Functional Impact Of 14 Single Nucleotide Polymorphisms Causing Missense Mutations Of Human α7 Nicotinic Receptor

The α7nicotinic receptor (nAChR) is a major subtype of the nAChRs in the central nervous system, and the receptor plays an important role in brain function. In the dbSNP database, there are 55 single nucleotide polymorphisms (SNPs) that cause missense mutations of the human α7nAChR in the coding region. In this study, we tested the impact of 14 SNPs that cause missense mutations in the agonist binding site or the coupling region between binding site and channel gate on the receptor function. The wild type or mutant receptors were expressed or co-expressed in Xenopus oocytes, and the agonist-induced currents were tested using two-electrode voltage clamp. Our results demonstrated that 6 mutants were nonfunctional, 4 mutants had reduced current expression, and 1 mutants altered ACh and nicotine efficacy in the opposite direction, and one additional mutant had slightly reduced agonist sensitivity. Interestingly, the function of most of these nonfunctional mutants could be rescued by α7nAChR positive allosteric modulator PNU-120596 and agonist-PAM 4BP-TQS. Finally, when coexpressed with the wild type, the nonfunctional mutants could also influence the receptor function. These changes of the receptor properties by the mutations could potentially have an impact on the physiological function of the α7nAChR-mediated cholinergic synaptic transmission and anti-inflammatory effects in the human SNP carriers. Rescuing the nonfunctional mutants could provide a novel way to treat the related disorders. Copyright

Effects of natural covers on soil evaporation of the shelterbelt along the Tarim Desert Highway

The control of soil evaporation is one of important approaches to save water. The artificially simulated evaporation experiments have been conducted in the hinterland of the Taklimakan Desert to reveal the effects of the natural covers on the soil evaporation of the Tarim Desert Highway shelterbelt as well as provide some insights in the efficient utilization of water resources and optimization of irrigation systems. The results showed that (1) All the covers, including the sand deposit, the salt crust, the litter, the sand-litter mixed layer and so on, can significantly inhibit the soil water evaporation. Specifically, the daily evaporation, the total evaporation, and the evaporation rate in covered sands were much smaller than that of sands without cover. The cover inhibition effects increased with the cover thickness. Particularly, the soil evaporation of the covered sands was less affected by external and internal factors than that of the bare sands. Moreover, the variation of daily evaporation of covered sands was smaller than that of bare sands. The cumulative evaporation varied linearly with time in the covered sands whereas it varied logarithmically in the bare sands. In addition, the soil evaporation in the bare sands showed significantly different characteristics in the early and late stages of the evaporation. (2) All the covers exhibited the significant inhibiting effect on the soil evaporation, and the inhibition efficiency increased logarithmically with the cover thickness. However, as the cover thickness was above a certain value, the increase in the inhibition efficiency was slow. Particularly, at a cover thickness of 2 cm, there was no obvious difference in the inhibition efficiency among all kinds of covers. The maximum inhibition efficiency as calculated from the daily evaporation on the first day of irrigation was: sand-litter mixed layer (79.92%) > litter layer (78.96%) > salt crust (75.58%) > sand bed (74.11%), whereas the average inhibiting efficiency as calculated from the cumulative soil evaporation at the end of an irrigation cycle (the fourth day) was: salt crust (67.78%) > sand-litter mixed layer (66.72%) > sand deposit (63.28%) > litter layer (61.74%)

Classification and regionalization of the forming environment of windblown sand disasters along the Tarim Desert Highway

Through the systematic field survey and observations, the factor quantification as well as setting the criteria, the sand disaster-forming environment along the Tarim Desert Highway can be divided into four grades by the classification and regionalization based on fuzzy mathematics. The length of the regions with significant sand disaster accounted for 37.1% of the total highway length. Particularly, the area along the Tarim Desert Highway, based on the sand disaster-forming environment classification as well as the difference in the five basic landform units along the highway, combined with the difference of wind regime, can be divided into five regions, in which the length of the regions suffering severe sand damage occupied 64.3% of the total highway length. In addition, the index of disaster formation grade along the highway decreased from north to south, showing a repeated spatial pattern in small length scales

Integrative transcriptomic profiling of mRNA, miRNA, circRNA, and lncRNA in alveolar macrophages isolated from PRRSV-infected porcine

