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Abstract Premise Competition from naturalized species and habitat loss are common threats to native biodiversity and may act synergistically to increase competition for decreasing habitat availability. We use Hawaiian dryland ferns as a model for the interactions between land‐use change and competition from naturalized species in determining habitat availability. Methods We used fine‐resolution climatic variables and carefully curated occurrence data from herbaria and community science repositories to estimate the distributions of Hawaiian dryland ferns. We quantified the degree to which naturalized ferns tend to occupy areas suitable for native species and mapped the remaining available habitat given land‐use change. Results Of all native species, Doryopteris angelica had the lowest percentage of occurrences of naturalized species in its suitable area while D. decora had the highest. However, all Doryopteris spp. had a higher percentage overlap, while Pellaea ternifolia had a lower percentage overlap, than expected by chance. Doryopteris decora and D. decipiens had the lowest proportions (

Summary: In mammals, nicotinamide (NAM) is the primary NAD precursor available in circulation, a signaling molecule, and a precursor for methyl-nicotinamide (M-NAM) synthesis. However, our knowledge about how the body regulates tissue NAM levels is still limited. Here we demonstrate that dietary vitamin B3 partially regulates plasma NAM and NAM-derived metabolites, but not their tissue levels. We found that NAD de novo synthesis from tryptophan contributes to plasma and tissue NAM, likely by providing substrates for NAD-degrading enzymes. We also demonstrate that tissue NAM is mainly generated by endogenous metabolism and that the NADase CD38 is the main enzyme that produces tissue NAM. Tissue-specific CD38-floxed mice revealed that CD38 activity on endothelial and immune cells is the major contributor to tissue steady-state levels of NAM in tissues like spleen and heart. Our findings uncover the presence of different pools of NAM in the body and a central role for CD38 in regulating tissue NAM levels.

Advanced paternal age has increasingly been recognized as a risk factor for male fertility and progeny health. While underlying causes are not well understood, aging is associated with a continuous decline of blood and tissue NAD+ levels, as well as a decline of testicular functions. The important basic question to what extent ageing-related NAD+ decline is functionally linked to decreased male fertility has been difficult to address due to the pleiotropic effects of aging, and the lack of a suitable animal model in which NAD+ levels can be lowered experimentally in chronologically young adult males. We therefore developed a transgenic mouse model of acquired niacin dependency (ANDY), in which NAD+ levels can be experimentally lowered using a niacin-deficient, chemically defined diet. Using ANDY mice, this report demonstrates for the first time that decreasing body-wide NAD+ levels in young adult mice, including in the testes, to levels that match or exceed the natural NAD+ decline observed in old mice, results in the disruption of spermatogenesis with small testis sizes and reduced sperm counts. ANDY mice are dependent on dietary vitamin B3 (niacin) for NAD+ synthesis, similar to humans. NAD+-deficiency the animals develop on a niacin-free diet is reversed by niacin supplementation. Providing niacin to NAD+-depleted ANDY mice fully rescued spermatogenesis and restored normal testis weight in the animals. The results suggest that NAD+ is important for proper spermatogenesis and that its declining levels during aging are functionally linked to declining spermatogenesis and male fertility. Functions of NAD+ in retinoic acid synthesis, which is an essential testicular signaling pathway regulating spermatogonial proliferation and differentiation, may offer a plausible mechanism for the hypospermatogenesis observed in NAD+-deficient mice.

How PRC1 recognises and interacts with its target genes remains poorly understood. Here, the authors use genome engineering and single particle tracking to dissect how PRC1 binds to chromatin in live mouse embryonic stem cells, revealing that this repressor is highly dynamic, with only a small fraction stably interacting with chromatin.

Epigenetic information is transmitted from mother to daughter cells through mitosis. Here, the authors isolate native chromosomes from metaphase-arrested cells and perform LC-MS/MS to identify chromosome-bound proteins in pluripotent stem cells during mitosis and reveal that PRC2, DNA methylation and Mecp2 are required to maintain chromosome compaction.

Compared to motherhood, the molecular changes associated with fatherhood are less understood. Here, the authors investigate gene expression changes associated with paternal care in male stickleback fish, and compare them with patterns in territorial aggression.

Summary: How chromosome organization is related to genome function remains poorly understood. Cohesin, loop extrusion, and CCCTC-binding factor (CTCF) have been proposed to create topologically associating domains (TADs) to regulate gene expression. Here, we examine chromosome conformation in embryonic stem cells lacking cohesin and find, as in other cell types, that cohesin is required to create TADs and regulate A/B compartmentalization. However, in the absence of cohesin, we identify a series of long-range chromosomal interactions that persist. These correspond to regions of the genome occupied by the polycomb repressive system and are dependent on PRC1. Importantly, we discover that cohesin counteracts these polycomb-dependent interactions, but not interactions between super-enhancers. This disruptive activity is independent of CTCF and insulation and appears to modulate gene repression by the polycomb system. Therefore, we discover that cohesin disrupts polycomb-dependent chromosome interactions to modulate gene expression in embryonic stem cells. : Using Hi-C, Capture-C, and DNA-FISH, Rhodes et al. discover that interactions between polycomb target genes occur independently of cohesin in embryonic stem cells. This relies on PRC1, and these interactions are disrupted by cohesin-mediated loop extrusion. Upon removal of cohesin, gene repression is enhanced at polycomb-occupied genes with increased interactions. Keywords: cohesin, Polycomb, TADs, loop extrusion, Hi-C, gene regulation

In 1983 Ted Leonsis survived a crash landing of a plane he was on.This fateful event proved to be a pivotal point in his life. One of the byproducts of that near-death experiences is Leonsisʼ list of 101 things to do before he died‐a “bucket list” before the movie of that title came out. Leonsis has managed to accomplish more than two-thirds of the things on his list including owning a sports franchise (the Washington Capitals), changing someoneʼs life via a charity, sailing the Caribbean, and being on the cover of a magazine. As impressive as these accomplishments are, they do not reveal the person underneath these accomplishments or what has driven this serial entrepreneur. In previous interviews appearing in NEJE, we have explored how a personʼs faith tradition impacts how they run and manage their businesses. In this interview Leonsis reveals how his life was shaped by both his early childhood and the transformational experience of a crash landing. This interview examines not only what drove Leonsis to success, but also why he feels failure is important. Along, the way he offers his perspective on corporate social responsibility and why it is so critical for individuals and companies to give back to society. And finally, Leonsis shares what he has learned about the secret to happiness.

The Harry F. Byrd, Jr. School of Business at Shenandoah University engaged in an intense planning process in the fall of 2004. In addition to clarifying its mission and strategic directions, the Byrd School clearly articulated its vision: to become recognized as a provider of individualized business education driven by entrepreneurial thinking, global understanding, and ethical practice. The development of the Institute for Entrepreneurship described in this article is a critical step in actualizing this vision.

Premise: Competition from naturalized species and habitat loss are common threats to native biodiversity and may act synergistically to increase competition for decreasing habitat availability. We use Hawaiian dryland ferns as a model for the interactions between land‐use change and competition from naturalized species in determining habitat availability. Methods: We used fine‐resolution climatic variables and carefully curated occurrence data from herbaria and community science repositories to estimate the distributions of Hawaiian dryland ferns. We quantified the degree to which naturalized ferns tend to occupy areas suitable for native species and mapped the remaining available habitat given land‐use change. Results: Of all native species, Doryopteris angelica had the lowest percentage of occurrences of naturalized species in its suitable area while D. decora had the highest. However, all Doryopteris spp. had a higher percentage overlap, while Pellaea ternifolia had a lower percentage overlap, than expected by chance. Doryopteris decora and D. decipiens had the lowest proportions (<20%) of suitable area covering native habitat. Discussion: Areas characterized by shared environmental preferences of native and naturalized ferns may decrease due to human development and fallowed agricultural lands. Our study demonstrates the value of place‐based application of a recently developed correlative ecological niche modeling approach for conservation risk assessment in a rapidly changing and urbanized island ecosystem. [ABSTRACT FROM AUTHOR]

Advanced paternal age has increasingly been recognized as a risk factor for male fertility and progeny health. While underlying causes are not well understood, aging is associated with a continuous decline of blood and tissue NAD+ levels, as well as a decline of testicular functions. The important basic question to what extent ageing-related NAD+ decline is functionally linked to decreased male fertility has been difficult to address due to the pleiotropic effects of aging, and the lack of a suitable animal model in which NAD+ levels can be lowered experimentally in chronologically young adult males. We therefore developed a transgenic mouse model of acquired niacin dependency (ANDY), in which NAD+ levels can be experimentally lowered using a niacin-deficient, chemically defined diet. Using ANDY mice, this report demonstrates for the first time that decreasing body-wide NAD+ levels in young adult mice, including in the testes, to levels that match or exceed the natural NAD+ decline observed in old mice, results in the disruption of spermatogenesis with small testis sizes and reduced sperm counts. ANDY mice are dependent on dietary vitamin B3 (niacin) for NAD+ synthesis, similar to humans. NAD+-deficiency the animals develop on a niacin-free diet is reversed by niacin supplementation. Providing niacin to NAD+-depleted ANDY mice fully rescued spermatogenesis and restored normal testis weight in the animals. The results suggest that NAD+ is important for proper spermatogenesis and that its declining levels during aging are functionally linked to declining spermatogenesis and male fertility. Functions of NAD+ in retinoic acid synthesis, which is an essential testicular signaling pathway regulating spermatogonial proliferation and differentiation, may offer a plausible mechanism for the hypospermatogenesis observed in NAD+-deficient mice. [ABSTRACT FROM AUTHOR]

