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Current malaria treatments are threatened by drug resistance, and new drugs are urgently needed. In a phenotypic screen for new antimalarials, we identified (S)-SW228703 ((S)-SW703), a tyrosine amide with asexual blood and liver stage activity and a fast-killing profile. Resistance to (S)-SW703 is associated with mutations in the Plasmodium falciparum cyclic amine resistance locus (PfCARL) and P. falciparum acetyl CoA transporter (PfACT), similarly to several other compounds that share features such as fast activity and liver-stage activity. Compounds with these resistance mechanisms are thought to act in the ER, though their targets are unknown. The tyramine of (S)-SW703 is shared with some reported PfCARL-associated compounds; however, we observed that strict S-stereochemistry was required for the activity of (S)-SW703, suggesting differences in the mechanism of action or binding mode. (S)-SW703 provides a new chemical series with broad activity for multiple life-cycle stages and a fast-killing mechanism of action, available for lead optimization to generate new treatments for malaria.

Plasmodium falciparum requires a two-host system, moving between Anopheles mosquito and humans, to complete its life cycle. To overcome such dynamic growth conditions its histones undergo various post-translational modifications to regulate gene expression. The P. falciparum Bromodomain Protein 1 (PfBDP1) has been shown to interact with acetylated lysine modifications on histone H3 to regulate the expression of invasion-related genes. Here, we investigated the ability of the PfBDP1 bromodomain to interact with acetyllsyine modifications on additional core and variant histones. A crystal structure of the PfBDP1 bromodomain (PfBDP1-BRD) reveals it contains the conserved bromodomain fold, but our comparative analysis between the PfBDP1-BRD and human bromodomain families indicates it has a unique binding mechanism. Solution NMR spectroscopy and ITC binding assays carried out with acetylated histone ligands demonstrate that it preferentially recognizes tetra-acetylated histone H4, and we detected weaker interactions with multi-acetylated H2A.Z in addition to the previously reported interactions with acetylated histone H3. Our findings indicate PfBDP1 may play additional roles in the P. falciparum life cycle, and the distinctive features of its bromodomain binding pocket could be leveraged for the development of new therapeutic agents to help overcome the continuously evolving resistance of P. falciparum against currently available drugs.

Contributions: The main contribution is to share a series of practical methods that improve the writing quality of capstone reports. Background: The ability to write well is critical to the success of an engineering technology graduate. However, the evidence points to the fact that industries are disappointed with the quality of writing skills graduates demonstrate. Intended Outcomes: A faculty review of capstone reports showed little improvement in writing quality from the first course to the second in a two-semester capstone sequence. Therefore, the instructors explored what actions were needed to improve the writing quality of the capstone reports. Application Design: Several changes in the capstone courses were developed and implemented. The changes included: 1) using instructional technology as a scaffolding to help frame the writing required for the course and 2) engaging students in iterative writing with feedback. Findings: The assessment data showed a significant improvement, at the 5% level. The iterative process of writing and rewriting the report, coupled with frequent meetings with faculty mentors, proved to be a powerful combination for improving the writing process of the students.

The purpose of this study was to characterize a representative body of research to demonstrate the advantage of disseminating educational research in ways that reach the broadest audience. Using the Education Resources Information Center (ERIC) database, I compiled a set of research findings on a number of broad educational themes. Focusing on journal articles and reports, I examined the public availability of the publications, publication quality as determined by peer review, and authorship. In all, 65% of the journal articles were behind a paywall, and 35% were available either as PDFs or freely available on the publisher website; 61% of the peer-reviewed literature was locked behind a paywall. This study also examined a subset of reports—research studies not published in journals but issued by organizations, think tanks, or policy institutes; 27% of the reports were authored by institutions identified with a neoliberal or free-market ideology

This article explores how librarians and lecturers at the University of California, Berkeley, worked together to make their union more participatory in a context of increasing corporatization in public higher education. Written as a case study, we examine this ongoing revitalization process initiated by lecturers in the summer of 2016 and how it transformed librarian activism and bargaining strategy. For context, we also examine the history and unique nature of the University Council–American Federation of Teachers, the union representing both librarians and lecturers. We discuss why librarians had become ambivalent about their union and how an active group of librarians changed the culture in the organization and worked to bring members' voices into the 2018/2019 librarian contract negotiations. Engaging membership and encouraging participation required a group of committed organizers, with the support of paid union staff, to actively seek feedback from members, to communicate regularly, and to organize solidarity events. Throughout this process, the local worked to build coalitions with other campus unions, and members became increasingly aware of the important role unions play in protecting and advancing the mission of a public university and as a site for social justice activism.

We conducted a survey of the winners of University of California (UC) Berkeley’s Library Prize for Undergraduate Research (2003-2016) to learn about the long-term impact of undergraduate research projects on students, find out what winners gained from the experience, and compare their careers post-graduation with other students. Seventy-four winners responded and reported increased academic engagement during their undergraduate experience, and demonstrated greater than average academic achievement post-graduation. The winners became more confident of their research skills and their aptitude for post-graduate work as a result of winning. More than 3 times as many prize winners went on to graduate school as the typical UC graduate. We also examined usage statistics of winning papers that had been posted to UC’s open access publishing platform and observed that papers continue to be accessed by the general public years after students graduate.

