Significant Species Differences Research Articles

Seasonal variations and sources of the dew from stable isotopes in alpine meadows

AbstractThe dew is closely related to the micro‐use water of plants and the large‐scale hydrological processes, its formation on grassland plays a vital role especially in maintaining the eco‐hydrological cycle. We used structural equation modelling to investigate how environmental factors would affect dew formation on alpine graminoid‐Kobresia meadow in northern Qinghai‐Tibet Plateau. The stable isotope information of dew, ambient vapour, soil water, plant water, creek water and precipitation were tracked to explore the source of dew, the dew transport route of the six dominant species by Mix SIAR model. Our results showed that the frequency of dew on the graminoid‐Kobresia meadow in 2020 and 2021 was 42.86% and 45.83%, respectively. Both atmospheric pressure (r = 0.4) and temperature (r = 0.382) showed significant positive effects dew formation while wind speed (r = −0.309) had a negative effect. The contribution rates of soil water, plant water and ambient water vapour to dew were 48.20 ± 5.46%, 38.30 ± 5.07%, and 13.50 ± 1.82%, respectively. The proportion of dew utilization in the dominant species had no significant species differences. Our results provided an improved understanding of dew formation based on isotope technology on alpine meadow in northern Qinghai‐Tibet Plateau.

Preparation of glucuronides using liver microsomes and their characterization by 1D/2D NMR spectroscopy and mass spectrometry: Application to fentanyl metabolites.

A simple, low-cost method for preparing glucuronic acid-conjugated metabolites was developed using fentanyl, a potent synthetic opioid, as a model drug. Five glucuronic acid-conjugated metabolites of fentanyl were measured in the culture medium of fresh human hepatocytes incubated with fentanyl. These glucuronides were also formed by incubation of their corresponding substrates (e.g., 4'-hydroxy-fentanyl and β-hydroxy-fentanyl) with uridine 5'-diphosphoglucuronic acid and human liver microsomes (HLM). Experiments using liver microsomes of several animals revealed that significant species differences exist in the glucuronide formation patterns; fentanyl glucuronide was only formed in HLM, and 4'-hydroxy-fentanyl glucuronide was formed much more in rat liver microsomes (RLM) than HLM and dog liver microsomes. Furthermore, surprisingly, HLM and RLM showed opposite substrate selectivity for the enantiomers of β-hydroxy-fentanyl. Submilligram amounts of three of these metabolites, namely, 4'-hydroxy-fentanyl glucuronide and two glucuronides of β-hydroxy-fentanyl, were prepared by using HLM or RLM. The products were readily purified with a reversed-phase/anion-exchange mixed-mode solid-phase extraction cartridge, and then, their chemical structures were confirmed by 1D/2D nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry data. In addition, the products were quantitated by quantitative NMR, and the yields were 3.6-69%.

Diversity characterization of bacteria and fungi in water, sediments and biofilms from Songhua River in Northeast China

Water, sediments, and biofilms are the typical microbial carriers in natural water environments. However, comparative analysis of the distribution of bacterial and fungal communities in different carriers within the same habitat is relatively lacking. Therefore, this study employed 16 S and ITS rRNA gene sequencing to identify bacterial and fungal community structures in water, sediments, and biofilm. The results show that (1) the OTUs numbers revealed that the bacterial abundance, at the levels of species, genus, and family, followed the order of sediments > water > biofilms, while the fungal abundance order was water > sediments > biofilms. In addition, bacteria were mainly present in sediments, while fungi were mainly present in water. (2) The α diversity index (Shannon, ACE, Simpson, and Chao1) order, for bacteria was: sediments > water > biofilms, indicating that the diversity and homogeneity of bacteria in sediments were relatively higher; for fungi was: water > sediments > biofilms, indicating that the diversity and abundance of fungi in water were high. (3) The core phylum of bacterial in the water, sediments, and biofilms was Cyanobacteria (31.3–46.1%) and Actinobacteria (27.6–36.1%); Proteobacteria (35.0–41.8%), Cyanobacteria (14.7–36.6%); and Proteobacteria (63.3–69.2%), respectively. (4) The mainly colonized fungal phyla in biofilms in the water, sediments, and biofilms were Basidiomycota (29.3–38.7%) and Ascomycota (16.2–27.7%); Zygomycota (13.1–17.5%), Basidiomycota (5.6–17.6%); and Zygomycota (23.8–44.2%). (5) There were significant species differences in bacterial and fungal communities in water, sediments, and biofilm by NMDS analysis. Findings are useful for guiding significance for the Biogeochemical cycle of elements, the environmental fate of pollutants, and the study of water ecosystems.

