Senior Recital:Jamie Quiram, Flute

Kemp Recital Hall Saturday Noon April 28, 2001 12:00 Noo

Great Bay Nitrogen Non-Point Source Study

The Great Bay Estuary is 21 square miles of tidal waters located in southeastern New Hampshire. It is one of 28 “estuaries of national significance” established under the Environmental Protection Agency’s National Estuary Program. The estuary is experiencing the signs of eutrophication, specifically, low dissolved oxygen, macroalgae blooms, and declining eelgrass habitat (DES, 2012). Sixty-eight percent of the nitrogen that ends up in the Great Bay Estuary originates from sources spread across the watershed; the remainder derives from direct discharges of municipal wastewater treatment facilities (DES, 2010; PREP, 2013). In this report, these sources of nitrogen are called non-point sources and consist of atmospheric deposition, fertilizers, human waste disposed into septic systems, and animal waste. The purpose of this study is to determine how much nitrogen each non-point source type contributes to the estuary. The nitrogen loads from municipal wastewater treatment facilities have been reported elsewhere (DES, 2010; PREP, 2012; PREP, 2013) and, therefore, are not included in this study except to provide context. The intended use of this study is for planning purposes, and is not meant for regulatory allocations or specific reduction requirements. The results of the model may be useful for towns or watershed groups for prioritizing nitrogen reduction efforts or as a starting point for more detailed studies of non-point sources. However, more detailed inventories of non-point sources will be needed to track the effects of nitrogen reduction efforts in smaller areas. In addition, the model makes no conclusions about the benefits of nitrogen reductions to receiving waters or overall estuarine health

Considerations for increasing the competences and capacities of the public health workforce: assessing the training needs of public health workers in Texas

BACKGROUND: Over the last two decades, concern has been expressed about the readiness of the public health workforce to adequately address the scientific, technological, social, political and economic challenges facing the field. A 1988 report from the Institute of Medicine (IOM) served as a catalyst for the re-examination of the public health workforce. The IOM's call to increase the relevance of public health education and training prompted a renewed effort to identify competences needed by public health personnel and the organizations that employ them. METHODS: A recent evaluation sought to address the role of the 10 essential public health services in job services among the Texas public health workforce. Additionally, the evaluation examined the Texas public health workforce's need for training in the 10 essential public health services. RESULTS AND CONCLUSION: Overall, the level of perceived training needs varied dramatically by job category and health department type. When comparing aggregate training needs, public health workers with greater day-to-day contact (nurses, health educators) indicated a greater need for training than their peers who did not, such as those working in administrative positions. When prioritizing and designing future training modules regarding the 10 essential public health services, trainers should consider the effects of job function, location and contact with the public

Novel chlorhexidine-loaded polymeric nanoparticles for root canal treatment

Persistence of microorganisms in dentinal tubules after root canal chemo-mechanical preparation has been well documented. The complex anatomy of the root canal and dentinal buffering ability make delivery of antimicrobial agents difficult. This work explores the use of a novel trilayered nanoparticle (TNP) drug delivery system that encapsulates chlorhexidine digluconate, which is aimed at improving the disinfection of the root canal system. Chlorhexidine digluconate was encapsulated inside polymeric self-assembled TNPs. These were self-assembled through water-in-oil emulsion from poly(ethylene glycol)-b-poly(lactic acid) (PEG-b-PLA), a di-block copolymer, with one hydrophilic segment and another hydrophobic. The resulting TNPs were physicochemically characterized and their antimicrobial effectiveness was evaluated against Enterococcus faecalis using a broth inhibition method. The hydrophilic interior of the TNPs successfully entrapped chlorhexidine digluconate. The resulting TNPs had particle size ranging from 140–295 nm, with adequate encapsulation efficiency, and maintained inhibition of bacteria over 21 days. The delivery of antibacterial irrigants throughout the dentinal matrix by employing the TNP system described in this work may be an effective alternative to improve root canal disinfection

Approaches to Retinal Detachment Prophylaxis among Patients with Stickler Syndrome

Stickler syndrome is the most common cause of pediatric rhegmatogenous retinal detachments. Given the dramatic long term visual impact and difficult surgical management of these detachments, there is increasing interest in determining whether prophylactic treatment can be used to prevent retinal detachments in this population. However, severity of ocular findings in Stickler syndrome can vary by subtype. Three commonly used modalities to provide prophylactic treatment against retinal detachments in patients with Stickler syndrome include scleral buckle, laser retinopexy, and cryotherapy. While laser retinopexy is the most common approach to prophylactic treatment, treatment settings can vary by specialist. In addition, the decision to treat and manage Stickler syndrome is nuanced and requires careful consideration of the individual patient. After reviewing the literature on prophylactic treatment approaches, this chapter will also over guidelines in management of this complex patient population

