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Simple Summary: In this study, we present the characterization of Aedes aegypti mosquito salivary protein, LTRIN (lymphotoxin β receptor inhibitor), a key facilitator of ZIKV transmission. Injected into the human host during blood-feeding, LTRIN interacts with the human receptor LTβR. We found that LTRIN exists as a thermostable protein with homodimers consisting of an alpha helix-dominant secondary structure with two EF-hand motifs, crucial for withstanding temperature fluctuations during blood-feeding. Despite being an EF-hand protein, its secondary structure remains unaffected by Ca2+ binding. ELISA assays and HDX-MS experiments identified the binding region of LTRIN with LTβR. Disrupting the calcium-binding ability in the second EF-hand motif significantly impacted the interaction between LTRIN, particularly the 15 kDa C-terminal protein, ΔLTRIN, and LTβR. Moreover, the decrease in binding affinity of full-length LTRIN suggests the presence of only the truncated form, ΔLTRIN, in the mosquito's saliva, as the N-terminal region likely covers the interaction site. This insight provides a basis for developing inhibitors against LTRIN as a potential treatment or vaccine target for ZIKV. Salivary proteins from mosquitoes have received significant attention lately due to their potential to develop therapeutic treatments or vaccines for mosquito-borne diseases. Here, we report the characterization of LTRIN (lymphotoxin beta receptor inhibitor), a salivary protein known to enhance the pathogenicity of ZIKV by interrupting the LTβR-initiated NF-κB signaling pathway and, therefore, diminish the immune responses. We demonstrated that the truncated C-terminal LTRIN (ΔLTRIN) is a dimeric protein with a stable alpha helix-dominant secondary structure, which possibly aids in withstanding the temperature fluctuations during blood-feeding events. ΔLTRIN possesses two Ca2+ binding EF-hand domains, with the second EF-hand motif playing a more significant role in interacting with LTβR. Additionally, we mapped the primary binding regions of ΔLTRIN on LTβR using hydrogen–deuterium exchange mass spectrometry (HDX-MS) and identified that 91QEKAHIAEHMDVPIDTSKMSEQELQFHY118 from the N-terminal of ΔLTRIN is the major interacting region. Together, our studies provide insight into the recognition of LTRIN by LTβR. This finding may aid in a future therapeutic and transmission-blocking vaccine development against ZIKV. [ABSTRACT FROM AUTHOR]

Salivary proteins from mosquitoes have received significant attention lately due to their potential to develop therapeutic treatments or vaccines for mosquito-borne diseases. Here, we report the characterization of LTRIN (lymphotoxin beta receptor inhibitor), a salivary protein known to enhance the pathogenicity of ZIKV by interrupting the LTβR-initiated NF-κB signaling pathway and, therefore, diminish the immune responses. We demonstrated that the truncated C-terminal LTRIN (ΔLTRIN) is a dimeric protein with a stable alpha helix-dominant secondary structure, which possibly aids in withstanding the temperature fluctuations during blood-feeding events. ΔLTRIN possesses two Ca2+ binding EF-hand domains, with the second EF-hand motif playing a more significant role in interacting with LTβR. Additionally, we mapped the primary binding regions of ΔLTRIN on LTβR using hydrogen–deuterium exchange mass spectrometry (HDX-MS) and identified that 91QEKAHIAEHMDVPIDTSKMSEQELQFHY118 from the N-terminal of ΔLTRIN is the major interacting region. Together, our studies provide insight into the recognition of LTRIN by LTβR. This finding may aid in a future therapeutic and transmission-blocking vaccine development against ZIKV.

The regulation of air quality is important for ensuring the health of a population. Current air quality decision support systems are very useful if the user possesses sufficient data to operate them and the necessary expertise to interpret their results. In general, these systems suffer as a result of their excessive complexity. The present study describes the development of a scalable air quality decision support system using the CALPUFF air dispersion model and a Geospatial Information System (GIS). This system uses receptor level exposure modeling and outputs from CALPUFF to estimate the relative impacts on human populations from multiple air pollution sources by calculating intake, defined as the amount of pollution that is inhaled by a population and intake fraction, defined as the fraction of pollutant emitted by a pollution source that is inhaled by a population. Unlike ground level pollution concentration, intake and intake fraction consider receptors and offer a more valuable estimate of pollution exposure, especially when faced with limited input data. The system also leverages the inherent strength of GIS to improve accessibility of geospatial data by generating maps of ground level pollutant concentration, intake, and intake fraction using graduated color schemes. This enables any user to identify potentially hazardous pollution sources and prioritize decisions such as development, maintenance, and decommission. [ABSTRACT FROM AUTHOR]

