Probing of Carbohydrate-Protein Interactions Using Galactonoamidine Inhibitors

Glycoside hydrolases are ubiquitous and one of the most catalytically proficient enzymes known, and thus understanding their mechanisms are crucial. Most research has focused on the interaction of the glycon of substrates and their inhibitors within the active site of glycoside hydrolases. The inhibitors employed to probe these interactions generally had small aglycons (i.e. a hydrogen atom, amidines, small aliphatic groups, or benzyl groups). Here, the interactions of the aglycon with glycoside hydrolases are examined by probing the active sites with a library of 25 galactonoamidines. The studies described in this dissertation aim to increase the understanding of stabilization of the transition state by glycoside hydrolases, which allows for the acceleration of substrate hydrolysis by the enzymes up to 1017 over non-enzymatic hydrolysis. To understand this stabilization, the active sites of beta-galactosidases from Aspergillus oryzae, bovine liver, and Escherichia coli were evaluated using spectroscopic, molecular docking, and modeling analyses to determine transition state analogs (TSAs) and how the TSAs interact within the active site of glycoside hydrolases. The probing with the galactonoamidine library revealed hydrophobic interactions, pi-pi interactions, and CH-pi interactions within the active sites to varying extent. Further, three TSAs were found for the hydrolysis of substrates by beta-galactosidase (A. oryzae), and two TSAs for the beta-galactosidases from bovine liver and E. coli. Upon TSA binding to the three beta-galactosidases, conformational changes occurred to stabilize the galactonoamidines within the active sites, which did not occur when fortuitous binders interacted with the enzyme. The conformational changes within the active sites of beta-galactosidases from bovine liver and E. coli closes off the active site via a loop movement resulting in a substantially higher binding affinity than those observed with beta-galactosidase (A. oryzae). A subsequent evaluation of galactonoamidine specificity in the presence of other proteins revealed an increase of inhibitory activity two orders of magnitude more than a purified beta-galactosidase (E. coli)

Whose expertise is it? Evidence for autistic adults as critical autism experts

This is the final version. Available on open access from Frontiers Media via the DOI in this recordAutistic and non-autistic adults' agreement with scientific knowledge about autism, how they define autism, and their endorsement of stigmatizing conceptions of autism has not previously been examined. Using an online survey, we assessed autism knowledge and stigma among 636 adults with varied relationships to autism, including autistic people and nuclear family members. Autistic participants exhibited more scientifically based knowledge than others. They were more likely to describe autism experientially or as a neutral difference, and more often opposed the medical model. Autistic participants and family members reported lower stigma. Greater endorsement of the importance of normalizing autistic people was associated with heightened stigma. Findings suggest that autistic adults should be considered autism experts and involved as partners in autism research.Professional Staff CongressCity University of New Yor

Sex Differences in Adult Cognitive Deficits after Adolescent Nicotine Exposure in Rats

This study was designed to determine whether deficits in adult serial pattern learning caused by adolescent nicotine exposure persist as impairments in asymptotic performance, whether adolescent nicotine exposure differentially retards learning about pattern elements that are inconsistent with “perfect” pattern structure, and whether there are sex differences in rats’ response to adolescent nicotine exposure as assessed by a serial multiple choice task. The current study replicated the results of our initial report (Fountain, Rowan, Kelley, Willey, & Nolley, 2008) using this task by showing that adolescent nicotine exposure (1.0 mg/kg/day nicotine for 35 days) produced a specific cognitive impairment in male rats that persisted into adulthood at least a month after adolescent nicotine exposure ended. In addition, sex differences were observed even in controls, with additional evidence that adolescent nicotine exposure significantly impaired learning relative to same-sex controls for chunk boundary elements in males and for violation elements in females. All nicotine-induced impairments were overcome by additional training so that groups did not differ at asymptote. An examination of the types of errors rats made indicated that adolescent nicotine exposure slowed learning without affecting rats’ cognitive strategy in the task. This data pattern suggests that exposure to nicotine in adolescence may have impaired different aspects of adult stimulus-response discrimination learning processes in males and females, but left abstract rule learning processes relatively spared in both sexes. These effects converge with other findings in the field and reinforce the concern that adolescent nicotine exposure poses an important threat to cognitive capacity in adulthood

Transhiatal esophagectomy in the profoundly obese: implications and experience.