The interspecific competition of tree plants in the presence of AM fungi and litter facilitates root morphological development and nutrition when compared with intraspecific competition.

Arbuscular mycorrhizal (AM) fungi can affect plant growth by regulating competition. Nutrient-deficient karst habitats contain abundant plants that compete for nutrients through interspecific or intraspecific competition, involving the nutritional transformation of litter decomposition. However, how plant competition in the presence of AM fungi and litter affects root development and nutrition remains unclear. A potted experiment was conducted, including AM fungus treatment with or without Glomus etunicatum, the competition treatment concerning intraspecific or interspecific competition through planting Broussonetia papyrifera and Carpinus pubescens seedlings, and the litter treatment with or without the mixture of B. papyrifera and C. pubescens litter leaves. The root morphological traits were analyzed, and nitrogen (N), phosphorus (P), and potassium (K) were measured. The results showed that AM fungus differently affected the root morphological development and nutrition of both competitive plants, significantly promoting B. papyrifera roots in the increase of dry weight, length, volume, surface area, tips, and branches as well as N, P, and K acquisitions regardless of litter addition. However, there was no apparent influence for C. pubescens roots, except for the diameter in the interspecific competition with litter. The root dry weight, length, volume, surface area, and tips of B. papyrifera under two competitive styles were significantly greater than C. pubescens regulated by AM fungus, presenting significant species differences. The responses of the relative competition intensity (RCI) on root morphological and nutritional traits indicated that AM fungus and litter both asymmetrically alleviated more competitive pressure for B. papyrifera than C. pubescens, and the interspecific competition facilitated more root morphological development and nutrition utilization by endowing B. papyrifera root superiority relative to C. pubescens compared with the intraspecific competition. In conclusion, interspecific competition is more beneficial for plant root development and nutrition than intraspecific competition in the presence of AM fungus and litter via asymmetrically alleviating competitive pressure for different plants.

Equivalence of combined decoction and mixed single decoctions of Gegen Qinlian Decoction in alleviating chemotherapy-associated diarrhea

This study compared the chemical profiles, component content, dry paste yield, and pharmacological effects of samples obtained from the mixed single decoctions and the combined decoction of Gegen Qinlian Decoction(GQD), aiming to provide an experimental foundation for evaluating the equivalence of the two decocting methods and the suitability of TCM formula granules in clinical application. The same decoction process was used to prepare the combined decoction and mixed single decoctions of GQD. Ultra-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap MS) was employed to compare the chemical profiles between the two groups. High-performance liquid chromatography(HPLC) was used to compare the content of nine characteristic components between the two groups. Then, a delayed diarrhea mouse model induced by irinotecan was established to compare the pharmacological effects of the two groups on chemotherapy-induced diarrhea. The UPLC-Q-Exactive Orbitrap MS in ESI~+ and ESI~- modes identified 59 chemical components in the compound decoction and mixed single decoctions, which showed no obvious differences in component species. The content of baicalin and wogonoside was higher in the compound decoction, while that of puerarin, daidzein-8-C-apiosylglucoside, berberine, epiberberine, wogonin, glycyrrhizic acid, and daidzein was higher in the mixed single decoctions. Further statistical analysis revealed no significant difference in the content of the nine characteristic components between the compound decoction and the mixed single decoctions. The dry paste yield had no significant difference between the two groups. Compared with the model group, both compound decoction and mixed single decoctions alleviated the weight loss and reduced diarrhea index in mice. Both of them lowered the levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), cyclooxygenase-2(COX-2), intercellular adhesion molecule-1(ICAM-1), interleukin-10(IL-10), malondialdehyde(MDA), and nitric oxide(NO) in the colon tissue. Furthermore, they significantly increased the levels of glutathione peroxidase(GSH-Px) and superoxide dismutase(SOD). Hematoxylin-eosin(HE) staining showed that colon tissue cells were tightly arranged with clear nuclei in both groups without obvious difference. The compound decoction and mixed single decoctions showed no significant differences in chemical component species, content of nine characteristic components, dry paste yield, or the pharmacological effects on alleviating chemotherapy-induced diarrhea. The findings provide a reference for evaluating the flexibility and superiority of combined or single decocting method in the preparation of TCM decoctions or formula granules.

