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Analysis of people’s perceptions toward wildlife is fundamental in conservation planning. Also fundamental is dissemination of information about wildlife ecology. In Mexico, conservation of carnivores, who frequently come into conflict with human communities, is of utmost importance. We designed a workshop about the ecological aspects of pumas and jaguars; 232 children in elementary schools in rural, semiurban, and urban zones of Central Mexico participated. We analyzed the children’s knowledge of, perceptions of, and behavior in relation to pumas and jaguars before and after the workshop. We compared the three aspects by separating the data by grade and zone and found positive changes after the workshop. Knowledge was greater in the rural zone, but pro-conservation behavior was higher in the urban zone. Sixth-grade children displayed pro-conservation behavior and had more knowledge and more positive perceptions. We discuss the importance of involving children in conservation projects and disseminating information about large carnivores. [ABSTRACT FROM AUTHOR]

Invasive species can have complex direct and indirect impacts on ecosystems. The impacts of invasive prey species on native prey can be difficult to observe if the latter migrate seasonally, and when the interaction is indirect. We hypothesize that invasive lagomorphs and snow dynamics indirectly drive predation risk for guanaco by puma. We employed camera-trapping data collected over multiple years and seasons in an altitudinal gradient in the Andes of Central Chile. We predicted a high spatial and temporal association between puma and lagomorph detections, given these prey species comprise most of puma diet in the area. We also expected a higher spatiotemporal association between guanaco and puma detections towards higher snow cover in the study area, because of downward altitudinal migration of the ungulate. We obtained 4863 mammalian detections. Our data shows that the detection of puma was positively associated with hare capture rate year-round. In addition, puma detection was positively associated with the interaction of snow cover and guanaco capture rate. Puma temporal activity strongly overlapped with hare, whereas puma apparently increased diurnal activity with an increase in guanaco capture rate. Predation risk for guanaco increased when snow cover was higher and decreased when guanaco migrated to higher altitudes during dryer months. We conclude it is of conservation concern that lagomorphs may be subsidizing pumas and modifying patterns of consumptive and non-consumptive effects of the predator on native prey populations. [ABSTRACT FROM AUTHOR]

Artificial light at night (ALAN) is increasing in extent and intensity across the globe. It has been shown to interfere with animal sensory systems, orientation and distribution, with the potential to cause significant ecological impacts. We analysed the locations of 102 mountain lions (Puma concolor) in a light-polluted region in California. We modelled their distribution relative to environmental and human-disturbance variables, including upward radiance (nearby lights), zenith brightness (sky glow) and natural illumination from moonlight. We found that mountain lion probability of presence was highly related to upward radiance, that is, related to lights within approximately 500 m. Despite a general pattern of avoidance of locations with high upward radiance, there were large differences in degree of avoidance among individuals. The amount of light from artificial sky glow was not influential when included together with upward radiance in the models, and illumination from moonlight was not influential at all. Our results suggest that changes in visibility associated with lunar cycles and sky glow are less important for mountain lions in their selection of light landscapes than avoiding potential interactions with humans represented by the presence of nearby lights on the ground. This article is part of the theme issue Light pollution in complex ecological systems.

Abnormal proliferation of aggressive fibroblast-like synoviocytes (FLS) and perpetuate synovial inflammation can inevitably accelerate the progression of rheumatoid arthritis (RA). Herein, a strategy of simultaneously promoting FLS apoptosis and inhibiting inflammation as mediated by macrophages is proposed to restore synovial homeostasis for effective RA therapy. A hyaluronic acid-based dissolvable microneedle (MN) is fabricated for transdermal delivery of dual human serum albumin (HSA)-contained biomimetic nanocomplexes to regulate RA FLS and macrophages. Upon skin insertion, dual nanocomplexes are released rapidly from the MN and accumulate in RA joint microenvironment through both passive and active targeting as mediated by HSA. Thioketal-crosslinked fluorinated polyethyleneimine 1.8 K (TKPF) was constructed to bind the plasmid encoding pro-apoptotic gene PUMA with HSA coating layer (TKPF/pPUMA@HSA, TPH). TPH nanocomplexes can upregulate PUMA through RA FLS transfection to trigger efficient apoptosis. Also, HSA nanocomplexes encapsulating the classic anti-inflammatory natural product celastrol (Cel@HSA, CH) can inhibit inflammation of macrophages through blocking NF-κB pathway activation. TPH/CH MN can deplete RA FLS and inhibit M1 macrophage activation, suppress synovial hyperplasia as well as reduce bone and cartilage erosion in a collagen-induced arthritis (CIA) mouse model, demonstrating a promising strategy for efficient RA treatment.

El presente artículo forma parte de las estrategias del Programa Nacional de Conservación de Felinos de El Salvador, el cual consiste en realizar diferentes investigaciones sobre distribución de felinos y sus presas, este artículo parte de los resultados obtenidos durante el primer año de funcionamiento de la estación de fototrampeo en el Área Natural Protegida “San Carlos” Cacahuatique en el departamento de Morazán, con el objetivo de evidenciar la presencia, actividad y alimentación de felinos entre otra información etológica; con ello se logró evidencia fotográfica y videográfica de la dieta de las especies de felinos silvestres presentes en el área entre las cuales se enlistan especies de la familia Didelphidae, Prociónidos, Erethizontidae, Cervidae y del orden Rodentia, de esta forma la estación de fototrampeo está generando información importante para la conservación de estas especies y de la salud de los ecosistemas. Con las 37 cámaras de fototrampeo ubicadas estratégicamente en arroyos, senderos, madrigueras y lugares con características potenciales de presencia de felinos, esto ha enriquecido la información existente en estas zonas que han sido identificadas por el equipo técnico y de guardarrecursos del Ministerio de Medio Ambiente y Recursos Naturales.

