Connecting women in the age of difference: Re-thinking gender in twenty-first century Aotearoa New Zealand

Editorial: This special issue of the Women’s Studies Journal is an exploration of the theme of difference and diversity among women in Aotearoa New Zealand in the twenty-first century. As a construct within feminist literature, ‘difference’ has, for over three decades, irrevocably altered the landscape of feminist politics – in both its scholarship and its praxis. Fundamental to the theories of difference that have emerged since the 1980s is the idea that women’s lived realities differ vastly depending on, amongst other variables, their sexual orientation, racial and ethnic background, religious beliefs, age and income status

A Shift in Central Metabolism Accompanies Virulence Activation in Pseudomonas aeruginosa.

The availability of energy has significant impact on cell physiology. However, the role of cellular metabolism in bacterial pathogenesis is not understood. We investigated the dynamics of central metabolism during virulence induction by surface sensing and quorum sensing in early-stage biofilms of the multidrug-resistant bacterium Pseudomonas aeruginosa We established a metabolic profile for P. aeruginosa using fluorescence lifetime imaging microscopy (FLIM), which reports the activity of NADH in live cells. We identified a critical growth transition period during which virulence is activated. We performed FLIM measurements and direct measurements of NADH and NAD+ concentrations during this period. Here, planktonic (low-virulence) and surface-attached (virulence-activated) populations diverged into distinct metabolic states, with the surface-attached population exhibiting FLIM lifetimes that were associated with lower levels of enzyme-bound NADH and decreasing total NAD(H) production. We inhibited virulence by perturbing central metabolism using citrate and pyruvate, which further decreased the enzyme-bound NADH fraction and total NAD(H) production and suggested the involvement of the glyoxylate pathway in virulence activation in surface-attached populations. In addition, we induced virulence at an earlier time using the electron transport chain oxidase inhibitor antimycin A. Our results demonstrate the use of FLIM to noninvasively measure NADH dynamics in biofilms and suggest a model in which a metabolic rearrangement accompanies the virulence activation period.IMPORTANCE The rise of antibiotic resistance requires the development of new strategies to combat bacterial infection and pathogenesis. A major direction has been the development of drugs that broadly target virulence. However, few targets have been identified due to the species-specific nature of many virulence regulators. The lack of a virulence regulator that is conserved across species has presented a further challenge to the development of therapeutics. Here, we identify that NADH activity has an important role in the induction of virulence in the pathogen P. aeruginosa This finding, coupled with the ubiquity of NADH in bacterial pathogens, opens up the possibility of targeting enzymes that process NADH as a potential broad antivirulence approach

Small Businesses Go Digital: Benefits, Trends, and Barriers of Digitalization

Digitalization—the conversion of business practices to digital tools— among small businesses has been growing rapidly. A website is just the beginning.The COVID-19 pandemic forced small businesses to rethink the ways they operate and accelerated digital tool adoption. In just half a year, the global rate of business digitalization accelerated by seven years. In July 2020, 60% of products or services were digitalized in North America, compared to only 33% in June 2017. According to the Census Bureau's Small Business Pulse Survey, on average 26.6% of businesses surveyed adopted or expanded their use of digital tools since the start of the pandemic.Small businesses make up around 44% of all U.S. economic activity, with about 92% of all small businesses being microbusinesses—defined as having fewer than 10 employees. Microbusinesses face a separate set of challenges when it comes to digitalization, particularly with cost and time. Despite challenges to digitalization, the adoption of digital tools has a largely positive impact on the businesses that digitalize and the economy at large. Consider, for example, that businesses that use many digital tools were significantly more likely to report revenue growth in the past year.Small businesses utilize a range of digital tools for a variety of reasons but there is potential for greater levels of adoption. The Bipartisan Policy Center (BPC) and Intuit have partnered to study the effects of and barriers to digitalization among microbusinesses

Environmental Programmatic Agreements (and MOUs) in Indiana

In this session we will discuss various programmatic agreements (PAs) used during the NEPA process: the Section 106 Minor Projects PA, Categorical Exclusion PA, Historic Bridge PA, Karst MOU, Tribal MOU, and Indiana and Northern Long-Eared Bat Range-Wide PA

Genetic factors regulating lung vasculature and immune cell functions associate with resistance to pneumococcal infection

Streptococcus pneumoniae is an important human pathogen responsible for high mortality and morbidity worldwide. The susceptibility to pneumococcal infections is controlled by as yet unknown genetic factors. To elucidate these factors could help to develop new medical treatments and tools to identify those most at risk. In recent years genome wide association studies (GWAS) in mice and humans have proved successful in identification of causal genes involved in many complex diseases for example diabetes, systemic lupus or cholesterol metabolism. In this study a GWAS approach was used to map genetic loci associated with susceptibility to pneumococcal infection in 26 inbred mouse strains. As a result four candidate QTLs were identified on chromosomes 7, 13, 18 and 19. Interestingly, the QTL on chromosome 7 was located within S. pneumoniae resistance QTL (Spir1) identified previously in a linkage study of BALB/cOlaHsd and CBA/CaOlaHsd F2 intercrosses. We showed that only a limited number of genes encoded within the QTLs carried phenotype-associated polymorphisms (22 genes out of several hundred located within the QTLs). These candidate genes are known to regulate TGFb signalling, smooth muscle and immune cells functions. Interestingly, our pulmonary histopathology and gene expression data demonstrated, lung vasculature plays an important role in resistance to pneumococcal infection. Therefore we concluded that the cumulative effect of these candidate genes on vasculature and immune cells functions as contributory factors in the observed differences in susceptibility to pneumococcal infection. We also propose that TGFbmediated regulation of fibroblast differentiation plays an important role in development of invasive pneumococcal disease.This work was supported by the European Union-funded Pneumopath Project HEALTH-F3-2009-222983. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer-reviewedPublisher Versio

