A Study Of The Discriminative Function Of Six Variables In 9-12-Year-Old Males With Learning Disabilities

Problem Greater discriminative power to clarify the diagnostic category of learning disabilities is needed. Research identifies many types of learning disabled populations. Studies do not indicate that the six variables used in this project had been combined and used in a project prior to this. Using measures such as Sentence Repeat, Synonyms, Digits Forward/Backwards, Design Copy, Nonsense Words, and Visual Pattern Matching, this project studied the responses of an LD sample to these subtests and their ability to discriminate among a verbally impaired sample, a spatially impaired sample, and a control group. Method Six subtests were developed, which, according to the literature, measured auditory discrimination and memory (Sentence Repeat); auditory and verbal comprehension and general verbal background (Synonyms); immediate auditory memory, attention, concentration, double tracking, and reversal of mental operations (Digits Forward/Backwards); visual perceptual-motor functioning (Design Copy); lexical processing (Nonsense Words); and visual memory and visual-perceptual learning (Visual Pattern Matching). The basic null hypothesis was that there is no linear combination of six variables which significantly discriminates among the three groups. The instrument was subjected to a pilot study before the final data collection took place. The data were analyzed using one-way analysis of variance, multivariate analysis of variance, and discriminant function analysis. Results Two subtests dominated in their ability to discriminate among the groups--Synonyms and Digits Forward/Backwards. Both the verbal and spatial groups were found to have shared deficits, but differed significantly from the control group on most of the measures. The null hypothesis was rejected. Conclusion The 9-12-year-old males in this sample with learning disabilities expressed deficits only in verbally related areas--specifically auditory/verbal comprehension and short-term auditory memory, attention, and concentration. Based on the literature and data gathering experience, it was also revealed that students should not be placed in LD programs based on one test, and a home visit should take place

The Circadian Clock Protein CRY1 Is a Negative Regulator of HIF-1 alpha

The circadian clock and the hypoxia-signaling pathway are regulated by an integrated interplay of positive and negative feedback limbs that incorporate energy homeostasis and carcinogenesis. We show that the negative circadian regulator CRY1 is also a negative regulator of hypoxia-inducible factor (HIF). Mechanistically, CRY1 interacts with the basic-helix-loop-helix domain of HIF-1a via its tail region. Subsequently, CRY1 reduces HIF-1a half-life and binding of HIFs to target gene promoters. This appeared to be CRY1 specific because genetic disruption of CRY1, but not CRY2, affected the hypoxia response. Furthermore, CRY1 deficiency could induce cellular HIF levels, proliferation, and migration, which could be reversed by CRISPR/Cas9- or short hairpin RNA-mediated HIF knockout. Altogether, our study provides a mechanistic explanation for genetic association studies linking a disruption of the circadian clock with hypoxia-associated processes such as carcinogenesis

Proteomic Candidate Biomarkers of Drug-Induced Nephrotoxicity in the Rat

Improved biomarkers of acute nephrotoxicity are coveted by the drug development industry, regulatory agencies, and clinicians. In an effort to identify such biomarkers, urinary peptide profiles of rats treated with two different nephrotoxins were investigated. 493 marker candidates were defined that showed a significant response to cis-platin comparing a cis-platin treated cohort to controls. Next, urine samples from rats that received three consecutive daily doses of 150 or 300 mg/kg gentamicin were examined. 557 potential biomarkers were initially identified; 108 of these gentamicin-response markers showed a clear temporal response to treatment. 39 of the cisplatin-response markers also displayed a clear response to gentamicin. Of the combined 147 peptides, 101 were similarly regulated by gentamicin or cis-platin and 54 could be identified by tandem mass spectrometry. Most were collagen type I and type III fragments up-regulated in response to gentamicin treatment. Based on these peptides, classification models were generated and validated in a longitudinal study. In agreement with histopathology, the observed changes in classification scores were transient, initiated after the first dose, and generally persistent over a period of 10–20 days before returning to control levels. The data support the hypothesis that gentamicin-induced renal toxicity up-regulates protease activity, resulting in an increase in several specific urinary collagen fragments. Urinary proteomic biomarkers identified here, especially those common to both nephrotoxins, may serve as a valuable tool to investigate potential new drug candidates for the risk of nephrotoxicity

Evaluating the Stability of RNA-Seq Transcriptome Profiles and Drug-Induced Immune-Related Expression Changes in Whole Blood.

Methods were developed to evaluate the stability of rat whole blood expression obtained from RNA sequencing (RNA-seq) and assess changes in whole blood transcriptome profiles in experiments replicated over time. Expression was measured in globin-depleted RNA extracted from the whole blood of Sprague-Dawley rats, given either saline (control) or neurotoxic doses of amphetamine (AMPH). The experiment was repeated four times (paired control and AMPH groups) over a 2-year span. The transcriptome of the control and AMPH-treated groups was evaluated on: 1) transcript levels for ribosomal protein subunits; 2) relative expression of immune-related genes; 3) stability of the control transcriptome over 2 years; and 4) stability of the effects of AMPH on immune-related genes over 2 years. All, except one, of the 70 genes that encode the 80s ribosome had levels that ranked in the top 5% of all mean expression levels. Deviations in sequencing performance led to significant changes in the ribosomal transcripts. The overall expression profile of immune-related genes and genes specific to monocytes, T-cells or B-cells were well represented and consistent within treatment groups. There were no differences between the levels of ribosomal transcripts in time-matched control and AMPH groups but significant differences in the expression of immune-related genes between control and AMPH groups. AMPH significantly increased expression of some genes related to monocytes but down-regulated those specific to T-cells. These changes were partially due to changes in the two types of leukocytes present in blood, which indicate an activation of the innate immune system by AMPH. Thus, the stability of RNA-seq whole blood transcriptome can be verified by assessing ribosomal protein subunits and immune-related gene expression. Such stability enables the pooling of samples from replicate experiments to carry out differential expression analysis with acceptable power