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Biomedical subjects

J Conners

Publications and source records attributed to J Conners.

8 recordsLinked to original sources

Homeobox gene Nkx6.1 lies downstream of Nkx2.2 in the major pathway of beta-cell formation in the pancreas.

Most insulin-producing beta-cells in the fetal mouse pancreas arise during the secondary transition, a wave of differentiation starting at embryonic day 13. Here, we show that disruption of homeobox gene Nkx6.1 in mice leads to loss of beta-cell precursors and blocks beta-cell neogenesis specifically during the secondary transition. In contrast, islet development in Nkx6. 1/Nkx2.2 double mutant embryos is identical to Nkx2.2 single mutant islet development: beta-cell precursors survive but fail to differentiate into beta-cells throughout development. Together, these experiments reveal two independently controlled pathways for beta-cell differentiation, and place Nkx6.1 downstream of Nkx2.2 in the major pathway of beta-cell differentiation.

Animals↗

Skill acquisition in the implementation of functional analysis methodology.

Functional analysis methodology is a powerful assessment tool for identifying contingencies that maintain a wide range of behavior disorders and for developing effective treatment programs. Nevertheless, concerns have been raised about the feasibility of conducting functional analyses in typical service settings. In this study, we examined the issue of skill acquisition in implementing functional analyses by evaluating an instructional program designed to establish a basic set of competencies. Eleven undergraduate students enrolled in a laboratory course in applied behavior analysis served as participants. Their performance was assessed during scripted simulations in which they played the roles of "therapists" who conducted functional analyses and trained graduate students played the roles of "clients" who emitted self-injurious and destructive behaviors. To approximate conditions under which an individual might conduct an assessment with limited prior training, participants read a brief set of materials prior to conducting baseline sessions. A multiple baseline design was used to assess the effects of training, which consisted of reading additional materials, watching a videotaped simulation demonstrating correct procedural implementation, passing a written quiz, and receiving feedback on performance during sessions. Results showed that participants scored a relatively high percentage of correct therapist responses during baseline, and that all achieved an accuracy level of 95% or higher following training that lasted about 2 hr. These results suggest that basic skills for conducting functional analyses can be acquired quickly by individuals who have relatively little clinical experience.

Feasibility Studies↗

Differential responding in the presence and absence of discriminative stimuli during multielement functional analyses.

We evaluated the extent to which discriminative stimuli (S(D)s) facilitate differential responding during multielement functional analyses. Eight individuals, all diagnosed with mental retardation and referred for assessment and treatment of self-injurious behavior (SIB) or aggression, participated. Functional analyses consisted of four or five assessment conditions alternated in multielement designs. Each condition was initially correlated with a specific therapist and a specific room color (S(D)s), and sessions continued until higher rates of target behaviors were consistently observed under a specific test condition. In a subsequent analysis, the programmed S(D)s were removed (i.e., all conditions were now conducted by the same therapist in the same room), and sessions continued until differential responding was observed or until twice as many sessions were conducted with the S(D)s absent (as opposed to present), whichever came first. Results indicated that the inclusion of programmed S(D)s facilitated discrimination among functional analysis conditions for half of the participants. These results suggest that the inclusion of salient cues may increase either the efficiency of functional analyses or the likelihood of obtaining clear assessment outcomes.

Adult↗

Relative influences of establishing operations and reinforcement contingencies on self-injurious behavior during functional analyses.

In the typical functional analysis in which the antecedent and consequent events associated with problem behavior are manipulated, the control condition involves elimination of both the relevant establishing operation (EO) and its associated contingency through a schedule of noncontingent reinforcement (usually fixed-time [FT] 30 s). In some functional analyses, however, antecedent events are manipulated in the absence of differential consequences, and a common test condition in such analyses also involves the delivery of reinforcement on an FT 30-s schedule. Thus, the same schedule of reinforcement (FT 30 s) is not considered to be an EO in the former type of analysis but is considered to be an EO in the latter. We examined the relative influences of EOs and reinforcement contingencies on problem behavior by exposing 6 individuals who engaged in self-injurious behavior (SIB) to four combinations of functional analysis conditions: EO present/contingency present, EO absent/contingency present, EO present/contingency absent, and EO absent/contingency absent. Results indicated that the only condition in which high rates of SIB were observed consistently was one in which the EO and the reinforcement contingency were both present. Implications of these results for the design of functional analysis test and control conditions are discussed.

Adult↗

Examination of ambiguous stimulus preferences with duration-based measures.

Items that produced ambiguous results in an approach-based preference assessment were reassessed using a duration-based assessment. The reinforcing effects of three items on free-operant responding were subsequently tested. The results suggested that the duration-based assessment produced slightly more differentiated results and that predictions about reinforcer value, based on this assessment, were accurate.

Adult↗

Effects of reinforcement for alternative behavior during punishment of self-injury.

A number of variables influence the effectiveness of punishment and may determine the extent to which less intrusive forms of punishment may be used as alternatives to more intrusive interventions. For example, it has been suggested that response suppression during punishment may be facilitated if reinforcement is concurrently available for an alternative response. However, results of basic research demonstrating this finding have not been replicated with interventions more commonly prescribed as treatments for problem behavior. We evaluated the effects of relatively benign punishment procedures (reprimands or brief manual restraint) on the self-injurious behavior of 4 individuals who had been diagnosed with mental retardation, when access to reinforcement for alternative behavior (manipulation of leisure materials) was and was not available. In all cases, punishment produced greater response suppression when reinforcement for an alternative response was available.

Adult↗

IL-4 and insulin-like growth factor-I inhibit the decline in Bcl-2 and promote the survival of IL-3-deprived myeloid progenitors.

The proto-oncogene product Bcl-2 regulates cell survival in both the immune and central nervous systems. We withdrew growth factors from IL-3-dependent murine myeloid progenitor cells (factor dependent cell progenitors (FDCP)) and measured a time-dependent 80% reduction in endogenous expression of Bcl-2. This decline in Bcl-2 is directly associated with a fourfold increase in the apoptotic population after 12 h and an eightfold increase after 24 h. Since IL-4 and insulin-like growth factor-I (IGF-I) regulate myeloid cell growth, we used IL-3-deprived FDCP cells to determine whether IL-4 and IGF-I maintain Bcl-2 expression and prevent apoptosis. We demonstrate that IL-4, like IGF-I and IL-3, promotes survival of FDCP cells by reducing the apoptotic population. Flow cytometric measurement of intracellular Bcl-2 established that IL-4 and IGF-I maintain 10-fold higher levels of Bcl-2 than in IL-3-deprived cells. Similarly, Western analysis of Bcl-2 in lysates of IL-3-deprived myeloid progenitors confirmed that both IL-4 and IGF-I share with IL-3 the ability to maintain intact Bcl-2 protein. However, IL-4 and IGF-I do not change expression of the apoptotic inducer, Bax, although they maintain high levels of Bcl-2 that coimmunoprecipitate with Bax. Collectively, these data demonstrate that IL-4 and IGF-I, like IL-3, inhibit apoptosis in myeloid progenitors and maintain high levels of Bcl-2/Bax heterodimers, suggesting that Bcl-2 is a critical convergence point in the signaling pathways used by IL-4 and IGF-I.

Animals↗