Mouse embryonic stem cell-derived blood–brain barrier model: applicability to studying antibody triggered receptor mediated transcytosis

Blood brain barrier (BBB) models in vitro are an important tool to aid in the pre-clinical evaluation and selection of BBB-crossing therapeutics. Stem cell derived BBB models have recently demonstrated a substantial advantage over primary and immortalized brain endothelial cells (BECs) for BBB modeling. Coupled with recent discoveries highlighting significant species differences in the expression and function of key BBB transporters, the field is in need of robust, species-specific BBB models for improved translational predictability. We have developed a mouse BBB model, composed of mouse embryonic stem cell (mESC-D3)-derived brain endothelial-like cells (mBECs), employing a directed monolayer differentiation strategy. Although the mBECs showed a mixed endothelial-epithelial phenotype, they exhibited high transendothelial electrical resistance, inducible by retinoic acid treatment up to 400 Ω cm2. This tight cell barrier resulted in restricted sodium fluorescein permeability (1.7 × 10–5 cm/min), significantly lower than that of bEnd.3 cells (1.02 × 10–3 cm/min) and comparable to human induced pluripotent stem cell (iPSC)-derived BECs (2.0 × 10–5 cm/min). The mBECs expressed tight junction proteins, polarized and functional P-gp efflux transporter and receptor mediated transcytosis (RMT) receptors; collectively important criteria for studying barrier regulation and drug delivery applications in the CNS. In this study, we compared transport of a panel of antibodies binding species selective or cross-reactive epitopes on BBB RMT receptors in both the mBEC and human iPSC-derived BEC model, to demonstrate discrimination of species-specific BBB transport mechanisms.

Motilin receptor in GtoPdb v.2023.1

Motilin receptors (provisional nomenclature) are activated by motilin, a 22 amino-acid peptide derived from a precursor (MLN, P12872), which may also generate a motilin-associated peptide. There are significant species differences in the structure of motilin and its receptor, and in the functions of motilin. In humans and large mammals such as dog, activation of these receptors by motilin released from endocrine cells in the duodenal mucosa during fasting, induces propulsive phase III movements. This activity is associated with promoting hunger in humans. In humans and other mammals drugs and other non-peptide compounds which activate the motilin receptor may generate a more long-lasting ability to increase cholinergic activity within the upper gut, to promote upper gastrointestinal motility; this activity is suggested to be responsible for the gastrointestinal prokinetic effects of certain macrolide antibacterials (often called motilides; e.g. erythromycin, azithromycin), although for many of these molecules the evidence is sparse. Relatively high doses may induce vomiting and in humans, nausea.

Mass Balance of the IDO Inhibitor Navoximod (GDC-0919) in Rats and Dogs: Unexpected Cyanide Release from Imidazo[5,1-a]isoindole and Species Differences in Glucuronidation.

Navoximod (GDC-0919) is a small molecule inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1), developed to reduce T cell immunosuppression associated with cancer. This study describes the absorption, metabolism, and excretion (AME) of navoximod in rats and dogs following a single oral dose of [14C]-navoximod. An unexpected thiocyanate metabolite M1 and a chiral inversion metabolite M51 were captured as the major circulating metabolites in rats, accounting for 30% and 18% of 0-24 hr exposure, respectively. These two metabolites combined had much lower systemic exposure in dogs and humans (<6% and <1%). The novel cyanide release is proposed to occur via 4,5-epoxidation on the fused imidazole ring, leading to ring opening and rearrangement along with the release of cyanide. The decyanated metabolites were identified and confirmed by synthetic standards, which supported the proposed mechanism. In dogs, glucuronidation to M19 was the major clearance mechanism, representing 59% of the dose in the bile of bile duct-cannulated (BDC) dogs and 19% of the dose in the urine of intact dogs. Additionally, M19 also represented 52% of drug related exposure in circulation in dogs. In comparison, in humans, navoximod was mainly cleared through glucuronidation to M28 and excreted in urine (60% of the dose). The differences in the metabolism and elimination observed in vivo were qualitatively recapitulated in vitro with liver microsomes, suspended hepatocytes and co-cultured primary hepatocytes. The striking species differences in regioselective glucuronidation is likely explained by the species differences in UGT1A9, which was mainly responsible for M28 formation in humans. Significance Statement The results from this study demonstrated significant species differences in metabolism (especially glucuronidation) and elimination of navoximod among rats, dogs, and humans. The study also illustrated the mechanism of a novel cyanide release metabolism from the fused imidazo[5,1-a]isoindole ring. Such biotransformation should be kept in mind when working with imidazole containing new chemical entities (NCE) in drug discovery and development.

