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The obligate endosymbiont Wolbachia induces pathogen interference in the primary disease vector Aedes aegypti, facilitating the utilization of Wolbachia-based mosquito control for arbovirus prevention, particularly against dengue virus (DENV). However, the mechanisms underlying Wolbachia-mediated virus blockade have not been fully elucidated. Here, we report that Wolbachia activates the host cytoplasmic miRNA biogenesis pathway to suppress DENV infection. Through the suppression of the long noncoding RNA aae-lnc-2268 by Wolbachia wAlbB, aae-miR-34-3p, a miRNA upregulated by the Wolbachia strains wAlbB and wMelPop, promoted the expression of the antiviral effector defensin and cecropin genes through the Toll pathway regulator MyD88. Notably, anti-DENV resistance induced by Wolbachia can be further enhanced, with the potential to achieve complete virus blockade by increasing the expression of aae-miR-34-3p in Ae. aegypti. Furthermore, the downregulation of aae-miR-34-3p compromised Wolbachia-mediated virus blockade. These findings reveal a novel mechanism by which Wolbachia establishes crosstalk between the cytoplasmic miRNA pathway and the Toll pathway via aae-miR-34-3p to strengthen antiviral immune responses against DENV. Our results will aid in the advancement of Wolbachia for arbovirus control by enhancing its virus-blocking efficiency. Author summary: Although the involvement of miRNAs has been reported in the symbiosis of Wolbachia in Ae. aegypti, the role of miRNAs in the significant strong virus inhibition by Wolbachia wAlbB is poorly understood. To our knowledge, we illustrated a novel miRNA-based antiviral mechanism involved in Wolbachia-mediated viral interference according to the first global analysis of miRNA differential expression triggered by Wolbachia wAlbB. Our findings could improve the understanding of miRNA functions involved in interactions among symbiotic bacteria, arboviruses, and mosquito hosts. In particular, we identified an antiviral miRNA that could enhance the Wolbachia-mediated antiviral immune response in Ae. aegypti, suggesting that this novel molecule could improve mosquito control techniques to combat the current resurgence of dengue and other arbovirus diseases. [ABSTRACT FROM AUTHOR]

Independent innovation emphasizes the self-reliance and control of all key links. Slack resources within an organization, especially for innovation, are the critical resources that are controllable for independent innovation. However, existing research still lacks evidence on the areas of slack innovation resources and independent innovation for deeper exploration. This research addresses this gap by providing an empirical analysis of the relationship between R&D human resource slack and firms' independent innovation. Based on the unbalanced panel data of China's listed manufacturing firms for eleven years, this research explores the effects of R&D human resource slack on firms' independent innovation, the mediating mechanism of technological diversification, and the boundary effects of top management team functional heterogeneity. The results reveal that R&D human resource slack positively affects firms' independent innovation; R&D human resource slack can promote firms' independent innovation through related technological diversification, while the mediating effect of unrelated technological diversification is not statistically significant; the top management team functional heterogeneity strengthens the positive impact of R&D human resource slack on firm independent innovation. [ABSTRACT FROM AUTHOR]

Thin-bed soft rock is one of the main factors causing large deformations of tunnels. In addition to relying on some innovative construction techniques, detecting thin beds early during surface geological exploration and advanced geological prediction can provide a basis for planning and implementing effective coping measures. The commonly used seismic methods cannot meet the requirement for thin beds detection accuracy. A high-resolution (HR) seismic signal processing method is proposed by introducing a sequential convolutional neural network (SCNN). The deep learning dataset including low-resolution (LR) and HR seismic is firstly prepared through forward modeling. Then, a one-dimension (1D) SCNN architecture is proposed to establish the mapping relationship between LR and HR sequences. Training on the prepared dataset, the HR seismic processing model with high accuracy is achieved and applied to some practical seismic data. The applications on both poststack and prestack seismic data demonstrate that the trained HR processing model can effectively improve the seismic resolution and restore the high-frequency seismic energy so that to recognize the thin-bed rocks. [ABSTRACT FROM AUTHOR]

Craniopharyngiomas are rare tumors of the central nervous system that typically present with symptoms such as headache and visual impairment, and those reflecting endocrine abnormalities, which seriously affect the quality of life of patients. Patients with craniopharyngiomas are at higher cardiometabolic risk, defined as conditions favoring the development of type 2 diabetes and cardiovascular disease. However, the underlying common pathogenic mechanisms of craniopharyngiomas and type 2 diabetes are not clear. Especially due to the difficulty of conducting in vitro or in vivo experiments on craniopharyngioma, we thought the common pathway analysis between craniopharyngioma and type 2 diabetes based on bioinformatics is a powerful and feasible method. In the present study, using public datasets (GSE94349, GSE68015, GSE38642 and GSE41762) obtained from the GEO database, the gene expression associated with adamantinomatous craniopharyngioma, a subtype of craniopharyngioma, and type 2 diabetes were analyzed using a bioinformatic approach. We found 11 hub genes using a protein–protein interaction network analysis. Of these, seven (DKK1, MMP12, KRT14, PLAU, WNT5B, IKBKB, and FGF19) were also identified by least absolute shrinkage and selection operator analysis. Finally, single-gene validation and receptor operating characteristic analysis revealed that four of these genes (MMP12, PLAU, KRT14, and DKK1) may be involved in the common pathogenetic mechanism of adamantinomatous craniopharyngioma and type 2 diabetes. In addition, we have characterized the differences in immune cell infiltration that characterize these two diseases, providing a reference for further research. [ABSTRACT FROM AUTHOR]

Background: Although there is evidence that ribonucleotide reductase subunit M2 (RRM2) is associated with numerous cancers, pan-cancer analysis has seldom been conducted. This study aimed to explore the potential carcinogenesis of RRM2 in pan-cancer using datasets from The Cancer Genome Atlas (TCGA). Methods: Data from the UCSC Xena database were analyzed to investigate the differential expression of RRM2 across multiple cancer types. Clinical data such as age, race, sex, tumor stage, and status were acquired to analyze the influence of RRM2 on the clinical characteristics of the patients. The role of RRM2 in the onset and progression of multiple cancers has been examined in terms of genetic changes at the molecular level, including tumor mutational burden (TMB), microsatellite instability (MSI), biological pathway changes, and the immune microenvironment. Results: RRM2 was highly expressed in most cancers, and there was an obvious correlation between RRM2 expression and patient prognosis. RRM2 expression is associated with the infiltration of diverse immune and endothelial cells, immune checkpoints, tumor mutational burden (TMB), and microsatellite instability (MSI). Moreover, the cell cycle is involved in the functional mechanisms of RRM2. Conclusions: Our pan-cancer study provides a comprehensive understanding of the carcinogenesis of RRM2 in various tumors. [ABSTRACT FROM AUTHOR]

The incidence of cancer in acromegaly patients may be higher than that in the general population, although this has not been fully elucidated yet. This study analyzed the risk of various important types of cancer in acromegaly patients. The study was registered in INPLASY (registration number: INPLASY202340037). The PubMed, Web of Science, and EMBASE databases were searched for studies based on strict inclusion and exclusion criteria, from the time of database inception up to June 30, 2022. All observational studies of acromegaly patients with cancer were included, without language restrictions. We used the Newcastle–Ottawa scale (NOS) checklist to assess the quality of evidence. A meta-analysis revealed the relationship between acromegaly and cancer using the standardized incidence rates (SIRs) and 95% confidence intervals (CIs) retrieved from the included studies. Nineteen studies were included and analyzed. The overall incidence of cancer (SIR = 1.45, 95%CI = 1.20–1.75), as well as that of thyroid (SIR = 6.96, 95%CI = 2.51–19.33), colorectal and anal (SIR = 1.95, 95%CI = 1.32–2.87), brain and central nervous system (SIR = 6.14, 95%CI = 2.73–13.84), gastric (SIR = 3.09, 95%CI = 1.47–6.50), urinary (SIR = 2.66, 95%CI = 1.88–3.76), hematological (SIR = 1.89, 95%CI = 1.17–3.06), pancreatic and small intestine (SIR = 2.59, 95%CI = 1.58–4.24), and connective tissue (SIR = 3.15, 95%CI = 1.18–8.36) cancers, was higher among patients with acromegaly than among the general population. No association between acromegaly and hepatobiliary, respiratory, reproductive, skin, breast, or prostate cancer was observed. This study demonstrated that acromegaly patients have a modestly increased chance of cancer as compared to the general population. Risk factors for cancer need to be further explored to monitor patients with acromegaly at a high risk for cancer more carefully. [ABSTRACT FROM AUTHOR]

