Lag, Constant and Decay Release Characteristic of St-PVOH Encapsulated Urea as a Function of Coating Thickness Using Different Empirical Models

Uncoated urea, when applied to crops is susceptible to losses from volatilization, leaching, nitrous emission and water eutrophication. Plants require varying quantities of nutrients during different stages of growth; they need smaller amounts during infancy and larger amounts during the development of roots, stalk and stem. In this research, controlled release coated urea (CRCU) was synthesized via encapsulation with starch- polyvinyl alcohol biocomposite (St-PVOH). Lag, constant and decay release characteristic of the CRCU were simulated using different empirical models as a function of coating thickness. Structural elucidation and morphology of the raw urea and CRCU were determined using FTIR and SEM analytical techniques, respectively. FTIR confirm esterification reaction for St-PVOH. The SEM image of the raw urea appears rough and have fine openings while that of CRCU possesses a seemingly decrease in membrane porosity, ordered and uniform layer. This characteristic qualifies the CRCU as a semi-permeable membrane. Simulation results revealed that coating thickness of 4.3 and 6.4 are best desirable in designing a CRCU for plant at infancy stage, root, and stalk and stem development. Overall, sigmoidal law shows best robust prediction to expanded varying coating thicknesses

SEXUAL ABUSE OF DOCTORS BY DOCTORS PROFESSIONALISM COMPLEXITY AND THE POTENTIAL FOR HEALING

Contemporary attitudes to sexual abuse are changing. The Royal Commission into Institutional Responses to Child Sexual Abuse, the response of the Australian Defence Force to allegations of sexual abuse in the military and the work of the Australian Human Rights Commission around sexual harassment in the workplace all indicate a shift in community values. They also represent a shift in our understanding of the nature and scope of professionalism. As each respected institution has its professional failures exposed, it becomes obvious that no group is immune. Existing codes of professional conduct have not protected colleagues or clients from toxic behaviour

Cell cycle of transdifferentiating supporting cells in the basilar papilla

Mitosis of supporting cells has been shown to contribute to the cellular repopulation of the basilar papilla after acoustic trauma. In the present work we report data obtained with light and transmission electron microscopy after acoustic trauma in chicks. We report changes that occur in cell shape, surface morphology, intercellular junctions, nuclear shape and location, and cytoplasmic organization of supporting cells after trauma. The findings strongly suggest that supporting cells transdifferentiate and that the proliferative pattern is similar to interkinetic nuclear migration, as previously shown in the developing neural tube and basilar papilla. S-phase nuclei were positioned adjacent to the basement membrane, suggesting that interaction with the extracellular matrix may occur during the cell cycle. Supporting cells divided with the long axis of the spindle parallel to the reticular lamina and displayed no signs of intercellular communication during mitosis. This suggested to us that the fate of the progeny cells is determined prior to mitosis and that the progeny may be of identical phenotypic fate. Dividing cells had a smooth apical surface. The smooth surface may provide a marker to help identify dividing cells with scanning electron microscope analysis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31271/1/0000177.pd

Dual inhibition of the Echinococcus multilocularis energy metabolism.

