This paper explores the integration of interdisciplinary, standards-based making in elementary classrooms through an investigation of teachers' navigation of contradictions between traditional ...academic practices and the playful, imaginative, and collaborative design thinking that characterizes making. Empirical findings are reported from a three-year, NSF-funded research project that involved the integration of standards-based Mobile Maker Kits into 15 elementary schools within a suburban-rural Southern school district. Drawing on a framework that recognizes making and formal learning as interactive activity systems, this qualitative study illustrates how teachers experienced and resolved contradictions as they integrated the kits into their classrooms. We conclude by discussing how integrating standards-based making provides opportunities for transformative learning that allows students and teachers to engage in creative production, design thinking, and experimentation.
Pyruvoyl Tetrahydropterin Synthase (PTPS) Deficiency is the most common form of BH4 deficiency resulting in hyperphenylalaninemia. It can have variable clinical severity and there is limited ...information on the clinical presentation, natural history and effectiveness of newborn screening for this condition.
Retrospective data (growth and clinical parameters, biochemical and genetic testing results, treatment) were collected from 19 patients with PTPS deficiency in different centers, to evaluate biochemical and clinical outcomes. Descriptive statistics was used for qualitative variables, while linear regression analysis was used to correlate quantitative variables.
Patients with PTPS deficiency had an increased incidence of prematurity (4/18) with an average gestational age only mildly reduced (37.8 ± 2.4 weeks) and low birth weight (−1.14 ± 0.97 SD below that predicted for gestational age). With time, weight and height approached normal. Values. All patients were identified by newborn screening for an elevated phenylalanine level. However, phenylalanine levels were normal in two whose testing was performed at or before 24 h of age. Sapropterin dihydrochloride treatment normalized phenylalanine levels. Molecular testing identified novel variants in the PTS gene, some of which present in more than one affected family. The neurotransmitter derivatives 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) in the CSF were decreased in most cases except in 2 families with the peripheral form of PTPS deficiency. With time, HVA and 5HIAA became abnormally low in two of these patients requiring therapy. Prolactin (whose secretion is inhibited by dopamine) levels were elevated in several patients with PTPS deficiency and inversely correlated with the z-scores for height (p < 0.01) and weight (p < 0.05). Most patients with PTPS deficiency had delayed development early in life, improving around school age with IQs mostly in the normal range, with a small decline in older individuals. From a neurological standpoint, most patients had normal brain MRI and minor EEG anomalies, although some had persistent neurological symptoms.
Patients with PTPS deficiency have not only an increased incidence of prematurity, but also decreased birth weight when corrected for gestational age. Hyperphenylalaninemia can be absent in the first day of life. Therapy with sapropterin dihydrochloride normalizes phenylalanine levels and neurotransmitter precursors can improve CSF neurotransmitter metabolites levels. Insufficient dopaminergic stimulation (as seen from elevated prolactin) might result in decreased height in patients with PTPS deficiency. Despite early delays in development, many patients can achieve independence in adult life, with usually normal neuroimaging and EEG.
► Recycling bins without a trash bin nearby have lower recycling accuracy. ► Putting all recyclables in one-bin results in an increase in wet paper. ► A change in signage many not produce an increase ...in recycling accuracy.
Commercial institutions have many factors to consider when implementing an effective recycling program. This study examined the effectiveness of three different types of recycling bins on recycling accuracy by determining the percent weight of recyclable material placed in the recycling bins, comparing the percent weight of recyclable material by type of container used, and examining whether a change in signage increased recycling accuracy. Data were collected over 6weeks totaling 30days from 3 different recycling bin types at a Midwest University medical center. Five bin locations for each bin type were used. Bags from these bins were collected, sorted into recyclable and non-recyclable material, and weighed. The percent recyclable material was calculated using these weights. Common contaminates found in the bins were napkins and paper towels, plastic food wrapping, plastic bags, and coffee cups. The results showed a significant difference in percent recyclable material between bin types and bin locations. Bin type 2 was found to have one bin location to be statistically different (p=0.048), which may have been due to lack of a trash bin next to the recycling bin in that location. Bin type 3 had significantly lower percent recyclable material (p<0.001), which may have been due to lack of a trash bin next to the recycling bin and increased contamination due to the combination of commingled and paper into one bag. There was no significant change in percent recyclable material in recycling bins post signage change. These results suggest a signage change may not be an effective way, when used alone, to increase recycling compliance and accuracy. This study showed two or three-compartment bins located next to a trash bin may be the best bin type for recycling accuracy.
Drawing on analysis of a researcher-practitioner partnership, this study positions computational thinking as a key scientific literacy that promotes deeper understandings of disciplinary content.
