RESUMEN
Climate change presents a major threat to species distribution and persistence. Understanding what abiotic or biotic factors influence the thermal tolerances of natural populations is critical to assessing their vulnerability under rapidly changing thermal regimes. This study evaluates how body mass, local climate, and pathogen intensity influence heat tolerance and its population-level variation (SD) among individuals of the solitary bee Xenoglossa pruinosa. We assess the sex-specific relationships between these factors and heat tolerance given the differences in size between sexes and the ground-nesting behavior of the females. We collected X. pruinosa individuals from 14 sites across Pennsylvania, USA, that varied in mean temperature, precipitation, and soil texture. We measured the critical thermal maxima (CTmax) of X. pruinosa individuals as our proxy for heat tolerance and used quantitative PCR to determine relative intensities of three parasite groups-trypanosomes, Spiroplasma apis (mollicute bacteria), and Vairimorpha apis (microsporidian). While there was no difference in CTmax between the sexes, we found that CTmax increased significantly with body mass and that this relationship was stronger for males than for females. Air temperature, precipitation, and soil texture did not predict mean CTmax for either sex. However, population-level variation in CTmax was strongly and negatively correlated with air temperature, which suggests that temperature is acting as an environmental filter. Of the parasites screened, only trypanosome intensity correlated with heat tolerance. Specifically, trypanosome intensity negatively correlated with the CTmax of female X. pruinosa but not males. Our results highlight the importance of considering size, sex, and infection status when evaluating thermal tolerance traits. Importantly, this study reveals the need to evaluate trends in the variation of heat tolerance within and between populations and consider implications of reduced variation in heat tolerance for the persistence of ectotherms in future climate conditions.
RESUMEN
Honey bees are crucial pollinators for agricultural and natural ecosystems, but are experiencing heavy mortality in North America and Europe due to a complex suite of factors. Understanding the relative importance of each factor would enable beekeepers to make more informed decisions and improve assessment of local and regional habitat suitability. We used 3 years of Pennsylvania beekeepers' survey data to assess the importance of weather, topography, land use, and management factors on overwintering mortality at both apiary and colony levels, and to predict survival given current weather conditions and projected climate changes. Random Forest, a tree-based machine learning approach suited to describing complex nonlinear relationships among factors, was used. A Random Forest model predicted overwintering survival with 73.3% accuracy for colonies and 65.7% for apiaries where Varroa mite populations were managed. Growing degree days and precipitation of the warmest quarter of the preceding year were the most important predictors at both levels. A weather-only model was used to predict colony survival probability, and to create a composite map of survival for 1981-2019. Although 3 years data were likely not enough to adequately capture the range of possible climatic conditions, the model performed well within its constraints.
RESUMEN
Advances in surgical, radiation, and interventional radiology therapies carry a reduction in morbidity associated with therapy. Aggressive management of patients with oligometastatic non-small cell lung cancer offers the potential for improved disease-free survival and quality of life compared with traditional systemic therapy alone.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Calidad de Vida , Carcinoma de Pulmón de Células no Pequeñas/terapia , Supervivencia sin Enfermedad , Humanos , Neoplasias Pulmonares/terapia , Metástasis de la Neoplasia , Radiocirugia , Resultado del TratamientoRESUMEN
OBJECTIVE: HDR brachytherapy to the vaginal cuff using rigid intracavitary cylinders has a limited capacity to adapt to patient-specific anatomy. This study describes the use and dosimetry of a new method of anatomically conformal post-operative vaginal cuff HDR brachytherapy using an intra-vaginal balloon applicator. METHODS: Thirty consecutive patients with endometrial carcinoma underwent a hysterectomy and received adjuvant HDR brachytherapy in 6 weekly fractions using an intra-vaginal balloon. Optimal distension of the balloon to conform to the vaginal cuff was clinically determined to achieve complete balloon surface apposition with the vaginal mucosa and was confirmed radiographically. Radiation dose was prescribed to the vaginal mucosa and brachytherapy CT simulation was performed to optimize the irradiation dose in 3-D. RESULTS: 180 brachytherapy procedures were performed. The mean volume of balloon distension was 47.3 cc (range 20.8-83.8 cc; +/-11.3 cc). The mean dose from brachytherapy to the 2 cc volume of the bladder and rectum was 48.6% and 71.1% of the prescribed vaginal mucosal dose, respectively. Bladder and rectal doses increased as a function of balloon volume. 100% of the prescribed dose covered an average of 95.6% of the vaginal cuff. There were no acute complications or vaginal cuff recurrences at a mean follow-up of 13 months. CONCLUSIONS: Post-operative vaginal cuff HDR brachytherapy using an intra-vaginal balloon applicator which conforms to the individual patient's vaginal cuff provides excellent radiation dose coverage of the vaginal mucosa with acceptable doses to the bladder and rectum.