BMPRII+ neural precursor cells isolated and characterized from organotypic neurospheres: an in vitro model of human fetal spinal cord development.

Roof plate secretion of bone morphogenetic proteins (BMPs) directs the cellular fate of sensory neurons during spinal cord development, including the formation of the ascending sensory columns, though their biology is not well understood. Type-II BMP receptor (BMPRII), the cognate receptor, is expressed by neural precursor cells during embryogenesis; however, an in vitro method of enriching BMPRII+ human neural precursor cells (hNPCs) from the fetal spinal cord is absent. Immunofluorescence was undertaken on intact second-trimester human fetal spinal cord using antibodies to BMPRII and leukemia inhibitory factor (LIF). Regions of highest BMPRII+ immunofluorescence localized to sensory columns. Parenchymal and meningeal-associated BMPRII+ vascular cells were identified in both intact fetal spinal cord and cortex by co-positivity with vascular lineage markers, CD34/CD39. LIF immunostaining identified a population of somas concentrated in dorsal and ventral horn interneurons, mirroring the expression of LIF receptor/CD118. A combination of LIF supplementation and high-density culture maintained culture growth beyond 10 passages, while synergistically increasing the proportion of neurospheres with a stratified, cytoarchitecture. These neurospheres were characterized by BMPRII+/MAP2ab+/-/βIII-tubulin+/nestin-/vimentin-/GFAP-/NeuN- surface hNPCs surrounding a heterogeneous core of βIII-tubulin+/nestin+/vimentin+/GFAP+/MAP2ab-/NeuN- multipotent precursors. Dissociated cultures from tripotential neurospheres contained neuronal (βIII-tubulin+), astrocytic (GFAP+), and oligodendrocytic (O4+) lineage cells. Fluorescence-activated cell sorting-sorted BMPRII+ hNPCs were MAP2ab+/-/βIII-tubulin+/GFAP-/O4- in culture. This is the first isolation of BMPRII+ hNPCs identified and characterized in human fetal spinal cords. Our data show that LIF combines synergistically with high-density reaggregate cultures to support the organotypic reorganization of neurospheres, characterized by surface BMPRII+ hNPCs. Our study has provided a new methodology for an in vitro model capable of amplifying human fetal spinal cord cell numbers for > 10 passages. Investigations of the role BMPRII plays in spinal cord development have primarily relied upon mouse and rat models, with interpolations to human development being derived through inference. Because of significant species differences between murine biology and human, including anatomical dissimilarities in central nervous system (CNS) structure, the findings made in murine models cannot be presumed to apply to human spinal cord development. For these reasons, our human in vitro model offers a novel tool to better understand neurodevelopmental pathways, including BMP signaling, as well as spinal cord injury research and testing drug therapies.

Effect of mTOR inhibitors on sodium taurocholate cotransporting polypeptide (NTCP) function in vitro.

The sodium taurocholate cotransporting polypeptide (NTCP; gene name SLC10A1) is the primary hepatic basolateral uptake transporter for conjugated bile acids and the entry receptor for the hepatitis B and D virus (HBV/HDV). Regulation of human NTCP remains a knowledge gap due to significant species differences in substrate and inhibitor selectivity and plasma membrane expression. In the present study, various kinase inhibitors were screened for inhibition of NTCP function and taurocholate (TCA) uptake using NTCP-transfected HuH-7 cells. This study identified everolimus, an mTOR inhibitor and macrocyclic immunosuppressive drug, as an NTCP inhibitor with modest potency (IC50 = 6.7-8.0µM). Further investigation in differentiated HuH-7 cells expressing NTCP and NTCP-overexpressing Flp-In T-REx 293 cells revealed that the mechanism of action of everolimus on NTCP is direct inhibition and mTOR-independent. Structural analogs of everolimus inhibited NTCP-mediated TCA uptake, however, functional analogs did not affect NTCP-mediated TCA transport, providing further evidence for direct inhibition. This work contributes to the growing body of literature suggesting that NTCP-mediated bile acid uptake may be inhibited by macrocyclic peptides, which may be further exploited to develop novel medications against HBV/HDV.

