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Microtubule-severing protein (MTSP) is critical for the survival of both mitotic and postmitotic cells. However, the study of MTSP during meiosis of mammalian oocytes has not been reported. We found that spastin, a member of the MTSP family, was highly expressed in oocytes and aggregated in spindle microtubules. After knocking down spastin by specific siRNA, the spindle microtubule density of meiotic oocytes decreased significantly. When the oocytes were cultured in vitro, the oocytes lacking spastin showed an obvious maturation disorder. Considering the microtubule-severing activity of spastin, we speculate that spastin on spindles may increase the number of microtubule broken ends by severing the microtubules, therefore playing a nucleating role, promoting spindle assembly and ensuring normal meiosis. In addition, we found the colocalization and interaction of collapsin response mediator protein 5 (CRMP5) and spastin in oocytes. CRMP5 can provide structural support and promote microtubule aggregation, creating transportation routes, and can interact with spastin in the microtubule activity of nerve cells (30). Knocking down CRMP5 may lead to spindle abnormalities and developmental disorders in oocytes. Overexpression of spastin may reverse the abnormal phenotype caused by the deletion of CRMP5. In summary, our data support a model in which the interaction between spastin and CRMP5 promotes the assembly of spindle microtubules in oocytes by controlling microtubule dynamics, therefore ensuring normal meiosis.
Inflammation might play a role in bipolar disorder (BD), but it remains unclear the relationship between inflammation and brain structural and functional abnormalities in patients with BD. In this study, we focused on the alterations of functional connectivity (FC), peripheral pro-inflammatory cytokines and their correlations to investigate the role of inflammation in FC in BD depression.
In this study, 42 unmedicated patients with BD II depression and 62 healthy controls (HCs) were enrolled. Resting-state-functional magnetic resonance imaging was performed in all participants and independent component analysis was used. Serum levels of Interleukin-6 (IL-6) and Interleukin-8 (IL-8) were measured in all participants. Correlation between FC values and IL-6 and IL-8 levels in BD was calculated.
Compared with the HCs, BD II patients showed decreased FC in the left orbitofrontal cortex (OFC) implicating the limbic network and the right precentral gyrus implicating the somatomotor network. BD II showed increased IL-6 (p = 0.039), IL-8 (p = 0.002) levels. Moreover, abnormal FC in the right precentral gyrus were inversely correlated with the IL-8 (r = −0.458, p = 0.004) levels in BD II. No significant correlation was found between FC in the left OFC and cytokines levels.
Our findings that serum IL-8 levels are associated with impaired FC in the right precentral gyrus in BD II patients suggest that inflammation might play a crucial role in brain functional abnormalities in BD.
Shifts in the maternal gut microbiota have been implicated in the development of gestational diabetes mellitus (GDM). Understanding the interaction between gut microbiota and host glucose metabolism will provide a new target of prediction and treatment. In this nested case-control study, we aimed to investigate the causal effects of gut microbiota from GDM patients on the glucose metabolism of germ-free (GF) mice. Stool and peripheral blood samples, as well as clinical information, were collected from 45 GDM patients and 45 healthy controls (matched by age and prepregnancy body mass index (BMI)) in the first and second trimester. Gut microbiota profiles were explored by next-generation sequencing of the 16S rRNA gene, and inflammatory factors in peripheral blood were analyzed by enzyme-linked immunosorbent assay. Fecal samples from GDM and non-GDM donors were transferred to GF mice. The gut microbiota of women with GDM showed reduced richness, specifically decreased Bacteroides and Akkermansia, as well as increased Faecalibacterium. The relative abundance of Akkermansia was negatively associated with blood glucose levels, and the relative abundance of Faecalibacterium was positively related to inflammatory factor concentrations. The transfer of fecal microbiota from GDM and non-GDM donors to GF mice resulted in different gut microbiota colonization patterns, and hyperglycemia was induced in mice that received GDM donor microbiota. These results suggested that the shifting pattern of gut microbiota in GDM patients contributed to disease pathogenesis.
