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Web-based research and consulting including developing new ideas, new technologies and inventions and making them available to problem solvers.
We join with professionals finding solutions, formulating new ideas for their problems. We invite, as with Ideaconnection.com an affiliated organization on the Internet, like-minded people to recruit resource personnel, viz. engineers, professional managers and scientists, to bring theory or concept to practice and eventually a reality.
We featured a "hot topic" on parallels in Vit D and fructan metabolism in atherosclerosis, diabetes and cancer and implications on drug discovery recently. Despite lack of head way, we would like, however, to broaden the base of research with our regular, web-based features including journal articles (with references). A recent addition coming out will be on multiple sclerosis and the modulation of the immune response. Antigens can be used with monoclonals or with new nanotechnology. This is exciting to us as it has required consultation and collaboration between industry and academe including medical practitioners. There is an approach with Vit D and fructan metabolism that presents future potential for drug discovery.
Inflammation is now also implicated, some better studied than others, in asthma (pulmonary disease), rheumatoid arthritis, Alzheimer's and perhaps multiple sclerosis. There has and recently been more investigation with possible or more conclusive biomolecular links that imply and illustrate a role for inflammation in certain diseased conditions as lower bowel health, including irritable bowel syndrome, colo-rectal cancer and cancer, in general, cardiovascular health including atherosclerosis and insulinaemic-resistance and the diabetic condition. Drug discovery has already begun including as proposed in this paper with agents that act as nutritionals or small molecule drug agents. Finally, it should be noted that a phenomenon not uncommon called the 'cytokine storm' is a reaction of the immune system to a site of infection with T cells, macrophages and cytokines and has been shown to have been involved in the demise of recent H1N1 flu deaths thus implying deleterious effects to the immune system and may be at levels higher than chronic inflammation. Levels along with immunogeneicity with small molecular agents or drug targets implied here would moderate it further to the norm. There is a need to further elucidate the synthetic biology and medicinal chemistry with small molecular or drug agents. It is open to question as to whether small molecular agents or drug targets involved with chronic inflammation response and/or disease processes will cross react with the immune system.
With cardionemic foods there is a dual effect on physio-musculo tissue function which one can speculate as to putative biogenic factors in tissue acting to improve or facilitate cardio-musculo health and other aspects of cardiovascular health. The focus on omega-3 fatty acids as the so-called 'in toto factor', is one area that is to be further explored.
Flax seed oil supplements (a source of omega-3 fatty acid) is implicated in reducing inflammation with auto-immune disease such as lupus and may have implications in cardio-health as do all omega-3-fatty acid sources including fish and olive oil. As well, the use of complex carbohydrates implicated in maintaining cardio-health and implicated here with inflammation is likewise a factor in cardiohealth risk.
The investigation of whether it is possible to produce a low glycaemic corn meal flour due to slow-release starch and protein that relates to insulinaemia that could be possibly processed and made, relates to cf. "mining" the low molecular weight (LMW) proteome and finding "common" mechanisms between glucose receptivity and that of amino acids which are antagonists (from biopharma) with insulin. This approach would be novel in light of other drug approaches in treating diabetes type II which involve: insulin, decreased glucose synthesis and release from liver stores and increased excretion in urine and faeces. It should be a classed as a preventative modality in treatment of the disease of diabetes.
The metabolosome [see: MEDBIOSE (Bio-pharmacor)] is beginning to be studied although little attention has been given to genetic predisposition or genomics and phenotype (viz. longevity or "good genes"; the mystery of "protective genes" against life-style related diseases) and the use of in vitro, ex vivo studies with possible biomarker candidates with electrophoresis/MS (mass spectrophotometry) and down the road for drug discovery. As developments unfold we will be featuring possible papers (with references) on this research topic.
Nutrigenomics/nutrigenetics and the discovery of new protein targets for nutritionals and/or drugs (smaller organo-chemical or metabolite molecules) offers the following approaches for drug discovery: - mRNA assays with up/down regulation with in vitro/ ex vivo studies, for e. g. with nutritionals, search of the LMW (low molecular weight) proteome with LC (liquid chromatography)/MS for biomarkers directly or indirectly associated with drug targets, -transcription factors (drug targets in cancer and inflammation) binding studies [e. g. Oligonucleotide Array-based Transcription Factor Assay (OATFA)], - EMSA (electrophoretic mobility shift assay) for RNA/DNA binding studies with proteins & antibodies with non-denaturing gel electrophoresis, - leads-based fragments of smaller molecules against target proteins that are identified and elaborated on to create leads/drugs with, for e. g., use of PSR (plasmon surface resonance) antigen fragment antibody binding studies, - competitive proteome (i. e. enzyme targets)-drug/inhibitor studies on fluorescent-scanned PAGE gel electrophoresis (fluorescent chemical probes linked to enzymes) and - 2D (pIxMW) electrophoretic (50-500 protein capacity) assays. Drug therapeutics as follows: - monoclonals against antigenic targets and - vaccines (antigenic agents) using new nanotechnology as presented to the immune system in the spleen as opposed to white blood cells (WBC).