Crustaceans functional diversity in mangroves and adjacent mudflats of the Persian Gulf and Gulf of Oman

The effects of mangrove vegetation on functional features of crustacean assemblages were investigated using the Biological Traits Analysis (BTA). The study was carried out at four major sites in the arid mangrove ecosystem of the Persian Gulf and Gulf of Oman. Samples of Crustacea and associated environmental variables were taken seasonally (February 2018 and June 2019) from two habitats: a vegetated area with both mangrove trees and pneumatophores, and an adjacent mudflat. In each site, functional traits for the species were assigned using seven categories based on bioturbation, adult mobility, feeding habits and life-strategy traits. The results showed that the crabs (i.e., Opusia indica, Nasima dotilliformis and Ilyoplax frater) were widely distributed across all sites and habitats. The vegetated habitats supported higher taxonomic diversity than the mudflats, which highlights the importance of mangrove structural complexity for crustacean assemblages. Species inhabiting vegetated habitats were characterized by stronger presence of conveyor building species, detritivore, predator, grazer, lecithotrophic larval development, body size of 50–100 mm, and swimmer trait modalities. While, mudflat habitat enhanced the occurrences of surface deposit feeder, planktotrophic larval development, body size of <5 mm, and life span of 2–5 years. The results of our study showed that taxonomic diversity increased from the mudflats to the mangrove vegetated habitats. However, functional diversity did not differ between habitats. The significant differences in species and functional trait composition were observed between vegetated habitats and adjacent mudflats, stressing that different habitats may harbor different species and trait sets, likely as a result of habitat complexity. The use of taxonomic and functional attributes generate complementary information that can helps us to reach more efficient conclusions in terms of biodiversity conservation and ecosystem functionality in mangrove ecosystems.

Biotransformation of Penindolone, an Influenza A Virus Inhibitor.

Penindolone (PND) is a novel broad-spectrum anti-Influenza A Virus (IAV) agent blocking hemagglutinin-mediated adsorption and membrane fusion. The goal of this work was to reveal the metabolic route of PND in rats. Ultra-high-performance liquid chromatography tandem high-resolution mass spectrometry (UHPLC-HRMS) was used for metabolite identification in rat bile, feces and urine after administration of PND. A total of 25 metabolites, including 9 phase I metabolites and 16 phase II metabolites, were characterized. The metabolic pathways were proposed, and metabolites were visualized via Global Natural Product Social Molecular Networking (GNPS). It was found that 65.24-80.44% of the PND presented in the formation of glucuronide conjugate products in bile, and more than 51% of prototype was excreted through feces. In in vitro metabolism of PND by rat, mouse and human liver microsomes (LMs) system, PND was discovered to be eliminated in LMs to different extents with significant species differences. The effects of chemical inhibitors of isozymes on the metabolism of PND in vitro indicated that CYP2E1/2C9/3A4 and UGT1A1/1A6/1A9 were the metabolic enzymes responsible for PND metabolism. PND metabolism in vivo could be blocked by UGTs inhibitor (ibrutinib) to a certain extent. These findings provided a basis for further research and development of PND.

Special properties of adult neurogenesis in the human hippocampus: Implications for its clinical applications.

Special properties of adult neurogenesis in the human hippocampus: Implications for its clinical applications.

Biotransformation of the Novel Myeloperoxidase Inhibitor AZD4831 in Preclinical Species and Humans.

We report herein an in-depth analysis of the metabolism of the novel myeloperoxidase inhibitor AZD4831 ((R)-1-(2-(1-aminoethyl)-4-chlorobenzyl)-2-thioxo-2,3-dihydro-1H-pyrrolo[3,2-d]pyrimidin-4(5H)-one) in animals and human. Quantitative and qualitative metabolite profiling were performed on samples collected from mass balance studies in rats and humans. Exposure of circulating human metabolites with comparable levels in animal species used in safety assessment were also included. Structural characterization of 20 metabolites was performed by liquid chromatography high-resolution mass spectrometry, and quantification was performed by either 14C analysis using solid phase scintillation counting or accelerator mass spectrometry and, where available, authentication with synthesized metabolite standards. A complete mass balance study in rats is presented, while data from dogs and human are limited to metabolite profiling and characterization. The metabolism of AZD4831 is mainly comprised of reactions at the primary amine nitrogen and the thiourea sulfur, resulting in several conjugated metabolites with or without desulfurization. A carbamoyl glucuronide metabolite of AZD4831 (M7) was the most abundant plasma metabolite in both human healthy volunteers and heart failure patients after single and repeated dose administration of AZD4831, accounting for 75%-80% of the total drug-related exposure. Exposures to M7 and other human circulating metabolites were covered in rats and/or dogs, the two models most frequently used in the toxicology studies, and were also highly abundant in the mouse, the second model other than rat used in carcinogenicity studies. The carbamoyl glucuronide M7 was the main metabolite in rat bile, while a desulfurized and cyclized metabolite (M5) was abundant in rat plasma and excreta. SIGNIFICANCE STATEMENT: The biotransformation of AZD4831, a novel myeloperoxidase inhibitor inhibiting xanthine derivative bearing thiourea and primary aliphatic amine functions, is described. Twenty characterized metabolites demonstrate the involvement of carbamoylation with glucuronidation, desulfurization, and cyclization as main biotransformation reactions. The carbamoyl glucuronide was the main metabolite in human plasma, likely governed by a significant species difference in plasma protein binding for this metabolite, but this and other human plasma metabolites were covered in animals used in the toxicity studies.

