Tumor microenvironment as the “regulator” and “target” for gene therapy

In this review, we focus on strategies for designing functional nano gene carriers, as well as choosing therapeutic genes targeting the tumor microenvironment. Gene mutations have a great impact on the occurrence of cancer. Thus, gene therapy plays a major role in cancer therapy and has the potential to cure cancer. Well‐designed gene therapy largely relies on effective gene carriers, which can be divided into viral carriers and non‐viral carriers. A gene carrier delivers functional genes to their intracellular target and avoids nucleic acids being degraded by nucleases in the serum. Most conventional cancer gene therapies only target cancer cells and do not appear to be sufficintly efficient to pass clinical trials. Accumulating evidence has shown that extending the therapeutic strategies to the tumor microenvironment, rather than the tumor cell itself, can allow more options for achieving robust anti‐cancer efficiency. In addition, unusual features between tumor microenvironment and normal tissues, such as a lower pH, higher glutathione and reactive oxygen species concentrations, and overexpression of some enzymes, facilitate the design of smart stimuli‐responsive gene carriers regulated by the tumor microenvironment. These carriers interact with nucleic acids and then form stable nanoparticles under physiological conditions. By regulation of the tumor microenvironment, stimuli‐responsive gene carriers are able to change their properties and achieve high gene delivery efficiency. Considering the tumor microenvironment as the “regulator” and “target” when designing gene carriers and choosing therapeutic genes shows significant benefit with respect to improving the accuracy and efficiency of cancer gene therapy.     

Restoring Intertidal Boulder‐Fields as Habitat for “Specialist” and “Generalist” Animals

Restoration is important in urban areas where habitat destruction is greatest. It incorporates many levels of intervention, with creation of new habitat the most extreme form. Most research on habitat creation has been terrestrial, or in marine habitats dominated by large structuring biota, such as mangroves. Intertidal boulder‐fields in urban areas are vulnerable to disturbances and habitat loss, which adversely affect numerous habitat specialists. This study describes experiments in which quarried stones were used to create new habitat outside natural boulder‐fields as a practical approach to restoring habitat. Colonization by specialist fauna and by common algae and invertebrates was measured for a year after deployment. Despite sessile assemblages on new boulders differing from those on natural boulders, common and rare animals rapidly colonized the new habitat. There was no clear succession, but colonization was variable and patchy at all scales examined, although diversities and abundances of some species in this novel habitat matched those of natural boulders within a few months. Rare and common animals generally colonized the new habitat as adults moving in from surrounding areas. Creating new boulder‐fields using quarried rocks is a successful approach to restoration and conservation of fauna where natural boulder‐fields are threatened.     

Various strategies for obtaining artificial hemoproteins: From “hemoabzymes” to “hemozymes”

The design of artificial hemoproteins that could lead to new biocatalysts for selective oxidation reactions of organic compounds presents a huge interest especially in pharmacology, both for a better understanding of the metabolic profile of drugs and for the synthesis of enantiomerically pure molecules that could be involved in the design of drugs.The present results show that the so-called “host-guest strategy” that involves the non-covalent incorporation of anionic water-soluble iron-porphyrins into xylanase A from Streptomyces lividans, a low cost protein, leads to such an artificial hemoprotein that is able to perform the stereoselective oxidation of sulfides.     

A Revised Method for the “Quad” Stain

Since the original publication of this staining method (Stain Techn., 18, 95), various improvements have been made. These are chiefly in the formula for acid alizarine blue, Solution 2, given below and the composition of Solution 4. The author substituted ammonia alum for aluminum sulphate, and Richard C. Webster of our department did the work with the acetic-acid-sodium-acetate buffer. He found that the final staining solution of pH 2.9 gave the sharpest and bluest nuclei and clearest transparent and contrasting cytoplasm of a pinkish hue. With our previous formula, muscle fibrils often stained so deeply that they detracted from the value of the slides, made them too opaque and obscured the nuclei. This has now been overcome. This also allows the elastic tissue to show better and to contrast with muscle fibers. This is especially noted in studies of the heart and blood vessels.     