El PNCF ha sido definido para una duración de 10 años, y busca la colaboración y participación de diversos actores e instituciones para su adecuada ejecución, teniendo como objetivo primordial ser el instrumento que oriente la implementación de acciones y estrategias necesarias, para la conservación, que permitan mitigar o reducir las amenazas no solo de las únicas cuatro especies de felinos, que aún se reportan en El Salvador, sino también de sus hábitats, logrando así poblaciones saludables. Todo esto con el involucramiento activo y el trabajo conjunto de diversas instituciones y actores claves de la sociedad.

Se realizó revisión bibliográfica de libros (cuatro), artículos científicos (tres) y visitas a un sitio arqueológico (Casa Blanca) y MUNA. Como producto de este proceso se obtuvo datos de representaciones de individuos de la familia Felidae Orden Carnívora, a partir de 13 registros de piezas de cerámica (cinco) como de lítica (ocho). La procedencia de las piezas proviene de seis departamentos (Santa Ana, Ahuachapán, La Libertad, San Salvador, San Vicente y San Miguel). Consultando las diversas fuentes revisadas, siete de los 11 registros constituyen, de acuerdo a los especialistas, jaguares (Panthera onca) y el resto felinos (Felidae: Carnívora). Con respecto a toponimia, se documento cuatro sitios, todos del occidente de El Salvador, cuyos nombres son alusivos a felinos.

Mitigating human-caused mortality for large carnivores is a pressing global challenge for wildlife conservation. However, mortality is almost exclusively studied at local (within-population) scales creating a mismatch between our understanding of risk and the spatial extent most relevant to conservation and management of wide-ranging species. Here, we quantified mortality for 590 radio-collared mountain lions statewide across their distribution in California to identify drivers of human-caused mortality and investigate whether human-caused mortality is additive or compensatory. Human-caused mortality, primarily from conflict management and vehicles, exceeded natural mortality despite mountain lions being protected from hunting. Our data indicate that human-caused mortality is additive to natural mortality as population-level survival decreased as a function of increasing human-caused mortality and natural mortality did not decrease with increased human-caused mortality. Mortality risk increased for mountain lions closer to rural development and decreased in areas with higher proportions of citizens voting to support environmental initiatives. Thus, the presence of human infrastructure and variation in the mindset of humans sharing landscapes with mountain lions appear to be primary drivers of risk. We show that human-caused mortality can reduce population-level survival of large carnivores across large spatial scales, even when they are protected from hunting.

Large carnivores play critical roles in terrestrial ecosystems but have suffered dramatic range contractions over the past two centuries. Developing an accurate understanding of large carnivore diets is an important first step towards an improved understanding of their ecological roles and addressing the conservation challenges faced by these species.The puma is one of seven large felid species in the world and the only one native to the non-tropical regions of the New World. We conducted a meta-analysis of puma diets across the species' range in the Americas and assessed the impact of varying environmental conditions, niche roles, and human activity on puma diets. Pumas displayed remarkable dietary flexibility, consuming at least 232 different prey species, including one Critically Endangered and five Endangered species.Our meta-analysis found clear patterns in puma diets with changing habitat and environmental conditions. Pumas consumed more larger-bodied prey species with increasing distance from the equator, but consumption of medium-sized species showed the opposite trend.Puma diets varied with their realized niche; however, contrary to our expectations, puma consumption of large species did not change with their trophic position, and pumas consumed more small prey and birds as apex predators. Consumption of domestic species was negatively correlated with consumption of medium-sized wild species, a finding which underscores the importance of maintaining intact native prey assemblages.The tremendous dietary flexibility displayed by pumas represents both an opportunity and a challenge for understanding the puma's role in ecosystems and for the species' management and conservation. Future studies should explore the linkages between availability and selection of primary and other wild prey, and consequent impacts on predation of domestic species, in order to guide conservation actions and reduce conflict between pumas and people.

Los pumas a veces se pueden confundir con gatos monteses, perros y coyotes. En este documento se proporcionan datos e imágenes que pueden ayudar a cualquier persona a identificar a un puma.

Humans have outsized effects on ecosystems, in part by initiating trophic cascades that impact all levels of the food chain.1,2 Theory suggests that disease outbreaks can reverse these impacts by modifying human behavior,3,4 but this has not yet been tested. The COVID-19 pandemic provided a natural experiment to test whether a virus could subordinate humans to an intermediate link in the trophic chain, releasing a top carnivore from a landscape of fear. Shelter-in-place orders in the Bay Area of California led to a 50% decline in human mobility, which resulted in a relaxation of mountain lion aversion to urban areas. Rapid changes in human mobility thus appear to act quickly on food web functions, suggesting an important pathway by which emerging infectious diseases will impact not only human health but ecosystems as well.

