Sds22 regulates aurora B activity and microtubule-kinetochore interactions at mitosis

Sds22 defines protein phosphatase 1 location and function at kinetochores and subsequent activity of aurora B in mitosis

Accessing Nature’s diversity through metabolic engineering and synthetic biology

In this perspective, we highlight recent examples and trends in metabolic engineering and synthetic biology that demonstrate the synthetic potential of enzyme and pathway engineering for natural product discovery. In doing so, we introduce natural paradigms of secondary metabolism whereby simple carbon substrates are combined into complex molecules through “scaffold diversification”, and subsequent “derivatization” of these scaffolds is used to synthesize distinct complex natural products. We provide examples in which modern pathway engineering efforts including combinatorial biosynthesis and biological retrosynthesis can be coupled to directed enzyme evolution and rational enzyme engineering to allow access to the “privileged” chemical space of natural products in industry-proven microbes. Finally, we forecast the potential to produce natural product-like discovery platforms in biological systems that are amenable to single-step discovery, validation, and synthesis for streamlined discovery and production of biologically active agents

Improving formaldehyde consumption drives methanol assimilation in engineered E. coli

Due to volatile sugar prices, the food vs fuel debate, and recent increases in the supply of natural gas, methanol has emerged as a promising feedstock for the bio-based economy. However, attempts to engineer Escherichia coli to metabolize methanol have achieved limited success. Here, we provide a rigorous systematic analysis of several potential pathway bottlenecks. We show that regeneration of ribulose 5-phosphate in E. coli is insufficient to sustain methanol assimilation, and overcome this by activating the sedoheptulose bisphosphatase variant of the ribulose monophosphate pathway. By leveraging the kinetic isotope effect associated with deuterated methanol as a chemical probe, we further demonstrate that under these conditions overall pathway flux is kinetically limited by methanol dehydrogenase. Finally, we identify NADH as a potent kinetic inhibitor of this enzyme. These results provide direction for future engineering strategies to improve methanol utilization, and underscore the value of chemical biology methodologies in metabolic engineering

Mass casualty events: what to do as the dust settles?

Care during mass casualty events (MCE) has improved during the last 15 years. Military and civilian collaboration has led to partnerships which augment the response to MCE. Much has been written about strategies to deliver care during an MCE, but there is little about how to transition back to normal operations after an event. A panel discussion entitled The Day(s) After: Lessons Learned from Trauma Team Management in the Aftermath of an Unexpected Mass Casualty Event at the 76th Annual American Association for the Surgery of Trauma meeting on September 13, 2017 brought together a cadre of military and civilian surgeons with experience in MCEs. The events described were the First Battle of Mogadishu (1993), the Second Battle of Fallujah (2004), the Bagram Detention Center Rocket Attack (2014), the Boston Marathon Bombing (2013), the Asiana Flight 214 Plane Crash (2013), the Baltimore Riots (2015), and the Orlando Pulse Night Club Shooting (2016). This article focuses on the lessons learned from military and civilian surgeons in the days after MCEs

Integration of Consumer-Based Activity Monitors into Clinical Practice for Children with Type 1 Diabetes: A Feasibility Study

Current technology commonly utilized in diabetes care includes continuous glucose monitors (CGMs) and insulin pumps. One often overlooked critical component to the human glucose response is daily physical activity habits. Consumer-based activity monitors may be a valid way for clinics to collect physical activity data, but whether or not children with type 1 diabetes (T1D) would wear them or use the associated mobile application is unknown. Therefore, the purpose of this study was to test the feasibility of implementing a consumer-based accelerometer directly into ongoing care for adolescents managing T1D. Methods: Adolescents with T1D were invited to participate in this study and instructed to wear a mobile physical activity monitor while also completing a diet log for a minimum of 3 days. Clinical compliance was defined as the number of participants who were compliant with all measures while also having adequate glucose recordings using either a CGM, insulin pump, or on the diet log. Feasibility was defined as \u3e50% of the total sample reaching clinical compliance. Results: A total of 57 children and teenagers between the ages of 7 and 19 agreed to participate in this study and were included in the final analysis. Chi-square results indicated significant compliance for activity tracking (p \u3c 0.001), diet logs (p = 0.04), and overall clinical compliance (p = 0.04). Conclusion: More than half the children in this study were compliant for both activity monitoring and diet logs. This indicates that it is feasible for children with T1D to wear a consumer-based activity monitor while also recording their diet for a minimum of three days