Objective: To assess the responses to taper in endurance athletes using meta-analysis. Methods: Systematic searches were conducted in China National Knowledge Infrastructure, PubMed, Web of Science, SPORTDiscus, and EMBASE databases. Standardized mean difference (SMD) and 95% confidence interval (CI) of outcome measures were calculated as effect sizes. Results: 14 studies were included in this meta-analysis. Significant improvements were found between pre- and post-tapering in time–trial (TT) performance (SMD = −0.45; P < 0.05) and time to exhaustion (TTE) performance (SMD = 1.28; P < 0.05). However, There were no improvements in maximal oxygen consumption (V˙O2max) and economy of movement (EM) (P > 0.05) between pre- and post-tapering. Further subgroup analysis showed that tapering combined with pre-taper overload training had a more significant effect on TT performance than conventional tapering (P < 0.05). A tapering strategy that reduced training volume by 41–60%, maintained training intensity and frequency, lasted ≤7 days, 8–14 days, or 15–21 days, used a progressive or step taper could significantly improve TT performance (P < 0.05). Conclusions: The tapering applied in conjunction with pre-taper overload training seems to be more conducive to maximize performance gains. Current evidence suggests that a ≤21-day taper, in which training volume is progressively reduced by 41–60% without changing training intensity or frequency, is an effective tapering strategy. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii is the most successful parasite worldwide. It is of great interest to understand how T. gondii induce different immune responses in different hosts. In this study, we found that a peptide of T. gondii microneme protein MIC3 induced TNF-α production, NF-κB phosphorylation, iNOS transcription and Ly6C expression in mouse macrophage RAW264.7 cells. MyD88 inhibition, small interfering RNA against Tlr11 and CRISPR/Cas9-mediated knock-out of Tlr11 all reduced MIC3-induced TNF-α production, NF-κB phosphorylation, iNOS transcription and Ly6C expression. Additionally, we determined the location of MIC3 peptide in mouse macrophages using immunofluorescence. MIC3 could both adhere to the cell membrane of mouse macrophages and enter the cells. These results suggest that MIC3 trigger the immune responses in mouse macrophages via TLR11/MyD88/NF-κB pathway. It is known that human macrophages lacking TLR11. We predicted that the immune responses induced by MIC3 in human macrophages were significantly different from those in mouse macrophages. As expected, MIC3 peptide failed to induce TNF-α expression, iNOS expression and NF-κB phosphorylation in human THP-1 derived macrophages. MIC3 induces macrophage immune responses via TLR11. Intriguingly, the amino acid sequence of MIC3 is completely different from the well-known TLR11 ligand profilin, which generates a potent IL-12p40, TNF-α and IL-6 response. In marked contrast to profilin, MIC3 could not induce IL-12p40 expression in both mouse RAW264.7 cells and human THP-1 derived macrophages. Furthermore, the simulated tertiary structure of MIC3 peptide shows poor similarity with the crystal structure of profilin, suggesting that MIC3 might be a different ligand from profilin. These findings about MIC3 and TLR11 will provide us with important insights into the pathogenesis of toxoplasmosis and coevolution during host-parasite interaction. Author summary: To be the most successful parasite worldwide, Toxoplasma gondii develops fascinating ways to coexist with its host and fulfil its life cycle. After infection with T. gondii, the survival time of mice is short, while human beings can coexist with T. gondii for lifetime. Remarkably, in this study we found that a short peptide from T. gondii microneme protein MIC3, which was known to be the circulating antigen after T. gondii infection, was sufficient to trigger the TLR11/MyD88/NF-κB pathway and induced macrophage TNF-α production, NF-κB phosphorylation, iNOS transcription and Ly6C expression in mouse macrophages. Human macrophages lacking TLR11 failed to induce such inflammatory reaction in response to MIC3. Therefore, we speculate that the TLR11-driven deleterious inflammatory immune responses impede the long-term coexistence of host and T. gondii, which might provide the evolutionary pressures for TLR11 expression. Additionally, the amino acid sequence, simulated tertiary structure and triggered immune responses of MIC3 are completely different from the well-known TLR11 ligand profilin. All together, these findings propose MIC3 as a potential different ligand from profilin, and what we learn about MIC3 and TLR11 provides important insights into the evolutionary roles of T. gondii and other TLR11 sensing pathogens. [ABSTRACT FROM AUTHOR]

In recent years, as the Ether platform has grown by leaps and bounds. Numerous unscrupulous individuals have used illegal transaction to defraud large sums of money, causing billions of dollars of losses to investors worldwide. Facing the endless stream of the illegal transaction based on Ether smart contracts problems, such as illegal transaction, money laundering, financial fraud, phishing. Currently, illegal transaction are only detected by a single view of the smart contract's contract code view feature and account transaction view feature, which is not only incomplete, but also not fully representative of the smart contract's features. More importantly, the single view detection model cannot accurately capture the global structure and semantic features between the Tokens of the view features. In this case, it is particularly important that all view features are shared among themselves. In this paper, we investigate a Transformer-based model for contrasting illegal transaction detection networks under multiple views (TranMulti-View Net). The model in this paper is based on Transformer to learn a multi-view fusion representation, which aims to maximise the fusion of the interaction information of different view features under the same condition. In this model we first use the Transformer model to learn global structure and semantic features from a sequence of Tokens tokenised by a view, capturing the remote dependencies of Tokens in the view features, and then we share the contract code view features and the account transaction view features across all views to learn important semantic information between views from each other. In addition, we find that the approach of semi-supervised training of multi-view features using contrast learning outperforms the scheme of prediction based on direct fusion of different view features, resulting in stronger correlation between view features. As a result, the underlying semantic information can be captured more accurately, leading to more accurate predictions of illegal transaction. The experimental results show that our proposed TranMulti-View Net obtains good detection results with a Precision score of 98%. [ABSTRACT FROM AUTHOR]

Malaria during pregnancy is a major global health problem caused by infection with Plasmodium falciparum parasites. Severe effects arise from the accumulation of infected erythrocytes in the placenta. Here, erythrocytes infected by late blood-stage parasites adhere to placental chondroitin sulphate A (CS) via VAR2CSA-type P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion proteins. Immunity to placental malaria is acquired through exposure and mediated through antibodies to VAR2CSA. Through evolution, the VAR2CSA proteins have diversified in sequence to escape immune recognition but retained their overall macromolecular structure to maintain CS binding affinity. This structural conservation may also have allowed development of broadly reactive antibodies to VAR2CSA in immune women. Here we show the negative stain and cryo-EM structure of the only known broadly reactive human monoclonal antibody, PAM1.4, in complex with VAR2CSA. The data shows how PAM1.4's broad VAR2CSA reactivity is achieved through interactions with multiple conserved residues of different sub-domains forming conformational epitope distant from the CS binding site on the VAR2CSA core structure. Thus, while PAM1.4 may represent a class of antibodies mediating placental malaria immunity by inducing phagocytosis or NK cell-mediated cytotoxicity, it is likely that broadly CS binding-inhibitory antibodies target other epitopes at the CS binding site. Insights on both types of broadly reactive monoclonal antibodies may aid the development of a vaccine against placental malaria. Author summary: Placental malaria remains a major global health problem. The disease is caused by the accumulation of malaria parasite-infected red blood cells in the placenta. The parasites export members of the polymorphic VAR2CSA protein family onto the red blood cell surface to bind placental chondroitin sulphate A (CS). The VAR2CSA protein family have diversified in sequence to avoid immune recognition, but recent CryoEM structures of VAR2CSA shows that all variants fold into a large, dense and stable core comprised of multiple interwoven "DBL" domains, and a flexible two-DBL domain tail. Immunity to placental malaria is acquired through exposure and thought to be mediated by broadly reactive antibodies acting through neutralizing CS binding or opsonizing infected red blood cells for cell-mediated killing. Here, we used negative stain and cryo-EM to resolve the first molecular structure of a broadly reactive antibody (PAM1.4) against VAR2CSA. We find that the antibody binds a highly conserved conformational epitope on the VAR2CSA core structure, distant from previously determined CS binding sites. This aligns with new data showing negligible PAM1.4 neutralization of parasite binding to CSA. As a well-characterized non-neutralizing monoclonal antibody, PAM1.4 and Fc-modifications thereof, can now be used for reference and benchmarking in future studies aiming to map, identify and qualify functional antibodies against VAR2CSA in the continued quest for vaccines or therapeutics against placental malaria. [ABSTRACT FROM AUTHOR]

Background: Scrub typhus has become a serious public health concern in the Asia-Pacific region including China. There were new natural foci continuously recognized and dramatically increased reported cases in mainland China. However, the epidemiological characteristics and spatiotemporal patterns of scrub typhus in Fujian province have yet to be investigated. Objective: This study proposes to explore demographic characteristics and spatiotemporal dynamics of scrub typhus cases in Fujian province, and to detect high-risk regions between January 2012 and December 2020 at county/district scale and thereby help in devising public health strategies to improve scrub typhus prevention and control measures. Method: Monthly cases of scrub typhus reported at the county level in Fujian province during 2012–2020 were collected from the National Notifiable Disease Surveillance System. Time-series analyses, spatial autocorrelation analyses and space-time scan statistics were applied to identify and visualize the spatiotemporal patterns of scrub typhus cases in Fujian province. The demographic differences of scrub typhus cases from high-risk and low-risk counties in Fujian province were also compared. Results: A total of 11,859 scrub typhus cases reported in 87 counties from Fujian province were analyzed and the incidence showed an increasing trend from 2012 (2.31 per 100,000) to 2020 (3.20 per 100,000) with a peak in 2018 (4.59 per 100,000). There existed two seasonal peaks in June-July and September-October every year in Fujian province. A significant positive spatial autocorrelation of scrub typhus incidence in Fujian province was observed with Moran's I values ranging from 0.258 to 0.471 (P<0.001). Several distinct spatiotemporal clusters mainly concentrated in north and southern parts of Fujian province. Compared to low-risk regions, a greater proportion of cases were female, farmer, and older residents in high-risk counties. Conclusions: These results demonstrate a clear spatiotemporal heterogeneity of scrub typhus cases in Fujian province, and provide the evidence in directing future researches on risk factors and effectively assist local health authorities in the refinement of public health interventions against scrub typhus transmission in the high risk regions. Author summary: Scrub typhus is a vector-borne zoonotic disease caused by Orientia tsutsugamushi and is popular in the Asia-Pacific area. Nowadays scrub typhus has been recognized as a considerable burden on public health in Fujian province. We explored the epidemiological characteristics, spatiotemporal patterns and diffusion characteristics of scrub typhus, and detected high-risk regions at the county level in Fujian province between January 2012 and December 2020. Our results indicated that the majority of cases were reported in June-July and September-October and that that middle aged and elderly people were more prone to infection every year in Fujian province. The spatial autocorrelation analysis revealed clustering in geographic distribution of cases and several distinct spatiotemporal clusters were identified in north and southern parts of Fujian province. Compared with cases from low-risk areas, a higher proportion of cases were female, farmer, and older residents in high-risk counties. [ABSTRACT FROM AUTHOR]

