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In eukaryotes, pre-mRNA splicing is vital for RNA processing and orchestrated by the spliceosome, whose assembly starts with the interaction between U1-70K and SR proteins. Despite the significance of the U1-70K/SR interaction, the dynamic nature of the complex and the challenges in obtaining soluble U1-70K have impeded a comprehensive understanding of the interaction at the structural level for decades. We overcome the U1-70K solubility issues, enabling us to characterize the interaction between U1-70K and SRSF1, a representative SR protein. We unveil specific interactions: phosphorylated SRSF1 RS with U1-70K BAD1, and SRSF1 RRM1 with U1-70K RRM. The RS/BAD1 interaction plays a dominant role, whereas the interaction between the RRM domains further enhances the stability of the U1-70K/SRSF1 complex. The RRM interaction involves the C-terminal extension of U1-70K RRM and the conserved acid patches on SRSF1 RRM1 that is involved in SRSF1 phase separation. Our circular dichroism spectra reveal that BAD1 adapts an α-helical conformation and RS is intrinsically disordered. Intriguingly, BAD1 undergoes a conformation switch from α-helix to ß-strand and random coil upon RS binding. In addition to the regulatory mechanism via SRSF1 phosphorylation, the U1-70K/SRSF1 interaction is also regulated by U1-70K BAD1 phosphorylation. We find that U1-70K phosphorylation inhibits the U1-70K and SRSF1 interaction. Our structural findings are validated through in vitro splicing assays and in-cell saturated domain scanning using the CRISPR method, providing new insights into the intricate regulatory mechanisms of pre-mRNA splicing.
Asunto(s)
Ribonucleoproteína Nuclear Pequeña U1 , Factores de Empalme Serina-Arginina , Empalmosomas , Factores de Empalme Serina-Arginina/metabolismo , Factores de Empalme Serina-Arginina/química , Factores de Empalme Serina-Arginina/genética , Fosforilación , Empalmosomas/metabolismo , Empalmosomas/química , Humanos , Ribonucleoproteína Nuclear Pequeña U1/metabolismo , Ribonucleoproteína Nuclear Pequeña U1/química , Ribonucleoproteína Nuclear Pequeña U1/genética , Empalme del ARN , Unión Proteica , Precursores del ARN/metabolismo , Precursores del ARN/genética , Precursores del ARN/químicaRESUMEN
Many animals avoid predation using aposematic displays that pair toxic/dangerous defences with conspicuous achromatic warning patterns, such as high-contrast stripes. To understand how these prey defences work, we need to understand the decision-making of visual predators. Here we gave two species of jumping spiders (Phidippus regius and Habronattus trimaculatus) choice tests using live termites that had their back patterns manipulated using paper capes (solid white, solid black, striped). For P. regius, black and striped termites were quicker to capture attention. Yet despite this increased attention, striped termites were attacked at lower rates than either white or black. This suggests that the termite's contrast with the background elicits attention, but the internal striped body patterning reduces attacks. Results from tests with H. trimaculatus were qualitatively similar but did not meet the threshold for statistical significance. Additional exploratory analyses suggest that attention to and aversion to stripes is at least partially innate and provide further insight into how decision-making played out during trials. Because of their rich diversity (over 6500 species) that includes variation in natural history, toxin susceptibility and degree of colour vision, jumping spiders are well suited to test broad generalizations about how and why aposematic displays work.
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On behalf of the Canadian Association of Medical Oncologists, we are pleased to present the abstracts of the 2023 Annual Scientific Meeting. The CAMO Annual Scientific Meeting (ASM) took place on 27 April 2023 in an in-person event in Toronto, ON. Thirty-two (32) abstracts were selected for presentation as oral presentations, in-person poster presentations, and virtual poster presentations. Awards for the top four (4) abstracts were presented during the ASM; they have been marked as "Award Recipient". We congratulate all presenters on their research work and contribution.
Asunto(s)
Oncólogos , Humanos , CanadáRESUMEN
Intraspecific weapon polymorphisms that arise via conditional thresholds may be affected by juvenile experience such as predator encounters, yet this idea has rarely been tested. The New Zealand harvestman Forsteropsalis pureora has three male morphs: majors (alphas and betas) are large-bodied with large chelicerae used in male-male contests, while minors (gammas) are small-bodied with small chelicerae and scramble to find mates. Individuals use leg autotomy to escape predators and there is no regeneration of the missing leg. Here, we tested whether juvenile experience affects adult morph using leg autotomy scars as a proxy of predator encounters. Juvenile males that lost at least one leg (with either locomotory or sensory function) had a 45 times higher probability of becoming a minor morph at adulthood than intact juvenile males. Leg loss during development may affect foraging, locomotion, and/or physiology, potentially linking a juvenile's predator encounters to their final adult morph and future reproductive tactic.