Genetically predisposed and environmentally acquired mistakes for repair on double-stranded DNA and other single nucleopolymorphisms (SNPs) on DNA may in future be treated via natural cell repair mechanisms in vivo together with the depleted low molecular weight [LMW]-proteome acting in the cell signaling pathway to the nucleosome to repair and for disease processes prophylactically reversed or treated.
Psychotropy is a tool in developmental disabilities where mental illness, retardation and epilepsy can be conditions. Psychotropic drugs are said to facilitate mental processing and together with anti-psychotics can improve one's mental status in regards to processing information, social withdrawal, energy, obsessive-compulsive disorders, learning, execution with multi-tasking or organization and short-term memory deficits. Psychotropy, too, is an issue with all mental conditions including dementia or Alzheimer's in geriatrics. The act of a drug that can enhance mental performance is a powerful concept and one that is both contentious and forbidding from a scientific standpoint. Is it possible for example to increase and even override the lack of capacity of a brain damaged individual's ability to process information or think? In terms of calibre and speed, these are issues that need to be addressed further with possibilities that psychotropic drugs seem to offer other conditions. There are other theories regards mental health and its maintenance in the brain. Nutritionals and their biopharmacopoeia of the the brain may be one possibility of which there are known examples. Electrophysiological interventives may be another. Brain and developmental function (anatomical function or process) is now being proposed as the background for characterization of the condition regarding its genetics, onset or beginning (usually in the late teens or early adult age), progression and even reversal, with this approach. Interventive actions and stage may be issues. Is nutrigenomics a tantalizing subject in this area? The theories of anatomical development, function and nutrition or its relationship as a support are fundamental standpoints. Is there a bionutritional pharmacopoeia with nutrigenomics (i. e. interventive biomolecules or agents to nutritionals) to mine in this area?
SKYENEWS: It has been observed that metabolises of energy is variable in human beings (viz. energy levels and drive vary depending on a human being's energy status) and that a human being's weight gain on an as per intake basis can vary which has recently been highlighted by findings investigated at the Univ. of New South Wales, Sydney that protein KLF3 mutant and adipolin from adipocytes can increase glucose metabolism (and fat deposition) leading one to speculate whether drugs can be developed to interact with KLF3 protein and the expression of adipolin hormone. Weight watchers look out for that energizer drink on your store shelf- a new generation, perhaps, that could be understating it.
SKYENEWS: A new finding of a new gene type "in triplicate", a mutant gene for haemophilia was recently solved and could lead to new discoveries with drugs that treat cardio insufficiency, arrhythmia and hypertension as examples. The third gene in the puzzle, ONECUT in haemophilia B Leyden completed the picture. The new drugs would bind the gene(s) coding for clotting factor IX and help suppress the gene(s).
SKYENEWS: We are searching for problem solvers to help find enzyme technology in regards to buffers and their capacity to preserve ensilage biomass for feeding and energy with comparing practices, viz. the variability of adding molasses, ground grains, dried beet or citrus pulp, soy hulls, hominy, and dried brewer’s grains and the latter being relatively expensive, heat damaging (solar) cut grasses or legumes in the field which curtails buffers or buffering capacity, moisture or wetness and increases osmolarity which are required to decrease nitrogen (N) degradation and the measure of interest here which somewhat in degree is practiced. There are genetically modified (GM) prebiotics traits planned for such as decreasing protease activity, increasing water-soluble carbohydrate (WSC) (e. g. fructan) and breaking down buffering substances in intact forage. It is speculated that reducing buffering capacity would have the added benefit of direct loading of ensilage to the silo in a mechanized setting and without need for weather conditions.
