While expository texts are an efficient and dominant genre used by science teachers in the United States, they generally lack justification for their claims and fail to reflect science as practice. ...In contrast, epistemically considerate texts detail specific scientific experiments, providing the reader insight into the methods and data of a biological discovery. This multi-case exploratory comparison analysed videos of students in introductory and advanced high school biology classes who individually read and then discussed the main ideas, sources of justification, and questions raised expository and alternate biology texts. Videos of eight class periods were analysed with a focus on the types of statements students made during the discussion, points of comprehension, questions posed, and whether and how students identified sources of justification for the texts' claims. The epistemically considerate texts were perceived as more difficult to comprehend, but for both developmental levels, and particularly for students in the advanced class, these alternate texts elicited more sequences of productive talk and more elaborative, cognitively deep questions, particularly related to the practices of science. We discuss the potential implications for developing complementary sets of texts to optimise students' science learning and link elements of genre to students' reading and discussion experiences.
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BFBNIB, NUK, PILJ, SAZU, UL, UM, UPUK
Teachers continuously engage in the relational work of sensemaking with students, but they generally do so isolated from colleagues, making individual decisions about their classrooms. Professional ...learning communities (PLCs), provide opportunities for collaborative professional reflection and development among peers centered on the analysis of teaching practice. However, PLCs can be difficult to implement in ways that reflect theories of adult learning and are manageable in light of the responsibilities of a teacher. We conducted a year-long case study of a PLC that engaged a group of middle school science teachers using artifacts from a digital portfolio and a framework for high-quality science teaching to explore their teaching practice. The PLC was divided into sessions facilitated externally by a member of the research team and sessions facilitated internally by the teachers themselves. Videos of all PLC sessions and baseline and final interviews indicated that unlike some PLCs described in the literature, participants focused their conversation and interactions on the content of science teaching regardless of who facilitated the session. The discussion was mediated by the digital portfolio tool, its artifacts and an introduced analytical framework. However, externally facilitated sessions revealed far more analysis of practice, compared to extensive reporting on portfolio artifacts when facilitated internally. The findings suggest that digital portfolios, when combined with analytical frameworks of practice can be important tools for teacher reflection, but attention must be paid to PLC structures and norms that move teachers past 'show and tell' and toward more in-depth conversations about practice.
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BFBNIB, NUK, PILJ, SAZU, UL, UM, UPUK
Despite the fact that photographic stimuli are used across experimental contexts with both human and nonhuman subjects, the nature of individuals' perceptions of these stimuli is still not well ...understood. In the present experiments, we tested whether three orangutans and 36 human children could use photographic information presented on a computer screen to solve a perceptually corresponding problem in the physical domain. Furthermore, we tested the cues that aided in this process by pitting featural information against spatial position in a series of probe trials. We found that many of the children and one orangutan were successfully able to use the information cross-dimensionally; however, the other two orangutans and almost a quarter of the children failed to acquire the task. Species differences emerged with respect to ease of task acquisition. More striking, however, were the differences in cues that participants used to solve the task: Whereas the orangutan used a spatial strategy, the majority of children used a feature one. Possible reasons for these differences are discussed from both evolutionary and developmental perspectives. The novel results found here underscore the need for further testing in this area to design appropriate experimental paradigms in future comparative research settings.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
Increased relative medial thickness (RMT) of smooth muscle in small pulmonary arteries, peripheral extension of smooth muscle into the alveolar wall arteries, and right ventricular hypertrophy (RVH), ...in response to purported prolonged hypoxia, have been reported in sudden infant death syndrome (SIDS). Prone sleep position, an important risk factor for SIDS, predisposes infants to hypoxia from airway obstruction or rebreathing. Since publication of the earlier pulmonary artery studies, the SIDS definition has been expanded, and sudden infant death investigational protocols have been implemented. Our aims in this study were to (1) compare RMT in preacinar arteries (PA), intra-acinar arteries accompanying small airways (SIA), and alveolar wall arteries (AW) in SIDS infants and controls; (2) correlate RMT with postmortem variables; (3) determine if peripheral extension occurred more often in SIDS infants than in controls; and (4) determine if RVH occurred in SIDS. Movat-stained sections from standardized tissue blocks taken prospectively from the apex of the right upper lobe from 88 SIDS cases and 17 controls were evaluated using a computer-assisted digitizing system with images obtained from a microscope with an attached video camera. When adjusted for age, the RMT values for the SIA arteries were significantly greater in controls, while the PA and AW arteries were not statistically different between the SIDS cases and controls. Peripheral medial smooth muscle extension did not differ between the groups, and RVH was not seen in SIDS cases. Given the recent identification of brain stem abnormalities interfering with protective cardiorespiratory responses against acute life-threatening hypoxia perhaps precipitated by prone sleeping, our data suggest that SIDS is an acute event not preceded by recurrent or prolonged apnea and hypoxia.