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The Florida State Collection of Arthropods (FSCA) is one of the largest and most diverse insect collections in North America and the largest in the southeastern United States with over twelve million curated specimens and significant amounts of materials in bulk collections and other unprocessed samples. The order Hemiptera currently comprises approximately 95,000 species in three suborders. The FSCA houses type material in the auchenorrhynchan families Cicadidae, Cicadellidae, Cixiidae, Delphacidae, Derbidae, and Membracidae; the heteropteran families Coreidae, Corixidae, Curaliidae, Lygaeidae, Miridae, Pentatomidae, Reduviidae, Schizopteridae, Scutelleridae, and Tingidae; the sternorrhynchan families Aleyrodidae, Aphalaridae, Aphididae, Coccidae, Diaspididae, Matsucoccidae, Pseudococcidae, Phacopteronidae, and Triozidae. This catalog documents the FSCA primary type material for 167 species in 79 genera in 24 families across the three suborders.
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Áfidos , Hemípteros , Reduviidae , Humanos , Animales , FloridaRESUMEN
BACKGROUND: Patients with chronic kidney disease are commonly excluded from clinical trials. The impact of chronic kidney disease on outcomes in patients with locally advanced rectal cancer has not been previously studied. OBJECTIVE: This study aimed to investigate the impact of chronic kidney disease on outcomes in patients with locally advanced rectal cancer. DESIGN: This is a multi-institutional, retrospective cohort study. SETTINGS: This study was conducted at academic and community cancer centers participating in the Canadian Health Outcomes Research Database Consortium Rectal Cancer Database. PATIENTS: Consecutive patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiation before curative-intent surgery from 2005 to 2013 were selected. MAIN OUTCOME MEASURES: Disease-free survival, overall survival, pathologic complete response, and neoadjuvant chemotherapy/radiotherapy completion rate were the primary outcomes measured. RESULTS: A total of 1254 patients were included. Median age was 62, and 29%/69% had clinical stage II and III disease. Median estimated creatinine clearance was 93 mL/min, with 11% <60 mL/min (n = 136). There was no significant difference in the completion rate of neoadjuvant chemotherapy (82% vs 85%, p = 0.36) or radiotherapy (93% vs 95%, p = 0.45) between patients with and without chronic kidney disease. Patients with chronic kidney disease were less likely to receive adjuvant chemotherapy (63% vs 77%, p < 0.01). On multivariate analysis, patients with chronic kidney disease had decreased disease-free survival (HR, 1.37; 95% CI, 1.03-1.82; p = 0.03) but not overall survival (HR, 1.23; 95% CI, 0.88-1.75; p = 0.23) or pathologic complete response (OR, 0.83; 95% CI, 0.50-1.39; p = 0.71). LIMITATIONS: This study was limited by its retrospective design and by limited events for overall survival analysis. CONCLUSIONS: In patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiation, baseline chronic kidney disease was associated with less use of adjuvant chemotherapy and decreased disease-free survival. Chronic kidney disease was not independently associated with neoadjuvant chemotherapy/radiotherapy completion rate, pathologic complete response, or overall survival. These data suggest that patients with locally advanced rectal cancer with chronic kidney disease may have distinct outcomes and, accordingly, the results of landmark clinical trials may not be generalizable to this population. See Video Abstract at http://links.lww.com/DCR/B694. LA REPERCUSIN DE LA ENFERMEDAD RENAL CRNICA EN PACIENTES CON CNCER DE RECTO LOCALMENTE AVANZADO TRATADOS CON QUIMIORRADIOTERAPIA NEOADYUVANTE: ANTECEDENTES:Los pacientes con enfermedad renal crónica generalmente se excluyen de los ensayos clínicos. La repercusión de la enfermedad renal crónica en el desenlace en pacientes con cáncer de recto localmente avanzado no se ha estudiado previamente.OBJETIVO:Investigar la repercusión de la enfermedad renal crónica en los desenlaces en pacientes con cáncer de recto localmente avanzado.DISEÑO:Estudio de cohorte retrospectivo multiinstitucional.ESCENARIO:Centros oncológicos académicos y comunitarios que participan en la base de datos de cáncer rectal del consorcio CHORD.PACIENTES:Pacientes consecutivos con cáncer de recto localmente avanzado, tratados con quimiorradioterapia neoadyuvante, previa a la cirugía con intención curativa del 2005 al 2013.PRINCIPALES VARIABLES EVALUADAS:Sobrevida libre de enfermedad, sobrevida