Background: Worldwide, 10% of babies are born preterm, defined as a live birth before 37 weeks of gestation. Preterm birth is the leading cause of neonatal death, and survivors face lifelong risks of adverse outcomes. New approaches with large sample sizes are needed to identify strategies to predict and prevent preterm birth. The primary aims of the Washington University Prematurity Research Cohort Study were to conduct three prospective projects addressing possible causes of preterm birth and provide data and samples for future research. Study design: Pregnant patients were recruited into the cohort between January 2017 and January 2020. Consenting patients were enrolled into the study before 20 weeks' gestation and followed through delivery. Participants completed demographic and lifestyle surveys; provided maternal blood, placenta samples, and cord blood; and participated in up to three projects focused on underlying physiology of preterm birth: cervical imaging (Project 1), circadian rhythms (Project 2), and uterine magnetic resonance imaging and electromyometrial imaging (Project 3). Results: A total of 1260 participants were enrolled and delivered during the study period. Of the participants, 706 (56%) were Black/African American, 494 (39%) were nulliparous, and 185 (15%) had a previous preterm birth. Of the 1260 participants, 1220 (97%) delivered a live infant. Of the 1220 with a live birth, 163 (14.1%) had preterm birth, of which 74 (6.1%) were spontaneous preterm birth. Of the 1220 participants with a live birth, 841 participated in cervical imaging, 1047 contributed data and/or samples on circadian rhythms, and 39 underwent uterine magnetic resonance imaging. Of the 39, 25 underwent electromyometrial imaging. Conclusion: We demonstrate feasibility of recruiting and retaining a diverse cohort in a complex prospective, longitudinal study throughout pregnancy. The extensive clinical, imaging, survey, and biologic data obtained will be used to explore cervical, uterine, and endocrine physiology of preterm birth and can be used to develop novel approaches to predict and prevent preterm birth. [ABSTRACT FROM AUTHOR]

Skeletal muscle regeneration is essential for maintaining muscle function in injury and muscular disease. Myogenesis plays key roles in forming new myofibers during the process. Here, through bioinformatic screen for the potential regulators of myogenesis from 5 independent microarray datasets, we identify an overlapping differentially expressed gene (DEG) optineurin (OPTN). Optn knockdown (KD) delays muscle regeneration in mice and impairs C2C12 myoblast differentiation without affecting their proliferation. Conversely, Optn overexpression (OE) promotes myoblast differentiation. Mechanistically, OPTN increases nuclear levels of β-catenin and enhances the T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription activity, suggesting activation of Wnt signaling pathway. The activation is accompanied by decreased protein levels of glycogen synthase kinase 3β (GSK3β), a negative regulator of the pathway. We further show that OPTN physically interacts with and targets GSK3β for autophagic degradation. Pharmacological inhibition of GSK3β rescues the impaired myogenesis induced by Optn KD during muscle regeneration and myoblast differentiation, corroborating that GSK3β is the downstream effector of OPTN-mediated myogenesis. Together, our study delineates the novel role of OPTN as a potential regulator of myogenesis and may open innovative therapeutic perspectives for muscle regeneration. Skeletal muscle regeneration is essential for maintaining muscle function in injury and muscular disease. This study identifies optineurin as a promoter of myoblast differentiation and potential regulator of myogenesis, showing that it interacts with GSK3β and targets it for autophagic degradation. [ABSTRACT FROM AUTHOR]

Hulless barley (Hordeum vulgare L. var. nudum), also called naked barley, is a unique variety of cultivated barley. The genome-wide specific length amplified fragment sequencing (SLAF-seq) method is a rapid deep sequencing technology that is used for the selection and identification of genetic loci or markers. In this study, we collected 300 hulless barley accessions and used the SLAF-seq method to identify candidate genes involved in plant height (PH) and tiller number (TN). We obtained a total of 1407 M paired-end reads, and 228,227 SLAF tags were developed. After filtering using an integrity threshold of >0.8 and a minor allele frequency of >0.05, 14,504,892 single-nucleotide polymorphisms (SNP) loci were screened out. The remaining SNPs were used for the construction of a neighbour-joining phylogenetic tree, and the three subcluster members showed no obvious differentiation among regional varieties. We used a genome wide association study approach to identify 1006 and 113 SNPs associated with TN and PH, respectively. Based on best linear unbiased predictors (BLUP), 41 and 29 SNPs associated with TN and PH, respectively. Thus, several of genes, including Hd3a and CKX5, may be useful candidates for the future genetic breeding of hulless barley. Taken together, our results provide insight into the molecular mechanisms controlling barley architecture, which is important for breeding and yield. [ABSTRACT FROM AUTHOR]

Background: The relationship between severe anemia, red blood cell transfusion and Neonatal necrotizing enterocolitis (NEC) remains controversial. The purpose of this study was to determine the association of severe anemia and RBC transfusion with NEC in neonates. Methods: The clinical characteristics of NEC were observed in 467 infants with different birth weights from January 2012 to July 2020. A 1:1 ratio case-control study was performed in very low birth weight (VLBW) infants. Severe anemia, RBC transfusion, and confounding factors, including maternal and perinatal complications, feeding, and antibiotics administration were collected in both groups. Univariate and multivariate analyses were used to investigate effects on the risk of NEC. Results: The day of NEC onset and mortality were inversely associated with birth weight. In VLBW infants, adjusting for other factors, severe anemia within 72 h [OR = 2.404, P = 0.016], RBC transfusion within 24 h [OR = 4.905, P = 0.016], within 48 h [OR = 5.587, P = 0.008], and within 72 h [OR = 2.858, P = 0.011] increased the risk of NEC. Conclusion: Both severe anemia and RBC transfusion appears to increase the risk of NEC in VLBW infants. The early prevention and treatment of anemia, strict evaluation of the indications for transfusion and enhanced monitoring after transfusion is encouraged in the NICU. [ABSTRACT FROM AUTHOR]

Canavan disease is a severe progressive neurodegenerative disorder that is characterized by swelling and spongy degeneration of brain white matter. The disease is genetically linked to polymorphisms in the aspartoacylase (ASPA) gene, including the substitution C152W. ASPA C152W is associated with greatly reduced protein levels in cells, yet biophysical experiments suggest a wild-type like thermal stability. Here, we use ASPA C152W as a model to investigate the degradation pathway of a disease-causing protein variant. When we expressed ASPA C152W in Saccharomyces cerevisiae, we found a decreased steady state compared to wild-type ASPA as a result of increased proteasomal degradation. However, molecular dynamics simulations of ASPA C152W did not substantially deviate from wild-type ASPA, indicating that the native state is structurally preserved. Instead, we suggest that the C152W substitution interferes with the de novo folding pathway resulting in increased proteasomal degradation before reaching its stable conformation. Systematic mapping of the protein quality control components acting on misfolded and aggregation-prone species of C152W, revealed that the degradation is highly dependent on the molecular chaperone Hsp70, its co-chaperone Hsp110 as well as several quality control E3 ubiquitin-protein ligases, including Ubr1. In addition, the disaggregase Hsp104 facilitated refolding of aggregated ASPA C152W, while Cdc48 mediated degradation of insoluble ASPA protein. In human cells, ASPA C152W displayed increased proteasomal turnover that was similarly dependent on Hsp70 and Hsp110. Our findings underscore the use of yeast to determine the protein quality control components involved in the degradation of human pathogenic variants in order to identify potential therapeutic targets. Author summary: Canavan disease is a fatal neurodegenerative disorder which is genetically linked to polymorphisms in the aspartoacylase (ASPA) gene. Although the molecular mechanism of most disease-causing substitutions remains to be examined, some variants have been suggested to cause the loss-of-function phenotype by perturbing the structural stability of ASPA. So far the cellular fate of these variants have not been examined. Here we examine the stability and degradation pathways of the disease-causing ASPA variant C152W. In yeast cells, ASPA C152W showed decreased steady-state protein levels as a result of increased proteasomal turnover. Our molecular dynamics simulations showed that the C152W substitution did not globally perturb the native structure of ASPA. Instead we propose that ASPA C152W is targeted by the protein quality control system during de novo folding. Specifically, we found that the molecular chaperone Hsp70, its co-chaperone Hsp110, and the E3 ubiquitin-protein ligase Ubr1 promote degradation of ASPA C152W. When we expressed ASPA C152W in cultured human cells, we found that Hsp70 and Hsp110 similarly mediated degradation. Therefore, we propose that Hsp110 should be further examined as a potential therapeutic target in Canavan disease and other protein misfolding diseases. [ABSTRACT FROM AUTHOR]

