Microglial Cell Activation Increases Saturated and Decreases Monounsaturated Fatty Acid Content,but Both Lipid Species are Proinflammatory

Neuroinflammation is a component of age-related neurodegenerative diseases and cognitive decline. Saturated (SFA) and monounsaturated (MUFA) fatty acids are bioactive molecules that may play different extrinsic and intrinsic roles in neuroinflammation, serving as exogenous ligands for cellular receptors, or endogenous components of cell structural, energetic and signaling pathways. We determined the fatty acyl profile of BV2 microglial cells before and after acute activation with lipopolysaccharide (LPS). We also investigated the effect of SFA and MUFA pretreatment on the production of an invasive, neurotoxic phenotype in BV2 cells. Acute activation of BV2 microglia resulted in an increase in the relative content of SFA (12:0, 16:0, 18:0, 20:0, 22:0, and 24:0 increased significantly), and a relative decrease in the content of MUFA (16:1n7, 18:1n7, 18:1n9, 20:1n9, 24:1n9 decreased significantly). In agreement, the major stearoyl-CoA desaturase (SCD) isoform in BV2 cells, SCD2, was significantly down-regulated by LPS. We next treated cells with SFA (16:0 or 18:0) or MUFA (16:1n7 or 18:1n9), and found that levels of secreted IL6 were increased, as was secreted MMP9-mediated proteolytic activity. To test the functional significance, we treated SH-SY5Y neuronal cells with conditioned medium from BV2 cells pretreated with fatty acids, and found a small but significant induction of cell death. Our findings suggest differential intrinsic roles for SFA and MUFA in activated microglial cells, but similar extrinsic roles for these fatty acid species in inducing activation. Expansion of SFA is important during microglial cell activation, but either supplemental SFA or MUFA may contribute to chronic low-grade neuroinflammation.     

Antibody-Based Tracers for PET/SPECT Imaging of Chronic Inflammatory Diseases

Chronic inflammatory diseases are often progressive, resulting not only in physical damage to patients but also social and economic burdens, making early diagnosis of them critical. Nuclear medicine techniques can enhance the detection of inflammation by providing functional as well as anatomical information when combined with other modalities such as magnetic resonance imaging, computed tomography or ultrasonography. Although small molecules and peptides were mainly used for the treatment and imaging of chronic inflammatory diseases in the past, antibodies and their fragments have also been emerging for chronic inflammatory diseases as they show high specificity to their targets and can have various biological half-lives depending on how they are engineered. In addition, imaging with antibodies or their fragments can visualize the in vivo biodistribution of the probes or help monitor therapeutic responses, thereby providing physicians with a greater understanding of drug behavior in vivo and another means of monitoring their patients. In this review, we introduce various targets and radiolabeled antibody-based probes for the molecular imaging of chronic inflammatory diseases in preclinical and clinical studies. Targets can be classified into three different categories: 1) cell-adhesion molecules, 2) surface markers on immune cells, and 3) cytokines or enzymes. The limitations and future directions of using radiolabeled antibodies for imaging inflammatory diseases are also discussed.     

Gene Discovery in Gelsemium Highlights Conserved Gene Clusters in Monoterpene Indole Alkaloid Biosynthesis

Genome mining is a routine technique in microbes for discovering biosynthetic pathways. In plants, however, genomic information is not commonly used to identify novel biosynthesis genes. Here, we present the genome of the medicinal plant and oxindole monoterpene indole alkaloid (MIA) producer Gelsemium sempervirens (Gelsemiaceae). A gene cluster from Catharanthus roseus, which is utilized at least six enzymatic steps downstream from the last common intermediate shared between the two plant alkaloid types, is found in G. sempervirens, although the corresponding enzymes act on entirely different substrates. This study provides insights into the common genomic context of MIA pathways and is an important milestone in the further elucidation of the Gelsemium oxindole alkaloid pathway.     

The Innate Immune Glycoprotein Lactoferrin Represses the Helicobacter pylori cag Type IV Secretion System

Chronic infection with Helicobacter pylori increases risk of gastric diseases including gastric cancer. Despite development of a robust immune response, H. pylori persists in the gastric niche. Progression of gastric inflammation to serious disease outcomes is associated with infection with H. pylori strains which encode the cag Type IV Secretion System (cag T4SS). The cag T4SS is responsible for translocating the oncogenic protein CagA into host cells and inducing pro-inflammatory and carcinogenic signaling cascades. Our previous work demonstrated that nutrient iron modulates the activity of the T4SS and biogenesis of T4SS pili. In response to H. pylori infection, the host produces a variety of antimicrobial molecules, including the iron-binding glycoprotein, lactoferrin. Our work shows that apo-lactoferrin exerts antimicrobial activity against H. pylori under iron-limited conditions, while holo-lactoferrin enhances bacterial growth. Culturing H. pylori in the presence of holo-lactoferrin prior to co-culture with gastric epithelial cells, results in repression of the cag T4SS activity. Concomitantly, a decrease in biogenesis of cag T4SS pili at the host-pathogen interface was observed under these culture conditions by high-resolution electron microscopy analyses. Taken together, these results indicate that acquisition of alternate sources of nutrient iron plays a role in regulating the pro-inflammatory activity of a bacterial secretion system and present novel therapeutic targets for the treatment of H. pylori-related disease.     

