Ammonia (NH₃)-oxidizing bacteria (AOB) emit substantial amounts of nitric oxide (NO) and nitrous oxide (N₂O), both of which contribute to the harmful environmental side effects of large-scale ...agriculture. The currently accepted model for AOB metabolism involves NH₃ oxidation to nitrite (NO₂⁻) via a single obligate intermediate, hydroxylamine (NH₂OH). Within this model, the multiheme enzyme hydroxylamine oxidoreductase (HAO) catalyzes the four-electron oxidation of NH₂OH to NO₂⁻. We provide evidence that HAO oxidizes NH₂OH by only three electrons to NO under both anaerobic and aerobic conditions. NO₂⁻ observed in HAO activity assays is a nonenzymatic product resulting from the oxidation of NO by O₂ under aerobic conditions. Our present study implies that aerobic NH₃ oxidation by AOB occurs via two obligate intermediates, NH₂OH and NO, necessitating a mediator of the third enzymatic step.
Since the publication of the first edition of Student Conduct Practice in 2008 the landscape of student conduct has matured and shifted dramatically. As the composition of the overall population and ...of the student body on campuses across the nation has changed, institutions of higher learning have a greater awareness of the importance of preparing students to function competently in a diverse society. They are seeing student behaviors, such as challenging mores, rules and policies, that reflect the growing polarization and complexity we see in our larger society, and such trends as a marked increase in student mental health challenges as well as changing social dynamics, all of which require a new awareness and a rethinking of policies and responses by conduct professionals, including embracing the a social justice as a lens by which we perform our work.
This updated and considerably expanded edition maintains the objectives of the first--to constitute a compendium of current best practices in the administration of student conduct, to summarize the latest thinking on key issues facing practitioners today, and to provide an overview of the role and status of conduct administrators within their institutions.
This text invites student conduct administrators to examine current programs and policies to ensure that the spaces that they create during interactions with students are spaces in which all students feel welcome and heard. As we strive to prepare students not only to be productive members of today's workforce, and more importantly to be good people and upright citizens, this text accentuates the delicate balance between responding to regulatory mandates and meeting the educational aims of student conduct. The aim is to offer those with an interest in student conduct and those professionals who are new or seasoned student conduct administrators with both a compendium of chapters on best practices and the background to grapple with the thought-provoking situations
Nitrogen is fundamental to all of life and many industrial processes. The interchange of nitrogen oxidation states in the industrial production of ammonia, nitric acid, and other commodity chemicals ...is largely powered by fossil fuels. A key goal of contemporary research in the field of nitrogen chemistry is to minimize the use of fossil fuels by developing more efficient heterogeneous, homogeneous, photo-, and electrocatalytic processes or by adapting the enzymatic processes underlying the natural nitrogen cycle. These approaches, as well as the challenges involved, are discussed in this Review.
The ventricular arrhythmia Torsades de Pointes (TdP) is a common form of drug‐induced cardiotoxicity, but prediction of this arrhythmia remains an unresolved issue in drug development. Current assays ...to evaluate arrhythmia risk are limited by poor specificity and a lack of mechanistic insight. We addressed this important unresolved issue through a novel computational approach that combined simulations of drug effects on dynamics with statistical analysis and machine‐learning. Drugs that blocked multiple ion channels were simulated in ventricular myocyte models, and metrics computed from the action potential and intracellular (Ca2+) waveform were used to construct classifiers that distinguished between arrhythmogenic and nonarrhythmogenic drugs. We found that: (1) these classifiers provide superior risk prediction; (2) drug‐induced changes to both the action potential and intracellular (Ca2+) influence risk; and (3) cardiac ion channels not typically assessed may significantly affect risk. Our algorithm demonstrates the value of systematic simulations in predicting pharmacological toxicity.
We present the first results of the Fermilab National Accelerator Laboratory (FNAL) Muon g-2 Experiment for the positive muon magnetic anomaly a_{μ}≡(g_{μ}-2)/2. The anomaly is determined from the ...precision measurements of two angular frequencies. Intensity variation of high-energy positrons from muon decays directly encodes the difference frequency ω_{a} between the spin-precession and cyclotron frequencies for polarized muons in a magnetic storage ring. The storage ring magnetic field is measured using nuclear magnetic resonance probes calibrated in terms of the equivalent proton spin precession frequency ωover ˜_{p}^{'} in a spherical water sample at 34.7 °C. The ratio ω_{a}/ωover ˜_{p}^{'}, together with known fundamental constants, determines a_{μ}(FNAL)=116 592 040(54)×10^{-11} (0.46 ppm). The result is 3.3 standard deviations greater than the standard model prediction and is in excellent agreement with the previous Brookhaven National Laboratory (BNL) E821 measurement. After combination with previous measurements of both μ^{+} and μ^{-}, the new experimental average of a_{μ}(Exp)=116 592 061(41)×10^{-11} (0.35 ppm) increases the tension between experiment and theory to 4.2 standard deviations.
