Immune profile diversity is achieved with synthetic TLR4 agonists combined with the RG1-VLP vaccine in mice.

The TLR4 (Toll-like receptor 4)-activating agonist MPLA (monophosphoryl lipid A) is a key component of the adjuvant systems AS01 and AS04, utilized in marketed preventive vaccines for several infectious pathogens. As MPLA is a biologically-derived product containing a mixture of several lipid A congeners with a 4' phosphoryl group and varying numbers of acyl chains with distinct activities, extensive efforts to refine its production and immunogenicity are ongoing; notably, the development of the BECC (Bacterial Enzymatic Combinatorial Chemistry) system in which bacteria express lipid A-modifying enzymes to produce a panoply of lipid A congeners. In an effort to characterize the adjuvant activity of these lipid A congeners, we compared biologically-derived and synthetic versions of BECC470 and BECC438 for adjuvant activity in BALB/c mice vaccinated with the HPV (Human papilloma virus) VLP-based vaccine, RG1-VLP.

Transfer RNA acetylation regulates in vivo mammalian stress signaling.

Transfer RNA (tRNA) modifications are crucial for protein synthesis, but their position-specific physiological roles remain poorly understood. Here we investigate the impact of N4-acetylcytidine (acC), a highly conserved tRNA modification, using a Thumpd1 knockout mouse model. We find that loss of Thumpd1-dependent tRNA acetylation leads to reduced levels of tRNA, increased ribosome stalling, and activation of eIF2α phosphorylation.

Analysis of Nanoparticles' Effects on Drug-Induced Psoriasis.

Psoriasis, an auto-inflammatory disorder, has major manifestations in the skin but can affect other organs. Currently, this condition has no cure, and the treatments include anti-inflammatory medications. Nanoparticles are widely used for drug delivery and have found successful applications in therapy for cancer and infectious diseases.

Organoids and metastatic orthotopic mouse model for mismatch repair-deficient colorectal cancer.

Background: Genome integrity is essential for the survival of an organism. DNA mismatch repair (MMR) genes (e.g.

Cross-neutralizing protection of vaginal and oral mucosa from HPV challenge by vaccination in a mouse model.

The species and tissue specificities of HPV (human papillomavirus) for human infection and disease complicates the process of prophylactic vaccine development in animal models. HPV pseudoviruses (PsV) that carry only a reporter plasmid have been utilized in vivo to demonstrate cell internalization in mouse mucosal epithelium. The current study sought to expand the application of this HPV PsV challenge model with both oral and vaginal inoculation and to demonstrate its utility for testing vaccine-mediated dual-site immune protection against several HPV PsV types.

Evaluation of Nonmodified Wireframe DNA Origami for Acute Toxicity and Biodistribution in Mice.

Wireframe DNA origami can be used to fabricate virus-like particles for a range of biomedical applications, including the delivery of nucleic acid therapeutics. However, the acute toxicity and biodistribution of these wireframe nucleic acid nanoparticles (NANPs) have not been previously characterized in animal models. In the present study, we observed no indications of toxicity in BALB/c mice following a therapeutically relevant dosage of nonmodified DNA-based NANPs via intravenous administration, based on liver and kidney histology, liver and kidney biochemistry, and body weight.

Evaluation of non-modified wireframe DNA origami for acute toxicity and biodistribution in mice.

Wireframe DNA origami can be used to fabricate virus-like particles for a range of biomedical applications, including the delivery of nucleic acid therapeutics. However, the acute toxicity and biodistribution of these wireframe nucleic acid nanoparticles (NANPs) have not previously been characterized in animal models. In the present study, we observed no indications of toxicity in BALB/c mice following therapeutically relevant dosage of unmodified DNA-based NANPs via intravenous administration, based on liver and kidney histology, liver biochemistry, and body weight.

Mesothelioma Mouse Models with Mixed Genomic States of Chromosome and Microsatellite Instability.

Malignant mesothelioma (MMe) is a rare malignancy originating from the linings of the pleural, peritoneal and pericardial cavities. The best-defined risk factor is exposure to carcinogenic mineral fibers (e.g.

Modelling mobile-based technology adoption among people with dementia.

The work described in this paper builds upon our previous research on adoption modelling and aims to identify the best subset of features that could offer a better understanding of technology adoption. The current work is based on the analysis and fusion of two datasets that provide detailed information on background, psychosocial, and medical history of the subjects. In the process of modelling adoption, feature selection is carried out followed by empirical analysis to identify the best classification models.

Targeted multicolor in vivo imaging over 1,000 nm enabled by nonamethine cyanines.

Recent progress has shown that using wavelengths between 1,000 and 2,000 nm, referred to as the shortwave-infrared or near-infrared (NIR)-II range, can enable high-resolution in vivo imaging at depths not possible with conventional optical wavelengths. However, few bioconjugatable probes of the type that have proven invaluable for multiplexed imaging in the visible and NIR range are available for imaging these wavelengths. Using rational design, we have generated persulfonated indocyanine dyes with absorbance maxima at 872 and 1,072 nm through catechol-ring and aryl-ring fusion, respectively, onto the nonamethine scaffold.