global, respuesta patológica completa, tasa de conclusión de quimioterapia / radioterapia neoadyuvante.RESULTADOS:Se incluyeron 1254 pacientes. El promedio de edad fue de 62, y el 29% / 69% tenían enfermedad en estadio clínico II y III, respectivamente. El promedio de la depuración de creatinina estimada fue de 93 mililitros / minuto, con un 11% <60 mililitros / minuto (n = 136). No hubo diferencias significativas en la tasa de conclusión de la quimioterapia neoadyuvante (82% vs 85%, p = 0,36) o radioterapia (93% vs 95%, p = 0,45) entre pacientes con y sin enfermedad renal crónica. Los pacientes con enfermedad renal crónica tenían menos probabilidades de recibir quimioterapia adyuvante (63% contra el 77%, p <0,01). En el análisis multivariado, los pacientes con enfermedad renal crónica tenían una sobrevida libre de enfermedad menor (HR 1,37, IC 95% 1,03-1,82, p = 0,03) pero no en la sobrevida global (HR 1,23, IC 95% 0,88-1,75, p = 0,23) o respuesta patológica completa (OR 0,83, IC 95% 0,50-1,39, p = 0,71).LIMITACIONES:Diseño retrospectivo y acontecimientos limitados para el análisis de sobrevida global.CONCLUSIONES:En pacientes con cáncer de recto localmente avanzado tratados con quimiorradioterapia neoadyuvante, la enfermedad renal crónica de base se asoció con un menor uso de quimioterapia adyuvante y una menor sobrevida libre de enfermedad. La enfermedad renal crónica no se asoció de forma independiente con la tasa de conclusión de la quimioterapia / radioterapia neoadyuvante, la respuesta patológica completa o la sobrevida global. Estos datos sugieren que los pacientes con cáncer de recto localmente avanzado con enfermedad renal crónica pueden tener resultados distintos y, en consecuencia, los resultados de los ensayos clínicos de referencia pueden no ser generalizables a esta población. Consulte Video Resumen en http://links.lww.com/DCR/B694.
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Terapia Neoadyuvante/métodos , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/radioterapia , Insuficiencia Renal Crónica/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Canadá/epidemiología , Quimioradioterapia/métodos , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Estadificación de Neoplasias/métodos , Evaluación de Resultado en la Atención de Salud , Neoplasias del Recto/patología , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/fisiopatología , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
On behalf of the Canadian Association of Medical Oncologists, we are pleased to present the Abstracts of the 2021 Annual Meeting. The National CAMO Residents Research Day was held virtually on 1 April 2021 and the CAMO Virtual Annual Scientific Meeting (ASM) & Annual General Meeting (AGM) took place on 22 April 2021. Twenty (20) abstracts were selected for presentation as oral presentations and rapid-fire presentations. Awards for the top three (3) abstracts were presented during the ASM and AGM. All of them were marked as "Award Recipient". We congratulate all the presenters on their research work and contribution.
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To avoid predation, many animals mimic behaviours and/or coloration of dangerous prey. Here we examine potential sex-specific mimicry in the jumping spider Habronattus pyrrithrix. Previous work proposed that males' conspicuous dorsal coloration paired with characteristic leg-waving (i.e. false antennation) imperfectly mimics hymenopteran insects (e.g. wasps and bees), affording protection to males during mate-searching and courtship. By contrast, less active females are cryptic and display less leg-waving. Here we test the hypothesis that sexually dimorphic dorsal colour patterns in H. pyrrithrix are most effective when paired with sex-specific behaviours. We manipulated spider dorsal coloration with makeup to model the opposite sex and exposed them to a larger salticid predator (Phidippus californicus). We predicted that males painted like females should suffer higher predation rates than sham-control males. Likewise, females painted like males should suffer higher predation rates than sham-control females. Contrary to expectations, spiders with male-like coloration were attacked more than those with female-like coloration, regardless of their actual sex. Moreover, males were more likely to be captured, and were captured sooner, than females (regardless of colour pattern). With these unexpected negative results, we discuss alternative functional hypotheses for H. pyrrithrix colours, as well as the evolution of defensive coloration generally.