Birth weight influences not only brain development, but also mental health outcomes, including depression, but the underlying mechanism is unclear.
The phenotypic data of 12,872–91,009 participants (59.18–63.38% women) from UK Biobank were included to test the associations between the birth weight, depression, and brain volumes through the linear and logistic regression models. As birth weight is highly heritable, the polygenic risk scores (PRSs) of birth weight were calculated from the UK Biobank cohort (154,539 participants, 56.90% women) to estimate the effect of birth weight-related genetic variation on the development of depression and brain volumes. Finally, the mediation analyses of step approach and mediation analysis were used to estimate the role of brain volumes in the association between birth weight and depression. All analyses were conducted sex stratified to assess sex-specific role in the associations.
We observed associations between birth weight and depression (odds ratio [OR] = 0.968, 95% confidence interval [CI] = 0.957–0.979, p = 2.29 × 10−6). Positive associations were observed between birth weight and brain volumes, such as gray matter (B = 0.131, p = 3.51 × 10−74) and white matter (B = 0.129, p = 1.67 × 10−74). Depression was also associated with brain volume, such as left thalamus (OR = 0.891, 95% CI = 0.850–0.933, p = 4.46 × 10−5) and right thalamus (OR = 0.884, 95% CI = 0.841–0.928, p = 2.67 × 10−5). Additionally, significant mediation effects of brain volume were found for the associations between birth weight and depression through steps approach and mediation analysis, such as gray matter (B = –0.220, p = 0.020) and right thalamus (B = –0.207, p = 0.014).
Our results showed the associations among birth weight, depression, and brain volumes, and the mediation effect of brain volumes also provide evidence for the sex-specific of associations.
Leg weakness (LW) issues are a great concern for pig breeding industry. And it also has a serious impact on animal welfare. To dissect the genetic architecture of limb-and-hoof firmness in commercial pigs, a genome-wide association study was conducted on bone mineral density (BMD) in three sow populations, including Duroc, Landrace and Yorkshire. The BMD data were obtained by ultrasound technology from 812 pigs (including Duroc 115, Landrace 243 and Yorkshire 454). In addition, all pigs were genotyped using genome-by-sequencing and a total of 224 162 single-nucleotide polymorphisms (SNPs) were obtained. After quality control, 218 141 SNPs were used for subsequent genome-wide association analysis. Nine significant associations were identified on chromosomes 3, 5, 6, 7, 9, 10, 12 and 18 that passed Bonferroni correction threshold of 0.05/(total SNP numbers). The most significant locus that associated with BMD (P value = 1.92e−14) was detected at approximately 41.7 Mb on SSC6 (SSC stands for Sus scrofa chromosome). CUL7, PTK7, SRF, VEGFA, RHEB, PRKAR1A and TPO that are located near the lead SNP of significant loci were highlighted as functionally plausible candidate genes for sow limb-and-hoof firmness. Moreover, we also applied a new method to measure the BMD data of pigs by ultrasound technology. The results provide an insight into the genetic architecture of LW and can also help to improve animal welfare in pigs.
We completely classify the possible extensions between semistable vector bundles on the Fargues–Fontaine curve (over an algebraically closed perfectoid field), in terms of a simple condition on Harder–Narasimhan (HN) polygons. Our arguments rely on a careful study of various moduli spaces of bundle maps, which we define and analyze using Scholze’s language of diamonds. This analysis reduces our main results to a somewhat involved combinatorial problem, which we then solve via a reinterpretation in terms of the Euclidean geometry of HN polygons.
Indoor positioning systems have received increasing attention for supporting location-based services in indoor environments. Wi-Fi based indoor localisation has become attractive due to its extensive distribution and low cost properties. IEEE 802.11-2016 now includes a Wi-Fi Fine Time Measurement (FTM) protocol which can be used for Wi-Fi ranging between intelligent terminal and Wi-Fi access point. This paper introduces a framework of Wi-Fi FTM data acquisition and processing that can be used for indoor localisation. We analyse the main factors that affect the accuracy of Wi-Fi ranging and propose a calibration, filtering and modelling algorithm that can effectively reduce the ranging error caused by clock deviation, non-line-of-sight (NLOS) and multipath propagation. Experimental results show that the proposed calibration and filtering method is able to achieve metre-level ranging accuracy in case of line-of-sight by using large bandwidth. Estimation results also show that the proposed Wi-Fi ranging model provides an accurate ranging performance in NLOS and multipath contained indoor environment; the final positioning error is less than 2·2 m with a stable output frequency of 3 Hz.
