HUM-MOLGEN companies: PHISIO-BANK INFORMATIONAL ENTERPRISES OF CANADA

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News I:   Neuropharma and Cognitive Enhancement Therapeutics in Psychosocial & Kinesiological Rehabilitation. A new "star attraction", the element lithium, has proven to be significant as a neurotropic drug both as experimental spinal cord injury (cf. quadraplegia, paraplegia) rehabilitation and has in the past been practiced in mental health conditions as an effective mood stabilizer and for cognitive enhancement therapy. It remains to be seen what relationships exist between the lithium agent and "neurolepsis" in neuronal systems and what can be learned from cellular anatomy-cell functional relationships of the CNS (cf. the media liaison at the U. of S & T, Hong Kong.)

News II:   Neurhormonal Immunomodulation. At "SkyeBlue" there are ideas about activation of the human humoral immune system via cause-effect relationships between the cerebral CNS and primal neuronal-hormonal agents that can cause a cascade effect to bring about what we can term here an "immuno-shower". "SkyeBlue" believes that both the humoral cascade effect and a repeated challenge from environmentally sourced, low-level stimulation results in a protective effect against some Cancers, although this could be genetically influences by other factors. Could it be true that mood and higher cerebral functions impacts neuronally immune function?

News III:  Molecular Medicine and Nutrigenomics. This exciting field is opening up frontiers in healthcare for various candidate nutraceuticals in food that may accelerate preventative healthcare through dietary intervention and tailored in clinical settings to conditions like immunomodulation, production in animal livestock and their welfare in care. "SkyeBlue" is planning to publish an upcoming paper on integrating functional feeds and their role with sustainable lower-quality feeding including pretreatment, supplementation and rumen probiotics.

News IV:  Manipulation with Probiotics of Rumen Digestion in Ruminant Nutrition. "SkyeBlue" is searching for candidates to explore avenues for RNA-based silencing techniques other than PNA-B12 for microbial and mammalian cell metabolic regulation (see: Center for New Technologies, U. of Warzawa, PL) in BC Canada for yeast-based fishmeal feeding with salmon and marine seagrasses reared in vertical farming (greenhousing) being aware of differing phylogeny in metabolic-based molecular genetics. The use of B12 is just beginning to open a new field of agent-derived "go-betweens" or "delivery modality" between direct application (DAs) and molecular cell genetics in differing microbiota, animal and plant phylogenies. A so-called new ortho-biopharma field involving metabolic genetics in metabolomics.

Currently investigated is a recent report that has surfaced, but nevertheless rare medical condition or phenomenon where brain concussion or 'knock-out' (unconsciousness) can lead to over-compensation upon apparent recovery and overactivation of brain centre(s) and function(s). One e. g. is perceiving fractal geometries in everyday objects, not perceived before. The second e. g. we have evidence for are under two 'equilibrated' drug regimens using two relatively new anti-psychotics, like Invega(R) (generic drug name=paliperidone), and that mental function such as information processing so as to perform everyday tasks or activities, is activatable and/or maintainable. These reports corroborate new ones with use of these drugs in practice amongst other mental health consumers in the community. It would be of further interest to probe what if any neuropeptides, neurhormones and balance of neurotransmitters and if in the long term developmental changes occur in the brain's neuro-circuitry subject to severity. Note, the LMW-proteome in circulating in the bloodstream is just beginning to be investigated from the brain, an e. g. of which are the stress hormones.

Cognitive enhancers are coming now into the fore and are also within theories of 'plasticity' of brain structure and function. We have always speculated as to whether cognitive enhancers (e. g. processing, problem solving, storage, and retrieval functions) earlier on have further down the line could have a neuroprotective effect, a new frontier of research in neuroscience, against Alzheimers or other dementias. We speculate that dementias are a type of developmental disorder of the brain to be protected against onset or progression. The brain progresses in stages as it is hypothesized we have put forward new concepts of: cognitive enhancement, neuroplasticity, neurodevelopmental disorders and neuroprotective interventions.

The recent studies of Reelin proteins in the brain that can reverse the overt signs of abberant cellular anatomical plaque and amyloid-beta fibril entanglements can 'reverse' this clinical phenotype of Alzheimers via the Reelin cell signaling pathways and recovery of cognate cognitive deficits. (See also the story by pasting this link on you browser: http://www.ub.edu/web/ub/en/menu_ eines/noticies/2014/03/010.html.)