Copyright of Biotropica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Energetic demands and fear of predators are considered primary factors shaping animal behavior, and both are likely drivers of movement decisions that ultimately determine the spatial ecology of wildlife. Yet energetic constraints on movement imposed by the physical landscape have only been considered separately from those imposed by risk avoidance, limiting our understanding of how short-term movement decisions scale up to affect long-term space use. Here, we integrate the costs of both physical terrain and predation risk into a common currency, energy, and then quantify their effects on the short-term movement and long-term spatial ecology of a large carnivore living in a human-dominated landscape. Using high-resolution GPS and accelerometer data from collared pumas (Puma concolor), we calculated the short-term (i.e., 5-min) energetic costs of navigating both rugged physical terrain and a landscape of risk from humans (major sources of both mortality and fear for our study population). Both the physical and risk landscapes affected puma short-term movement costs, with risk having a relatively greater impact by inducing high-energy but low-efficiency movement behavior. The cumulative effects of short-term movement costs led to reductions of 29% to 68% in daily travel distances and total home range area. For male pumas, long-term patterns of space use were predominantly driven by the energetic costs of human-induced risk. This work demonstrates that, along with physical terrain, predation risk plays a primary role in shaping an animal's "energy landscape" and suggests that fear of humans may be a major factor affecting wildlife movements worldwide.

The most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is a GGGGCC repeat expansion in the C9orf72 gene. We developed a platform to interrogate the chromatin accessibility landscape and transcriptional program within neurons during degeneration. We provide evidence that neurons expressing the dipeptide repeat protein poly(proline-arginine), translated from the C9orf72 repeat expansion, activate a highly specific transcriptional program, exemplified by a single transcription factor, p53. Ablating p53 in mice completely rescued neurons from degeneration and markedly increased survival in a C9orf72 mouse model. p53 reduction also rescued axonal degeneration caused by poly(glycine-arginine), increased survival of C9orf72 ALS/FTD-patient-induced pluripotent stem cell (iPSC)-derived motor neurons, and mitigated neurodegeneration in a C9orf72 fly model. We show that p53 activates a downstream transcriptional program, including Puma, which drives neurodegeneration. These data demonstrate a neurodegenerative mechanism dynamically regulated through transcription-factor-binding events and provide a framework to apply chromatin accessibility and transcription program profiles to neurodegeneration.

For today the exact mechanisms of myocardial infarction and ischemia/reperfusion injury are still not fully understood. ER stress and integrated stress response pathways are thought to play an essential role in myocardial damage. This includes activation of endoplasmic reticulum kinase (PERK), induction of activating transcription factor 4 (ATF4), expression of pro-apoptotic transcription factor (CHOP) and P53 up-regulated modulator of apoptosis (PUMA) involved in apoptosis control. We used a rat model of isoproterenol-induced myocardial damage to elucidate the possible cardioprotective effect of Ginger through the influence on ER stress-induced apoptotic pathway. We also compared its effect with Captopril, inhibitor of angiotensin-converting enzyme. Male albino Wistar rats received 1.0 or 2.0 ml of Zingiber officinale (Ginger) powder suspension (200 mg/ml) daily by intra-gastric intubation for 28 days. Isoproterenol at a dose of 85 mg/kg was IP injected on the 27th and 28th days. Serum aspartate transaminase (AST) level was measured using kinetic kit. Heart tissue was used for RNA extraction, evaluation of gene expression by Q-RT-PCR, immuno-histochemical determination of caspase-3 expression and histopathological studies. Our results showed that Isoproterenol administration increased CHOP-mRNA expression 4 folds in cardiac muscle tissue compared to normal control. Ginger pretreatment significantly decreased both CHOP and ATF4, and PUMA mRNA expression compared to Isoproterenol-treated groups. A significant reduction in ATF4 mRNA expression in a group pretreated with Captopril and Ginger compared to normal control group was observed. The results showed that Ginger reduced AST serum levels which correlated with results of histopathological studies of heart tissue. Our findings suggest that the protective effects of Ginger against myocardium damage induced by Isoproterenol may be mediated by reducing­ the endoplasmic reticulum stress by affecting the ATF4-CHOP-PUMA pathway.

Context: A central problem in road ecology is the need to minimise roadkill without exacerbating fragmentation. The best current solution to this problem is wildlife-exclusion fencing combined with crossing structures. However, because species vary in their propensity to use crossing structures, optimising their design for a suite of species remains a challenge. Aims: We investigated medium- and large-mammal use of undercrossings along Highway 101 in the Central Coast of California. Specifically, we quantified how undercrossing size, surrounding habitat, and the presence of a wildlife-exclusion fence, influenced overall species richness, as well as use by black bear, mule deer, puma, and bobcat. Methods: Using wildlife cameras, we documented mammal use at 11 undercrossings in our study area. We calculated the openness index of each undercrossing and remotely measured habitat features, such as percentage tree cover, and distance to nearest stream. We determined the relative importance of these factors on overall species richness, and the activity of focal species, using generalised linear mixed models in an information-theoretic framework. Key results: Mesocarnivores used a wider variety of undercrossings, and used them more frequently, than did larger mammals. Species richness and bear activity were greater closer to streams, and there was more bear activity at undercrossings within the wildlife-exclusion fence zone than outside it. Deer activity was strongly and positively related to undercrossing openness. Our puma and bobcat analyses were uninformative, likely because we detected puma too infrequently, and because bobcats showed little variation in use across sites. Conclusions: Our results support previous research highlighting natural travel corridors (e.g. riparian areas) as important places for wildlife crossings, both for a diversity of medium–large mammals and a low-density large carnivore. Ungulates may be the most selective taxa in respect to undercrossing use. Implications: Large, open undercrossings along natural travel routes accommodate the greatest diversity of medium–large mammal species. Designing wildlife crossing structures for a suite of species remains a challenge. We monitored 11 crossings along a major highway in California from 2012 to 2017 and found that mammal species richness and black bear use were greater closer to streams, whereas mule deer almost exclusively used large undercrossings. Large undercrossings associated with natural corridors are likely to promote connectivity for the most species of medium–large mammals. Photograph by the authors. [ABSTRACT FROM AUTHOR]