In this research communication, a cell model with elevated β-CASEIN synthesis was established by stimulating bovine mammary epithelial cells with 0.6 mM methionine, and the genome-wide gene expression profiles of methionine-stimulated cells and untreated cells were investigated by RNA sequencing. A total of 458 differentially expressed genes (DEGs; 219 upregulated and 239 downregulated) were identified between the two groups. Gene Ontology (GO) analysis showed that the two highest-ranked GO terms in ‘molecular function’ category were ‘binding’ and ‘catalytic activity’, suggesting that milk protein synthesis in methionine-stimulated cells requires induction of gene expression to increase metabolic activity. Kyoto Encyclopedia of Genes and Genomes analysis revealed that within the ‘environmental information processing’ category, the subcategory that is most highly enriched for DEGs was ‘signal transduction’. cGMP-PKG, Rap1, calcium, cAMP, PI3K-AKT, MAPK, and JAK-STAT are the pathways with the highest number of DEGs, suggesting that these signaling pathways have potential roles in mediating methionine-induced milk protein synthesis in bovine mammary epithelial cells. This study provides valuable insights into the physiological and metabolic adaptations in cells stimulated with methionine. Understanding the regulation of this transition is essential for effective intervention in the lactation process.
The experiment was conducted to investigate the effects of dietary threonine (Thr) on growth performance and muscle growth, protein synthesis and antioxidant-related signalling pathways of hybrid catfish Pelteobagrus vachelli♀ × Leiocassis longirostris♂. A total of 1200 fish (14·19 (se 0·13) g) were randomly distributed into six groups with four replicates each, fed six diets with graded level of Thr (9·5, 11·5, 13·5, 15·4, 17·4 and 19·3 g/kg diets) for 56 d. Results showed (P < 0·05) that dietary Thr (1) increased percentage weight gain, specific growth rate, feed efficiency and protein efficiency ratio; (2) up-regulated growth hormone (GH), insulin-like growth factor 1 (IGF-1), proliferating cell nuclear antigen, myogenic regulation factors (MyoD, Myf5, MyoG and Mrf4) and myosin heavy chain (MyHC) mRNA levels; (3) increased muscle protein content via regulating the protein kinase B/target of rapamycin signalling pathway and (4) decreased malondialdehyde and protein carbonyl contents, increased catalase, glutathione-S-transferase, glutathione reductase and GSH activities, up-regulated mRNA levels of antioxidant enzymes related to NFE2-related factor 2 and γ-glutamylcysteine ligase catalytic subunit. These results suggest that Thr has a potential role to improve muscle growth and protein synthesis, which might be due to the regulation of GH-IGF system, muscle growth-related gene, antioxidative capacity and protein synthesis-related signalling pathways. Based on the quadratic regression analysis of specific growth rate, the Thr requirement of hybrid catfish (14·19–25·77 g) was estimated to be 13·77 g/kg of the diet (33·40 g/kg of dietary protein).
The microbiota–gut–brain axis, especially the microbial tryptophan (Trp) biosynthesis and metabolism pathway (MiTBamp), may play a critical role in the pathogenesis of major depressive disorder (MDD). However, studies on the MiTBamp in MDD are lacking. The aim of the present study was to analyze the gut microbiota composition and the MiTBamp in MDD patients.
We performed shotgun metagenomic sequencing of stool samples from 26 MDD patients and 29 healthy controls (HCs). In addition to the microbiota community and the MiTBamp analyses, we also built a classification based on the Random Forests (RF) and Boruta algorithm to identify the gut microbiota as biomarkers for MDD.
