Explore the vast range of titles available.

miRNA, short non-coding RNA, are rapidly emerging as important regulators in cell homeostasis, as well as potential players in cellular degeneration. The latter has led to interest in them as both biomarkers and as potential therapeutics. Retinal ganglion cells (RGC), whose axons connect the eye to the brain, are central nervous system cells of great interest, yet their study is largely restricted to animals due to the difficulty in obtaining healthy human RGC. Using a CRISPR/Cas9-based reporter embryonic stem cell line, human RGC were generated and their miRNA profile characterized using NanoString miRNA assays. We identified a variety of retinal specific miRNA upregulated in ESC-derived RGC, with half of the most abundant miRNA also detectable in purified rat RGC. Several miRNA were however identified to be unique to RGC from human. The findings show which miRNA are abundant in RGC and the limited congruence with animal derived RGC. These data could be used to understand miRNA’s role in RGC function, as well as potential biomarkers or therapies in retinal diseases involving RGC degeneration.

As partisanship strengthens in the United States, unaffiliated voter registration is also increasing. We conducted an original survey experiment to understand voter registration choices among registered voters in Florida and North Carolina, two states with substantial shares of unaffiliated registrants and persistent partisan polarization, but with differing primary participation rules. Institutionally, Florida holds closed primaries where only those registered with a political party may participate in the respective primary for that party. North Carolina holds semi-closed primaries that allow those not registered with a political party (i.e., unaffiliated registrants) to vote in party primary elections. The results of our experiment demonstrate that institutional context matters. Specifically, informing respondents of primary participation rules shapes voter registration recommendations. Among registrants who identify as independents, exposure to Florida’s closed primary rule causes them to be more likely to recommend party registration, whereas awareness of the semi-closed North Carolina primary rule makes independents and partisans more likely to advise unaffiliated registration. However, in the absence of information explaining rules for primary participation, respondents are more likely to suggest that their friend register in alignment with their own political identity. In summary, our study provides valuable insights into how registration choices are conditioned by political identities and exposure to treatments that emphasize political conditions and primary participation rules.

Educated by Initiative moves beyond previous evaluations of public policy to emphasize the educational importance of the initiative process itself. Since a majority of ballots ultimately fail or get overturned by the courts, Smith and Tolbert suggest that the educational consequences of initiative voting may be more important than the outcomes of the ballots themselves. The result is a fascinating and thoroughly-researched book about how direct democracy teaches citizens about politics, voting, civic engagement and the influence of special interests and political parties. Designed to be accessible to anyone interested in the future of American democracy, the book includes boxes (titled \"What Matters\") that succinctly summarize the authors' data into easily readable analyses.

North Carolina offers its residents the opportunity to cast early in-person (EIP) ballots prior to Election Day, a practice known locally as “One-Stop” voting. Following a successful legal challenge to the state’s controversial 2013 Voter Information and Verification Act, North Carolina’s 100 counties were given wide discretion over the hours and locations of EIP voting for the 2016 General Election. This discretion yielded a patchwork of election practices across the state, providing us with a set of natural experiments to study the effect of changes in early voting hours on voter turnout. Drawing on individual-level voting records from the North Carolina State Board of Elections, our research design matches voters on race, party, and geography. We find little evidence that changes to early opportunities in North Carolina had uniform effects on voter turnout. Nonetheless, we do identify areas in the presidential battleground state where voters appear to have reacted to local changes in early voting availability, albeit not always in directions consistent with the existing literature. We suspect that effects of changes to early voting rules are conditional on local conditions, and future research on the effects of election law changes on turnout should explore these conditions in detail.

Dominant mutations or DNA amplification of tyrosine kinases are rare among the oncogenic alterations implicated in prostate cancer. We demonstrate that castration-resistant prostate cancer (CRPC) in men exhibits increased tyrosine phosphorylation, raising the question of whether enhanced tyrosine kinase activity is observed in prostate cancer in the absence of specific tyrosine kinase mutation or DNA amplification. We generated a mouse model of prostate cancer progression using commonly perturbed non-tyrosine kinase oncogenes and pathways and detected a significant up-regulation of tyrosine phosphorylation at the carcinoma stage. Phosphotyrosine peptide enrichment and quantitative mass spectrometry identified oncogene-specific tyrosine kinase signatures, including activation of EGFR, ephrin type-A receptor 2 (EPHA2), and JAK2. Kinase:substrate relationship analysis of the phosphopeptides also revealed ABL1 and SRC tyrosine kinase activation. The observation of elevated tyrosine kinase signaling in advanced prostate cancer and identification of specific tyrosine kinase pathways from genetically defined tumor models point to unique therapeutic approaches using tyrosine kinase inhibitors for advanced prostate cancer.

