“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.     

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.     

Evolution of Protein Targeting into “Complex” Plastids: The “Secretory Transport Hypothesis”

Abstract: In algae different types of plastids are known, which vary in pigment content and ultrastructure, providing an opportunity to study their evolutionary origin. One interesting feature is the number of envelope membranes surrounding the plastids. Red algae, green algae and glaucophytes have plastids with two membranes. They are thought to originate from a primary endocytobiosis event, a process in which a prokaryotic cyanobacterium was engulfed by a eukaryotic host cell and transformed into a plastid. Several other algal groups, like euglenophytes and heterokont algae (diatoms, brown algae, etc.), have plastids with three or four surrounding membranes, respectively, probably reflecting the evolution of these organisms by so‐called secondary endocytobiosis, which is the uptake of a eukaryotic alga by a eukaryotic host cell. A prerequisite for the successful establishment of primary or secondary endocytobiosis must be the development of suitable protein targeting machineries to allow the transport of nucleus‐encoded plastid proteins across the various plastid envelope membranes. Here, we discuss the possible evolution of such protein transport systems. We propose that the secretory system of the respective host cell might have been the essential tool to establish protein transport into primary as well as into secondary plastids.     

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.     

Paleodemography: “Not quite dead”

As Kim Hill¹ recently noted in Evolutionary Anthropology, humans are unique among the hominoids with regard to the length of their lives, as well as other elements in the individual life histories. The evolutionary details that modified a basic pongid life history into a hominid one remain obscure, but aspects of recent human demographic history are assailable. Study of the last 10,000 years or so is an important part of ongoing anthropological discourse, for demographic changes may be intimately linked to such major developments as agriculture and urbanization.^2-8 Whether demographic changes are antecedents for or consequences of these major developments is a matter of great contention, but at the least we should attempt to document the nature of human demographic changes in the recent past. Although this documentation can take different forms, the principal sources are archeological information on past settlement patterns and analyses of prehistoric human skeletal material.     

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.     

“Micro-Film” In Photomicrography

Micro-File film (Eastman Kodak Co.) gave excellent results when used for photomicrography. A 35 mm. reflex camera attached to one tube of a binocular microscope provided a convenient means of recording cells of special interest in chromosome studies. Micro-File was found to give better contrast than Plus-X and required less processing time.     

“Uncovering” Industrial Symbiosis

Since 1989, efforts to understand the nature of interfirm resource sharing in the form of industrial symbiosis and to replicate in a deliberate way what was largely self‐organizing in Kalundborg, Denmark have followed many paths, some with much success and some with very little. This article provides a historical view of the motivations and means for pursuing industrial symbiosis—defined to include physical exchanges of materials, energy, water, and by‐products among diversified clusters of firms. It finds that “uncovering” existing symbioses has led to more sustainable industrial development than attempts to design and build eco‐industrial parks incorporating physical exchanges. By examining 15 proposed projects brought to national and international attention by the U.S. President's Council on Sustainable Development beginning in the early 1990s, and contrasting these with another 12 projects observed to share more elements of self‐organization, recommendations are offered to stimulate the identification and uncovering of already existing “kernels” of symbiosis. In addition, policies and practices are suggested to identify early‐stage precursors of potentially larger symbioses that can be nurtured and developed further. The article concludes that environmentally and economically desirable symbiotic exchanges are all around us and now we must shift our gaze to find and foster them.