Immunologic unresponsiveness of mouse spleen sensitized to allogenic tumors.

CS7BL/6 mice were sensitized with an ip injection of allogeneic P-815 mastocytoma cells. Fifteen days later the spleen cells of the tumor allosensitized mice were cultured and tested for their responsiveness to mitogens and alloantigens, and for their ability to generate cytotoxic cells in vitro. The results indicate that 15 day tumor-sensitized spleen cells are hypo-responsive in mixed lymphocyte culture (MLC) with DBA/2 or AKR as stimulating spleen cells. The cells which are hypo-responsive in MLC can proliferate in response to mitogens and they also can generate cytotoxic cells in vitro. MLC reactivity recovers in about 2–3 months which is $\text{1}\text{1}\text{2}\text{–2}\text{1}\text{2}$ months after the mice have rejected their tumors. The mechanism of MLC hypo-responsiveness was investigated. The results suggest the presence of a suppressor cell which does not appear to be a macrophage or a B-cell. The suppressor cell can be separated from the cytotoxic cell and therefore appears to be a noncytotoxic T-cell.     

Role of epidermal stem cells in repair of partial-thickness burn injury after using Moist Exposed Burn Ointment (MEBO) histological and immunohistochemical study

Moist Exposed Burn Ointment (MEBO^®) is widely used topical agent applied on skin burn. This study investigated the effect of MEBO topical application on activation and proliferation of epidermal stem cells through the immunohistochemical localization of cytokeratin 19 (CK19) as a known marker expressed in epidermal stem cells. Biopsies from normal skin and burn wounds were taken from 21 patients with partial thickness burn 1, 4, 7, 14, 21, and 28 days after treatment with MEBO. Tissue sections were prepared for histological study and for CK19 immunohistochemical localization. In control skin, only few cells showed a positive CK19 immune-reaction. Burned skin showed necrosis of full thickness epidermis that extended to dermis. Gradual regeneration of skin accompanied with an enhancement in CK19 immune-reactivity was noted 4, 7, 14 and 21 days after treatment with MEBO. On day 28, a complete regeneration of skin was observed with a return of CK19 immune-reactivity to the basal pattern again. In conclusion, the enhancement of epidermal stem cell marker CK19 after treatment of partial thickness burn injuries with MEBO suggested the role of MEBO in promoting epidermal stem cell activation and proliferation during burn wound healing.     

Real time expression of ACC oxidase and PR-protein genes mediated by Methylobacterium spp. in tomato plants challenged with Xanthomonas campestris pv. vesicatoria

Biotic stress like pathogenic infection increases ethylene biosynthesis in plants and ethylene inhibitors are known to alleviate the severity of plant disease incidence. This study aimed to reduce the bacterial spot disease incidence in tomato plants caused by Xanthomonas campestris pv. vesicatoria (XCV) by modulating stress ethylene with 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity of Methylobacterium strains. Under greenhouse condition, Methylobacterium strains inoculated and pathogen challenged tomato plants had low ethylene emission compared to pathogen infected ones. ACC accumulation and ACC oxidase (ACO) activity with ACO related gene expression increased in XCV infected tomato plants over Methylobacterium strains inoculated plants. Among the Methylobacterium spp., CBMB12 resulted lowest ACO related gene expression (1.46 Normalized Fold Expression), whereas CBMB20 had high gene expression (3.42 Normalized Fold Expression) in pathogen challenged tomato. But a significant increase in ACO gene expression (7.09 Normalized Fold Expression) was observed in the bacterial pathogen infected plants. In contrast, Methylobacterium strains enhanced β-1,3-glucanase and phenylalanine ammonia-lyase (PAL) enzyme activities in pathogen challenged tomato plants. The respective increase in β-1,3-glucanase related gene expressions due to CBMB12, CBMB15, and CBMB20 strains were 66.3, 25.5 and 10.4% higher over pathogen infected plants. Similarly, PAL gene expression was high with 0.67 and 0.30 Normalized Fold Expression, in pathogen challenged tomato plants inoculated with CBMB12 and CBMB15 strains. The results suggest that ethylene is a crucial factor in bacterial spot disease incidence and that methylobacteria with ACC deaminase activity can reduce the disease severity with ultimate pathogenesis-related protein increase in tomato.     

Geometrical comparison of two protein structures using Wigner‐D functions

In this article, we develop a quantitative comparison method for two arbitrary protein structures. This method uses a root‐mean‐square deviation characterization and employs a series expansion of the protein's shape function in terms of the Wigner‐D functions to define a new criterion, which is called a “similarity value.” We further demonstrate that the expansion coefficients for the shape function obtained with the help of the Wigner‐D functions correspond to structure factors. Our method addresses the common problem of comparing two proteins with different numbers of atoms. We illustrate it with a worked example. Proteins 2014; 82:2756–2769. © 2014 Wiley Periodicals, Inc.     

Contribution of RNA Degradation to Intrinsic and Extrinsic Noise in Gene Expression

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Requirements for human‐induced pluripotent stem cells

‘Requirements for Human‐Induced Pluripotent Stem Cells’ is the first set of guidelines on human‐induced pluripotent stem cells in China, jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research. This standard specifies the technical requirements, test methods, and instructions for use, labeling, packaging, storage, transportation, and waste handling for human‐induced pluripotent stem cells, which apply to the production and quality control of human‐induced pluripotent stem cells. It was released by the Chinese Society for Cell Biology on 9 January 2021 and came into effect on 9 April 2021. We hope that the publication of these guidelines will promote institutional establishment, acceptance, and execution of proper protocols and accelerate the international standardization of human‐induced pluripotent stem cells for applications.     

