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Loss-of-function mutations at the retinoblastoma (RB1) gene are associated with increased mortality, metastasis, and poor therapeutic outcome in several cancers, including osteosarcoma. However, the mechanism(s) through which RB1 loss worsens clinical outcome remains understudied. Ubiquitin-like with PHD and Ring Finger domains 1 (UHRF1) has been identified as a critical downstream effector of the RB/E2F signaling pathway that is overexpressed in various cancers. Here, we determined the role and regulatory mechanisms of UHRF1 in rendering osteosarcoma cells more aggressive. Higher UHRF1 expression correlated with malignancy in osteosarcoma cell lines, clinical samples, and genetically engineered mouse models. Gain- and loss-of-function assays revealed that UHRF1 has cell-intrinsic and extrinsic functions promoting cell proliferation, migration, invasion, angiogenesis, and metastasis. UHRF1 overexpression induced angiogenesis by suppressing AMPK activation and Semaphorin 3E (SEMA3E) expression. Further, UHRF1-mediated migration and metastasis resulted, at least in part, through altered expression of extracellular vesicles and their cargo, including urokinase-type plasminogen activator (uPA). Novel osteosarcoma genetically engineered mouse models confirmed that knocking out Uhrf1 considerably decreased metastasis and reversed the poorer survival associated with Rb1 loss. This presents a new mechanistic insight into RB1 loss-associated poor prognosis and novel oncogenic roles of UHRF1 in the regulation of angiogenesis and exosome secretion, both critical for osteosarcoma metastasis. This provides substantial support for targeting UHRF1 or its downstream effectors as novel therapeutic options to improve current treatment for osteosarcoma.

Dengue, caused by the dengue virus (DENV), is a global health threat transmitted by Aedes mosquitoes, resulting in 400 million cases annually. The disease ranges from mild to severe, with potential progression to hemorrhagic dengue. Current research is focused on natural antivirals due to challenges in vector control. This study evaluates the antiviral potential of peptides derived from the microalgae Phaeodactylum tricornutum, known for its bioactive compounds. Microalgae were cultivated under controlled conditions, followed by protein extraction and hydrolysis to produce four peptide fractions. These fractions were assessed for cytotoxicity via the MTT assay and antiviral activity against DENV serotype 2 using flow cytometry and plaque formation assays. The 10–30 kDa peptide fraction, at 150 and 300 μg/mL concentrations, demonstrated no cytotoxicity and significantly reduced the percentage of infected cells and viral titers. These findings suggest that peptides derived from Phaeodactylum tricornutum exhibit promising antiviral activity against dengue virus serotype 2, potentially contributing to developing new therapeutic approaches for dengue.

Abstract Background The study objective was to determine if a nurturing care parenting intervention delivered in a humanitarian setting in Rwanda would benefit early development, learning, and care outcomes for young children under five years and their caregivers compared to standard care. Methodology Rwanda’s Mugombwa, Kansi, and Kigeme refugee camps and host communities implemented the parenting program. Via a quasi-experimental research design, the study assessed the effects of intervention delivered as a high dose (HD: 12 group sessions and four home visits) or low dose (LD: 6 group sessions and two home visits) on child and caregiver outcomes compared to the control group from similar settings receiving standard care. The Ages and Stages Questionnaires-3 (ASQ-3) assessed child development outcomes. The Multiple Indicator Cluster Survey questionnaire assessed parenting practices concerning early learning and stimulation. Findings The assessment included 733 children and families in total: HD = 314, LD = 240, control = 179. The researchers found no significant difference in child development scores between the intervention and control groups. Significantly higher proportion of caregivers exposed to HD and LD packages had engaged in early learning and stimulation practices compared to the control group, respectively, with 211(67.2%), 148 (61.7%) vs. 66 (36.9%), p

