Control of CD1d-restricted antigen presentation and inflammation by sphingomyelin.

Invariant natural killer T (iNKT) cells recognize activating self and microbial lipids presented by CD1d. CD1d can also bind non-activating lipids, such as sphingomyelin. We hypothesized that these serve as endogenous regulators and investigated humans and mice deficient in acid sphingomyelinase (ASM), an enzyme that degrades sphingomyelin. We show that ASM absence in mice leads to diminished CD1d-restricted antigen presentation and iNKT cell selection in the thymus, resulting in decreased iNKT cell levels and resistance to iNKT cell-mediated inflammatory conditions. Defective antigen presentation and decreased iNKT cells are also observed in ASM-deficient humans with Niemann-Pick disease, and ASM activity in healthy humans correlates with iNKT cell phenotype. Pharmacological ASM administration facilitates antigen presentation and restores the levels of iNKT cells in ASM-deficient mice. Together, these results demonstrate that control of non-agonistic CD1d-associated lipids is critical for iNKT cell development and function in vivo and represents a tight link between cellular sphingolipid metabolism and immunity.

Cholangiocytes Modulate CD100 Expression in the Liver and Facilitate Pathogenic T-Helper 17 Cell Differentiation.

BACKGROUND & AIMS: Chronic inflammation surrounding bile ducts contributes to the disease pathogenesis of most cholangiopathies. Poor efficacy of immunosuppression in these conditions suggests biliary-specific pathologic principles. Here we performed biliary niche specific functional interpretation of a causal mutation (CD100 K849T) of primary sclerosing cholangitis (PSC) to understand related pathogenic mechanisms. METHODS: Biopsy specimens of explanted livers and endoscopy-guided sampling were used to assess the CD100 expression by spatial transcriptomics, immune imaging, and high-dimensional flow cytometry. To model pathogenic cholangiocyte-immune cell interaction, splenocytes from mutation-specific mice were cocultured with cholangiocytes. Pathogenic pathways were pinpointed by RNA sequencing analysis of cocultured cells and cross-validated in patient materials. RESULTS: CD100 is mainly expressed by immune cells in the liver and shows a unique pattern around PSC bile ducts with RNA-level colocalization but poor detection at the protein level. This appears to be due to CD100 cleavage as soluble CD100 is increased. Immunophenotyping suggests biliary-infiltrating T cells as the major source of soluble CD100, which is further supported by reduced surface CD100 on T cells and increased metalloproteinases in cholangiocytes after coculturing. Pathogenic T cells that adhered to cholangiocytes up-regulated genes in the T-helper 17 cell differentiation pathway, and the CD100 mutation boosted this process. Consistently, T-helper 17 cells dominate biliary-resident CD4 T cells in patients. CONCLUSIONS: CD100 exerts its functional impact through cholangiocyte-immune cell cross talk and underscores an active, proinflammatory role of cholangiocytes that can be relevant to novel treatment approaches.

circUBE3C modulates myoblast development by binding to miR-191 and upregulating the expression of p27.

Noncoding RNAs, including miRNAs (microRNAs) and circRNAs (circular RNA), are crucial regulators of myoblast proliferation and differentiation during muscle development. However, the specific roles and molecular mechanisms of circRNAs in muscle development remain poorly understood. Based on the existing circRNA-miRNA-mRNA network, our study focuses on circUBE3C, exploring its differential expression in fetal and adult muscle tissue of the cattle and investigating its impact on myoblast proliferation, apoptosis, and differentiation. The functional analysis of overexpression plasmids and siRNAs (small interfering RNAs) targeting circUBE3C was comprehensively evaluated by employing an array of advanced assays, encompassing CCK-8 (cell counting kit-8), EdU (5-ethynyl-20-deoxyuridine), flow cytometry, western blot analysis, and RT-qPCR. In vivo investigations indicated that overexpression of circUBE3C impedes the process of skeletal muscle regeneration. Mechanistically, we demonstrated that circUBE3C interacts with miR-191 and alleviates the suppression of p27 through cytoplasmic separation, bioinformatics prediction, dual-luciferase reporter assay, and RIP (RNA immunoprecipitation). Our findings indicate that the novel circRNA circUBE3C competitively binds to miR-191, thereby inhibiting proliferation and promoting apoptosis in bovine primary myoblasts and unveiling a regulatory pathway in bovine skeletal muscle development. These findings expand our understanding of circRNA functions in mammals and provide a basis for further exploration of their role in myogenesis and muscle diseases.

