Project description:Methanotrophic bacteria represent a potential route to methane utilization and mitigation of methane emissions. In the first step of their metabolic pathway, aerobic methanotrophs use methane monooxygenases (MMOs) to activate methane, oxidizing it to methanol. There are two types of MMOs: a particulate, membrane-bound enzyme (pMMO) and a soluble, cytoplasmic enzyme (sMMO). The two MMOs are completely unrelated, with different architectures, metal cofactors, and mechanisms. The more prevalent of the two, pMMO, is copper-dependent, but the identity of its copper active site remains unclear. By contrast, sMMO uses a diiron active site, the catalytic cycle of which is well understood. Here we review the current state of knowledge for both MMOs, with an emphasis on recent developments and emerging hypotheses. In addition, we discuss obstacles to developing expression systems, which are needed to address outstanding questions and to facilitate future protein engineering efforts.
Project description:Several factors impact successful reintegration after incarceration. We sought to better understand these factors such as pre-release preparedness or access to financial resources in provincial correctional facilities in Ontario, Canada with an underlying focus on the role of personal identification (PID) among people at risk of homelessness. We conducted a qualitative study with one-on-one telephone interviews. Eligibility criteria included having been released from a provincial correctional facility in the preceding 2 years, being over the age of 18, speaking English and having telephone access. Participants were recruited between February 2021 and July 2021. All interviews were audio recorded and transcribed. Data was analyzed using a thematic analysis framework along with strategies from grounded theory research. We interviewed 12 individuals and identified six key themes including 1) Degree of Preparedness Pre-Release 2) Managing Priorities Post-Release 3) Impact of Support Post-Release 4) Obstacles with Accessing Services 5) Influence of Personal Identification 6) Emotions and Uncertainty. We found that people with mental health and addiction challenges are uniquely at risk post-release. Solutions must include comprehensive and proactive case management that bridges the pre-release and post-release periods, simplified processes for obtaining PID, better connections to health and social services, and improved pre-release planning for community support.
Project description:Small RNAs (sRNAs) are short, transcribed regulatory elements that are typically encoded in the intergenic regions (IGRs) of bacterial genomes. Several sRNAs, first recognized in Escherichia coli, are conserved among enteric bacteria, but because of the regulatory roles of sRNAs, differences in sRNA repertoires might be responsible for features that differentiate closely related species. We scanned the E. coli MG1655 and Salmonella enterica Typhimurium genomes for nonsyntenic IGRs as a potential source of uncharacterized, species-specific sRNAs and found that genome rearrangements have reconfigured several IGRs causing the disruption and formation of sRNAs. Within an IGR that is present in E. coli but was disrupted in Salmonella by a translocation event is an sRNA that is associated with the FNR/CRP global regulators and influences E. coli biofilm formation. A Salmonella-specific sRNA evolved de novo through point mutations that generated a σ(70) promoter sequence in an IGR that arose through genome rearrangement events. The differences in the sRNA pools among bacterial species have previously been ascribed to duplication, deletion, or horizontal acquisition. Here, we show that genomic rearrangements also contribute to this process by either disrupting sRNA-containing IGRs or creating IGRs in which novel sRNAs may evolve.
Project description:Polyphosphate kinases (PPKs) have become popular biocatalysts for nucleotide 5'-triphosphate (NTP) synthesis and regeneration. Two unrelated families are described: PPK1 and PPK2. They are structurally unrelated and use different catalytic mechanisms. PPK1 enzymes prefer the usage of adenosine 5'-triphosphate (ATP) for polyphosphate (polyP) synthesis while PPK2 enzymes favour the reverse reaction. With the emerging use of PPK enzymes in biosynthesis, a deeper understanding of the enzymes and their thermodynamic reaction course is of need, especially in comparison to other kinases. Here, we tested four PPKs from different organisms under the same conditions without any coupling reactions. In comparison to other kinases using phosphate donors with comparably higher phosphate transfer potentials that are characterised by reaction yields close to full conversion, the PPK-catalysed reaction reaches an equilibrium in which about 30% ADP is left. These results were obtained for PPK1 and PPK2 enzymes, and are supported by theoretical data on the basic reaction. At high concentrations of substrate, the different kinetic preferences of PPK1 and PPK2 can be observed. The implications of these results for the application of PPKs in chemical synthesis and as enzymes for ATP regeneration systems are discussed.
Project description:Event memories are characterized by the holistic retrieval of their constituent elements. Studies show that memory for individual event elements (e.g. person, object and location) are statistically related to each other, and that the same associative memory structure can be formed by learning all pairwise associations across separated encoding contexts (person-object, person-location, object-location). Counter to previous studies that have shown no differences in holistic retrieval between simultaneously and separately encoded event elements, adults did not show evidence of holistic retrieval from separately encoded event elements when using a similar paradigm adapted for children (Experiment 1). We conducted a further five online experiments to explore the conditions under which holistic retrieval emerges following separated encoding of within-event associations, testing for influences of trial length (Experiment 2), the number of events learned (Experiment 3a) and stimulus presentation format (Experiments 3b, 4a, 4b). Presentation of written words was optimal for integrating elements across encoding trials, whereas the addition of spoken words disrupted integration across separately presented associations. The use of picture stimuli also produced effect sizes smaller than those of previously published research. We discuss the ways in which memory integration processes may be disrupted by these differences in presentation format. The findings have practical implications for the utility of this paradigm across research and learning contexts.
