Nucleotide– and Mal3-dependent changes in fission yeast microtubules suggest a structural plasticity view of dynamics

Using cryo-electron microscopy, we characterize the architecture of microtubules assembled from Schizosaccharomyces pombe tubulin, in the presence and absence of their regulatory partner Mal3. Cryo-electron tomography reveals that microtubules assembled from S. pombe tubulin have predominantly B-lattice interprotofilament contacts, with protofilaments skewed around the microtubule axis. Copolymerization with Mal3 favors 13 protofilament microtubules with reduced protofilament skew, indicating that Mal3 adjusts interprotofilament interfaces. A 4.6-Å resolution structure of microtubule-bound Mal3 shows that Mal3 makes a distinctive footprint on the S. pombe microtubule lattice and that unlike mammalian microtubules, S. pombe microtubules do not show the longitudinal lattice compaction associated with EB protein binding and GTP hydrolysis. Our results firmly support a structural plasticity view of microtubule dynamics in which microtubule lattice conformation is sensitive to a variety of effectors and differently so for different tubulins

Gauge Theories on a 2+2 Anisotropic Lattice

The implementation of gauge theories on a four-dimensional anisotropic lattice with two distinct lattice spacings is discussed, with special attention to the case where two axes are finely and two axes are coarsely discretized. Feynman rules for the Wilson gauge action are derived and the renormalizability of the theory and the recovery of the continuum limit are analyzed. The calculation of the gluon propagator and the restoration of Lorentz invariance in on-shell states is presented to one-loop order in lattice perturbation theory for $SU(N_c)$ on both 2+2 and 3+1 lattices.Comment: 27 pages, uses feynmf. Font compatibility adjuste

Cryo-EM structure (4.5-Å) of Yeast Kinesin-5–Microtubule Complex reveals a distinct binding footprint and mechanism of drug resistance

Kinesin-5s are microtubule-dependent motors that drive spindle pole separation during mitosis. We used cryo-electron microscopy to determine the 4.5 Å resolution structure of the motor domain of the fission yeast kinesin-5 Cut7 bound to fission yeast microtubules, and explored the topology of the motor-microtubule interface and the susceptibility of the complex to drug binding. Despite their non-canonical architecture and mechanochemistry, S. pombe microtubules were stabilized by epothilone at the taxane binding pocket. The overall Cut7 footprint on the S. pombe microtubule surface is altered compared to mammalian tubulin microtubules because of their different polymer architectures. However, the core motor-microtubule interaction is tightly conserved, reflected in similar Cut7 ATPase activities on each microtubule type. AMPPNP-bound Cut7 adopts a kinesin-conserved ATP-like conformation including cover neck bundle formation. However, the Cut7 ATPase is not blocked by a mammalian-specific kinesin-5 inhibitor, consistent with the non-conserved sequence and structure of its loop5 insertion

Modulation control and spectral shaping of optical fiber supercontinuum generation in the picosecond regime

Numerical simulations are used to study how fiber supercontinuum generation seeded by picosecond pulses can be actively controlled through the use of input pulse modulation. By carrying out multiple simulations in the presence of noise, we show how tailored supercontinuum Spectra with increased bandwidth and improved stability can be generated using an input envelope modulation of appropriate frequency and depth. The results are discussed in terms of the non-linear propagation dynamics and pump depletion.Comment: Aspects of this work were presented in Paper ThJ2 at OECC/ACOFT 2008, Sydney Australia 7-10 July (2008). Journal paper submitted for publication 30 July 200

Risk Factors for Mycobacterium ulcerans Infection, Southeastern Australia

Epidemiologic evidence shows that mosquitoes play a role in transmission to humans

Should science educators deal with the science/religion issue?

I begin by examining the natures of science and religion before looking at the ways in which they relate to one another. I then look at a number of case studies that centre on the relationships between science and religion, including attempts to find mechanisms for divine action in quantum theory and chaos theory, creationism, genetic engineering and the writings of Richard Dawkins. Finally, I consider some of the pedagogical issues that would need to be considered if the science/religion issue is to be addressed in the classroom. I conclude that there are increasing arguments in favour of science educators teaching about the science/religion issue. The principal reason for this is to help students better to learn science. However, such teaching makes greater demands on science educators than has generally been the case. Certain of these demands are identified and some specific suggestions are made as to how a science educator might deal with the science/religion issue. © 2008 Taylor & Francis

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Advances in multidisciplinary therapy for meningiomas

Surgery has long been established as the first-line treatment for the majority of symptomatic and enlarging meningiomas, and evidence for its success is derived from retrospective case series. Despite surgical resection, a subset of meningiomas display aggressive behavior with early recurrences that are difficult to treat. The decision to radically resect meningiomas and involved structures is balanced against the risk for neurological injury in patients. Radiation therapy has largely been used as a complementary and safe therapeutic strategy in meningiomas with evidence primarily stemming from retrospective, single-Institution reports. Two of the first cooperative group studies (RTOG 0539 and EORTC 22042) evaluating the outcomes of adjuvant radiation therapy in higher-risk meningiomas have shown promising preliminary results. Historically, systemic therapy has resulted in disappointing results in meningiomas. However, several clinical trials are under way evaluating the efficacy of chemotherapies, such as trabectedin, and novel molecular agents targeting Smoothened, AKT1, and focal adhesion kinase in patients with recurrent meningiomas