Effects of hydroxycinnamic acids on the glycolysis pathway

Glycolysis is a metabolic pathway vital to the production of energy and some organisms rely on it solely to meet their energy requirements. It is also a central pathway in the metabolism of carbohydrates and a source of therapeutic targets against diabetes and cancer. Caffeoylquinic acids (CQAs) have been extensively studied for their role in the treatment and prevention of diabetes (and cancer) but their mechanisms of action remain mostly unknown. As such, molecular docking was used to find possible targets of CQAs in the glycolysis pathway. The molecular docking assays showed that CQAs were docked preferably to the Rossman fold (nicotinamide adenine dinucleotide — NAD(H) binding site) of oxidoreductases, that use NAD(H) as a cofactor, than to any other site. In-vitro assays were then performed using two NAD(H) dependent oxidoreductases from glycolysis (alcohol dehydrogenase and L-lactate dehydrogenase) in order confirm if CQAs would compete with the cofactor to inhibit the reaction. The results from these assays indicate that CQAs can act as both inhibitors and activators of NAD(H) dependent oxidoreductases of the glycolysis pathway.info:eu-repo/semantics/publishedVersio

Normalization of clonal diversity in gene therapy studies using shape constrained splines

Viral vectors are used to insert genetic material into semirandom genomic positions of hematopoietic stem cells which, after reinfusion into patients, regenerate the entire hematopoietic system. Hematopoietic cells originating from genetically modified stem cells will harbor insertions in specific genomic positions called integration sites, which represent unique genetic marks of clonal identity. Therefore, the analysis of vector integration sites present in the genomic DNA of circulating cells allows to determine the number of clones in the blood ecosystem. Shannon diversity index is adopted to evaluate the heterogeneity of the transduced population of gene corrected cells. However, this measure can be affected by several technical variables such as the DNA amount used and the sequencing depth of the library analyzed and therefore the comparison across samples may be affected by these confounding factors. We developed an advanced spline-regression approach that leverages on confounding effects to provide a normalized entropy index. Our proposed method was first validated and compared with two state of the art approaches in a specifically designed in vitro assay. Subsequently our approach allowed to observe the expected impact of vector genotoxicity on entropy level decay in an in vivo model of hematopoietic stem cell gene therapy based on tumor prone mice

The Feeding Tube- a Simple Yet Handy Aid to Intubate an Unanticipated Difficult Pediatric Airway

Pediatric intubation requires certain unique set of additional skills compared to intubating adults. The challenges of successfully intubation of a child increases as the age and size of the child decrease and are compounded when airway difficulties arise for various reasons. Often in the rural setting, such procedures may have to be carried out by health care personnel who get trained on-the-job, and in the absence of adequate technological back-up. This leads to an increased incidence of failed intubations which can have devastating complications, especially in the pediatric age group. We describe a simple technique which helped us while intubate a 40-day old infant, without any major catastrophes. Keywords: airway management; infant; newborn; intubation; endotracheal

Influence of physician empathy on the outcome of botulinum toxin treatment for upper limb spasticity in patients with chronic stroke: A cohort study.

To examine the relationship between patient-rated physician empathy and outcome of botulinum toxin treatment for post-stroke upper limb spasticity.Cohort study.Twenty chronic stroke patients with upper limb spasticity.All patients received incobotulinumtoxinA injection in at least one muscle for each of the following patterns: flexed elbow, flexed wrist and clenched fist. Each treatment was performed by 1 of 5 physiatrists with equivalent clinical experience. Patient-rated physician empathy was quantified with the Consultation and Relational Empathy Measure immediately after botulinum toxin treatment. Patients were evaluated before and at 4 weeks after botulinum toxin treatment by means of the following outcome measures: Modified Ashworth Scale; Wolf Motor Function Test; Disability Assessment Scale; Goal Attainment Scaling.Ordinal regression analysis showed a significant influence of patient-rated physician empathy (independent variable) on the outcome (dependent variables) of botulinum toxin treatment at 4 weeks after injection, as measured by Goal Attainment Scaling (p<0.001).These findings support the hypothesis that patient-rated physician empathy may influence the outcome of botulinum toxin treatment in chronic stroke patients with upper limb spasticity as measured by Goal Attainment Scaling

