Tuning Electronic Structure To Control Manganese Nitride Activation

Investigation of a series of oxidized nitridomanganese(V) salen complexes with different para ring substituents (R = CF3, tBu, and NMe2) demonstrates that nitride activation is dictated by remote ligand electronics. For R = CF3 and tBu, oxidation affords a Mn(VI) species and nitride activation, with dinitrogen homocoupling accelerated by the more electron-withdrawing CF3 substituent. Employing an electron-donating substituent (R = NMe2) results in a localized ligand radical species that is resistant to N coupling of the nitrides and is stable in solution at both 195 and 298 K

Dilemmas in doing insider research in professional education

This article explores the dilemmas I encountered when researching social work education in England as an insider researcher who was simultaneously employed as an educator in the host institution. This was an ethnographic project deploying multiple methods and generating rich case study material which informed the student textbook Becoming a Social Worker the four-year period of the project. First, ethical dilemmas emerged around informed consent and confidentiality when conducting surveys of students and reading their portfolios. Second, professional dilemmas stemmed from the ways in which my roles as a researcher, academic tutor, social worker and former practice educator converged and collided. Third, political dilemmas pertained to the potential for the project to crystallize and convey conflicts among stakeholders in the university and community. Since the majority of research in social work education is conducted by insiders, we have a vital interest in making sense of such complexity

Electronic Structure Description of a Doubly Oxidized Bimetallic Cobalt Complex with Pro-Radical Ligands

The geometric and electronic structure of a doubly oxidized bimetallic Co complex containing two redox-active salen moieties connected via a 1,2-phenylene linker has been investigated and compared to an oxidized monomeric analogue. Both complexes, CoL1 and Co2L2 are oxidized to the mono- and di-cations respectively with AgSbF6 and characterized by X-ray crystallography for the monomer, and Vis-NIR spectroscopy, electron paramagnetic (EPR) spectroscopy, SQUID magnetometry and density functional theory (DFT) calculations for both the monomer and dimer. Both complexes exhibit a water molecule coordinated in the apical position upon oxidation. [CoL1-H2O]+ displays a broad NIR band at 8500 cm-1 (8400 M-1cm-1) which is consistent with recent reports on oxidized Co salen complexes (Kochem, A. et. al., Inorg Chem., 2012, 51, 10557-10571, Kurahashi, T. et. al., Inorg. Chem., 2013, 52, 3908-3919). DFT calculations predict a triplet ground state with significant ligand and metal contributions to the singularly occupied molecular orbital (SOMO). The majority (~75%) of the total spin density is localized on the metal, highlighting both high spin Co(III) and Co(II)L• character in the electronic ground state. Further oxidation of CoL1 to the dication affords a low spin Co(III) phenoxyl radical species. The NIR features for [Co2L2-2H2O]2+ at 8600 cm-1 (17800 M-1cm-1) are doubly intense in comparison to [CoL1-H2O]+ owing to the description of [Co2L2-2H2O]2+ as two non-interacting oxidized Co salen complexes bound via the central phenylene linker. Interestingly, TD-DFT calculations predict two electronic transitions that are 353 cm-1 apart. The NIR spectrum of the analogous Ni complex, [Ni2L2]2+, exhibits two intense transitions (4890 cm-1/26500 M-1cm-1 and 4200 cm-1/21200 M-1cm-1) due to exciton coupling in the excited state. Only one broad band is observed in the NIR spectrum for [Co2L2-2H2O]2+ as a result of the contracted donor and acceptor orbitals and overall CT character

Probable Innocence Revisited

International audienceOften we wish to ensure that the identity of the user performing a certain action is maintained secret. This property is called anonymity. Examples of situations in which we may wish to provide anonymity include: publishing on the web, retrieving information from the web, sending a message, etc. Many protocols have been designed for this purpose, for example, Crowds [15], Onion Routing [23], the Free Haven [7], Web MIX [1] and Freenet [4]

Gourds and squashes (Cucurbita spp.) adapted to megafaunal extinction and ecological anachronism through domestication.

The genus Cucurbita (squashes, pumpkins, gourds) contains numerous domesticated lineages with ancient New World origins. It was broadly distributed in the past but has declined to the point that several of the crops' progenitor species are scarce or unknown in the wild. We hypothesize that Holocene ecological shifts and megafaunal extinctions severely impacted wild Cucurbita, whereas their domestic counterparts adapted to changing conditions via symbiosis with human cultivators. First, we used high-throughput sequencing to analyze complete plastid genomes of 91 total Cucurbita samples, comprising ancient (n = 19), modern wild (n = 30), and modern domestic (n = 42) taxa. This analysis demonstrates independent domestication in eastern North America, evidence of a previously unknown pathway to domestication in northeastern Mexico, and broad archaeological distributions of taxa currently unknown in the wild. Further, sequence similarity between distant wild populations suggests recent fragmentation. Collectively, these results point to wild-type declines coinciding with widespread domestication. Second, we hypothesize that the disappearance of large herbivores struck a critical ecological blow against wild Cucurbita, and we take initial steps to consider this hypothesis through cross-mammal analyses of bitter taste receptor gene repertoires. Directly, megafauna consumed Cucurbita fruits and dispersed their seeds; wild Cucurbita were likely left without mutualistic dispersal partners in the Holocene because they are unpalatable to smaller surviving mammals with more bitter taste receptor genes. Indirectly, megafauna maintained mosaic-like landscapes ideal for Cucurbita, and vegetative changes following the megafaunal extinctions likely crowded out their disturbed-ground niche. Thus, anthropogenic landscapes provided favorable growth habitats and willing dispersal partners in the wake of ecological upheaval.Research was supported by The Pennsylvania State University Huck Institutes of the Life Sciences and College of the Liberal Arts (G.H.P.), Wenner–Gren post-PhD Research Grant 8770 and Natural Environment Research Council Independent Research Fellowship NE/L012030/1 (to L.K.), and the Smithsonian Institution (B.D.S.). Instrumentation was funded by the National Science Foundation through Grant OCI–0821527.This is the author accepted manuscript. The final version is available from PNAS via http://dx.doi.org/10.1073/pnas.151610911

