Young children's performance on a task sensitive to the memory functions of the medial temporal lobe in adults: The delayed nonmatching-to-sample task reveals problems that are due to non-memory-related task demands.

Delayed nonmatching-to-sample performance was examined in children and found to be poor from 12 mo until almost 2 yrs even at 5-sec delay, although 5 sec is well within such children's memory capacity. After 12 mo of age, performance did not differ by delay (5 or 30 sec). Because children's problems seemed largely unrelated to the task's memory demands, the 2 final studies explored the role of other cognitive abilities (deduction of an abstract rule, speed of processing, and resistance to interference or distraction). Telling children the rule or quadrupling sample presentation time had little effect. Because a salient stimulus (the reward) might interfere with keeping one's attention on the sample, the reward was omitted during initial sample presentation. This helped; at the 5-sec delay, 15-mo-olds performed at least as well as 21-mo-olds in the basic condition, and 12-mo-olds performed almost as well. Implications for the cognitive abilities improving during the 2nd year and for the functions of the medial temporal lobe are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

siRNA Modified with 2′‐Deoxy‐2′‐C‐methylpyrimidine Nucleosides

(2′S)‐2′‐Deoxy‐2′‐C‐methyluridine and (2′R)‐2′‐deoxy‐2′‐C‐methyluridine were incorporated in the 3′‐overhang region of the sense and antisense strands and in positions 2 and 5 of the seed region of siRNA duplexes directed against Renilla luciferase, whereas (2′S)‐2′‐deoxy‐2′‐C‐methylcytidine was incorporated in the 6‐position of the seed region of the same constructions. A dual luciferase reporter assay in transfected HeLa cells was used as a model system to measure the IC₅₀ values of 24 different modified duplexes. The best results were obtained by the substitution of one thymidine unit in the antisense 3′‐overhang region by (2′S)‐ or (2′R)‐2′‐deoxy‐2′‐C‐methyluridine, reducing IC₅₀ to half of the value observed for the natural control. The selectivity of the modified siRNA was measured, it being found that modifications in positions 5 and 6 of the seed region had a positive effect on the ON/OFF activity.     

Interaction between ferric ions,phospholipid hydroperoxides,and the lipid phosphate moiety at physiological pH

Iron-catalyzed lipid peroxidation was examined using ¹H NMR in a biphasic aqueous-chloroform system. At physiological pH (7.4), mole ratios of phospholipids/Fe³⁺ as low as 1300∶1 catalyzed the rapid disappearance of endogenous lipid hydroperoxides with a loss of two of the four double bonds in PC containing palmitic (16∶0) and arachidonic (20∶4) acids in the sn-1 and sn-2 positions, respectively. The predominant phospholipid products after 1 h at 20°C were a 9-carbon monounsaturated carbonyl and a phospholipid with an 11-carbon Δ^5,8 FA in the sn-2 position. PC with linoleic acid (18∶2) in the sn-2 position lost one double bond and formed a phospholipid with a 9-carbon FA. Cardiolipin (linoleic acid-rich) also lost about 40% of its double bonds. No detectable loss was seen for PC containing oleic acid (18∶1) or neutral lipids with PUFA. At arachidonyl PC/Fe³⁺ ratios less than 20∶1, significant broadening of the choline methyl proton peak was evident, indicating that Fe³⁺ may form a complex with the adjacent phosphate group and that the complex involves both the phosphate and the hydroperoxide adjacent to the Δ¹¹ double bond. The results demonstrate that, at physiological pH, Fe³⁺-catalyzed peroxidation in polyunsaturated phospholipids occurs selectively adjacent to specific double bonds (Δ⁹ or Δ¹¹). These PC-derived products have been shown to activate components of the inflammatory system. This suggests that the episodic release of ferric ions may play a significant role in generating inflammatory mediators.     

Responses of dairy heifers to the visual cliff formed by a herringbone milking pit: Evidence of fear of heights in cows (Bos taurus).

The ability of cows (Bos taurus) to perceive depth has never been experimentally investigated. If cows can perceive depth, the milking pit in commercial milking facilities may be fear provoking for dairy cows, as past research has shown that most land-dwelling species possess an instinctive fear of heights. In the current study, 12 dairy heifers (1-year-old cows) were exposed to a milking pit (depth-exposed group) and 13 heifers (control group) were exposed to a standard change in the environment while they moved through a milking facility over a 5-day treatment period. Heifers in the depth-exposed group showed a higher heart rate (p     

The study of change in psychotherapy: A reexamination of the process–outcome correlation paradigm. Comment on Stiles and Shapiro (1994).

W. B. Stiles and D. A. Shapiro (see record 1995-10433-001) present a provocative argument that the yield of process research has been minimal because of researchers' overreliance on the drug metaphor and its corollary, the correlational design. Although Stiles and Shapiro raise excellent points regarding the possible misinterpretations of correlational research, their conclusion that the process-outcome correlation paradigm is flawed and has outlived its usefulness is questioned. The basic thesis is that Stiles and Shapiro did not provide a fair test of the correlation paradigm. The process variables used to test the paradigm do not have the strong theoretical and empirical grounding necessary to support the assumption that they should be related to outcome. In this article, examples are described, of programmatic process research that has used the correlation paradigm, along with other methods of inquiry, to advance the understanding of how change occurs and to improve treatment efficacy. It is contended that the correlational method is one useful tool of discovery and that it has contributed significantly to the advancement of the field when the process variables studied are grounded in solid theory and research. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Functionalization of the 3′‐Ends of DNA and RNA Strands with N‐ethyl‐N‐coupled Nucleosides: A Promising Approach To Avoid 3′‐Exonuclease‐Catalyzed Hydrolysis of Therapeutic Oligonucleotides

The development of nucleic acid derivatives to generate novel medical treatments has become increasingly popular, but the high vulnerability of oligonucleotides to nucleases limits their practical use. We explored the possibility of increasing the stability against 3′‐exonucleases by replacing the two 3′‐terminal nucleotides by N‐ethyl‐N‐coupled nucleosides. Molecular dynamics simulations of 3′‐N‐ethyl‐N‐modified DNA:Klenow fragment complexes suggested that this kind of alteration has negative effects on the correct positioning of the adjacent scissile phosphodiester bond at the active site of the enzyme, and accordingly was expected to protect the oligonucleotide from degradation. We verified that these modifications conferred complete resistance to 3′‐exonucleases. Furthermore, cellular RNAi experiments with 3′‐N‐ethyl‐N‐modified siRNAs showed that these modifications were compatible with the RNAi machinery. Overall, our experimental and theoretical studies strongly suggest that these modified oligonucleotides could be valuable for therapeutic applications.