A generalized multinomial probabilistic model for SARS-COV-2 infection prediction and public health intervention assessment in an indoor environment.

SARS-CoV-2 Omicron and its sub-lineages have become the predominant variants globally since early 2022. As of January 2023, over 664 million confirmed cases and over 6.7 million deaths had been reported globally.

Somatic Mutations and Alzheimer's Disease.

Alzheimer's disease (AD) represents a global health challenge, with an estimated 55 million people suffering from the non-curable disease across the world. While amyloid-β plaques and tau neurofibrillary tangles in the brain define AD proteinopathy, it has become evident that diverse coding and non-coding regions of the genome may significantly contribute to AD neurodegeneration. The diversity of factors associated with AD pathogenesis, coupled with age-associated damage, suggests that a series of triggering events may be required to initiate AD.

Outdoor PM concentration and rate of change in COVID-19 infection in provincial capital cities in China.

This study investigates thoroughly whether acute exposure to outdoor PM concentration, P, modifies the rate of change in the daily number of COVID-19 infections (R) across 18 high infection provincial capitals in China, including Wuhan. A best-fit multiple linear regression model was constructed to model the relationship between P and R, from 1 January to 20 March 2020, after accounting for meteorology, net move-in mobility (NM), time trend (T), co-morbidity (CM), and the time-lag effects. Regression analysis shows that P (β = 0.

Head Transplantation: The Immune System, Phantom Sensations, and the Integrated Mind.

The principal focus of this paper is to consider the implications of head and neck transplantation surgery on the issue of personal identity. To this end, it is noted that the immune system has not only been established to impose a level of self-identity on bodily cells, it has also been implicated in mental development and the regulation of mental state. In this it serves as a paradigm for the mind as the product of cephalic and extracephalic systems.

Failure to upregulate cell surface PD-1 is associated with dysregulated stimulation of T cells by TGN1412-like CD28 superagonist.

The CD28 superagonist (CD28SA) TGN1412 was administered to humans as an agent that can selectively activate and expand regulatory T cells but resulted in uncontrolled T cell activation accompanied by cytokine storm. The molecular mechanisms that underlie this uncontrolled T cell activation are unclear. Physiological activation of T cells leads to upregulation of not only activation molecules but also inhibitory receptors such as PD-1.

Therapeutic immunisation plus cytokine and hormone therapy improves CD4 T-cell counts, restores anti-HIV-1 responses and reduces immune activation in treated chronic HIV-1 infection.

Background: This randomised, open label, phase I, immunotherapeutic study investigated the effects of interleukin (IL)-2, granulocyte-macrophage colony-stimulating factor (GM-CSF), recombinant human growth hormone (rhGH), and therapeutic immunisation (a Clade B DNA vaccine) on combination antiretroviral therapy (cART)-treated HIV-1-infected individuals, with the objective to reverse residual T-cell dysfunction.

Methods: Twelve HIV-1(+) patients on suppressive cART with baseline CD4 T-cell counts >400 cells/mm(3) blood were randomised into one of three groups: (1) vaccine, IL-2, GM-CSF and rhGH (n=3); (2) vaccine alone (n=4); or (3) IL-2, GM-CSF and rhGH (n=5). Samples were collected at weeks 0, 1, 2, 4, 6, 8, 12, 16, 24 and 48.

T-cell signalling in antiretroviral-treated, aviraemic HIV-1-positive individuals is present in a raised state of basal activation that contributes to T-cell hyporesponsiveness.

Objective: Successful antiretroviral therapy (ART) suppresses plasma HIV-1 RNA below detection limits, reducing the chronic insult to the immune systems of infected individuals and supporting a degree of immunological recovery. However, the surface phenotypic profile of T cells in ART-treated patients does not resemble that of healthy, uninfected individuals, but rather shows upregulation of proteins associated with an exhausted immune system. We sought to address whether aviraemic HIV-1 infection, therefore, contributed to long-term alterations in intracellular signalling events within the T cells of infected individuals that contributed to the exhausted phenotype.

Effects of recombinant human growth hormone on HIV-1-specific T-cell responses, thymic output and proviral DNA in patients on HAART: 48-week follow-up.

Background: Efficacious immune-based therapy in treated chronic HIV-1 infection requires the induction of virus-specific CD4+ T cells and subsequent maturation and maintenance of specific memory CD8+ T cells. Concomitant daily administration of recombinant human growth hormone (rhGH) with highly active antiretroviral therapy (HAART) was used in chronically infected patients with lipodystrophy in an attempt to reconstitute these virus-specific T-cell responses.

Methods: Individuals with chronic HIV-1 infection on HAART were enrolled on a randomized, double-blinded, placebo-controlled study to receive rhGH therapy.

T-cell signalling and immune system disorders.

T-cell receptor (TCR) engagement initiates intracellular signalling cascades that lead to T-cell proliferation, cytokine production and differentiation into effector cells. These cascades comprise an array of protein-tyrosine kinases, phosphatases, GTP-binding proteins and adaptor proteins that regulate generic and specialised functions. The integration of these signals is essential for the normal development, homeostasis and function of T cells.

Frequency and distribution of AP-1 sites in the human genome.

The AP-1-binding sequences are promoter/enhancer elements that play an essential role in the induction of many genes in mammalian cells; however, the number of genes containing AP-1 sites remains unknown. In order to better address the overall effect of AP-1 on expression of genes encoded by the entire genome, a genome-wide analysis of the frequency and distribution of AP-1 sites would be useful; yet to date, no such analysis of AP-1 sites or any other promoter/enhancer elements has been performed. We present here our study of the consensus AP-1 site and two single-bp variants showing that the frequency of AP-1 sites in promoter regions is significantly lower than their average rate of occurrence in the whole genomic sequence, as well as the frequency of a random heptanucleotide suggesting that nature has selected for a decrease in the frequency of AP-1 sites in the regulatory regions of genes.