Deep ACS Imaging in the Globular Cluster NGC6397: Dynamical Models

We present N-body models to complement deep imaging of the metal-poor core-collapsed cluster NGC6397 obtained with the Hubble Space Telescope. All simulations include stellar and binary evolution in-step with the stellar dynamics and account for the tidal field of the Galaxy. We focus on the results of a simulation that began with 100000 objects (stars and binaries), 5% primordial binaries and Population II metallicity. After 16 Gyr of evolution the model cluster has about 20% of the stars remaining and has reached core-collapse. We compare the color-magnitude diagrams of the model at this age for the central region and an outer region corresponding to the observed field of NGC6397 (about 2-3 half-light radii from the cluster centre). This demonstrates that the white dwarf population in the outer region has suffered little modification from dynamical processes - contamination of the luminosity function by binaries and white dwarfs with non-standard evolution histories is minimal and should not significantly affect measurement of the cluster age. We also show that the binary fraction of main-sequence stars observed in the NGC6397 field can be taken as representative of the primordial binary fraction of the cluster. For the mass function of the main-sequence stars we find that although this has been altered significantly by dynamics over the cluster lifetime, especially in the central and outer regions, that the position of the observed field is close to optimal for recovering the initial mass function of the cluster stars (below the current turn-off mass). More generally we look at how the mass function changes with radius in a dynamically evolved stellar cluster and suggest where the best radial position to observe the initial mass function is for clusters of any age.Comment: 34 pages, 11 figures, submitted to AJ, companion paper to 0708.403

Lightweight Bulldozer Attachment for Construction and Excavation on the Lunar Surface

A lightweight bulldozer blade prototype has been designed and built to be used as an excavation implement in conjunction with the NASA Chariot lunar mobility platform prototype. The combined system was then used in a variety of field tests in order to characterize structural loads, excavation performance and learn about the operational behavior of lunar excavation in geotechnical lunar simulants. The purpose of this effort was to evaluate the feasibility of lunar excavation for site preparation at a planned NASA lunar outpost. Once the feasibility has been determined then the technology will become available as a candidate element in the NASA Lunar Surface Systems Architecture. In addition to NASA experimental testing of the LANCE blade, NASA engineers completed analytical work on the expected draft forces using classical soil mechanics methods. The Colorado School of Mines (CSM) team utilized finite element analysis (FEA) to study the interaction between the cutting edge of the LANCE blade and the surface of soil. FEA was also used to examine various load cases and their effect on the lightweight structure of the LANCE blade. Overall it has been determined that a lunar bulldozer blade is a viable technology for lunar outpost site preparation, but further work is required to characterize the behavior in 1/6th G and actual lunar regolith in a vacuum lunar environment

Kinetochore alignment within the metaphase plate is regulated by centromere stiffness and microtubule depolymerases

During mitosis in most eukaryotic cells, chromosomes align and form a metaphase plate halfway between the spindle poles, about which they exhibit oscillatory movement. These movements are accompanied by changes in the distance between sister kinetochores, commonly referred to as breathing. We developed a live cell imaging assay combined with computational image analysis to quantify the properties and dynamics of sister kinetochores in three dimensions. We show that baseline oscillation and breathing speeds in late prometaphase and metaphase are set by microtubule depolymerases, whereas oscillation and breathing periods depend on the stiffness of the mechanical linkage between sisters. Metaphase plates become thinner as cells progress toward anaphase as a result of reduced oscillation speed at a relatively constant oscillation period. The progressive slowdown of oscillation speed and its coupling to plate thickness depend nonlinearly on the stiffness of the mechanical linkage between sisters. We propose that metaphase plate formation and thinning require tight control of the state of the mechanical linkage between sisters mediated by centromeric chromatin and cohesion

A Spectroscopic Survey of a Sample of Active M Dwarfs

A moderate resolution spectroscopic survey of Fleming's sample of 54 X-ray selected M dwarfs with photometric distances less than 25 pc is presented. Radial and rotation velocities have been measured by fits to the H-alpha profiles. Radial velocities have been measured by cross correlation. Artificial broadening of an observed spectrum has produced a relationship between H-alpha FWHM and rotation speed, which we use to infer rotation speeds for the entire sample by measurement of the H-alpha emission line. We find 3 ultra-fast rotators (UFRs, vsini > 100km/s), and 8 stars with 30 < vsini < 100 km/s. The UFRs have variable emission. Cross-correlation velocities measured for ultra-fast rotators (UFRs) are shown to depend on rotation speed and the filtering used. The radial velocity dispersion of the sample is 17 km/s. A new double emission line spectroscopic binary with a period of 3.55 days has been discovered, and another known one is in the sample. Three other objects are suspected spectroscopic binaries, and at least six are visual doubles. The only star in the sample observed to have significant lithium is a known TW Hya Association member, TWA 8A. These results show that there are a number of young (< 10^8 yr) and very young (< 10^7 yr) low mass stars in the immediate solar neighbourhood. The H-alpha activity strength does not depend on rotation speed. Our fast rotators are less luminous than similarly fast rotators in the Pleiades. They are either younger than the Pleiades, or gained angular momentum in a different way.Comment: 38 pages incl. 14 figures and 4 tables, plus 12 pages of table for electronic journal only; LaTeX, aastex.cls. Accepted 07/18/02 for publication in The Astronomical Journa