Asunto(s)
Braquiterapia/métodos , Neoplasias Endometriales/radioterapia , Adenocarcinoma/patología , Adenocarcinoma/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Braquiterapia/efectos adversos , Carcinoma Endometrioide/patología , Carcinoma Endometrioide/radioterapia , Cateterismo/métodos , Neoplasias Endometriales/patología , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Traumatismos por Radiación/etiología , Recto/efectos de la radiación , Vejiga Urinaria/efectos de la radiación , Vagina/anatomía & histologíaRESUMEN
We have shown that parthenolide, a sesquiterpene lactone, is a radiation sensitizer for human CGL1 hybrid cells that have constitutively activated NF-kappaB and wild-type p53. Since many malignant cells have nonfunctional p53, we investigated whether parthenolide could alter the X-ray sensitivity of PC-3 prostate cancer cells, a p53 null cell line with constitutively activated NF-kappaB. The addition of 5 microM parthenolide induced non-apoptotic cell death, inhibited PC-3 proliferation, and increased the population doubling time from 23+/-1 h to 49+/-4 h. Parthenolide also inhibited constitutive and radiation-induced NF-kappaB binding activity and enhanced the X-ray sensitivity of these p53 null PC-3 cells by a dose modification factor of 1.7. Cell cycle analysis of PC-3 cells treated with parthenolide showed only small alterations in G1 and G2/M cells, and these appeared to be insufficient to explain the observed radiosensitization. Split-dose studies using clinically relevant 2- and 4-Gy fractions demonstrated that parthenolide completely inhibited split-dose repair in PC-3 cells. We hypothesized that inhibition of NF-kappaB activity by parthenolide was responsible for the observed X-ray sensitization and inhibition of split-dose repair. To test this hypothesis, we knocked down the expression of NF-kappaB p65 protein, an active component of NF-kappaB in both PC-3 and CGL1 cells, by siRNA. Inhibition of NF-kappaB activity by knockdown of p65 increased radiation sensitivity and completely inhibited split-dose repair in both cell lines in a nearly identical manner as parthenolide treatment alone. Treating p65-depleted PC-3 cells with 5 microM parthenolide did not further increase their radiation sensitivity or the inhibition of split-dose repair. We propose that the suppression of radiation-induced NF-kappaB activity by parthenolide leads to X-ray sensitization through inhibition of split-dose repair in p53 null PC-3 prostate cancer cells.
Asunto(s)
FN-kappa B/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Sesquiterpenos/farmacología , Proteína p53 Supresora de Tumor/metabolismo , Antiinflamatorios no Esteroideos/farmacología , Ciclo Celular , Línea Celular Tumoral , Relación Dosis-Respuesta en la Radiación , Humanos , Masculino , Modelos Biológicos , ARN Interferente Pequeño/metabolismo , Tolerancia a Radiación , Factor de Transcripción ReIA/metabolismo , Rayos XRESUMEN
We examined the role of programmed cell death (PCD) pathways in retinal degeneration caused by a mutation in the norpA gene. norpA degeneration shows morphological hallmarks of programmed cell death, specifically cytoplasmic condensation and engulfment of the dying photoreceptor cells by neighboring retinal pigment cells. However, genetic mosaic analysis of adult photoreceptors lacking rpr, hid, and grim show that these PCD inducers are not required for norpA degeneration. We showed previously that ectopic expression of either rpr or hid triggers rapid PCD in adult photoreceptors, and this is completely suppressed by the coexpression of the baculoviral P35 caspase inhibitor. In contrast, expression of P35 does not suppress norpA retinal degeneration, although a small delay in the rate of degeneration is observed in low light-low temperature conditions. P35 does not alter the morphological characteristics of norpA cell death. Overexpression of the Drosophila inhibitor of apoptosis Diap1 or a dominant-negative form of the Dronc caspase, even when coexpressed with P35, does not dramatically alter the time course of norpA degeneration. These results establish that the pathways responsible for PCD in development do not play a major role in adult retinal degeneration caused by norpA.