Problem As programmes to deliver antiretroviral therapy (ART) are implemented in resource-constrained settings, the problem becomes not how these programmes are going to be financed but who will be responsible for delivering and sustaining them. Approach Physician-led models of HIV treatment and care that have evolved in industrialized countries are not replicable in settings with a high prevalence of HIV infection and limited access to medical staff. Therefore, models of care need to make better use of available human resources. Local setting Using Botswana as an example, we discuss how nurses are underutilized in long-term clinical management of patients requiring ART. Relevant changes We argue that for ART-delivery programmes to be sustainable, nurses will need to provide a level of clinical care of patients receiving this therapy, including prescribing ART and managing common adverse effects. Lessons learned Practicalities involved in scaling up nurse-led models of ART delivery include overcoming political and professional barriers, identifying educational requirements, agreeing on the limitations of nursing practice, developing clear referral pathways between medical and nursing personnel, and developing mechanisms to monitor and supervise practice. Operational research is required to demonstrate that such models are safe, effective and sutainable. Problematique Avec la mise en oeuvre dans des pays a ressources limitees de programmes de delivrance de traitements antiretroviraux (ART), le probleme n&apos;est plus de savoir comment ces programmes seront finances, mais de determiner qui se chargera de leur mise en oeuvre et de leur maintien. Demarche Les systemes de delivrance du traitement et de prestation des soins lies au VIH/sida geres par des medecins qui ont ete mis en place dans les pays industrialises ne peuvent etre reproduits dans les pays o le VIH/sida est fortement prevalent et l&apos;acces au personnel medical tres restreint. Il faut donc que les systemes de soins exploitent mieux les ressources humaines disponibles. Contexte local A partir de l&apos;exemple du Botswana, nous etudions la sous-utilisation du personnel infirmier dans la prise en charge a long terme des patients ayant besoin d&apos;un traitement antiretroviral. Modifications pertinentes Pour que les programmes de delivrance de traitements ART soient durables, il faut, a notre avis, que le personnel infirmier assure des soins cliniques d&apos;un certain niveau aupres des patients recevant ce type de traitement, et notamment la prescription des ART et la prise en charge des effets indesirables courants. Enseignements tires Parmi les considerations pratiques intervenant dans l&apos;extension des systemes de delivrance des traitements ART geres par du personnel infirmier, figurent l&apos;elimination des barrieres politiques et professionnelles, l&apos;identification des besoins en matiere de formation, la concertation sur les limites a fixer aux pratiques infirmieres, l&apos;elaboration de procedures claires pour l&apos;orientation vers du personnel medical ou infirmier et la mise au point de mecanismes pour surveiller et superviser ces pratiques. Des etudes relevant de la recherche operationnelle sont necessaires pour demontrer la securite, l&apos;efficacite et la durabilite de tels systemes. Problema A medida que se aplican los programas destinados a suministrar tratamiento antirretroviral (TAR) en entornos con recursos limitados, el problema no es tanto encontrar la manera de financiar esos programas como determinar quien se responsabilizara de su implementacion y mantenimiento. Metodos Los modelos de tratamiento y atencion de la infeccion por VIH dirigidos por el medico que han surgido en los pafses industrializados no son reproducibles en los entornos con alfa prevalencia de esa infeccion y acceso limitado a personal medico. Es preciso, por tanto, que los modelos de atencion aprovechen mejor los recursos humanos disponibles. Contexto local Tomando Botswana como ejemplo, analizamos la infrautilizacion que se hace del personal de enfermerfa en el manejo clinico a largo plazo de los pacientes que requieren TAR. Cambios destacables Argumentamos que, para que los programas de TAR sean sostenibles, las enfermeras tendron que asumir parte de la atencion clinica de los pacientes que reciban esa terapia, incluidos la prescripcion de TAR y el manejo de efectos adversos comunes. Ensefianzas extraidas Entre los aspectos practicos que plantea la expansion de los modelos de suministro de TAR dirigidos por personal de enfermeria cabe citar la necesidad de superar barreras politicas y profesionales, la identificacion de las necesidades educacionales, el establecimiento de vias de derivacion claras entre los medicos y el personal de enfermerfa, y la formulacion de mecanismos de vigilancia y supervision de las practicas. Es necesario emprender investigaciones operacionales para comprobar si esos modelos son seguros, eficaces y sostenibles., Introduction Expanding access to antiretroviral therapy (ART) to treat HIV in low-resource settings has demonstrated benefits in terms of health and survival (1-7) and, contrary to earlier claims, high levels [...]