Catalytic conversion of nitrogen to ammonia by an iron model complex

The reduction of nitrogen (N_2) to ammonia (NH_3) is a requisite transformation for life. Although it is widely appreciated that the iron-rich cofactors of nitrogenase enzymes facilitate this transformation, how they do so remains poorly understood. A central element of debate has been the exact site or sites of N_2 coordination and reduction. In synthetic inorganic chemistry, an early emphasis was placed on molybdenum because it was thought to be an essential element of nitrogenases and because it had been established that well-defined molybdenum model complexes could mediate the stoichiometric conversion of N_2 to NH_3 (ref. 9). This chemical transformation can be performed in a catalytic fashion by two well-defined molecular systems that feature molybdenum centres. However, it is now thought that iron is the only transition metal essential to all nitrogenases, and recent biochemical and spectroscopic data have implicated iron instead of molybdenum as the site of N_2 binding in the FeMo-cofactor. Here we describe a tris(phosphine)borane-supported iron complex that catalyses the reduction of N_2 to NH_3 under mild conditions, and in which more than 40 per cent of the proton and reducing equivalents are delivered to N_2. Our results indicate that a single iron site may be capable of stabilizing the various N_xH_y intermediates generated during catalytic NH_3 formation. Geometric tunability at iron imparted by a flexible iron–boron interaction in our model system seems to be important for efficient catalysis. We propose that the interstitial carbon atom recently assigned in the nitrogenase cofactor may have a similar role, perhaps by enabling a single iron site to mediate the enzymatic catalysis through a flexible iron–carbon interaction

A Paper Shield? Whether State Privilege Protections Apply to Student Journalists

Most states recognize a privilege for journalists to protect confidential sources from compelled disclosure. The privilege varies from state to state, and a major difference is how they define a journalist—i.e., a person qualified to claim the privilege. Some schemes are narrow and limit their coverage to employees of professional news organizations. Others are broad and cover freelancers, filmmakers, bloggers, and others who gather information for publication. But what about student journalists? Are they covered? In recent years, as traditional media have adapted to changing circumstances, student journalists have played a vital role in meeting their communities’ needs for news. This Article explores whether state reporter’s privilege protections cover student journalists by reviewing existing privilege schemes, ultimately finding that most exclude student journalists. This poses a unique problem because, as one commentator put it, “[i]f we’re going to ask students to fulfill the responsibility of being front-line newsgatherers, the least we can do is send them out into the field with the confidence of meaningful legal protection.” With that in mind, the Article offers solutions and calls for legislative action, arguing that student journalists need more than a paper shield to fulfill their editorial responsibilities. This is the first comprehensive scholarly analysis of these issues

Effect of Local Norms on Racial and Ethnic Representation in Gifted Education

Educators have sought to understand and address the disproportional representation of students from certain student subgroups in gifted education. Most gifted identification decisions are made with national comparisons where students must score above a certain percentage of test takers. However, this approach is not always consistent with the overall goal of gifted education. Scholars have long argued for the use of local normative criteria to increase the diversity of students identified for gifted services, and although some districts across the country have applied such recommendations, little research has been carried out. In this study, we use a large data set to assess the extent to which identifying gifted students with either school-level norms or a combination of national and school-level norms would improve gifted education representation rates for students who are from African American and Latinx families. A preprint of this registered report and this project’s preregistration documentation are available at https://osf.io/z2egy/

Academic leadership: changing conceptions, identities and experiences in UK Higher Education

© Leadership Foundation for Higher EducationThis report presents the findings from a research project on academic leadership in UK higher education. The overall aim of this project was to explore and understand ‘academic leadership’ that relates directly to the core academic functions of teaching, research and service (including academic administration and outreach), as distinct from managerial aspects of leading higher education institutions (HEIs) such as financial and strategic planning, marketing and human resource management (HRM).Leadership Foundation for Higher Educatio

Synthesis and preliminary biological evaluation of radiolabeled 5-BDBD analogs as new candidate PET radioligands for P2X4 receptor