BACKGROUND: Historically, obesity contraindicated an abdominal approach to the esophagogastric junction. The technique of transhiatal esophagectomy (THE) evolved without specific regard to body habitus. The dramatic increase in obese patients requiring an esophagectomy for complications of reflux disease prompted this evaluation of the impact of obesity on the outcomes of esophagectomy to determine whether profound obesity should contraindicate the transhiatal approach. METHODS: We used our Esophagectomy Database to identify 133 profoundly obese patients (body mass index [BMI] > or = 35 kg/m2) from among 2176 undergoing a THE from 1977 to 2006. This group was matched to a randomly selected, non-obese (BMI, 18.5 to 30 kg/m2) control population of 133 patients. Intraoperative, postoperative, and long-term follow-up results were compared retrospectively. RESULTS: Profoundly obese patients had significantly greater intraoperative blood loss (mean, 492.2 mL versus 361.8 mL, p = 0.001), need for partial sternotomy (18 versus 3, p = 0.001), and frequency of recurrent laryngeal nerve injury (6 versus 0, p = 0.04). The two groups did not differ significantly in the occurrence of chylothorax, wound infection, or dehiscence rate; length of hospital stay or need for intensive care unit stay; or hospital or operative mortality. Follow-up results for dysphagia, dumping, regurgitation, and overall functional score were also comparable between the two groups. CONCLUSIONS: With appropriate instrumentation, transhiatal esophagectomy in obese patients has similar morbidity and outcomes as in non-obese patients. Obesity, even when profound, does not contraindicate a transhiatal esophagectomy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/57503/6/Scipione 2007.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/57503/5/Benign BMI Control.txthttp://deepblue.lib.umich.edu/bitstream/2027.42/57503/4/Benign BMI CS07.txthttp://deepblue.lib.umich.edu/bitstream/2027.42/57503/3/CA BMI Control no pt id.txthttp://deepblue.lib.umich.edu/bitstream/2027.42/57503/2/CA BMI 35 CS.tx

Lake Whatcom Monitoring Project 2018/2019 Report

This report describes the results from the 2018/2019 Lake Whatcom monitoring program conducted by the Institute for Watershed Studies at Western Washington University (www.wwu.edu/iws). The major objectives in 2018/2019 were to continue long-term baseline water quality monitoring in Lake Whatcom and its major tributaries; collect storm runoff water quality data from representative streams in the watershed; and continue collection of hydrologic data from Austin and Smith Creeks

The effects of stimulants and depressants on cocaine self-administration behavior in the Rhesus monkey

The effects of acute intramuscular pretreatment with several dosages of a variety of centrally acting compounds on intravenous cocaine self-administration behavior were ascertained. Pretreatment with morphine and pentobarbital produced no change in this behavior until dosages (2.0 mg/kg and 15.0 mg/kg respectively) were administered which grossly depressed grooming, exploratory, and locomotor activity behaviors, d -amphetamine (0.5–4.0 mg/kg) and phenmetrazine (2.0–12.0 mg/kg) pretreatment produced a dose-related decrease in cocaine self-administration. Trifluoperazine in dosages of 0.01–0.1 mg/kg increased the frequency of this behavior; whereas, higher dosages (0.2, 0.4 mg/kg) grossly depressed behavior. Imipramine (10–50 mg/kg) produced a dose-related decrease in cocaine self-administration. Potential mechanisms of these drug—behavior and drug—drug interactions are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46388/1/213_2004_Article_BF00421274.pd

The Making of a Self-Neglect Severity Scale

Research in elder self-neglect has lagged behind that of other forms of mistreatment, despite the fact that self-neglect is the most common allegation reported to Adult Protective Service agencies throughout the US. The lack of a gold-standard to measure self-neglect has hampered efforts to study this phenomenon. Researchers designed the Self-neglect Severity Scale (SSS) based on interviews with Adult Protective Service workers and a national expert panel. The SSS is based on observation and interview and is administered in the home to include an environmental assessment. It was piloted, extensively field tested and then revised. The CREST SSS was developed using survey data and consultation with experts in the field. This instrument utilizes observer ratings, interview responses, and assesses subjects physical and environmental domains. It also assesses functional status as it relates to health and safety issues. After field and pilot testing the SSS was finalized and is currently undergoing reliability and validity testing. The CREST SSS was developed as a state scale to provide a common language for describing cases of self-neglect. It is the first self-neglect severity scale available to researchers. If found to be both reliable and valid it can be used in future intervention studies

Lake Whatcom Monitoring Project 2016/2017 Report

This report describes the results from the 2016/2017 Lake Whatcom monitoring program conducted by the Institute for Watershed Studies at Western Washington University (www.wwu.edu/iws). The major objectives in 2016/2017 were to continue long-term baseline water quality monitoring in Lake Whatcom and its major tributaries; collect storm runoff water quality data from representative streams in the watershed; and continue collection of hydrologic data from Austin and Smith Creeks

Lake Whatcom Monitoring Project 2017/2018 Report

This report describes the results from the 2017/2018 Lake Whatcom monitoring program conducted by the Institute for Watershed Studies at Western Washington University (www.wwu.edu/iws). The major objectives in 2017/2018 were to continue long-term baseline water quality monitoring in Lake Whatcom and its major tributaries; collect storm runoff water quality data from representative streams in the watershed; and continue collection of hydrologic data from Austin and Smith Creeks

Lake Whatcom Monitoring Project 2022/2023 Report

This report describes the results from the 2022/2023 Lake Whatcom monitoring program conducted by the Institute for Watershed Studies at Western Washington University (https://diatom.cenv.wwu.edu/). The major objectives of the 2022/2023 Lake Whatcom monitoring program were to continue long-term baseline water quality monitoring in Lake Whatcom and its major tributaries; collect storm runoff water quality data from representative streams in the watershed; and continue collection of hydrologic data from Austin and Smith Creeks