Alveolar echinococcosis is caused by the metacestode stage of the zoonotic parasite Echinococcus multilocularis. Current chemotherapeutic treatment options rely on benzimidazoles, which have limited curative capabilities and can cause severe side effects. Thus, novel treatment options are urgently needed. In search for novel targetable pathways we focused on the mitochondrial energy metabolism of E. multilocularis. The parasite relies hereby on two pathways: The classical oxidative phosphorylation including the electron transfer chain (ETC), and the anaerobic malate dismutation (MD). We screened 13 endochin-like quinolones (ELQs) in vitro for their activities against two isolates of E. multilocularis metacestodes and isolated germinal layer cells by the phosphoglucose isomerase (PGI) assay and the CellTiter Glo assay. For the five most active ELQs (ELQ-121, ELQ-136, ELQ-271, ELQ-400, and ELQ-437), EC50 values against metacestodes were assessed by PGI assay, and IC50 values against mammalian cells were measured by Alamar Blue assay. Further, the gene sequence of the proposed target, the mitochondrial cytochrome b, was analyzed. This allowed for a limited structure activity relationship study of ELQs against E. multilocularis, including analyses of the inhibition of the two functional sites of the cytochrome b. By applying the Seahorse XFp Extracellular Flux Analyzer, oxygen consumption assays showed that ELQ-400 inhibits the E. multilocularis cytochrome bc 1 complex under normoxic conditions. When tested under anaerobic conditions, ELQ-400 was hardly active against E. multilocularis metacestodes. These results were confirmed by transmission electron microscopy. ELQ-400 treatment increased levels of parasite-released succinate, the final electron acceptor of the MD. This suggests that the parasite switched to MD for energy generation. Therefore, MD was inhibited with quinazoline, which did not induce damage to metacestodes under anaerobic conditions. However, it reduced the production of succinate compared to control treated parasites (i.e., inhibited the MD). The combination treatment with quinazoline strongly improved the activity of the bc 1 inhibitor ELQ-400 against E. multilocularis metacestodes under anaerobic conditions. We conclude that simultaneous targeting of the ETC and the MD of E. multilocularis is a possible novel treatment approach for alveolar echinococcosis, and possibly also other foodborne diseases inflicted by platyhelminths, which cause substantial economic losses in livestock industry

Effects of DAPT and Atoh1 Overexpression on Hair Cell Production and Hair Bundle Orientation in Cultured Organ of Corti from Neonatal Rats

BACKGROUND: In mammals, hair cells do not undergo spontaneous regeneration when they are damaged and result in permanent hearing loss. Previous studies in cultured Organ of Corti dissected from neonatal animals have shown that both DAPT (r-secretase inhibitor in the Notch signal pathway) treatment and Atoh1 overexpression can induce supernumerary hair cells. The effects of simultaneous DAPT treatment and Atoh1 over expression in the cells of cultured Organ of Corti from neonatal rats are still obscure. PRINCIPAL FINDINGS: In this study, we set out to investigate the interaction of DAPT treatment and Atoh1 overexpression as well as culture time and the location of basilar fragment isolated form neonatal rat inner ear. Our results showed that DAPT treatment induced more hair cells in the apical turn, while Atoh1 overexpression induced more extra hair cells in the middle turn of the cultured Organ of Corti. When used together, their effects are additive but not synergistic. In addition, the induction of supernumerary hair cells by both DAPT and Atoh1 overexpression is dependent on the treatment time and the location of the cochlear tissue. Moreover, DAPT treatment causes dramatic changes in the orientation of the stereociliary bundles of hair cells, whereas Atoh1 overexpression didn't induce drastic change of the polarity of stereociliary bundles. CONCLUSIONS/SIGNIFICANCE: Taken together, these results suggest that DAPT treatment are much more potent in inducing supernumerary hair cells than Atoh1 overexpression and that the new hair cells mainly come from the trans-differentiation of supporting cells around hair cells. The orientation change of stereociliary bundle of hair cells may be attributed to the insertion of the newly formed hair cells. The immature hair bundles on the newly formed hair cells may also contribute to the overall chaos of the stereociliary bundle of the sensory epithelia

Benchtop flow-NMR for rapid online monitoring of RAFT and free radical polymerisation in batch and continuous reactors

A “Benchtop” NMR spectrometer is used for detailed monitoring of controlled and free radical polymerisations performed in batch and continuous reactors both offline and in real-time. This allows detailed kinetic analysis with unprecedented temporal resolution for reactions which reach near completion in under five minutes

WDR1 colocalizes with ADF and actin in the normal and noise-damaged chick cochlea