IntroductionThe porcine reproductive and respiratory syndrome virus (PRRSV) continues to pose a significant threat to the global swine industry, attributed largely to its immunosuppressive properties and the chronic nature of its infection. The absence of effective vaccines and therapeutics amplifies the urgency to deepen our comprehension of PRRSV’s intricate pathogenic mechanisms. Previous transcriptomic studies, although informative, are partially constrained by their predominant reliance on in vitro models or lack of long-term infections. Moreover, the role of circular RNAs (circRNAs) during PRRSV invasion is yet to be elucidated.MethodsIn this study, we employed an in vivo approach, exposing piglets to a PRRSV challenge over varied durations of 3, 7, or 21 days. Subsequently, porcine alveolar macrophages were isolated for a comprehensive transcriptomic investigation, examining the expression patterns of mRNAs, miRNAs, circRNAs, and long non-coding RNAs (lncRNAs).ResultsDifferentially expressed RNAs from all four categories were identified, underscoring the dynamic interplay among these RNA species during PRRSV infection. Functional enrichment analyses indicate that these differentially expressed RNAs, as well as their target genes, play a pivotal role in immune related pathways. For the first time, we integrated circRNAs into the lncRNA-miRNA-mRNA relationship, constructing a competitive endogenous RNA (ceRNA) network. Our findings highlight the immune-related genes, CTLA4 and SAMHD1, as well as their associated miRNAs, lncRNAs, and circRNAs, suggesting potential therapeutic targets for PRRS. Importantly, we corroborated the expression patterns of selected RNAs through RT-qPCR, ensuring consistency with our transcriptomic sequencing data.DiscussionThis study sheds lights on the intricate RNA interplay during PRRSV infection and provides a solid foundation for future therapeutic strategizing

Helium, argon and carbon isotopic compositions of spring gases in the Hainan Island, China

Chemical and isotopic compositions have been measured for N2-He-rich bubbling gases discharging from hot springs in the Hainan Island, Southern China. Observed 3He/4He ratios (0.1–1.3 RA) indicate the occurrence of a mantle component throughout the island, which has been highly diluted by a crustal radiogenic 4He component. The occurrence of mantle-derived helium is high in the northern island (12%–16% of total He) and gradually decreases towards southern coast (l%–3% of total He). Such a distribution pattern is most likely controlled by the Pleocene-Quaternary volcanic activities in the northern island and groundwater circulation along the deep major faults. The 40Ar/36Ar and N2/Ar ratios suggest that N2 and Ar of the hot spring gases are mostly meteoric. Although δ13C values of CO2 (–20‰ to −27‰) with low concentrations are consistent with the biogenic origin, the combination of 3He/4He and δ13CCO2 suggests a two end-member mixing of mantle and crustal components with CO2/3He ratios of 2×109 and 8×1011, respectively. However, the low CO2/3He ratios (1–22×106) can not be ascribed in terms of the simple mixing but has to be explained by the addition of radiogenic 4He and loss of CO2 by calcite precipitation in the hydrothermal system, which is most likely controlled by the degree of gas-water-rock interaction

Bounds on feedback numbers of de Bruijn graphs, Taiwanese

Abstract. The feedback number of a graph G is the minimum number of vertices whose removal from G results in an acyclic subgraph. We use f (d, n) to denote the feedback number of the de Bruijn graph U B (d, n). R. Královic and P. Ruzicka [Minimum feedback vertex sets in shuffle-based interconnection networks. Information Processing Letters, 86 . This paper gives the upper bound o

Remarkable response to pazopanib plus vivolumab in a patient with pericardial synovial sarcoma carrying a novel genotype BRCA2 c.968dupT: A case report

Abstract Pericardial synovial sarcomas (PSS) have a low incidence rate and are highly invasive with a dismal prognosis. Standard treatment includes surgery, radiotherapy and chemotherapy but with limited response. Here, we report the case of a 15‐year‐old nonsmoking youngster diagnosed with PSS who developed disease relapsed from surgery after 1 month. Next‐generation sequencing (NGS) using baseline tissue was performed, and BRCA2 c.968dupT was detected. Then pazopanib (a multitargeted inhibitor) plus nivolumab (an immune checkpoint inhibitor) was administered, with a partial response and progression‐free survival of 14 months. BRCA2 c.968dupT has not previously been reported in PSS and its response to targeted combination immunotherapy are not well characterized. Here, we report the efficacy of pazopanib combined with nivolumab in a PSS patient harboring BRCA2 c.968dupT and also provide the clinical evidence of the utility of NGS in exploring actionable mutations for solid tumor. Combination therapy based on immunotherapy may be a potential treatment choice for PSS harboring BRCA2 mutation

Feedback numbers of de Bruijn digraphs

AbstractA subset of vertices of a graph G is called a feedback vertex set of G if its removal results in an acyclic subgraph. Let f(d,n) denote the minimum cardinality over all feedback vertex sets of the de Bruijn digraph B(d,n). This paper proves that for any integers d≥2 and n≥2f(d,n)={1n∑i∣ndiφ(ni)for 2≤n≤4;dnn+O(ndn−4)for n≥5, where i∣n means i divides n, and φ(i) is the Euler totient function