Chondrogenesis and mineralization during in vitro culture of human mesenchymal stem cells on three-dimensional woven scaffolds.

Human mesenchymal stem cells (hMSCs) and three-dimensional (3D) woven poly(ɛ-caprolactone) (PCL) scaffolds are promising tools for skeletal tissue engineering. We hypothesized that in vitro culture duration and medium additives can individually and interactively influence the structure, composition, mechanical, and molecular properties of engineered tissues based on hMSCs and 3D poly(ɛ-caprolactone). Bone marrow hMSCs were suspended in collagen gel, seeded on scaffolds, and cultured for 1, 21, or 45 days under chondrogenic and/or osteogenic conditions. Structure, composition, biomechanics, and gene expression were analyzed. In chondrogenic medium, cartilaginous tissue formed by day 21, and hypertrophic mineralization was observed in the newly formed extracellular matrix at the interface with underlying scaffold by day 45. Glycosaminoglycan, hydroxyproline, and calcium contents, and alkaline phosphatase activity depended on culture duration and medium additives, with significant interactive effects (all p < 0.0001). The 45-day constructs exhibited mechanical properties on the order of magnitude of native articular cartilage (aggregate, Young's, and shear moduli of 0.15, 0.12, and 0.033 MPa, respectively). Gene expression was characteristic of chondrogenesis and endochondral bone formation, with sequential regulation of Sox-9, collagen type II, aggrecan, core binding factor alpha 1 (Cbfα1)/Runx2, bone sialoprotein, bone morphogenetic protein-2, and osteocalcin. In contrast, osteogenic medium produced limited osteogenesis. Long-term culture of hMSC on 3D scaffolds resulted in chondrogenesis and regional mineralization at the interface between soft, newly formed engineered cartilage, and stiffer underlying scaffold. These findings merit consideration when developing grafts for osteochondral defect repair.

Utility of telomerase-pot1 fusion protein in vascular tissue engineering.

While advances in regenerative medicine and vascular tissue engineering have been substantial in recent years, important stumbling blocks remain. In particular, the limited life span of differentiated cells that are harvested from elderly human donors is an important limitation in many areas of regenerative medicine. Recently, a mutant of the human telomerase reverse transcriptase enzyme (TERT) was described, which is highly processive and elongates telomeres more rapidly than conventional telomerase. This mutant, called pot1-TERT, is a chimeric fusion between the DNA binding protein pot1 and TERT. Because pot1-TERT is highly processive, it is possible that transient delivery of this transgene to cells that are utilized in regenerative medicine applications may elongate telomeres and extend cellular life span while avoiding risks that are associated with retroviral or lentiviral vectors. In the present study, adenoviral delivery of pot1-TERT resulted in transient reconstitution of telomerase activity in human smooth muscle cells, as demonstrated by telomeric repeat amplification protocol (TRAP). In addition, human engineered vessels that were cultured using pot1-TERT-expressing cells had greater collagen content and somewhat better performance in vivo than control grafts. Hence, transient delivery of pot1-TERT to elderly human cells may be useful for increasing cellular life span and improving the functional characteristics of resultant tissue-engineered constructs.

Popular culture, relational history, and the question of power in Palestine and Israel

The marginalization of popular culture in radical scholarship on Palestine and Israel is symptomatic of the conceptual limits that still define much Middle East studies scholarship: namely, the prevailing logic of the nation-state on the one hand and the analytic tools of classical Marxist historiography and political economy on the other. This essay offers a polemic about the form that alternative scholarly projects might take through recourse to questions of popular culture. The authors argue that close allention to the ways that popular culture "articulates" with broader political, social, and economic processes can expand scholarly understandings of the terrain of power in Palestine and Israel, and hence the possible arenas and modalities of struggle. © 2004 by the Institute for Palestine Studies. All rights reserved.

Barriers to and facilitators of interventions to counter publication bias: thematic analysis of scholarly articles and stakeholder interviews.

BACKGROUND: When the nature and direction of research results affect their chances of publication, a distortion of the evidence base - termed publication bias - results. Despite considerable recent efforts to implement measures to reduce the non-publication of trials, publication bias is still a major problem in medical research. The objective of our study was to identify barriers to and facilitators of interventions to prevent or reduce publication bias. METHODS: We systematically reviewed the scholarly literature and extracted data from articles. Further, we performed semi-structured interviews with stakeholders. We performed an inductive thematic analysis to identify barriers to and facilitators of interventions to counter publication bias. RESULTS: The systematic review identified 39 articles. Thirty-four of 89 invited interview partners agreed to be interviewed. We clustered interventions into four categories: prospective trial registration, incentives for reporting in peer-reviewed journals or research reports, public availability of individual patient-level data, and peer-review/editorial processes. Barriers we identified included economic and personal interests, lack of financial resources for a global comprehensive trial registry, and different legal systems. Facilitators identified included: raising awareness of the effects of publication bias, providing incentives to make data publically available, and implementing laws to enforce prospective registration and reporting of clinical trial results. CONCLUSIONS: Publication bias is a complex problem that reflects the complex system in which it occurs. The cooperation amongst stakeholders to increase public awareness of the problem, better tailoring of incentives to publish, and ultimately legislative regulations have the greatest potential for reducing publication bias.

The frequency of voluntary and involuntary autobiographical memories across the life span.

In the present study, ratings of the memory of an important event from the previous week on the frequency of voluntary and involuntary retrieval, belief in its accuracy, visual imagery, auditory imagery, setting, emotional intensity, valence, narrative coherence, and centrality to the life story were obtained from 988 adults whose ages ranged from 15 to over 90. Another 992 adults provided the same ratings for a memory from their confirmation day, when they were at about age 14. The frequencies of involuntary and voluntary retrieval were similar. Both frequencies were predicted by emotional intensity and centrality to the life story. The results from the present study-which is the first to measure the frequency of voluntary and involuntary retrieval for the same events-are counter to both cognitive and clinical theories, which consistently claim that involuntary memories are infrequent as compared with voluntary memories. Age and gender differences are noted.

People believe it is plausible to have forgotten memories of childhood sexual abuse.

Pezdek, Blandon-Gitlin, and Gabbay (2006) found that perceptions of the plausibility of events increase the likelihood that imagination may induce false memories of those events. Using a survey conducted by Gallup, we asked a large sample of the general population how plausible it would be for a person with longstanding emotional problems and a need for psychotherapy to be a victim of childhood sexual abuse, even though the person could not remember the abuse. Only 18% indicated that it was implausible or very implausible, whereas 67% indicated that such an occurrence was either plausible or very plausible. Combined with Pezdek et al.s' findings, and counter to their conclusions, our findings imply that there is a substantial danger of inducing false memories of childhood sexual abuse through imagination in psychotherapy.