Allenes, Alkenes & Alkynes: My Piece of the π …in Water at Room Temperature…

I. An environmentally responsible, mild method for the synthesis of functionalized 1,3-butadienes is presented. It utilizes allenic esters of varying substitution patterns, as well as a wide range of boron-based nucleophiles under palladium catalysis, generating sp−sp2, sp2−sp2, and sp2−sp3 bonds. Functional group tolerance measured via robustness screening, along with room temperature and aqueous reaction conditions highlight the methodology’s breadth and potential utility in synthesis.II. A mild method for the synthesis of highly functionalized [3]–[6]dendralenes is reported, representing a general strategy to diversely substituted higher homologues of the dendralenes. The methodology utilizes allenoates bearing various substitution patterns, along with a wide range of boron and alkenyl nucleophiles that couple under palladium catalysis leading to sp-, sp2-, and sp3-substituted arrays. Regioselective transformations of the newly formed unsymmetrical dendralene derivatives are demonstrated. The use of micellar catalysis, where water is the global reaction medium, and room temperature reaction conditions, highlights the green nature of this technology.III. A copper-catalyzed oxidative cleavage of electron-rich olefins into their corresponding carbonyl derivatives is described as an alternative to ozonolysis. The scope includes various precursors to aryl ketone derivatives, as well as oxidations of enol ethers bearing atypical alkyl and dialkyl substitution, the first of their kind among such metal catalyzed alkene cleavage reactions. The use of an inexpensive copper salt, room temperature conditions, an aerobic atmosphere, and water as the global reaction medium highlight the green features of this new method. Associated mechanistic investigations are also presented

The Tem1 Small GTPase Controls Actomyosin and Septin Dynamics during Cytokinesis

Cytokinesis in budding yeast involves an actomyosin-based ring which assembles in a multistepped fashion during the cell cycle and constricts during cytokinesis. In this report, we have investigated the structural and regulatory events that occur at the onset of cytokinesis. The septins, which form an hour-glass like structure during early stages of the cell cycle, undergo dynamic rearrangements prior to cell division: the hourglass structure splits into two separate rings. The contractile ring, localized between the septin double rings, immediately undergoes contraction. Septin ring splitting is independent of actomyosin ring contraction as it still occurs in mutants where contraction fails. We hypothesize that septin ring splitting may remove a structural barrier for actomyosin ring to contract. Because the Tem1 small GTPase (Tem1p) is required for the completion of mitosis, we investigated its role in regulating septin and actomyosin ring dynamics in the background of the net1-1 mutation, which bypasses the anaphase cell cycle arrest in Tem1-deficient cells. We show that Tem1p plays a specific role in cytokinesis in addition to its function in cell cycle progression. Tem1p is not required for the assembly of the actomyosin ring but controls actomyosin and septin dynamics during cytokinesis

Antitumor activity of an anti-CD98 antibody.

CD98 is expressed on several tissue types and specifically upregulated on fast-cycling cells undergoing clonal expansion. Various solid (e.g., nonsmall cell lung carcinoma) as well as hematological malignancies (e.g., acute myeloid leukemia) overexpress CD98. We have identified a CD98-specific mouse monoclonal antibody that exhibits potent preclinical antitumor activity against established lymphoma tumor xenografts. Additionally, the humanized antibody designated IGN523 demonstrated robust tumor growth inhibition in leukemic cell-line derived xenograft models and was as efficacious as standard of care carboplatin in patient-derived nonsmall lung cancer xenografts. In vitro studies revealed that IGN523 elicited strong ADCC activity, induced lysosomal membrane permeabilization and inhibited essential amino acid transport function, ultimately resulting in caspase-3 and -7-mediated apoptosis of tumor cells. IGN523 is currently being evaluated in a Phase I clinical trial for acute myeloid leukemia (NCT02040506). Furthermore, preclinical data support the therapeutic potential of IGN523 in solid tumors

Collaboration between Librarians and Learning Technologists to enhance the learning of health sciences students.

Collaboration between Librarians and Learning Technologists at Bournemouth University (BU) has been stimulated and cemented by Pathfinder funding from the Higher Education Academy. This paper will consider four case studies collected as part of the eRes Project that describe the use of Web 2.0 technologies in the School of Health and Social Care at BU. The project aimed to enhance the student learning experience in an increasingly electronic environment. This was achieved by developing and disseminating innovative pedagogical frameworks, bringing together learning activities and academically led quality e-resources within the unit of study. An e-reading strategy which encompasses models for resource discovery and e-literacy was developed, drawing on the experiences and findings of the case studies. Issues considered in this paper will include accessing academic electronic reading materials and using a social bookmarking tool integrated within BU’s virtual learning environment with students studying away from the main campus. Additionally the paper will consider how technology can be used to motivate students, especially in large groups and how it can be used to engage students with a subject perceived as “dry” or “difficult”. The rich possibilities of health science materials can be exploited more fully using new technologies embedded within the curriculum