Tricarboxylic acid cycle enzyme activities in a mouse model of methylmalonic aciduria

Methylmalonic acidemia (MMA) is a propionate pathway disorder caused by dysfunction of the mitochondrial enzyme methylmalonyl-CoA mutase (MMUT). MMUT catalyzes the conversion of methylmalonyl-CoA to succinyl-CoA, an anaplerotic reaction which feeds into the tricarboxylic acid (TCA) cycle. As part of the pathological mechanisms of MMA, previous studies have suggested there is decreased TCA activity due to a toxic inhibition of TCA cycle enzymes by MMA related metabolites, in addition to reduced anaplerosis. Here, we have utilized mitochondria isolated from livers of a mouse model of MMA (Mut-ko/ki) and their littermate controls (Ki/wt) to examine the amounts and enzyme functions of most of the TCA cycle enzymes. We have performed mRNA quantification, protein semi-quantitation, and enzyme activity quantification for TCA cycle enzymes in these samples. Expression profiling showed increased mRNA levels of fumarate hydratase in the Mut-ko/ki samples, which by contrast had reduced protein levels as detected by immunoblot, while all other mRNA levels were unaltered. Immunoblotting also revealed decreased protein levels of 2-oxoglutarate dehydrogenase and malate dehydrogenase 2. Interesting, the decreased protein amount of 2-oxoglutarate dehydrogenase was reflected in decreased activity for this enzyme while there is a trend towards decreased activity of fumarate hydratase and malate dehydrogenase 2. Citrate synthase, isocitrate dehydrogenase 2/3, succinyl-CoA synthase, and succinate dehydrogenase are not statistically different in terms of quantity of enzyme or activity. Finally, we found decreased activity when examining the function of methylmalonyl-CoA mutase in series with succinate synthase and succinate dehydrogenase in the Mut-ko/ki mice compared to their littermate controls, as expected. This study demonstrates decreased activity of certain TCA cycle enzymes and by corollary decreased TCA cycle function, but it supports decreased protein quantity rather than toxic inhibition as the underlying mechanism of action. SUMMARY: Methylmalonic acidemia (MMA) is an inborn metabolic disorder of propionate catabolism. In this disorder, toxic metabolites are considered to be the major pathogenic mechanism for acute and long-term complications. However, despite optimized therapies aimed at reducing metabolite levels, patients continue to suffer from late complications, including metabolic stroke and renal insufficiency. Since the propionate pathway feeds into the tricarboxylic acid (TCA) cycle, we investigated TCA cycle function in a constitutive MMA mouse model. We demonstrated decreased amounts of the TCA enzymes, Mdh2 and Ogdh as semi-quantified by immunoblot. Enzymatic activity of Ogdh is also decreased in the MMA mouse model compared to controls. Thus, when the enzyme amounts are decreased, we see the enzymatic activity also decreased to a similar extent for Ogdh. Further studies to elucidate the structural and/or functional links between the TCA cycle and propionate pathways might lead to new treatment approaches for MMA patients

Lexical organization in deaf children who use British Sign Language: Evidence from a semantic fluency task

We adapted the semantic fluency task into British Sign Language (BSL). In Study 1, we present data from twenty-two deaf signers aged four to fifteen. We show that the same ‘cognitive signatures’ that characterize this task in spoken languages are also present in deaf children, for example, the semantic clustering of responses. In Study 2, we present data from thirteen deaf children with Specific Language Impairment (SLI) in BSL, in comparison to a subset of children from Study 1 matched for age and BSL exposure. The two groups' results were comparable in most respects. However, the group with SLI made occasional word-finding errors and gave fewer responses in the first 15 seconds. We conclude that deaf children with SLI do not differ from their controls in terms of the semantic organization of the BSL lexicon, but that they access signs less efficiently

Review paper: Evaluation of Techniques for Algae Removal from Wastewater Stabilization Ponds