The distribution,density, and biomass of the zebra mussel (Dreissena polymorpha) on natural substrates in Lake Winnipeg 2017–2019

The distribution, density, biomass and size-structure of the zebra mussel (Dreissena polymorpha) population in Lake Winnipeg were examined between 2017 and 2019. Zebra mussels have colonized most of the available hard substrate in the south basin and Narrows region, but colonization of the north basin remains low at present, even on suitable substrate. Numerical densities and shell free biomass peaked at 5530 ± 953 m^?2 and 64.7 ± 57.9 g shell free dry mass m^?2 respectively. The distribution appeared to be strongly limited by substrate type and availability, with further limitations on the distribution imposed by physical disturbance in shallow waters and unsuitable substrate in deeper areas of the lake. Zebra mussels <1 year old dominated the populations, and individuals >18 mm were exceedingly rare. Poor recruitment was observed at sites along the eastern side of the south basin compared to elsewhere in the lake. The proximate causes of these differences in colonization success and recruitment are not clear, but may be in part due to heterogeneous patterns of key physico-chemical environmental conditions such as calcium concentrations required for successful development of juvenile mussels and colder water temperatures in the north basin. This study provides a baseline of information on which to track further expansion of zebra mussels in Lake Winnipeg and assist efforts to develop an understanding of how zebra mussels may affect the ecology of Lake Winnipeg.     

Susceptibility of Escherichia coli O157 to chitosan‐arginine in beef liquid purge is affected by bacterial cell growth phase

Here, we evaluated the impact of bacterial growth stage on the effect of chitosan‐arginine (Ch‐arg) on Escherichia coli O157:H7 cell numbers and metabolic activity within contaminated beef juice held at room temperature. Using a lux‐marked metabolic reporter strain of E. coli O157:H7, the results showed that Ch‐arg was most bioactive against cells in the lag phase and exponential phase. In comparison, there was a reduced, although still significant, inhibitory effect of Ch‐arg on the viability and metabolic activity of E. coli O157 held in stationary phase. Ch‐arg reduced, but did not eliminate E. coli O157 growth in the meat juice over 48 h. Based on the evidence presented here and elsewhere, we conclude that Ch‐arg can limit the growth and activity of food spoilage bacteria; however, it cannot completely eliminate bacterial contaminants originally present. Ch‐arg should therefore be viewed as a potentially protective measure rather than a biocidal agent that completely eliminates the risk of pathogen transfer in the food chain.     

Calcium and Vitamin D in the Regulation of Energy Balance: Where Do We Stand?

There is a pandemic of obesity and associated chronic diseases. Dietary calcium and vitamin D have many extra-skeletal roles in human health. In this review we have summarized the current understanding of their influence on human energy balance by examining the epidemiological, clinical, animal, cellular and molecular evidence. We opine that while calcium and vitamin D are functional nutrients in the battle against obesity, there is a need for prospective human trials to tilt the balance of evidence in favour of these nutrients.     

Community Solar Presents Rewards and Risks

Communities, private companies, and households are increasingly turning to community solar as a way to fulfill sustainability and renewable energy goals. And for good reason—community solar can provide significant financial, social, environmental, and public relations benefits. However, due to the relatively new market and variability in financial projections and because each solar garden program and project is unique, participation in community solar comes with its own benefits, limitations, and uncertainties.     

Alternative work schedule interventions in the Australian construction industry: a comparative case study analysis

Project‐based construction workers in the Australian construction industry work long and irregular hours and experience higher levels of work‐to‐family conflict and burnout than office‐based workers, giving rise to an interest in alternative work schedules as a means of supporting work–life balance. Alternative work schedules were implemented in four case study construction projects in Australia. Interventions differed between projects, with two implementing a compressed work week, and the others introducing reduced hours schedules (one of which was optional). Data were collected from each case study project, using various combinations of focus groups, surveys, interviews and daily diary collection methods. The results were mixed. The compressed work week appears to have been favourably received where it was introduced. However, waged workers still expressed concerns about the impact on their weekly ‘take‐home’ pay. Attempts to reduce work hours by changing from a six‐ to a five‐day schedule (without extending the length of the working day between Monday and Friday) were less favourably received. Waged workers, in particular, did not favour reduced hours schedules. The results confirm the existence of two distinct labour markets operating in the Australian construction industry and markedly different responses to alternative work schedules, based upon whether workers are waged or salaried. The results clearly show that attempts to improve work–life balance must take the structural characteristics of the industry's labour markets into consideration in the design of interventions. The impact of alternative work schedules is likely to be moderated by institutional working time regimes within the construction industry.