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As the optimal therapeutic goal for post-MI treatment would be to reduce fibrosis and to induce the regeneration of the myocardial tissue through the generation of novel cardiomyocytes, the fibroblasts and myofibroblasts that invade the injured area in order to replace the damaged tissue with a scar represent an attractive target for therapeutic intervention. Indeed, because of the injury-induced fibroblast-myofibroblast transdifferentiation process, these cells might represent a population of plastic cells that can be more easily reprogrammed further into another cell type. The direct reprogramming of fibroblasts/myofibroblasts into induced cardiomyocyte-like cells (iCMs) with the help of cardiac transcription factor overexpression was first reported by Ieda et al. in 2010 (Ieda et al. 2010 ), and since then, several groups have reported successful cardiac reprogramming with various strategies, both in vitro (Table adidas Adidas Crazy 8 ADV ASW Ftw / Ftw / Real Purple V0S36Y1Lq
) and in vivo (Table 3 ; for reviews, see, for example, Srivastava and Berry Stella McCartney Woman Studded Appliquéd Faux Leather Pumps Size 37 Gkg2bvUrSn
; Fu and Srivastava 2015 ; Sahara et al. A2 by Aerosoles Shore Enough Bootie 6FViLLQq
; Srivastava and Yu 2015 ).

Table 2

Conditions used in vitro to induce direct reprogramming of fibroblasts into cardiomyocytes (, bone morphogenetic protein 4, chemically-defined medium, cardiac fibroblasts, combination of CHIR99021, PD0325901, LIF, and insulin, combination of CHIR99021, RepSox, forskolin, and valproic acid, cardiac troponin T, embryonic fibroblasts, embryonic stem cell-derived fibroblasts, Janus kinase, MyoD transactivation domain fused to Mef2c, protein kinase B, combination of SB431542, CHIR99021, parnate, and forskolin, skin fibroblasts, tail-tip fibroblasts)

Efficiency is expressed as % of cells at the time of analysis, unless otherwise stated

Table 3

Conditions used in vivo to induce direct reprogramming of fibroblasts into cardiomyocytes ( cardiomyocyte, cardiac troponin T, ejection fraction, fibroblast, immunohistochemistry, vascular endothelial growth factor)

Direct comparison of reprogramming efficiency between the different approaches is difficult because of differences in the experimental setup and the outcome measures used for cardiomyocyte classification. In particular, the time point and the criteria used for classifying cells as iCMs have a dramatic effect on the reported reprogramming efficiency. Classification based on cardiac protein expression (cardiac troponin T [cTnT] or cardiac α-actinin) results in significantly higher reported efficiency than classification by using a functional measure such as Ca 2+ activity combined with a cardiac-specific reporter or than classification based on the presence of sarcomeres. Nevertheless, certain conclusions with regard to reprogramming efficiency can be drawn from the plethora of studies published. When Ca 2+ activity was used as the outcome, the combination of Hand2 , Nkx2.5 , Gata4 , Mef2c , and Tbx5 was found to be >50-fold more efficient than the three-factor combination of Gata4 , Mef2c , and Tbx5 (Addis et al. 2013 ), suggesting that additional transcription factors, although not necessary for the expression of cardiac proteins such as cTnT, might be important in the maturation of iCMs to functional cardiomyocytes. The highest reprogramming efficiency reported, with cTnT + cells used as a measure of iCMs, is a remarkable 67% (Zhao et al. Puma Suede Heart Celebrate Wns / 3WOHzwBY
). This was achieved by the overexpression of four cardiac transcription factors ( Gata4 , Hand2 , Mef2c , Tbx5 ) and two miRNAs (miR-1, miR-133) combined with the pharmacological inhibition of TGF-β. Inhibition of fibrotic signaling with TGF-β or Rho-associated kinase (ROCK) inhibitors improves reprogramming efficiency, as does the overexpression of Akt/protein kinase B (Ifkovits et al. 2014 ; Zhao et al. Frye Tina Whipstitch Tassel Bootie KYrKG
; Zhou et al. 2015 ).

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KidsHealth / For Parents / Teaching Your Child Tolerance
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en español Cómo enseñar tolerancia a sus hijos

America is the great "melting pot," a rich blend of cultural traditions from all over the world. Many American families can trace their histories to immigrant ancestors who traveled great distances, enduring risk and hardship, to make a home where they would be guaranteed basic freedoms. And for many American families these freedoms came with a struggle. Their parents and grandparents were denied the basic rights we value.

American society was founded on freedom from religious persecution and on tolerance of differences in beliefs and cultural heritage. The differences (or diversity) that come from people from all over the world enrich our culture, bringing new ideas and energy.

Today, more than ever, kids interact with people of differing ethnicities, religions, and cultures. Classrooms are increasingly diverse, reflecting the communities where families live and work.

A World of Difference

Some parents welcome the fact that we live in an increasingly diverse society. Others may feel more hesitant, especially if they haven't had much exposure to people different from themselves. Many kids are way ahead of their parents regarding exposure to cultural differences. Their circle of friends, their schoolmates, and their athletic teams are much more varied than those of even a generation ago.

Still, parents should help their kids prepare to live, learn, and work in communities that will become even more diverse. Teaching tolerance is important not just because it is part of our American heritage, but because the person who learns to be open to differences will have more opportunities in education, business, and many other aspects of life.

In short, your child's success depends on it. Success in today's world — and tomorrow's — depends on being able to understand, appreciate, and work with others.

Tolerance refers to an attitude of openness and respect for the differences that exist among people. Although originally used to refer to ethnic and religious differences, the concepts of diversity and tolerance can also be applied to gender, people with physical and intellectual disabilities, and other differences, too.

Tolerance means respecting and learning from others, valuing differences, bridging cultural gaps, rejecting unfair stereotypes, discovering common ground, and creating new bonds. Tolerance, in many ways, is the opposite of prejudice.

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