A new level of conotoxin diversity, a non-native disulfide bond connectivity in alpha-conotoxin AuIB reduces structural definition but increases biological activity

alpha-Conotoxin AuIB and a disulfide bond variant of AuIB have been synthesized to determine the role of disulfide bond connectivity on structure and activity. Both of these peptides contain the 15 amino acid sequence GCCSYPPCFATNPDC, with the globular (native) isomer having the disulfide connectivity Cys(2-8 and 3-15) and the ribbon isomer having the disulfide connectivity Cys(2-15 and 3-8). The solution structures of the peptides were determined by NAIR spectroscopy, and their ability to block the nicotinic acetylcholine receptors on dissociated neurons of the rat parasympathetic ganglia was examined. The ribbon disulfide isomer, although having a less well defined structure, is surprisingly found to have approximately 10 times greater potency than the native peptide. To our knowledge this is the first demonstration of a non-native disulfide bond isomer of a conotoxin exhibiting greater biological activity than the native isomer

The Synthesis, Structural Characterization, and Receptor Specificity of the {alpha}-Conotoxin Vc1.1

The {alpha}-conotoxin Vc1.1 is a small disulfide-bonded peptide currently in development as a treatment for neuropathic pain. This study describes the synthesis, determination of the disulfide connectivity, and the determination of the three-dimensional structure of Vc1.1 using NMR spectroscopy. Vc1.1 was shown to inhibit nicotine-evoked membrane currents in isolated bovine chromaffin cells in a concentration-dependent manner and preferentially targets peripheral nicotinic acetylcholine receptor (nAChR) subtypes over central subtypes. Specifically, Vc1.1 is selective for {alpha}3-containing nAChR subtypes. The three-dimensional structure of Vc1.1 comprises a small {alpha}-helix spanning residues Pro6 to Asp11 and is braced by the I-III, II-IV disulfide connectivity seen in other {alpha}-conotoxins. A comparison of the structure of Vc1.1 with other {alpha}-conotoxins, taken together with nAChR selectivity data, suggests that the conserved proline at position 6 is important for binding, whereas a number of residues in the C-terminal portion of the peptide contribute toward the selectivity. The structure reported here should open new opportunities for further development of Vc1.1 or analogues as analgesic agents

Defective Presynaptic Choline Transport Underlies Hereditary Motor Neuropathy

The neuromuscular junction (NMJ) is a specialized synapse with a complex molecular architecture that provides for reliable transmission between the nerve terminal and muscle fiber. Using linkage analysis and whole-exome sequencing of DNA samples from subjects with distal hereditary motor neuropathy type VII, we identified a mutation in SLC5A7, which encodes the presynaptic choline transporter (CHT), a critical determinant of synaptic acetylcholine synthesis and release at the NMJ. This dominantly segregating SLC5A7 mutation truncates the encoded product just beyond the final transmembrane domain, eliminating cytosolic-C-terminus sequences known to regulate surface transporter trafficking. Choline-transport assays in both transfected cells and monocytes from affected individuals revealed significant reductions in hemicholinium-3-sensitive choline uptake, a finding consistent with a dominant-negative mode of action. The discovery of CHT dysfunction underlying motor neuropathy identifies a biological basis for this group of conditions and widens the spectrum of disorders that derive from impaired NMJ transmission. Our findings compel consideration of mutations in SLC5A7 or its functional partners in relation to unexplained motor neuronopathies

alpha-conotoxins PnIA and [A10L] PnIA stabilize different states of the alpha 7-L247T nicotinic acetylcholine receptor

The effects of the native alpha-conotoxin PnIA, its synthetic derivative [ A10L] PnIA and alanine scan derivatives of [ A10L] PnIA were investigated on chick wild type alpha7 and alpha7-L247T mutant nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus oocytes. PnIA and [A10L] PnIA inhibited acetylcholine (ACh)-activated currents at wtalpha7 receptors with IC50 values of 349 and 168 nM, respectively. Rates of onset of inhibition were similar for PnIA and [ A10L] PnIA; however, the rate of recovery was slower for [ A10L] PnIA, indicating that the increased potency of [ A10L] PnIA at alpha7 receptors is conveyed by its slower rate of dissociation from the receptors. All the alanine mutants of [ A10L] PnIA inhibited ACh-activated currents at wtalpha7 receptors. Insertion of an alanine residue between position 5 and 13 and at position 15 significantly reduced the ability of [ A10L] PnIA to inhibit ACh-evoked currents. PnIA inhibited the non-desensitizing ACh-activated currents at alpha7-L247T receptors with an IC50 194 nM. In contrast, [ A10L] PnIA and the alanine mutants potentiated the ACh-activated current alpha7-L247T receptors and in addition [ A10L] PnIA acted as an agonist. PnIA stabilized the receptor in a state that is non-conducting in both the wild type and mutant receptors, whereas [ A10L] PnIA stabilized a state that is non-conducting in the wild type receptor and conducting in the alpha7-L247T mutant. These data indicate that the change of a single amino acid side-chain, at position 10, is sufficient to change the toxin specificity for receptor states in the alpha7-L247T mutant

CELL-SELEX: Novel Perspectives of Aptamer-Based Therapeutics

Aptamers, single stranded DNA or RNA molecules, generated by a method called SELEX (systematic evolution of ligands by exponential enrichment) have been widely used in various biomedical applications. The newly developed Cell-SELEX (cell based-SELEX) targeting whole living cells has raised great expectations for cancer biology, -therapy and regenerative medicine. Combining nanobiotechnology with aptamers, this technology opens the way to more sophisticated applications in molecular diagnosis. This paper gives a review of recent developments in SELEX technologies and new applications of aptamers