day's follow-up. The mean response to each e-mail was 48,5% (SD 7,5%). CONCLUSIONS: In 2019, the Emilia-Romagna's active surveillance system reached the sensitivity, completeness of case investigation and follow-up required to achieve the minimum levels for certification standard surveillance

Top-Down Proteomics of Human Saliva Highlights Anti-inflammatory, Antioxidant, and Antimicrobial Defense Responses in Alzheimer Disease

Alzheimer disease (AD) is the most prevalent neurodegenerative disease in the elderly, characterized by accumulation in the brain of misfolded proteins, inflammation, and oxidative damage leading to neuronal cell death. By considering the viewpoint that AD onset and worsening may be influenced by environmental factors causing infection, oxidative stress, and inflammatory reaction, we investigated the changes of the salivary proteome in a population of patients with respect to that in healthy controls (HCs). Indeed, the possible use of saliva as a diagnostic tool has been explored in several oral and systemic diseases. Moreover, the oral cavity continuously established adaptative and protective processes toward exogenous stimuli. In the present study, qualitative/quantitative variations of 56 salivary proteoforms, including post-translationally modified derivatives, have been analyzed by RP-HPLC-ESI-IT-MS and MS/MS analyses, and immunological methods were applied to validate MS results. The salivary protein profile of AD patients was characterized by significantly higher levels of some multifaceted proteins and peptides that were either specific to the oral cavity or also expressed in other body districts: (i) peptides involved in the homeostasis of the oral cavity; (ii) proteins acting as ROS/RNS scavengers and with a neuroprotective role, such as S100A8, S100A9, and their glutathionylated and nitrosylated proteoforms; cystatin B and glutathionylated and dimeric derivatives; (iii) proteins with antimicrobial activity, such as α-defensins, cystatins A and B, histatin 1, statherin, and thymosin β4, this last with a neuroprotective role at the level of microglia. These results suggested that, in response to injured conditions, Alzheimer patients established defensive mechanisms detectable at the oral level. Data are available via ProteomeXchange with identifier PXD021538

Monitoring COVID-19 Transmission Risks by Quantitative RealTime PCR Tracing of Droplets in Hospital and Living Environments

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) environmental contamination occurs through droplets and biological fluids released in the surroundings from patients or asymptomatic carriers. Surfaces and objects contaminated by saliva or nose secretions represent a risk for indirect transmission of coronavirus disease 2019 (COVID-19). We assayed surfaces from hospital and living spaces to identify the presence of viral RNA and the spread of fomites in the environment. Anthropic contamination by droplets and biological fluids was monitored by detecting the microbiota signature using multiplex quantitative real-time PCR (qPCR) on selected species and massive sequencing on 16S amplicons. A total of 92 samples (flocked swabs) were collected from critical areas during the pandemic, including indoor (three hospitals and three public buildings) and outdoor surfaces exposed to anthropic contamination (handles and handrails, playgrounds). Traces of biological fluids were frequently detected in spaces open to the public and on objects that are touched with the hands (.80%). However, viral RNA was not detected in hospital wards or other indoor and outdoor surfaces either in the air system of a COVID hospital but only in the surroundings of an infected patient, in consistent association with droplet traces and fomites. Handled objects accumulated the highest level of multiple contaminations by saliva, nose secretions, and fecal traces, further supporting the priority role of handwashing in prevention. In conclusion, anthropic contamination by droplets and biological fluids is widespread in spaces open to the public and can be traced by qPCR. Monitoring fomites can support evaluation of indirect transmission risks for coronavirus or other flu-like viruses in the environment

Earth’s evolving geodynamic regime recorded by titanium isotopes

Earth’s mantle has a two-layered structure, with the upper and lower mantle domains separated by a seismic discontinuity at about 660 km (refs.). The extent of mass transfer between these mantle domains throughout Earth’s history is, however, poorly understood. Continental crust extraction results in Ti-stable isotopic fractionation, producing isotopically light melting residues. Mantle recycling of these components can impart Ti isotope variability that is trackable in deep time. We report ultrahigh-precision ⁴⁹Ti/⁴⁷Ti ratios for chondrites, ancient terrestrial mantle-derived lavas ranging from 3.8 to 2.0 billion years ago (Ga) and modern ocean island basalts (OIBs). Our new Ti bulk silicate Earth (BSE) estimate based on chondrites is 0.052 ± 0.006‰ heavier than the modern upper mantle sampled by normal mid-ocean ridge basalts (N-MORBs). The ⁴⁹Ti/⁴⁷Ti ratio of Earth’s upper mantle was chondritic before 3.5 Ga and evolved to a N-MORB-like composition between approximately 3.5 and 2.7 Ga, establishing that more continental crust was extracted during this epoch. The +0.052 ± 0.006‰ offset between BSE and N-MORBs requires that <30% of Earth’s mantle equilibrated with recycled crustal material, implying limited mass exchange between the upper and lower mantle and, therefore, preservation of a primordial lower-mantle reservoir for most of Earth’s geologic history. Modern OIBs record variable ⁴⁹Ti/⁴⁷Ti ratios ranging from chondritic to N-MORBs compositions, indicating continuing disruption of Earth’s primordial mantle. Thus, modern-style plate tectonics with high mass transfer between the upper and lower mantle only represents a recent feature of Earth’s history.ISSN:0028-0836ISSN:1476-468