Chagas' disease (CD), caused by the hemoflagellate protozoan, Trypanosoma cruzi, is endemic in most countries of Latin America. Heart failure (HF) is often a late manifestation of chronic CD, and is associated with high morbidity and mortality. Inflammatory processes mediated by cytokines play a key role in the pathogenesis and progression of CD. Keeping in view the inflammatory nature of CD, this study investigated the possible role of 21 different inflammatory cytokines as biomarkers for prediction and prognosis of CD. The plasma concentration of these cytokines was measured in a group of patients with CD (n = 94), and then compared with those measured in patients with dilated cardiomyopathy (DCM) from idiopathic causes (n = 48), and with control subjects (n = 25). Monovariately, plasma levels of cytokines such as stem cell growth factor beta (SCGF beta), hepatocyte growth factor (HGF), monokine induced by interferon gamma (CXCL9), and macrophage inhibitory factor (MIF) were significantly increased in CD patients with advanced HF compared to control group. None of the cytokines could demonstrate any prognostic potency in CD patients, and only MIF and stromal derived factor-1 alpha (CXCL12) showed significance in predicting mortality and necessity for heart transplant in DCM patients. However, multivariate analysis prognosticated a large proportion of CD and DCM patients. In CD patients, HGF and Interleukin-12p40 (IL-12p40) together separated 81.9% of 3-year survivors from the deceased, while in DCM patients, CXCL12, stem cell factor (SCF), and CXCL9 together discriminated 77.1% of survivors from the deceased. The significant increase in plasma concentrations of cytokines such as HGF and CXCL9 in CD patients, and the ability of these cytokines to prognosticate a large proportion of CD and DCM patients multivariately, encourages further studies to clarify the diagnostic and prognostic potential of cytokines in such patients. Author summary: Chagas' disease (CD), caused by the parasite, Trypanosoma cruzi, is endemic in most of Latin America. Cardiac involvement is the most frequent in chronic CD. Heart failure (HF) is often a late manifestation of chronic CD and is associated with high morbidity and mortality. Early identification of patients with CD would be desirable as early intervention may help improve prognosis. Inflammatory biomarkers can play a vital role in early diagnosis, as inflammation mediated by cytokines plays an important role in pathogenesis and progression of CD. This study investigated the possible role of 21 different inflammatory cytokines as biomarkers for discrimination and risk stratification of CD and idiopathic dilated cardiomyopathy (DCM). Plasma concentrations of various cytokines were significantly increased in CD and DCM patients with advanced HF, however, they were unable to show predictive or prognostic potency in CD. Using various cytokines together, analyses prognosticated fatal outcome in a large proportion of CD and DCM patients, but could still not discriminate CD from idiopathic DCM. Our promising data encourages research on identifying further inflammatory biomarkers that could, in combination with the 21 measured in this study, be used as tools for early diagnosis and prognosis of CD. [ABSTRACT FROM AUTHOR]

Wide Area Protection System (WAPS) undertakes the important task of maintaining system reliability and stability when the power system is subject to abnormal or predetermined unstable conditions. The existing WAPS adopts a centralized mechanism to record and audit communication messages, which faces the risk of excessive authority and tampering with communication records and audit logs, thus making it impossible to achieve true transparency and fairness. Due to the involvement of multiple parties and equipment maintained by different manufacturers in the communication of WAPS, there are difficulties in tracing the cause of the accident and determining the at-fault party following misoperations and miss trips. To address this issue, we propose a semi-centralized blockchain system with multi-chain for auditing communications of WAPS. We first propose a semi-centralized system architecture according to the system architecture and management requirements of WAPS. Then, we utilize the blockchain network as a self-recording channel to achieve tamper-proof and non-repudiation verification interaction. We also design a multi-chain structure and classification node mechanism to meet the communication auditing requirements of multiple WAPS. We have designed a new block structure that conforms to the communication protocol of WAPS. To reduce the storage burden caused by the ever-expanding blockchain ledger, we propose a deletable blockchain scheme while maintaining the integrity and security of blockchain. Analysis and experiments show that the proposed blockchain system can support the secure, transparent, tamper-proof and traceable communication recording and auditing of WAPS along with high performance. [ABSTRACT FROM AUTHOR]

Owing to their plasticity, intrinsically disordered and multidomain proteins require descriptions based on multiple conformations, thus calling for techniques and analysis tools that are capable of dealing with conformational ensembles rather than a single protein structure. Here, we introduce DEER-PREdict, a software program to predict Double Electron-Electron Resonance distance distributions as well as Paramagnetic Relaxation Enhancement rates from ensembles of protein conformations. DEER-PREdict uses an established rotamer library approach to describe the paramagnetic probes which are bound covalently to the protein.DEER-PREdict has been designed to operate efficiently on large conformational ensembles, such as those generated by molecular dynamics simulation, to facilitate the validation or refinement of molecular models as well as the interpretation of experimental data. The performance and accuracy of the software is demonstrated with experimentally characterized protein systems: HIV-1 protease, T4 Lysozyme and Acyl-CoA-binding protein. DEER-PREdict is open source (GPLv3) and available at github.com/KULL-Centre/DEERpredict and as a Python PyPI package pypi.org/project/DEERPREdict. Author summary: The accurate description of the structure of a protein is pivotal to fully understand its biological function. A large fraction of eukaryotic proteins is intrinsically disordered or consists of multiple folded domains connected by disordered regions. The structure of these proteins is highly flexible and can only be described by large ensembles of conformations. The characterization of these ensembles can be achieved by integrating in silico molecular modelling and simulations with experiments. Here, we present DEER-PREdict, an open-source software program to conveniently and efficiently calculate the observables of two biophysical methods, namely double electron-electron resonance (DEER) and paramagnetic relaxation enhancement (PRE) nuclear magnetic resonance. Both techniques provide distance information for highly dynamic systems and involve labelling proteins at one or more sites with flexible nitroxide molecules. The DEER-PREdict package combines previously developed and validated methods for placing multiple conformations of the nitroxide molecule at the protein sites with the rapid calculation of DEER and PRE observables from large ensembles of protein structures. Through examples, we illustrate the use of DEER-PREdict as a tool for interpreting experimental results, validating molecular models of flexible proteins as well as designing experiments. [ABSTRACT FROM AUTHOR]

Growth curve measurements are commonly used in microbiology, while the use of microplate readers for such measurements provides better temporal resolution and higher throughput. However, evaluating bacterial growth with microplate readers has been hurdled by barriers such as multiple scattering. Here, we report our development of a method based on the time derivatives of the optical density (OD) and/or fluorescence (FL) of bacterial cultures to overcome these barriers. First, we illustrated our method using quantitative models and numerical simulations, which predicted the number of bacteria and the number of fluorescent proteins in time as well as their time derivatives. Then, we systematically investigated how the time derivatives depend on the parameters in the models/simulations, providing a framework for understanding the FL growth curves. In addition, as a demonstration, we applied our method to study the lag time elongation of bacteria subjected to treatment with silver (Ag+) ions and found that the results from our method corroborated well with that from growth curve fitting by the Gompertz model that has been commonly used in the literature. Furthermore, this method was applied to the growth of bacteria in the presence of silver nanoparticles (AgNPs) at various concentrations, where the OD curve measurements failed. We showed that our method allowed us to successfully extract the growth behavior of the bacteria from the FL measurements and understand how the growth was affected by the AgNPs. [ABSTRACT FROM AUTHOR]

Collaboration among logistics facilities in a multicenter logistics delivery network can significantly improve the utilization of logistics resources through resource sharing including logistics facilities, vehicles, and customer services. This study proposes and tests different resource sharing schemes to solve the optimization problem of a collaborative multicenter logistics delivery network based on resource sharing (CMCLDN-RS). The CMCLDN-RS problem aims to establish a collaborative mechanism of allocating logistics resources in a manner that improves the operational efficiency of a logistics network. A bi-objective optimization model is proposed with consideration of various resource sharing schemes in multiple service periods to minimize the total cost and number of vehicles. An adaptive grid particle swarm optimization (AGPSO) algorithm based on customer clustering is devised to solve the CMCLDN-RS problem and find Pareto optimal solutions. An effective elite iteration and selective endowment mechanism is designed for the algorithm to combine global and local search to improve search capabilities. The solution of CMCLDN-RS guarantees that cost savings are fairly allocated to the collaborative participants through a suitable profit allocation model. Compared with the computation performance of the existing nondominated sorting genetic algorithm-II and multi-objective evolutionary algorithm, AGPSO is more computationally efficient. An empirical case study in Chengdu, China suggests that the proposed collaborative mechanism with resource sharing can effectively reduce total operational costs and number of vehicles, thereby enhancing the operational efficiency of the logistics network. [ABSTRACT FROM AUTHOR]

We studied livestock abortion and various associated risk factors in the Ili region of northwest China. Livestock abortion prevalence was estimated and correlated with infections (Brucellosis, Salmonellosis, Mycoplasma and Chlamydia seropositivity) and management (farming type and contact with other herds/flocks) risk factors. A total of 2996 serum samples (1406 cow, 1590 sheep) were identified by RBPT (Rose Bengal Plate Test) and c-ELISA (competitive-enzyme linked immunosorbent assay), and they showed the overall seroprevalence of brucellosis in the study area was cow 6.76%, sheep 9.50%. The seroprevalence of brucellosis in X county was cow 7.06%, sheep 9.12%; in H county was cow 11.70%, sheep 10.80%; and in Q county was cow 4.22%, sheep 9.11%. The overall seroprevalence of Mycoplasma in the study area was cow 3.20%, sheep 6.42%. The seroprevalence of Mycoplasma in X county was cow 3.39%, sheep 7.98%; in H county was cow 5.26%, sheep 9.97%; and in Q county was cow 2.11%, sheep 4.33%. The Odds ratio of brucellosis for cow and sheep, respectively, were 45.909 [95% CI 26.912–78.317, P<0.001] and 70.507 [95% CI 43.783–113.544, P<0.001] times higher than other abortion-related factors including mixed farming, contact with other flocks and Mycoplasma infection. A total of 54 samples, including aborted cow (22), sheep (30) fetuses and milk samples (2), were identified as Brucella melitensis (B. melitensis) positive. A total of 38 Brucella were isolated from 16 aborted cow, 20 sheep fetuses and 2 milk samples. All of these isolates were identified, and confirmed, as B. melitensis. A phylogenetic tree showed that the Brucella isolates closely matched the B. melitensis biovar 3 isolated in Inner Mongolia, China, and B. melitensis isolated from Norway and India. These results suggest that B. melitensis biovar 3 is the main pathogen responsible for cow and sheep abortion and also pose a human health risk. Additionally, livestock reproduction can also be influenced by Mycoplasma infection and managerial factors (farming type and contact with other herds/flocks), especially in remote areas. [ABSTRACT FROM AUTHOR]