Introduction: Approximately 90 percent of the wastewater lagoons in the United States are located in small communities of 5,000 people or less. These communities, many with an average daily wastewater flow of only 175,000 - 200,000 gallons, do not have the resources to keep man at the lagoon sites throughout the day (38). A high degree of technical knowhow is usually lacking in these communities. Often only periodic inspection or maintenance is carried out by the general municipal work force. Therefore, the development of a relatively inexpensive method that does not require sophisticated and constant operation or extensive maintenance is needed to polish these effluents. Most regulatory agencies are adopting more stringent water quality standards, enforcement of which will necessitate changes in present treatment methods and the philosophy of wastewater treatment. Small communities utilizing stabilization ponds will be affected most drastically by new standards. Because most communities utilizing ponds are relatively small and installed ponds primariliy to avoid operating costs, it is unlikely that modifications requiring significant increases in operation will be acceptable. Therefore, the most sophisticated alternatives for upgrading treatment must be excluded from a practicable solution to solids removal from stabilization pond effluent

Cultural and economic complementarities of spatial agglomeration in the British television broadcasting industry: Some explorations.

This paper considers the processes supporting agglomeration in the British television broadcasting industry. It compares and contrasts the insights offered by the cultural turn in geography and more conventionally economic approaches. It finds that culture and institutions are fundamental to the constitution of production and exchange relationships and also that they solve fundamental economic problems of coordinating resources under conditions of uncertainty and limited information. Processes at a range of spatial scales are important, from highly local to global, and conventional economics casts some light on which firms are most active and successful

Care coordination among pediatricians and dentists: a cross-sectional study of opinions of North Carolina dentists

Abstract: Background: Care coordination between physicians and dentists remains a challenge. This study of dentists providing pediatric dental care examined their opinions about physicians’ role in oral health and identified factors associated with these opinions. Methods: North Carolina general and pediatric dentists were surveyed on their opinions of how physicians should proceed after caries risk assessment and evaluation of an 18-month-old, low risk child. We estimated two multinomial logistic regression models to examine dentists’ responses to the scenario under the circumstances of an adequate and a limited dental workforce. Results: Among 376 dentists, 52% of dentists indicated physicians should immediately refer this child to a dental home with an adequate dental workforce. With a limited workforce, 34% recommended immediate referral. Regression analysis indicated that with an adequate workforce guideline awareness was associated with a significantly lower relative risk of dentists’ recommending the child remain in the medical home than immediate referral. Conclusions: Dentists’ opinions and professional guidelines on how physicians should promote early childhood oral health differ and warrant strategies to address such inconsistencies. Without consistent guidelines and their application, there is a missed opportunity to influence provider opinions to improve access to dental care

The acquisition of Sign Language: The impact of phonetic complexity on phonology

Research into the effect of phonetic complexity on phonological acquisition has a long history in spoken languages. This paper considers the effect of phonetics on phonological development in a signed language. We report on an experiment in which nonword-repetition methodology was adapted so as to examine in a systematic way how phonetic complexity in two phonological parameters of signed languages — handshape and movement — affects the perception and articulation of signs. Ninety-one Deaf children aged 3–11 acquiring British Sign Language (BSL) and 46 hearing nonsigners aged 6–11 repeated a set of 40 nonsense signs. For Deaf children, repetition accuracy improved with age, correlated with wider BSL abilities, and was lowest for signs that were phonetically complex. Repetition accuracy was correlated with fine motor skills for the youngest children. Despite their lower repetition accuracy, the hearing group were similarly affected by phonetic complexity, suggesting that common visual and motoric factors are at play when processing linguistic information in the visuo-gestural modality

