DAB2IP loss in luminal a breast cancer leads to NF-κB-associated aggressive oncogenic phenotypes.

Despite proven therapy options for estrogen receptor-positive (ER+) breast tumors, a substantial number of patients with ER+ breast cancer exhibit relapse with associated metastasis. Loss of expression of RasGAPs leads to poor outcomes in several cancers, including breast cancer. Mining the The Cancer Genome Atlas (TCGA) breast cancer RNA-Seq dataset revealed that low expression of the RasGAP DAB2IP was associated with a significant decrease in relapse-free survival in patients with Luminal A breast cancer.

Quantifying in vitro B. anthracis growth and PA production and decay: a mathematical modelling approach.

Protective antigen (PA) is a protein produced by Bacillus anthracis. It forms part of the anthrax toxin and is a key immunogen in US and UK anthrax vaccines. In this study, we have conducted experiments to quantify PA in the supernatants of cultures of B.

Marmosets as models of infectious diseases.

Animal models of infectious disease often serve a crucial purpose in obtaining licensure of therapeutics and medical countermeasures, particularly in situations where human trials are not feasible, i.e., for those diseases that occur infrequently in the human population.

Layering vaccination with antibiotic therapy results in protection and clearance of in Balb/c mice.

Melioidosis is a disease that is difficult to treat due to the causative organism, being inherently antibiotic resistant and it having the ability to invade, survive, and replicate in an intracellular environment. Combination therapy approaches are routinely being evaluated in animal models with the aim of improving the level of protection and clearance of colonizing bacteria detected. In this study, a subunit vaccine layered with the antibiotic finafloxacin was evaluated against an inhalational infection with in Balb/c mice.

A self-amplifying RNA vaccine provides protection in a murine model of bubonic plague.

Mice were immunized with a combination of self-amplifying (sa) RNA constructs for the F1 and V antigens of at a dose level of 1 μg or 5 μg or with the respective protein sub-units as a reference vaccine. The immunization of outbred OF1 mice on day 0 and day 28 with the lowest dose used (1 μg) of each of the saRNA constructs in lipid nanoparticles protected 5/7 mice against subsequent sub-cutaneous challenge on day 56 with 180 cfu (2.8 MLD) of a 2021 clinical isolate of termed 10-21/S whilst 5/7 mice were protected against 1800cfu (28MLD) of the same bacteria on day 56.

Tumour Necrosis Factor-α, Chemokines, and Leukocyte Infiltrate Are Biomarkers for Pathology in the Brains of Venezuelan Equine Encephalitis (VEEV)-Infected Mice.

Venezuelan equine encephalitis virus (VEEV) is a disease typically confined to South and Central America, whereby human disease is characterised by a transient systemic infection and occasionally severe encephalitis, which is associated with lethality. Using an established mouse model of VEEV infection, the encephalitic aspects of the disease were analysed to identify biomarkers associated with inflammation. Sequential sampling of lethally challenged mice (infected subcutaneously) confirmed a rapid onset systemic infection with subsequent spread to the brain within 24 h of the challenge.

Fouling Resistance of Brush-Modified Elastomers.

The most effective antifouling coatings are designed to slowly release biocides that target a broad spectrum of marine organisms. However, as biocides have a deleterious effect on marine life, there is demand for environmentally friendly coatings that resist fouling through physical interactions. We propose a simple platform for the development of such coatings based on bottlebrush-modified elastomers.

Assessment of CD200R Activation in Combination with Doxycycline in a Model of Melioidosis.

Antimicrobial resistance continues to be a global issue. Pathogens, such as Burkholderia pseudomallei, have evolved mechanisms to efflux certain antibiotics and manipulate the host response. New treatment strategies are therefore required, such as a layered defense approach.

Tailoring the Wettability and Substrate Adherence of Thin Polymer Films with Surface-Segregating Bottlebrush Copolymer Additives.

We developed "reactive" bottlebrush polymers based on styrene (S) and -butyl acrylate (tBA) as additives for polystyrene (PS) coatings. The bottlebrush polymers spontaneously bloom to both the air and substrate interfaces during solution casting. While neat PS films are hydrophobic and poorly adhere to the native oxide on clean silicon wafers, the hydrophilicity and substrate adherence of bottlebrush-incorporating PS films can be tailored through the thermally activated deprotection of tBA to produce acrylic acid (AA) and acrylic anhydride (AH).

Efficacy of finafloxacin in a murine model of inhalational glanders.

, the causative agent of glanders, is principally a disease of equines, although it can also infect humans and is categorized by the U.S. Centers for Disease Control and Prevention as a category B biological agent.

Considerations in the design of animal infection pilot studies.

Ethical research with experimental systems (animals or humans) requires a rationale for the number of subjects to be included in a study. Standard methods for estimating sample size are not fit-for-purpose when the experimenter cannot predict the effect size/outcome with any certainty. These types of studies are often designated "pilot study"; however, there are few guidelines for sample size needed for a pilot study.

An Investigation into the Re-Emergence of Disease Following Cessation of Antibiotic Treatment in Balb/c Mice Infected with Inhalational .

is the causative agent of melioidosis, a multifaceted disease. A proportion of the mortality and morbidity reported as a result of infection with this organism may be due to the premature cessation of antibiotic therapy typically lasting for several months. The progression of re-emergent disease was characterised in Balb/c mice following cessation of a 14 day treatment course of co-trimoxazole or finafloxacin, delivered at a human equivalent dose.