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BACKGROUND: Women with breast cancer are more likely to develop cognitive impairment (CI), insomnia, fatigue, and mood disturbance than individuals with other cancers. The main objectives of this study were to establish the prevalence of CI and examine the relationships between CI, insomnia, fatigue, and mood over the first year of breast cancer treatment. METHODS: Participants were recruited after diagnosis and completed validated measures of insomnia, objective and perceived CI, fatigue, and mood disturbance at four time points during the first year of treatment. A random intercepts cross-lagged panel model assessed relationships among symptoms over time. RESULTS: The sample included 98 women. Prevalence of objective CI ranged from 3.1% to 8.2% throughout the year, whereas 36.7% demonstrated a clinically meaningful decline in perceived CI from baseline to 4 months, which remained relatively stable. Greater perceived CI was associated with more fatigue (ß = -0.78, z = 17.48, p < .01) and symptoms of insomnia (ß = -0.58, z = 5.24, p < .01). Short-term fluctuations in perceived CI (p < .05), but not fatigue or insomnia, predicted future perceived CI. Fatigue (p < .001) was a significant predictor of future reported symptoms of fatigue and insomnia. CONCLUSION: Subjective CI is more prevalent than objective impairments. Fatigue, insomnia, and perceived CI remain stable and are associated during the first year of treatment. Changes in insomnia and fatigue may have little effect on future perceived cognition. Women with breast cancer likely require targeted intervention for these side effects.
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Neoplasias de la Mama/psicología , Disfunción Cognitiva/patología , Trastornos del Humor/patología , Adulto , Anciano , Anciano de 80 o más Años , Ansiedad/etiología , Ansiedad/patología , Ansiedad/psicología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Disfunción Cognitiva/etiología , Disfunción Cognitiva/psicología , Depresión/etiología , Depresión/patología , Depresión/psicología , Fatiga/etiología , Fatiga/patología , Fatiga/psicología , Femenino , Humanos , Persona de Mediana Edad , Trastornos del Humor/etiología , Trastornos del Humor/psicología , Calidad de Vida , Sueño/fisiología , Trastornos del Inicio y del Mantenimiento del Sueño/etiología , Trastornos del Inicio y del Mantenimiento del Sueño/patología , Trastornos del Inicio y del Mantenimiento del Sueño/psicologíaRESUMEN
Sexually selected weapons often function as honest signals of fighting ability. If poor-quality individuals produce high-quality weapons, then receivers should focus on other, more reliable signals. Cost is one way to maintain signal integrity. The costs of weapons tend to increase with relative weapon size, and thereby restrict large weapons to high-quality individuals who can produce and maintain them. Weapon cost, however, appears to be unpredictably variable both within and across taxa, and the mechanisms underlying this variation remain unclear. We suggest variation in weapon cost may result from variation in weapon composition-specifically, differences in the amount of muscle mass directly associated with the weapon. We test this idea by measuring the metabolic cost of sexually selected weapons in seven arthropod species and relating these measures to weapon muscle mass. We show that individuals with relatively large weapon muscles have disproportionately high resting metabolic rates and provide evidence that this trend is driven by weapon muscle mass. Overall, our results suggest that variation in weapon cost can be partially explained by variation in weapon morphology and that the integrity of weapon signals may be maintained by increased metabolic cost in species with relatively high weapon muscle mass.
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Artrópodos/fisiología , Músculos , Conducta Sexual , Animales , Fenotipo , ArmasRESUMEN
BACKGROUND: Mastectomy is often chosen by women for treatment of breast cancer, even when breast-conserving surgery (BCS) is an option. Newfoundland and Labrador has a high mastectomy rate. We documented the number of breast cancers over a given period in the province and their related surgical treatments, and explored the impact of several variables on surgical choice. METHODS: A retrospective cohort design linked diagnosis data from the Newfoundland and Labrador tumour registry to surgery data from the Canadian Institute for Health Information Discharge Abstract Database. Data were extracted for all women aged 19 years or more in whom breast cancer was diagnosed in 2009-2014. RESULTS: A total of 2346 cases of breast cancer with a linked surgical procedure were included. Most operations (1605 [68.4%]) were mastectomy procedures, with the remainder being BCS. Logistic regression analysis revealed that women were 1.82 times (95% confidence interval [CI] 1.64-2.02) more likely to have mastectomy for each unit of stage increase from 0 to IV and 1.15 times (95% CI 1.11-1.21) more likely for each unit of driving time increase. CONCLUSION: Tumour stage and driving time to a radiation facility significantly predicted Newfoundland and Labrador women's surgical treatment choices for breast cancer. Notably, mastectomy was the favoured choice across all age groups, tumour stages and geographical regions of the province. We hope that these results will galvanize efforts to better understand local surgical practices and assist in improving the quality of surgical care of women with breast cancer.