Two species of large cats found at the Tanzanian Pliocene australopithecine locality of Laetoli have been controversial since their first description in 1987. A lion-sized form was referred to Panthera onca gombaszoegensis, P. palaeosinensis, P. shawi, P. leo or to a related form, and most recently compared to P. onca. A leopard-sized species was attributed to P. pardus or to Puma pardoides. Accepting the leopard-like form as the oldest evidence of the genus Panthera to calibrate molecular dating, this site started to play an important role in understanding felid evolution. A new discussion of the extremely scanty material now revises the earlier classifications and shows that the Laetoli "lion" is not a lion and the Laetoli "leopard" is not a leopard. There seems to be no doubt that the lion-sized cat is a species of its own, representing an early stage of Panthera intrageneric evolution, the metapopulation around the first node as defined by molecular phylogenetics. Taxonomically it is introduced as Panthera principialis sp. nov. The Early Pleistocene lion-sized cat from the South African sites Bolt's Farm, Swartkrans and Kromdraai is here attributed species rank, P. shawi, and understood to represent the metapopulation around the lion-leopard evolutionary node. The leopard-sized Laetoli cat qualifies as an early African member of the genus Puma, but it is not the same as the later Early Pleistocene Swartkrans form. The latter, originally described as Panthera pardus incurva, is proposed here to have arisen by introgressive hybridization of an African puma with an early Panthera species and named Puma incurva. The results of this review give definite support for one of competing sets of molecular dating. [ABSTRACT FROM AUTHOR]

Abstract Background Aberrant expression of Secretory Leukocyte Protease Inhibitor (SLPI) has been associated with human cancer growth and its suppression was identified as a potential target for anti-cancer drugs, particularly in colorectal cancer. However, the underlying mechanism by which SLPI affected the development of drug resistance in CRC remains unclear. Objective This study investigated the role of SLPI in the p53-up-regulated modulator of apoptosis (PUMA)-mediated CRC cells’ apoptosis and their chemosensitivity to Cisplatin. Methods A series of qRT-PCR and western blot analyses were performed to characterize the expressions of SLPI, PUMA, and Akt in CRC lines. Tunel, transwell, and CCK-8 analyses were monitored to define the impacts of the siRNA-mediated knockdown of SLPI on CRC cell development. Furthermore, in vivo development of CRC was evaluated in nude mice infected with siSLPI or Cisplatin alone or both, and Ki67 and caspase-3 immunohistochemistry assay was monitored on multiple tissue microarray from the same cohort. Results Our results showed that SLPI inhibition strongly promoted the expressions of the pro-apoptotic protein PUMA, cleaved-caspase3 and Bax and reduced the cell viability of HT29 and HT116 cell lines in vitro. In addition, siSLPI knockdown effectively suppressed both Akt and FoxO3 proteins and improved the sensitivity to cisplatin chemotherapy. Xenograft tumor assay revealed a lowered growth in mice treated with Cisplatin, while combined treatment of siSLPI achieved more significant anticancer effects than Cisplatin alone. Conclusions Taken together, these findings demonstrated that suppression of SLPI might repress the growth of human colorectal cancer cells both in vitro and in vivo. These results suggested SLPI as a novel resistance factor to Cisplatin, and a combination of Cisplatin and SLPI inhibitor be beneficial for colorectal cancer therapy.

Targeting of MAP kinase pathways by BRAF inhibitors has evolved as a key therapy for BRAF-mutated melanoma. However, it cannot be applied for BRAF-WT melanoma, and also, in BRAF-mutated melanoma, tumor relapse often follows after an initial phase of tumor regression. Inhibition of MAP kinase pathways downstream at ERK1/2, or inhibitors of antiapoptotic Bcl-2 proteins, such as Mcl-1, may serve as alternative strategies. As shown here, the BRAF inhibitor vemurafenib and the ERK inhibitor SCH772984 showed only limited efficacy in melanoma cell lines, when applied alone. However, in combination with the Mcl-1 inhibitor S63845, the effects of vemurafenib were strongly enhanced in BRAF-mutated cell lines, and the effects of SCH772984 were enhanced in both BRAF-mutated and BRAF-WT cells. This resulted in up to 90% loss of cell viability and cell proliferation, as well as in induction of apoptosis in up to 60% of cells. The combination of SCH772984/S63845 resulted in caspase activation, processing of poly (ADP-ribose) polymerase (PARP), phosphorylation of histone H2AX, loss of mitochondrial membrane potential, and cytochrome c release. Proving the critical role of caspases, a pan-caspase inhibitor suppressed apoptosis induction, as well as loss of cell viability. As concerning Bcl-2 family proteins, SCH772984 enhanced expression of the proapoptotic Bim and Puma, as well as decreased phosphorylation of Bad. The combination finally resulted in downregulation of antiapoptotic Bcl-2 and enhanced expression of the proapoptotic Noxa. In conclusion, combined inhibition of ERK and Mcl-1 revealed an impressive efficacy both in BRAF-mutated and WT melanoma cells, and may thus represent a new strategy for overcoming drug resistance. [ABSTRACT FROM AUTHOR]