Effects of stocking density on juvenile Amphioctopus fangsiao (Mollusca: Cephalopodasca: Cephalopoda): Survival, growth, behavior, stress tolerance and biochemical response

Stocking density determines the welfare, growth performance, and even survival of aquatic organisms in aquaculture. However, how stocking density affects cephalopods are still unclear. Here we selected Amphioctopus fangsiao, a promising cephalopod for mariculture, to examine the effect of stocking density on survival, growth, physiology and behavior. Juvenile A. fangsiao (≈ two months post-hatch, 2.41 g ± 0.03) were reared for 21 days under different stocking density groups: 30, 45, 60 and 75 individual/m2 (ind./m2) (G1, G2, G3 and G4, respectively). Subsequently, the growth performance, aggressive acts, survival rate, stress response, oxidative stress and glucolipid metabolism were analyzed. This study showed that the high stocking density had a negative impact on growth performance. A. fangsiao reared in G3 and G4 had a significantly lower final body weight, weight gain and specific growth rate than those reared in G1 and G2 (p < .05), and hepatosomatic index in different treatment groups have a similar trend of difference (p < .05). Increased stocking density also caused more fights of A. fangsiao, resulting in a high mortality rate for farmed individuals. The individual numbers of released ink after touch and the recovery time of the breathing rate after air emersion showed that the low stocking density lowered the basal stress level and reduced the recovery time after acute stress of juvenile A. fangsiao. In addition, this study demonstrated that high stocking density has caused oxidative stress and lipid disturbance of A. fangsiao. There were significant differences in reactive oxygen species (ROS), lipid peroxidation's level (MDA content), the activities of superoxide dismutase (SOD) and catalase (CAT), pyruvic acid level (Pyr), total cholesterol level (T-CHO) and triglyceride (TG) between the highest density group (G4) and the lowest density group (G1). Overall, high stocking density (G3 and G4) had a negative effect on reared A. fangsiao. However, there were no significant differences between G1 and G2. Therefore, to improve the welfare of reared A. fangsiao and maximize the economic benefits for producers, juveniles are recommended to rear at a medium density (about 45 ind./m2).

Structure–activity relationship of pyrazol-4-yl-pyridine derivatives and identification of a radiofluorinated probe for imaging the muscarinic acetylcholine receptor M4

There is an accumulating body of evidence implicating the muscarinic acetylcholine receptor 4 (M4) in schizophrenia and dementia with Lewy bodies, however, a clinically validated M4 positron emission tomography (PET) radioligand is currently lacking. As such, the aim of this study was to develop a suitable M4 PET ligand that allows the non-invasive visualization of M4 in the brain. Structure-activity relationship studies of pyrazol-4-yl-pyridine derivates led to the discovery of target compound 12 - a subtype-selective positive allosteric modulator (PAM). The radiofluorinated analogue, [18F]12, was synthesized in 28±10% radiochemical yield, >37 GBq/μmol and an excellent radiochemical purity >99%. Initial invitro autoradiograms on rodent brain sections were performed in the absence of carbachol and showed moderate specificity as well as a low selectivity of [18F]12 for the M4-rich striatum. However, in the presence of carbachol, a significant increase in tracer binding was observed in the rat striatum, which was reduced by >60% under blocking conditions, thus indicating that orthosteric ligand interaction is required for efficient binding of [18F]12 to the allosteric site. Remarkably, however, the presence of carbachol was not required for high specific binding in the non-human primate (NHP) and human striatum, and did not further improve the specificity and selectivity of [18F]12 in higher species. These results pointed towards significant species-differences and paved the way for a preliminary PET study in NHP, where peak brain uptake of [18F]12 was found in the putamen and temporal cortex. In conclusion, we report on the identification and preclinical development of the first radiofluorinated M4 PET radioligand with promising attributes. The availability of a clinically validated M4 PET radioligand harbors potential to facilitate drug development and provide a useful diagnostic tool for non-invasive imaging.

