Microglia are a heterogenous group of monocyte-derived cells serving multiple roles within the brain, many of which are associated with immune and macrophage like properties. These cells are known to ...serve a critical role during brain injury and to maintain homeostasis; yet, their defined roles during development have yet to be elucidated. Microglial actions appear to influence events associated with neuronal proliferation and differentiation during development, as well as, contribute to processes associated with the removal of dying neurons or cellular debris and management of synaptic connections. These long-lived cells display changes during injury and with aging that are critical to the maintenance of the neuronal environment over the lifespan of the organism. These processes may be altered by changes in the colonization of the brain or by inflammatory events during development. This review addresses the role of microglia during brain development, both structurally and functionally, as well as the inherent vulnerability of the developing nervous system. A framework is presented considering microglia as a critical nervous system-specific cell that can influence multiple aspects of brain development (e.g., vascularization, synaptogenesis, and myelination) and have a long term impact on the functional vulnerability of the nervous system to a subsequent insult, whether environmental, physical, age-related, or disease-related.
Adaptation of organisms to environmental niches is a hallmark of evolution. One prevalent example is that of thermal adaptation, in which two descendants evolve at different temperature extremes
. ...Underlying the physiological differences between such organisms are changes in enzymes that catalyse essential reactions
, with orthologues from each organism undergoing adaptive mutations that preserve similar catalytic rates at their respective physiological temperatures
. The sequence changes responsible for these adaptive differences, however, are often at surface-exposed sites distant from the substrate-binding site, leaving the active site of the enzyme structurally unperturbed
. How such changes are allosterically propagated to the active site, to modulate activity, is not known. Here we show that entropy-tuning changes can be engineered into distal sites of Escherichia coli adenylate kinase, allowing us to quantitatively assess the role of dynamics in determining affinity, turnover and the role in driving adaptation. The results not only reveal a dynamics-based allosteric tuning mechanism, but also uncover a spatial separation of the control of key enzymatic parameters. Fluctuations in one mobile domain (the LID) control substrate affinity, whereas dynamic attenuation in the other domain (the AMP-binding domain) affects rate-limiting conformational changes that govern enzyme turnover. Dynamics-based regulation may thus represent an elegant, widespread and previously unrealized evolutionary adaptation mechanism that fine-tunes biological function without altering the ground state structure. Furthermore, because rigid-body conformational changes in both domains were thought to be rate limiting for turnover
, these adaptation studies reveal a new model for understanding the relationship between dynamics and turnover in adenylate kinase.
Curcumin exerts a wide range of beneficial physiological and pharmacological activities, including antioxidant, anti-amyloid, anti-inflammatory, anti-microbial, anti-neoplastic, immune-modulating, ...metabolism regulating, anti-depressant, neuroprotective and tissue protective effects. However, its poor solubility and poor absorption in the free form in the gastrointestinal tract and its rapid biotransformation to inactive metabolites greatly limit its utility as a health-promoting agent and dietary supplement. Recent advances in micro- and nano-formulations of curcumin with greatly enhanced absorption resulting in desirable blood levels of the active forms of curcumin now make it possible to address a wide range of potential applications, including pain management, and as tissue protective. Using these forms of highly bioavailable curcumin now enable a broad spectrum of appropriate studies to be conducted. This review discusses the formulations designed to enhance bioavailability, metabolism of curcumin, relationships between solubility and particle size relative to bioavailability, human pharmacokinetic studies involving formulated curcumin products, the widely used but inappropriate practice of hydrolyzing plasma samples for quantification of blood curcumin, current applications of curcumin and its metabolites and promising directions for health maintenance and applications.
ABSTRACT
Crowdsourcing platforms are online organizations that organize work by sourcing tasks to their members. As participation on crowdsourcing platforms is completely voluntary, getting members ...to actively participate in tasks on an ongoing basis is essential for the survival of these online platforms. Why members would be active on an ongoing basis, however, is currently not well understood. To understand ongoing member activity on crowdsourcing platforms, we build on the group engagement model, which postulates that feelings of pride and respect influence engagement because they foster identification with the group. We argue that, although in general the nature of crowdsourcing platforms limits the effects of identification processes on member behaviour, feelings of pride and respect will still play central roles in such online organizations, because feelings of pride and respect can directly drive members’ cooperative behaviors towards the platform organization. Moreover, we posit that the way in which platform organizations communicate with their members affects these feelings of pride and respect. We test these ideas in a longitudinal, multisource field study and find that feelings of pride drive ongoing member activity on an online crowdsourcing platform directly and that platform management can increase members’ feelings of pride and respect by engaging in specific organizational communication practices.