Body size correlates with various biological attributes. Hence, its evolution has attracted considerable attention. The family Felidae (Mammalia: Carnivora) has extensive variation in body size among extant species, with a few species being strikingly larger. The body size of extremely large species compared with phylogenetically related species may have evolved through directional selection toward increased size in a particular lineage, although lineage-specific directional selection has not been explicitly incorporated into standard models of body size evolution on a phylogeny. We used simulation-based likelihood and approximate Bayesian computation to examine the effect of lineage-specific directional selection on body mass evolution in extant felids. Our analyses revealed the occurrence of lineage-specific directional selection that favors larger body mass in the genus Panthera (lion, Panthera leo; jaguar, Panthera onca; leopard, Panthera pardus; tiger, Panthera tigris; and snow leopard, Panthera uncia), as well as in the cheetah (Acinonyx jubatus) and puma (Puma concolor). Lineage-specific directional selection was not detected in the clouded leopard (Neofelis nebulosa), which, along with the genus Panthera, diverged early from all other extant felids. The cheetah, puma, and jaguarundi (Puma yagouarondi) compose a monophyletic group in which body size may have decreased during the evolution of the jaguarundi, although our analyses revealed no lineage-specific directional selection for smaller sizes in the species. Directional selection for increased body size shown herein seems to be associated with a lifestyle dependent on relatively large prey. This selection may be accelerated by the features of solitary hunters in felids. [ABSTRACT FROM AUTHOR]

Pumas are the most widely distributed felid in the Western Hemisphere. Increasingly, however, human persecution and habitat loss are isolating puma populations. To explore the genomic consequences of this isolation, we assemble a draft puma genome and a geographically broad panel of resequenced individuals. We estimate that the lineage leading to present-day North American pumas diverged from South American lineages 300-100 thousand years ago. We find signatures of close inbreeding in geographically isolated North American populations, but also that tracts of homozygosity are rarely shared among these populations, suggesting that assisted gene flow would restore local genetic diversity. The genome of a Florida panther descended from translocated Central American individuals has long tracts of homozygosity despite recent outbreeding. This suggests that while translocations may introduce diversity, sustaining diversity in small and isolated populations will require either repeated translocations or restoration of landscape connectivity. Our approach provides a framework for genome-wide analyses that can be applied to the management of similarly small and isolated populations.

Domestic dogs are the most abundant large carnivore on the planet, and their ubiquity has led to concern regarding the impacts of dogs as predators of and competitors with native wildlife. If native large carnivores perceive dogs as threatening, impacts could extend to the community level by altering interactions between large carnivores and their prey. Dog impacts may be further exacerbated if these human-associated predators are also perceived as indicators of risk from humans. However, observational approaches used to date have led to ambiguity regarding the effects of dog presence on wildlife. We experimentally quantified dog impacts on the behavior of a native large carnivore, presenting playbacks of dog vocalizations to pumas in central California. We show that the perceived presence of dogs has minimal impacts on puma behavior at their kill sites, and is no more likely to affect total feeding time at kills than non-threatening controls. We previously demonstrated that pumas exhibit strong responses to human cues, and here show that perceived risk from human presence far exceeds that from dogs. Our results suggest that protected areas management policies that restrict dogs but permit human access may in some cases be of limited value for large carnivores.

Copyright of Revista Mundo de Antes is the property of Revista Mundo de Antes and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Simple Summary: Glioblastomas are aggressive and incurable brain tumors, being resistant to therapy. N6-isopentenyladenosine (i6A or iPA) is a naturally derived molecule that has been studied for its anti-glioma effects. We found that iPA treatment induces an alteration of cellular metabolism due to inhibition of EGFR translocation on mitochondria and activation of cell death following PUMA upregulation. Our findings suggest that inducing dysfunctional mitochondria through iPA might be a promising therapeutic avenue in the treatment of glioblastoma. Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor and is poorly susceptible to cytotoxic therapies. Amplification of the epidermal growth factor receptor (EGFR) and deletion of exons 2 to 7, which generates EGFR variant III (vIII), are the most common molecular alterations of GBMs that contribute to the aggressiveness of the disease. Recently, it has been shown that EGFR/EGFRvIII-targeted inhibitors enhance mitochondrial translocation by causing mitochondrial accumulation of these receptors, promoting the tumor drug resistance; moreover, they negatively modulate intrinsic mitochondria-mediated apoptosis by sequestering PUMA, leading to impaired apoptotic response in GBM cells. N6-isopentenyladenosine (i6A or iPA), a cytokinin consisting of an adenosine linked to an isopentenyl group deriving from the mevalonate pathway, has antiproliferative effects on numerous tumor cells, including GBM cells, by inducing cell death in vitro and in vivo. Here, we observed that iPA inhibits the mitochondrial respiration in GBM cells by preventing the translocation of EGFR/EGFRvIII to the mitochondria and allowing PUMA to interact with them by promoting changes in mitochondrial activity, thus playing a critical role in cell death. Our findings clearly demonstrate that iPA interferes with mitochondrial bioenergetic capacity, providing a rationale for an effective strategy for treating GBM. [ABSTRACT FROM AUTHOR]