P2X4 receptor has become an interesting molecular target for treatment and PET imaging of neuroinflammation and associated brain diseases such as Alzheimer’s disease. This study reports the first design, synthesis, radiolabeling and biological evaluation of new candidate PET P2X4 receptor radioligands using 5-BDBD, a specific P2X4 receptor antagonist, as a scaffold. 5-(3-Hydroxyphenyl)-1-[11C]methyl-1,3-dihydro-2H-benzofuro[3,2-e][1,4]diazepin-2-one (N-[11C]Me-5-BDBD analog, [11C]9) and 5-(3-Bromophenyl)-1-[11C]methyl-1,3-dihydro-2H-benzofuro[3,2-e][1,4]diazepin-2-one (N-[11C]Me-5-BDBD, [11C]8c) were prepared from their corresponding desmethylated precursors with [11C]CH3OTf through N-[11C]methylation and isolated by HPLC combined with SPE in 30–50% decay corrected radiochemical yields with 370–1110 GBq/µmol specific activity at EOB. 5-(3-[18F]Fluorophenyl)-1,3-dihydro-2H-benzofuro[3,2-e][1,4]diazepin-2-one ([18F]F-5-BDBD, [18F]5a) and 5-(3-(2-[18F]fluoroethoxy)phenyl)-1,3-dihydro-2H-benzofuro[3,2-e][1,4]diazepin-2-one ([18F]FE-5-BDBD, [18F]11) were prepared from their corresponding nitro- and tosylated precursors by nucleophilic substitution with K[18F]F/Kryptofix 2.2.2 and isolated by HPLC-SPE in 5–25% decay corrected radiochemical yields with 111–740 GBq/µmol specific activity at EOB. The preliminary biological evaluation of radiolabeled 5-BDBD analogs indicated these new radioligands have similar biological activity with their parent compound 5-BDBD

Identification of quantitative proteomic differences between Mycobacterium tuberculosis lineages with altered virulence

Evidence currently suggests that as a species Mycobacterium tuberculosis exhibits very little genomic sequence diversity. Despite limited genetic variability, members of the M. tuberculosis complex (MTBC) have been shown to exhibit vast discrepancies in phenotypic presentation in terms of virulence, elicited immune response and transmissibility. Here, we used qualitative and quantitative mass spectrometry tools to investigate the proteomes of seven clinically-relevant mycobacterial strains four M. tuberculosis strains, M. bovis, M. bovis BCG, and M. avium that show varying degrees of pathogenicity and virulence, in an effort to rationalize the observed phenotypic differences. Following protein preparation, liquid chromatography mass spectrometry (LC MS/MS) and data capture were carried out using an LTQ Orbitrap Velos. Data analysis was carried out using a novel bioinformatics strategy, which yielded high protein coverage and was based on high confidence peptides. Through this approach, we directly identified a total of 3788 unique M. tuberculosis proteins out of a theoretical proteome of 4023 proteins and identified an average of 3290 unique proteins for each of the MTBC organisms (representing 82% of the theoretical proteomes), as well as 4250 unique M. avium proteins (80% of the theoretical proteome). Data analysis showed that all major classes of proteins are represented in every strain, but that there are significant quantitative differences between strains. Targeted selected reaction monitoring (SRM) assays were used to quantify the observed differential expression of a subset of 23 proteins identified by comparison to gene expression data as being of particular relevance to virulence. This analysis revealed differences in relative protein abundance between strains for proteins which may promote bacterial fitness in the more virulent W. Beijing strain. These differences may contribute to this strain's capacity for surviving within the host and resisting treatment, which has contributed to its rapid spread. Through this approach, we have begun to describe the proteomic portrait of a successful mycobacterial pathogen. Data are available via ProteomeXchange with identifier PXDO04165

Synthesis and preliminary biological evaluation of [11C]methyl (2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-d-leucinate for the fractalkine receptor (CX3CR1)

The reference standard methyl (2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-d-leucinate (5) and its precursor 2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-d-leucine (6) were synthesized from 6-amino-2-mercaptopyrimidin-4-ol and BnBr with overall chemical yield 7% in five steps and 4% in six steps, respectively. The target tracer [11C]methyl (2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-d-leucinate ([11C]5) was prepared from the acid precursor with [11C]CH3OTf through O-[11C]methylation and isolated by HPLC combined with SPE in 40–50% radiochemical yield, based on [11C]CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the specific activity (SA) at EOB was 370–1110 GBq/μmol with a total synthesis time of ∼40-min from EOB. The radioligand depletion experiment of [11C]5 did not display specific binding to CX3CR1, and the competitive binding assay of ligand 5 found much lower CX3CR1 binding affinity