The Bacteroidetes abundance was strongly reduced whereas that of Actinobacteria was significantly increased in the MDD patients compared with the abundance in the HCs. Most noteworthy, the MDD patients had increased levels of Bifidobacterium, which is commonly used as a probiotic. Four Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) (K01817, K11358, K01626, K01667) abundances in the MiTBamp were significantly lower in the MDD group. Furthermore, we found a negative correlation between the K01626 abundance and the HAMD scores in the MDD group. Finally, RF classification at the genus level can achieve an area under the receiver operating characteristic curve of 0.890.
The present findings enabled a better understanding of the changes in gut microbiota and the related Trp pathway in MDD. Alterations of the gut microbiota may have the potential as biomarkers for distinguishing MDD patients form HCs.
The acquisition and tracking strategies of the BeiDou navigation satellite signals are affected by the modulation of Neumann-Hoffman code (NH code), which increases the complexity of receiver baseband signal processing. Based on the analysis of probability statistics of the NH code, a special sequence of incoming signals is proposed to evade the bit transitions caused by the NH code, and an NH Code Evasion and Stripping method (NCES) based on the NH-pre-modulated code is proposed. The NCES can be applied in both 20-bit NH code and 10-bit NH code. The fine acquisition eliminates the impact of NH code on the traditional tracking loop. These methods were verified with a BeiDou PC-based software-defined receiver using the actual sampled signals. Compared with other acquisition schemes which try to determine or ignore the NH code phase, the NCES needs fewer incoming signals and the actual runtime is greatly reduced without sacrificing much time to search in the secondary code dimension, and the success rate of acquisition is effectively improved. An extension of Fast Fourier Transform (FFT)-based parallel code-phase search acquisition gives the NCES an advantage in engineering applications.
MnOx–CeO2/t-ZrO2 catalyst was prepared by impregnation of nanotetragonal zirconia. The NO conversion of 5 wt% MnOx–CeO2/t-ZrO2 catalyst was 68.1% at 100 °C while that of 30 wt% MnOx–CeO2/t-ZrO2 catalyst was 97.4%. The x-ray diffraction, Brunner–Emmet–Teller measurements (BET), and H2-TPR showed surface properties of the prepared catalysts were good for selective catalytic reduction reactions. X-ray photoelectron spectroscopy analysis indicated that Mn4+ and Ce4+ oxidation states were predominant on the surface of the catalyst and so was lattice oxygen which was conducive to Lewis acid sites. NH3-TPD test results demonstrated that Lewis acid sites are predominant on the surface of catalyst. The presence of SO2 reduced the catalyst activity. The realized conversion dramatically decreased to 47% from nearly 100% after 8 h. Characterization of fresh and spent catalysts indicated the deterioration of active component and deposition of NH4HSO4 or (NH4)2SO4 contribute to SO2 poisoning.
The objective of this study was to determine the protective effect of glutamate (Glu) in Cu-induced oxidative injury in fish intestine in vivo and enterocytes in vitro. The results indicated that exposure to 6 mg/l Cu for 72 h induced the production of reactive oxygen species, thereby increasing protein oxidation and lipid peroxidation in enterocytes of grass carp in vitro. Cells exposed to Cu alone resulted in a significant increase in lactate dehydrogenase release, which is accompanied by depletions of antioxidants, including total superoxide dismutase (T-SOD), glutathione S-transferase (GST), glutathione reductase (GR), anti-superoxide anion (ASA), anti-hydroxy radical (AHR) activities and GSH content. Pre-treatment with Glu remarkably prevented the toxic effects of Cu on the T-SOD, GST, GR, AHR, and ASA activities and GSH content in enterocytes. However, Cu induced an adaptive increase in the activities of catalase and glutathione peroxidase (GPx). Glu supplementation further increased GPx activity in enterocytes. Interestingly, the experiment in vivo showed that Glu pre-supplementation significantly elevated SOD, GPx, GST, GR, ASA and AHR activities, as well as GSH content. Further results showed that pre-treatment with Glu could alleviate Cu-induced oxidative injury by elevating antioxidant enzyme activities through regulating the expression of NF-E2-related nuclear factor 2 (Nrf2) mRNA. Together, these results indicated that Glu could attenuate Cu-induced cellular oxidative damage in fish intestine, likely mediated through Nrf2 signalling pathways regulating mRNA expressions of antioxidant enzyme genes and synthesis of GSH.
