The Effect of Various Stratification Lengths on Seed Sources of Ambrosia artemisiifolia Across Latitudes

Faculty advisor: David A. MoellerSeeds dormancy, a period of ceased physiological activity, is an adaptive trait promoting survival of seeds. Many plants exhibit different germination rates when seeds from various locations where seeds exposed to winter length and temperatures of their origins, are treated to equal amount of cold stratification length. This particular trait is expressed in common ragweed (Ambrosia artemisiifolia). Ragweed has high reproduction of dormant seeds that persist in the soil for many years while maintaining germination ability. Seeds are dependent on environmental conditions such as day length, temperature and humidity to break seed dormancy. That way, the dependence of seeds on environmental condition acts as a monitor system to determine the optimal germination timing and avoid improper environmental conditions. One of the most crucial environmental conditions for ragweed seeds is stratification or a period of cold temperatures, which is the first process that induces the dormancy and later promotes germination. Ragweed seeds collected from various locations corresponding to different latitudes may have different germination rates because of different temperatures and stratification from their own habitats. A study by Sorenson et al. (1990) indicated northern seeds of species western larch (Larix occidentalis Nutt.) have higher germination rates under longer stratification lengths. In the other hand, a study by Karlsson et al. (2007) indicated South African, where maintain high temperatures, seeds of species Papaver aculeatum have higher germination rates under warmer stratification. Accordingly, ragweed seeds from northern locations may require longer stratification and colder temperature to break dormancy because of its strong dormant. By contrast, seeds from southern locations may not require such long periods of stratification for germination because they lack extended winters. As difference in germination rates from different seed populations can be evident in response to various stratification lengths with fixed temperature, in this experiment I investigated the effect of different stratification lengths on germination rates of seeds from populations with different winter length.This research was supported by the Undergraduate Research Opportunities Program (UROP)

Harsh parenting among veterans: parents' military-related PTSD, mentalization, and pre-military trauma

ObjectivesVeteran parents experiencing posttraumatic stress disorder (PTSD) may resort to harsh parenting. The indirect pathway from parental military-related PTSD to harsh parenting, and the moderating role of parents' pre-military trauma histories, has been less explored. Informed by mentalization theory, as well as trauma-sensitive and posttraumatic growth perspectives, we aim to explore the associations between veteran parents' military-related PTSD, mentalization, harsh parenting, and prior trauma before military service.MethodsData were collected from an online research panel of 509 veteran parents with children under 10. We employed Structural Equation Models to test indirect and moderating effects.ResultsWe identified an indirect effect of parental pre-mentalization from military PTSD to harsh parenting [corporal punishment: b = 0.35, p < 0.001, 95% CI (0.23, 0.46); psychological aggression: b = 0.14, p < 0.001, 95% CI (0.09, 0.19)]. Multi-group analysis on four parent groups (parents with only pre-military physical trauma, parents with only pre-military psychological trauma, parents with both pre-military physical and psychological trauma, and parents with no pre-military physical or psychological trauma) highlighted differences in these associations, particularly between parents with only pre-military physical trauma and those without any physical and psychological trauma. The military-related PTSD effects on psychological aggression, corporal punishment, and pre-mentalization were all significantly higher for parents without pre-military physical and psychological trauma.ConclusionModifying parents' interpretation of their child's mental states can potentially counteract the effects of veterans' military PTSD on harsh parenting. Family-based programs should be created considering veteran parents' pre-military trauma histories

Advances in modeling the immune microenvironment of colorectal cancer

Colorectal cancer (CRC) is the third most common cancer and second leading cause of cancer-related death in the US. CRC frequently metastasizes to the liver and these patients have a particularly poor prognosis. The infiltration of immune cells into CRC tumors and liver metastases accurately predicts disease progression and patient survival. Despite the evident influence of immune cells in the CRC tumor microenvironment (TME), efforts to identify immunotherapies for CRC patients have been limited. Here, we argue that preclinical model systems that recapitulate key features of the tumor microenvironment-including tumor, stromal, and immune cells; the extracellular matrix; and the vasculature-are crucial for studies of immunity in the CRC TME and the utility of immunotherapies for CRC patients. We briefly review the discoveries, advantages, and disadvantages of curren

Differences in Disease Severity but Similar Telomere Lengths in Genetic Subgroups of Patients with Telomerase and Shelterin Mutations

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Identification of a Blood-Based Protein Biomarker Panel for Lung Cancer Detection

Lung cancer is the deadliest cancer worldwide, mainly due to its advanced stage at the time of diagnosis. A non-invasive method for its early detection remains mandatory to improve patients’ survival. Plasma levels of 351 proteins were quantified by Liquid Chromatography-Parallel Reaction Monitoring (LC-PRM)-based mass spectrometry in 128 lung cancer patients and 93 healthy donors. Bootstrap sampling and least absolute shrinkage and selection operator (LASSO) penalization were used to find the best protein combination for outcome prediction. The PanelomiX platform was used to select the optimal biomarker thresholds. The panel was validated in 48 patients and 49 healthy volunteers. A 6-protein panel clearly distinguished lung cancer from healthy individuals. The panel displayed excellent performance: area under the receiver operating characteristic curve (AUC) = 0.999, positive predictive value (PPV) = 0.992, negative predictive value (NPV) = 0.989, specificity = 0.989 and sensitivity = 0.992. The panel detected lung cancer independently of the disease stage. The 6-protein panel and other sub-combinations displayed excellent results in the validation dataset. In conclusion, we identified a blood-based 6-protein panel as a diagnostic tool in lung cancer. Used as a routine test for high- and average-risk individuals, it may complement currently adopted techniques in lung cancer screening.publishedVersio