Role of bacteria and microbial metabolites in immune modulation during early life.

Host-microbiome interplay from birth is essential for immune imprinting and tuning. Live gut microbes and microbial-derived metabolites regulate the development and modulation of the immune system, but whether microbial metabolites solely are sufficient to induce immune maturation remains unclear. Sterile faecal filtrates (FFT) were generated from murine gut contents. Newborn germ-free (GF) mice were treated twice daily with FFT (GF-FFT) or saline (GF-NaCl) from post-natal day 5 until 4 weeks of age. A third group of GF neonates were conventionalized by the transfer of caecal microbiota with live gut microbes. Host immune compartments were comprehensively immunophenotyped and systemically analysed in all available immune-related organs using flow cytometry. Oral FFT was associated with reduced survival among neonates (n = 7/19; 36.8% mortality), while saline treatment was well tolerated (n = 1/17, 5.9% mortality). Four-week-old FFT-treated pups were comparable in body weight to GF-NaCl, and the major B-cell, conventional T-cell and unconventional T-cell subsets were unchanged from saline-treated mice. Live bacteria administered during early life induced clear changes in proportions of B cells, T cells and T-cell subsets in all mucosal tissues and secondary lymphoid organs compared to GF-FFT, including restoration of intestinal natural killer T (NKT) cells with characteristics similar to conventional pups. Our findings show that oral administration of a FFT made of microbial metabolites, antigens and bacteriophages alone is insufficient to induce normal immune development elicited by the presence of live bacteria. Reduced survival during neonatal FFT treatment suggests a potential bioactive attribute of sterile faecal filtrates.

Microbial exposure during early life regulates development of bile duct inflammation.

OBJECTIVES: The early life microbiome has been linked to inflammatory diseases in adulthood and a role for the microbiome in bile duct inflammation is supported by both human and murine studies. We utilized the NOD.c3c4 mouse model that develops a spontaneous immune-driven biliary disease with a known contribution of the microbiome to evaluate the temporal effects of the early life microbiome. MATERIALS AND METHODS: Germ-free (GF) NOD.c3c4 mice were conventionalized into a specific pathogen free environment at birth (conventionally raised, CONV-R) or at weaning (germ-free raised, GF-R) and compared with age and gender-matched GF and conventional (CONV) NOD.c3c4 mice. At 9 weeks of age, liver pathology was assessed by conventional histology and flow cytometry immunophenotyping. RESULTS: Neonatal exposure to microbes (CONV-R) increased biliary inflammation to similar levels as regular conventional NOD.c3c4 mice, while delayed exposure to microbes (GF-R) restrained the biliary inflammation. Neutrophil infiltration was increased in all conventionalized mice compared to GF. An immunophenotype in the liver similar to CONV was restored in both CONV-R and GF-R compared to GF mice displaying a proportional increase of B cells and reduction of T cells in the liver. CONCLUSIONS: Microbial exposure during early life has a temporal impact on biliary tract inflammation in the NOD.c3c4 mouse model suggesting that age-sensitive interaction with commensal microbes have long-lasting effects on biliary immunity that can be of importance for human cholangiopathies.

Deep Reinforcement Learning for Optimizing Restricted Access Window in IEEE 802.11ah MAC Layer.