The Berkeley Research Impact Initiative (BRII) was one of the first campus-based open access (OA) funds to be established in North America and one of the most active, distributing more than $244,000 to support University of California (UC) Berkeley authors. In April 2015, we conducted a qualitative study of 138 individuals who had received BRII funding to survey their opinions about the benefits and funding of open access. Most respondents believe their articles had a greater impact as open access, expect to tap multiple sources to fund open access fees, and support the UC Open Access Policy and its goal of making research public and accessible. Results of the survey and a discussion of their impact on the BRII program follow.

The Berkeley Research Impact Initiative (BRII) was one of the first campus-based open access (OA) funds to be established in North America and one of the most active, distributing more than $244,000 to support University of California (UC) Berkeley authors. In April 2015, we conducted a qualitative study of 138 individuals who had received BRII funding to survey their opinions about the benefits and funding of open access. Most respondents believe their articles had a greater impact as open access, expect to tap multiple sources to fund open access fees, and support the UC Open Access Policy and its goal of making research public and accessible. Results of the survey and a discussion of their impact on the BRII program follow.

The goal of this webliography is to provide an introduction to standards resources for librarians that support post-secondary engineering and technology programs, as well as engineering and technology faculty members and students. It serves as a reference on standards collection development and integrating standards information literacy into engineering and technology curricula. This webliography is a selective compilation of the following: major standards bodies that create or approve standards frequently used by engineers and technologists, standards database aggregators, web sites that provide free or low cost, full-text access to standards, and standards education resources. Only major standards bodies that operate in the U.S. or on an international level are incorporated, excluding non-U.S. national and regional bodies that create or coordinate standards activities in other countries. The standards education resources listed are appropriate for university-level students.

How might engineering technology students make use of patent information in the engineering design process? Librarians analyzed team project reports and personal reflections created by students in an undergraduate mechanical engineering technology design course, revealing that the students used patents to consider the patentability of their ideas, to explore the state of the art in given areas of technology, and to inspire creative problem solving. These results have implications for future patent-related instruction and for conducting information literacy outreach to engineering and engineering technology departments.

A poster presented at the Berlin 9 Open Access Conference, November 9-10, 2011 in Washington D.C.

Malaria caused by Plasmodium falciparum is a disease that is responsible for 880,000 deaths per year worldwide. Vaccine development has proved difficult and resistance has emerged for most antimalarial drugs. To discover new antimalarial chemotypes, we have used a phenotypic forward chemical genetic approach to assay 309,474 chemicals. Here we disclose structures and biological activity of the entire library-many of which showed potent in vitro activity against drug-resistant P. falciparum strains-and detailed profiling of 172 representative candidates. A reverse chemical genetic study identified 19 new inhibitors of 4 validated drug targets and 15 novel binders among 61 malarial proteins. Phylochemogenetic profiling in several organisms revealed similarities between Toxoplasma gondii and mammalian cell lines and dissimilarities between P. falciparum and related protozoans. One exemplar compound displayed efficacy in a murine model. Our findings provide the scientific community with new starting points for malaria drug discovery.

Viruses produce more viruses by manipulating the metabolic and replication systems of their host cells. Many have acquired metabolic genes from ancestral hosts and use the encoded enzymes to subvert host metabolism. The polyamine spermidine is required for bacteriophage and eukaryotic virus replication, and herein, we have identified and functionally characterized diverse phage- and virus-encoded polyamine metabolic enzymes and pathways. These include pyridoxal 5′-phosphate (PLP)-dependent ornithine decarboxylase (ODC), pyruvoyl-dependent ODC and arginine decarboxylase (ADC), arginase, S-adenosylmethionine decarboxylase (AdoMetDC/speD), spermidine synthase, homospermidine synthase, spermidine N-acetyltransferase, and N-acetylspermidine amidohydrolase. We identified homologs of the spermidine-modified translation factor eIF5a encoded by giant viruses of the Imitervirales. Although AdoMetDC/speD is prevalent among marine phages, some homologs have lost AdoMetDC activity and have evolved into pyruvoyl-dependent ADC or ODC. The pelagiphages that encode the pyruvoyl-dependent ADCs infect the abundant ocean bacterium Candidatus Pelagibacter ubique, which we have found encodes a PLP-dependent ODC homolog that has evolved into an ADC, indicating that infected cells would contain both PLP- and pyruvoyldependent ADCs. Complete or partial spermidine or homospermidine biosynthetic pathways are found encoded in the giant viruses of the Algavirales and Imitervirales, and in addition, some viruses of the Imitervirales can release spermidine from the inactive N-acetylspermidine. In contrast, diverse phages encode spermidine N-acetyltransferase that can sequester spermidine into its inactive N-acetyl form. Together, the virome-encoded enzymes and pathways for biosynthesis and release or biochemical sequestration of spermidine or its structural analog homospermidine consolidate and expand evidence supporting an important and global role of spermidine in virus biology [ABSTRACT FROM AUTHOR]