CONTEXTE: Les femmes atteintes d'un cancer du sein optent souvent pour la mastectomie, même lorsque la chirurgie mammaire conservatrice (CMC) est possible. Considérant que la province de Terre-Neuve-et-Labrador enregistre des taux de mastectomie élevés, nous y avons recensé durant une période donnée les cas de cancer du sein et les traitements chirurgicaux associés, et avons étudié l'influence de plusieurs variables sur le choix d'intervention. MÉTHODES: Suivant un modèle de cohorte rétrospective, nous avons apparié les données diagnostiques du registre des cancers de Terre-Neuve-et-Labrador aux données chirurgicales correspondantes de la Base de données sur les congés des patients de l'Institut canadien d'information sur la santé. Nous avons extrait les données de toutes les femmes de 19 ans et plus qui ont reçu un diagnostic de cancer du sein entre 2009 et 2014. RÉSULTATS: Nous avons retenu 2346 cas de cancer du sein avec prise en charge chirurgicale. La majorité des interventions (1605, ou 68,4â¯%) étaient des mastectomies; les autres étaient des CMC. Une analyse de régression logistique a révélé qu'avec chaque augmentation unitaire du stade (de 0 à 4), les femmes devenaient 1,82 fois plus susceptibles d'opter pour la mastectomie (intervalle de confiance [IC] de 95â¯% 1,64 à 2,02), et 1,15 fois plus susceptibles de le faire avec chaque augmentation unitaire du temps de conduite (IC de 95â¯% 1,11 à 1,21). CONCLUSION: Le stade de la tumeur et le temps nécessaire pour se rendre dans un établissement de radiothérapie étaient des facteurs prédictifs significatifs du choix de traitement chirurgical du cancer du sein chez les femmes de Terre-Neuve-et-Labrador. Fait intéressantâ¯: tous les groupes, quels que soient leur âge, le stade de leur tumeur et leur région de la province, avaient une préférence pour la mastectomie. Nous espérons que ces résultats mèneront à d'autres analyses des pratiques chirurgicales locales et contribueront à améliorer la qualité de la prise en charge chirurgicale des femmes atteintes d'un cancer du sein.
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Neoplasias de la Mama/terapia , Toma de Decisiones Clínicas , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Mastectomía/métodos , Sistema de Registros/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Femenino , Humanos , Mastectomía/estadística & datos numéricos , Persona de Mediana Edad , Estadificación de Neoplasias , Terranova y Labrador , Selección de Paciente , Radioterapia Adyuvante/estadística & datos numéricos , Estudios Retrospectivos , Factores de TiempoRESUMEN
OBJECTIVES: Use of adjuvant chemotherapy (AC) following neoadjuvant chemoradiation (nCRT) is controversial in rectal cancer (RC). We assessed a multi-institutional database to determine if there was benefit from AC for pathologic stage II RC patients and whether the addition of oxaliplatin to fluoropyrimidine (OXAC) therapy impacted outcomes. MATERIALS AND METHODS: We included patients who underwent nCRT and had pathologic stage II (ypT3/4 ypN0) tumors. Disease-free survival and overall survival were assessed. Multivariate Cox models adjusting for age, sex, Eastern Cooperative Oncology Group, high-risk features (pT4, poor differentiation, <12 nodes removed, lymphovascular/perineural invasion, or obstruction/perforation), and clinical stage were constructed. RESULTS: Of 485 patients, 73.6% received AC, of which 25.5% received OXAC. Patients receiving AC were younger (median age 61 vs. 64; P=0.003) and had higher rates of total mesorectal excision (81.5% vs. 78.9%; P=0.049), but had similar high-risk features, performance status, clinical stage, margin status, preoperative carcinoembryonic antigen, and nCRT regimen. In univariate analysis, overall survival was improved with fluoropyrimidine AC compared with no AC or OXAC (P=0.049), but not disease-free survival (P=0.33). In multivariate analysis, any AC, fluoropyrimidine AC, or OXAC did not improve outcomes. After stratifying patients by the presence of high-risk features, elevated carcinoembryonic antigen, margin status, or preoperative clinical stage, we did not identify a group with improved outcomes following AC. CONCLUSIONS: In this multi-institutional cohort of yp stage II RC patients, we failed to identify a group that derives benefit from AC following nCRT. The addition of oxaliplatin did not appear to improve outcomes when compared with fluoropyrimidine alone.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia , Quimioterapia Adyuvante/mortalidad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Cuidados Posoperatorios , Neoplasias del Recto/tratamiento farmacológico , Terapia Recuperativa , Anciano , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Pronóstico , Neoplasias del Recto/patología , Neoplasias del Recto/terapia , Tasa de SupervivenciaRESUMEN
Male courtship display is common in many animals; in some cases, males engage in courtship indiscriminately, spending significant time and energy courting heterospecifics with whom they have no chance of mating or producing viable offspring. Due to high costs and few if any benefits, we might expect mechanisms to evolve to reduce such misdirected courtship (or 'reproductive interference'). In Habronattus jumping spiders, males frequently court heterospecifics with whom they do not mate or hybridize; females are larger and are voracious predators, posing a severe risk to males who court indiscriminately. In this study, we examined patterns of misdirected courtship in a natural community of four sympatric Habronattus species (H. clypeatus, H. hallani, H. hirsutus, and H. pyrrithrix). We used direct field observations to weigh support for two hypotheses (differential microhabitat use and species recognition signaling) to explain how these species reduce the costs associated with misdirected courtship. We show that, while the four species of Habronattus do show some differences in microhabitat use, all four species still overlap substantially, and in three of the four species individuals equally encountered heterospecifics and conspecifics. Males courted females at every opportunity, regardless of species, and in some cases, this led to aggression and predation by the female. These results suggest that, while differences in microhabitat use might reduce misdirected courtship to some extent, co-existence of these four species may be possible due to complex communication (i.e. species-specific elements of a male's courtship display). This study is the first to examine misdirected courtship in jumping spiders. Studies of misdirected courtship and its consequences in the field are limited and may broaden our understanding of how biodiversity is maintained within a community.