Auditory hair cells of birds, unlike hair cells in the mammalian organ of Corti, can regenerate following sound-induced loss. We have identified several genes that are upregulated following such an insult. One gene, WDR1 , encodes the vertebrate homologue of actin-interacting protein 1, which interacts with actin depolymerization factor (ADF) to enhance the rate of actin filament cleavage. We examined WDR1 expression in the developing, mature, and noise-damaged chick cochlea by in situ hybridization and immunocytochemistry. In the mature cochlea, WDR1 mRNA was detected in hair cells, homogene cells, and cuboidal cells, all of which contain high levels of F-actin. In the developing inner ear, WDR1 mRNA was detected in homogene cells and cuboidal cells by embryonic day 7, in the undifferentiated sensory epithelium by day 9, and in hair cells at embryonic day 16. We also demonstrated colocalization of WDR1, ADF, and F-actin in all three cell types in the normal and noise-damaged cochlea. Immediately after acoustic overstimulation, WDR1 mRNA was seen in supporting cells. These cells contribute to the structural integrity of the basilar papilla, the maintenance of the ionic barrier at the reticular lamina, and the generation of new hair cells. These results indicate that one of the immediate responses of the supporting cell after noise exposure is to induce WDR1 gene expression and thus to increase the rate of actin filament turnover. These results suggest that WDR1 may play a role either in restoring cytoskeletal integrity in supporting cells or in a cell signaling pathway required for regeneration. J. Comp. Neurol. 448:399–409, 2002. © 2002 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34464/1/10265_ftp.pd

Phoenix Is Required for Mechanosensory Hair Cell Regeneration in the Zebrafish Lateral Line

In humans, the absence or irreversible loss of hair cells, the sensory mechanoreceptors in the cochlea, accounts for a large majority of acquired and congenital hearing disorders. In the auditory and vestibular neuroepithelia of the inner ear, hair cells are accompanied by another cell type called supporting cells. This second cell population has been described as having stem cell-like properties, allowing efficient hair cell replacement during embryonic and larval/fetal development of all vertebrates. However, mammals lose their regenerative capacity in most inner ear neuroepithelia in postnatal life. Remarkably, reptiles, birds, amphibians, and fish are different in that they can regenerate hair cells throughout their lifespan. The lateral line in amphibians and in fish is an additional sensory organ, which is used to detect water movements and is comprised of neuroepithelial patches, called neuromasts. These are similar in ultra-structure to the inner ear's neuroepithelia and they share the expression of various molecular markers. We examined the regeneration process in hair cells of the lateral line of zebrafish larvae carrying a retroviral integration in a previously uncharacterized gene, phoenix (pho). Phoenix mutant larvae develop normally and display a morphologically intact lateral line. However, after ablation of hair cells with copper or neomycin, their regeneration in pho mutants is severely impaired. We show that proliferation in the supporting cells is strongly decreased after damage to hair cells and correlates with the reduction of newly formed hair cells in the regenerating phoenix mutant neuromasts. The retroviral integration linked to the phenotype is in a novel gene with no known homologs showing high expression in neuromast supporting cells. Whereas its role during early development of the lateral line remains to be addressed, in later larval stages phoenix defines a new class of proteins implicated in hair cell regeneration

Gene Expression Analysis of Forskolin Treated Basilar Papillae Identifies MicroRNA181a as a Mediator of Proliferation

Auditory hair cells spontaneously regenerate following injury in birds but not mammals. A better understanding of the molecular events underlying hair cell regeneration in birds may allow for identification and eventually manipulation of relevant pathways in mammals to stimulate regeneration and restore hearing in deaf patients.Gene expression was profiled in forskolin treated (i.e., proliferating) and quiescent control auditory epithelia of post-hatch chicks using an Affymetrix whole-genome chicken array after 24 (n = 6), 48 (n = 6), and 72 (n = 12) hours in culture. In the forskolin-treated epithelia there was significant (p<0.05; >two-fold change) upregulation of many genes thought to be relevant to cell cycle control and inner ear development. Gene set enrichment analysis was performed on the data and identified myriad microRNAs that are likely to be upregulated in the regenerating tissue, including microRNA181a (miR181a), which is known to mediate proliferation in other systems. Functional experiments showed that miR181a overexpression is sufficient to stimulate proliferation within the basilar papilla, as assayed by BrdU incorporation. Further, some of the newly produced cells express the early hair cell marker myosin VI, suggesting that miR181a transfection can result in the production of new hair cells.These studies have identified a single microRNA, miR181a, that can cause proliferation in the chicken auditory epithelium with production of new hair cells