SKYENEWS: Biomass fermentation for energy is limited commercially by viability in terms of costs of inputs and fixed costs. Would it be possible to design an ion channelling system that is powered by ATP for the uptake of nutrients or electrolytes and cycles out recombinant protein products (RPPs) or bioenergy substrates which bypasses a step in cell disruption and the collection of cell detritus and directly extracts the products from solution in continuous flow fermentation. X-ray crystallography is used for defining structures although freezing at -70 deg C and cryo-transmission electron miscroscopy (cTEM) by cryo-fixation on macromolecular assemblies can define total structure including domains, fine-structure, subunits, etc. It is speculated as to whether "component" parts can be constructively or purposefully assembled for a given mechanism at the molecular level as with transmembrane porins or channels to carry out this function (i. e. nanotechnology). There are also single-base nucleotide polymorphisms (SNPs) that can be used to fine-tune structure of porins and attach protein leader sequences to facilitate the efflux of substrates through porins.
SKYENEWS: The whole-body <organosome> system is to be considered as several systems available for further analyses to guage aspects and relative importance of metabolic processes, homeostasis, regulation, and cellular communication, with the body's: skin and rest of its outer enveloppe:irradiation; gastroenteric system and associated organs:inputs to all nutrients, and the respiratory-circulatory system:gases C-sinking for metabolises to energy, tissue maintenance and tissue synthesis. Further to this, the mind<->body axis will explore possible relationships between <organosomes> and their <metabolosomes> and that of the brain's central nervous system (CNS) neuronal system and its proteome of neuropeptides, neurhormones and neurotransmitters, amongst others. We are implying here that nutrients may have the most greatest potential and bearing on discovery or finds on metabolism and for drug discovery to occur regards its <organosome> and the input types it is impacted with.
SKYENEWS: Studying the gastroenteric system (and its associated exocrine organ system) as a whole <organosome> is called for due to ample evidence that water-soluble carbohydrates (WSCs) and pre-formed amino acids (PFAAs) (amino acids+peptides) have an adventitious effect on beneficial or commensal gut microflora of the lower bowel, e.g. protection from colonic cancer. It may also be that a CNS (brain) neurocrine/endocrine <organosome> occurs in a mind <-> body axis. Search for a lower molecular weight [LMW] proteome is a start in probing targets for psychoactives and/or endocrine agents. The recent problem in the production of increasingly economically valuable sheep products with the barber's pole worm infestation of susceptible sheep, an issue facing Meat & Livestock Australia where chemical drenching is currently used, is an example, where an immunogeneic system can be engineered or more simply the chronic inflammatory response and the cytokine storm phenomena be used for further biopharma drug discovery in the gastro-enteric gut.
SKYENEWS: The schema of <organosomal> analyses to breakdown bodily systems or functions with intent to study any possible <mind-body> axes relationships and use as an approach for <major drug discovery> was proposed above in the preceding has been supported by other studies outlined in Wikipedia under the term "Nutrigenomics". Genetic groupings underlying the various <organosomes> are: 1) respiratory/circulatory metabolism, vascular flow and tissue development, and including cardio-vascular development and health, 2) gastroenteric system and dietary antioxidants and detoxification, bone structure regulation and in disease with the inflammatory response and glucose balance (both in T2Diabetes). The third <organosome>, the skin and body's outer enveloppe plays the role with genetics of VitD activation in liver and kidneys from de novo synthesis in the skin (or from dietary intake) and receptors (or VDRs) in various metabolic networks, being one example. The latter was not included in the outline in Wikipedia.
SKYENEWS: Multi-level senior care facilities face major chronic disease states in their elderly and other extended-care clients including mental health issues, physiotherapeutic rehabilitation, psychosocial or occupational therapeutic care and the host of all other gerontologically-related health issues. Chronic gastrointestinal (G.I.) tract disorders including constipation and viral attacks periodically occur including Norwalk virus including recently mutated lethal forms that have been addressed with conventional vaccines and still new occurences are issues in public health. There is a proposal for approaching the G. I. tract as a whole <organosome> and the need to explore immunogeneic response systems including those involving cell signaling and boosting the <organosomes> anti-viral response. The use of multi-cellular modeling and their activation and active protein agents or products to boost response should be explored.
SKYENEWS: As a postscript to the subject we treated recently (see: http://dannflores5.wordpress.com/2013/08/22//)on possible common causative factors between Vit D and fructans (e. g. inulins) we should have mentioned the intake of omega-3-fatty acids (a polyunsaturated fatty acid, PUFA) that elicit molecular events that contribute to inhibiting the pro-inflammatory response. However, as we mentioned in our proprietary oleo L-fat blend as a margarine substitute for gravies, dairy and baked confectionaries, this may require the inclusion of strong and significant amounts of antioxidants (note: citric and ascorbic acids and anti-oxidants present in fruits and vegetables of which grapes, blueberries and cocoa are examples) as preservative to offset the cell membrane's response in adipocytes to oxidative stress and the opposite response to elicit instead pro-inflammatory events. Further epideomological investigations ('true to reality' studies of scenarios under statistical studies) will shed further light on this claim to implicate a possible role in preventing diseases such as type-2 diabetes (T2D).