Stem Cell Therapy for Spinal Cord Injuries

Stem cell-based therapies are an emerging branch of medicine with the purpose of restoring tissue function for patients with serious injuries, such as a spinal cord injury. As a result, scientists and engineers are increasing research efforts in the field of regenerative medicine. Due to the delicate nature of stem cells, producing the large quantity required for a successful therapy has proved challenging. In recent years, research has shown the potential of stem cell-based therapies, and thus there is a need for the commercialization of these treatments. The proposed facility targets the demand for spinal cord injury treatments and can support production for both clinical trials and a commercial release. Bioreactors designed specifically for the culture and growth of stem cells have flexibility in their ability to support different stem cell lines for various therapies. Small reactors in parallel can easily adapt to changes in production size. This process also takes advantage of the best options currently available for purification and preservation to maximize the product yield. Due to the strict regulations set in place by the FDA and lack of adequate funding, there is an untapped market for stem cell therapies for spinal cord injuries. Approximately 250,000 people in the United States suffer from spinal cord injuries, varying in severity, and this patient base increases at a rate of 12,000 new injuries every year (“Spinal Cord Injury Facts and Figures”, 2009). Future markets include expansion into Europe and Asia. There are two steps to this proposal: the upstream process and the downstream process. The upstream process includes the scale-up, differentiation, and purification of human embryonic stem cells; the downstream process consists of the scale-up of neurons for injection. The upstream process will be built initially and yield enough cells for clinical trials, without incurring the capital costs of building the entire plant. Upon success of the clinical trials, the downstream process will be built for maximum production. The profitability of this proposal is based on running 26 batches a year at 1.02x1010 cells per batch or 2.66x1011 cells per year. By targeting 5,000 patients, two percent of the current market, and charging $45,000 per dose, a profitable profile can be created. Assuming 50$961,892,600, and 242.81% respectively. Using a 50% production capacity allows for higher profit margins upon expansion. The proposed plan will meet the need of this growing market

Expression and upregulation of cathepsin S and other early molecules required for antigen presentation in activated hepatic stellate cells upon IFN-γ treatment

AbstractHepatic stellate cells (HSCs) have been shown to be able to activate T-cells and upregulate expression of surface molecules essential for this process, when treated with IFN-γ. But little is known about the early molecules expressed by activated hepatic stellate cells under the same treatment. In this study, we investigate the effect of IFN-γ on the transcription and expression of these early molecules in hepatic stellate cells. We show on the molecular level that activated rat hepatic stellate cells express the class II transactivator, the invariant chain (CD74), the MHC class II molecules, as well as cathepsin S, all of which are known to be responsible for the initial steps of successful antigen presentation. The mRNA and the protein expression level of these molecules is upregulated by IFN-γ. Importantly, IFN-γ increases cathepsin S activity, suggesting a possible involvement of this protease in CD74 processing. Our data also show that not only can the HSCs take up antigenic proteins, they can also process them. Our comparative study indicates that the rat HSC-T6 cell line displays sufficient similarity to the activated rat HSCs in order to serve as a model for in vitro studies on the molecular mechanisms of inflammatory response

Simulation Study of an LWFA-based Electron Injector for AWAKE Run 2

The AWAKE experiment aims to demonstrate preservation of injected electron beam quality during acceleration in proton-driven plasma waves. The short bunch duration required to correctly load the wakefield is challenging to meet with the current electron injector system, given the space available to the beamline. An LWFA readily provides short-duration electron beams with sufficient charge from a compact design, and provides a scalable option for future electron acceleration experiments at AWAKE. Simulations of a shock-front injected LWFA demonstrate a 43 TW laser system would be sufficient to produce the required charge over a range of energies beyond 100 MeV. LWFA beams typically have high peak current and large divergence on exiting their native plasmas, and optimisation of bunch parameters before injection into the proton-driven wakefields is required. Compact beam transport solutions are discussed.Comment: Paper submitted to NIMA proceedings for the 3rd European Advanced Accelerator Concepts Workshop. 4 pages, 3 figures, 1 table Changes after revision: Figure 2: figures 2 and 3 of the previous version collated with plots of longitudinal electric field Line 45: E_0 = 96 GV/m Lines 147- 159: evaluation of beam loading made more accurate Lines 107 - 124: discussion of simulation geometry move