The IEEE 802.11ah standard is introduced to address the growing scale of internet of things (IoT) applications. To reduce contention and enhance energy efficiency in the system, the restricted access window (RAW) mechanism is introduced in the medium access control (MAC) layer to manage the significant number of stations accessing the network. However, to achieve optimized network performance, it is necessary to appropriately determine the RAW parameters, including the number of RAW groups, the number of slots in each RAW, and the duration of each slot. In this paper, we optimize the configuration of RAW parameters in the uplink IEEE 802.11ah-based IoT network. To improve network throughput, we analyze and establish a RAW parameters optimization problem. To effectively cope with the complex and dynamic network conditions, we propose a deep reinforcement learning (DRL) approach to determine the preferable RAW parameters to optimize network throughput. To enhance learning efficiency and stability, we employ the proximal policy optimization (PPO) algorithm. We construct network environments with periodic and random traffic in an NS-3 simulator to validate the performance of the proposed PPO-based RAW parameters optimization algorithm. The simulation results reveal that using the PPO-based DRL algorithm, optimized RAW parameters can be obtained under different network conditions, and network throughput can be improved significantly.

Bile from Patients with Primary Sclerosing Cholangitis Contains Mucosal-Associated Invariant T-Cell Antigens.

Primary sclerosing cholangitis (PSC) is associated with altered microbiota of the gut and bile. Mucosal-associated invariant T (MAIT) cells, enriched in human liver, uniquely recognize microbial-derived metabolites. This study aimed to determine whether bile from patients with PSC contains antigens activating MAIT cells. Bile was collected at the time of liver transplantation from patients with PSC (n = 28). The bile samples were either directly incubated with peripheral blood mononuclear cells from healthy donors or with antigen-presenting cells followed by co-culture with peripheral blood mononuclear cells. MAIT cell activation was assessed by flow cytometry. An anti-MR1 antibody was used to determine whether the activation was major histocompatibility complex class I-related protein (MR1) restricted. Biliary microbiota profiles were generated using 16S rRNA amplicon sequencing, and the abundance of the bacterial gene ribD was predicted. Eight of 28 bile samples could activate MAIT cells. This activation was partly MR1-dependent in five of eight bile samples. Microbial DNA was detected in 15 of 28 bile samples, including the five bile samples leading to MR1-dependent activation. A higher abundance of the ribD gene expression in the group of bile samples that could activate MAIT cells was predicted on the basis of the 16S sequencing. In co-culture experiments, cholangiocytes could take up and present biliary antigens to MAIT cells. These findings suggest a pathophysiological pathway in PSC connecting the immune system and the microbiome.

Satellite-to-ground quantum key distribution.

Quantum key distribution (QKD) uses individual light quanta in quantum superposition states to guarantee unconditional communication security between distant parties. However, the distance over which QKD is achievable has been limited to a few hundred kilometres, owing to the channel loss that occurs when using optical fibres or terrestrial free space that exponentially reduces the photon transmission rate. Satellite-based QKD has the potential to help to establish a global-scale quantum network, owing to the negligible photon loss and decoherence experienced in empty space. Here we report the development and launch of a low-Earth-orbit satellite for implementing decoy-state QKD-a form of QKD that uses weak coherent pulses at high channel loss and is secure because photon-number-splitting eavesdropping can be detected. We achieve a kilohertz key rate from the satellite to the ground over a distance of up to 1,200 kilometres. This key rate is around 20 orders of magnitudes greater than that expected using an optical fibre of the same length. The establishment of a reliable and efficient space-to-ground link for quantum-state transmission paves the way to global-scale quantum networks.

Insertion/deletions within the bovine FoxO1 gene and their association analysis with growth traits in three Chinese cattle breeds.

FOXO1 (FKHR) gene, as a transcription factor, plays a vital role in animal growth and development, participating in many biological processes. The aim of this study was to ascertain Insertion/deletions (Indels) polymorphism within bovine FoxO1 gene in 679 Chinese adult cows and associate them with stature traits. Two Indels (named as Indel-3 and Indel-4, recorded as rs383545622 and rs525318770 in NCBI, respectively) were successfully genotyped by the Once PCR method, which was reliable, rapid and cost effective for simultaneous detection of two or more Indels. Indel-3 and Indel-4 were located at the second intron. All four different haplotypes (H1: D3D4, H2: I3D4, H3: D3I4, H4: I3I4) could be identified, and the D (del-) allele, DD (del-/del-) genotype and D3D4 haplotype retained the highest frequency. However, individuals with DI (D3I3, D4I4 or H1H4/H2H3 genotype) showed significantly better phenotypic traits than those with the other genotypes in Nanyang cattle, showing a hybrid vigor. The results implied that this DI genotype can be applied to early selective breeding to improve the productivity of Nanyang cattle. Our results suggested that these two Indels within the bovine FoxO1 gene might be used as genetic markers for marker-assisted selection (MAS) in cattle breeding and genetics.