Biopharmacogeneic Therapeutic Activation of the Cellular Immune System. The humeral immune response system model rudiments: --Cytotoxic T cells recruited by helper T cells (initiates T and B cells) kills infected body cells by pathogens or invaders (parasitic, bacterial and viral) --Natural killer (NK) cells recognizes and kills cells infected by a broad range of invaders --Killer (K) cells also kills infected cells coated with antibodies X-reacted with their antigenic determinants --Biopharmacogeneic drugs that effect cell signalling activating cellular immunity --Cytotoxic complement-like cell destruction by humeral cellular factors --Cancer (melanoma) is acted on by circulatory leukocyte and endothelial cells (as a model) --At this time there are regulatory homeostatic factors that affect phagocytosis such as calreticulin; what factors for enhancement and/or optimization are possible together with bio-pharma in biotech is a question. T, B, NK, and K cells, complement, and phagocytosis all are involved in the total immunogeneic response. The most recent news to come out of Skye Blue in regards to our hypothetical modeling of sheep immunogeneic cell lines is as follows: 1) a humeral haemocytotic germinal cell line primed with hormonal cell blockers to growing cancer cells; could an e. g. be anti-CD47 signaling agent or hormone encouraging an effective macrophagic phagocytotic outcome, 2) a systemic CNS –sourced neurhormonal activation of complement cytotoxicity and phagocytosis of cancer cells (an e. g. in the literature is with acetylcholine and other anti-tumour cytotoxic T-cell immune response mechanisms).

"Chronic Inflammation, Immunogeneicity and Disease: the promise of new drug discovery." We are publishing this new paper on the links between chronic inflammation, immunogeneic response and disease states, such as diabetes, atherosclerosis and cancer, and their links to both nutritionals, Vit D and fructans, in the lower gut, a clue to the linkage between the two factors and other diseases also linked to the prolonged chronic elicitation or aggravation of the inflammation response. We invite editorial oversight on the investigation of the inflammation process including published/unpublished research findings on this exciting and growing field in health research. There are new monoclonal antibodies administered by subcutaneous injection that can be used against products of genes that help activate inflammation or possibly act to enhance the production of gene products that help modulate the inflammation cascade, with nutritionals. Vaccines would of course not be a functional route, unlike the in vitro, ex vivo therapeutic modality of producing monoclonal antibodies. The immune response as outlined and small molecules in the inflammatory response could interact in future drug trials and thus affect immunogeneicity in a negative way in fighting disease. Systemic inflammatory response syndrome (SIRS) could be used as a model for the study of whether drug trials will have this issue of interactions with the immune system and affect disease fighting ability of the body. The cytokine storm as described elsewhere is an uncontrolled feedback cascade eliciting T cell response and macrophages to the site of infection; however, over response can lead to complications and even death. (Thank you to our respondent who mentioned with the Wordpress.com blog feedback on the 'cytokine storm'.)

In our continued search and development with the use of synthetic biology for the advancement of Vit D activated-forms of the drugs and their pharmacogenic effects to T2Diabetes, atherosclerosis and heart disease or health (in general) and cancers, including lower bowel cancer, we propose a precursor derivative (a steroidal 'lipoic' aldehyde) synthesized (see: Flores, 1980, Kalamazoo College MI U.S.A.) through the body's natural metabolic synthetic pathways to Vit D's activated forms to act as 'agonistes' against the feedback inhibition (FBI) to the drug with <increases in effectivity in therapeutic indices>. There are, as we speak, alternative approaches which may be less effective using Vit D at its receptors for various tissues types and/or gene-selectivity with Vit D receptor modulators (VDRMs) that act with ligands (it is interesting to note here that recent use of non-seco-steroidal VDR ligands, unlike activated forms of steroid-like Vit D, have been developed for this) resulting in their increased effect. Synthetic biology uses chemical protocols and inferences to solve mechanistic problems useful for medicinal chemistry. There are two sides to this problem on the sterol lanosterol.

Manipulation with Probiotics of Rumen Digestion in Ruminants: Direct-Applied (DA) Post-Transcriptional Gene-Silencing for the Regulatory Manipulation of Rumen Microbes via Transcription Factor Engineering.

1) Recommended: Yeast, an e. g. of which is Saccharomyces cerevisiae fed continuously at 5g/d to improve fibre digestion attacking the carbohydrate-lignin complexes in plant residues.

2) Recommended: Yeast, an e. g. of which is Saccharomyces cerevisiae fed continuously at 5g/d with a grass diet that would support amino acid synthesis and microbial growth.

3) Recommended: Aspergillus oryzae is known to retain like yeast in the rumen and will be fed at a given rate (g/d). To provide A. oryzae as a 'surrogate' amplified protein unspecified at this time if it can retain in the rumen although 'tweaking' the energy supply pool which increases energy availability from fibre by deregulation of feed-back inhibition (FBI) might serve this purpose (see: Flores, 1988, MAppSc thesis).

These are all here-to-fore untested options. We believe there is a moratorium on any further genetic engineering in the rumen (consulting ILRI, Addis Ababa, Ethiopia for further advise and any opinions on this matter is suggested).

4) Recommended: Growth stimulation for Cropping with PNA-Auxin/ARFs, e. g. XL-Grow varieties for seagrass aquaculture.

5) Recommended: Antimicrobials, e. g. mastitic creams for the dairy cow's udder with PNA-B12 or our own proprietary PNA-K2(x5).

6) Other Examples: Biostimulants to improve biofertilizer performance as DA Biologics.

Oligosaccharides & Peptides/Amino Acids and Possible Effects on Cell Proliferation.