Effects of temperature on metabolic rate and lower dissolved oxygen tolerance of juvenile speckled peacock bass Cichla temensis

The speckled peacock bass Cichla temensis is a popular sport and food fish that generates substantial angling tourism and utilitarian harvest within its range. Its popularity and value make this species important for management and a potential aquaculture candidate for both fisheries enhancement and food fish production. However, little is known of optimal physiochemical conditions in natural habitats, which also are important for the development of hatchery protocols for handling, spawning and grow-out. Speckled peacock bass have been documented to have high sensitivity to extreme temperatures, but the metabolic underpinnings have not been evaluated. In this study, the effects of temperature (25, 30 and 35°C) on the standard metabolic rate (SMR) and lower dissolved oxygen tolerance (LDOT) of juvenile speckled peacock bass (mean ± standard error total length 153 ± 2 mm and wet weight 39.09 ± 1.37 g) were evaluated using intermittent respirometers after an acclimation period of 2 weeks. Speckled peacock bass had the highest SMR at 35°C (345.56 ± 19.89 mgO₂ kg⁻¹ h⁻¹), followed by 30°C (208.16 ± 12.45 mgO₂ kg⁻¹ h⁻¹) and 25°C (144.09 ± 10.43 mgO₂ kg⁻¹ h⁻¹). Correspondingly, the Q₁₀, or rate of increase in aerobic metabolic rate (MO₂) relative to 10°C, for 30–35°C was also greater (2.76) than from 25 to 30°C (2.08). Similarly, speckled peacock bass were the most sensitive to hypoxia at the warmest temperature, with an LDOT at pO₂ of 90 mmHg (4.13 mg l⁻¹) at 35°C compared to pO₂ values of 45 mmHg (2.22 mg l⁻¹) and 30 mmHg (1.61 mg l⁻¹) at 30 and 25°C, respectively. These results indicate that speckled peacock bass are sensitive to temperatures near 35°C, therefore we recommend managing and rearing this species at 25–30°C.     

Toll-like receptor 9 signaling has anti-inflammatory effects on the early phase of Helicobacter pylori-induced gastritis

Helicobacter pylori (H. pylori)-induced immune responses in the gastric mucosa are skewed toward T helper (Th) 1 phenotype, which is characterized by predominant production of tumor necrosis factor (TNF)-α and interferon (IFN)-γ by helper T cells. Toll-like receptors (TLRs) play an essential role in mucosal defense against microbes through the recognition of bacterial molecules. Among the members of the TLR family, TLR9 recognizes bacterial unmethylated CpG DNA sites, and signal transduction of TLR9 induces production of a variety of cytokines, including type-I IFN (IFN-α/β). We investigated the expression and role of TLR9 in H. pylori-induced gastritis in mice. Expression of TLR9 mRNA in the gastric tissue increased after infection with H. pylori. TLR9 was mainly expressed in the macrophages, dendritic cells, and CD3⁺ cells in the gastric mucosa. Neutrophil infiltration and the expression levels of TNF-α and IFN-γ mRNA were higher in TLR9 knockout (KO) mice than in wild-type mice at 2 and 4 months after H. pylori inoculation. These differences in inflammatory parameters between H. pylori-infected wild-type and TLR9 KO mice disappeared 6 months after H. pylori inoculation. Expression of interleukin-4 mRNA, typical Th2 cytokine, in the gastric tissue did not differ between H. pylori-infected wild-type and TLR9 KO mice. Expression level of IFN-α/β mRNA in the TLR9 KO mice was lower than that in wild-type mice by 4 months after inoculation. Administration of IFN-α reduced H. pylori infection-induced increase in neutrophil infiltration and the expression levels of TNF-α and IFN-γ mRNA in TLR9 KO mice. Our findings suggest that TLR9 signaling plays important roles in the suppression of H. pylori-induced gastritis in the early phase via downregulation of Th1-type cytokines modulated by IFN-α.     

Fractal genome sequences

The existence of fractal sets of DNA sequences have long been suspected on the basis of statistical analyses of genome data. In this article we identify for the first time explicitly the GA-sequences as a class of fractal genomic sequences that are easy to recognize and to extract, and are scattered densely throughout the chromosomes of a large number of genomes from different species and kingdoms including the human genome. Their existence and their fractality may have significant consequences for our understanding of the origin and evolution of genomes. Furthermore, as universal and natural markers they may be used to chart and explore the non-coding regions.     

Optimal promising zone designs

Clinical trials with adaptive sample size reassessment based on an unblinded analysis of interim results are perhaps the most popular class of adaptive designs (see Elsäßer et al., 2007). Such trials are typically designed by prespecifying a zone for the interim test statistic, termed the promising zone, along with a decision rule for increasing the sample size within that zone. Mehta and Pocock (2011) provided some examples of promising zone designs and discussed several procedures for controlling their type‐1 error. They did not, however, address how to choose the promising zone or the corresponding sample size reassessment rule, and proposed instead that the operating characteristics of alternative promising zone designs could be compared by simulation. Jennison and Turnbull (2015) developed an approach based on maximizing expected utility whereby one could evaluate alternative promising zone designs relative to a gold‐standard optimal design. In this paper, we show how, by eliciting a few preferences from the trial sponsor, one can construct promising zone designs that are both intuitive and achieve the Jennison and Turnbull (2015) gold‐standard for optimality.