Hand2 represses non-cardiac cell fates through chromatin remodeling at cis- regulatory elements.

Developmental studies have revealed the importance of the transcription factor Hand2 in cardiac development. Hand2 promotes cardiac progenitor differentiation and epithelial maturation, while repressing other tissue types. The mechanisms underlying the promotion of cardiac fates are far better understood than those underlying the repression of alternative fates. Here, we assess Hand2-dependent changes in gene expression and chromatin remodeling in cardiac progenitors of zebrafish embryos. Cell-type specific transcriptome analysis shows a dual function for Hand2 in activation of cardiac differentiation genes and repression of pronephric pathways. We identify functional cis- regulatory elements whose chromatin accessibility are increased in hand2 mutant cells. These regulatory elements associate with non-cardiac gene expression, and drive reporter gene expression in tissues associated with Hand2-repressed genes. We find that functional Hand2 is sufficient to reduce non-cardiac reporter expression in cardiac lineages. Taken together, our data support a model of Hand2-dependent coordination of transcriptional programs, not only through transcriptional activation of cardiac and epithelial maturation genes, but also through repressive chromatin remodeling at the DNA regulatory elements of non-cardiac genes.

Exercise performance in adolescents with autonomic dysfunction.

OBJECTIVE: To test the hypothesis that excessive postural tachycardia is associated with deconditioning rather than merely being an independent sign of autonomic dysfunction in patients with postural orthostatic tachycardia syndrome (POTS). STUDY DESIGN: We retrospectively analyzed records from 202 adolescents who underwent both head up-tilt and maximal exercise testing. Patients were classified as POTS if they had ≥ 30 min(-1) rise in heart rate (HR) after tilt-table test; and deconditioned if peak O(2) uptake was < 80% predicted. Changes in HR during exercise and recovery were compared between groups. RESULTS: Two-thirds of patients were deconditioned, irrespective of whether they fulfilled diagnostic criteria for POTS, but peak O(2) uptake among patients with POTS was similar to patients without POTS. HR was higher at rest and during exercise; whereas stroke volume was lower during exercise, and HR recovery was slower in patients with POTS compared with patients without POTS. CONCLUSIONS: Most patients who presented with chronic symptoms of dizziness, fatigue, or pre-syncope, were deconditioned, but, because the proportion of deconditioned patients was similar in POTS vs non-POTS groups, we conclude that HR changes in POTS are not solely because of inactivity resulting in deconditioning.

Urinary incontinence.

Preview Many older patients with urinary incontinence hesitate to tell their healthcare providers, and even if they do, the condition may not be properly assessed or treated. As a result, patients may restrict or even totally avoid social activities. In this article, Drs Yim and Peterson stress the need for greater awareness of the problem and describe basic types of incontinence, diagnostic studies, and treatment options that can improve the quality of life of affected patients.