Sequence conservation, domain architectures, and phylogenetic distribution of the HD-GYP type c-di-GMP phosphodiesterases

The HD-GYP domain, named after two of its conserved sequence motifs, was first described in 1999 as a specialized version of the widespread HD phosphohydrolase domain that had additional highly conserved amino acid residues. Domain associations of HD-GYP indicated its involvement in bacterial signal transduction and distribution patterns of this domain suggested that it could serve as a hydrolase of the bacterial second messenger c-di-GMP, in addition to or instead of the EAL domain. Subsequent studies confirmed the ability of various HD-GYP domains to hydrolyze c-di-GMP to linear pGpG and/or GMP. Certain HD-GYP-containing proteins hydrolyze another second messenger, cGAMP, and some HD-GYP domains participate in regulatory protein-protein interactions. The recently solved structures of HD-GYP domains from four distinct organisms clarified the mechanisms of c-di-GMP binding and metal-assisted hydrolysis. However, the HD-GYP domain is poorly represented in public domain databases, which causes certain confusion about its phylogenic distribution, functions, and domain architectures. Here, we present a refined sequence model for the HD-GYP domain and describe the roles of its most conserved residues in metal and/or substrate binding. We also calculate the numbers of HD-GYPs encoded in various genomes and list the most common domain combinations involving HD-GYP, such as the RpfG (REC-HD-GYP), Bd1817 (DUF3391-HD-GYP), and PmGH (GAF-HD-GYP) protein families. We also provide the descriptions of six HD-GYP-associated domains, including four novel integral membrane sensor domains. This work is expected to stimulate studies of diverse HD-GYP-containing proteins, their N-terminal sensor domains, and the signals to which they respond.

A Step Change in the Digital Oilfield Arena: Cloud Computing and Workflow Integration for Production Operations Solutions

Digital oilfield applications have been implemented in numerous operating companies to streamline processes and automate workflows to optimize oil and gas production in real-time. These applications are mostly deployed using traditional on-premises systems; where maintenance, accessibility and scalability serves as a major bottleneck for an efficient outcome. In addition to this challenge, the sector still faces limitations in data integration from disparate data sources, liberation of consolidated data for consumption and cross domain workflow orchestration of that data. The dimensional change brought by digital transformation strategies has paved a path for the Cloud- based solutions, which have recently gained momentum in the oil and gas industry pertaining to their wider accessibility, simpler customization, greater system stability and scalability to support larger amount of data in a performant way. To address the challenges mentioned earlier, we have embarked on a journey with Production Data Foundation which brings together production and equipment data from across an organization. In this paper, we will highlight how Production Data Foundation, hosted on the cloud, provides the underlying infrastructure, services, interfaces required to support and unify production data ingestion, workflow orchestration, and through the alignment of the common domain and digital concepts, improve collaboration between people in distinct roles, such as production engineers, reservoir engineers, drilling engineers, deployment engineers, software developers, data scientists, architects, and subject matter experts (SME) working with production operations products and solutions.

Heterodimers of functionally divergent ARF-GEF paralogues prevented by self-interacting dimerisation domain

Functionally divergent paralogs of homomeric proteins do not form potentially deleterious heteromers, which requires distinction between self and non-self (Hochberg et al., 2018; Marchant et al, 2019; Marsh and Teichmann, 2015). In Arabidopsis, two ARF guanine-nucleotide exchange factors (ARF-GEFs) related to mammalian GBF1, named GNOM and GNL1, can mediate coatomer complex (COPI)-coated vesicle formation in retrograde Golgi-endoplasmic reticulum (ER) traffic (Geldner et al., 2003; Richter et al., 2007; Teh and Moore, 2007). Unlike GNL1, however, GNOM is also required for polar recycling of endocytosed auxin efflux regulator PIN1 from endosomes to the plasma membrane. Here we show that these paralogues form homodimers constitutively but no heterodimers. We also address why and how GNOM and GNL1 might be kept separate. These paralogues share a common domain organisation and each N-terminal dimerisation (DCB) domain can interact with the complementary fragment (DDCB) of its own and the other protein. However, unlike self-interacting DCBGNOM (Grebe et al., 2000; Anders et al., 2008), DCBGNL1 did not interact with itself nor DCBGNOM. DCBGNOM removal or replacement with DCBGNL1, but not disruption of cysteine bridges that stabilise DCB-DCB interaction, resulted in GNOM-GNL1 heterodimers which impaired developmental processes such as lateral root formation. We propose precocious self-interaction of the DCBGNOM domain as a mechanism to preclude formation of fitness-reducing GNOM-GNL1 heterodimers.

