A Comparative Study of Reading Achievement Growth and Attitude toward Reading When Instructed Through a Basal Reader Manual or Sanders’ Questioning Technique

The purpose of this study was to evaluate the reading achievement growth and to analyze the reading attitudes of seventh grade students when they are subjected to different methods of teacher questions. The two approaches used were: (1) the Basal Text Guidebook questioning approach, and (2) the Sanders\u27 Questioning technique

Cognitive testing for dementia is adversely affected by administration in a foreign location

BACKGROUND: It is colloquially considered that cognitive tests can be adversely affected by administration in a foreign location. However, a definitive demonstration of this is lacking in the literature. To determine whether or not this is the case, we compared the results of cognitive testing in a familiar versus foreign environment by single test administrator of individuals diagnosed with Alzheimer\u27s disease randomized to placebo in a multi-site clinical study. FINDINGS: Cognitive tests were administered to 6 long-term residents of an assisted living facility at their residence (the Familiar cohort). The identical tests were administered to a newly admitted resident and to 2 community-dwelling individuals who drove to the administrator\u27s office for the first time (the Foreign cohort). Secondary testing was administered 3 months later at the same respective locations. Caregivers of participants completed reports of mood, behavior and activities of daily living. The Familiar cohort performed equally well at both visits. The Foreign cohort performed significantly worse than the Familiar cohort at baseline. They improved statistically, and matched Familiar cohort performance, by their second visit. Caregiver reports for both cohorts were unchanged between visits. CONCLUSIONS: These findings support the notion that a foreign location can adversely affect performance on cognitive tests, and therefore support cognitive testing in a familiar location

The systematic functional characterisation of Xq28 genes prioritises candidate disease genes

BACKGROUND: Well known for its gene density and the large number of mapped diseases, the human sub-chromosomal region Xq28 has long been a focus of genome research. Over 40 of approximately 300 X-linked diseases map to this region, and systematic mapping, transcript identification, and mutation analysis has led to the identification of causative genes for 26 of these diseases, leaving another 17 diseases mapped to Xq28, where the causative gene is still unknown. To expedite disease gene identification, we have initiated the functional characterisation of all known Xq28 genes. RESULTS: By using a systematic approach, we describe the Xq28 genes by RNA in situ hybridisation and Northern blotting of the mouse orthologs, as well as subcellular localisation and data mining of the human genes. We have developed a relational web-accessible database with comprehensive query options integrating all experimental data. Using this database, we matched gene expression patterns with affected tissues for 16 of the 17 remaining Xq28 linked diseases, where the causative gene is unknown. CONCLUSION: By using this systematic approach, we have prioritised genes in linkage regions of Xq28-mapped diseases to an amenable number for mutational screens. Our database can be queried by any researcher performing highly specified searches including diseases not listed in OMIM or diseases that might be linked to Xq28 in the future

A Nutritional Formulation for Cognitive Performance and Mood in Alzheimer’s Disease and Mild Cognitive Impairment: A Phase II Multi-site Randomized Trial with an Open-label Extension

Background: It is increasingly recognized that interventions for dementia must shift towards prevention to obtain maximal efficacy and any significant degree of disease modification. Nutritional supplementation with single agents has shown varied results, suggesting the need for combinatorial intervention. Methods: We conducted a 3-month, randomized, multi-site, phase II study in which 141 individuals diagnosed with Alzheimer’s disease (AD) and 34 individuals with Mild Cognitive Impairment received a nutraceutical formulation (NF; folate, alpha-tocopherol, B12, S-adenosyl methioinine, N-acetyl cysteine, acetyl-L-carnitine) or indistinguishable placebo under double-blind conditions, followed by an open-label extension in which all individuals received NF for a total of 1yr. An additional 38 individuals with AD received NF under open-label conditions from baseline for 1yr. The primary outcome was defined as cognitive performance. Secondary outcomes were defined as behavioral and psychological symptoms of dementia and activities of daily living. Results: Participants randomized to NF improved statistically within 3 months in cognitive performance as ascertained by Clox-1 and the Dementia Rating Scale, and their caregivers reported improvement in Neuropsychiatric Inventory. Participants receiving NF either continued to improve or maintained their baseline performance during open-label extensions. Participants randomized to placebo did not improve, but during open-label extensions displayed similar improvement within 3 months to that of participants initially randomized to NF. Caregivers reported no change in Activities of Daily Living for either cohort. Conclusions: These findings confirm and extend prior phase I studies in which NF improved or maintained cognitive performance and behavioral symptoms for individuals with AD, and improved cognitive performance for community-dwelling individuals without dementia. In published studies with transgenic mice NF reduced PS-1 expression, beta and gamma secretase activity, Abeta deposits, phospho-tau, homocysteine and oxidative damage, and increased acetylcholine and glutathione. This comprehensive impact of NF on AD-related neuropathology supports the possibility that NF may harbor disease-modifying properties

