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Abstract The compressive strength is very important for petroleum and other engineering studies. However, the effect of pore size and fluid distribution on the rock’s strength is not fully understood. We developed comprehensive research to study the controlling factors of the compressive strength based on low field nuclear magnetic resonance (NMR) measurements and pseudo-triaxial compression test for tight sandstones. The relationship between the compressive strength and the NMR obtained parameters are investigated completely, aiming for a better estimation of the compressive strength using the NMR data. The result shows that the rock’s strength is strongly controlled by the pore size distribution and the fluid existing state. Generally, the compressive strength is negatively correlated with the average transversal relaxation time, the movable water saturation, and the porosity, but positively correlated with the irreducible water saturation. The result reveals that the rock with larger pore radius and higher percentage of movable fluid is easier to reach the failure state. Further, the precision of the empirical model by multiple regression of the geometric mean of the relaxation time and the porosity is greatly improved compared with the model established by the brittle minerals, which is potentially to be use for geophysical prospecting when the NMR logging data is available.

ABSTRACTRotavirus (RV) replication takes place in the viroplasms, cytosolic inclusions that allow the synthesis of virus genome segments and their encapsidation in the core shell, followed by the addition of the second layer of the virion. The viroplasms are composed of several viral proteins, including NSP5, which serves as the main building block. Microtubules, lipid droplets, and miRNA-7 are among the host components recruited in viroplasms. We investigated the interaction between RV proteins and host components of the viroplasms by performing a pull-down assay of lysates from RV-infected cells expressing NSP5-BiolD2. Subsequent tandem mass spectrometry identified all eight subunits of the tailless complex polypeptide I ring complex (TRiC), a cellular chaperonin responsible for folding at least 10% of the cytosolic proteins. Our confirmed findings reveal that TRiC is brought into viroplasms and wraps around newly formed double-layered particles. Chemical inhibition of TRiC and silencing of its subunits drastically reduced virus progeny production. Through direct RNA sequencing, we show that TRiC is critical for RV replication by controlling dsRNA genome segment synthesis, particularly negative-sense single-stranded RNA. Importantly, cryo-electron microscopy analysis shows that TRiC inhibition results in defective virus particles lacking genome segments and polymerase complex (VP1/VP3). Moreover, TRiC associates with VP2 and NSP5 but not with VP1. Also, VP2 is shown to be essential for recruiting TRiC in viroplasms and preserving their globular morphology. This study highlights the essential role of TRiC in viroplasm formation and in facilitating virion assembly during the RV life cycle.IMPORTANCEThe replication of rotavirus takes place in cytosolic inclusions termed viroplasms. In these inclusions, the distinct 11 double-stranded RNA genome segments are co-packaged to complete a genome in newly generated virus particles. In this study, we show for the first time that the tailless complex polypeptide I ring complex (TRiC), a cellular chaperonin responsible for the folding of at least 10% of the cytosolic proteins, is a component of viroplasms and is required for the synthesis of the viral negative-sense single-stranded RNA. Specifically, TRiC associates with NSP5 and VP2, the cofactor involved in RNA replication. Our study adds a new component to the current model of rotavirus replication, where TRiC is recruited to viroplasms to assist replication.

Several studies have described functional regulation of high-risk human papillomaviruses (HPVs), E6 and E7 oncoproteins via posttranslational modifications (PTMs). However, how these PTMs modulate the activity of E6 and E7, particularly in their targeting of cellular proteins, is not completely understood. In this study, we show that HPV16 E7 can be phosphorylated by casein kinase I (CKI) and glycogen synthase kinase 3 (GSK3). This principal phosphorylation occurs at threonine residues 5 and 7 with a more minor role for residues 19–20 in the N-terminal region of 16 E7. Intriguingly, whilst mutational analyses suggest that residues 5 and 7 may be dispensable for the transformation of primary baby rat kidney cells by E7, intact residues 19 and 20 are required. Furthermore, negative charges at these residues (TT19-20DD) enhance the pRb-E7 interaction and cells display increased proliferation and invasion capacities. Using a proteomic approach with a phosphorylated peptide spanning the TT19-20 region of HPV16 E7, we have identified a panel of new, phospho-specific E7 interacting partners. These results shed new light on the complexity of N-terminal phosphorylation of E7 and how this can contribute towards expanding the repertoire of E7 targeted pathways.

Defective in cullin neddylation 1 domain containing 1 (DCUN1D1) is an E3 ligase for the neddylation, a post-translational process similar to and occurring in parallel to ubiquitin proteasome pathway. Although established as an oncogene in a variety of squamous cell carcinomas, the precise role of DCUN1D1 in prostate cancer (PCa) has not been previously explored thoroughly. Here, we investigated the role of DCUN1D1 in PCa and demonstrated that DCUN1D1 is upregulated in cell lines as well as human tissue samples. Inhibition of DCUN1D1 significantly reduced PCa cell proliferation and migration and remarkably inhibited xenograft formation in mice. Applying both genomics and proteomics approaches, we provide novel information about the DCUN1D1 mechanism of action. We identified CUL3, CUL4B, RBX1, CAND1 and RPS19 proteins as DCUN1D1 binding partners. Our analysis also revealed the dysregulation of genes associated with cellular growth and proliferation, developmental, cell death and cancer pathways and the WNT/β-catenin pathway as potential mechanisms. Inhibition of DCUN1D1 leads to the inactivation of β-catenin through its phosphorylation and degradation which inhibits the downstream action of β-catenin, reducing its interaction with Lef1 in the Lef1/TCF complex that regulates Wnt target gene expression. Together our data point to an essential role of the DCUN1D1 protein in PCa which can be explored for potential targeted therapy.