SKYENEWS: It is critical to, as we have communicated to the Editor, J. Biotech. (Elsevier, The Netherlands) that the efficiency differential offered by WSCs and PFAAs in support of increased energy 'pool' requirements in GMO probiotics and their increased transport by genetic modification and the fact that amino acid 'pools' stimulate cellulolytics and their activities providing more sugar for the ATP 'pool' should suggest these manipulations with such probiotics in future.
SKYENEWS: The current controversy over the use of probiotics in the rumen and their persistence, albeit, except known inoculants of certain fungi and yeast cultures, is interesting to note in that in the case of K. Gregg et al. (1992), they tracked fluorometrically in the rumen species of hosts transformed for enzymes that breakdown fluoroacetate, a toxic substance in plants typically ingested by sheep, which suggests microbes bound to particulat feed are a prerequisite for recombinant microbes compromised by their transformation to persist in a considerably competitively turning over environment. A solution to this technical hurdle is to earmark microbial hosts in future that are particle-bound and so with their secreted enzymes either on the microbial surface or feed particles. A recent astounding find from a technical standpoint has been the use of the 'functional cellulosome' or units composed of cellulases (e. g. endocellulases, exocellulases, cellobiases), dockerins and adhesins, amongst others that can be combined recombinantly producing units that are more 'physiologically accurate' and 'functional'.
SKYENEWS: The study of endogastric symbionts and their 'subsistence' in the rumen including the need for persistence with their modified GMO cousins and evidence of a mechanism(s) that may shed light on their ability to transiently persist in the rumen via adherence and nutrification through the gut mucosa, their lifecycle between liquid and/or solid phases in rumen digesta and their hypothesized 'mucosal habitat', if proven significant will figure in their manipulation to increase survivability and growth rate with turnover in rumen GMO probiotic feeding and management.
SKYENEWS: New findings in muscle biotechnology from basic studies with fish muscle development in embryogenesis with so-called MRFs (muscle regulatory factors), in particular MRF4 in flounder with its structure and pattern of expression revealed that flounder is a close model for vertebrate smooth muscle but only in the developmental stages. This would suggest either genetically manipulating their expression using reproductive techniques and with further exploration of the low molecular weight [LMW] proteome and its ‘pharma’. In sheep the particular study of stem cell ‘niching’ (stem cells are primordial cells of muscle cells) involving the myofibre of skeletal muscle tissue that grows and hypertrophies as influenced by factors in the microenvironment matrix near the basal lamina via which microprotein factors communicate extracellularly between myofibres and stem cells also called satellite cells in myofibres. The picture is one of reaching an optimum with cell surface-expressed dlk-1factor homologue expressed by pre-adipocytes in muscle tissue whose over expression leads to hypertrophy of muscle fibre. Thus it may be that marbling and hypertophy may be related and should be regulated with the soon to be discovered [LMW] proteomic ‘pharma’. It is still to be seen if the MRF family in vertebrates and their manipulation will enter the picture in this studied phenomenon stem cell ‘niching’. Another issue to be also further researched in future is meat quality such as marbling and cartillage with adipocytes and fibroblasts which regulates and interacts with satellite cell and muscle tissue development.
New Title of Journal: Animal, Growth, Reproduction
and Development journal
Other desktop publishers' titles: Development Biotechnology journal (5 papers in preparation); Biomolecular and Medical journal; Current Topics in Practical and Theoretical Synthetic Biology. For more information on submission instructions and guidelines on style and content for authors, editors and referees pls. write to the Editor, at Agroscientific, Hum-Molgen.De.
PART A. Animal Research & Technology: An article that might be launched is with growth, proliferation and differentiation and development of the immune system against cancer cells and pathogens. As it has been mentioned immunogeneisis with the use of activated mobilized systemic lymphocytotic germinal cell line anti-proliferative hormonal cell blockers and cell proliferative factors with cell-targeting from complement-like cytocytosis and phagocytosis, an example of oncogeneic therapeutics with in vivo cell lines with sheep and others yet to be investigated.