Genomic sequencing with analyses of specific genes using a microarray approach with rumen microbial cell modeling, similar to mammalian cells, for putative products archaetypical in procaryotic rumen microbial cells, that will require significant investigation as was discovered for mammalian p38, MK2 and alpha-TNFproducts and a 3'-UTR sequence, with an ARE sequence, that is untranslated coding for a transcript that normally suppresses alpha-TNF products implicated in mitogenesis, with the correlation of treatment effects in in vitro culture with inulin (e. g. +fructan in complete media) and pre-formed amino acids (peptides or +peptones in basal media). There are several reviews (see: G. Pang et al., 2012) one that implicated the role of receptors or proteins in the gut (G.I. tract) serving to translocate intracellularly to the nucleus as transcription factors (TFs) that may suggest further details as to how this proposed mechanism might work. p38 as a member of the major MAPK family of proteins would be involved with fructan and pre-formed amino acids targeting receptor proteins that act in cell signaling with p38 metabolically through known modifications of enzymes and other binding proteins and/or their subunits, for e. g., via phosphorylation with kinases and/or acetylation of sugars, which is possible.

SKYEVIEW: In a recent review (2012) it has been suggested that functional foods such as VitD and fructan (FOS) be now measured as to their effects via "gold standard" measurements as with chemokines and cytokines (e.g. ILs), are define inflammatory or anti-inflammatory (e. g. fish sauce proteins lead to increase in the type of characteristic markers that are described as anti-inflammatory). In a very recent review from Quebec, Canada researchers in 2014 studied dairy and its products have been more closely correlated between those natural ingredients and inflammatory markers (above) which are: TNF-alpha, IL1-beta, Il-6, Il-8, MCP-1, and as opposed to IL-10, which is considered anti-inflammatory. The overall picture of VitD/fructan and their effect on chronic inflammation and disease aetiology (see: here, elsewhere) leads one to think about the very possibilities of such schema for such "gold standards" in blood measurements upon ingestion of functional foods. The inflammatory profile from the blood biochemical profiles of how high/low these inflammatory markers are vs. anti-inflammatory markers could served as a starting schema. It should be added that the organ that comes to mind here first of all amongst others would be the lower G.I. tract which have measurable glycan-type receptors for FOS and nuclear steroid or VitD receptors (VDRs) in the gut lining to bring about cell signaling. Which brings us further to the point of which operative drug agents (small organic molecules) that could be designed to bring about functional food-type, anti-inflammatory action over the long term to prevent, alleviate or help bring about a cure to chronic inflammatory-type diseases in various organ tissues such as atherosclerosis, diabetes type-II and colonic cancers. There is also question further to this here as to how to fortify plant products with the family of phytosterols, including VitD, and for that matter fructan and other fat-soluble vitamins and minerals (note: beta-carotene from daffodil has already been considered a success to be tested in India in future and further what with the new developments to use genome engineering) that have similar effects like VitE to be anti-cancer and have wildly great potential in huge middle class markets in the developing world for multi-nationals wishing an ROI on earlier crop R&D development. Cows milk could also be enriched in our view not by what could be more slow, less effective breeding programmes for anti-inflammatory milk-type protein-enriched milk products using the more publicly acceptable genome engineering techniques which are likely to be reconsidered seriously commercially by the USDA in the coming years as just one of the agenda items with SkyeBlue in genome engineering and using amongst other strategies like disease resistance and increased hardiness and greater productivity in plant or crop and animal biotechnology. Amino acid nutrition and metabolism can lead to new hypotheses regards new mechanisms in the CNS with neurmodulation including putative effects on increased LBM mass accretion and fat loss via hGH with the pituitary and hypothalamus where both NEAAs and HIS are implicated at this time to be tested in animal feeding studies.

SKYEVIEW: There is a new possibility with endocrine and humeral, with greater specificity, systems regarding ageing as a process with the male vs female sex as different models and perhaps adding to the hypothesis that the unique difference in physiology in males could be marked considerably when manipulated with both stress and sleep related hormones and healthy protein levels enriched in the diet including other immune balancing regimens with dietary nutritionals such as PUFAs, complex CHOs, at this time, unknown at this time, oligopeptides and oligosaccharides (including chosen disaccharides and monosaccharides) of animal (tuna is one studied protein and processed for per os encapsulized delivery) and vegan origin (beets is one studied and commercialized). We know in general in their late 70s or early 80s that people are gradually ageing more and that males live about 2 years shorter than their female cohorts. If we plumb the basis of the 2 cases we will know how to increase longevity effectively in addition to lifestyle habits - stress, dietary and exercise perhaps additionally with medical supervision together with requisite pharma dispensed for health reasons (e. g. cholesterol, blood sugar, hypertension, sleep (for deeper sleep), hi-protein supplementation, PUFA supplementation, VitD2,3 for immune support and bone density and various other vitamines & minerals). It is believed by "SkyeBlue" that "bulk" action of complex-CHOs and other simpler sugars are best addressed by more rationale approaches like specific oligsaccharides, and other sugars in modicum dietarily, in capsule form, and there is conjecture to believe that even dietary pectin as from fruit is invaluable for its healthy nutrition as with heart health, heart pumping action (regulated with hypertension) and in and around it with arterial atherosclerotic development. As the adage goes: "an apple a day keeps the doctor away."

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