Transcriptome analysis of Sf9 insect cells during production of recombinant Adeno‐associated virus

The insect cell-baculovirus expression vector system (IC-BEVS) has emerged as an alternative time- and cost-efficient production platform for recombinant Adeno-associated virus (AAV) for gene therapy. However, a better understanding of the underlying biological mechanisms of IC-BEVS is fundamental to further optimize this expression system toward increased product titer and quality. Here, gene expression of Sf9 insect cells producing recombinant AAV through a dual baculovirus expression system, with low multiplicity of infection (MOI), was profiled by RNA-seq. An 8-fold increase in reads mapping to either baculovirus or AAV transgene sequences was observed between 24 and 48 h post-infection (hpi), confirming a take-over of the host cell transcriptome by the baculovirus. A total of 336 and 4784 genes were identified as differentially expressed at 24 hpi (vs non-infected cells) and at 48 hpi (vs. infected cells at 24 hpi), respectively, including dronc, birc5/iap5, and prp1. Functional annotation found biological processes such as cell cycle, cell growth, protein folding, and cellular amino acid metabolic processes enriched along infection. This work uncovers transcriptional changes in Sf9 in response to baculovirus infection, which provide new insights into cell and/or metabolic engineering targets that can be leveraged for rational bioprocess engineering of IC-BEVS for AAV production.publishersversionpublishe

Production of embryos and a live offspring using post mortem reproductive material from bison (Bison bison bison) originating in Yellowstone National Park, USA

Bison from Yellowstone National Park (YNP) have an important genetic history. As one of the few wild herds of bison with no evidence of cattle DNA introgression and a large enough population to maintain genetic diversity, they are considered a conservation priority for the species. Unfortunately, there is a high prevalence of the zoonotic disease brucellosis in the herd. Part of the management strategy for controlling the disease and herd size in YNP is to remove bison from the population during the winter migration out of the park. This interagency management cull provides an opportunity to collect a large number of oocytes from a wild bison population for genetic banking and research purposes. During the winters of 2014–2018, which is the nonbreeding season for bison, oocytes were collected post mortem and used to determine the effects of donor reproductive maturity and pregnancy status on oocyte quality and in vitro fertilization (IVF) outcomes, and to demonstrate the feasibility of producing healthy offspring. Cumulus oocyte complexes (COCs) were placed into an in vitro embryo production (IVP) system, and on days 7, 7.5, and 8 of in vitro culture (Day 0 = day of in vitro fertilization) embryos were assessed for developmental stage and quality prior to vitrification. Embryos were then stored in liquid nitrogen until the breeding season when a subset were warmed, cultured for 6 h, evaluated for survival, and transferred to healthy bison recipients. There were no significant differences in the ability of recovered COCs to support blastocyst development based on female reproductive maturity or pregnancy status (juvenile 79/959 (8.2%) vs sexually mature 547/6544 (8.4%); non-pregnant 188/2302 (8.2%) vs pregnant 556/6122 (9.1%)). Following the transfer of 15 embryos to 10 recipients, one healthy female calf was born. This work demonstrates that live offspring can be generated from COCs collected from YNP bison post mortem in the non-breeding season, and that gamete recovery can be a valuable tool for conservation of valuable genetics for this species while mitigating diseases like brucellosis

Leveraging single-cell and bulk transcriptomics towards improved insect cell factories for biopharmaceuticals

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Impact of exercise on innate immunity in multiple sclerosis progression and symptomatology

Multiple Sclerosis (MS), an idiopathic progressive immune-mediated neurological disorder of the central nervous system (CNS), is characterized by recurrent episodes of inflammatory demyelination and consequent axonal deterioration. It accounts for functional deterioration and lasting disability among young adults. A body of literature demonstrates that physical activity counteracts fatigue and depression and may improve overall quality of life in MS patients. Furthermore, much data indicates that exercise ameliorates chronic neuroinflammation and its related pathologies by tipping cytokine profiles toward an anti-inflammatory signature. Recent data has focused on the direct impact of exercise training on the innate immune system by targeting toll-like receptors (TLRs), signaling pattern recognition receptors that govern the innate immune response, shedding light on the physiological role of TLRs in health and disease. Indeed, TLRs continue to emerge as players in the neuroinflammatory processes underpinning MS. This review will highlight evidence that physical activity and exercise are potential immunomodulatory therapies, targeting innate signaling mechanism(s) to modulate MS symptom development and progression