Accurate animal cell division requires precise coordination of changes in the structure of the microtubule-based spindle and the actin-based cell cortex. Here, we use a series of perturbation ...experiments to dissect the relative roles of actin, cortical mechanics, and cell shape in spindle formation. We find that, whereas the actin cortex is largely dispensable for rounding and timely mitotic progression in isolated cells, it is needed to drive rounding to enable unperturbed spindle morphogenesis under conditions of confinement. Using different methods to limit mitotic cell height, we show that a failure to round up causes defects in spindle assembly, pole splitting, and a delay in mitotic progression. These defects can be rescued by increasing microtubule lengths and therefore appear to be a direct consequence of the limited reach of mitotic centrosome-nucleated microtubules. These findings help to explain why most animal cells round up as they enter mitosis.
•Actin is only needed for efficient spindle assembly in confined mitotic HeLa cells•A failure to round up delays spindle assembly and causes spindle pole splitting•Spindle defects in flattened cells result from the limited reach of microtubules•Mitotic rounding provides the space for efficient spindle morphogenesis
The function of actin-driven mitotic cell rounding in animals is poorly understood despite its ubiquity. By systematically altering mitotic cell geometry, Lancaster et al. show that rounding aids chromosome capture during spindle formation and stabilizes the spindle. The mitotic cortex ensures that rounding occurs even in physically constrained tissue-like environments.
Abstract Women with germline mutations in the cancer susceptibility genes, BRCA1 or BRCA2 , associated with Hereditary Breast & Ovarian Cancer syndrome, have up to an 85% lifetime risk of breast ...cancer and up to a 46% lifetime risk of ovarian, tubal, and peritoneal cancers. Similarly, women with mutations in the DNA mismatch repair genes, MLH1 , MSH2 , MSH6 , or PMS2 , associated with the Lynch/Hereditary Non-Polyposis Colorectal Cancer (HNPCC) syndrome, have up to a 40–60% lifetime risk of both endometrial and colorectal cancers as well as a 9–12% lifetime risk of ovarian cancer. Mutations in other genes including TP53, PTEN, and STK11 are responsible for hereditary syndromes associated with gynecologic, breast, and other cancers. Evaluation of the likelihood of a patient having one of these gynecologic cancer predisposition syndromes enables physicians to provide individualized assessments of cancer risk, as well as the opportunity to provide tailored screening and prevention strategies such as surveillance, chemoprevention, and prophylactic surgery that may reduce the morbidity and mortality associated with these syndromes. Evaluation for the presence of a hereditary cancer syndrome is a process that includes assessment of clinical and tumor characteristics, education and counseling conducted by a provider with expertise in cancer genetics, and may include genetic testing after appropriate consent is obtained. This commentary provides guidance on identification of patients who may benefit from assessment for the presence of a hereditary breast and/or gynecologic cancer syndrome.
We report a mild and efficient electrochemical protocol to access a variety of vicinally C–O and C–N difunctionalized compounds from simple alkenes. Detailed mechanistic studies revealed a distinct ...reaction pathway from those previously reported for TEMPO-mediated reactions. In this mechanism, electrochemically generated oxoammonium ion facilitates the formation of azidyl radical via a charge-transfer complex with azide, TEMPO–N3. DFT calculations together with spectroscopic characterization provided a tentative structural assignment of this charge-transfer complex. Kinetic and kinetic isotopic effect studies revealed that reversible dissociation of TEMPO–N3 into TEMPO• and azidyl precedes the addition of these radicals across the alkene in the rate-determining step. The resulting azidooxygenated product could then be easily manipulated for further synthetic elaborations. The discovery of this new reaction pathway mediated by the TEMPO+/TEMPO• redox couple may expand the scope of aminoxyl radical chemistry in synthetic contexts.
The metallobiochemistry underlying the formation of the inorganic N–N-bond-containing molecules nitrous oxide (N2O), dinitrogen (N2), and hydrazine (N2H4) is essential to the lifestyles of diverse ...organisms. Similar reactions hold promise as means to use N-based fuels as alternative carbon-free energy sources. This review discusses research efforts to understand the mechanisms underlying biological N–N bond formation in primary metabolism and how the associated reactions are tied to energy transduction and organismal survival. These efforts comprise studies of both natural and engineered metalloenzymes as well as synthetic model complexes.
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