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Determining the bacterial composition of the canine oral microbiome is of interest for two primary reasons. First, while the human oral microbiome has been well studied using molecular techniques, ...the oral microbiomes of other mammals have not been studied in equal depth using culture independent methods. This study allows a comparison of the number of bacterial taxa, based on 16S rRNA-gene sequence comparison, shared between humans and dogs, two divergent mammalian species. Second, canine oral bacteria are of interest to veterinary and human medical communities for understanding their roles in health and infectious diseases. The bacteria involved are mostly unnamed and not linked by 16S rRNA-gene sequence identity to a taxonomic scheme. This manuscript describes the analysis of 5,958 16S rRNA-gene sequences from 65 clone libraries. Full length 16S rRNA reference sequences have been obtained for 353 canine bacterial taxa, which were placed in 14 bacterial phyla, 23 classes, 37 orders, 66 families, and 148 genera. Eighty percent of the taxa are currently unnamed. The bacterial taxa identified in dogs are markedly different from those of humans with only 16.4% of oral taxa are shared between dogs and humans based on a 98.5% 16S rRNA sequence similarity cutoff. This indicates that there is a large divergence in the bacteria comprising the oral microbiomes of divergent mammalian species. The historic practice of identifying animal associated bacteria based on phenotypic similarities to human bacteria is generally invalid. This report describes the diversity of the canine oral microbiome and provides a provisional 16S rRNA based taxonomic scheme for naming and identifying unnamed canine bacterial taxa.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The ancient UbiB protein kinase-like family is involved in isoprenoid lipid biosynthesis and is implicated in human diseases, but demonstration of UbiB kinase activity has remained elusive for ...unknown reasons. Here, we quantitatively define UbiB-specific sequence motifs and reveal their positions within the crystal structure of a UbiB protein, ADCK3. We find that multiple UbiB-specific features are poised to inhibit protein kinase activity, including an N-terminal domain that occupies the typical substrate binding pocket and a unique A-rich loop that limits ATP binding by establishing an unusual selectivity for ADP. A single alanine-to-glycine mutation of this loop flips this coenzyme selectivity and enables autophosphorylation but inhibits coenzyme Q biosynthesis in vivo, demonstrating functional relevance for this unique feature. Our work provides mechanistic insight into UbiB enzyme activity and establishes a molecular foundation for further investigation of how UbiB family proteins affect diseases and diverse biological pathways.
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•A UbiB family protein crystal structure reveals an atypical kinase-like fold•An A-rich loop determines coenzyme selectivity and inhibits autophosphorylation•UbiB-specific features are required for coenzyme Q biosynthesis in vivo•Pathogenic ADCK3 and ADCK4 mutations disrupt protein stability
The largely uncharacterized UbiB protein kinase-like family is conserved across all superkingdoms of life. Stefely et al. find that ADCK3, a mitochondrial UbiB protein, adopts an atypical structure with unique features positioned to inhibit protein kinase activity. Altering these features enables in vitro autophosphorylation, but compromises in vivo coenzyme Q biosynthesis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
ABSTRACT
To identify genetic causes of intellectual disability (ID), we screened a cohort of 986 individuals with moderate to severe ID for variants in 565 known or candidate ID‐associated genes ...using targeted next‐generation sequencing. Likely pathogenic rare variants were found in ∼11% of the cases (113 variants in 107/986 individuals: ∼8% of the individuals had a likely pathogenic loss‐of‐function LoF variant, whereas ∼3% had a known pathogenic missense variant). Variants in SETD5, ATRX, CUL4B, MECP2, and ARID1B were the most common causes of ID. This study assessed the value of sequencing a cohort of probands to provide a molecular diagnosis of ID, without the availability of DNA from both parents for de novo sequence analysis. This modeling is clinically relevant as 28% of all UK families with dependent children are single parent households. In conclusion, to diagnose patients with ID in the absence of parental DNA, we recommend investigation of all LoF variants in known genes that cause ID and assessment of a limited list of proven pathogenic missense variants in these genes. This will provide 11% additional diagnostic yield beyond the 10%–15% yield from array CGH alone.
For diseases caused by high new mutation rates e.g. intellectual disability, the availability of DNA from both parents for trio analysis is invaluable. However, in single parent households, a loss of function variant analysis of a panel of known disease‐causing genes plus analysis of a limited list of previously established pathogenic missense variants can yield a diagnostic rate of 11%. This strategy has significant clinical utility where samples from both parents are unavailable.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Cholesterol metabolism has been implicated in the pathogenesis of several neurodegenerative diseases, including the abnormal accumulation of amyloid-β, one of the pathological hallmarks of Alzheimer ...disease (AD). Acyl-CoA:cholesterol acyltransferases (ACAT1 and ACAT2) are two enzymes that convert free cholesterol to cholesteryl esters. ACAT inhibitors have recently emerged as promising drug candidates for AD therapy. However, how ACAT inhibitors act in the brain has so far remained unclear. Here we show that ACAT1 is the major functional isoenzyme in the mouse brain. ACAT1 gene ablation (A1-) in triple transgenic (i.e., 3XTg-AD) mice leads to more than 60% reduction in full-length human APPswe as well as its proteolytic fragments, and ameliorates cognitive deficits. At 4 months of age, A1- causes a 32% content increase in 24-hydroxycholesterol (24SOH), the major oxysterol in the brain. It also causes a 65% protein content decrease in HMG-CoA reductase (HMGR) and a 28% decrease in sterol synthesis rate in AD mouse brains. In hippocampal neurons, A1- causes an increase in the 24SOH synthesis rate; treating hippocampal neuronal cells with 24SOH causes rapid declines in hAPP and in HMGR protein levels. A model is provided to explain our findings: in neurons, A1- causes increases in cholesterol and 24SOH contents in the endoplasmic reticulum, which cause reductions in hAPP and HMGR protein contents and lead to amelioration of amyloid pathology. Our study supports the potential of ACAT1 as a therapeutic target for treating certain forms of AD.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
This survey by the Southern Euboea Exploration Project provides a wealth of intriguing information about fluctuations in long-term use and habitation in the Bouros-Kastri peninsula at the ...south-eastern tip of the Greek island of Euboia, and how the peninsula's use was connected to that of the main urban centre at Karystos.
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