Association analysis of indels in the VISFATIN gene with five cattle breeds and their growth traits.

VISFATIN is an adipose cytokine that has been proved to correlate with growth and development traits. In a previous study from our lab, two insertion/deletions (indels; including a 35-bp insertion at its intron 4 and a 6-bp deletion in intron 5) were identified within the VISFATIN gene. To validate these indels and evaluate their association with growth traits in Chinese cattle, a total of 413 samples from four Chinese indigenous breeds and 217 samples from Chinese breeds were detected. Three genotypes (WW, WI and II) at intron 4 were detected based on the 35-bp insertion (allele I) or deletion (allele W) and showed moderate polymorphism in all samples. Two genotypes (WW and WD) at intron 5 were detected based on the 6-bp deletion (allele D) or insertion (allele W) in Xianan (XN) cattle and Jinnan (JN) cattle population but showed poor polymorphisms. Association analysis illustrated that the indel at intron 4 is significantly associated with chest girth, rump length and body weight in Ji'an (JA) cattle and the indel at intron 5 can cause a significant difference in rump length in JN cattle. To our knowledge, it is the first time it has been shown that indels within the VISFATIN gene are associated with growth traits in the two Chinese indigenous cattle breeds. These findings suggest that the VISFATIN gene can be used as a molecular marker for JN and JA cattle breeding.

Analysis of genetic diversity and genetic structure of Qinchuan cattle conservation population using whole-genome resequencing.

In the conservation of livestock and poultry resources, population genetic diversity and genetic structure of the conservation population are important factors affecting the effectiveness of conservation. In this study, whole-genome resequencing technology was used to detect genomic variation in 100 Qinchuan cattle (30 bulls and 70 cows). By analyzing population genetic diversity, runs of homozygosity (ROH) distribution features, kinship relationships, and family structure, the conservation effectiveness of Qinchuan cattle was comprehensively evaluated. The results showed that a total of 20,968,017 high-quality SNPs were detected in 100 Qinchuan cattle, the average minimum allele frequency was 0.191±0.124, the average polymorphic information content was 0.279±0.131, and the average observed heterozygosity was 0.275±0.131, the average expected heterozygosity is 0.279±0.131, indicating that the genetic diversity of the Qinchuan cattle conservation population is relatively rich. The average identity by state (IBS) distance of the Qinchuan conservation population was 0.243±0.020, with a value of 0.242±0.021 for the bulls. The results of the kinship G-matrix were consistent with the results of the IBS distance matrix, both showing that some individuals in the conservation population had close kinship. A total of 8258 genomic ROH were detected in 100 Qinchuan cattle, with a total length of 9.64 GB. The average length of ROH fragments was 1.167±1.203 Mb, 69.35% of the ROH were short ROH with a length of 0.5~1 Mb, and the average total length of ROH per individual was 96.40 Mb. The average inbreeding coefficient based on ROH was 0.039±0.039, with a value of 0.044±0.035 for the bulls, indicating that some bulls had a certain degree of inbreeding accumulation. The results of the phylogenetic tree combined with kinship analysis showed that the individuals in the Qinchuan cattle conservation population could be divided into eight families, including seven families with bulls and one family without bulls. This study demonstrated that the genetic diversity of the Qinchuan conservation population is relatively rich, with no significant inbreeding accumulation, but there is a risk of inbreeding among some individuals. Therefore, it is necessary to strengthen selection and mating to ensure the sustainable development of Qinchuan cattle resources.

Identification and Validation of Quantitative Trait Loci Mapping for Spike-Layer Uniformity in Wheat.