Bacillus thuringiensis chimeric proteins Cry1A.2 and Cry1B.2 to control soybean lepidopteran pests: New domain combinations enhance insecticidal spectrum of activity and novel receptor contributions

Two new chimeric Bacillus thuringiensis (Bt) proteins, Cry1A.2 and Cry1B.2, were constructed using specific domains, which provide insecticidal activity against key lepidopteran soybean pests while minimizing receptor overlaps between themselves, current, and soon to be commercialized plant incorporated protectants (PIP’s) in soybean. Results from insect diet bioassays demonstrate that the recombinant Cry1A.2 and Cry1B.2 are toxic to soybean looper (SBL) Chrysodeixis includens Walker, velvetbean caterpillar (VBC) Anticarsia gemmatalis Hubner, southern armyworm (SAW) Spodoptera eridania, and black armyworm (BLAW) Spodoptera cosmioides with LC50 values < 3,448 ng/cm2. Cry1B.2 is of moderate activity with significant mortality and stunting at > 3,448 ng/cm2, while Cry1A.2 lacks toxicity against old-world bollworm (OWB) Helicoverpa armigera. Results from disabled insecticidal protein (DIP) bioassays suggest that receptor utilization of Cry1A.2 and Cry1B.2 proteins are distinct from each other and from current, and yet to be commercially available, Bt proteins in soy such as Cry1Ac, Cry1A.105, Cry1F.842, Cry2Ab2 and Vip3A. However, as Cry1A.2 contains a domain common to at least one commercial soybean Bt protein, resistance to this common domain in a current commercial soybean Bt protein could possibly confer at least partial cross resistance to Cry1A2. Therefore, Cry1A.2 and Cry1B.2 should provide two new tools for controlling many of the major soybean insect pests described above.

Perceptions of coaching success: an exploratory analysis of Czech coaches views on success

A philosophical framework for success in coaching is established, upon which the results of 571 coaches’ views of success in coaching is consequently evaluated. The coaches are Czech nationals from seven sports, who coach all age groups from U8 to adult professional teams, with length of experience ranging from 1 to 26 years (mean 7.1). Success definitions were coded and categorized before being analyzed across sport, age group coached, experience and licensing level. Hal-lowell’s success cycle is used as a standard of evaluation. Results were also assessed in terms of modern coaching philosophies. Overall, it was shown that the most common definition of success by coaches fell into the Sport Growth domain (31.7%), by which they primarily meant Player Development (20.6% of these coaches). The second most common domain for defining success was Performance (28.2%), primarily defined in terms of Winning (15.5%). Emotional Growth (21.1%) and Personal Growth (7.6%), though emphasized in modern coaching philosophies, were largely undervalued by Czech coaches. Enjoyment, a key element of success from Aristotle to Seligman, and essential to Hallowell’s success cycle was evident in only a small number (5.6%) of the success definitions of coaches.

High Levels of Common Cold Coronavirus Antibodies in Convalescent Plasma Are Associated With Improved Survival in COVID-19 Patients

BackgroundCOVID-19 Convalescent plasma (CCP) is safe and effective, particularly if given at an early stage of the disease. Our study aimed to identify an association between survival and specific antibodies found in CCP.Patients and MethodsPatients ≥18 years of age who were hospitalized with moderate to severe COVID-19 infection and received CCP at the MD Anderson Cancer Center between 4/30/2020 and 8/20/2020 were included in the study. We quantified the levels of anti-SARS-CoV-2 antibodies, as well as antibodies against antigens of other coronavirus strains, in the CCP units and compared antibody levels with patient outcomes. For each antibody, a Bayesian exponential survival time regression model including prognostic variables was fit, and the posterior probability of a beneficial effect (PBE) of higher antibody level on survival time was computed.ResultsCCP was administered to 44 cancer patients. The median age was 60 years (range 37-84) and 19 (43%) were female. Twelve patients (27%) died of COVID-19-related complications. Higher levels of two non-SARS-CoV-2-specific antibodies, anti-HCoV-OC43 spike IgG and anti-HCoV-HKU1 spike IgG, had PBE = 1.00, and 4 SARS-CoV-2-specific antibodies had PBEs between 0.90 and 0.95. Other factors associated with better survival were shorter time to CCP administration, younger age, and female sex.ConclusionsCommon cold coronavirus spike IgG antibodies anti-HCoV-OC43 and anti-HCoV-HKU1 may target a common domain for SARS-CoV-2 and other coronaviruses. They provide a promising therapeutic target for monoclonal antibody production.