ABSTRACT Candida auris is an emerging human fungal pathogen, first described in Japan in 2009, and first detected in the United States in 2016. Here, we report the first-ever description of C. auris colonizing a human pet, the first identification of C. auris in a non-human mammal in the United States and the first C. auris isolate from the state of Kansas. While analyzing the oral mycobiome of dogs from a shelter in Kansas, the oral swab from one dog was found to contain C. auris as well as three other fungal species. The presence of C. auris in a dog suggests the possibility of zoonotic transmission to humans. The isolate is a member of Clade IV, which has been found in patients in Chicago and Florida, while Clades I and III are the most prevalent in the United States. The isolate is resistant to fluconazole, terbinafine, and amphotericin B but susceptible to caspofungin, consistent with the drug-resistant characteristics of many human C. auris isolates. The source of C. auris transient colonization in this dog is unknown, and there is no evidence that it was further transmitted to humans, other dogs in the shelter, or pets in its adopted household. Isolation of C. auris from a dog in Kansas has public health implications as a potential emerging source for the zoonotic spread of this pathogenic fungus, and for the development of antifungal resistance.IMPORTANCECandida auris is an emerging fungal infection of humans and is particularly problematic because it is multi-drug resistant and difficult to treat. It is also known to be spread from person to person by contact and can remain on surfaces for long periods of time. In this report, a dog in a shelter in Kansas is found to be colonized with Candida auris. This is the first study to document the presence of Candida auris on a pet, the first to document C. auris presence on a non-human mammal in the United States, and the first to report an isolate of C. auris within the state of Kansas. The presence of C. auris in a pet dog raises the possibility of zoonotic transmission from pets to human or vice versa.

Bursera microphylla A. Gray (Burseraceae) es una planta medicinal mexicana con un destacado potencial antiproliferativo y antiinflamatorio in vitro que ha sido asociado a la presencia de compuestos del tipo lignano y triterpenoide, sin embargo, las propiedades farmacocinéticas (absorción, distribución, metabolismo, y excreción - ADME) y los posibles blancos farmacológicos de estos compuestos son desconocidos. El objetivo del estudio fue establecer in-silico el perfil ADME de los metabolitos bioactivos de B. microphylla y analizar los principales objetivos moleculares que son potencialmente inhibidos por estos compuestos. El análisis ADME de los compuestos de B. microphylla (14 lignanos y 10 terpenos) se realizó utilizando la herramienta SwissADME. La determinación in-silico de los posibles blancos terapéuticos se realizó utilizando el programa SwissTargetPrediction. En general, los lignanos y terpenos de B. microphylla presentaron un perfil ADME favorable. El análisis predictivo arrojó que hinoquinina inhibe a los transportadores de dopamina (DAT) y norepinefrina (NET). Por su parte, β-cariofileno reconoce al receptor cannabinoide tipo 2 (CB2). Compuestos con actividad antiproliferativa como ariensina, burserano, dihidroclusina, picropoligamina y burseranina mostraron alta biodisponibilidad oral. Todos los compuestos analizados mostraron capacidad de inhibir enzimas del metabolismo hepático, como CYP1A2 y CYP2C19. Las propiedades farmacocinéticas y farmacodinámicas aceptables de los lignanos y terpenos de B. microphylla los posicionan como buenos prospectos para ser evaluados en modelos animales de inflamación, analgesia, cáncer y enfermedades psiquiátricas. La potencial inhibición de las CYP’s es un aspecto que debe ser considerado para evitar reacciones adversas en una terapia combinada.

Abstract Photodetectors operating across the short‐, mid‐, and long‐wave infrared (SWIR–LWIR, λ = 1–14 µm) underpin modern science, technology, and society in profound ways. Narrow bandgap semiconductors that form the basis for these devices require complex manufacturing, high costs, cooling, and lack compatibility with silicon electronics, attributes that remain prohibitive for their widespread usage and the development of emerging technologies. Here, a photoconductive detector, fabricated using a solution‐processed narrow bandgap conjugated polymer is demonstrated that enables charge carrier generation in the infrared and ultrasensitive SWIR–LWIR photodetection at room temperature. Devices demonstrate an ultralow electronic noise that enables outstanding performance from a simple, monolithic device enabling a high detectivity (D*, the figure of merit for detector sensitivity) >2.44 × 109 Jones (cm Hz1/2 W−1) using the ultralow flux of a blackbody that mirrors the background emission of objects. These attributes, ease of fabrication, low dark current characteristics, and highly sensitive operation overcome major limitations inherent within modern narrow–bandgap semiconductors, demonstrate practical utility, and suggest that uncooled detectivities superior to many inorganic devices can be achieved at high operating temperatures.