Spike-layer uniformity (SLU), the consistency of the spike distribution in the vertical space, is an important trait. It directly affects the yield potential and appearance. Revealing the genetic basis of SLU will provide new insights into wheat improvement. To map the SLU-related quantitative trait loci (QTL), 300 recombinant inbred lines (RILs) that were derived from a cross between H461 and Chinese Spring were used in this study. The RILs and parents were tested in fields from two continuous years from two different pilots. Phenotypic analysis showed that H461 was more consistent in the vertical spatial distribution of the spike layer than in Chinese Spring. Based on inclusive composite interval mapping, four QTL were identified for SLU. There were two major QTL on chromosomes 2BL and 2DL and two minor QTL on chromosomes 1BS and 2BL that were identified. The additive effects of QSlu.sicau-1B, Qslu.sicau-2B-2, and QSlu.sicau-2D were all from the parent, H461. The major QTL, QSlu.sicau-2B-2 and QSlu.sicau-2D, were detected in each of the conducted trials. Based on the best linear unbiased prediction values, the two loci explained 23.97% and 15.98% of the phenotypic variation, respectively. Compared with previous studies, the two major loci were potentially novel and the two minor loci were overlapped. Based on the kompetitive allele-specific PCR (KASP) marker, the genetic effects for QSlu.sicau-2B-2 were validated in an additional RIL population. The genetic effects ranged from 26.65% to 32.56%, with an average value of 30.40%. In addition, QSlu.sicau-2B-2 showed a significant (p < 0.01) and positive influence on the spike length, spikelet number, and thousand kernel weight. The identified QTL and the developed KASP marker will be helpful for fine-mapping these loci, finally contributing to wheat breeding programs in a marker-assisted selection way.

Atmospheric PM2.5 blocking up autophagic flux in HUVECs via inhibiting Sntaxin-17 and LAMP2.

Despite of growing evidence linking PM2.5 exposure to autophagic activity in various human cells, the functional significance of PM2.5 exposure affecting autophagy in the pathogenesis of human cardiovascular disease and the underlying molecular mechanisms remain unclear. In this study, the effects of ambient PM2.5 (with final concentration 0, 1, 5, 25 µg/mL) on the autophagic activity in human umbilical vein endothelial cells (HUVECs) were systematically studied. The results showed that the internalized PM2.5 mainly localized in the membrane-surrounded vacuoles in the cytoplasm. Compared with the negative control, dose-dependent increase of autophagosomes, puncta and protein levels of LC3-II and p62, and both dose- and time-dependent increase of AKT phosphorylation, with inversely time-dependent reduction of Beclin 1, ATG3 and ATG5 proteins, were presented in the PM2.5-treated HUVECs, indicating a clear impairment of autophagic degradation in the PM2.5-exposed HUVECs. Meanwhile, increase in lysosomes, LAMP1, proteases of CTSB and CTSD, and protein phosphorylation of ERK1/2 and TFEB was identified in the PM2.5-treated HUVECs, showing a PM2.5-mediated enhancement in lysosomal activity. A novel finding in this study is that both Sntaxin-17 and LAMP2, two key proteins involved in the control of membrane fusion between autophagosome and lysosome, were significantly decreased in the PM2.5-exposed HUVECs, suggesting that the fusion of autophagosome-lysosome was blocked up. Collectively, ambient PM2.5 exposure may block up the autophagic flux in HUVECs through inhibiting the expression of Sntaxin-17 and LAMP2. Autophagic activity in HUVECs is a useful biomarker for assessing risks of environmental factors to human cardiovascular health.

Phenotypic and genetic variation in phosphorus-deficiency-tolerance traits in Chinese wheat landraces.

