Accurate prediction of kinase-substrate networks using knowledge graphs

Phosphorylation of specific substrates by protein kinases is a key control mechanism for vital cell-fate decisions and other cellular processes. However, discovering specific kinasesubstrate relationships is time-consuming and often rather serendipitous. Computational predictions alleviate these challenges, but the current approaches suffer from limitations like restricted kinome coverage and inaccuracy. They also typically utilise only local features without reflecting broader interaction context. To address these limitations, we have developed an alternative predictive model. It uses statistical relational learning on top of phosphorylation networks interpreted as knowledge graphs, a simple yet robust model for representing networked knowledge. Compared to a representative selection of six existing systems, our model has the highest kinome coverage and produces biologically valid highconfidence predictions not possible with the other tools. Specifically, we have experimentally validated predictions of previously unknown phosphorylations by the LATS1, AKT1, PKA and MST2 kinases in human. Thus, our tool is useful for focusing phosphoproteomic experiments, and facilitates the discovery of new phosphorylation reactions. Our model can be accessed publicly via an easy-to-use web interface (LinkPhinder).Science Foundation Irelan

Fructose transport-deficient Staphylococcus aureus reveals important role of epithelial glucose transporters in limiting sugar-driven bacterial growth in airway surface liquid.

Hyperglycaemia as a result of diabetes mellitus or acute illness is associated with increased susceptibility to respiratory infection with Staphylococcus aureus. Hyperglycaemia increases the concentration of glucose in airway surface liquid (ASL) and promotes the growth of S. aureus in vitro and in vivo. Whether elevation of other sugars in the blood, such as fructose, also results in increased concentrations in ASL is unknown and whether sugars in ASL are directly utilised by S. aureus for growth has not been investigated. We obtained mutant S. aureus JE2 strains with transposon disrupted sugar transport genes. NE768(fruA) exhibited restricted growth in 10 mM fructose. In H441 airway epithelial-bacterial co-culture, elevation of basolateral sugar concentration (5-20 mM) increased the apical growth of JE2. However, sugar-induced growth of NE768(fruA) was significantly less when basolateral fructose rather than glucose was elevated. This is the first experimental evidence to show that S. aureus directly utilises sugars present in the ASL for growth. Interestingly, JE2 growth was promoted less by glucose than fructose. Net transepithelial flux of D-glucose was lower than D-fructose. However, uptake of D-glucose was higher than D-fructose across both apical and basolateral membranes consistent with the presence of GLUT1/10 in the airway epithelium. Therefore, we propose that the preferential uptake of glucose (compared to fructose) limits its accumulation in ASL. Pre-treatment with metformin increased transepithelial resistance and reduced the sugar-dependent growth of S. aureus. Thus, epithelial paracellular permeability and glucose transport mechanisms are vital to maintain low glucose concentration in ASL and limit bacterial nutrient sources as a defence against infection

The Impact of Human Resource Practices on Actual and Perceived Organizational Performance in a Middle Eastern Emerging Market

This is a study centered on the impact of the specific set of HRM practices on organizational performance (OP) within an emerging-market setting. It seeks to explore which HR practices are most closely associated with better OP within the financial services industry in Jordan based on a survey of managers and the annual reports of the companies encompassed by the study. It was found that the only HR practice seen to consistently impact on OP was training; in other words, we did not encounter any recognizable "bundle" of HR practices that optimized OP across the sector. We argue that this reflects the weaker and more partially coupled nature of institutions in many emerging markets, which makes it difficult to generate the type of complementarities associated between regulation and practice in mature markets. It also reflects the limited transferability of perceived best practice models in the context of emerging-market settings. Although belied by objective firm performance data, many respondents believed that it was not only training but also the extensive usage of extrinsic incentives (pay and promotion) that would translate into superior results. This highlights the limitations of relying on managerial reported performance data in exploring the consequences of specific HR practices

The long and the short of it: Mechanisms of synchronous and compensatory dynamics across temporal scales

Synchronous dynamics (fluctuations that occur in unison) are universal phenomena with widespread implications for ecological stability. Synchronous dynamics can amplify the destabilizing effect of environmental variability on ecosystem functions such as productivity, whereas the inverse, compensatory dynamics, can stabilize function. Here we combine simulation and empirical analyses to elucidate mechanisms that underlie patterns of synchronous versus compensatory dynamics. In both simulated and empirical communities, we show that synchronous and compensatory dynamics are not mutually exclusive but instead can vary by timescale. Our simulations identify multiple mechanisms that can generate timescale-specific patterns, including different environmental drivers, diverse life histories, dispersal, and non-stationary dynamics. We find that traditional metrics for quantifying synchronous dynamics are often biased toward long-term drivers and may miss the importance of short-term drivers. Our findings indicate key mechanisms to consider when assessing synchronous versus compensatory dynamics and our approach provides a pathway for disentangling these dynamics in natural systems

Staphylococcal Toxic Shock Syndrome 2000–2006: Epidemiology, Clinical Features, and Molecular Characteristics