A “Natural” Agglomerative Clustering Method for Biology

The authors consider that cluster analysis does not objectivize but represents the biologist's subjectivity as to (1) characters considered to be significant and to (2) the way of classification. The latter, however, in authors' opinion, must be specific to the field of application. To this effect some methods are suggested for biology. The methods originate in improvements or transformation of Buser and Baroni-Urbani's method, as well as Watanabe's method, and have the property of processing overall information with no loss or distortion. An agglomerative method which yields a necessarily unique result is suggested, being considered by the authors as a homologue of Watanabe's divisive method. The methods proposed are studied using examples logically constructed. These examples can provide from biology, especially from ecology.     

Dopamine for “Wanting” and Opioids for “Liking”: A Comparison of Obese Adults With and Without Binge Eating

Obesity research suffers from an overinclusion paradigm whereby all participants with a BMI beyond a certain cutoff value (e.g., 30) are typically combined in a single group and compared to those of normal weight. There has been little attempt to identify meaningful subgroups defined by their salient biobehavioral differences. In order to address this limitation, we examined genetic and psychological indicators of hedonic eating in obese adults with (n = 66) and without (n = 70) binge eating disorder (BED). Our analyses focused on dopamine (DA) and opioid genetic markers because of their conjoint association with the functioning of brain reward mechanisms. We targeted three functional polymorphisms related to the D2 receptor (DRD2) gene, as well as the functional A118G polymorphism of the mu‐opioid receptor (OPRM1) gene. We found that significantly more obese controls had the “loss‐of‐function” A1 allele of Taq1A compared to their BED counterparts, whereas the “gain‐of‐function” G allele of A118G occurred with greater frequency in the BED group. A significant gene–gene combination χ² analysis also indicated that of those participants with the gain‐gain genotype (G⁺ and A1), 80% were in the BED group whereas only 35% with the loss‐loss genotype (G^? and A1⁺) were in this group. Finally, BED subjects had significantly higher scores on a self‐report measure of hedonic eating. Our findings suggest that BED is a biologically based subtype of obesity and that the proneness to binge eating may be influenced by a hyper‐reactivity to the hedonic properties of food—a predisposition that is easily exploited in our current environment with its highly visible and easily accessible surfeit of sweet and fatty foods.     

The use of calcium alginate gels for “solids separation” and “diffusional chromatography” of biological materials

The use of calcium alginate gels for the “Solids Separation” techniques was demonstrated by entrapment of a yeast extract in calcium alginate pellets and the study of the release of alcohol dehydrogenase and NADH into a dilute calcium chloride solution. The use of calcium alginate gels for a “Diffusional Chromatography” technique was demonstrated in a model system by a fractionation of NAD and hemoglobin release following their entrapment in calcium alginate pellets. The advantages of these techniques and their potentials are discussed.     

“Inflammatory” Cytokines

If cytokines are constitutively expressed by and act on neurons in normal adult brain, then we may have to modify our current view that they are predominantly inflammatory mediators. We critically reviewed the literature to determine whether we could find experimental basis for such a modification. We focused on two "proinflammatory" cytokines, interleukin (IL)-1 and tumor necrosis factor-alpha (TNFalpha) because they have been most thoroughly investigated in shaping our current thinking. Evidence, although equivocal, indicates that the genes coding for these cytokines and their accessory proteins are expressed by neurons, in addition to glial cells, in normal brain. Their expression is region- and cell type-specific. Furthermore, bioactive cytokines have been extracted from various regions of normal brain. The cytokines' receptors selectively are present on all neural cell types, rendering them responsive to cytokine signaling. Blocking their action modifies multiple neural "housekeeping" functions. For example, blocking IL-1 or TNFalpha by several independent means alters regulation of sleep. This indicates that these cytokines likely modulate in the brain behavior of a normal organism. In addition, these cytokines are likely involved in synaptic plasticity, neural transmission, and Ca2+ signaling. Thus, the evidence strongly suggests that these cytokines perform neural functions in normal brain. We therefore propose that they should be thought of as neuromodulators in addition to inflammatory mediators.     