Asenapine is a novel psychopharmacologic agent under development for the treatment of schizophrenia and bipolar disorder. We determined and compared the human receptor binding affinities and functional characteristics of asenapine and several antipsychotic drugs. Compounds were tested under comparable assay conditions using cloned human receptors. In comparison with the antipsychotics, asenapine showed high affinity and a different rank order of binding affinities (pKi) for serotonin receptors (5-HT1A [8.6], 5-HT1B [8.4], 5-HT2A [10.2], 5-HT2B [9.8], 5-HT2C [10.5], 5-HT5 [8.8], 5-HT6 [9.6] and 5-HT7 [9.9]), adrenoceptors (α1 [8.9], α2A [8.9], α2B [9.5] and α2C [8.9]), dopamine receptors (D1 [8.9], D2 [8.9], D3 [9.4] and D4 [9.0]) and histamine receptors (H1 [9.0] and H2 [8.2]). It had much lower affinity (pKi ≤ 5) for muscarinic receptors and was the only agent with affinity for H2 receptors. Relative to its D2 receptor affinity, asenapine had a higher affinity for 5-HT2C, 5-HT2A, 5-HT2B, 5-HT7, 5-HT6, α2B and D3 receptors, suggesting stronger engagement of these targets at therapeutic doses. Asenapine behaved as a potent antagonist (pKB) at 5-HT1A (7.4), 5-HT1B (8.1), 5-HT2A (9.0), 5-HT2B (9.3), 5-HT2C (9.0), 5-HT6 (8.0), 5-HT7 (8.5), D2 (9.1), D3 (9.1), α2A (7.3), α2B (8.3), α2C (6.8) and H1 (8.4) receptors. These functional effects differed from those of risperidone (pKB <5 for 5-HT6) and olanzapine (pKB <5 for 5-HT1A and α2). Our results indicate that asenapine has a unique human receptor signature, with binding affinity and antagonistic properties that differ appreciably from those of antipsychotic drugs. [ABSTRACT FROM AUTHOR]

• The preliminary DCGL W for the surface soil of Kori Unit-1 was calculated. • The DCGL W of 134Cs, 137Cs, and 60Co did not exhibit significant differences. • The DCGL W of 90Sr, 241Pu, 3H and 63Ni exhibited significant differences. • The findings can provide insight for the considerations of the human receptor. The preliminary derived concentration guideline level (DCGL W) for the surface soil of Kori Unit-1 was calculated considering the habit data of residents living near the nuclear power plant in South Korea (a 1-y-old infant, a 10-y-old child, and an adult), following the ICRP 101a recommendation for radiation protection of the public. The radionuclides of interest were 3H, 14C, 60Co, 63Ni, 90Sr, 134Cs, 137Cs, and 241Pu. 14C, 3H. 14C, 3H, and 241Pu had the maximum total effective dose equivalent (TEDE) after a certain duration, whereas 60Co, 63Ni, 134Cs, 137Cs, and 90Sr had the maximum TEDE in the first year. In the initial period, 60Co, 134Cs, 137Cs, and 90Sr had the most dominant effect on TEDE in all the age groups, but their influence disappeared after 203.09 y and only doses of 241Pu and 90Sr were observed thereafter. The main exposure pathways of 60Co, 134Cs, and 137Cs were external pathways, but the main exposure pathways of 90Sr were plant (water-independent), meat (water-independent), and milk (water-independent). The maximum TEDEs caused by 60Co, 134Cs, and 137Cs were similar in all the age groups, but that caused by 90Sr considerably varied depending on the age group. The nuclides for which the DCGL W was notably different from the conservative DCGL W were as follows: 3H (increment of 109.21% and 183.08% for the child and adult, respectively), 63Ni (increment of 286.37% and 702.86% for the child and adult, respectively). The main exposure pathways for these radionuclides were ingestion pathways (water-dependent or independent), which led to internal exposure. The findings can provide insight for the considerations of the human receptor to calculate the DCGL W for the surface soil of Kori Unit-1 using RESRAD-ONSITE. [ABSTRACT FROM AUTHOR]