Background and Research Aims: Wildlife research in Panamá has focused primarily on protected areas along the Central Cordillera, where much of the remaining mature rainforest habitat is located. Information on large felid and prey habitat use in isolated habitats in Panamá is therefore limited. Here, we estimated occupancy and detection probabilities, as affected by habitat and anthropogenic influences, for 2 felid species (jaguars [ Panthera onca ] and pumas [ Puma concolor ]), and 2 prey species (white-lipped peccaries [ Tayassu pecari ] and collared peccaries [ Pecari tajacu ]). Methods: Camera trap surveys were conducted during 2014–2015 at Cerro Hoya National Park (CHNP), an isolated remnant of tropical rainforest habitat, and Darién National Park (DNP), a large tract of continuous rainforest habitat. We used single-season, single-species occupancy modeling to estimate probabilities of detection and habitat use of our focal species. Results: Three of the 4 focal species were detected at both sites, excluding white-lipped peccary at CHNP. Detection of jaguars and white-lipped peccaries at DNP was highest in February, while detection of collared peccaries at DNP and pumas at CHNP was highest in May and April, respectively. Peccary habitat use was uniform across sites and unaffected by habitat covariates. Both felids preferred habitat further away from anthropogenic disturbance, and jaguars preferred habitat at higher elevations than pumas. Conclusion: We further confirm the presence of jaguars and likely local extirpation of white-lipped peccaries in CHNP. Temporal variations influenced detections of focal species. Habitat use of felids was negatively affected by anthropogenic disturbance and elevation. Implications for Conservation Habitat fragmentation and human activities negatively influenced habitat use of felids at both study areas. Given that CHNP serves as one of the last remnants of forest habitat outside the Central Cordillera, we recommend that CHNP be considered a top priority area for wildlife conservation in Panamá. [ABSTRACT FROM AUTHOR]

As carnivores recolonize parts of their historical range, and such recolonization is increasingly recognized for its ability to reconfigure and revitalize degraded ecosystems, understanding where and when range expansion may continue is useful for facilitating scenario planning and identifying roles for conservation measures. We developed an individual-based model to predict carnivore range expansion and applied it to cougars (Puma concolor) in North America between 2023 and 2100. We parameterized our model with empirical movement, demographic, and survival data, and validated its performance by hindcasting nine observed recolonization events from the 1990s – 2023. Our model accurately recreated historical recolonization events and forecasted cougars reclaiming 2.1 % of unoccupied range by 2100, mostly in boreal Canada. Of currently unoccupied states/provinces ("jurisdictions"), only Manitoba received universal support across model runs for hosting a breeding population by 2100. Oklahoma, Minnesota, Kansas, and Iowa, requiring dispersal across nonhabitat, had 30 %, 30 %, 11 %, and 2 % probability of recolonization, respectively. No other jurisdictions were forecast to be recolonized. Mortality from harvest in Midwestern source populations and vehicle collisions dominated outcomes for eastward-moving females. Simulated management scenarios eliminating such hunting and adding nine wildlife crossing structures, however, did not significantly change recolonization probability. In areas where current cougar range abuts unoccupied breeding habitat, we estimated slower rates of expansion, varying from 2 to 3 km·yr−1, yielding roughly 150–230 km of linear expansion in those regions by 2100. Our mechanistic model and underlying empirical data provide a credible and transferable approach to forecast carnivore range expansion. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common malignancy in women worldwide, and the discovery of new effective breast cancer therapies with lower toxicity is still needed. We screened a series of chalcone derivatives and found that MY11 ((E)-1-(2-hydroxy-4,6-dimethoxyphenyl)-3-(4-piperazinylphenyl) prop-2-en-1-one) had the strongest anti-breast cancer activity. MY11 inhibited the growth of MDA-MB-231 and MCF-7 breast cancer cells by arresting the cell cycle and promoting apoptosis, through regulation of the cell cycle and apoptosis-related proteins. PDTC (Pyrrolidinedithiocarbamate ammonium), a specific inhibitor of the NF-κB pathway, abolished the inhibitory effect of MY11 treatment. NF-κB has been shown to regulate PUMA-dependent apoptosis. Our in vitro studies demonstrated that MY11 promoted breast cancer cell apoptosis by activating the NF-κB/PUMA/mitochondrial apoptosis pathway (including Bcl-2, Bax, and Caspase-9). MY11 also inhibited tumor growth in an orthotopic breast cancer mouse model by inducing apoptosis through the NF-κB signaling pathway, importantly, with minimal toxicity. In addition, MY11 was found by docking analysis to bind to p65, which might enhance the stability of the p65 protein. Taken together, our findings indicate that MY11 exerts a significant anticancer effect in breast cancer and that it may be a potential candidate for the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