The full-ORF clone resource of the German cDNA Consortium

<p>Abstract</p> <p>Background</p> <p>With the completion of the human genome sequence the functional analysis and characterization of the encoded proteins has become the next urging challenge in the post-genome era. The lack of comprehensive ORFeome resources has thus far hampered systematic applications by protein gain-of-function analysis. Gene and ORF coverage with full-length ORF clones thus needs to be extended. In combination with a unique and versatile cloning system, these will provide the tools for genome-wide systematic functional analyses, to achieve a deeper insight into complex biological processes.</p> <p>Results</p> <p>Here we describe the generation of a full-ORF clone resource of human genes applying the Gateway cloning technology (Invitrogen). A pipeline for efficient cloning and sequencing was developed and a sample tracking database was implemented to streamline the clone production process targeting more than 2,200 different ORFs. In addition, a robust cloning strategy was established, permitting the simultaneous generation of two clone variants that contain a particular ORF with as well as without a stop codon by the implementation of only one additional working step into the cloning procedure. Up to 92 % of the targeted ORFs were successfully amplified by PCR and more than 93 % of the amplicons successfully cloned.</p> <p>Conclusion</p> <p>The German cDNA Consortium ORFeome resource currently consists of more than 3,800 sequence-verified entry clones representing ORFs, cloned with and without stop codon, for about 1,700 different gene loci. 177 splice variants were cloned representing 121 of these genes. The entry clones have been used to generate over 5,000 different expression constructs, providing the basis for functional profiling applications. As a member of the recently formed international ORFeome collaboration we substantially contribute to generating and providing a whole genome human ORFeome collection in a unique cloning system that is made freely available in the community.</p

Omicron‐induced interferon signaling prevents influenza A H1N1 and H5N1 virus infection

Recent findings in permanent cell lines suggested that SARS‐CoV‐2 Omicron BA.1 induces a stronger interferon response than Delta. Here, we show that BA.1 and BA.5 but not Delta induce an antiviral state in air‐liquid interface cultures of primary human bronchial epithelial cells and primary human monocytes. Both Omicron subvariants caused the production of biologically active types I (α/β) and III (λ) interferons and protected cells from super‐infection with influenza A viruses. Notably, abortive Omicron infection of monocytes was sufficient to protect monocytes from influenza A virus infection. Interestingly, while influenza‐like illnesses surged during the Delta wave in England, their spread rapidly declined upon the emergence of Omicron. Mechanistically, Omicron‐induced interferon signaling was mediated via double‐stranded RNA recognition by MDA5, as MDA5 knockout prevented it. The JAK/STAT inhibitor baricitinib inhibited the Omicron‐mediated antiviral response, suggesting it is caused by MDA5‐mediated interferon production, which activates interferon receptors that then trigger JAK/STAT signaling. In conclusion, our study (1) demonstrates that only Omicron but not Delta induces a substantial interferon response in physiologically relevant models, (2) shows that Omicron infection protects cells from influenza A virus super‐infection, and (3) indicates that BA.1 and BA.5 induce comparable antiviral states

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation