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Biomedical subjects

Laura Wagner

Publications and source records attributed to Laura Wagner.

8 recordsLinked to original sources

Impaired trafficking of choline transporter-like protein-1 at plasma membrane and inhibition of choline transport in THP-1 monocyte-derived macrophages.

The present study investigates choline transport processes and regulation of choline transporter-like protein-1 (CTL1) in human THP-1 monocytic cells and phorbol myristate 13-acetate (PMA)-differentiated macrophages. Choline uptake is saturable and therefore protein-mediated in both cell types, but its transport characteristics change soon after treatments with PMA. The maximal rate of choline uptake intrinsic to monocytic cells is greatly diminished in differentiated macrophages as demonstrated by alterations in V(max) values from 1,973 +/- 118 to 380 +/- 18 nmol x mg(-1) x min(-1), when the binding affinity did not change significantly (K(m) values 56 +/- 8 and 53 +/- 6 microM, respectively). Treatments with hemicholinim-3 effectively inhibit most of the choline uptake, establishing that a choline-specific transport protein rather than a general transporter is responsible for the observed kinetic parameters. mRNA screening for the expression of various transporters reveals that CTL1 is the most plausible candidate that possesses the described kinetic and inhibitory properties. Fluorescence-activated cell sorting analyses at various times after PMA treatments further demonstrate that the disappearance of CTL1 protein from the cell surface follows the same trend as the reduction in choline uptake. Importantly, the loss of functional CTL1 from the cell surface occurs without significant changes in total CTL1 protein or its mRNA level indicating that an impaired CTL1 trafficking is the key contributing factor to the reduced choline uptake, subsequent to the PMA-induced THP-1 differentiation to macrophages.

Animals↗

Identification and expression of a mouse muscle-specific CTL1 gene.

In this study, a mouse gene and cDNA encoding for a novel skeletal muscle-specific choline transporter-like protein 1 (mCTL1) were identified and mCTL1 mRNA and protein expression characterized. The mCTL1 cDNA is 2888-bp long; consisting of a 653-amino-acid open-reading frame, 8-11 putative transmembrane domains, three N-glycosylation sites and seven protein kinase C phosphorylation sites. The mCTL1 gene is localized to chromosome 4B2, at 182 kb in length, and encoded by 17 exons. Although the mCTL1 mRNA was expressed in several mouse tissues such as muscle, brain, heart and testis, the protein analyses of multiple tissues and membrane vesicles reveal that mCTL1 is exclusively expressed in skeletal muscle. Expression of His-tagged mCTL1 in Cos-7 cells produces an increase in saturable choline uptake that is sensitive to a Na(+)-ion gradient, ethanolamine and the Ca(2+)-channel blocker verapamil, and insensitive to low concentrations of hemicholinium-3.

Animals↗

Individuation of objects and events: a developmental study.

This study investigates children's ability to use language to guide their choice of individuation criterion in the domains of objects and events. Previous work (Shipley, E. F., & Shepperson, B. (1990). Countable entities: developmental changes. Cognition, 34, 109-136.) has shown that children have a strong bias to use a spatio-temporal individuation strategy when counting objects and that children will ignore a conflicting linguistic description in favor of this spatio-temporal bias. Experiment 1 asked children (3-, 4-, and 5-year-olds) and adults to count objects and events under different linguistic descriptions. In the object task, subjects counted pictures of familiar objects split into multiple pieces (as in Shipley, E. F., & Shepperson, B. (1990). Countable entities: developmental changes. Cognition, 34, 109-136.) and described either using an appropriate kind label (e.g. "car") or the general term "thing". In the event task, subjects watched short animated movies consisting of a goal-oriented event achieved via multiple, temporally separated steps. The events were described either with an appropriate telic predicate targeting the goal (e.g. "paint a flower") or with an atelic predicate targeting the steps in the process (e.g. "paint") and the subjects' task was to count the events. Relative to adults, children preferred a spatio-temporal counting strategy in both tasks; there was no difference among the three groups of children. However, children were able to significantly change their counting strategy to follow the linguistic description in the event but not the object task. Experiment 2 extended the object task to include counting of other types of non-spatio-temporal units such as sub-parts of objects and collections. Results showed that children could use the linguistic descriptions to guide their counting strategy for these new items, though they continued to show a bias for a spatio-temporal individuation strategy with the collections. We suggest potential cognitive origins for the spatio-temporal individuation bias and how it interacts with children's developing linguistic knowledge.

Adult↗

Understanding completion entailments in the absence of agency cues.

This study investigated the role that agency information plays in children's early interpretations of grammatical aspect morphology, in particular, the progressive -ing and simple past forms. Fifty-nine children (two-, four- and five-year olds) were presented with a forced-choice sentence-to-scene matching task very similar to the one used by Weist and colleagues (Weist, 1991; Weist, Wysocka & Lyytinen, 1991; Weist, Lyytinen, Wysocka & Atanassova, 1997), except that here the scenes contained only information about the relative completion of the object of the event and no information about the state of the agent of the event. In contrast to previous research, the children here did not succeed at this object-oriented task until as late as age five; moreover, also contra previous work, when they did succeed, their performance tracked the formal entailments of grammatical aspect. Thus, subjects consistently matched the perfective sentence to the completed event (reflecting the perfective's entailment of completion) but never consistently matched the imperfective sentence to either scene (reflecting the imperfective's lack of entailments). It is argued that agent-oriented meaning, in particular, intentionality, has priority in the mapping process over object-oriented completion entailments.

Adult↗

Advance care planning and end-of-life care for hospitalized nursing home residents.

OBJECTIVES: To describe advance care planning (ACP) and end-of-life care for nursing home residents who are hospitalized in the last 6 weeks of life. DESIGN: Constant comparative analysis of deceased nursing home resident cases. SETTING: A not-for-profit Jewish nursing home. PARTICIPANTS: Forty-three deceased residents hospitalized within the last 6 weeks of life at a tertiary medical center. MEASUREMENTS: Trained nurse reviewers abstracted data from nursing home records and gerontological advanced practice nurse field notes. Clinical and outcome data from the original study were used to describe the sample. Data were analyzed using the constant comparative method and validated in interviews with a gerontological advanced practice nurse and social worker. RESULTS: The analysis revealed distinct characteristics and identifiable transition points in ACP and end-of-life care with frail nursing home residents. ACP was addressed by social workers as part of the nursing home admission process, focused primarily on cardiopulmonary resuscitation preference, and reviewed only after the crisis of acute illness and hospitalization. Advance directive forms specifying preferences or limitations for life-sustaining treatment contained inconsistent language and vague conditions for implementation. ACP review generally resulted in gradual limitation of life-sustaining treatment. Transition points included nursing home admission, acute illness or hospitalization, and decline toward death. Relatively few nursing home residents received hospice services, with most hospice referrals and palliative care treatment delayed until the week before death. Most residents in this sample died without family present and with little documented evidence of pain or symptom management. CONCLUSION: Limiting discussion of advance care plans to cardiopulmonary resuscitation falsely dichotomized and oversimplified the choices about medical treatment and care at end-of-life, especially palliative care alternatives, for these older nursing home residents. Formal hospice services were underutilized, and palliative care efforts by nursing home staff were often inconsistent with accepted standards. These results reinforce the need for research and program initiatives in long-term care to improve and facilitate individualized ACP and palliative care at end of life.

Advance Directives↗

Does legally mandated consent to psychotherapy ensure ethical appropriateness?: the Colorado experience.

We analyzed a sample of 356 forms containing information that Colorado law legally requires both licensed and unlicensed therapists to disclose to clients. The majority of forms contained the legally mandated information; fewer forms contained ethically desirable information. The average readability grade level was 15.74, corresponding to upper-level college, and 63.9% of the forms reached the highest (most difficult) readability grade of 17+. Therapists are obeying the law, but do not appear to be taking advantage of the opportunity to provide their clients useful information in an accessible way.

Cognition↗