Project description:Distinct from normal differentiated tissues, cancer cells reprogram nutrient uptake and utilization to accommodate their elevated demands for biosynthesis and energy production. A hallmark of these types of reprogramming is the increased utilization of, and dependency on glutamine, a nonessential amino acid, for cancer cell growth and survival. It is well-accepted that glutamine is a versatile biosynthetic substrate in cancer cells beyond its role as a proteinogenic amino acid. In addition, accumulating evidence suggests that glutamine metabolism is regulated by many factors, including tumor origin, oncogene/tumor suppressor status, epigenetic alternations and tumor microenvironment. However, despite the emerging understanding of why cancer cells depend on glutamine for growth and survival, the contribution of glutamine metabolism to tumor progression under physiological conditions is still under investigation, partially because the level of glutamine in the tumor environment is often found low. Since targeting glutamine acquisition and utilization has been proposed to be a new therapeutic strategy in cancer, it is central to understand how tumor cells respond and adapt to glutamine starvation for optimized therapeutic intervention. In this review, we first summarize the diverse usage of glutamine to support cancer cell growth and survival, and then focus our discussion on the influence of other nutrients on cancer cell adaptation to glutamine starvation as well as its implication in cancer therapy.
Project description:The linear relations between adsorption energies are one of the cornerstones of contemporary catalysis in view of the simplicity and predictive power of the computational models built upon them. Despite their extensive use, the exact nature of scaling relations is not yet fully understood, and a comprehensive theory of scaling relations is yet to be elaborated. So far, it is known that scalability is dictated by the degree of resemblance of the adsorbed species. In this work, density functional theory calculations show that CO and OH, two dissimilar species, scale or not depending on the surface facet where they adsorb at Pt alloys. This peculiar behavior arises from an interplay of ligand and geometric effects that can be used to modulate adsorption-energy scalability. This study opens new possibilities in catalysis, as it shows that surface coordination is a versatile tool to either balance or unbalance the similarities among adsorbates at alloy surfaces.
Project description:AudienceThe target audience for this small group session is emergency medicine residents, primarily for use in didactic conference. This session can also be utilized with medical students, or faculty looking to review relevant hand anatomy and common injuries.IntroductionThree-dimensional (3D) printing is an emerging technology that has the ability to produce highly accurate anatomic, cellular and medical device models. Limited research has shown promise in teaching anatomy,1 congenital heart disease2 and surgical pre-operative planning.3 Despite this potential, there is sparse evidence of 3D printing emergency medicine residency education. The Model of Clinical Practice of Emergency Medicine specifies content for American Board of Emergency Medicine certification and requires proficiency in a wide breadth of medical topics including upper extremity and hand injuries.4 The concepts of hand anatomy and function rely heavily on understanding spatial relationships between bones, tendons and ligaments. The instructional strategy of working with 3D printed hand models aligns with these learning goals. This project seeks to directly incorporate 3D printing into the orthopedic curriculum of emergency medicine residents during a required weekly didactic educational session.Educational objectivesBy the end of this session, learners should be able to name and identify all bones of the hand; arrange and construct an anatomically correct bony model of the hand; build functional phalangeal flexor and extensor tendon complexes onto a bony hand model; describe the mechanism of injury, exam findings, and management of the tendon injuries Jersey finger, Mallet finger, and central slip rupture; draw/recreate injury patterns on a bony hand model; and describe the mechanism of injury, exam findings, imaging findings, and management of scapholunate dissociation, perilunate dislocation and lunate dislocation, Bennett's fracture, Rolando fracture, Boxer's fracture and scaphoid.Educational methodsThis session was delivered in a small group session which utilized educational methods grounded in constructivist learning such as complex problem-solving, social negotiation, and spatial learning.Research methodsVerbal feedback was obtained after the session.ResultsOverall learners found the session engaging, interactive, and especially useful in demonstrating relevant hand anatomy and injuries. Learners felt that hands-on experience with the hand models reinforced knowledge and helped them better identify injuries in a spatial fashion.TopicsExtremity bony trauma, dislocations/subluxations, tendon injuries.
Project description:Multidrug products enable more effective therapies and simpler administration regimens, provided that a stable formulation is prepared, with the desired composition. In this view, solid solutions have the advantage of combining the stability of a single crystalline phase with the potential of stoichiometry variation of a mixture. Here a drug-prodrug solid solution of cortisone and cortisol (hydrocortisone) is described. Despite the structural differences of the two components, the new phase is obtained both from solution and by supercritical CO2 assisted spray drying. In particular, to enter the solid solution, hydrocortisone must violate Etter's rules for hydrogen bonding. As a result, its dissolution rate is almost doubled.
Project description:Biodiversity can reduce or increase disease transmission. These divergent effects suggest that community composition rather than diversity per se determines disease transmission. In natural plant communities, little is known about the functional roles of neighbouring plant species in belowground disease transmission. Here, we experimentally investigated disease transmission of a fungal root pathogen (Rhizoctonia solani) in two focal plant species in combinations with four neighbour species of two ages. We developed stochastic models to test the relative importance of two transmission-modifying mechanisms: (1) infected hosts serve as nutrient supply to increase hyphal growth, so that successful disease transmission is self-reinforcing; and (2) plant resistance increases during plant development. Neighbouring plants either reduced or increased disease transmission in the focal plants. These effects depended on neighbour age, but could not be explained by a simple dichotomy between hosts and nonhost neighbours. Model selection revealed that both transmission-modifying mechanisms are relevant and that focal host-neighbour interactions changed which mechanisms steered disease transmission rate. Our work shows that neighbour-induced shifts in the importance of these mechanisms across root networks either make or break disease transmission chains. Understanding how diversity affects disease transmission thus requires integrating interactions between focal and neighbour species and their pathogens.