Inhibitor library screening identifies ispinesib as a new potential chemotherapeutic agent for pancreatic cancers.

Screening custom-made libraries of inhibitors may reveal novel drugs for treating pancreatic cancer. In this manner, we identified ispinesib as a candidate and attempted to determine its clinical efficacy and the biological significance of its functional target Eg5 in pancreatic cancer. One hundred compounds in our library were screened for candidate drugs using cell cytotoxicity assays. Ispinesib was found to mediate effective antitumor effects in pancreatic cancer. The clinical significance of the expression of the ispinesib target Eg5 was investigated in 165 pancreatic cancer patients by immunohistochemical staining and in Eg5-positive pancreatic cancer patient-derived xenograft (PDX) mouse models. Patients with Eg5-positive tumors experienced significantly poorer clinical outcomes than those not expressing Eg5 (overall survival; P < .01, recurrence-free survival; P < .01). Ispinesib or Eg5 inhibition with specific siRNA significantly suppressed cell proliferation and induced apoptosis in pancreatic cancer cell lines. Mechanistically, ispinesib acted by inducing incomplete mitosis with nuclear disruption, resulting in multinucleated monoastral spindle cells. In the PDX mouse model, ispinesib dramatically reduced tumor growth relative to vehicle control (652.2 mm3 vs 18.1 mm3 in mean tumor volume, P < .01 by ANOVA; 545 mg vs 28 mg in tumor weight, P < .01, by ANOVA). Ispinesib, identified by inhibitor library screening, could be a promising novel therapeutic agent for pancreatic cancer. The expression of its target Eg5 is associated with poorer postoperative prognosis and is important for the clinical efficacy of ispinesib in pancreatic cancer.

Utilization of a Librarian in a Pharmacy Laboratory Course.

This report describes utilization of a librarian in a pharmacy laboratory course over two academic years. Library instruction evolved from a simple drug information review session to case-based, hands-on instruction, collaboratively taught with pharmacy faculty. Additionally, LibChat, an online chat service, was piloted in the pharmacy laboratory course so the librarian could be available to students at their point-of-need. Development of the drug information review sessions across both years, student utilization of LibChat, lessons learned, and ideas for improvement for future iterations of the course are described.

Effects of accreditation on United States and Canadian veterinary college libraries in the nineteenth and twentieth centuries.

OBJECTIVE: The authors' objective was to document the effects of evolving veterinary accreditation standards on the development of currently existing accredited US and Canadian veterinary school libraries in the late nineteenth and twentieth centuries. METHODS: We gathered historical standards that major veterinary accreditation agencies developed with respect to libraries and library services. Historical background on college libraries, their facilities, services, and personnel via surveys, literature searches, and archival documents was also collected. We then correlated the evolving standards with each library's development. RESULTS: There was a marked correlation between the prevailing accreditation standards and library development, particularly during the post-World War II era and through the mid-1980s. These impacts-which included new and separate facilities, hiring of professional librarians, and additional open hours-affected not only the twenty new developing veterinary schools, but also the libraries of the preexisting colleges. CONCLUSIONS: Professional veterinary accrediting standards were an important influence on the evolution of veterinary school libraries, particularly during the years of major growth in the number of new veterinary colleges in the United States and Canada. In the 1990s and beyond, both libraries and accreditation standards continue to evolve in response to changes in technology, economics, publishing methods, and more. This latter is a story yet to be told.

Janet-Schwartz-Ellenberger: the history of a triangular relationship through their unpublished correspondence (1926-48).

Leonhard Schwartz's importance in the history of psychology has probably not been fully appreciated, and this article is dedicated to the life and work of the Basel neurologist. It highlights the triangular relationship he maintained for 20 years with Pierre Janet, of whom he was a disciple, and Henri F. Ellenberger, to whom he passed on his passion for Janet's oeuvre.

Public Library Programs and Accommodations for Deaf and Hard-of-Hearing Children in the United States†.