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Preferencia en el Apareamiento Animal/fisiología , Conducta Sexual Animal/fisiología , Arañas/genética , Agresión/fisiología , Animales , Evolución Biológica , Color , Cortejo , Femenino , Masculino , Reproducción/genética , Reproducción/fisiología , Especificidad de la EspecieRESUMEN
Individual foraging specialization describes the phenomenon where conspecifics within a population of generalists exhibit differences in foraging behavior, each specializing on different prey types. Individual specialization is widespread in animals, yet is understudied in invertebrates, despite potential impacts to food web and population dynamics. Sceliphron caementarium (Hymenoptera: Sphecidae) is an excellent system to examine individual specialization. Females of these mud dauber wasps capture and paralyze spiders which they store in mud nests to provision their offspring. Individuals may make hundreds of prey choices in their short lifespan and fully intact prey items can be easily excavated from their mud nests, where each distinct nest cell represents a discrete foraging bout. Using data collected from a single population of S. caementarium (where all individuals had access to the same resources), we found evidence of strong individual specialization; individuals utilized different resources (with respect to prey taxa, prey ecological guild, and prey size) to provision their nests. The extent of individual specialization differed widely within the population with some females displaying extreme specialization (taking only prey from a single species) while others were generalists (taking prey from up to 6 spider families). We also found evidence of temporal consistency in individual specialization over multiple foraging events. We discuss these findings broadly in the context of search images, responses to changing prey availability, and intraspecific competition pressure.
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BACKGROUND: The PROSPECT trial (N1048) is evaluating the selective use of chemoradiation in patients with cT2N1 and cT3N0-1 rectal cancer undergoing sphincter-sparing low anterior resection. We evaluated outcomes of PROSPECT-eligible and -ineligible patients from a multi-institutional database. PATIENTS AND METHODS: Data from patients with locally advanced rectal cancer who received chemoradiation and low anterior resection from 2005 to 2014 were retrospectively collected from 5 Canadian centers. Overall survival, disease-free survival (DFS), recurrence-free survival (RFS), and time to local recurrence (LR) were estimated using the Kaplan-Meier method, and a multivariate analysis was performed adjusting for prognostic factors. RESULTS: A total of 566 (37%) of 1531 patients met the PROSPECT eligibility criteria. Eligible patients were more likely to have better PS (P = .0003) and negative circumferential resection margin (P < .0001). PROSPECT eligibility was associated with improved DFS (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.61-0.91), overall survival (HR, 0.73; 95% CI, 0.57-0.95), and RFS (HR, 0.68; 95% CI, 0.54-0.86) in univariate analyses. In multivariate analysis, only RFS remained significantly improved for PROSPECT-eligible patients (HR, 0.75; 95% CI, 0.57-1.00, P = .0499). The 3-year DFS and freedom from LR for PROSPECT-eligible patients were 79.1% and 97.4%, respectively, compared to 71.1% and 96.8% for PROSPECT-ineligible patients. CONCLUSION: Real-world data corroborate the eligibility criteria used in the PROSPECT study; the criteria identify a subgroup of patients in whom risk of recurrence is lower and in whom selective use of chemoradiation should be actively examined.