Africa's Silk Road Broadman, Harry G; Isik, Gozde
2006, 11-02-2006, 2007
eBook, Book
Odprti dostop
China and India's new-found interest in trade and investment with Africa - home to 300 million of the globe's poorest people and the world's most formidable development challenge - presents a ...significant opportunity for growth and integration of the Sub-Saharan continent into the global economy. Africa's Silk Road finds that China and India's South-South commerce with Africa is about far more than natural resources, opening the way for Africa to become a processor of commodities and a competitive supplier of goods and services to these countries - a major departure from its long established relations with the North. A growing number of Chinese and Indian businesses active in Africa operate on a global scale, work with world-class technologies, produce products and services according to the most demanding standards, and foster the integration of African businesses into advanced markets. There are significant imbalances, however, in these emerging commercial relationships. These can be addressed through a series of reforms in all countries:"At-the-border" reforms, such as elimination of China and India's escalating tariffs on Africa's leading exports, and elimination of Africa's tariffs on certain inputs that make exports uncompetitive "Behind-the-border" reforms in Africa, to unleash competitive market forces and strengthen its basic market institutions "Between-the-border" improvements in trade facilitation mechanisms to decrease transactions costs Reforms that leverage linkages between investment and trade, to allow African businesses to participate in global production networks that investments by Chinese and Indian firms can generate.
During nuclear waste disposal process, radioactive iodine as a fission product can be released. The widespread implementation of sustainable nuclear energy thus requires the development of efficient ...iodine stores that have simultaneously high capacity, stability and more importantly, storage density (and hence minimized system volume). Here, we report high I2 adsorption in a series of robust porous metal–organic materials, MFM-300(M) (M = Al, Sc, Fe, In). MFM-300(Sc) exhibits fully reversible I2 uptake of 1.54 g g–1, and its structure remains completely unperturbed upon inclusion/removal of I2. Direct observation and quantification of the adsorption, binding domains and dynamics of guest I2 molecules within these hosts have been achieved using XPS, TGA-MS, high resolution synchrotron X-ray diffraction, pair distribution function analysis, Raman, terahertz and neutron spectroscopy, coupled with density functional theory modeling. These complementary techniques reveal a comprehensive understanding of the host–I2 and I2–I2 binding interactions at a molecular level. The initial binding site of I2 in MFM-300(Sc), I2 I, is located near the bridging hydroxyl group of the ScO4(OH)2 moiety I2 I···H–O = 2.263(9) Å with an occupancy of 0.268. I2 II is located interstitially between two phenyl rings of neighboring ligand molecules I2 II···phenyl ring = 3.378(9) and 4.228(5) Å. I2 II is 4.565(2) Å from the hydroxyl group with an occupancy of 0.208. Significantly, at high I2 loading an unprecedented self-aggregation of I2 molecules into triple-helical chains within the confined nanovoids has been observed at crystallographic resolution, leading to a highly efficient packing of I2 molecules with an exceptional I2 storage density of 3.08 g cm–3 in MFM-300(Sc).
A large number of investigations have demonstrated a broad spectrum of pharmacological and therapeutic benefits of grape seed proanthocyanidins (GSP) against oxidative stress and degenerative ...diseases including cardiovascular dysfunctions, acute and chronic stress, gastrointestinal distress, neurological disorders, pancreatitis, various stages of neoplastic processes and carcinogenesis including detoxification of carcinogenic metabolites. GSP exhibited potent free radical scavenging abilities in both in vitro and in vivo models. GSP exerted significant in vivo protection against structurally diverse drug and chemical-induced hepatotoxicity, cardiotoxicity, neurotoxicity, nephrotoxicity and spleentoxicity. GSP also protected against idarubicin and 4-hydroxyperoxy-cyclophosphamide-induced cytotoxicity toward human normal liver cells. GSP exhibited selective cytotoxicity toward selected human cancer cells, while enhancing the growth and viability of normal cells. GSP exhibited potent modulatory effects of pro-apoptotic and apoptotic regulatory bcl-XL, p53, c-myc, c-JUN, JNK-1 and CD36 genes. Long-term exposure to GSP may serve as a novel chemoprotectant against three stages of DMN-induced liver carcinogenesis and tumorigenesis including initiation, promotion and progression. GSP may selectively protect against oxidative stress, genomic integrity and cell death patterns in vivo. These results demonstrate that GSP may serve as a novel therapeutic intervention against carcinogenesis.
How do firms learn to successfully acquire other firms? The authors first review early work, mostly from the 1980s to the mid-1990s, testing the learning curve perspective on acquisitions and ...exploring some contingencies. They then discuss three more recent streams of research on negative experience transfer, deliberate learning mechanisms, and learning from others, which provide deeper insight into the contingencies and mechanisms of organizational learning in strategic settings such as acquisitions. The article concludes with an agenda for future research.
The literature published during 2011 whose subject matter encompasses the cocrystallization of organic compounds having particular interest to pharmaceutical scientists has been summarized in an ...annual review. The papers cited in this review were drawn from the major physical, crystallographic, and pharmaceutical journals. After a brief introduction, the review is divided into sections that cover articles of general interest, the preparation of cocrystal systems and methodologies for their characterization, and more detailed discussion of cocrystal systems containing pharmaceutically relevant compounds. The review ends with a discussion of the draft Guidance for Industry document regarding the regulatory classification of pharmaceutical cocrystals that was issued at the end of 2011 by the Center for Drug Evaluation and Research (CDER) of the United States Food and Drug Administration.
PDF