PART B. Animal Production Science. Feeds processing (e. g. dehydration, pelleting) and formulation for avian and porcine species, so-called high-end producers with faster growth rates or improved feed efficiency. In Australia, their market, for example, values ovine species as a choice and because of comparative valuation is increasing in value or profitability with the consumer.
PART C. Biochemistry, Microbiology & Immunology. Intrinsic anti-viral immunity boosted performance and its possible prophylactic use after infection to control pandemic outbreaks. Cell-based systems can be explored and cell signaling could be a possible area in relation to cell-cell activation of these protein products.
The immunogeneic system as has been observed with subjects are higher <titred> than other cases in which cases body fluid secretions and the incidence of microbiota including faecal (e. g. fungi) and autochthonous colonies on skin surfaces, the buccal cavity (dental) and the scalp (dandruff) can in the future be controlled or regulated using immunogeneic tools to <titre>. Thus, personal hygiene, an important medical subject in addition to public health (human to human contact and food poisoning) will finally be solved. Microbiota balance in the digestive tract is presumed in equilibrium with immune boosting as health probiota balance them when taken internally.
PART D. Nutritional Biochemistry. Nutritionals such as Vit D and fructan related drug targets in metabolism and their effect on the inflammation response and diseases affecting the reactions in the adipose and muscle against insulin and glucose uptake (i. e. insulin resistance), inflammation of the interior arterial wall and infection leading to plaque and eventual occlusion in heart disease and the inflammation of the lower bowel and eventual development of polyps and metastasis of cancer cells. JNK1 and p38 are small molecules that play a key role and are to be further investigated for cognates and possible drug targets.
PART E. Digestive Metabolism & Physiology.
PART F. Gastroenterology.
PART G. Computational Biology. An example of use of bioinformatics by programming and sequencing to map linkages and loci using script software and using genetic correlation with phenotype with high capacity microarrays, and further, exploring use of modeling the organosome (see above) for developmental, proliferative, differentiation and growth of cellular systems with further investigation of the in vitro systemic and in situ, ex vivo low molecular weight [LMW] proteome and correlates.
PART H. Reproductive Endocrinology and Technology. Developmental endocrinology in reproductive biology and cloning techniques in fetal growth and development for a greater gestational size or live weight at birth (see: C. R. Krishnamurti, of the Univ. of British Columbia in CANADA).
The use of gene therapy pre-partum upon in vitro fertilization and after gestation, for example, as has been proposed for brain developmental-related diseases if there is a metabolic "lock" on the onset or progression of disease as diagnosed by its various symptoms is possible (see: MEDBIOSE, Hum-molgen.De).
PART I. Nanotechnology. The cellulosome as a nanomachine would be the functional unit of the family of cellulase enzymes from genetically modified organismal (GMO) bacterial or fungal sources. Although cellulases from GMOs grow readily on plates with a cellulose lawn that clear them, there is doubt that the same would occur in the same circumstances in the rumen unless a GMO is further modified, therefore there is the consideration of adding the other associated molecules that aid in providing associative binding required, perhaps not in bulk 'as is' feeds treatment but in the propulsive mixing and bulk flow of rumen contents during incubation or retention. There is the issue of particle-bound GMOs and the degree to which associative factors aid in binding them despite the mixing and flow in the rumen. There is perhaps a need for them to bind effectively to feed particles during digestion. There are the dockerins and cohesins forming hybrid scaffoldins with the cellulases. There are attempts at mimicry of the biological cellulosome. These have been performed recombinantly in the laboratory (Mingardon, F. et al., Appl. Environ. Microbiol. 73: 3822-3832, 2007).
PART J. Bioethics of Animal Care, Reproductive Biotechnology and their Natural Environment.The use of gene therapy pre-partum upon in vitro fertilization and after gestation, for example, as has been proposed for brain developmental-related diseases if there is a metabolic "lock" on the onset or progression of disease as diagnosed by its various symptoms is possible (see: MEDBIOSE, Hum-molgen.De).
Comments: The users of this schemata will notice that the categories cover animal research in an animal facility, animal production as the operational and economic management of livestock, medical biochemistry as connoted amalgamated as: biochemistry, microbiology and immunology, aspects of digestion and metabolism in gastroenterology including aspects of ruminant digestion and physiology, the new computational field of genetic analysis as the basis of solving the whole metabolosome and, finally, reproductive endocrinology and technology with breeding and genetics for improving efficiency with the end of bringing about genetic improvement and increasing herd size.
A MEDBIOS CO.
Last update of this entry: September 19, 2016
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