BACKGROUND: Phosphorus deficiency is a major limiting factors for affecting crop production globally. To understand the genetic variation of phosphorus-deficiency-tolerance, a total of 15 seedling traits were evaluated among 707 Chinese wheat landraces under application of phosphorus (AP) and non-application of phosphorus (NP). A total of 18,594 single-nucleotide polymorphisms and 38,678 diversity arrays technology sequencing markers were used to detect marker-trait associations under AP and NP. RESULTS: Top ten genotypes with extremely tolerance and bottommost ten genotypes with extremely sensitivity were selected from 707 Chinese wheat landraces for future breeding and genetic analysis. A total of 55 significant markers (81 marker-trait associations) for 13 traits by both CMLM and SUPER method. These were distributed on chromosomes 1A, 1B, 2A, 2B, 2D, 3A, 4B, 5A, 5B, 6A, 6B, 6D, 7A and 7B. Considering the linkage disequilibrium decay distance, 25 and 12 quantitative trait loci (QTL) were detected under AP and NP, respectively (9 QTL were specific to NP). CONCLUSIONS: The extremely tolerant landraces could be used for breeding phosphorus-deficiency-tolerant cultivars. The QTL could be useful in wheat breeding through marker-assisted selection. Our findings provide new insight into the genetic analysis of P-deficiency-tolerance, and will be helpful for breeding P-deficiency-tolerant cultivars.

Identification and validation of stable quantitative trait loci for grain filling rate in common wheat (Triticum aestivum L.).

KEY MESSAGE: We identified and validated two stable grain filling rate (GFR) quantitative trait loci (QTL) in wheat that positively influenced several yield-related traits. Among them, QGfr.sicau-7D.1 was a novel GFR QTL. The grain filling rate (GFR) plays a crucial role in determining grain yield. To advance the current understanding of the genetic characteristics underlying the GFR in common wheat, three recombinant inbred line populations were used to map and validate GFR quantitative trait loci (QTL). Using a high-density genetic linkage map, 10 GFR QTL were detected. They were located on chromosomes 2D, 4A, 4B, 5B, 6D, 7A and 7D, explained 4.99-12.62% of the phenotypic variation. Two of them, QGfr.sicau-6D and QGfr.sicau-7D.1, were detected in all four environments tested and their genetic effect was validated by closely linked kompetitive allele specific PCR (KASP) markers in different genetic backgrounds. The effects of these two GFR QTL on other yield-related traits were also estimated. QGfr.sicau-6D had a significant positive influence (p < 0.01) on thousand kernel weight, kernel width, kernel volume, and kernel surface area. QGfr.sicau-7D.1 had a significant positive influence (p < 0.01) on thousand kernel weight and kernel length. Furthermore, QGfr.sicau-7D.1 was a completely novel QTL for GFR; several genes associated with grain growth and development were predicted in its physical interval. These results will facilitate molecular marker-assisted selection of wheat with high-confidence QTL for GFR and fine mapping of genes associated with GFR, thereby contributing to yield improvement.

Effects of silymarin supplementation during transition and lactation on reproductive performance, milk composition and haematological parameters in sows.

Silymarin has been shown to be a multiple-functional plant extract having antioxidant, hepatoprotective, hypolipidemic, antihypertensive, antidiabetic and anti-obesity effects. In recent years, the galactagogue effects of silymarin in animals and humans have also been revealed. This research was conducted to test whether dietary inclusion of silymarin during transition and lactation could impact reproductive performance of sows and to explore the underlying mechanisms. From day 108 of gestation to weaning, sows were randomly assigned to receive dietary treatment of silymarin (40 g/day) or not and were designated as control group (CGP, n = 55) or treatment group (TGP, n = 55). The results showed that piglets' average daily gain and average weaning weight were higher in TGP than CGP sows. In comparison with the CGP sows, the TGP sows had higher serum concentrations of catalase (CAT) on day 18 of lactation and glutathione peroxidase (GSH-Px) on day 7 of lactation. The TGP sows had lower concentration of TNF-α on day 7 of lactation and significantly lower concentration of IL-1ß on day 18 of lactation than CGP sows. There was significantly higher serum concentration of PRL on day 7 of lactation in sows consuming silymarin than sows from the CGP group. On day 18 of lactation, the protein and urea contents in milk were significantly increased while the serum urea concentration was significantly decreased in TGP sows. In summary, our results indicate that silymarin supplementation during transition and lactation can increase circulating concentrations of PRL transiently, reduce oxidative stress, increase feed intake and enhance protein metabolism, thereby significantly increasing milk yield of sows and subsequently improving growth performance of their offsprings.

Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis.