Abstract The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5–90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This mega-analysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology.

Negative associations of prenatal tobacco and alcohol exposure (PTE and PAE) on birth outcomes and childhood development have been well documented, but less is known about underlying mechanisms. A possible pathway for the adverse fetal outcomes associated with PTE and PAE is the alteration of fetal autonomic nervous system development. This study assessed PTE and PAE effects on measures of fetal autonomic regulation, as quantified by heart rate (HR), heart rate variability (SD-HR), movement, and HR-movement coupling in a population of fetuses at ≥ 34 weeks gestational age. Participants are a subset of the Safe Passage Study, a prospective cohort study that enrolled pregnant women from clinical sites in Cape Town, South Africa, and the Northern Plains region, United States. PAE was defined by six levels: no alcohol, low quit early, high quit early, low continuous, moderate continuous, and high continuous; while PTE by 4 levels: no smoking, quit early, low continuous, and moderate/high continuous. Linear regression analyses of autonomic measures were employed controlling for fetal sex, gestational age at assessment, site, maternal education, household crowding, and depression. Analyses were also stratified by sleep state (1F and 2F) and site (South Africa, N = 4025, Northern Plains, N = 2466). The final sample included 6491 maternal-fetal-dyad assessed in the third trimester [35.21 ± 1.26 (mean ± SD) weeks gestation]. PTE was associated with a decrease in mean HR in state 2F, in a dose dependent fashion, only for fetuses of mothers who continued smoking after the first trimester. In state 1F, there was a significant increase in mean HR in fetuses whose mother quit during the first trimester. This effect was driven by the Norther Plains cohort. PTE was also associated with a significant reduction in fetal movement in the most highly exposed group. In South Africa a significant increase in mean HR both for the high quit early and the high continuous group was observed. In conclusion, this investigation addresses a critical knowledge gap regarding the relationship between PTE and PAE and fetal autonomic regulation. We believe these results can contribute to elucidating mechanisms underlying risk for adverse outcomes.

Medium containing Fetal Bovine Serum (FBS) provides a supportive environment for isolation and expansion of mesenchymal stromal/stem cells (MSCs); however, the inherent variability of FBS may contribute to inconsistencies in cell growth and yield between batches of stem cell products. For this reason, we set out to develop a serum-free medium capable of supporting the in vitro expansion of MSCs. First a naïve serum-free medium was formulated by Sato's approach. Once it was established that the naïve serum-free medium supported the expansion of canine adipose-derived MSCs (Ad-MSCs), the serum-free medium was optimized by addition of growth factors. Combinations of growth factors were chosen and compared by their effect on cell proliferation and colony formation. Growth characteristics of canine adipose-derived MSCs cultured in the serum-free medium were comparable to those cultured in standard FBS containing medium. In addition, cell surface marker expression and differentiation potential of serum-free and FBS-based cultures were also comparable. However, a commercial serum-free medium developed for human MSC culture did not support growth of canine Ad-MSCs. In summary, canine Ad-MSCs isolated and cultured in serum-free medium retained the basic characteristics of MSCs cultured in FBS containing medium.

Kumanan Rasanathan and colleagues argue that the potential of multisectoral collaboration for improving health remains untapped in many low- and middle-income countries.

Screening of 203 Bacillus sp. natural isolates for antimicrobial activity against phytopathogenic bacteria showed that 127 tested strains inhibit at least one sensitive strain, which illustrates their potential use as biocontrol agents. Among them, 104 isolates showed significant antagonism against Xanthomonas oryzae pv. oryzae, and only one of these (VPS50.2) synthesizes bacteriocin. An additional screening tested whether 51 isolates contained genes involved in the biosynthesis of lipopeptides of the iturin and surfactin classes. Results show that 33 isolates harbour the operon for iturin biosynthesis, and six of them carry the sfp gene, responsible for the biosynthesis of surfactin. Lipopeptide purification from the supernatant of isolate SS12.9 (identified as B. subtilis or B. amyloliquefaciens) was performed using ethyl acetate extraction, ultrafiltration and reversed phase HPLC. Mass spectrometry analysis confirmed that isolate SS12.9 produces a substance of the iturin class with potential for biocontrol of X. oryzae pv. oryzae.

Action research (AR), which emphasises collaboration between researchers and practitioners, is a qualitative research method that has much potential for the information systems (IS) field. AR studies of IS phenomena are now beginning to be published in the IS research literature. However, the rigour of many AR studies in IS can be improved. When AR has been published, the findings have frequently been emphasised at the expense of the process. In this article, we look at the process in AR projects, and look at some of the key choices and alternatives in controlling AR. We discuss three aspects of control: the procedures for initiating an AR project, those for determining authority within the project, and the degree of formalisation. We analyse seven recent AR projects in IS and from this analysis distil recommendations for determining these control structures. [ABSTRACT FROM AUTHOR]