In today's public libraries, children's librarians are challenged to provide inclusive programming that welcomes all individuals, including deaf and hard-of-hearing children at risk for delayed reading and literacy development. This study, using quantitative survey data and qualitative interview methods, investigated the programs and accommodations public libraries provide for deaf and hard-of-hearing children, the impetus for providing these programs, and the training required. Nearly 500 public libraries in the United States with service areas greater than 100,000 patrons were invited to participate in an online survey. Fifty-nine librarians completed the survey and 11 participated in an additional telephone interview. Results indicated less than half of the libraries surveyed provided services for deaf and hard-of-hearing children. Nearly all of the programs offered were inclusive; among the accommodations provided were books with sign language and sign language interpreters. Training was the most common limitation facing librarians in their role as community partners in the literacy development of deaf and hard-of-hearing children.

Information literacy instruction for pharmacy students: a pharmacy librarian reflects on a year of teaching.

Librarians have ever-expanding teaching responsibilities in many academic disciplines. Assessment of learning outcomes requires longitudinal evaluation to measure true retention of skills and knowledge. This is especially important in the health sciences, including pharmacy, where librarians take an active role in teaching students to help prepare them for a profession in which solid information literacy skills are required to safely and effectively provide evidence-based care to patients. In this commentary, I reflect on a year of teaching in a pharmacy program and consider the outcomes of my instruction, areas for improvement, student retention of learning, assessment challenges, faculty-librarian collaboration, and continued support for library instruction in the pharmacy curriculum.

phpMs: A PHP-Based Mass Spectrometry Utilities Library.

The recent establishment of cloud computing, high-throughput networking, and more versatile web standards and browsers has led to a renewed interest in web-based applications. While traditionally big data has been the domain of optimized desktop and server applications, it is now possible to store vast amounts of data and perform the necessary calculations offsite in cloud storage and computing providers, with the results visualized in a high-quality cross-platform interface via a web browser. There are number of emerging platforms for cloud-based mass spectrometry data analysis; however, there is limited pre-existing code accessible to web developers, especially for those that are constrained to a shared hosting environment where Java and C applications are often forbidden from use by the hosting provider. To remedy this, we provide an open-source mass spectrometry library for one of the most commonly used web development languages, PHP. Our new library, phpMs, provides objects for storing and manipulating spectra and identification data as well as utilities for file reading, file writing, calculations, peptide fragmentation, and protein digestion as well as a software interface for controlling search engines. We provide a working demonstration of some of the capabilities at http://pgb.liv.ac.uk/phpMs .

Reverse and Random Decoy Methods for False Discovery Rate Estimation in High Mass Accuracy Peptide Spectral Library Searches.

Spectral library searching (SLS) is an attractive alternative to sequence database searching (SDS) for peptide identification due to its speed, sensitivity, and ability to include any selected mass spectra. While decoy methods for SLS have been developed for low mass accuracy peptide spectral libraries, it is not clear that they are optimal or directly applicable to high mass accuracy spectra. Therefore, we report the development and validation of methods for high mass accuracy decoy libraries. Two types of decoy libraries were found to be suitable for this purpose. The first, referred to as Reverse, constructs spectra by reversing a library's peptide sequences except for the C-terminal residue. The second, termed Random, randomly replaces all non-C-terminal residues and either retains the original C-terminal residue or replaces it based on the amino-acid frequency of the library's C-terminus. In both cases the m/z values of fragment ions are shifted accordingly. Determination of FDR is performed in a manner equivalent to SDS, concatenating a library with its decoy prior to a search. The utility of Reverse and Random libraries for target-decoy SLS in estimating false-positives and FDRs was demonstrated using spectra derived from a recently published synthetic human proteome project (Zolg, D. P.; et al. Nat. Methods 2017, 14, 259-262). For data sets from two large-scale label-free and iTRAQ experiments, these decoy building methods yielded highly similar score thresholds and spectral identifications at 1% FDR. The results were also found to be equivalent to those of using the decoy-free PeptideProphet algorithm. Using these new methods for FDR estimation, MSPepSearch, which is freely available search software, led to 18% more identifications at 1% FDR and 23% more at 0.1% FDR when compared with other widely used SDS engines coupled to postprocessing approaches such as Percolator. An application of these methods for FDR estimation for the recently reported "hybrid" library search (Burke, M. C.; et al. J. Proteome Res. 2017, 16, 1924-1935) method is also made. The application of decoy methods for high mass accuracy SLS permits the merging of these results with those of SDS, thereby increasing the assignment of more peptides, leading to deeper proteome coverage.