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Adenocarcinoma/tratamiento farmacológico , Quimioterapia Adyuvante/métodos , Neoplasias del Recto/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/cirugía , Adulto , Anciano , Canadá , Ensayos Clínicos Fase II como Asunto , Ensayos Clínicos Fase III como Asunto , Terapia Combinada , Procedimientos Quirúrgicos del Sistema Digestivo , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias del Recto/mortalidad , Neoplasias del Recto/cirugía , Estudios RetrospectivosRESUMEN
BACKGROUND: Pathologic complete response (pCR) to neoadjuvant chemoradiation (CRT) for rectal cancer is associated with better long-term outcomes, and is used as an early indicator of response to novel agents. To assess the rate and predictors of pCR, we performed a retrospective multicenter study involving 5 Canadian cancer centers. PATIENTS AND METHODS: Cancer registries identified consecutive patients with locally advanced rectal adenocarcinoma from the Tom Baker Cancer Centre, Cross Cancer Institute, British Columbia Cancer Agency, Ottawa Hospital Cancer Centre, and the Dr H. Bliss Murphy Cancer Centre who received fluoropyrimidine-based CRT and had curative intent surgery from 2005 to 2012. Patient, tumor, and therapy characteristics were correlated with response. RESULTS: Of the 891 patients included, 885 patients had pCR data available. Of the included patients, 161 (18.2%) had a pCR to CRT, and 724 (81.8%) did not. Patients with a pCR had a lower pretreatment carcinoembryonic antigen (CEA) level, and higher hemoglobin level in univariate analysis. In multivariable analysis, statin use at baseline (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.02-2.92; P = .04), lower pretreatment CEA level (OR, 1.03; 95% CI, 1.01-1.06; P = .03), and distance closer to anal verge (OR, 1.07; 95% CI, 1.01-1.15; P = .04) were significant predictors of pCR. The 3-year disease-free survival was 86% in those with a pCR versus 62.5% in those without a pCR (P < .0001) and pCR was associated with improved overall survival (hazard ratio, 0.29; 95% CI, 0.17-0.51; P < .0001). CONCLUSION: Lower pretreatment CEA level, proximity to anal verge, and statin use are predictors of pCR in our large retrospective cohort. Clinical trials to investigate statins combined with neoadjuvant CRT might be warranted.
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Antígeno Carcinoembrionario/sangre , Quimioradioterapia/métodos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Terapia Neoadyuvante/métodos , Neoplasias del Recto/terapia , Canadá , Supervivencia sin Enfermedad , Humanos , Persona de Mediana Edad , Neoplasias del Recto/patología , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Patients with terminal deletions of chromosome 6q present with structural brain abnormalities including agenesis of corpus callosum, hydrocephalus, periventricular nodular heterotopia, and cerebellar malformations. The 6q27 region harbors genes that are important for the normal development of brain and delineation of a critical deletion region for structural brain abnormalities may lead to a better genotype-phenotype correlation. We conducted a detailed clinical and molecular characterization of seven unrelated patients with deletions involving chromosome 6q27. All patients had structural brain abnormalities. Using array comparative genomic hybridization, we mapped the size, extent, and genomic content of these deletions. The smallest region of overlap spans 1.7 Mb and contains DLL1, THBS2, PHF10, and C6orf70 (ERMARD) that are plausible candidates for the causation of structural brain abnormalities. Our study reiterates the importance of 6q27 region in normal development of brain and helps identify putative genes in causation of structural brain anomalies.
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Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Encéfalo/anomalías , Deleción Cromosómica , Cromosomas Humanos Par 6 , Encéfalo/patología , Preescolar , Bandeo Cromosómico , Hibridación Genómica Comparativa , Facies , Femenino , Genotipo , Humanos , Hibridación Fluorescente in Situ , Lactante , Recién Nacido , Imagen por Resonancia Magnética , FenotipoRESUMEN
Two methods are proposed for increasing the commercial value of wheat straw based on its chemical constituents. The first method involves the determination and extraction of the major organic components of wheat straw, and the second involves those found and extracted in the aqueous and viscous biooils derived from the straw by fast pyrolysis. We used pyrolysis-field ionization mass spectrometry to identify the fine chemicals, which have high commercial values. The most abundant organic compounds in the wheat straw and biooil used as precursors for green chemicals are N-heterocycles (16 to 29% of the Total Ion Intensities, TII) and fatty acids (19 to 26% of TIIs), followed by phenols and lignins (12 to 23% of TIIs). Other important precursors were carbohydrates and amino acids (1 to 8% TIIs), n-alkyl benzenes (3 to 5% of TIIs), and diols (4 to 9% TIIs). Steroids and flavonoids represented 1 to 5% of TIIs in the three materials. Examples of valuable chemical compounds that can be extracted from the wheat straw and biooils are m/z 256, 270, 278, 280, 282 and 284, which are the n-C16 and n-C17 fatty acids respectively, and the C18:3, C18:2 and C18:1 unsaturated fatty acids. In particular, the C18:2 (linoleic acid) is present at a concentration of 1.7% of TIIs. Pyrazole, pyrazine, pyridine, indoles, quinolines, carbazoles, and their identified derivatives are found in relatively high concentrations (1 to 8% of TIIs). Other useful compounds are sterols such as m/z 412 (stigmasterol), m/z 414 (ß-sitosterol), and steroids such m/z 394 (stigmastatriene), m/z 398 (stigmastene) and m/z 410 (stigmastadienone). Relative to the wheat straw, the relative concentration of all flavonoids such as m/z 222 (flavone) and m/z 224 (flavonone) doubled in the biooils. The conversion of wheat straw by fast pyrolysis, followed by chemical characterization with mass spectrometry, and extraction of fine chemicals, opens up new possibilities for increasing the monetary value of crop residues.