游荡型黄河滩涂植物群落多样性及种间联结性

PDF HTML阅读 XML下载 导出引用 引用提醒 游荡型黄河滩涂植物群落多样性及种间联结性 DOI: 10.5846/stxb202108202317 作者: 作者单位: 作者简介: 通讯作者: 中图分类号: 基金项目: 国家自然科学基金委员会重点项目(41930643);河南省高校科技创新人才(22HASTIT033);河南省重大科技专项(201300311700) Plant diversity and interspecific associations of different floodplains in the wandering Yellow River Author: Affiliation: Fund Project: 摘要 | 图/表 | 访问统计 | 参考文献 | 相似文献 | 引证文献 | 资源附件 | 文章评论 摘要:黄河干流流量季节性变化和小浪底"调水调沙"形成了黄河河南段特殊的游荡型滩涂生态系统,为揭示游荡型黄河滩涂(嫩滩、二滩、高滩和大堤)群落组成和种间关系及群落稳定性规律,于2015年9月至2018年11月,采用典型样方法在郑州黄河湿地自然保护区游荡型黄河滩涂开展群落学调查,利用149个草本层样方分析群落物种组成、多样性、种间联结性和群落稳定性。结果表明:(1)研究区植物共有90科289属445种,其中被子植物87科286属440种,裸子植物2科2属3种;蕨类植物仅见1属2种。(2)不同滩涂生境优势种具有显著差异,且总体狗牙根(Cynodon dactylon)、芦苇(Phragmites australis)和小蓬草(Erigeron canadensis)为优势种,国家二级保护植物野大豆(Glycine soja)呈斑块聚集分布,且为嫩滩和二滩亚优势种。(3)大堤物种多样性各指标取值最大,嫩滩次之,二滩和高滩较小。(4)χ2检验、Jaccard指数、Pearson相关检验和Spearman秩相关检验表明,优势种种对种间联结性不强,各物种间相对独立。(5)二滩总体联结性呈现不显著负关联,其他3种类型均为显著负关联,M. Godron稳定性分析说明群落总体均处于不稳定演替阶段。因此,游荡型黄河滩涂生态系统总体不稳定,河道的游荡多变导致滩涂植物更新频繁,这可为黄河流域生态保护和高质量发展国家战略提供重要基础数据和科学指导。 Abstract:The seasonal flow variation of the Yellow River mainstream and water-sediment regulation by the Xiaolangdi project have formed a special wandering floodplain ecosystem. In order to reveal the community composition, interspecific relationship and community stability of the wandering Yellow River floodplains (Newly-formed floodplain, Second floodplain, Highly-formed floodplain, Levee), we utilized the typical quadrat method to investigate plants in Zhengzhou Yellow River Wetland Provincial Nature Reserve of the typical wandering Yellow River floodplains from September 2015 to November 2018. We delved into the community species composition, species diversity, interspecific association and community stability based on 149 herb layer quadrats. The results showed that: (1) 445 species were occurred in our four floodplains, belonging to 289 genera and 90 families. Among them, there were 440 species, 286 genera and 87 families of angiosperms, and three species, two genera and two families of gymnosperms, and only one genus and two species of pteridophytes. (2) There were significant differences in dominant species among four floodplains. In general, Cynodon dactylon, Phragmites australis, and Erigeron canadensis were the dominant species. In Newly-formed floodplain and Second floodplain, Glycine soja (Class II protected plant, in China) was subdominant species, which distributed sporadically in patches. (3) The species diversity indices of the Levee were the largest, followed by the Newly-formed floodplain, and those of the Second floodplain and Highly-formed floodplain were smaller. (4) χ2 test, Jaccard index, Pearson correlation test and Spearman rank correlation test showed that the dominant species pairs were not strongly interspecific linked, and each species was relatively independent. (5) The overall association of Second floodplain showed non-significantly negative association, while that of the rest were significantly negatively associated. Combined with the M. Godron's stability analysis, the community was in an unstable successional stage. These results indicated that the wandering Yellow River floodplain ecosystem was generally unstable, and the wandering and variable river channel led to the frequent regeneration of floodplain community. This provides important basic data and scientific guidance for national strategies of ecological protection and high-quality development in the Yellow River Basin. 参考文献 相似文献 引证文献

