Tumor cell programmed death ligand 1-mediated T cell suppression is overcome by coexpression of CD80

Programmed death ligand 1 (PDL1, or B7-H1) is expressed constitutively or is induced by IFN-γ on the cell surface of most human cancer cells and acts as a "molecular shield" by protecting tumor cells from T cell-mediated destruction. Using seven cell lines representing four histologically distinct solid tumors (lung adenocarcinoma, mammary carcinoma, cutaneous melanoma, and uveal melanoma), we demonstrate that transfection of human tumor cells with the gene encoding the costimulatory molecule CD80 prevents PDL1-mediated immune suppression by tumor cells and restores T cell activation. Mechanistically, CD80 mediates its effects through its extracellular domain, which blocks the cell surface expression of PDL1 but does not prevent intracellular expression of PDL1 protein. These studies demonstrate a new role for CD80 in facilitating antitumor immunity and suggest new therapeutic avenues for preventing tumor cell PDL1-induced immune suppression.     

Animal models of human-derived cancer vaccines

Preclinical cancer vaccine studies must address vaccine safety, immunogenicity, and efficacy, as well as mechanism of vaccine action. Animal models of vaccines employing human tumor-associated antigen or epitopes (TAA, TAE) differ fundamentally from those employing tumor-specific antigens or epitopes (TSA, TSE). TSA and TSE vaccines will most likely demonstrate similar toxicity, immunogenicity, and efficacy in both tumor-bearing animals and patients. In contrast, TAA/TAE immunizations may have to overcome a host’s immunological tolerance to TAA/TAE expressed not only on tumor, but also on normal tissues; immunity to TAA/TAE will potentially target normal tissues and thus may induce autoimmunity. Various experimental models for human-derived TAA/TAE vaccines have been developed. These models include transgenic mice, mice with severe combined immunodeficiency (SCID), and non-human primates. Recently, unique animal models of TAA/TAE cancer vaccines have been developed, taking advantage of the discovery of animal tissue antigens with significant sequence homologies to human TAA/TAE. These models mimic perhaps most closely the situation in cancer patients.     

A study on distribution of natural radionuclide polonium-210 in a pond ecosystem

This paper presents the results of an investigation on the distribution of²¹⁰Po in Mutharasanallur pond ecosystem. It has been demonstrated that²¹⁰Po is non-uniformly distributed within the ecosystem. The results of the study show a dissolved²¹⁰Po concentration in pond water of 1 4mBq 1₋₁. The sediment samplso recorded a²¹⁰Po activity of 59 9 Bq kg₋₁. The aquatic organisms showed differential accumulation of the radionuclide with enhanced bioaccumulation in soft tissues and muscle. The²¹⁰Po activity in the biota fell within the range of 1·2–53 3 Bq kg₋₁ (wet wt). The bivalve mussel,Lamellidens marginalis was identified to accumulate higher concentration of²¹⁰Poin soft tissues, suggesting that these organisms could serve as a bio-monitor of²¹⁰Po radionuclide in a freshwater system. The concentration factors of²¹⁰Po for the biotic components ranged from ∼10²–∼10⁴. Analyses of the results indicate that prawn and fish represent an important source of supply of²¹⁰Po to humans via dietary intake. Results of²¹⁰Po activity in the abiotic and biotic components of the pond ecosystem were higher when compared with those of Cauvery river system, the primary water source of the pond.     

Modulation of Macrophage Polarization and HMGB1-TLR2/TLR4 Cascade Plays a Crucial Role for Cardiac Remodeling in Senescence-Accelerated Prone Mice

The aim of this study was to investigate the role of macrophage polarization in aging heart. Macrophage differentiation is pathogenically linked to many inflammatory and immune disorders. It is often preceded by myocardial inflammation, which is characterized by increased cardiac damage and pro-inflammatory cytokine levels. Therefore, we investigated the hypothesis that senescence accelerated-prone (SAMP8) mice cardiac tissue would develop macrophage polarization compared with senescence-resistant control (SAMR1) mice. Both SAMP8 and SAMR1 mice were sacrificed when they became six month old. We evaluated, histo-pathological changes and modifications in protein expression by Western blotting and immuno-histochemical staining for M1 and M2 macrophage markers, high mobility group protein (HMG)B1 and its cascade proteins, pro-inflammatory factors and inflammatory cytokines in cardiac tissue. We observed significant upregulation of HMGB1, toll-like receptor (TLR)2, TLR4, nuclear factor (NF)κB p65, tumor necrosis factor (TNF)α, cyclooxygenase (COX)2, interferon (IFN)γ, interleukin (IL)-1β, IL-6 and M1 like macrophage specific marker cluster of differentiation (CD)68 expressions in SAMP8 heart. In contrast, M2 macrophage specific marker CD36, and IL-10 expressions were down-regulated in SAMP8 mice. The results from the study demonstrated that, HMGB1-TLR2/TLR4 signaling cascade and induction of phenotypic switching to M1 macrophage polarization in SAMP8 mice heart would be one of the possible reasons behind the cardiac dysfunction and thus it could become an important therapeutic target to improve the age related cardiac dysfunction.     