Parkinson’s disease (PD) is a complex neurodegenerative condition characterized by alpha-synuclein aggregation and dysfunctional protein degradation pathways. This study investigates the differential gene expression of pivotal components (UBE2K, PSMC4, SKP1, and HSPA8) within these pathways in a Mexican-Mestizo PD population compared to healthy controls. We enrolled 87 PD patients and 87 controls, assessing their gene expression levels via RT-qPCR. Our results reveal a significant downregulation of PSMC4, SKP1, and HSPA8 in the PD group (p = 0.033, p = 0.003, and p = 0.002, respectively). Logistic regression analyses establish a strong association between PD and reduced expression of PSMC4, SKP1, and HSPA8 (OR = 0.640, 95% CI = 0.415–0.987; OR = 0.000, 95% CI = 0.000–0.075; OR = 0.550, 95% CI = 0.368–0.823, respectively). Conversely, UBE2K exhibited no significant association or expression difference between the groups. Furthermore, we develop a gene expression model based on HSPA8, PSMC4, and SKP1, demonstrating robust discrimination between healthy controls and PD patients. Notably, the model’s diagnostic efficacy is particularly pronounced in early-stage PD. In conclusion, our study provides compelling evidence linking decreased gene expression of PSMC4, SKP1, and HSPA8 to PD in the Mexican-Mestizo population. Additionally, our gene expression model exhibits promise as a diagnostic tool, particularly for early-stage PD diagnosis.

This Article responds to environmental justice arguments that undermine, rather than safeguard, health and environmental quality for low-income and minority populations.  Efforts by scholars and practitioners to clearly define “environmental injustice” to facilitate use of racial discrimination legal frameworks have had minimal success and are ultimately limiting the ability to embrace a broader arsenal of weapons in the fight against injustice.  The greatest weapon of the environmental justice movement is its people.  Environmental justice must evolve more rapidly beyond efforts to merely give communities voice, and actually redistribute power and decision making to open up opportunities for social movement intersection.  The struggle to define environmental justice is difficult because it attempts to crystalize the efforts of converging social movements that continue.  This Article advocates more explicit acceptance of environmental justice as a movement which requires focus on new strategies and tools that address historic pollution and prevent future inequitable environmental impacts.  Considering the past, present, and future of environmental justice, this article advocates for expedited cleanups of historically polluted areas, mandatory environmental justice assessments (EJA) in existing planning processes, and robust environmental justice components in local land use plans; these coordinated strategies would empower communities to realize a vison of land use freed of the historic imposition of inequity.

Studies on antihypertensive chickpea protein hydrolysates have rarely performed in vivo evaluations, limiting the entry of such hydrolysates into functional food development and clinical trials. Thus, our aim was to optimize the hydrolysis conditions to produce an alcalase-based chickpea hydrolysate with a hypotensive effect in vivo at convenient oral doses. The hydrolysis reaction time, temperature, and alcalase/substrate concentration were optimized using a response surface analysis (RSA). ACE-I inhibition was the response variable. The optimized hydrolysis conditions were time = 0.5 h, temperature = 40 °C, and E/S concentration = 0.254 (U/g). The IC50 of the optimized hydrolysate (OCPH) was 0.358 mg/mL. Five hydrolysates from the RSA worksheet (one of them obtained after 5 min of hydrolysis (CPH15)) had an ACE-I inhibitory potential similar to that of OCPH (p > 0.05). At 50 mg/kg doses, OCPH and CPH15 promoted a clinically relevant hypotensive effect in spontaneously hypertensive rats, up to −47.35 mmHg and −28.95 mmHg, respectively (p < 0.05 vs. negative control). Furthermore, the hypotensive effect was sustained for at least 7 h post-supplementation. Overall, OCPH and CPH15 are promising ingredients for functional food development and as test materials for clinical trials.

Crop quality has been compromised due to nutrient deficiencies. The macronutrient magnesium (Mg) is essential; however, it has not been considered in agronomic fertilization programs, affecting human health. The objective of the study was to increase the Mg content in the fruits of green beans cv. ‘Strike’ by applying Mg-nanofertilizer, as well as evaluating its effect on growth, performance and nutritional quality, versus magnesium sulfate (MgSO4). The experiment was carried out under shade mesh conditions in Delicias, Chihuahua, Mexico during the period August-October 2022. A completely randomized experimental design was used, with two Mg sources: Mg nanofertilizer (NanoMg) and MgSO4 at doses of 50, 100 and 200 ppm and a control without application, forming seven treatments with six repetitions each. The results indicate that the maximum yield was provided by NanoMg and MgSO4 at 200 ppm, with values greater than 300%. The Mg distribution pattern for the NanoMg treatments presented the following concentration order: root>leaf>stem>fruit; while, for the MgSO4 treatments it was: leaf>root>stem>fruit. The most efficient treatment in increasing the Mg content in the fruit was NanoMg at 200 ppm, which achieved a biofortification of more than 120% with respect to the control. Therefore, when consuming 100 g of green beans cv. ‘Strike’ biofortified by NanoMg, the recommended daily needs of the human being could be satisfied. Finally, it is concluded that nanofertilizers are the best option for a biofortification program since they offer a sustainable alternative by increasing productivity and quality in green bean fruits.