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Agricultura/métodos , Alimentación Animal/análisis , Espectrometría de Masa por Ionización de Electrospray/métodos , Triticum/química , Agricultura/economía , Alimentación Animal/economía , Aceites de Plantas/químicaRESUMEN
PURPOSE: Bone metastases occur in 65-75% of patients with metastatic breast cancer. These patients are at risk of developing skeletal-related events (SREs). SREs are defined as any pathological fracture, spinal cord compression, hypercalcemia, and surgery or radiation required for treatment of bone metastases. Bisphosphonates are used to prevent the development of SREs. The purpose of this study is to review the incidence of SREs in metastatic breast cancer patients with bony disease in Newfoundland and Labrador and to determine if there is an association between SREs and the type of bisphosphonate therapy given. METHODS: This retrospective chart review includes all metastatic breast cancer patients with bony disease treated at the Dr. H. Bliss Murphy Cancer Centre from 2008 to 2010. Patient demographics, treatment received, and treatment changes were collected. Patients at the Centre received bisphosphonate, pamidronate or zolendronic acid to prevent SREs. The prescribing pattern of bisphosphonates was collected. The occurrences of SREs were then compared to the type of treatment received. RESULTS: Sixty-five patients with breast cancer and bony metastasis were identified using the provincial tumor registry, three patients were excluded from the review as their charts could not be located. Following the initial diagnosis of bone metastasis, 8 patients (12.7%) were started on zolendronic acid, 50 patients (80.6%) were started on pamidronate, and 4 (6.4%) received no treatment. Six patients (75%) on zolendronic acid experienced one SRE; however, none experienced multiple SREs. Thirty-one patients (62%) on pamidronate experienced one SRE, and ten (20%) had multiple SREs. Of the 31 patients on pamidronate with an SRE, 4 (12.9%) were switched to zolendronic acid. Three of the four (75%) had multiple SREs despite treatment changes. Of the six patients on zolendronic acid with SREs, none were switched to pamidronate. CONCLUSION: Our results show that the majority of patients with breast cancer, who develop bony metastases in Newfoundland and Labrador, are initially treated with the bisphosphonate, pamidronate. Over 60% of these patients experienced at least one SRE, and 20% had more than two SREs. A small proportion of the patients were initially started on zolendronic acid, and this group had better outcomes with fewer SREs and none had more than two SREs. It appears that zolendronic acid is superior to pamidronate in preventing SREs; however, zolendronic acid is being used primarily as second-line in Newfoundland and Labrador.
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Conservadores de la Densidad Ósea/administración & dosificación , Enfermedades Óseas/prevención & control , Neoplasias Óseas/tratamiento farmacológico , Neoplasias de la Mama/complicaciones , Difosfonatos/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Óseas/etiología , Neoplasias Óseas/secundario , Neoplasias de la Mama/patología , Instituciones Oncológicas , Femenino , Fracturas Espontáneas/etiología , Fracturas Espontáneas/prevención & control , Humanos , Hipercalcemia/etiología , Hipercalcemia/prevención & control , Imidazoles/administración & dosificación , Persona de Mediana Edad , Pamidronato , Sistema de Registros , Estudios Retrospectivos , Compresión de la Médula Espinal/etiología , Compresión de la Médula Espinal/prevención & control , Ácido ZoledrónicoRESUMEN
Atrazine is one of the most commonly used herbicides in the United States. While effective on target plants, it has been associated with harmful health effects in non-target organisms such as fish, amphibians and mammals. In this study, growth effects on human liver cells were determined after exposure to increasing concentrations of this herbicide. Growth of immortalized human hepatoma HepG2 cells was inhibited by atrazine concentrations of 625 ppb after 72 h exposure and flow cytometry analysis demonstrated HepG2 cells exposed to 100 ppb atrazine accumulated in S phase after 48 h compared to untreated cells. Expression of cell cycle specific cyclin proteins was altered after atrazine exposure with cyclin E levels significantly decreased after a 24h exposure and cyclin B levels decreased after 48 h. This study demonstrates that relatively low levels of atrazine exposure can affect growth and lead to disruptions in the cell cycle regulation of immortalized human liver cells.