Investigation of a combination therapy approach for the treatment of melioidosis.

The efficacy of finafloxacin as a component of a layered defense treatment regimen was determined and against an infection with . Doxycycline was down-selected from a panel of antibiotics evaluated and used in combination with finafloxacin in a Balb/c mouse model of inhalational melioidosis. When treatment was initiated at 24 h post-infection with , there were no differences in the level of protection offered by finafloxacin or doxycycline (as monotherapies) when compared to the combination therapy.

Early Isolates of SARS-CoV-2 Result in Different Pathogenesis in the Transduced Mouse Model of COVID-19.

A transduced mouse model of SARS-CoV-2 infection was established using Balb/c mice. This was achieved through the adenovirus-vectored delivery of the hACE2 gene, to render the mice transiently susceptible to the virus. The model was characterised in terms of the dissemination of hACE2 receptor expression, the dissemination of three SARS-CoV-2 virus variants in vivo up to 10 days following challenge, the resulting histopathology and the clinical signs induced in the mice.

Histopathological and Immunological Findings in the Common Marmoset Following Exposure to Aerosolized SARS-CoV-2.

There is an enduring requirement to develop animal models of COVID-19 to assess the efficacy of vaccines and therapeutics that can be used to treat the disease in humans. In this study, six marmosets were exposed to a small particle aerosol (1-3 µm) of SARS-CoV-2 VIC01 that delivered the virus directly to the lower respiratory tract. Following the challenge, marmosets did not develop clinical signs, although a disruption to the normal diurnal temperature rhythm was observed in three out of six animals.

Predictors of Survival after Vaccination in a Pneumonic Plague Model.

The need for an updated plague vaccine is highlighted by outbreaks in endemic regions together with the pandemic potential of this disease. There is no easily available, approved vaccine. Here we have used a murine model of pneumonic plague to examine the factors that maximise immunogenicity and contribute to survival following vaccination.

The Innate Immune Response in the Marmoset during the Acute Pneumonic Disease Caused by Burkholderia pseudomallei.

Burkholderia pseudomallei is the causative agent of melioidosis, a severe human infection that is difficult to treat with antibiotics and for which there is no effective vaccine. Development of novel treatments rely upon appropriately characterized animal models. The common marmoset (Callithrix jacchus) has been established at Defense Science and Technology laboratories (DSTL) as a model of melioidosis.

Understanding interfacial segregation in polymer blend films with random and mixed side chain bottlebrush copolymer additives.

Bottlebrush polymers are complex macromolecules with tunable physical properties dependent on the chemistry and architecture of both the side chains and the backbone. Prior work has demonstrated that bottlebrush polymer additives can be used to control the interfacial properties of blends with linear polymers but has not specifically addressed the effects of bottlebrush side chain microstructures. Here, using a combination of experiments and self-consistent field theory (SCFT) simulations, we investigated the effects of side chain microstructures by comparing the segregation of bottlebrush additives having random copolymer side chains with bottlebrush additives having a mixture of two different homopolymer side chain chemistries.

A Stochastic Intracellular Model of Anthrax Infection With Spore Germination Heterogeneity.

We present a stochastic mathematical model of the intracellular infection dynamics of in macrophages. Following inhalation of spores, these are ingested by alveolar phagocytes. Ingested spores then begin to germinate and divide intracellularly.

Monoclonal Antibodies Opsonize spp. and Reduce Intracellular Actin Tail Formation in a Macrophage Infection Assay.

Melioidosis is a neglected tropical disease caused by the bacterium Burkholderia pseudomallei. The bacterium is intrinsically resistant to various antibiotics, and melioidosis is therefore difficult to treat successfully without a relapse in infection. B.

Investigative study into whether an insect repellent has virucidal activity against SARS-CoV-2.

A small-scale study with Mosi-guard Natural spray, an insect repellent containing Citriodiol, was performed to determine if it has virucidal activity against SARS-CoV-2. A liquid test examined the activity of the insect repellent and the individual components for virucidal activity. A surface contact test looked at the activity of the insect repellent when impregnated on a latex surface as a synthetic skin for potential topical prophylactic application.

How Should We Respond to Racist Legacies in Health Professions Education Originating in the Flexner Report?

The Flexner Report damaged and marginalized historically Black medical schools, which today produce more than their fair share of Black medical graduates. As physicians, graduates of Black medical schools have confronted head-on the inequities of American responses to COVID-19 that the pandemic has laid bare to the world. Black physicians' leadership roles in American health care and in American communities have informed the reimagination of health care and medical education as just and inclusive.

Finafloxacin Is an Effective Treatment for Inhalational Tularemia and Plague in Mouse Models of Infection.

Infection with aerosolized or can lead to lethal disease in humans if treatment is not initiated promptly. Finafloxacin is a novel fluoroquinolone which has demonstrated broad-spectrum activity against a range of bacterial species , and in humans, activity which is superior in acidic, infection-relevant conditions. Human-equivalent doses of finafloxacin or ciprofloxacin were delivered at 24 h (representing prophylaxis) or at 72 or 38 h (representing treatment) postchallenge with or , respectively, in BALB/c mouse models.