In 1995, eight female pumas from Texas (Puma concolor stanleyana) were introduced into five areas in South Florida to remediate morphological and biomedical correlates of inbreeding depression that threatened the long-term survival of Florida panthers (P. c. coryi). Initial analysis of the results of this genetic introgression initiative has highlighted its success, including growth of the population, increased genetic heterozygosity, and reduced frequencies of physical traits associated with inbreeding, including cryptorchidism. However, panthers remain isolated from other puma populations and natural gene flow is not currently plausible. Using data collected from 65 panthers in the post-genetic introgression era (1998–2020), we assessed the benefits accrued to male panther reproductive parameters via this management initiative, the effect of genetic variables, and compared results to historic data. Microsatellite data were used to determine individual heterozygosity levels and qualify panther genetic ancestry as admixed (i.e., panthers descended from crosses with female Texas puma) or canonical (i.e., panthers that comprised most of the population prior to genetic introgression). A total of 47 admixed and 10 canonical panthers were identified; mean individual heterozygosity of canonical panthers (0.39) was significantly different from admixed panthers (0.63; t54 = 4.7, P-value < 0.001). Admixed panthers exhibited higher mean values for total testicular volume, structurally normal spermatozoa, and total sperm in comparison to canonical panthers. The progressive improvement of sperm metrics demonstrates that the benefits of genetic introgression continue to have a positive impact on the population >25 years since the release of the Texas pumas. However, the Florida panther population remains small, isolated, and vulnerable to deterministic and stochastic events that warrants continued monitoring to assess when additional genetic introgression initiatives will need to be implemented in the future. [ABSTRACT FROM AUTHOR]

Colon cancer is a gastrointestinal malignancy that is one of the leading causes of tumor‐associated deaths. It has been reported that the mammalian target of rapamycin (mTOR) can lead to the progression of colon cancer. However, the mechanism by which mTOR inhibitor (OSI‐027) mediates the tumorigenesis of colon cancer remains largely unknown. Cell function of colon cancer was investigated by cell counting kit‐8 flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. In addition, quantitative real‐time polymerase chain reaction and Western blot were used to investigate the mechanism underlying the function of OSI‐027 in colon cancer. OSI‐027 dose‐dependently reduced colon cancer cell viability by inducing cell apoptosis. In addition, OSI‐027 induced the apoptosis of colon cancer cells via upregulation of PUMA. OSI‐027 promoted the expression of PUMA by activation of forkhead box protein O3a (FOXO3a), and c‐Myc knockdown partially increased FOXO3a and PUMA levels. Moreover, OSI‐027 attenuated the tumor growth of colon cancer through the mediation of the mTOR/c‐Myc/FOXO3a axis. OSI‐027 attenuates colon cancer progression through the mediation of the c‐Myc/FOXO3a/PUMA axis. Thereby, this study might shed new insights on exploring the strategies against colon cancer. [ABSTRACT FROM AUTHOR]

B-cell acute lymphoblastic leukemia (B-ALL) is a hematologic disorder characterized by the abnormal proliferation and accumulation of immature B-lymphoblasts arrested at various stages of differentiation. Despite advances in treatment, a significant percentage of pediatric patients with precursor B-ALL still relapse. Therefore, alternative therapies are needed to improve the cure rates for pediatric patients. TPEN (N, N, N', N'-tetrakis(2-pyridylmethyl)-ethylenediamine) is a pro-oxidant agent capable of selectively inducing apoptosis in leukemia cell lines. Consequently, it has been suggested that TPEN could be a potential agent for oxidative therapy. However, it is not yet known whether TPEN can selectively destroy leukemia cells in a more disease-like model, for example, the bloodstream and bone marrow (BM), ex vivo. This investigation is an extension of a previous study that dealt with the effect of TPEN on ex vivo isolated/purified refractory B-ALL cells. Here, we evaluated the effect of TPEN on whole BM from nonleukemic patients (control) or pediatric patients diagnosed with de novo B-ALL or refractory B-ALL cells by analyzing the hematopoietic cell lineage marker CD34/CD19. Although TPEN was innocuous to nonleukemic BM (n = 3), we found that TPEN significantly induced apoptosis in de novo (n = 5) and refractory B-ALL (n = 6) leukemic cell populations. Moreover, TPEN significantly increased the counts of cells positive for the oxidation of the stress sensor protein DJ-1, a sign of the formation of H2O2, and significantly increased the counts of cells positive for the pro-apoptotic proteins TP53, PUMA, and CASPASE-3 (CASP-3), indicative of apoptosis, in B-ALL cells. We demonstrate that TPEN selectively eliminates B-ALL cells (CD34 + /CD19 +) but no other cell populations in BM (CD34 + /CD19-; CD34-/CD19 + ; CD34-/CD19-) independent of age, diagnosis status (de novo or refractory), sex, karyotype, or immunophenotype. Understanding TPEN-induced cell death in leukemia cells provides insight into more effective therapeutic oxidation-inducing anticancer agents. [ABSTRACT FROM AUTHOR]

We identified a rustrela virus variant in a wild mountain lion (Puma concolor) in Colorado, USA. The animal had clinical signs and histologic lesions compatible with staggering disease. Considering its wide host range in Europe, rustrela virus should be considered as a cause for neurologic diseases among mammal species in North America.