CENP-A overexpression promotes aneuploidy with karyotypic heterogeneity.

Chromosomal instability (CIN) is a hallmark of many cancers. Restricting the localization of centromeric histone H3 variant CENP-A to centromeres prevents CIN. CENP-A overexpression (OE) and mislocalization have been observed in cancers and correlate with poor prognosis; however, the molecular consequences of CENP-A OE on CIN and aneuploidy have not been defined.

Improvement of RG1-VLP vaccine performance in BALB/c mice by substitution of alhydrogel with the next generation polyphosphazene adjuvant PCEP.

Current human papillomavirus (HPV) vaccines provide substantial protection against the most common HPV types responsible for oral and anogenital cancers, but many circulating cancer-causing types remain for which vaccine coverage is lacking. In addition, all current HPV vaccines rely on aluminum salt-based adjuvant formulations that function through unclear mechanisms with few substitutes available. In an effort to expand the toolbox of available adjuvants suitable for HPV vaccines, we compared the immunogenicity of the RG1-VLP (virus-like particle) vaccine in BALB/c mice when formulated with either the aluminum hydroxide adjuvant Alhydrogel or the novel polyphosphazene macromolecular adjuvant poly[di (carboxylatoethylphenoxy) phosphazene] (PCEP).

Switching to Tenofovir Alafenamide in Elvitegravir-Based Regimens: Pharmacokinetics and Antiviral Activity in Cerebrospinal Fluid.

Background: Tenofovir alafenamide fumarate (TAF) co-formulated with elvitegravir (EVG; E), cobicistat (C), and emtricitabine (F), a recommended antiretroviral regimen, was evaluated for distribution and antiviral activity in cerebrospinal fluid (CSF) as well as neurocognitive (NC) performance change in participants switching from E/C/F/tenofovir disoproxil fumarate (TDF) to E/C/F/TAF.

Methods: This was a 24-week, single-arm, open-label study in treatment-experienced adults living with human immunodeficiency virus (HIV). Nine participants switched from E/C/F/TDF (150/150/200/300 mg once daily) to E/C/F/TAF (150/150/200/10 mg once daily) at week 12.

Interaction Between Physical Activity and Genes Related to Neurotrophin Signaling in Late-Life Cognitive Performance: The Cache County Study.

Research indicates that lifestyle and genetic factors influence the course of cognitive impairment in aging, but their interactions have not been well-examined. This study examined the relationship between physical activity and genotypes related to brain-derived neurotrophic factor (BDNF) in predicting cognitive performance in a sample of older adults with up to 12 years of follow-up. Physical activity levels (sedentary, light, and moderate/vigorous) were determined for the sample of 3,591 participants (57% female) without dementia.

Neuropsychiatric symptoms in patients with dementia and the longitudinal costs of informal care in the Cache County population.

Introduction: Severity of dementia and neuropsychiatric symptoms contribute to increasing informal care costs. We examined which neuropsychiatric symptoms subdomains (NPS-SD) were associated with informal costs in a population-based sample.

Methods: Dementia progression and informal costs (2015 dollars) were estimated from the Cache County Dementia Progression Study.

Nutritional Status is Associated With Severe Dementia and Mortality: The Cache County Dementia Progression Study.

Purpose: Studies have reported faster cognitive/functional decline in persons with dementia (PWD) with malnutrition. We investigated whether baseline nutritional status predicted severe dementia and mortality in a population-based sample.

Patients: A maximum of 300 PWD were assessed annually for up to 8.

Use of FDA approved medications for Alzheimer's disease in mild dementia is associated with reduced informal costs of care.

Unlabelled: ABSTRACTBackground:The use of FDA approved medications for Alzheimer's disease [AD; FDAAMAD; (cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists)] has been associated with symptomatic benefit with a reduction in formal (paid services) and total costs of care (formal and informal costs). We examined the use of these medications and their association with informal costs in persons with dementia.

Method: Two hundred eighty participants (53% female, 72% AD) from the longitudinal, population-based Dementia Progression Study in Cache County, Utah (USA) were followed up to ten years.

Modelling assistive technology adoption for people with dementia.

Purpose: Assistive technologies have been identified as a potential solution for the provision of elderly care. Such technologies have in general the capacity to enhance the quality of life and increase the level of independence among their users. Nevertheless, the acceptance of these technologies is crucial to their success.

HIV Distal Neuropathic Pain Is Associated with Smaller Ventral Posterior Cingulate Cortex.

Objective: . Despite modern antiretroviral therapy, HIV-associated neuropathy is one of the most prevalent, disabling and treatment-resistant complications of HIV disease. The presence and intensity of distal neuropathic pain is not fully explained by the degree of peripheral nerve damage.

Closer caregiver and care-recipient relationships predict lower informal costs of dementia care: The Cache County Dementia Progression Study.

Introduction: Identifying factors associated with lower dementia care costs is essential. We examined whether two caregiver factors were associated with lower costs of informal care.

Methods: A total of 271 care dyads of the Cache County Dementia Study were included.