Many proteins contain multiple folded domains separated by flexible linkers, and the ability to describe the structure and conformational heterogeneity of such flexible systems pushes the limits of structural biology. Using the three-domain protein TIA-1 as an example, we here combine coarse-grained molecular dynamics simulations with previously measured small-angle scattering data to study the conformation of TIA-1 in solution. We show that while the coarse-grained potential (Martini) in itself leads to too compact conformations, increasing the strength of protein-water interactions results in ensembles that are in very good agreement with experiments. We show how these ensembles can be refined further using a Bayesian/Maximum Entropy approach, and examine the robustness to errors in the energy function. In particular we find that as long as the initial simulation is relatively good, reweighting against experiments is very robust. We also study the relative information in X-ray and neutron scattering experiments and find that refining against the SAXS experiments leads to improvement in the SANS data. Our results suggest a general strategy for studying the conformation of multi-domain proteins in solution that combines coarse-grained simulations with small-angle X-ray scattering data that are generally most easy to obtain. These results may in turn be used to design further small-angle neutron scattering experiments that exploit contrast variation through 1H/2H isotope substitutions. Author summary: Many proteins contain multiple folded domains separated by flexible linkers, and in order to understand how such multi-domain proteins function, we need to be able to describe how these domains are oriented in space. We have used the three-domain protein TIA-1 as an example to combine molecular simulations with biophysical experiments to describe the structural and dynamical properties of a multi-domain protein. We show that while standard simulations do not lead to good agreement with the experimental data, we can improve the agreement substantially by tuning a single parameter in the model that describes the interaction between protein and water. We can gain further information about the system by a more direct integration of the data, and we find that we can provide a detailed and robust description of the relative location of the different domains in TIA-1. The method is general and will be useful to study the relationship between structure, dynamics and function in multi-domain proteins in other systems. [ABSTRACT FROM AUTHOR]

Oil palm (Elaeis guineensis Jacq.) is a representative tropical oil crop that is sensitive to low temperature. Oil palm can experience cold damage when exposed to low temperatures for a long period. During these unfavorable conditions, a series of gene induction/repression and physico-chemical changes occur in oil palm. To better understand the link between these events, we investigated the expression levels of various genes (including COR410, COR413, CBF1, CBF2, CBF3, ICE1-1, ICE1-2, ICE1-4, SIZ1-1, SIZ1-2, ZAT10, ZAT12) and the accumulation of osmolytes (proline, malondialdehyde and sucrose). Likewise, the activity of superoxide dismutase (SOD) in oil palm under cold stress (4°C, 8°C and 12°C) was examined. The results showed a clear link among the expression of CBFs (especially CBF1 and CBF3) and the all genes examined under cold stress (12°C). The expression of CBF1 and CBF2 also exhibited a positive link with the accumulation of sucrose and proline under cold stress in oil palm. At 4°C, the proline content exhibited a very significant correlation with electrolyte leakage in oil palm. The results of this study provide necessary information regarding the mechanism of the response and adaption of oil palm to cold stress. Additionally, they offer clues for the selection or development of cold-tolerant cultivars from the available germplasms of oil palm. [ABSTRACT FROM AUTHOR]

Background: To assess the mRNA expression profile and explore the hub mRNAs and potential molecular mechanisms in the pathogenesis of human thoracic aortic dissection (TAD). Methodology: mRNA microarray expression signatures of TAD tissues (n = 6) and non-TAD tissues (NT; n = 6) were analyzed by an Arraystar human mRNA microarray. Real-time PCR (qRT-PCR) was used to validate the results of the mRNA microarray. Bioinformatic tools, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, were utilized. Protein-protein interaction (PPI) networks were constructed based on data from the STRING database. Molecular Complex Detection (MCODE) and cytoHubba analyses were used to predict the strongest hub gene and pathway. Results: The top 10 hub genes were CDK1, CDC20, CCNB2, CCNB1, MAD2L1, AURKA, C3AR1, NCAPG, CXCL12 and ASPM, which were identified from the PPI network. Module analysis revealed that TAD was associated with the cell cycle, oocyte meiosis, the p53 signaling pathway, and progesterone-mediated oocyte maturation. The qRT-PCR results showed that the expression of all hub genes was significantly increased in TAD samples (p < 0.05). Immunostaining of Ki-67 and CDK1 showed a high proliferation state and high expression in TAD, respectively. Conclusions: CDK1 could be used as a potential diagnostic biomarker and therapeutic target of TAD. [ABSTRACT FROM AUTHOR]

Objectives: Primary brain tumors are composed of tumor cells, neural/glial tissues, edema, and vasculature tissue. Conventional MRI has a limited ability to evaluate heterogeneous tumor pathologies. We developed a novel diffusion MRI-based method—Heterogeneity Diffusion Imaging (HDI)—to simultaneously detect and characterize multiple tumor pathologies and capillary blood perfusion using a single diffusion MRI scan. Methods: Seven adult patients with primary brain tumors underwent standard-of-care MRI protocols and HDI protocol before planned surgical resection and/or stereotactic biopsy. Twelve tumor sampling sites were identified using a neuronavigational system and recorded for imaging data quantification. Metrics from both protocols were compared between World Health Organization (WHO) II and III tumor groups. Cerebral blood volume (CBV) derived from dynamic susceptibility contrast (DSC) perfusion imaging was also compared with the HDI-derived perfusion fraction. Results: The conventional apparent diffusion coefficient did not identify differences between WHO II and III tumor groups. HDI-derived slow hindered diffusion fraction was significantly elevated in the WHO III group as compared with the WHO II group. There was a non-significantly increasing trend of HDI-derived tumor cellularity fraction in the WHO III group, and both HDI-derived perfusion fraction and DSC-derived CBV were found to be significantly higher in the WHO III group. Both HDI-derived perfusion fraction and slow hindered diffusion fraction strongly correlated with DSC-derived CBV. Neither HDI-derived cellularity fraction nor HDI-derived fast hindered diffusion fraction correlated with DSC-derived CBV. Conclusions: Conventional apparent diffusion coefficient, which measures averaged pathology properties of brain tumors, has compromised accuracy and specificity. HDI holds great promise to accurately separate and quantify the tumor cell fraction, the tumor cell packing density, edema, and capillary blood perfusion, thereby leading to an improved microenvironment characterization of primary brain tumors. Larger studies will further establish HDI's clinical value and use for facilitating biopsy planning, treatment evaluation, and noninvasive tumor grading. [ABSTRACT FROM AUTHOR]

C-to-U editing is an important event in post-transcriptional RNA processing, which converts a specific cytidine (C)-to-uridine (U) in transcripts of mitochondria and plastids. Typically, the pentatricopeptide repeat (PPR) protein, which specifies the target C residue by binding to its upstream sequence, is involved in the editing of one or a few sites. Here we report a novel PPR-DYW protein EMP21 that is associated with editing of 81 sites in maize. EMP21 is localized in mitochondria and loss of the EMP21 function severely inhibits the embryogenesis and endosperm development in maize. From a scan of 35 mitochondrial transcripts produced by the Emp21 loss-of-function mutant, the C-to-U editing was found to be abolished at five sites (nad7-77, atp1-1292, atp8-437, nad3-275 and rps4-870), while reduced at 76 sites in 21 transcripts. In most cases, the failure to editing resulted in the translation of an incorrect residue. In consequence, the mutant became deficient with respect to the assembly and activity of mitochondrial complexes I and V. As six of the decreased editing sites in emp21 overlap with the affected editing sites in emp5-1, and the editing efficiency at rpl16-458 showed a substantial reduction in the emp21-1 emp5-4 double mutant compared with the emp21-1 and emp5-4 single mutants, we explored their interaction. A yeast two hybrid assay suggested that EMP21 does not interact with EMP5, but both EMP21 and EMP5 interact with ZmMORF8. Together, these results indicate that EMP21 is a novel PPR-DYW protein required for the editing of ~17% of mitochondrial target Cs, and the editing process may involve an interaction between EMP21 and ZmMORF8 (and probably other proteins). [ABSTRACT FROM AUTHOR]

Cumulative evidence supports a role for neutralizing antibodies contributing to spontaneous viral clearance during acute hepatitis C virus (HCV) infection. Information on the timing and specificity of the B cell response associated with clearance is crucial to inform vaccine design. From an individual who cleared three sequential HCV infections with genotypes 1b, 1a and 3a strains, respectively, we employed peripheral B cells to isolate and characterize neutralizing human monoclonal antibodies (HMAbs) to HCV after the genotype 1 infections. The majority of isolated antibodies, designated as HMAbs 212, target conformational epitopes on the envelope glycoprotein E2 and bound broadly to genotype 1–6 E1E2 proteins. Further, some of these antibodies showed neutralization potential against cultured genotype 1–6 viruses. Competition studies with defined broadly neutralizing HCV HMAbs to epitopes in distinct clusters, designated antigenic domains B, C, D and E, revealed that the selected HMAbs compete with B, C and D HMAbs, previously isolated from subjects with chronic HCV infections. Epitope mapping studies revealed domain B and C specificity of these HMAbs 212. Sequential serum samples from the studied subject inhibited the binding of HMAbs 212 to autologous E2 and blocked a representative domain D HMAb. The specificity of this antibody response appears similar to that observed during chronic infection, suggesting that the timing and affinity maturation of the antibody response are the critical determinants in successful and repeated viral clearance. While additional studies should be performed for individuals with clearance or persistence of HCV, our results define epitope determinants for antibody E2 targeting with important implications for the development of a B cell vaccine. [ABSTRACT FROM AUTHOR]