Understanding crop water use in mixed crops over sole cropping is vital for developing optimum water management systems for crop production. In this study, a two-year field experiment with typical maize (Zea mays L.) and soybean [Glycine max (L.) Merr.] relay strip intercropping (2:2 maize-to-soybean rows; 200 cm bandwidth) was carried out in the 2013 and 2014 growing seasons. The quantitative effects of various planting patterns on the water-use efficiency (WUE) and water distribution were investigated. Our results indicated that soil volumetric water content and soil evaporation in the intercropping systems showed decreasing trends in the order: maize row (MM) < maize-to-soybean row (MS) < soybean row (SS). The highest leaf transpiration (1.91 and 2.07 mmol m−2 s−1) for the intercropped maize was measured in each of the two years in the 20 cm maize narrow-row planting pattern and decreased thereafter. Opposite trend was observed for the intercropped soybean; the highest soybean leaf transpiration (7.01 and 6.80 mmol m−2 s−1 for 2013 and 2014, respectively) was recorded in the 70 cm. The WUE of maize and soybean intercrops was lower than that of sole crop counterparts. However, the maximum group water use efficiency (GWUE) of 26.08 and 26.20 kg ha−1 mm−1 in the 40–50 cm maize narrow-row planting pattern was, respectively, 39.6% and 23% higher compared with that of sole crops. The water equivalent ratio (WER) values ranged from 1.60–1.79, suggesting better crop water use in the intercrops over sole cropping. Planting patterns provided by 40–50 cm maize narrow-row spacing were considered the most efficient in terms of maximum total yields, GWUE and WER. These results suggest that an appropriate reduction in the spacing of narrow maize row with wide soybean row could be an efficient crop management method to achieve optimal WUE and homogeneous water distribution in maize–soybean intercropping systems.
The present study was conducted to investigate the anti-inflammatory effect of vitamin D both in juvenile Jian carp (Cyprinus carpio var. Jian) in vivo and in enterocytes in vitro. In primary enterocytes, exposure to 10 mg lipopolysaccharide (LPS)/l increased lactate dehydrogenase activity in the culture medium (P<0·05) and resulted in a significant loss of cell viability (P<0·05). LPS exposure increased (P<0·05) the mRNA expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-8), which was decreased by pre-treatment with 1,25-dihydroxyvitamin D (1,25D3) in a dose-dependent manner (P<0·05). Further results showed that pre-treatment with 1,25D3 down-regulated Toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (Myd88) and NF-κB p65 mRNA expression (P<0·05), suggesting potential mechanisms against LPS-induced inflammatory response. In vivo, intraperitoneal injection of LPS significantly increased TNF-α, IL-1β, IL-6 and IL-8 mRNA expression in the intestine of carp (P<0·05). Pre-treatment of fish with vitamin D3 protected the fish intestine from the LPS-induced increase of TNF-α, IL-1β, IL-6 and IL-8 mainly by downregulating TLR4, Myd88 and NF-κB p65 mRNA expression (P<0·05). These observations suggest that vitamin D could inhibit LPS-induced inflammatory response in juvenile Jian carp in vivo and in enterocytes in vitro. The anti-inflammatory effect of vitamin D is mediated at least in part by TLR4-Myd88 signalling pathways in the intestine and enterocytes of juvenile Jian carp.