Patient-Specific Prosthetic Fingers by Remote Collaboration - A Case Study

The concealment of amputation through prosthesis usage can shield an amputee from social stigma and help improve the emotional healing process especially at the early stages of hand or finger loss. However, the traditional techniques in prosthesis fabrication defy this as the patients need numerous visits to the clinics for measurements, fitting and follow-ups. This paper presents a method for constructing a prosthetic finger through online collaboration with the designer. The main input from the amputee comes from the Computer Tomography (CT) data in the region of the affected and the non-affected fingers. These data are sent over the internet and the prosthesis is constructed using visualization, computer-aided design and manufacturing tools. The finished product is then shipped to the patient. A case study with a single patient having an amputated ring finger at the proximal interphalangeal joint shows that the proposed method has a potential to address the patient's psychosocial concerns and minimize the exposure of the finger loss to the public.Comment: Open Access articl

Insights into the Regulatory Characteristics of the Mycobacterial Dephosphocoenzyme A Kinase: Implications for the Universal CoA Biosynthesis Pathway

Being vastly different from the human counterpart, we suggest that the last enzyme of the Mycobacterium tuberculosis Coenzyme A biosynthetic pathway, dephosphocoenzyme A kinase (CoaE) could be a good anti-tubercular target. Here we describe detailed investigations into the regulatory features of the enzyme, affected via two mechanisms. Enzymatic activity is regulated by CTP which strongly binds the enzyme at a site overlapping that of the leading substrate, dephosphocoenzyme A (DCoA), thereby obscuring the binding site and limiting catalysis. The organism has evolved a second layer of regulation by employing a dynamic equilibrium between the trimeric and monomeric forms of CoaE as a means of regulating the effective concentration of active enzyme. We show that the monomer is the active form of the enzyme and the interplay between the regulator, CTP and the substrate, DCoA, affects enzymatic activity. Detailed kinetic data have been corroborated by size exclusion chromatography, dynamic light scattering, glutaraldehyde crosslinking, limited proteolysis and fluorescence investigations on the enzyme all of which corroborate the effects of the ligands on the enzyme oligomeric status and activity. Cysteine mutagenesis and the effects of reducing agents on mycobacterial CoaE oligomerization further validate that the latter is not cysteine-mediated or reduction-sensitive. These studies thus shed light on the novel regulatory features employed to regulate metabolite flow through the last step of a critical biosynthetic pathway by keeping the latter catalytically dormant till the need arises, the transition to the active form affected by a delicate crosstalk between an essential cellular metabolite (CTP) and the precursor to the pathway end-product (DCoA)

Sheep Updates 2007 - part 4

This session covers eight papers from different authors: GRAZING 1. The impact of high dietary salt and its implications for the management of livestock grazing saline land, Dean Thomas, Dominique Blache, Dean Revell, Hayley Norman, Phil Vercoe, Zoey Durmic, Serina Digby, Di Mayberry, Megan Chadwick, Martin Sillence and David Masters, CRC for Plant-based Management of Dryland Salinity, Faculty of Natural & Agricultural Sciences, The University of Western Australia, WA. 2. Sustainable Grazing on Saline Lands - outcomes from the WA1 research project, H.C. Norman1,2, D.G. Masters1,2, R. Silberstein1,2, F. Byrne2,3, P.G.H. Nichols2,4, J. Young3, L. Atkins1,2, M.G. Wilmot1,2, A.J. Rintoul1,2, T. Lambert1,2, D.R. McClements2,4, P. Raper4, P. Ward1,2, C. Walton5 and T. York6 1CSIRO Centre for Environment and Life Sciences, Wembley, WA 2CRC for Plant-based Management of Dryland Salinity. 3School of Agricultural and Resource Economics, University of Western Australia. 4Department of Agriculture and Food WA. 5Condering Hills, Yealering. 6Anameka Farms, Tammin. MEAT QUALITY 3. Development of intramuscular fat in prime lambs, young sheep and beef cattle, David Pethick1, David Hopkins2 and Malcolm McPhee3,1School of Veterinary and Biomedical Sciences, Murdoch University, Murdoch, WA, 2NSW Department of Primary Industries, Cowra, NSW,3NSW Dept. of Primary Industries, University of New England, Armidale, NSW, 4. Importance of drinking water temperature for managing heat stress in sheep, Savage DB, Nolan JV, Godwin IR, Aoetpah A, Nguyen T, Baillie N and Lawler C University of New England, Armidale, NSW, Australia EWE MANAGEMENT TOOLS 5. E - sheep Management of Pregnant Merino Ewes and their Finishing Lambs, Ken GeentyA, John SmithA, Darryl SmithB, Tim DyallA and Grant UphillA A Sheep CRC and CSIRO Livestock Industries, Chiswick, NSW B Turretfield Research Station, SARDI, Roseworthy, SA 6. Is it important to manage ewes to CS targets? John Young, Farming Systems Analysis Service, Kojonup, WA MULESING 7. Mulesing accreditation - Vital for Wool\u27s Future, Dr Michael Paton, Department of Agriculture and Food WA, 8. Mulesing Alternatives, Jules Dorrian, Affiliation Project Manager Blowfly Control Australian Wool Inovatio