The “azotopure” process for treating nitrogen-deficient aqueous wastes

Many chemical and food processing wastes are deficient in nitrogen, and must therefore be supplemented with domestic sewage or ammonia to dispose of them by conventional biological treatment. A more economical treatment, especially of strong wastes, is possible by maintaining a semipure culture of nitrogen-fixing bacteria in a stirred aerated tank. When operated as a chemostat with 4 to 6 hr detention time, removal of 85% of the COD is possible in a single step without the need for clarifiers or digesters. A clarified effluent could also be produced by flotation or sedimentation of the flocculated bacteria. In that case there would be 99% removal of COD and a reduction in the amount of sludge by two-thirds over the conventional activated sludge process.     

“Active” and “passive” ecological restoration strategies in meta‐analysis

One of the means of creating a more robust methodology for ecological restoration involves reducing the gap between ecological theory and restoration practices. A common strategy to do so is using meta‐analysis to understand key drivers of restoration outcomes. “Active” and “passive” is a dichotomy often used to separate restoration strategies in such meta‐analyses. We investigate previously raised concerns about selection bias and subjective categorization of strategies. We promote a paired experimental design in future empirical research and propose the use of three categories of restoration strategy in lieu of “passive” and “active” to alleviate inconsistency in definitions and categorization.     

Heterogeneous Single Atom Electrocatalysis,Where “Singles” Are “Married”

There is an intensive search for heterogeneous single atom catalysts (SACs) of high activity, efficiency, durability, and selectivity for a wide variety of electrocatalytic conversion and chemical reactions, such as the hydrogen evolution reaction (HER), oxygen evolution/reduction reaction (OER and ORR), CO₂ reduction reaction (CO₂ RR), and nitrogen reduction reaction (NRR). With the downsizing from nanoparticles and clusters to single atoms, there are steady changes in the bond and coordination environment for each and every atom involved. Indeed, the single atoms in these electrocatalysts are not “singles”; they are “married” to the supporting surfaces, and their performance is controlled by the bonding and coordination with the substrate surfaces. Herein, an overview is presented on the brief history leading to the rapid development of SACs and their current status, by focusing on their synthesis, control of composition, strategies to realize single atoms with the desired bonds and coordination, and targeted performance in selected reactions. Their applications in the selected spectrum of energy conversion and chemical reactions are discussed, in relation to their structures at varying length scales down to the atomic level. A particular emphasis is placed on on‐going research activities, together with the future perspectives and particular challenges for SACs.     

Creating a completely “cell‐free” system for protein synthesis

Cell‐free protein synthesis is a promising tool to take biotechnology outside of the cell. A cell‐free approach provides distinct advantages over in vivo systems including open access to the reaction environment and direct control over all chemical components for facile optimization and synthetic biology integration. Promising applications of cell‐free systems include portable diagnostics, biotherapeutics expression, rational protein engineering, and biocatalyst production. The highest yielding and most economical cell‐free systems use an extract composed of the soluble component of lysed Escherichia coli. Although E. coli lysis can be highly efficient (>99.999%), one persistent challenge is that the extract remains contaminated with up to millions of cells per mL. In this work, we examine the potential of multiple decontamination strategies to further reduce or eliminate bacteria in cell‐free systems. Two strategies, sterile filtration and lyophilization, effectively eliminate contaminating cells while maintaining the systems’ protein synthesis capabilities. Lyophilization provides the additional benefit of long‐term stability at storage above freezing. Technologies for personalized, portable medicine and diagnostics can be expanded based on these foundational sterilized and completely “cell‐free” systems. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:1716–1719, 2015