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

Variations in growth traits and wood physicochemical properties among Pinus koraiensis families in Northeast China

This study aimed to explore and improve the different economic values of Pinus koraiensis (Siebold and Zucc.) by examining the variations in 6 growth traits and 9 physicochemical wood properties among 53 P. koraiensis half-sib families. Growth traits assessed included height, diameter at breast height, volume, degree of stem straightness, stem form, and branch number per node, while wood properties assessed included density, fiber length and width, fiber length to width ratio, and cellulose, hemicellulose, holocellulose, lignin, and ash contents. Except for degree of stem straightness and branch number per node, all other traits exhibited highly significant variations (P < 0.01) among families. The coefficients of variation ranged from 5.3 (stem form) to 66.7% (ash content), whereas, the heritability ranged from 0.136 (degree of stem straightness) to 0.962 (ash content). Significant correlations were observed among growth traits and wood physicochemical properties. Principal component analysis identified four distinct groups representing growth traits, wood chemical and physical properties, and stem form traits. Multi-trait comprehensive evaluation identified three groups of elite families based on breeding objectives, including rapid growth, improved timber production for building and furniture materials, and pulpwood production. These specific families should be used to establish new plantations

The Manchurian Walnut Genome: Insights into Juglone and Lipid Biosynthesis

Background Manchurian walnut (Juglans mandshurica Maxim.) is a tree with multiple industrial uses and medicinal properties in the Juglandaceae family (walnuts and hickories). J. mandshurica produces juglone, which is a toxic allelopathic agent and has potential utilization value. Furthermore, the seed of J. mandshurica is rich in various unsaturated fatty acids and has high nutritive value. Findings Here, we present a high-quality chromosome-scale reference genome assembly and annotation for J. mandshurica (n = 16) with a contig N50 of 21.4 Mb by combining PacBio high-fidelity reads with high-throughput chromosome conformation capture data. The assembled genome has an estimated sequence size of 548.7 Mb and consists of 657 contigs, 623 scaffolds, and 40,453 protein-coding genes. In total, 60.99% of the assembled genome consists of repetitive sequences. Sixteen super-scaffolds corresponding to the 16 chromosomes were assembled, with a scaffold N50 length of 33.7 Mb and a BUSCO complete gene percentage of 98.3%. J. mandshurica displays a close sequence relationship with Juglans cathayensis, with a divergence time of 13.8 million years ago. Combining the high-quality genome, transcriptome, and metabolomics data, we constructed a gene-to-metabolite network and identified 566 core and conserved differentially expressed genes, which may be involved in juglone biosynthesis. Five CYP450 genes were found that may contribute to juglone accumulation. NAC, bZip, NF-YA, and NF-YC are positively correlated with the juglone content. Some candidate regulators (e.g., FUS3, ABI3, LEC2, and WRI1 transcription factors) involved in the regulation of lipid biosynthesis were also identified. Conclusions Our genomic data provide new insights into the evolution of the walnut genome and create a new platform for accelerating molecular breeding and improving the comprehensive utilization of these economically important tree species

The impact of gene polymorphism and hepatic insufficiency on voriconazole dose adjustment in invasive fungal infection individuals

Voriconazole (VRZ) is a broad-spectrum antifungal medication widely used to treat invasive fungal infections (IFI). The administration dosage and blood concentration of VRZ are influenced by various factors, posing challenges for standardization and individualization of dose adjustments. On the one hand, VRZ is primarily metabolized by the liver, predominantly mediated by the cytochrome P450 (CYP) 2C19 enzyme. The genetic polymorphism of CYP2C19 significantly impacts the blood concentration of VRZ, particularly the trough concentration (Ctrough), thereby influencing the drug’s efficacy and potentially causing adverse drug reactions (ADRs). Recent research has demonstrated that pharmacogenomics-based VRZ dose adjustments offer more accurate and individualized treatment strategies for individuals with hepatic insufficiency, with the possibility to enhance therapeutic outcomes and reduce ADRs. On the other hand, the security, pharmacokinetics, and dosing of VRZ in individuals with hepatic insufficiency remain unclear, making it challenging to attain optimal Ctrough in individuals with both hepatic insufficiency and IFI, resulting in suboptimal drug efficacy and severe ADRs. Therefore, when using VRZ to treat IFI, drug dosage adjustment based on individuals’ genotypes and hepatic function is necessary. This review summarizes the research progress on the impact of genetic polymorphisms and hepatic insufficiency on VRZ dosage in IFI individuals, compares current international guidelines, elucidates the current application status of VRZ in individuals with hepatic insufficiency, and discusses the influence of CYP2C19, CYP3A4, CYP2C9, and ABCB1 genetic polymorphisms on VRZ dose adjustments and Ctrough at the pharmacogenomic level. Additionally, a comprehensive summary and analysis of existing studies’ recommendations on VRZ dose adjustments based on CYP2C19 genetic polymorphisms and hepatic insufficiency are provided, offering a more comprehensive reference for dose selection and adjustments of VRZ in this patient population