Synthesis and assembly of cytochrome c oxidase in synchronous cultures of yeast

Yeast cells growing synchronously in glucose medium accumulate in the cytosol, the cytosolically made subunits of cytochrome oxidase, during the G1 and early-S phases. The mitochondrially made subunits, on the other hand, are detected only after the mid-S phase. The cytosolically synthesized subunits are integrated into the membrane after the mid-S phase.     

Binding site conformation dictates the color of the dye stains-all. A study of the binding of this dye to the eye lens proteins crystallins

The interaction of the cationic carbocyanine dye Stains-all (1-ethyl-2-[3-(1-ethyl-naphthol[1,2-d]thiazolin-2-ylidene)-2- methylpropenyl]naphthol[1,2-d]thiazolium bromide) with the eye lens proteins crystallins has been studied. alpha- and gamma-crystallins do not bind the dye, while beta- and delta-crystallins do, consistent with the fact that the latter two proteins bind the calcium ion. beta-Crystallin resembles parvalbumin in that it induces only the J-band of the bound dye. delta-crystallin, on the other hand, induces only the gamma-band. Analysis of the metachromasia induced in the dye by these and other proteins suggests that Stains-all is responsive to the conformational status of the region to which it binds in a protein. The J-band of the dye is activated when it binds to a globular domain, and the gamma-band is activated when it binds to a helical stretch of the protein.     

Safety and physiologic effects of intranasal midazolam and nitrous oxide inhalation based sedation in children visiting Saveetha Dental College and Hospitals,India

A large number of patients avoid dental care due to anxiety. Various techniques are available for behaviour related management. Therefore, safety and physiologic effects of intranasal midazolam and nitrous oxide inhalation based sedation in children aged 4 to 8 years visiting Saveetha Dental College and Hospitals, India is of interest. 35 anxious patients aged 4 to 8 years were included in the study. The patient received either intranasal midazolam/nitrous oxide in the first visit and vice versa at the second visit. The onset of sedation, recovery time and procedure duration were recorded using a timer. Physiological parameters were recorded using a monitor. Safety scale was used for assessing prevalence of adverse reactions. There was no significant difference between the groups in safety scale scores, recovery time and procedure duration. Midazolam group showed a statistically significant faster onset of sedation and a statistically significant increase in heart rate at four recorded time-points. All the vitals were within the physiological limits. Thus, intranasal midazolamis a safe alternative to nitrous-oxide sedation in completing the intended dental treatment while managing the anxious children in dental clinic.     

Diagnosis and classification of disorders specifically associated with stress: proposals for ICD‐11

The diagnostic concepts of post‐traumatic stress disorder (PTSD) and other disorders specifically associated with stress have been intensively discussed among neuro‐ and social scientists, clinicians, epidemiologists, public health planners and humanitarian aid workers around the world. PTSD and adjustment disorder are among the most widely used diagnoses in mental health care worldwide. This paper describes proposals that aim to maximize clinical utility for the classification and grouping of disorders specifically associated with stress in the forthcoming 11th revision of the International Classification of Diseases (ICD‐11). Proposals include a narrower concept for PTSD that does not allow the diagnosis to be made based entirely on non‐specific symptoms; a new complex PTSD category that comprises three clusters of intra‐ and interpersonal symptoms in addition to core PTSD symptoms; a new diagnosis of prolonged grief disorder, used to describe patients that undergo an intensely painful, disabling, and abnormally persistent response to bereavement; a major revision of “adjustment disorder” involving increased specification of symptoms; and a conceptualization of “acute stress reaction” as a normal phenomenon that still may require clinical intervention. These proposals were developed with specific considerations given to clinical utility and global applicability in both low‐ and high‐income countries.