1,298 research outputs found
Federal Technology Transfer: Should We Build Subarus in Bethesda
A critical examination of a policy designed to encourage commercial exploitation of federally funded biomedical research. The author argues that the implementation of this policy threatens the integrity of basic science in America
The Human Genome Project and the Downside of Federal Technology Transfer
Mr. Harnett argues that emphasizing technology transfer at institutions such as the National Institutes of Health will interfere with what should be regarded as their primary mission, basic research
Parasite excretory-secretory products and their effects on metabolic syndrome
Obesity, one of the main causes of metabolic syndrome (MetS), is an increasingly common health and economic problem worldwide, and one of the major risk factors for developing type 2 diabetes and cardiovascular disease. Chronic, low-grade inflammation is associated with MetS and obesity. A dominant type 2/anti-inflammatory response is required for metabolic homeostasis within adipose tissue: during obesity, this response is replaced by infiltrating, inflammatory macrophages and T cells. Helminths and certain protozoan parasites are able to manipulate the host immune response towards a TH2 immune phenotype that is beneficial for their survival and there is emerging data that there is an inverse correlation between the incidence of MetS and helminth infections, suggesting that, as with autoimmune and allergic diseases, helminths may play a protective role against MetS disease. Within this review, we will focus primarily on the excretory-secretory products that the parasites produce to modulate the immune system and discuss their potential use as therapeutics against MetS and its associated pathologies
How do nematodes transfer phosphorylcholine to carbohydrates?
An unusual aspect of the biology of nematodes is the attachment of phosphorylcholine (PC) to carbohydrate. The attachment appears to play an important role in nematode development and, in some parasitic species, in immunomodulation. This article considers the nature of the biosynthetic pathway of nematode PC-containing glycoconjugates and, in particular, the identity of the final component in the pathway - the enzyme that transfers PC to carbohydrate (the 'PC transferase'). We offer the opinion that the PC transferase could be a member of the fukutin family (fukutin refers to the mutated gene product that causes Fukuyama congenital muscular dystrophy), a group of enzymes with apparent phosphoryl-ligand transferase activity that are found in organisms ranging from bacteria to humans
Masses of Open-Flavour Heavy-Light Hybrids from QCD Sum-Rules
We use QCD Laplace sum-rules to predict masses of open-flavour heavy-light
hybrids where one of the hybrid's constituent quarks is a charm or bottom and
the other is an up, down, or strange. We compute leading-order, diagonal
correlation functions of several hybrid interpolating currents, taking into
account QCD condensates up to dimension-six, and extract hybrid mass
predictions for all , as well as explore possible
mixing effects with conventional quark-antiquark mesons. Within theoretical
uncertainties, our results are consistent with a degeneracy between the
heavy-nonstrange and heavy-strange hybrids in all channels. We find a
similar mass hierarchy of , , and states (a state
lighter than essentially degenerate and states) in both the
charm and bottom sectors, and discuss an interpretation for the states.
If conventional meson mixing is present the effect is an increase in the hybrid
mass prediction, and we estimate an upper bound on this effect.Comment: 24 pages, 8 figures. Mass predictions updated from previous version
to reflect corrected sign error in sum rule analysis. Mixing analysis and
examination of higher weight sum-rules added. To be published in JHE
Drug-like analogues of the parasitic worm-derived immunomodulator ES-62 are therapeutic in the MRL/Lpr model of systemic lupus erythematosus
Introduction ES-62, a phosphorylcholine (PC)-containing immunomodulator secreted by the parasitic worm Acanthocheilonema viteae, protects against nephritis in the MRL/Lpr mouse model of systemic lupus erythematosus (SLE). However, ES-62 is not suitable for development as a therapy and thus we have designed drug-like small molecule analogues (SMAs) based around its active PC-moiety. To provide proof of concept that ES-62-based SMAs exhibit therapeutic potential in SLE, we have investigated the capacity of two SMAs to protect against nephritis when administered to MRL/Lpr mice after onset of kidney damage.
Methods SMAs 11a and 12b were evaluated for their ability to suppress antinuclear antibody (ANA) generation and consequent kidney pathology in MRL/Lpr mice when administered after the onset of proteinuria.
Results SMAs 11a and 12b suppressed development of ANA and proteinuria. Protection reflected downregulation of MyD88 expression by kidney cells and this was associated with reduced production of IL-6, a cytokine that exhibits promise as a therapeutic target for this condition.
Conclusions SMAs 11a and 12b provide proof of principle that synthetic compounds based on the safe immunomodulatory mechanisms of parasitic worms can exhibit therapeutic potential as a novel class of drugs for SLE, a disease for which current therapies remain inadequate
The parasitic worm-derived immunomodulator, ES-62 and its drug-like small molecule analogues exhibit therapeutic potential in a model of chronic asthma
Chronic asthma is associated with persistent lung inflammation and long-term remodelling of the airways that have proved refractory to conventional treatments such as steroids, despite their efficacy in controlling acute airway contraction and bronchial inflammation. As its recent dramatic increase in industrialised countries has not been mirrored in developing regions, it has been suggested that helminth infection may protect humans against developing asthma. Consistent with this, ES-62, an immunomodulator secreted by the parasitic worm Acanthocheilonema viteae, can prevent pathology associated with chronic asthma (cellular infiltration of the lungs, particularly neutrophils and mast cells, mucus hyper-production and airway thickening) in an experimental mouse model. Importantly, ES-62 can act even after airway remodelling has been established, arresting pathogenesis and ameliorating the inflammatory flares resulting from repeated exposure to allergen that are a debilitating feature of severe chronic asthma. Moreover, two chemical analogues of ES-62, 11a and 12b mimic its therapeutic actions in restoring levels of regulatory B cells and suppressing neutrophil and mast cell responses. These studies therefore provide a platform for developing ES-62-based drugs, with compounds 11a and 12b representing the first step in the development of a novel class of drugs to combat the hitherto intractable disorder of chronic asthma
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THE ROLE OF ENVIRONMENT IN THE EVOLUTION OF CRANIAL CAPACITY IN HUMANS
Over the last 2 million years, the human brain has undergone an extraordinaryevolutionary journey, expanding in size to nearly thrice that of our ancient ancestors, Homohabilis. This remarkable growth far surpasses the evolutionary changes seen in other primates,indicating a unique path of human development. Scientists have suggested a wide range offactors to explain the dramatic increase in brain size, including environmental, dietary, social,and climatic influences. This paper uses environmental data joined with hominid fossil data tocreate a prediction model using linear regression. Four different models are created, with themost significant model showing that environment variables along with time explain 21 percent ofthe variance found in cranial capacity over the past 7 million years
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