Circulating strains of Staphylococcus aureus (SA) have changed in the last 30 years including the emergence of community-associated methicillin-resistant SA (MRSA). A report suggested staphylococcal toxic shock syndrome (TSS) was increasing over 2000-2003. The last population-based assessment of TSS was 1986.Population-based active surveillance for TSS meeting the CDC definition using ICD-9 codes was conducted in the Minneapolis-St. Paul area (population 2,642,056) from 2000-2006. Medical records of potential cases were reviewed for case criteria, antimicrobial susceptibility, risk factors, and outcome. Superantigen PCR testing and PFGE were performed on available isolates from probable and confirmed cases.Of 7,491 hospitalizations that received one of the ICD-9 study codes, 61 TSS cases (33 menstrual, 28 non-menstrual) were identified. The average annual incidence per 100,000 of all, menstrual, and non-menstrual TSS was 0.52 (95% CI, 0.32-0.77), 0.69 (0.39-1.16), and 0.32 (0.12-0.67), respectively. Women 13-24 years had the highest incidence at 1.41 (0.63-2.61). No increase in incidence was observed from 2000-2006. MRSA was isolated in 1 menstrual and 3 non-menstrual cases (7% of TSS cases); 1 isolate was USA400. The superantigen gene tst-1 was identified in 20 (80%) of isolates and was more common in menstrual compared to non-menstrual isolates (89% vs. 50%, p = 0.07). Superantigen genes sea, seb and sec were found more frequently among non-menstrual compared to menstrual isolates [100% vs 25% (p = 0.4), 60% vs 0% (p<0.01), and 25% vs 13% (p = 0.5), respectively].TSS incidence remained stable across our surveillance period of 2000-2006 and compared to past population-based estimates in the 1980s. MRSA accounted for a small percentage of TSS cases. tst-1 continues to be the superantigen associated with the majority of menstrual cases. The CDC case definition identifies the most severe cases and has been consistently used but likely results in a substantial underestimation of the total TSS disease burden

Phosphorus dynamics in a tropical forest soil restored after strip mining

Background and aims We hypothesized that successful early ecosystem and soil development in these P-deficient soil materials will initially depend on effective re-establishment of P storage and cycling through organic matter. This hypothesis was tested in a 26-year chronosequence of seven lightly fertilized, oxidic soil materials restored to eucalypt forest communities after bauxite mining. Methods Total P (Pt) status, Hedley P fractions and partial chemical speciation (NaOH-EDTA extraction and analysed using solution 31P NMR spectroscopy) were determined in the restored soils. Results Concentrations of Pt and most Hedley fractions changed with restoration period, declined with depth and were strongly positively correlated with C and N concentrations. Biological P dominated the Labile and Intermediate P fractions while Long-term P was dominantly inorganic. Organic P concentrations in NaOH-EDTA extracts and their chemical natures were similar in restored and unburned native forest sites. Phosphomonoesters were the dominant class of organic P. Conclusions Surprisingly rapid P accretion and fractional changes occurred over 26 years, largely in the surface soils and closely associated with organic matter status. Alkaline hydrolysis products of phosphodiesters and pyrophosphate indicated the importance of microbial P cycling. The important consequences for long-term ecosystem development and biological diversity require further study

Epidemiological, clinical, outcome and antibiotic susceptibility differences between PVL positive and PVL negative Staphylococcus aureus infections in Western Australia: A case control study

Background: Panton Valentine Leukocidin (PVL) has been associated with invasive Staphylococcus aureus soft tissue and pneumonic infections. Methods: From September 2007 to January 2009 at Royal Perth Hospital we tested for the PVL gene in S. aureus isolates from an invasive site, a suspected PVL-related soft tissue infection and all MRSA isolates. We could access medical records for 141 PVL positive (PVL + ve) infections and compared these to a control group comprised of 148 PVL negative (PVL-ve) infections. Results: In the PVL + ve group 62 isolates were MRSA (48 were ST93-MRSA-IV) and 79 isolates were methicillin-sensitive S. aureus, and in the PVL-ve group 56 were MRSA (50 were WA-MRSA strains) and 92 were methicillin-sensitive S. aureus. We found the presence of PVL to be significantly associated with younger age, aboriginality, intravenous drug use, community acquisition, shorter length of hospital stay and lower mortality at 1 year. Overall PVL + ve infections more often required surgical intervention (73.0% versus 44.6%, p &lt; 0.001) and were less often polymicrobial (8.5% versus 41.2%, p &lt; 0.001). PVL + ve isolates were more often susceptible to clindamycin (87.9% versus 73.0%, p = 0.002). Conclusions: This study demonstrates that PVL + ve infections are associated with a distinct clinical picture, predominantly pyogenic skin and soft tissue infections often requiring surgery, disproportionately affecting patients who are younger, indigenous or with fewer health-care risk factors

Report of the IAU/IAG Joint Working Group on Theory of Earth Rotation and Validation

This report focuses on some selected scientific outcomes of the activities developed by the IAU/IAG Joint Working Group on Theory of Earth rotation and validation along the term 2015–2019. It is based on its end-of-term report to the IAG Commission 3 published in the Travaux de l’IAG 2015–2019, which in its turn updates previous reports to the IAG and IAU, particularly the triennial report 2015–2018 to the IAU Commission A2, and the medium term report to the IAG Commission 3 (2015–2017). The content of the report has served as a basis for the IAG General Assembly to adopt Resolution 5 on Improvement of Earth rotation theories and models.JMF, AE, and JG were partially supported by Spanish Project AYA2016-79775-P (AEI/FEDER, UE). The work of RSG described in this paper was performed at the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration. Support for that work was provided by the Earth Surface and Interior Focus Area of NASA’s Science Mission Directorate