The purpose of this study was to characterize the variety and diversity of the oral mycobiome of domestic dogs and to identify the commensal and potentially pathogenic fungi present. Two hundred fifty-one buccal swabs from domestic dogs were obtained and struck onto a chromogenic fungal growth medium that distinguishes between fungal species based on colony color and morphology. After isolating and harvesting single colonies, genomic DNA was extracted from pure cultures. PCR was used to amplify a fungal-specific variable rDNA region of the genome, which was then sent for sequencing. Sequencing results were input into the NCBI BLAST database to identify individual components of the oral mycobiome of tested dogs. Of the 251 dogs swabbed, 73 had cultivable fungi present and 10 dogs had multiple fungal species isolated. Although the dogs did not show signs of oral infections at the time, we did find fungal species that cause pathogenicity in animals and humans. Among fungal isolates, Malassezia pachydermatis and species from the genus Candida were predominant. Following fungal isolate identification, antifungal drug susceptibility tests were performed on each isolate toward the medically important antifungal drugs including fluconazole, ketoconazole, and terbinafine. Drug susceptibility test results indicated that a large number of isolates had high MIC values for all three drugs. Exploring the oral mycobiome of dogs, as well as the corresponding drug susceptibility profiles, can have important implications for canine dental hygiene, health, and medical treatment. Identifying the microorganisms within the canine mouth can illustrate a common pathway for fungal pathogens of One Health concern to spread from our canine companions to humans.

Background Cerebral blood flow (CBF) is impaired in the early phase after return of spontaneous circulation. Sodium nitroprusside (SNP) administration via intracranial subdural catheters improves cerebral cortical microcirculation. We determined whether the SNP treatment improves CBF in the subcortical tissue and evaluated the effects of this treatment on cerebral lactate. Methods and Results Sixty minutes after return of spontaneous circulation following 14 minutes of untreated cardiac arrest, 14 minipigs randomly received 4 mg SNP or saline via intracranial subdural catheters. CBF was measured in regions of interest within the cerebrum and thalamus using dynamic susceptibility contrast‐magnetic resonance imaging. After return of spontaneous circulation, CBF was expressed as a percentage of the baseline value. In the saline group, the %CBF in the regions of interest within the cerebrum remained at approximately 50% until 3.5 hours after return of spontaneous circulation, whereas %CBF in the thalamic regions of interest recovered to approximately 73% at this time point. The percentages of the baseline values in the cortical gray matter and subcortical white matter were higher in the SNP group (group effect P=0.026 and 0.025, respectively) but not in the thalamus. The cerebral lactate/creatine ratio measured using magnetic resonance spectroscopy increased over time in the saline group but not in the SNP group (group–time interaction P=0.035). The thalamic lactate/creatine ratio was similar in the 2 groups. Conclusions SNP administered via intracranial subdural catheters improved CBF not only in the cortical gray matter but also in the subcortical white matter. The CBF improvement by SNP was accompanied by a decrease in cerebral lactate.

La investigación muestra la doble jornada (empresarial-formación académica), como una de las principales barreras para las universitarias microempresarias en Ciudad Juárez, Chihuahua. El objetivo principal fue evaluar el impacto del agotamiento físico y emocional en las universitarias microempresarias. El diseño de la investigación fue cualitativo descriptivo, documental no experimental; la muestra estuvo constituida por 30 entrevistas. Los resultados señalan que el tiempo y esfuerzo son el primer obstáculo, por lo que se proponen líneas de acción que ayuden a formar entornos más equitativos y justos para todas las mujeres. Palabras clave: doble jornada, microempresarias, mujeres, universitarias.

Mutations that result in the loss of function of pRB were first identified in retinoblastoma and since then have been associated with the propagation of various forms of cancer. pRB is best known for its key role as a transcriptional regulator during cell cycle exit. Beyond the ability of pRB to regulate transcription of cell cycle progression genes, pRB can remodel chromatin to exert several of its other biological roles. In this review, we discuss the diverse functions of pRB in epigenetic regulation including nucleosome mobilization, histone modifications, DNA methylation and non-coding RNAs.

