Mutations induced by DNA double-strand breaks: The influence of genomic site

The transgenic CHO cell line PL61, carrying a recombinant SV40-gpt gene, was treated with restriction endonucleases to assess mutagenesis from defined DNA double-strand breaks. Mutations ingpt were measured under two conditions: a stringent condition where selection ensured that the closely-linkedneo gene was retained functionally intact, or a relaxed condition without the requirement forneo gene function. Despite testing 18 different restriction endonucleases with various numbers of potential break-sites within the transgene, mutations were only found under relaxed selection conditions. These mutations commonly led to complete loss of the transgene, suggesting that large deletions predominate when selection is relaxed. It is argued, in comparison to mutation data for other genomic sites in CHO cells, that variations in the ‘effective target size’ for mutagenesis may explain the response of the transgene under different conditions.     

Mechanical performance of sutures in surgery.

In this study, we have compared the recommended configuration of a knot with specified sutures as ascertained by mechanical performance tests to that employed by a group of board-certified surgeons. Agreement between the surgeon and the results of the test was encountered in only one fourth of the instances. In another one fourth of the cases the surgeon overestimated the number of throws required for a knot to reach knot break. This additional suture material further handicaps the host's defenses, thereby inviting infection. Surgeons employed knots that untied without reaching knot break in the remaining half of the cases. The holding power of many of the knots that untied was substantially less than that of knots reaching knot break. On the basis of the study, it is recommended that results of the mechanical performance tests be made readily available to the surgeon so that his patient can receive maximal benefits from the knotted suture with the least damage to the host's defenses.     

Health care decision making in southern county

We combine two standard approaches to analyze power and influence in health policy formulation within a moderately large county in the south. Intrinsic methodologic weaknesses are discussed and several conclusions are drawn regarding power in the health care sector of that community. The most significant finding is the shift in power over time, away from the individuals to committees and health care organizations. The ignorance of most physicians about the broader health care issues that affect the community was reflected in their lack of recognition by others in the community as influential decision makers. The insular relationship of the university to the rest of the community was also noted. Past racial politics had a continuing effect on later health policy formulation. These findings are discussed in light of current and past issues. Because we had promised confidentiality to the persons we interviewed, fictitious names were given to the county, the institutions, and the interviewees.     

The effects of eticlopride on Morris water task performance in male and female rats neonatally treated with quinpirole

Rationale Previous studies have shown that neonatal quinpirole treatment which results in long-term dopamine D2 receptor supersensitization (D2 receptor priming) produces cognitive deficits in preweanling and adult rats behaviorally tested on the Morris water task (MWT).Objective This study was designed to analyze whether pretraining administration of the D2 antagonist eticlopride alleviates cognitive deficits produced by neonatal quinpirole treatment.Methods Both male and female Sprague–Dawley rats were treated with quinpirole HCl (1 mg/kg) or saline from postnatal days 1 to 21. From P22 to P24, rats were tested on the place version of the MWT in which a hidden platform remains stationary throughout training. From P25 to P28, rats were tested on the match-to-place version of the MWT, and rats are given a pair of daily training trials to locate the hidden platform that was moved to a new location each day. Fifteen minutes before each training session, rats were intraperitoneally administered with eticlopride (0.01 or 0.02 mg/kg) or saline.Results Pretraining eticlopride treatment alleviated cognitive deficits produced by neonatal quinpirole treatment in both male and female rats on the place version of the MWT, as well as in males tested on the match-to-place version of the MWT. However, there were no significant deficits produced by neonatal quinpirole treatment in females tested on the match-to-place version of the MWT, and control males demonstrated superiority over control females on this version of the task.Conclusions Pretraining administration of the dopamine D2 antagonist eticlopride alleviated cognitive deficits produced by neonatal quinpirole treatment. However, it appears that the dopamine D2 receptor may have a more important influence on cognitive performance in males than in females, which may be related to increased sensitivity of the D2 receptor in males.     

Understanding 'not': neuropsychological dissociations between hand and head markers of negation in BSL

Simple negation in natural languages represents a complex interrelationship of syntax, prosody, semantics and pragmatics, and may be realised in various ways: lexically, morphologically and prosodically. In almost all spoken languages, the first two of these are the primary realisations of syntactic negation. In contrast, in many signed languages negation can occur without lexical or morphological marking. Thus, in British Sign Language (BSL), negation is obligatorily expressed using face-head actions alone (facial negation) with the option of articulating a manual form alongside the required face-head actions (lexical negation). What are the processes underlying facial negation? Here, we explore this question neuropsychologically. If facial negation reflects lexico-syntactic processing in BSL, it may be relatively spared in people with unilateral right hemisphere (RH) lesions, as has been suggested for other 'grammatical facial actions' [Language and Speech 42 (1999) 307; Emmorey, K. (2002). Language, cognition and the brain: Insights from sign language research. Mahwah, NJ: Erlbaum (Lawrence)]. Three BSL users with RH lesions were specifically impaired in perceiving facial compared with manual (lexical and morphological) negation. This dissociation was absent in three users of BSL with left hemisphere lesions and different degrees of language disorder, who also showed relative sparing of negation comprehension. We conclude that, in contrast to some analyses [Applied Psycholinguistics 18 (1997) 411; Emmorey, K. (2002). Language, cognition and the brain: Insights from sign language research. Mahwah, NJ: Erlbaum (Lawrence); Archives of Neurology 36 (1979) 837], non-manual negation in sign may not be a direct surface realisation of syntax [Language and Speech 42 (1999) 143; Language and Speech 42 (1999) 127]. Difficulties with facial negation in the RH-lesion group were associated with specific impairments in processing facial images, including facial expressions. However, they did not reflect generalised 'face-blindness', since the reading of (English) speech patterns from faces was spared in this group. We propose that some aspects of the linguistic analysis of sign language are achieved by prosodic analysis systems (analysis of face and head gestures), which are lateralised to the minor hemisphere.