Src family kinases (SFKs) are pleiotropic activators that are responsible for integrating signal transduction for multiple receptors that regulate cellular proliferation, invasion, and metastasis in a variety of human cancers. Independent groups have identified increased expression of individual SFK members during prostate cancer progression, raising the question of whether SFKs display functional equivalence. Here, we show that Src kinase, followed by Fyn kinase and then Lyn kinase, exhibit ranked tumorigenic potential during both paracrine-induced and cell-autonomous-initiated prostate cancer. This quantitative variation in transformation potential appears to be regulated in part by posttranslational palmitoylation. Our data indicate that development of inhibitors against specific SFK members could provide unique targeted therapeutic strategies.

Since the onset in early 2020 of the COVID-19 pandemic in the United States, mail-in voting rates in states that have held elections have surged, presumably reflecting the fact that voting by mail is a relatively safe mode of ballot casting during a public health crisis. Matters of health notwithstanding, postal delivery disruptions can place mail-in ballots at risk of rejection on the grounds of lateness. With Maine as a case study, we show that, in the past four general elections, over 10% of vote-by-mail ballots arrived at local elections offices either on Election Day itself or one day earlier. Moreover, of the vote-by-mail ballots most vulnerable to postal delivery disruptions, a greater share of them were cast by unaffiliated voters and Democrats than by Republicans. Our results highlight the fragility of voting by mail in light of concerns about the reliability of the United States Postal Service. While existing research shows that the opportunity to vote by mail is neutral with respect to partisanship, our results highlight an aspect of mail-in balloting that nonetheless has a partisan hue—the extent to which vote-by-mail ballots are vulnerable to mail delays.

The introduction of high throughput sequence analysis in the past decade and the decrease in sequencing costs has made available an enormous amount of genomic data. These data have shaped the landscape of cancer genome, which encompasses mutations determining tumorigenesis, the signaling pathways involved in cancer growth, the tumor heterogeneity, and its role in development of metastases. Tumors develop acquiring a series of driver mutations over time. Of the many mutated genes present in cancer, only few specific mutations are responsible for invasiveness and metastatic potential, which, in many cases, have characteristic imaging appearance. Ten signaling pathways, each with targetable components, have been identified as responsible for cancer growth. Blockage of any of these pathways form the basis for molecular targeted therapies, which are associated with specific pattern of response and toxicities. Tumor heterogeneity, responsible for the different mutation pattern of metastases and primary tumor, has been classified in intratumoral, intermetastatic, intrametastatic, and interpatient heterogeneity, each with specific imaging correlates. The purpose of this article is to introduce the key components of the landscapes of cancer genome and their imaging counterparts, describing the types of mutations associated with tumorigenesis, the pathways of cancer growth, the genetic heterogeneity involved in metastatic disease, as well as the current challenges and opportunities for cancer genomics research.

Variation in the melanocortin-1 receptor (Mc1r) is associated with pigmentation diversity in wild and domesticated populations of vertebrates, including several species of birds. Among domestic bird species, pigmentation variation in the rock pigeon (Columbalivia) is particularly diverse. To determine the potential contribution of Mc1r variants to pigment diversity in pigeons, we sequenced Mc1r in a wide range of pigeon breeds and identified several single nucleotide polymorphisms, including a variant that codes for an amino acid substitution (Val85Met). In contrast to the association between Val85Met and eumelanism in other avian species, this change was associated with pheomelanism in pigeons. In vitro cAMP accumulation and protein expression assays revealed that Val85Met leads to decreased receptor function and reduced cell surface expression of the mutant protein. The reduced in vitro function is consistent with the observed association with reduced eumelanic pigmentation. Comparative genetic and cellular studies provide important insights about the range of mechanisms underlying diversity among vertebrates, including different phenotypic associations with similar mutations in different species.

Provisional ballots constitute a failsafe for voters who have their registration or voter identification questioned by poll workers. Scholars have yet to examine who is more likely to cast a provisional ballot, and more importantly, why some provisional ballots are rejected. We suggest that beyond individual-level factors, there are administrative reasons why some prospective voters are more likely to be required to cast provisional ballots than others, and why some provisional ballots are rejected. Drawing on county data collected by the U.S. Election Assistance Commission’s (EAC) biennial Election Administration and Voting Surveys (EAVS) from 2012 to 2016, and individual records of provisional ballots cast in the 2016 Presidential Election in North Carolina, we examine aggregate- and individual-level reasons to explain who casts provisional ballots and why some are rejected. Our findings raise normative questions concerning whether voters casting provisional ballots are treated equally under the law.