Time-dynamic effects on the global temperature when harvesting logging residues for bioenergy

The climate mitigation potential of using logging residues (tree tops and branches) for bioenergy has been debated. In this study, a time-dependent life cycle assessment (LCA) was performed using a single-stand perspective. Three forest stands located in different Swedish climate zones were studied in order to assess the global temperature change when using logging residues for producing district heating. These systems were compared with two fossil reference systems in which the logging residues were assumed to remain in the forest to decompose over time, while coal or natural gas was used for energy. The results showed that replacing coal with logging residues gave a direct climate benefit from a single-stand perspective, while replacing natural gas gave a delayed climate benefit of around 8-12 years depending on climate zone. A sensitivity analysis showed that the time was strongly dependent on the assumptions for extraction and combustion of natural gas. The LCA showed that from a single-stand perspective, harvesting logging residues for bioenergy in the south of Sweden would give the highest temperature change mitigation potential per energy unit. However, the differences between the three climate zones studied per energy unit were relatively small. On a hectare basis, the southern forest stand would generate more biomass compared to the central and northern locations, which thereby could replace more fossil fuel and give larger climate benefits

Using verbal autopsy to measure causes of death: the comparative performance of existing methods

Background: Monitoring progress with disease and injury reduction in many populations will require widespread use of verbal autopsy (VA). Multiple methods have been developed for assigning cause of death from a VA but their application is restricted by uncertainty about their reliability. Methods: We investigated the validity of five automated VA methods for assigning cause of death: InterVA-4, Random Forest (RF), Simplified Symptom Pattern (SSP), Tariff method (Tariff), and King-Lu (KL), in addition to physician review of VA forms (PCVA), based on 12,535 cases from diverse populations for which the true cause of death had been reliably established. For adults, children, neonates and stillbirths, performance was assessed separately for individuals using sensitivity, specificity, Kappa, and chance-corrected concordance (CCC) and for populations using cause specific mortality fraction (CSMF) accuracy, with and without additional diagnostic information from prior contact with health services. A total of 500 train-test splits were used to ensure that results are robust to variation in the underlying cause of death distribution. Results: Three automated diagnostic methods, Tariff, SSP, and RF, but not InterVA-4, performed better than physician review in all age groups, study sites, and for the majority of causes of death studied. For adults, CSMF accuracy ranged from 0.764 to 0.770, compared with 0.680 for PCVA and 0.625 for InterVA; CCC varied from 49.2% to 54.1%, compared with 42.2% for PCVA, and 23.8% for InterVA. For children, CSMF accuracy was 0.783 for Tariff, 0.678 for PCVA, and 0.520 for InterVA; CCC was 52.5% for Tariff, 44.5% for PCVA, and 30.3% for InterVA. For neonates, CSMF accuracy was 0.817 for Tariff, 0.719 for PCVA, and 0.629 for InterVA; CCC varied from 47.3% to 50.3% for the three automated methods, 29.3% for PCVA, and 19.4% for InterVA. The method with the highest sensitivity for a specific cause varied by cause. Conclusions: Physician review of verbal autopsy questionnaires is less accurate than automated methods in determining both individual and population causes of death. Overall, Tariff performs as well or better than other methods and should be widely applied in routine mortality surveillance systems with poor cause of death certification practices. © 2014 Murray et al.; licensee BioMed Central Ltd