[Not Available] / Randnotizen als Lebensspuren?

Are marginal notes marginal? Backed by a book from the private library of Emil von Behring the paper reflects whether annotations are peripheral sources or whether they can give some hints concerning biographical details. Behring's traces of reading are exposed and discussed by using the example of Otto Rot's Arzneimittel der heutigen Medicin (1877). The marginal notes demonstrate Behring's intensive work on hypnotics, sedativs, and analgetics which were possibly used for the therapy of others or himself. The findings will be compared to other sources of Behring's personal papers.

High-Throughput Screening for Identification of Blood-Brain Barrier Integrity Enhancers: A Drug Repurposing Opportunity to Rectify Vascular Amyloid Toxicity.

The blood-brain barrier (BBB) is a dynamic interface that maintains brain homeostasis and protects it from free entry of chemicals, toxins, and drugs. The barrier function of the BBB is maintained mainly by capillary endothelial cells that physically separate brain from blood. Several neurological diseases, such as Alzheimer's disease (AD), are known to disrupt BBB integrity. In this study, a high-throughput screening (HTS) was developed to identify drugs that rectify/protect BBB integrity from vascular amyloid toxicity associated with AD progression. Assessing Lucifer Yellow permeation across in-vitro BBB model composed from mouse brain endothelial cells (bEnd3) grown on 96-well plate inserts was used to screen 1280 compounds of Sigma LOPAC®1280 library for modulators of bEnd3 monolayer integrity. HTS identified 62 compounds as disruptors, and 50 compounds as enhancers of the endothelial barrier integrity. From these 50 enhancers, 7 FDA approved drugs were identified with EC50 values ranging from 0.76-4.56 µM. Of these 7 drugs, 5 were able to protect bEnd3-based BBB model integrity against amyloid toxicity. Furthermore, to test the translational potential to humans, the 7 drugs were tested for their ability to rectify the disruptive effect of Aß in the human endothelial cell line hCMEC/D3. Only 3 (etodolac, granisetron, and beclomethasone) out of the 5 effective drugs in the bEnd3-based BBB model demonstrated a promising effect to protect the hCMEC/D3-based BBB model integrity. These drugs are compelling candidates for repurposing as therapeutic agents that could rectify dysfunctional BBB associated with AD.

What Does It Mean to be Central? A Botanical Geography of Paris 1830-1848.

This paper focuses on the geography of the botanical community in Paris, under the July Monarchy (1830-1848). At that time, the Muséum d'Histoire naturelle (MHN) was at its institutional acme and, under the impulse of François Guizot, its budget was increasing dramatically. However, closer attention to manuscript sources (correspondence, travel diaries) reveals that the botanists of the time favoured other private institutions, located both on the Right and Left Banks of the Seine. The MHN was prestigious for its collections and professors but it was relatively remote from the centre of Paris, and its plant samples were sometimes difficult to access. Several other first-class private herbaria granted liberal access to botanists: those of Jacques Gay, Phillip Barker Webb, and Benjamin Delessert. Thanks to their wealth, these plant amateurs had ownership of historical herbaria consisting of species types alongside rich botanical libraries. Botanists visiting Paris from foreign countries or other provinces of France also spent some time studying less general plant collections, like those of Count Jaubert, or specialized collections, like Montagne's or Léveillé's on cryptogams. Other botanists also enjoyed renown at the time, although they published little, if anything (like Maire). Living in crammed apartments, literally in the middle of their plant samples, these botanists were key nodes in botanical networks, although they had no relation with the prestigious MHN.