Background: Hemorrhagic fever with renal syndrome (HFRS) is a zoonosis caused by hantavirus (belongs to Hantaviridae family). A large amount of HFRS cases occur in China, especially in the Heilongjiang Province, raising great concerns regarding public health. The distribution of these cases across space-time often exhibits highly heterogeneous characteristics. Hence, it is widely recognized that the improved mapping of heterogeneous HFRS distributions and the quantitative assessment of the space-time disease transition patterns can advance considerably the detection, prevention and control of epidemic outbreaks. Methods: A synthesis of space-time mapping and probabilistic logic is proposed to study the distribution of monthly HFRS population-standardized incidences in Heilongjiang province during the period 2005–2013. We introduce a class-dependent Bayesian maximum entropy (cd-BME) mapping method dividing the original dataset into discrete incidence classes that overcome data heterogeneity and skewness effects and can produce space-time HFRS incidence estimates together with their estimation accuracy. A ten-fold cross validation analysis is conducted to evaluate the performance of the proposed cd-BME implementation compared to the standard class-independent BME implementation. Incidence maps generated by cd-BME are used to study the spatiotemporal HFRS spread patterns. Further, the spatiotemporal dependence of HFRS incidences are measured in terms of probability logic indicators that link class-dependent HFRS incidences at different space-time points. These indicators convey useful complementary information regarding intraclass and interclass relationships, such as the change in HFRS transition probabilities between different incidence classes with increasing geographical distance and time separation. Results: Each HFRS class exhibited a distinct space-time variation structure in terms of its varying covariance parameters (shape, sill and correlation ranges). Given the heterogeneous features of the HFRS dataset, the cd-BME implementation demonstrated an improved ability to capture these features compared to the standard implementation (e.g., mean absolute error: 0.19 vs. 0.43 cases/105 capita) demonstrating a point outbreak character at high incidence levels and a non-point spread character at low levels. Intraclass HFRS variations were found to be considerably different than interclass HFRS variations. Certain incidence classes occurred frequently near one class but were rarely found adjacent to other classes. Different classes may share common boundaries or they may be surrounded completely by another class. The HFRS class 0–68.5% was the most dominant in the Heilongjiang province (covering more than 2/3 of the total area). The probabilities that certain incidence classes occur next to other classes were used to estimate the transitions between HFRS classes. Moreover, such probabilities described the dependency pattern of the space-time arrangement of HFRS patches occupied by the incidence classes. The HFRS transition probabilities also suggested the presence of both positive and negative relations among the main classes. The HFRS indicator plots offer complementary visualizations of the varying probabilities of transition between incidence classes, and so they describe the dependency pattern of the space-time arrangement of the HFRS patches occupied by the different classes. Conclusions: The cd-BME method combined with probabilistic logic indicators offer an accurate and informative quantitative representation of the heterogeneous HFRS incidences in the space-time domain, and the results thus obtained can be interpreted readily. The same methodological combination could also be used in the spatiotemporal modeling and prediction of other epidemics under similar circumstances. [ABSTRACT FROM AUTHOR]

Insect-resistance of transgenic Bacillus thuringiensis (Bt) cotton varies among plants organs and with different environmental conditions. The objective of this study was to examine the influence of soil salinity on Bt protein concentration in cotton squares and to elucidate the potential mechanism of Bt efficacy reduction. Two cotton cultivars (NuCOTN 33B and CCRI 07, salt-sensitive and salt-tolerant) were subjected to salinity stress under four natural saline levels in field conditions in 2015 and 2016 and seven regimes of soil salinity ranged from 0.5 to 18.8 dS m-1 in greenhouse conditions in 2017. Results of field studies revealed that Bt protein content was not significantly changed at 7.13 dS m-1 salinity, but exhibited a significant drop at the 10.41 and 14.16 dS m-1 salinity. The greenhouse experiments further showed similar trends that significant declines of the insecticidal protein contents in squares were detected when soil salinity exceeded 9.1 dS m-1. Meanwhile, high salinity resulted in significant reduction in contents of soluble protein and total nitrogen, activities of nitrate reductase (NR), glutamine synthetase (GS) and glutamic-pyruvic transaminase (GPT), but increased amino acid content, activities of protease and peptidase in cotton squares. High salinity also decreased root vigor (RV), root total absorption area (RTA) and root active absorption area (RAA). The extent of decrease of Bt protein content was more pronounced in NuCOTN 33B than CCRI 07, and CCRI07 exhibited stronger enzymes activities involved in square protein synthesis and higher levels of RV, RTA and RAA. Therefore, the results of our present study indicated that insecticidal protein expression in cotton squares were significantly affected by higher salinity (equal to or higher than 9.1 dS m-1), reduced protein synthesis and increased protein degradation in squares and reduced metabolic activities in roots might lead to the decrease of Bt protein content in squares. [ABSTRACT FROM AUTHOR]

Objective: To quantitatively evaluate maxillary complete dentures fabricated from polylactic acid (PLA) using fused deposition modelling (FDM) technology. Methods: A digital maxillary complete denture was prepared based on a standard maxillary edentulous plaster model. The PLA pattern was printed by a FDM machine, with 5 repetitions, while another 5 wax patterns were printed as control group, using a high accuracy three-dimensional (3D) wax printer. The patterns were scanned with a 3D scanner. A light-body silicone film was made after each denture pattern had been totally seated on the plaster model, and was scanned to determine its thickness, which reflected the 3D space between the plaster model and the tissue surface of the denture pattern. The overall area was separated into four parts: primary stress-bearing area, secondary stress-bearing area, border seal area and relief area, and the average deviation of these four parts were measured. The values were analyzed by independent t-test. Results: The overall mean value and standard deviation of space between PLA denture patterns and plaster model was 0.277 ± 0.021 mm, while that of the wax denture patterns was 0.279 ± 0.045 mm, which showed a good fit overall. No statistically significant (푃 > 0.05) difference was observed between the PLA patterns and wax patterns. Conclusions: The adaptation of the PLA pattern of maxillary complete denture printed by FDM technology is comparable to that prepared by wax printer, and can satisfy the accuracy requirements. [ABSTRACT FROM AUTHOR]

Background: Hemorrhagic fever with renal syndrome (HFRS) is a rodent-associated zoonosis caused by hantavirus. The HFRS was initially detected in northeast China in 1931, and since 1955 it has been detected in many regions of the country. Global climate dynamics influences HFRS spread in a complex nonlinear way. The quantitative assessment of the spatiotemporal variation of the “HFRS infections-global climate dynamics” association at a large geographical scale and during a long time period is still lacking. Methods and findings: This work is the first study of a recently completed dataset of monthly HFRS cases in Eastern China during the period 2005–2016. A methodological synthesis that involves a time-frequency technique, a composite space-time model, hotspot analysis, and machine learning is implemented in the study of (a) the association between HFRS incidence spread and climate dynamics and (b) the geographic factors impacting this association over Eastern China during the period 2005–2016. The results showed that by assimilating core and city-specific knowledge bases the synthesis was able to depict quantitatively the space-time variation of periodic climate-HFRS associations at a large geographic scale and to assess numerically the strength of this association in the area and period of interest. It was found that the HFRS infections in Eastern China has a strong association with global climate dynamics, in particular, the 12, 18 and 36 mos periods were detected as the three main synchronous periods of climate dynamics and HFRS distribution. For the 36 mos period (which is the period with the strongest association), the space-time correlation pattern of the association strength indicated strong temporal but rather weak spatial dependencies. The generated space-time maps of association strength and association hotspots provided a clear picture of the geographic variation of the association strength that often-exhibited cluster characteristics (e.g., the south part of the study area displays a strong climate-HFRS association with non-point effects, whereas the middle-north part displays a weak climate-HFRS association). Another finding of this work is the upward climate-HFRS coherency trend for the past few years (2013–2015) indicating that the climate impacts on HFRS were becoming increasingly sensitive with time. Lastly, another finding of this work is that geographic factors affect the climate-HFRS association in an interrelated manner through local climate or by means of HFRS infections. In particular, location (latitude, distance to coastline and longitude), grassland and woodland are the geographic factors exerting the most noticeable effects on the climate-HFRS association (e.g., low latitude has a strong effect, whereas distance to coastline has a wave-like effect). Conclusions: The proposed synthetic quantitative approach revealed important aspects of the spatiotemporal variation of the climate-HFRS association in Eastern China during a long time period, and identified the geographic factors having a major impact on this association. Both findings could improve public health policy in an HFRS-torn country like China. Furthermore, the synthetic approach developed in this work can be used to map the space-time variation of different climate-disease associations in other parts of China and the World. [ABSTRACT FROM AUTHOR]

African oil palm (Elaeis guineensis) is an important oil crop grown in tropical region and sensitive to low temperature along with high tolerance to salt and drought stresses. Since the WRKY transcription factor family plays central roles in the regulation of plant stress tolerance, 95 genes belonging to the WRKY family were identified and characterized in oil palm genome. Gene structure analysis showed that EgWRKY genes have considerable variation in intron number (0 to 12) and gene length (477bp to 89,167 bp). Duplicated genes identification indicated 32 EgWRKY genes originated from segmental duplication and two from tandem duplication. Based on transcriptome data, most EgWRKY genes showed tissue-specific expression patterns and their expression could be induced under cold stress. Furthermore, six EgWRKY genes with more than two-folded increased expression level under cold stress were validated by RT-qPCR, which has higher expression level in cold, drought and high salinity treatment. The identification and characterization of WRKY gene family showed that EgWRKY were associated with a wide range of abiotic stress responses in Elaeis guineensis and some EgWRKY members with high expression levels could be selected for further research in analyzing their functions in the stress response in African oil palm. [ABSTRACT FROM AUTHOR]