Fluidized Bed Steam Reforming of INEEL SBW Using THORsm Mineralizing Technology

Sodium bearing waste (SBW) disposition is one of the U.S. Department of Energy (DOE) Idaho Operation Office’s (NE-ID) and State of Idaho’s top priorities at the Idaho National Engineering and Environmental Laboratory (INEEL). Many studies have resulted in the identification of five treatment alternatives that form a short list of perhaps the most appropriate technologies for the DOE to select from. The alternatives are (a) calcination with maximum achievable control technology (MACT) upgrade, (b) steam reforming, (c) cesium ion exchange (CsIX) with immobilization, (d) direct evaporation, and (e) vitrification. Each alternative has undergone some degree of applied technical development and preliminary process design over the past four years. DOE desired further experimental data, with regard to steam reforming technology, to make informed decisions concerning selection of treatment technology for SBW. Mineralizing steam reforming technology, offered by THOR Treatment Technologies, LLC would produce a denitrated, granular mineral waste form using a high-temperature fluidized bed process. A pilot scale demonstration of the technology was performed in a 15-cm-diameter reactor vessel September 27 through October 1, 2004. The pilot scale equipment is owned by the DOE, and located at the Science and Technology Applications Research (STAR) Center in Idaho Falls, ID. Flowsheet chemistry and operational parameters were defined through a collaborative effort involving Idaho National Engineering and Environmental Laboratory, Savannah River National Laboratory (SRNL), and THOR Treatment Technologies personnel. Personnel from Science Applications International Corporation, owners of the STAR Center, operated the pilot plant. The pilot scale test was terminated as planned after achieving a total of 100 hrs of cumulative/continuous processing operation. About 230 kg of SBW surrogate were processed that resulted in about 88 kg of solid product, a mass reduction of about 62%. The process achieved about a 90% turnover of the starting bed. Samples of mineralized solid product materials were analyzed for chemical/physical properties. Results of product performance testing conducted by SRNL will be reported separately by SRNL

Fluidized Bed Steam Reforming of Hanford LAW Using THORsm Mineralizing Technology

The U.S. Department of Energy (DOE) documented, in 2002, a plan for accelerating cleanup of the Hanford Site, located in southeastern Washington State, by at least 35 years. A key element of the plan was acceleration of the tank waste program and completion of ''tank waste treatment by 2028 by increasing the capacity of the planned Waste Treatment Plant (WTP) and using supplemental technologies for waste treatment and immobilization.'' The plan identified steam reforming technology as a candidate for supplemental treatment of as much as 70% of the low-activity waste (LAW). Mineralizing steam reforming technology, offered by THOR Treatment Technologies, LLC would produce a denitrated, granular mineral waste form using a high-temperature fluidized bed process. A pilot scale demonstration of the technology was completed in a 15-cm-diameter reactor vessel. The pilot scale facility was equipped with a highly efficient cyclone separator and heated sintered metal filters for particulate removal, a thermal oxidizer for reduced gas species and NOx destruction, and a packed activated carbon bed for residual volatile species capture. The pilot scale equipment is owned by the DOE, but located at the Science and Technology Applications Research (STAR) Center in Idaho Falls, ID. Pilot scale testing was performed August 2–5, 2004. Flowsheet chemistry and operational parameters were defined through a collaborative effort involving Idaho National Engineering and Environmental Laboratory, Savannah River National Laboratory (SRNL), and THOR Treatment Technologies personnel. Science Application International Corporation, owners of the STAR Center, personnel performed actual pilot scale operation. The pilot scale test achieved a total of 68.7 hrs of cumulative/continuous processing operation before termination in response to a bed de-fluidization condition. 178 kg of LAW surrogate were processed that resulted in 148 kg of solid product, a mass reduction of about 17%. The process achieved essentially complete bed turnover within approximately 40 hours. Samples of mineralized solid product materials were analyzed for chemical/physical properties. SRNL will report separately the results of product performance testing that were accomplished

Does Nonrandom Nest Placement Imply Nonrandom Nest Predation?: a Reply

In response to the critique by Schmidt and Whelan (Condor 101 (4): 916-920, 1999), we find that the relationship between nest success and tree selectivity is dependent upon inclusion or exclusion of particular tree species, whether or not years are pooled, and the selectivity index used. We question their use of point estimates of nest success with extremely high variances, defend our index, question the application of the Chesson (1983) index to our data, and explain the need to analyze years separately. Bottomland hardwood forest systems are extremely variable; hydroperiods alter the suitability of nesting substrates, availability of alternative food, and behavior of predators and their prey. Given these features, actively searching for Acadian Flycatcher (Empidonax virescens) nests is seldom an efficient predator foraging strategy. Therefore, these predation events are best described as random; nests are principally encountered opportunistically by generalist predators while searching for other prey