Irisin Is Controlled by Farnesoid X Receptor and Regulates Cholesterol Homeostasis

ObjectiveThe aim of this study was to investigate whether the nuclear receptor farnesoid X receptor (FXR) could regulate FNDC5/Irisin expression and the role of Irisin in hyperlipidemia and atherosclerosis in ApoE-/- mice.Methods and ResultsWe treated primary human hepatocytes, HepG2 cells, and Rhesus macaques with FXR agonist (CDCA, GW4064, and ivermectin). FNDC5 expression was highly induced by CDCA and GW4064 in hepatocytes, HepG2 cells, and the circulating level of Irisin increased in Rhesus macaques. Luciferase reporter and CHIP assays were used to determine whether FXR could regulate FNDC5 promoter activity. Irisin-ApoE-/- and ApoE-/- mice were used to study the metabolic function of Irisin in dyslipidemia and atherosclerosis. Irisin-ApoE-/- mice showed improved hyperlipidemia and alleviated atherosclerosis as compared with ApoE-/- mice. Irisin upregulated the expression of Abcg5/Abcg8 in liver and intestine, which increased the transport of biliary cholesterol and fecal cholesterol output.ConclusionActivation of FXR induces FNDC5 mRNA expression in human and increased the circulating level of Irisin in Rhesus macaques. FNDC5/Irisin is a direct transcriptional target of FXR. Irisin may be a novel therapeutic strategy for dyslipidemia and atherosclerosis

Chinese steamed bread and novel wheat products

Wheat is one of the most important agricultural crops globally, and the third-largest food crop after rice and maize in China; in particular, wheat is one of the primary provisions in human diets in Northern China. Research on the quality of wheat flour is important for wheat food production. Steam bread was one of staple foods in the northern part of China due to the combination of unique cultures and dietary habits. The Chinese steamed bread-making process is a complex system. There is significant value in research on the aroma characteristics of wheat flour, fermented dough, and steamed bread. The solid phase micro-extraction (SPME) GC-MS was used to investigate the compounds of volatile aroma in gelatinized-flour. Volatile compounds of steamed bread vary depending on the content of gluten in wheat flour. In the three physical stages of making Chinese steamed bread, the quantity of hydrocarbons and aldehydes first decreased and then increased. Chinese steamed bread made from wheat flour with added 3% of stachyose, has the greatest elasticity and extensibility, and has the highest scores when conducted for sensory evaluation, thus making nutrient fortified steamed bread. Along with the developing and applying of the modern food process technology, wheat also can be made for novel wheat products with different flavors, such as wheat bran, wheat germ flour, wheat germ oil and “popwheat”, and further caramel treats. In addition, volatile compounds of wheat bran and germ differ between high gluten, middle gluten and low gluten flour. Therefore, the research on the processing quality of wheat dough has been a hot topic.</p

Identification and Differential Expression of a Candidate Sex Pheromone Receptor in Natural Populations of Spodoptera litura.

Olfaction is primarily mediated by highly specific olfactory receptors (ORs), a subfamily of which are the pheromone receptors that play a key role in sexual communication and can contribute to reproductive isolation. Here we cloned and identified an olfactory receptor, SlituOR3 (Genbank NO. JN835270), from Spodoptera litura, to be the candidate pheromone receptor. It exhibited male-biased expression in the antennae, where they were localized at the base of sensilla trichoidea. Conserved orthologues of these receptors were found amongst known pheromone receptors within the Lepidoptera, and SlituOR3 were placed amongst a clade of candidate pheromone receptors in a phylogeny tree of insect ORs. SlituOR3 is required for the EAG responses to both Z9E11-14:OAc and Z9E12-14:OAc SlituOR3 showed differential expression in S. litura populations attracted to traps baited with a series of sex pheromone blends composed of different ratios of (9Z,11E)-tetradecadienyl acetate (Z9E11-14:OAc) and (9Z,12E)-tetradecadienyl acetate (Z9E12-14:OAc). The changes in the expression level of SlitOR3 and antennal responses after SlitOR3 silencing suggested that SlitOR3 is required for the sex pheromone signaling. We infer that variation in transcription levels of olfactory receptors may modulate sex pheromone perception in male moths and could affect both of pest control and monitoring efficiency by pheromone application after long time mass trapping with one particular ratio of blend in the field