N-acetylglutamate synthase deficiency (NAGSD, MIM #237310) is an autosomal recessive urea cycle disorder caused either by decreased expression of the
NAGS
gene or defective NAGS enzyme resulting in ...decreased production of N-acetylglutamate (NAG), an allosteric activator of carbamylphosphate synthetase 1 (CPS1). NAGSD is the only urea cycle disorder that can be effectively treated with a single drug, N-carbamylglutamate (NCG), a stable NAG analog, which activates CPS1 to restore ureagenesis. We describe three patients with NAGSD due to four novel non-coding sequence variants in the
NAGS
regulatory regions. All three patients had hyperammonemia that resolved upon treatment with NCG. Sequence variants NM_153006.2:c.427–222G>A and NM_153006.2:c.427–218A>C reside in the 547 bp long first intron of
NAGS
and define a novel
NAGS
regulatory element that binds retinoic X receptor α. Sequence variants NC_000017.10:g.42078967A>T (NM_153006.2:c.−3065A>T) and NC_000017.10:g.42078934C>T (NM_153006.2:c.−3098C>T) reside in the
NAGS
enhancer, within known HNF1 and predicted glucocorticoid receptor binding sites, respectively. Reporter gene assays in HepG2 and HuH-7 cells demonstrated that all four substitutions could result in reduced expression of
NAGS
. These findings show that analyzing non-coding regions of
NAGS
and other urea cycle genes can reveal molecular causes of disease and identify novel regulators of ureagenesis.
Optimal lysosome function requires maintenance of an acidic pH maintained by proton pumps in combination with a counterion transporter such as the Cl−/H+ exchanger, CLCN7 (ClC-7), encoded by CLCN7. ...The role of ClC-7 in maintaining lysosomal pH has been controversial. In this paper, we performed clinical and genetic evaluations of two children of different ethnicities. Both children had delayed myelination and development, organomegaly, and hypopigmentation, but neither had osteopetrosis. Whole-exome and -genome sequencing revealed a de novo c.2144A>G variant in CLCN7 in both affected children. This p.Tyr715Cys variant, located in the C-terminal domain of ClC-7, resulted in increased outward currents when it was heterologously expressed in Xenopus oocytes. Fibroblasts from probands displayed a lysosomal pH approximately 0.2 units lower than that of control cells, and treatment with chloroquine normalized the pH. Primary fibroblasts from both probands also exhibited markedly enlarged intracellular vacuoles; this finding was recapitulated by the overexpression of human p.Tyr715Cys CLCN7 in control fibroblasts, reflecting the dominant, gain-of-function nature of the variant. A mouse harboring the knock-in Clcn7 variant exhibited hypopigmentation, hepatomegaly resulting from abnormal storage, and enlarged vacuoles in cultured fibroblasts. Our results show that p.Tyr715Cys is a gain-of-function CLCN7 variant associated with developmental delay, organomegaly, and hypopigmentation resulting from lysosomal hyperacidity, abnormal storage, and enlarged intracellular vacuoles. Our data supports the hypothesis that the ClC-7 antiporter plays a critical role in maintaining lysosomal pH.
N‐acetylglutamate synthase deficiency is an autosomal recessive urea cycle disorder caused either by decreased expression of the NAGS gene or defective NAGS enzyme resulting in decreased production ...of N‐acetylglutamate (NAG), an allosteric activator of carbamylphosphate synthetase 1 (CPS1). NAGSD is the only urea cycle disorder that can be effectively treated with a single drug, N‐carbamylglutamate (NCG), a stable NAG analog, which activates CPS1 to restore ureagenesis. We describe three patients with NAGSD due to four novel noncoding sequence variants in the NAGS regulatory regions. All three patients had hyperammonemia that resolved upon treatment with NCG. Sequence variants NM_153006.2:c.427‐222G>A and NM_153006.2:c.427‐218A>C reside in the 547 bp‐long first intron of NAGS and define a novel NAGS regulatory element that binds retinoic X receptor α. Sequence variants NC_000017.10:g.42078967A>T (NM_153006.2:c.‐3065A>T) and NC_000017.10:g.42078934C>T (NM_153006.2:c.‐3098C>T) reside in the NAGS enhancer, within known HNF1 and predicted glucocorticoid receptor binding sites, respectively. Reporter gene assays in HepG2 and HuH‐7 cells demonstrated that all four substitutions could result in reduced expression of NAGS. These findings show that analyzing noncoding regions of NAGS and other urea cycle genes can reveal molecular causes of disease and identify novel regulators of ureagenesis.
We identified a novel regulatory element in the first intron of the N‐acetylglutamate (NAGS) gene based on bioinformatic analysis and sequence variants found in two patients with NAGS deficiency; two more sequence variants associated with NAGS deficiency were found in the −3 kb enhancer of the NAGS gene. All four sequence variants caused reduced reporter gene expression. Functional assays combined with bioinformatic analyses can be used to identify previously unreported gene regulatory elements and authenticate pathogenic sequence variants in noncoding regions of the NAGS gene.
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