The ovary is the main regulator of female fertility. Granulosa cell dysfunction may be involved in various reproductive endocrine disorders. Here we investigated the effect of insulin resistance on the metabolism and function of ovarian granulosa cells, and dissected the functional status of the mitogen-activated protein kinase signaling pathway in these cells. Our data showed that dexamethasone-induced insulin resistance in mouse granulosa cells reduced insulin sensitivity, accompanied with an increase in phosphorylation of p44/42 mitogen-activated protein kinase. Furthermore, up-regulation of cytochrome P450 subfamily 17 and testosterone and down-regulation of progesterone were observed in insulin-resistant mouse granulosa cells. Inhibition of p44/42 mitogen-activated protein kinase after induction of insulin resistance in mouse granulosa cells decreased phosphorylation of p44/42 mitogen-activated protein kinase, downregulated cytochrome P450 subfamily 17 and lowered progesterone production. This insulin resistance cell model can successfully demonstrate certain mechanisms such as hyperandrogenism, which may inspire a new strategy for treating reproductive endocrine disorders by regulating cell signaling pathways. [ABSTRACT FROM AUTHOR]

Arabidopsis thaliana high-affinity potassium transporter 1 (AtHKT1) limits the root-to-shoot sodium transportation and is believed to be essential for salt tolerance in A. thaliana. Nevertheless, natural accessions with ‘weak allele’ of AtHKT1, e.g. Tsu-1, are mainly distributed in saline areas and are more tolerant to salinity. These findings challenge the role of AtHKT1 in salt tolerance and call into question the involvement of AtHKT1 in salinity adaptation in A. thaliana. Here, we report that AtHKT1 indeed drives natural variation in the salt tolerance of A. thaliana and the coastal AtHKT1, so-called weak allele, is actually hyper-functional in reducing flowers sodium content upon salt stress. Our data showed that AtHKT1 positively contributes to saline adaptation in a linear manner. Forward and reverse genetics analysis established that the single AtHKT1 locus is responsible for the variation in the salinity adaptation between Col-0 and Tsu-1. Reciprocal grafting experiments revealed that shoot AtHKT1 determines the salt tolerance of Tsu-1, whereas root AtHKT1 primarily drives the salt tolerance of Col-0. Furthermore, evidence indicated that Tsu-1 AtHKT1 is highly expressed in stems and is more effective compared to Col-0 AtHKT1 at limiting sodium flow to the flowers. Such efficient retrieval of sodium to the reproductive organ endows Tsu-1 with stronger fertility compared to Col-0 upon salt stress, thus improving Tsu-1 adaptation to a coastal environment. To conclude, our data not only confirm the role of AtHKT1 in saline adaptation, but also sheds light on our understanding of the salt tolerance mechanisms in plants. [ABSTRACT FROM AUTHOR]

We validated an 18-gene classifier (GC) initially developed to predict local/regional recurrence after mastectomy in estimating distant metastasis risk. The 18-gene scoring algorithm defines scores as: <21, low risk; ≥21, high risk. Six hundred eighty-three patients with primary operable breast cancer and fresh frozen tumor tissues available were included. The primary outcome was the 5-year probability of freedom from distant metastasis (DMFP). Two external datasets were used to test the predictive accuracy of 18-GC. The 5-year rates of DMFP for patients classified as low-risk (n = 146, 21.7%) and high-risk (n = 537, 78.6%) were 96.2% (95% CI, 91.1%–98.8%) and 80.9% (74.6%–81.9%), respectively (median follow-up interval, 71.8 months). The 5-year rates of DMFP of the low-risk group in stage I (n = 62, 35.6%), stage II (n = 66, 20.1%), and stage III (n = 18, 10.3%) were 100%, 94.2% (78.5%–98.5%), and 90.9% (50.8%–98.7%), respectively. Multivariate analysis revealed that 18-GC is an independent prognostic factor of distant metastasis (adjusted hazard ratio, 5.1; 95% CI, 1.8–14.1; p = 0.0017) for scores of ≥21. External validation showed that the 5-year rate of DMFP in the low- and high-risk patients was 94.1% (82.9%–100%) and 80.3% (70.7%–89.9%, p = 0.06) in a Singapore dataset, and 89.5% (81.9%–94.1%) and 73.6% (67.2%–79.0%, p = 0.0039) in the GEO-GSE20685 dataset, respectively. In conclusion, 18-GC is a viable prognostic biomarker for breast cancer to estimate distant metastasis risk. [ABSTRACT FROM AUTHOR]

Congenital cytomegalovirus (CMV) infection is the most common non-hereditary cause of sensorineural hearing loss (SNHL) yet the mechanisms of hearing loss remain obscure. Natural Killer (NK) cells play a critical role in regulating murine CMV infection via NK cell recognition of the Ly49H cell surface receptor of the viral-encoded m157 ligand expressed at the infected cell surface. This Ly49H NK receptor/m157 ligand interaction has been found to mediate host resistance to CMV in the spleen, and lung, but is much less effective in the liver, so it is not known if this interaction is important in the context of SNHL. Using a murine model for CMV-induced labyrinthitis, we have demonstrated that the Ly49H/m157 interaction mediates host resistance in the temporal bone. BALB/c mice, which lack functional Ly49H, inoculated with mCMV at post-natal day 3 developed profound hearing loss and significant outer hair cell loss by 28 days of life. In contrast, C57BL/6 mice, competent for the Ly49H/m157 interaction, had minimal hearing loss and attenuated outer hair cell loss with the same mCMV dose. Administration of Ly49H blocking antibody or inoculation with a mCMV viral strain deleted for the m157 gene rendered the previously resistant C57BL/6 mouse strain susceptible to hearing loss to a similar extent as the BALB/c mouse strain indicating a direct role of the Ly49H/m157 interaction in mCMV-dependent hearing loss. Additionally, NK cell recruitment to sites of infection was evident in the temporal bone of inoculated susceptible mouse strains. These results demonstrate participation of NK cells in protection from CMV-induced labyrinthitis and SNHL in mice. [ABSTRACT FROM AUTHOR]

For over 130 years, invasive pneumococcal disease has been associated with the presence of extracellular planktonic pneumococci, i.e. diplococci or short chains in affected tissues. Herein, we show that Streptococcus pneumoniae that invade the myocardium instead replicate within cellular vesicles and transition into non-purulent biofilms. Pneumococci within mature cardiac microlesions exhibited salient biofilm features including intrinsic resistance to antibiotic killing and the presence of an extracellular matrix. Dual RNA-seq and subsequent principal component analyses of heart- and blood-isolated pneumococci confirmed the biofilm phenotype in vivo and revealed stark anatomical site-specific differences in virulence gene expression; the latter having major implications on future vaccine antigen selection. Our RNA-seq approach also identified three genomic islands as exclusively expressed in vivo. Deletion of one such island, Region of Diversity 12, resulted in a biofilm-deficient and highly inflammogenic phenotype within the heart; indicating a possible link between the biofilm phenotype and a dampened host-response. We subsequently determined that biofilm pneumococci released greater amounts of the toxin pneumolysin than did planktonic or RD12 deficient pneumococci. This allowed heart-invaded wildtype pneumococci to kill resident cardiac macrophages and subsequently subvert cytokine/chemokine production and neutrophil infiltration into the myocardium. This is the first report for pneumococcal biofilm formation in an invasive disease setting. We show that biofilm pneumococci actively suppress the host response through pneumolysin-mediated immune cell killing. As such, our findings contradict the emerging notion that biofilm pneumococci are passively immunoquiescent. [ABSTRACT FROM AUTHOR]

A metaproteomic approach was used to analyse the proteins expressed and provide functional evidence of key metabolic pathways in the combined production of hydrogen and methane by anaerobic fermentation (CHMP-AF) for reed straw utilisation. The functions and structures of bacteria and archaea populations show significant succession in the CHMP-AF process. There are many kinds of bacterial functional proteins, mainly belonging to phyla Firmicutes, Proteobacteria, Actinobacteria and Bacteroidetes, that are involved in carbohydrate metabolism, energy metabolism, lipid metabolism, and amino acid metabolism. Ferredoxin-NADP reductase, present in bacteria in genus Azotobacter, is an important enzyme for NADH/NAD+ equilibrium regulation in hydrogen production. The archaeal functional proteins are mainly involved in methane metabolism in energy metabolism, such as acetyl-CoA decarboxylase, and methyl-coenzyme M reductase, and the acetic acid pathway exhibited the highest proportion of the total. The archaea of genus Methanosarcina in phylum Euryarchaeota can produce methane under the effect of multi-functional proteins through acetic acid, CO2 reduction, and methyl nutrient pathways. The study demonstrates metaproteomics as a new way of uncovering community functional and metabolic activity. The combined information was used to identify the metabolic pathways and organisms crucial for lignocellulosic biomass degradation and biogas production. This also regulates the process from its protein levels and improves the efficiency of biogas production using reed straw biomass. [ABSTRACT FROM AUTHOR]

Intramuscular fat (IMF) content and fatty acid composition of longissimus dorsi muscle (LM) change with growth, which partially determines the flavor and nutritional value of goat (Capra hircus) meat. However, unlike cattle, little information is available on the transcriptome-wide changes during different postnatal stages in small ruminants, especially goats. In this study, the sequencing reads of goat LM tissues collected from kid, youth, and adult period were mapped to the goat genome. Results showed that out of total 24 689 Unigenes, 20 435 Unigenes were annotated. Based on expected number of fragments per kilobase of transcript sequence per million base pairs sequenced (FPKM), 111 annotated differentially expressed genes (DEGs) were identified among different postnatal stages, which were subsequently assigned to 16 possible expression patterns by series-cluster analysis. Functional classification by Gene Ontology (GO) analysis was used for selecting the genes showing highest expression related to lipid metabolism. Finally, we identified the node genes for lipid metabolism regulation using co-expression analysis. In conclusion, these data may uncover candidate genes having functional roles in regulation of goat muscle development and lipid metabolism during the various growth stages in goats. [ABSTRACT FROM AUTHOR]