Genetic Improvement in Juglans mandshurica and Its Uses in China: Current Status and Future Prospects

Juglans mandshurica is an economically and ecologically valuable species that is used for various construction purposes, making luxurious furniture, as food and sources of medicinal substances and landscaping because of its excellent wood, edible fruits and rich in various types of chemical compounds. In the past few decades, several genetic improvements of J. mandshurica were made, with a focus on the selection of improved varieties and on breeding technology. Many elite provenances and families were selected based on growth traits or wood properties. In recent years, with the increasing demand for high-quality seedlings in Chinese forestry production, the breeding goals of genetic improvement for J. mandshurica were redefined to include other traits, such as fruit yield and contents of medicinal component. However, the improvement processes were still slow due to the long breeding cycle and the limited use of advanced breeding technologies, resulting in the selection of fewer improved varieties. In this review, we summarized the research progresses on genetic improvements of J. mandshurica and other related works, and discussed research gaps and suggested future directions for genetic improvement of the species. The review provides valuable insight for the selection of improved varieties and production of excellent germplasms

Protein fortification of wheat bread using dry fractionated chickpea protein-enriched fraction or its sourdough

Chickpea protein-enriched ingredients were prepared by combining dry milling, air classification, and optionally solid-state fermentation. The fermentation was carried out with the autochthonous LAB strain Pediococcus acidilactici to reduce the level of antinutritional factors. A protein-enriched chickpea fraction and its sourdough were used to partially replace wheat flour with 20%–30% w/w in wheat bread. The protein content of bread increased by 38.5% on dry basis with a 30% w/w replacement. As the substitution level increased from 0% to 20% and 30%, a longer dough mixing time was required, the specific volume of the bread decreased, and the crumb structure became denser. The levels of raffinose, stachyose, and verbascose in the sourdough bread were reduced by 75.4%, 97.6%, and 90.0% compared to the unfermented bread, respectively. With sourdough addition the crust showed less browning and exhibited a better microbiological stability compared to that of the other breads.</p

Effects of Fertilizer Application Patterns on Foxtail Millet Root Morphological Construction and Yield Formation during the Reproductive Stage in the Loess Plateau of China

With crop yields continually increasing, chemical fertilizer consumption in China is increasing in parallel. The excessive use of synthetic fertilizer can lead to soil compaction, acidification, and degeneration, which can all be mitigated through additional organic manure application. The combined application of organic manure and inorganic fertilizer plays crucial roles in the root morphology and yield formation of dryland crops. In this study, foxtail millet (Chang Sheng 07) was used as the experimental material and sown in a dry farming area with five different fertilizing patterns, which were composed of chemical N, P, organic manure, and microbial manure. These patterns included a single application of 45 kg·ha−1 of nitrogen fertilizer as the control (N45), the combined application of 60 kg·ha−1 of nitrogen fertilizer with 30 kg·ha−1 of phosphorus fertilizer (N60P30), the combined application of 90 kg·ha−1 of nitrogen fertilizer with 45 kg·ha−1 of phosphorus fertilizer (N90P45), 60 kg·ha−1 of nitrogen fertilizer and 40 kg·ha−1 of phosphorus fertilizer with 2000 kg·ha−1 of organic manure (N60P40-O), and 60 kg·ha−1 of nitrogen fertilizer and 40 kg·ha−1 of phosphorus fertilizer with 5 kg·ha−1 of microbial manure (N60P40-M). Each treatment was performed with four repeats. The results show that (1) the different fertilization patterns had significant effects on the morphological construction of foxtail millet roots, and the root length (RL) with N60P40–O underwent a significant increase of 88.23% and 61.59% in the two stages, respectively, (2) as confirmed by the correlation analysis, the root surface area (RSA) was positively correlated with the RL and root volume (RV), (3) the yields with N90P45 and N60P30 exhibited a significant increase of 54.43% and 59.86%, and those with N60P40–O and N60P40–M stably increased by 13.12–24.11% compared to those with N45, and (4) the water use efficiency (WUE) of foxtail millet under the N60P30 and N90P45 patterns significantly increased by 33.40–62.39%, while that under the N60P40–O and N60P40–M patterns increased by 12.89–29.20%. In summary, the application of additional organic matter and microbial manure promoted the morphological construction of foxtail millet roots, led to better stability in grain production, and is an ecofriendly option in terms of sustainable land use