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

The ALMA Interferometric Pipeline Heuristics

We describe the calibration and imaging heuristics developed and deployed in the ALMA interferometric data processing pipeline, as of ALMA Cycle 9. The pipeline software framework is written in Python, with each data reduction stage layered on top of tasks and toolkit functions provided by the Common Astronomy Software Applications package. This framework supports a variety of tasks for observatory operations, including science data quality assurance, observing mode commissioning, and user reprocessing. It supports ALMA and VLA interferometric data along with ALMA and NRO45m single dish data, via different stages and heuristics. In addition to producing calibration tables, calibrated measurement sets, and cleaned images, the pipeline creates a WebLog which serves as the primary interface for verifying the data quality assurance by the observatory and for examining the contents of the data by the user. Following the adoption of the pipeline by ALMA Operations in 2014, the heuristics have been refined through annual development cycles, culminating in a new pipeline release aligned with the start of each ALMA Cycle of observations. Initial development focused on basic calibration and flagging heuristics (Cycles 2-3), followed by imaging heuristics (Cycles 4-5), refinement of the flagging and imaging heuristics with parallel processing (Cycles 6-7), addition of the moment difference analysis to improve continuum channel identification (2020 release), addition of a spectral renormalization stage (Cycle 8), and improvement in low SNR calibration heuristics (Cycle 9). In the two most recent Cycles, 97% of ALMA datasets were calibrated and imaged with the pipeline, ensuring long-term automated reproducibility. We conclude with a brief description of plans for future additions, including self-calibration, multi-configuration imaging, and calibration and imaging of full polarization data.Comment: accepted for publication by Publications of the Astronomical Society of the Pacific, 65 pages, 20 figures, 10 tables, 2 appendice

Is Genetic Background Important in Lung Cancer Survival?

BACKGROUND:In lung cancer, a patient's survival is poor with a wide variation in survival within the stage of disease. The aim of this study was to investigate the familial concordance in lung cancer survival by means of analyses of pairs with different degrees of familial relationships. METHODS:Our population-based Swedish family database included three million families and over 58,100 lung cancer patients. We modelled the proband (parent, sibling, spouse) survival utilizing a multivariate proportional hazard (Cox) model adjusting for possible confounders of survival. Subsequently, the survival in proband's relative (child, sibling, spouse) was analysed with a Cox model. FINDINGS:By use of Cox modelling with 5 years follow-up, we noted a decreased hazard ratio for death in children with good parental survival (Hazard Ratio [HR] = 0.71, 95% CI = 0.51 to 0.99), compared to those with poor parental survival. Also for siblings, a very strong protective effect was seen (HR = 0.14, 95% CI = 0.030 to 0.65). Finally, in spouses no correlation in survival was found. INTERPRETATION:Our findings suggest that genetic factors are important in lung cancer survival. In a clinical setting, information on prognosis in a relative may be vital in foreseeing the survival in an individual newly diagnosed with lung cancer. Future molecular studies enhancing the understanding of the underlying mechanisms and pathways are needed

Medulloblastoma Exome Sequencing Uncovers Subtype-Specific Somatic Mutations

Medulloblastomas are the most common malignant brain tumors in children1. Identifying and understanding the genetic events that drive these tumors is critical for the development of more effective diagnostic, prognostic and therapeutic strategies. Recently, our group and others described distinct molecular subtypes of medulloblastoma based on transcriptional and copy number profiles2–5. Here, we utilized whole exome hybrid capture and deep sequencing to identify somatic mutations across the coding regions of 92 primary medulloblastoma/normal pairs. Overall, medulloblastomas exhibit low mutation rates consistent with other pediatric tumors, with a median of 0.35 non-silent mutations per megabase. We identified twelve genes mutated at statistically significant frequencies, including previously known mutated genes in medulloblastoma such as CTNNB1, PTCH1, MLL2, SMARCA4 and TP53. Recurrent somatic mutations were identified in an RNA helicase gene, DDX3X, often concurrent with CTNNB1 mutations, and in the nuclear co-repressor (N-CoR) complex genes GPS2, BCOR, and LDB1, novel findings in medulloblastoma. We show that mutant DDX3X potentiates transactivation of a TCF promoter and enhances cell viability in combination with mutant but not wild type beta-catenin. Together, our study reveals the alteration of Wnt, Hedgehog, histone methyltransferase and now N-CoR pathways across medulloblastomas and within specific subtypes of this disease, and nominates the RNA helicase DDX3X as a component of pathogenic beta-catenin signaling in medulloblastoma