OBJECTIVE: Primary sclerosing cholangitis (PSC) is a genetically complex, inflammatory bile duct disease of largely unknown aetiology often leading to liver transplantation or death. Little is known about the genetic contribution to the severity and progression of PSC. The aim of this study is to identify genetic variants associated with PSC disease progression and development of complications. DESIGN: We collected standardised PSC subphenotypes in a large cohort of 3402 patients with PSC. After quality control, we combined 130 422 single nucleotide polymorphisms of all patients-obtained using the Illumina immunochip-with their disease subphenotypes. Using logistic regression and Cox proportional hazards models, we identified genetic variants associated with binary and time-to-event PSC subphenotypes. RESULTS: We identified genetic variant rs853974 to be associated with liver transplant-free survival (p=6.07×10-9). Kaplan-Meier survival analysis showed a 50.9% (95% CI 41.5% to 59.5%) transplant-free survival for homozygous AA allele carriers of rs853974 compared with 72.8% (95% CI 69.6% to 75.7%) for GG carriers at 10 years after PSC diagnosis. For the candidate gene in the region, RSPO3, we demonstrated expression in key liver-resident effector cells, such as human and murine cholangiocytes and human hepatic stellate cells. CONCLUSION: We present a large international PSC cohort, and report genetic loci associated with PSC disease progression. For liver transplant-free survival, we identified a genome-wide significant signal and demonstrated expression of the candidate gene RSPO3 in key liver-resident effector cells. This warrants further assessments of the role of this potential key PSC modifier gene.

Quantitative trait loci analysis of root traits under phosphorus deficiency at the seedling stage in wheat.

Deficiency of available phosphorus (P) in soil limits wheat production and creates a need to develop P-deficiency-tolerant cultivars. Plant roots, important organs for absorbing nutrients and synthesizing growth regulators, are good candidates for P-efficiency screening. In this study, we evaluated five root traits under hydroponic culture conditions either with (AP) or without (NP) applied P in a recombinant inbred line population (H461/CM107) of Triticum aestivum L. at the seedling stage. Four significant quantitative trait loci (QTL) were detected, on chromosomes 1D, 2D, 3D, and 7D in NP-treated plants, explaining up to 13.0%, 11.0%, 14.4%, and 12.8% of the phenotypic variance, respectively. Among these QTL, Qrt.sicau-3D and Qrt.sicau-7D showed pleiotropic and additive effects. All QTL were found to be novel. The diversity array technology markers flanking the QTL were converted to simple sequence repeat markers that can be deployed in future genetic studies of P deficiency. These QTL lead to an increase in root biomass and respond to P-deficiency stress; these characteristics are crucial to improve root traits for breeding or further investigation of the gene(s) involved in P-deficiency tolerance.

[From Grid Cells to Place Cells:A Gauss Distribution Activation Function Model].

It has been found that in biological studies,the simple linear superposition mathematical model cannot be used to express the feature mapping relationship from multiple activated grid cells' grid fields to a single place cell's place field output in the hippocampus of the cerebral cortex of rodents.To solve this problem,people introduced the Gauss distribution activation function into the area.We in this paper use the localization properties of the function to deal with the linear superposition output of grid cells' input and the connection weights between grid cells and place cells,which filters out the low activation rate place fields.We then obtained a single place cell field which is consistent with biological studies.Compared to the existing competitive learning algorithm place cell model,independent component analysis method place cell model,Bayesian positon reconstruction method place cell model,our experimental results showed that the model on the neurophysiological basis can not only express the feature mapping relationship between multiple activated grid cells grid fields and a single place cell's place field output in the hippocampus of the cerebral cortex of rodents,but also make the algorithm simpler,the required grid cells input less and the accuracy rate of the output of a single place field higher.

Automated Verification of IGRT-based Patient Positioning.

A system for automated quality assurance in radiotherapy of a therapist's registration was designed and tested in clinical practice. The approach compliments the clinical software's automated registration in terms of algorithm configuration and performance, and constitutes a practical approach for ensuring safe patient setups. Per our convergence analysis, evolutionary algorithms perform better in finding the global optima of the cost function with discrepancies from a deterministic optimizer seen sporadically.