A defect in the intestinal barrier is one of the characteristics of Crohn's disease (CD). The tight junction (TJ) changes and death of epithelial cells caused by intestinal inflammation play an important role in the development of CD. DHA, a long-chain PUFA, has been shown to be helpful in treating inflammatory bowel disease in experimental models by inhibiting the NF-κB pathway. The present study aimed at investigating the specific effect of DHA on the intestinal barrier function in IL-10-deficient mice. IL-10-deficient mice (IL-10− / −) at 16 weeks of age with established colitis were treated with DHA (i.g. 35·5 mg/kg per d) for 2 weeks. The severity of their colitis, levels of pro-inflammatory cytokines, epithelial gene expression, the distributions of TJ proteins (occludin and zona occludens (ZO)-1), and epithelial apoptosis in the proximal colon were measured at the end of the experiment. DHA treatment attenuated the established colitis and was associated with reduced infiltration of inflammatory cells in the colonic mucosa, lower mean histological scores and decreased levels of pro-inflammatory cytokines (IL-17, TNF-α and interferon-γ). Moreover, enhanced barrier function was observed in the DHA-treated mice that resulted from attenuated colonic permeability, rescued expression and corrected distributions of occludin and ZO-1. The results of the present study indicate that DHA therapy may ameliorate experimental colitis in IL-10− / − mice by improving the intestinal epithelial barrier function.
Little is known about the potential adherence to and the effectiveness of a low-carbohydrate (LC) diet on weight loss and cardiometabolic risk factors in Chinese adults with a habitually high carbohydrate intake. In the present controlled feeding trial, fifty overweight or obese women (age 47·9 (sem 0·9) years; BMI 26·7 (sem 0·3) kg/m2) were randomly assigned to a LC non-energy-restricted diet (initial carbohydrate intake 20 g/d, with a 10 g increase weekly) or an energy-restricted (ER) diet (carbohydrate intake 156–205 g/d, ER to 5021 or 6276 kJ/d, 35 % average energy reduction) for 12 weeks. Over the intervention period, the two diets had comparable compliance (96 %) and self-reported acceptability. At week 12, carbohydrate intake in the LC and ER groups contributed to 36·1 and 51·1 % of total energy, respectively (P< 0·001). Although both diets showed similarly decreased mean body weight (LC − 5·27 (95 % CI − 6·08, − 4·46) kg; ER − 5·09 (95 % CI − 5·50, − 4·67) kg, P= 0·67) and percentage of fat mass measured by dual-energy X-ray absorptiometry (LC − 1·19 (95 % CI − 1·88, − 0·50) %; ER − 1·56 (95 % CI − 2·20, − 0·92) %, P= 0·42), participants in the LC group had greater reductions in the ratio of total cholesterol:HDL-cholesterol (P= 0·03) and also in the ratio of TAG:HDL-cholesterol (P= 0·01) than those in the ER group. The present 12-week diet trial suggested that both a LC non-energy-restricted diet and an ER diet were acceptable to Chinese women and both diets were equally effective in reducing weight and fat mass. Moreover, the LC diet showed beneficial effects on blood lipid profiles.
Background: Although knowledge of established risk factors for Alzheimer's disease (AD) can logically contribute to the search for predictors of the progression of cognitive impairment, it has not yet been firmly established where in the cognitive impairment process these risk factors exert their effects and how to predict quantitatively for the progression of mild cognitive impairments (MCI) to AD. This study aimed to determine whether known risk factors increased the risk of progression from MCI to AD and to make prediction based on transition probabilities.
Methods: Based on ten examinations of 600 community-dwelling MCI residents and cognitive assessments to classify individuals into MCI, global impairment, and AD, a multi-state Markov Cox's regression model was used and the hazard ratios with their confidence intervals and transition probabilities were estimated.
Results: Multivariate analysis showed that gender, age, and hypertension were statistically significant predictors of transition from MCI to global impairment; age, education, and reading statistically influenced transition from global impairment to MCI; gender, age, hypertension, diabetes, and apolipoprotein E geneε4 status were statistically associated with transition from global impairment to AD. Subjects at MCI were more likely (67%) to remain in that cognitive state at the next cognitive assessment than to transition to cognitive deterioration. For global impairment, probability of remaining in the same state was only 18% and that of forward transition was three times more likely than that of backward transition.
Conclusions: Known risk factors influenced differently for different transitions. Transition from global impairment was more likely to worsen to severe cognitive deterioration than transition from MCI.