Su Shih's Copy of the "Letter on the Controversy over Seating Protocol"

This is the publisher's version, also available electronically from http://www.jstor.org/stable/20111205?seq=1#page_scan_tab_contents

PARP-1 regulates DNA repair factor availability.

PARP-1 holds major functions on chromatin, DNA damage repair and transcriptional regulation, both of which are relevant in the context of cancer. Here, unbiased transcriptional profiling revealed the downstream transcriptional profile of PARP-1 enzymatic activity. Further investigation of the PARP-1-regulated transcriptome and secondary strategies for assessing PARP-1 activity in patient tissues revealed that PARP-1 activity was unexpectedly enriched as a function of disease progression and was associated with poor outcome independent of DNA double-strand breaks, suggesting that enhanced PARP-1 activity may promote aggressive phenotypes. Mechanistic investigation revealed that active PARP-1 served to enhance E2F1 transcription factor activity, and specifically promoted E2F1-mediated induction of DNA repair factors involved in homologous recombination (HR). Conversely, PARP-1 inhibition reduced HR factor availability and thus acted to induce or enhance BRCA-ness . These observations bring new understanding of PARP-1 function in cancer and have significant ramifications on predicting PARP-1 inhibitor function in the clinical setting

Novel Oncogenic Transcription Factor Cooperation in RB-Deficient Cancer

The retinoblastoma tumor suppressor (RB) is a critical regulator of E2F-dependent transcription, controlling a multitude of protumorigenic networks including but not limited to cell-cycle control. Here, genome-wide assessment of E2F1 function after RB loss in isogenic models of prostate cancer revealed unexpected repositioning and cooperation with oncogenic transcription factors, including the major driver of disease progression, the androgen receptor (AR). Further investigation revealed that observed AR/E2F1 cooperation elicited novel transcriptional networks that promote cancer phenotypes, especially as related to evasion of cell death. These observations were reflected in assessment of human disease, indicating the clinical relevance of the AR/E2F1 cooperome in prostate cancer. Together, these studies reveal new mechanisms by which RB loss induces cancer progression and highlight the importance of understanding the targets of E2F1 function. SIGNIFICANCE: This study identifies that RB loss in prostate cancer drives cooperation between AR and E2F1 as coregulators of transcription, which is linked to the progression of advanced disease

The circadian cryptochrome, CRY1, is a pro-tumorigenic factor that rhythmically modulates DNA repair.

Mechanisms regulating DNA repair processes remain incompletely defined. Here, the circadian factor CRY1, an evolutionally conserved transcriptional coregulator, is identified as a tumor specific regulator of DNA repair. Key findings demonstrate that CRY1 expression is androgen-responsive and associates with poor outcome in prostate cancer. Functional studies and first-in-field mapping of the CRY1 cistrome and transcriptome reveal that CRY1 regulates DNA repair and the G2/M transition. DNA damage stabilizes CRY1 in cancer (in vitro, in vivo, and human tumors ex vivo), which proves critical for efficient DNA repair. Further mechanistic investigation shows that stabilized CRY1 temporally regulates expression of genes required for homologous recombination. Collectively, these findings reveal that CRY1 is hormone-induced in tumors, is further stabilized by genomic insult, and promotes DNA repair and cell survival through temporal transcriptional regulation. These studies identify the circadian factor CRY1 as pro-tumorigenic and nominate CRY1 as a new therapeutic target

EXPORTS Measurements and Protocols for the NE Pacific Campaign

EXport Processes in the Ocean from Remote Sensing (EXPORTS) is a large-scale NASA-led and NSF co-funded field campaign that will provide critical information for quantifying the export and fate of upper ocean net primary production (NPP) using satellite information and state of the art technology

Enhancing Student Success in Introductory Biology through Cross-Disciplinary Research

Introductory Biology courses are “gateway” courses for many majors, and, as in many colleges and universities, attrition and achievement problems are a barrier to student success and program effectiveness. Class sizes have been steadily rising in elementary, high school, and college classrooms. We aim to study how this impacts student achievement

From Gatekeeper to Gateway: Improving Student Success in an Introductory Biology Course

Introductory science, math, and engineering courses often have problems related to student engagement, achievement, and course completion. To begin examining these issues in greater depth, this pilot study compared student engagement, achievement, and course completion in a small and large section of an introductory biology class. Results based on t-tests indicate that students in the small section of the course were more engaged and had higher achievement scores than students in the large section. Additionally, students in the small section were more likely to complete the course than students in the large section. Although further research is needed, reduced class size has the potential to be an effective strategy for improving student engagement, achievement, and course completion in an introductory biology course that has too often been a gatekeeper instead of a gateway for students who intend to be science, technology, engineering, and math majors

Enhancing Student Success in Introductory Biology through Cross-Disciplinary Research

Introductory Biology courses are “gateway” courses for many majors, and, as in many colleges and universities, attrition and achievement problems are a barrier to student success and program effectiveness. Class sizes have been steadily rising in elementary, high school, and college classrooms. We aim to study how this impacts student achievement

Assessing the Coverage of US Cancer Center Primary Catchment Areas.

Background: Cancer centers are expected to engage communities and reduce the burden of cancer in their catchment areas. However, the extent to which cancer centers adequately reach the entire US population is unknown. Methods: We surveyed all members of the Association of American Cancer Institutes (N ¼ 102 cancer centers) to document and map each cancer center’s primary catchment area. Catchment area descriptions were aggregated to the county level. Catchment area coverage scores were calculated for each county and choropleths generated representing coverage across the US. Similar analyses were used to overlay US population density, cancer incidence, and cancer-related mortality compared with each county’s cancer center catchment area coverage. Results: Roughly 85% of US counties were included in at least one cancer center’s primary catchment area. However, 15% of US counties, or roughly 25 million Americans, do not reside in a catchment area. When catchment area coverage was integrated with population density, cancer incidence, and cancer-related mortality metrics, geographical trends in both over- and undercoverage were apparent. Conclusions: Geographic gaps in cancer center catchment area coverage exist and may be propagating cancer disparities. Efforts to ensure coverage to all Americans should be a priority of cancer center leadership. Impact: This is the first known geographic analysis and interpretation of the primary catchment areas of all US-based cancer centers and identifies key geographic gaps important to target for disparities reduction