THE LAST DECADE DEVELOPMENT OF PROJECT DATA MANAGEMENT THROUGH THE BIM

In the last decade, the management of data through information systems has become more widespread in the field of AEC. BIM represents a complete and integrated methodological approach based on a new process of modeling and interpreting reality into an information system. Starting from the data acquisition and collection, an initial geometric 3D model of the building can be designed. The lack of a direct connection between different information systems (e.g. BIM and GIS) for the same object forces to determine a common domain through the definition of an ontology. This semantic ontology will represent the basis of this knowledge model based on data coming from different information systems allowing data standardization and data enrichment operations. Thanks to the ontology, the threshold of interoperability between BIM and other information system in a semantic web environment can be overcome. After a process of data conversion in exchange data format, a graph database can be built which collects all the heterogeneous data of the whole project. Ensuring the access to anyone to the web graph database, it is possible to formulate query for the information recognition.

Joint Transferable Dictionary Learning and View Adaptation for Multi-view Human Action Recognition

Multi-view human action recognition remains a challenging problem due to large view changes. In this article, we propose a transfer learning-based framework called transferable dictionary learning and view adaptation (TDVA) model for multi-view human action recognition. In the transferable dictionary learning phase, TDVA learns a set of view-specific transferable dictionaries enabling the same actions from different views to share the same sparse representations, which can transfer features of actions from different views to an intermediate domain. In the view adaptation phase, TDVA comprehensively analyzes global, local, and individual characteristics of samples, and jointly learns balanced distribution adaptation, locality preservation, and discrimination preservation, aiming at transferring sparse features of actions of different views from the intermediate domain to a common domain. In other words, TDVA progressively bridges the distribution gap among actions from various views by these two phases. Experimental results on IXMAS, ACT4 2 , and NUCLA action datasets demonstrate that TDVA outperforms state-of-the-art methods.

High levels of common cold coronavirus antibodies in convalescent plasma are associated with improved survival in COVID-19 patients

BackgroundCOVID-19 Convalescent plasma (CCP) is safe and effective, particularly if given at an early stage of the disease. Our study aimed to identify an association between survival and specific antibodies found in CCP.Patients and MethodsPatients ≥18 years of age who were hospitalized with moderate to severe COVID-19 infection and received CCP at the MD Anderson Cancer Center between 4/30/2020 and 8/20/2020 were included in the study. We quantified the levels of anti-SARS-CoV-2 antibodies, as well as antibodies against antigens of other coronavirus strains, in the CCP units and compared antibody levels with patient outcomes. For each antibody, a Bayesian exponential survival time regression model including prognostic variables was fit, and the posterior probability of a beneficial effect (PBE) of higher antibody level on survival time was computed.ResultsCCP was administered to 44 cancer patients. The median age was 60 years (range 37-84) and 19 (43%) were female. Twelve patients (27%) died of COVID-19-related complications. Higher levels of two non-SARS-CoV-2-specific antibodies, anti-HCoV-OC43 spike IgG and anti-HCoV-HKU1 spike IgG, had PBE = 1.00, and 4 SARS-CoV-2-specific antibodies had PBEs between 0.90 and 0.95. Other factors associated with better survival were shorter time to CCP administration, younger age, and female sex.ConclusionsCommon cold coronavirus spike IgG antibodies anti-HCoV-OC43 and anti-HCoV-HKU1 may target a common domain for SARS-CoV-2 and other coronaviruses. They provide a promising therapeutic target for monoclonal antibody production.

Spotlight on USP4: Structure, Function, and Regulation

The deubiquitinating enzyme (DUB)–mediated cleavage of ubiquitin plays a critical role in balancing protein synthesis and degradation. Ubiquitin-specific protease 4 (USP4), a member of the largest subfamily of cysteine protease DUBs, removes monoubiquitinated and polyubiquitinated chains from its target proteins. USP4 contains a DUSP (domain in USP)–UBL (ubiquitin-like) domain and a UBL-insert catalytic domain, sharing a common domain organization with its paralogs USP11 and USP15. USP4 plays a critical role in multiple cellular and biological processes and is tightly regulated under normal physiological conditions. When its expression or activity is aberrant, USP4 is implicated in the progression of a wide range of pathologies, especially cancers. In this review, we comprehensively summarize the current knowledge of USP4 structure, biological functions, pathological roles, and cellular regulation, highlighting the importance of exploring effective therapeutic interventions to target USP4.