A mature understanding of the sandstone gas reservoir in the Xiaoheba Formation in the southeastern Sichuan Basin remains lacking. To assess the reservoir characteristics and the origin of the high-quality reservoir in the Xiaoheba Formation, this paper uses systematic field investigations, physical property analysis, thin section identification, scanning electron microscopy and electron microprobe methods. The results indicate that the Xiaoheba sandstone is an ultra-tight and ultra-low permeability reservoir, with an average porosity of 2.97% and an average permeability of 0.56×10−3 μm2. This promising reservoir is mainly distributed in the Lengshuixi and Shuangliuba regions and the latter has a relatively high-quality reservoir with an average porosity of 5.28% and average permeability of 0.53×10−3 μm2. The reservoir space comprises secondary intergranular dissolved pores, moldic pores and fractures. Microfacies, feldspar dissolution and fracture connectivity control the quality of this reservoir. The relatively weak compaction and cementation in the interbedded delta front distal bar and interdistributary bay microfacies indirectly protected the primary intergranular pores and enhanced late-stage dissolution. Late-stage potassium feldspar dissolution was controlled by the early-stage organic acid dissolution intensity and the distance from the hydrocarbon generation center. Early-stage fractures acted as pathways for organic acid migration and were therefore important factors in the formation of the reservoir. Based on these observations, the area to the west of the Shuangliuba and Lengshuixi regions has potential for gas exploration. [ABSTRACT FROM AUTHOR]

We report a robust nonparametric descriptor, J′(r), for quantifying the density of clustering molecules in single-molecule localization microscopy. J′(r), based on nearest neighbor distribution functions, does not require any parameter as an input for analyzing point patterns. We show that J′(r) displays a valley shape in the presence of clusters of molecules, and the characteristics of the valley reliably report the clustering features in the data. Most importantly, the position of the J′(r) valley () depends exclusively on the density of clustering molecules (ρc). Therefore, it is ideal for direct estimation of the clustering density of molecules in single-molecule localization microscopy. As an example, this descriptor was applied to estimate the clustering density of ptsG mRNA in E. coli bacteria. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness and safety of gonadotropin-releasing hormone antagonist (GnRH-ant) protocol and gonadotropin-releasing hormone agonist (GnRH-a) long protocol in patients with normal ovarian reserve. Methods: We searched the PubMed (1992–2016), Cochrane Library (1999–2016), Web of Science (1950–2016), Chinese Biomedical Database (CBM, 1979–2016), and China National Knowledge Infrastructure (CNKI, 1994–2016). Any randomized controlled trials (RCTs) that compared GnRH-ant protocol and GnRH-a long protocol in patients with normal ovarian reserve were included, and data were extracted independently by two reviewers. The meta-analysis was performed by Revman 5.3 software. Results: Twenty-nine RCTs (6399 patients) were included in this meta-analysis. Stimulation days (mean difference (MD) [95% confidence interval (CI)] = -0.8 [-1.36, -0.23], P = 0.006), gonadotrophin (Gn) dosage (MD [95% CI] = -3.52 [-5.56, -1.48], P = 0.0007), estradiol (E2) level on the day of human chorionic gonadotrophin (HCG) administration (MD [95% CI] = -365.49 [-532.93, -198.05], P<0.0001), the number of oocytes retrieved (MD [95% CI] = -1.41 [-1.84, -0.99], P<0.00001), the embryos obtained (MD [95% CI] = -0.99 [-1.38, -0.59], P<0.00001), incidence of ovarian hyperstimulation syndrome (OHSS) (OR [95% CI] = 0.69 [0.57, 0.83], P<0.0001) were statistically significantly lower in GnRH-ant protocol than GnRH-a long protocol. However, the clinical pregnancy rate (OR [95% CI] = 0.90 [0.80, 1.01], P = 0.08), ongoing pregnancy rate (OR [95% CI] = 0.88 [0.77, 1.00], P = 0.05), live birth rate (OR [95% CI] = 0.95 [0.74, 1.09], P = 0.27), miscarriage rate (OR [95% CI] = 0.98 [0.69, 1.40], P = 0.93), and cycle cancellation rate (OR [95% CI] = 0.86 [0.52, 1.44], P = 0.57) showed no significant differences between the two groups. Conclusion: GnRH-ant protocol substantially decreased the incidence of OHSS without influencing the pregnancy rate and live birth rate compared to GnRH-a long protocol among patients with normal ovarian reserve. [ABSTRACT FROM AUTHOR]

Background: Valvular heart diseases (VHD) is very common in clinical practice and has became the subject of growing attention in the field of cardiovascular medicine. Our aim was to assess the prevalence and correlates of VHD in the general population in Xinjiang, China. Methods: Using a 4-stage stratified cluster random sampling method, a total of 14618 participants were recruited in the Cardiovascular Risk Survey (CRS) study. The participants’ personal information, medical history were assessed by questionnaire. VHD was diagnosed by transthoracic echocardiography. We carried out the statistical analysis utilizing SPSS Statistics version 19.0. Results: In the total study group, VHD was observed in 1397 (9.65%) individuals. The prevalence rates of VHD in Han, Uygur and Kazak group are 13.51%, 2.71% and 12.29% respectively. The prevalence rates of VHD increased strikingly with age (all P < 0.001). The results of multinomial regression analysis indicated that VHD were related to age in Han group, to age smoking and hypertension in Uygur group, to age and hypertension in Kazak group. Conclusion: Our research provides a unique prevalence rate of VHD in Xinjiang natural population. The result suggests that VHD are notably common in this population (9.65%) and increase with age. There exists significant difference of prevalence rate between ethnics. The main risk factors of VHD are age, hypertension and smoking. Valvular heart diseases should be regarded as a serious and growing public-health problem. [ABSTRACT FROM AUTHOR]

Background: Subsyndromal symptomatic depression (SSD) is a subtype of subthreshold depressive and can lead to significant psychosocial functional impairment. Although the pathogenesis of major depressive disorder (MDD) and SSD still remains poorly understood, a set of studies have found that many same genetic factors play important roles in the etiology of these two disorders. Nowadays, the differential gene expression between MDD and SSD is still unknown. In our previous study, we compared the expression profile and made the classification with the leukocytes by using whole-genome cRNA microarrays among drug-free first-episode subjects with SSD, MDD and matched healthy controls (8 subjects in each group), and finally determined 48 gene expression signatures. Based on these findings, we further clarify whether these genes mRNA was different expressed in peripheral blood in patients with SSD, MDD and healthy controls (60 subjects respectively) Method: With the help of the quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR), we gained gene relative expression levels among the three groups. Results: We found that there are three of the forty eight co-regulated genes had differential expression in peripheral blood among the three groups, which are CD84, STRN, CTNS gene (F = 3.528, p = 0.034; F = 3.382, p = 0.039; F = 3.801, p = 0.026, respectively) while there were no significant differences for other genes. Conclusion: CD84, STRN, CTNS gene may have significant value for performing diagnostic functions and classifying SSD, MDD and healthy controls. [ABSTRACT FROM AUTHOR]

The general transcription factor TBP (TATA-box binding protein) and its associated factors (TAFs) together form the TFIID complex, which directs transcription initiation. Through RNAi and mutant analysis, we identified a specific TBP family protein, TRF2, and a set of TAFs that regulate lipid droplet (LD) size in the Drosophila larval fat body. Among the three Drosophila TBP genes, trf2, tbp and trf1, only loss of function of trf2 results in increased LD size. Moreover, TRF2 and TAF9 regulate fatty acid composition of several classes of phospholipids. Through RNA profiling, we found that TRF2 and TAF9 affects the transcription of a common set of genes, including peroxisomal fatty acid β-oxidation-related genes that affect phospholipid fatty acid composition. We also found that knockdown of several TRF2 and TAF9 target genes results in large LDs, a phenotype which is similar to that of trf2 mutants. Together, these findings provide new insights into the specific role of the general transcription machinery in lipid homeostasis. [ABSTRACT FROM AUTHOR]

Objectives: Hypoxia in solid tumors occurs when metabolic demands in tumor cells surpass the delivery of oxygenated blood. We hypothesize that the 18F-fluorodeoxyglucose (18F-FDG) metabolism and tumor blood flow mismatch would correlate with tumor hypoxia. Methods: Liver perfusion computed tomography (CT) and 18F-FDG positron emission tomography (PET) imaging were performed in twelve rabbit livers implanted with VX2 carcinoma. Under CT guidance, a fiber optic probe was inserted into the tumor to measure the partial pressure of oxygen (pO2). Tumor blood flow (BF) and standardized uptake value (SUV) were measured to calculate flow-metabolism ratio (FMR). Tumor hypoxia was further identified using pimonidazole immunohistochemical staining. Pearson correlation analysis was performed to determine the correlation between the imaging parameters and pO2 and pimonidazole staining. Results: Weak correlations were found between blood volume (BV) and pO2 level (r = 0.425, P = 0.004), SUV and pO2 (r = -0.394, P = 0.007), FMR and pimonidazole staining score (r = -0.388, P = 0.031). However, there was stronger correlation between tumor FMR and pO2 level (r = 0.557, P < 0.001). Conclusions: FMR correlated with tumor oxygenation and pimonidazole staining suggesting it may be a potential hypoxic imaging marker in liver tumor. [ABSTRACT FROM AUTHOR]