ABSTRACT Loss of function mutations at the retinoblastoma ( RB1 ) gene are associated with increased mortality, metastasis and poor therapeutic outcome in several cancers, including osteosarcoma (OS). However, the mechanism(s) through which RB1 loss worsens clinical outcome remain to be elucidated. Ubiquitin-like with PHD and Ring Finger domains 1 (UHRF1) has been identified as a critical downstream effector of the RB/E2F signaling pathway that is overexpressed in various cancers. Here, we show that UHRF1 upregulation is critical in rendering OS cells more aggressive. Using novel OS genetically engineered mouse models, we determined that knocking-out Uhrf1 considerably reverses the poorer survival associated with Rb1 loss. We also found that high UHRF1 expression correlates with increased clinical presentation of metastatic disease. Based on gain- and loss-of-function assays, we found that UHRF1 promotes cell proliferation, migration, invasion, and metastasis. UHRF1-mediated cell mobility results as a consequence of altered extracellular vesicles and their cargo, including urokinase-type plasminogen activator (uPA). Our work presents a new mechanistic insight into RB1 loss-associated poor prognosis and a novel oncogenic role of UHRF1 through regulation of exosome secretion that is critical for OS metastasis. This study provides substantial support for targeting UHRF1 or its downstream effectors as novel therapeutic options to improve current treatment for OS.

The United States’ history is marred by systemic oppression, even within parks and protected areas, including national parks. Major barriers for people of color to public lands include accessibility, welcomeness, and safety concerns. Although national parks are one of the nation’s greatest ideas, and while the National Park Service states that diversity and inclusion are priorities, it has not been wholly successful in creating meaningful change to reach these goals. This article examines some of the National Park Service’s efforts to diversify visitation demographics and offers recommendations on how to further increase and diversify visitors to the national park system. This is not intended to discredit the National Park Service, but rather to offer suggestions and context for ways it can remain relevant as our nation deals with times of uncertainty. Alleviating transportation constraints, providing adequate opportunities for non-white recreation and personal experiences, and transitioning from Eurocentric narratives within historical interpretation to local, minority-driven narratives are the main recommendations. The purpose of this article is to illuminate the vitality of accessibility and unbiased historical interpretation as means to increase diversity of visitation to national parks. As such, while this article focuses on the National Park Service, it is intended to benefit any public land-managing agency aiming to remain relevant to its constituents. Movement away from Eurocentric historical narratives and recreational activities is beneficial to all as a means to catalyze empathy and understanding for every American’s lived experience. [This is a paper from “Systemic Threats to Parks & Protected Areas,” the 2020 George Wright Society Student Summit.]

Over the past decade, the fishery of Pacific hake, Merluccius productus (Ayres, 1855), has increased in the Gulf of California, Mexico; therefore, any biological–fisheries information is highly relevant for the management of this fishery, and information on age and individual growth would be fundamental to evaluate populations. The objective of the presently study was to assess age, based on otolith structure, and estimate growth parameters through a multimodel approach. Specimens were collected during research cruises of BIP XI from 2014 to 2019. Pacific hake from the Gulf of California ranged in length from 12.5 to 105 cm TL, reaching a maximum age of 13 years, and females were four years older than males. The logistic model was the best model to describe age–size data for both sexes. Females reached 50% of the maximum length at five years old and males reached that length at four years old.

Abstract Loss-of-function mutations at the retinoblastoma (RB1) gene are associated with increased mortality, metastasis, and poor therapeutic outcome in several cancers, including osteosarcoma. However, the mechanism(s) through which RB1 loss worsens clinical outcome remains understudied. Ubiquitin-like with PHD and Ring Finger domains 1 (UHRF1) has been identified as a critical downstream effector of the RB/E2F signaling pathway that is overexpressed in various cancers. Here, we determined the role and regulatory mechanisms of UHRF1 in rendering osteosarcoma cells more aggressive. Higher UHRF1 expression correlated with malignancy in osteosarcoma cell lines, clinical samples, and genetically engineered mouse models. Gain- and loss-of-function assays revealed that UHRF1 has cell-intrinsic and extrinsic functions promoting cell proliferation, migration, invasion, angiogenesis, and metastasis. UHRF1 overexpression induced angiogenesis by suppressing AMPK activation and Semaphorin 3E (SEMA3E) expression. Further, UHRF1-mediated migration and metastasis resulted, at least in part, through altered expression of extracellular vesicles and their cargo, including urokinase-type plasminogen activator (uPA). Novel osteosarcoma genetically engineered mouse models confirmed that knocking out Uhrf1 considerably decreased metastasis and reversed the poorer survival associated with Rb1 loss. This presents a new mechanistic insight into RB1 loss-associated poor prognosis and novel oncogenic roles of UHRF1 in the regulation of angiogenesis and exosome secretion, both critical for osteosarcoma metastasis. This provides substantial support for targeting UHRF1 or its downstream effectors as novel therapeutic options to improve current treatment for osteosarcoma.