The alpine scrubs and dwarf heaths of the Balkan Peninsula - an exceptional center of floristic richness and endemism

Alpine scrubs (Roso pendulinae-Pinetea mugo) and dwarf heaths (Loiseleurio procumbentis-Vaccinietea) are an exceptional assemblage of rich floristic units which contribute significantly to the overall diversity on the Balkan Peninsula. The main edificators of these types of habitats are mostly glacial relicts. Additionally, they are of the arctic, alpine, and boreal distribution types, which further emphasises their importance from the conservation point of view. We investigated their taxonomic richness, endemism, patterns of spatial distribution and diversification in the central Balkans as well as their coenotic composition using a comprehensive dataset (15,609 species occurrence data). The analyses were conducted at three hierarchical levels taking into account the ecological and geographic diversity of the alpine scrubs and dwarf heaths in the study area. The results obtained showed that in the alpine scrubs and dwarf heaths of the central Balkans 902 taxa (829 species and 73 subspecies) had been recorded, and that the proportion of endemics in these habitats is extremely high (ca. 22%). Our results further showed that in 180 randomly selected plots of medium size (? 10 and &lt; 100 m2), the registered regional floristic richness for the unique sample size was 527 species, placing the alpine region of the Balkan Peninsula in second place among the richest alpine regions in the world. Moreover, significant regional differences in species composition were observed within the research area, with floristic richness and diversity increasing from north to south.

Amniotic fluid and vaginal microbiota in pregnant women with gestational diabetes mellitus by metagenomics

AimsTo compared the amniotic fluid and vaginal microbiota of pregnant women, who developed gestational diabetes mellitus to those who did not, and explored if any differences exist in the composition and functional genes of their amniotic fluid and vaginal microbiota. MethodsWe compared the amniotic fluid and vaginal microbiota of five GDM patients and five non-GDM pregnant women in the third trimester of pregnancy by using metagenomics, and analyzed the characteristics, functions, and differences between two groups. ResultsThe analysis of the amniotic fluid showed significant differences in genus and species. In contrast, there was no significant difference in vaginal microbial community structure between two groups. The alpha diversity in the GDM group was higher than the control, but the difference was not statistically significant. There was a statistically significant difference in the species-level beta-diversity measured by Bray–Curtis distance of the amniotic fluid communities between two groups, while no significant differences were observed in the vaginal microbiota. Regarding the functions, we observed that the microbial communities of the amniotic fluid and vaginal secretions were involved in the regulation of a variety of host metabolic pathways, including carbohydrate metabolism, membrane transport, energy, amino acid metabolism, nucleotide metabolism, etc. No significant differences were observed between two groups, but different sites exist. ConclusionThe amniotic fluid of this study was discovered to have a heterogeneous, albeit small in number, community of microorganisms.Our research suggests that gestational diabetes has a very limited impact on the amniotic fluid and vaginal microbiome. The composition and the functions of the microbiota at different sites are different.

Species-Specific Activation of Transient Receptor Potential Ankyrin 1 by Phthalic Acid Monoesters.

Phthalic acid (PA) diesters are widely used in consumer products, as plasticizers, and are ubiquitous environmental pollutants. There is a growing concern about their adjuvant effect on allergic diseases. Although its precise mechanism remains unknown, possible involvement of transient receptor potential ankyrin 1 (TRPA1) has been suggested. Hence, in this study, the activation of human and mouse TRPA1s by a series of PA di- and monoesters was investigated using a heterologous expression system in vitro. Consequently, it was found that monoesters activated human TRPA1, where EC50 values were in the order of mono-hexyl > mono-heptyl > mono-n-octyl > mono-2-ethylhexyl > mono-isononyl and mono-isodecyl esters. Significant species differences in TRPA1 activation by PA monoesters were also discovered; PA monoesters activated human TRPA1 but not mouse TRPA1 in a concentration-dependent manner up to 50 µM. These findings suggest that PA esters may exert TRPA1-dependent adverse effects on humans, which have never been demonstrated in experimental animals.