Direction of arrival (DOA) estimation of coherent sources with a uniform circular array (UCA) is an intractable problem. The method-of-direction-estimation (MODE) algorithm has strong superiority in handling coherent sources compared with the classical MUSIC, and ESPRIT algorithms. However, MODE is sensitive to source numbers and does not work well in the UCA scenario. In order to improve the performance of MODE, a robust DOA estimation method named UCA-PUMA (principal-eigenvector-utilization for- modal-analysis) is proposed. The complicated non-Vandermonde structured steering vector of UCA is transformed into a virtual Vandermonde structured steering vector in mode space. The proposed method gives a closed-form solution compared with the original UCA-MODE algorithm. The performance of the UCA-PUMA method is evaluated by simulations. Simulation results demonstrate that the UCA-PUMA is more robust to source numbers than the UCA-MODE, and coherent sources can be handled without spatial smoothing. In addition, the UCA-PUMA fully takes advantage of the UCA, which is able to discriminate sources coming from a 360° azimuthal field of view. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a predominant movement disorder caused mainly due to selective loss of the dopaminergic neurons in the substantia nigra pars compacta of the mid brain. There is currently no cure for PD barring treatments to manage symptoms. The reasons might be due to lack of precise understanding of molecular mechanisms leading to neurodegeneration. Aberrant cell cycle activation has been implicated in neuronal death pathways of various neurodegenerative diseases including PD. This study investigates the role of cell cycle regulator Cell division cycle 25A (Cdc25A) in a PD-relevant neuron death model induced by 6-OHDA treatment. We find Cdc25A is rapidly elevated, activated and is playing a key role in neuron death by regulating Rb phosphorylation and E2F1 activity. Knockdown of Cdc25A via shRNA downregulates the levels of pro-apoptotic PUMA, an E2F1 target and cleaved Caspase-3 levels, suggesting Cdc25A may regulate neuronal apoptosis through these effectors. Our work sheds light on the intricate signaling networks involved in neurodegeneration and highlights Cdc25A as a potential therapeutic target for mitigating aberrant cell cycle re-entry underlying PD pathogenesis. These novel insights into molecular mechanisms provide a foundation for future development of neuroprotective strategies to slow or prevent progression of this debilitating disease. [Display omitted] • 6-OHDA triggers Cdc25A upregulation in dopamine neurons. • Cdc25A plays required role in neuronal cell death in response to 6-OHDA. • Cdc25A induces neuronal apoptosis by upregulating PUMA via E2F1-Rb pathway. • Cdc25A could be a potential therapeutic target for PD. [ABSTRACT FROM AUTHOR]

• EGCG enhanced ER stress activation and cytoskeleton disruption in MM cells. • EGCG induced MM cells apoptosis through ER stress activation and cytoskeletal disruption. • EGCG inhibited tumor progression process and enhanced drugs' antitumor activity. • EGCG may have a great clinical potential for MM treatment and prevention. Multiple myeloma (MM) is an incurable plasma cell malignancy that has prompted investigations into new potential therapeutic avenues. Epigallocatechin-3-gallate (EGCG), a major component of green tea, confers antioxidant, anti-inflammatory, and anti-tumor properties. Previous studies have shown that EGCG inhibits proliferation and induces apoptosis of multiple myeloma cells, however its underlying molecular mechanisms are largely unknown. In this study, we accordingly sought to examine the therapeutic effects and underlying mechanisms of EGCG on MM. Initially, using CCK8 (Cell Counting Kit-8) assays and Annexin V-FITC/PI staining, we demonstrated that EGCG dose-dependently reduced cell viability and induced apoptosis in the MM cell lines MM.1S and RPMI 8226. Subsequently, mRNA sequencing of EGCG-treated MM.1S cells revealed a significant upregulation of genes associated with endoplasmic reticulum stress (ERS), including P-eIF2α (phosphorylation-eukaryotic translation initiation factor 2 alpha), ATF4 (activating transcription factor 4), CHOP (C/EBP homologous protein, DDIT3), and PUMA (p53 upregulated modulator of apoptosis, BBC3), which were confirmed at the protein level by western blotting. Furthermore, treatment with the eIF2α inhibitor ISRIB reduced the rates of EGCG-induced apoptosis and promoted increases in the protein expression of all four ER stress-related molecules in MM cells. Additionally, mRNA-seq data revealed a downregulation of α-Tubulin 1b (TUBA1B) expression in EGCG-treated MM cells, which was confirmed by western blotting and immunofluorescence analyses. Moreover, we utilized a mouse model to show that EGCG inhibited myeloma tumor growth, which was inhibited by ISRIB. In summary, the findings of this novel study indicated that EGCG promotes apoptosis of MM cells, both via activation of the ER stress pathway and disruption of cytoskeletal integrity. These findings highlight the multi-faceted anti-tumor effects of EGCG and its potential clinical application in MM treatment. [ABSTRACT FROM AUTHOR]

Cost-benefit trade-offs for individuals participating in social behaviors are the basis for current theories on the evolution of social behaviors and societies. However, research on social strategies has largely ignored solitary animals, in which we assume that rare interactions are explained by courtship or territoriality or, in special circumstances, resource distributions or kinship. We used directed network analysis of conspecific tolerance at food sources to provide evidence that a solitary carnivore, the puma (Puma concolor), exhibited adaptive social strategies similar to more social animals. Every puma in our analysis participated in the network, which featured densely connected communities delineated by territorial males. Territorial males also structured social interactions among pumas. Contrary to expectations, conspecific tolerance was best characterized by direct reciprocity, establishing a fitness benefit to individuals that participated in social behaviors. However, reciprocity operated on a longer time scale than in gregarious species. Tolerance was also explained by hierarchical reciprocity, which we defined as network triangles in which one puma (generally male) received tolerance from two others (generally females) that also tolerated each other. Hierarchical reciprocity suggested that males might be cheating females; nevertheless, we suspect that males and females used different fitness currencies. For example, females may have benefited from tolerating males through the maintenance of social niches that support breeding opportunities. Our work contributes evidence of adaptive social strategies in a solitary carnivore and support for the applicability of theories of social behavior across taxa, including solitary species in which they are rarely tested.