Comparing and Contrasting Knowledge on Mules and Hinnies as a Tool to Comprehend Their Behavior and Improve Their Welfare.

Mules and hinnies are the hybrids between donkeys (Equus asinus) and horses (Equus caballus). For centuries, mankind has used them for agrarian purposes, the military, or recreation. Contrasting literature with behavioral observations, we seek a better behavioral understanding andthus comprehensive solutions for their welfare enhancement. Over the past 6 years, we have assessed physical and behavioral welfare in over 900 mules by surveying owners from Egypt, Peru, Portugal, Spain, Mexico, and the U.S. These mules participated in shows, brick kiln work, cart-pulling, packing, tourism, and cattle herding. Observations are discussed alongside facts from the literature. Unfortunately, their behavior has been misunderstood by many, and harsh treatment and equipment has been used to control them. Few studies have attempted to define or use learning theory to understand how and why mules and hinnies behave as they do. Hence, understanding their health considerations, natural behavior, and training theory is crucial for those who work with them.Solutions to welfare improvement partially lie in an individual's ability to handle mules and hinnies from birth, and to proceed slowly through training. Conclusively, this review sets forth a clearer understanding of these hybrids' behaviors and promotes positive handling, allowing their access to more routine healthcare and ultimately, a higher welfare standard

Native Elder and Youth Perspectives on Mental Well-being, the Value of the Horse, and Navigating Two Worlds

Purpose: Native American youth experience significant challenges to mental well-being. As part of a larger study to evaluate hope and resilience in a Plains tribal population, the purpose of this study was to learn from Native American elders and youths what they feel is needed to for youth to grow up healthy on the reservation, and to identify connections between horse use and mental well-being.Sample: Six Native American elders and eight Native American youths from the same Plains tribe.Method: The research team conducted Talking Circles with youths and elders. during the Talking Circles, participants identified community-specific questions for inclusion in a resilience measurement and provided personal stories regarding the relevance of the horse to well-being.Findings: Both groups felt cultural traditions and language, education, relationships, and interactions with horses have significant roles in enhancing identity development and resilience in youth. However, elders indicated that tribal youth seem to struggle in navigating two worlds. Elders expressed that for youth to be well, they need to return to traditional ways within the realms of culture, language, education, and relationships. On the other hand, the youths were more confident in their ability to navigate two worlds, and wished to seek opportunities to blend their traditional and contemporary lives.Conclusion: The challenges of navigating two worlds for Native Americans are experienced across generations. Both youths and elders said that resilient youth are able to successfully navigate these challenges when they: (a) know their indigenous identity, (b) participate in cultural activities, (c) have strong family ties, and (d) are able to learn in an environment where their culture is championed. We propose that future efforts must include community-based participatory methods in the development of interventions that include use of the horse to strengthen Native American youth resilience and foster health and well-being

NOTCH1 Signaling Promotes Human T-Cell Acute Lymphoblastic Leukemia Initiating Cell Regeneration in Supportive Niches

Leukemia initiating cells (LIC) contribute to therapeutic resistance through acquisition of mutations in signaling pathways, such as NOTCH1, that promote self-renewal and survival within supportive niches. Activating mutations in NOTCH1 occur commonly in T cell acute lymphoblastic leukemia (T-ALL) and have been implicated in therapeutic resistance. However, the cell type and context specific consequences of NOTCH1 activation, its role in human LIC regeneration, and sensitivity to NOTCH1 inhibition in hematopoietic microenvironments had not been elucidated.We established humanized bioluminescent T-ALL LIC mouse models transplanted with pediatric T-ALL samples that were sequenced for NOTCH1 and other common T-ALL mutations. In this study, CD34(+) cells from NOTCH1(Mutated) T-ALL samples had higher leukemic engraftment and serial transplantation capacity than NOTCH1(Wild-type) CD34(+) cells in hematopoietic niches, suggesting that self-renewing LIC were enriched within the NOTCH1(Mutated) CD34(+) fraction. Humanized NOTCH1 monoclonal antibody treatment reduced LIC survival and self-renewal in NOTCH1(Mutated) T-ALL LIC-engrafted mice and resulted in depletion of CD34(+)CD2(+)CD7(+) cells that harbor serial transplantation capacity.These results reveal a functional hierarchy within the LIC population based on NOTCH1 activation, which renders LIC susceptible to targeted NOTCH1 inhibition and highlights the utility of NOTCH1 antibody targeting as a key component of malignant stem cell eradication strategies