Characterizing the Inhibition of Katanin Using Tubulin Carboxy-Terminal Tail Constructs

Understanding how the cellular cytoskeleton is maintained and regulated is important to elucidate the functions of many structures such as the mitotic spindle, cilia and flagella. Katanin p60, microtubule-severing enzymes from the ATPase associated with cellular activities (AAA+) family, has previously been shown in our lab to be inhibited by free tubulin as well as α- and β-tubulin carboxy-terminal tail (CTT) constructs. Here we investigate the inhibition ability of several different tubulin CTT sequences. We quantify the effect of the addition of these constructs on the severing and binding activity of katanin. We find that some constructs inhibit katanin better than others and two constructs that appear to enhance katanin activity. Our findings add nuance to our previous findings that consensus α-tubulin tails are less inhibitory of katanin than consensus β-tubulin [3]. Surprisingly, we find that a polyglutamate sequence activates katanin while it has previously been shown to inhibit spastin, a different microtubule-severing enzyme associated with the neuromuscular disease Hereditary Spastic Paraplegia [23]. These results highlight that different CTT sequences can control the activity of severing enzymes and ultimately affect the cytoskeletal network organization in a cell type and location-dependent manner

Studies of nucleon-gold collisions at 200 GeV per nucleon pair using tagged d+Au interactions

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Physics, 2006.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Includes bibliographical references (p. 201-212).The spectra of charged hadrons produced near mid-rapidity in d+Au, p+Au and n+Au collisions at - = 200 GeV are presented as a function of transverse momentum and centrality. These measurements were performed using the PHOBOS detector at the Relativistic Heavy Ion Collider (RHIC). Nucleon-nucleus interactions were extracted from the d+Au data by identifying the deuteron spectators. The deuteron spectators were measured using two calorimeters; one that detected forward-going single neutrons and a newly installed calorimeter that detected forward-going single protons. The large suppression of high-pr hadron production in central Au+Au interactions relative to a naive superposition of p+p collisions has been interpreted as evidence of partonic energy loss in a dense medium. This interpretation is founded upon the absence of such suppression in the yield of d+Au collisions. The validity of using d+Au interactions in place of a nucleon-nucleus reference is tested. It is shown that hadron production in d+Au agrees with a simple binary collision scaling of hadron production in p+Au. An ideal reference for Au+Au collisions is constructed using a weighted combination of p+Au and n+Au yields and is found to be similar to the d+Au reference.(cont.) Further, hadron production in p+Au interactions is compared to that of n+Au interactions. The single charge difference between a p+Au and a n+Au collision allows for a unique study of the ability of the interaction to transport the proton from the initial deuteron to mid-rapidity. However, no asymmetry between the positively and negatively charged hadron spectra of p+Au and n+Au interactions is observed at (qr) = 0.8. Collision centrality was determined using several different observables, including those based on the multiplicity in different regions of pseudorapidity and those based on the amount of nuclear spectator material. It is shown that measurements made on small collision systems in the mid-rapidity region are biased by centrality variables based on the mid-rapidity multiplicity. Despite this bias, a smooth evolution with centrality is observed in the Cronin enhancement of hadrons produced in d+Au collisions. It is shown that this smooth progression is independent of the choice of centrality variable when centrality is parametrized by the multiplicity measured near mid-rapidity.by Corey Reed.Ph.D

Direct oral anticoagulants or warfarin for A fib?

A recent study evaluated the effectiveness of 3 direct oral anticoagulants and warfarin in patients with atrial fibrillation. So which agents came out on top? PRACTICE CHANGER: Use direct oral anticoagulants instead of warfarin in patients with atrial fibrillation because they are just as effective at preventing ischemic stroke and systemic emboli as warfarin, and because apixaban and dabigatran have lower bleeding rates. Stength of recommendation: B: Based on a single, prospective, cohort study

Does exercise relieve vasomotor menopausal symptoms?

Q: Does exercise relieve vasomotor menopausal symptoms? A: NO. Exercise doesn't decrease the frequency or severity of vasomotor menopausal symptoms (VMS) in perimenopausal and postmenopausal women (strength of recommendation: A, systematic review of randomized controlled trials [RCTs] and consistent RCT).Authors: Corey Lyon, DO; Rebecca Mullen, MD; Brandy Deffenbacher, MD; Alex Reed, PhD University of Colorado Family Medicine Residency, Denver; Joan Nashelsky, MLS Family Physicians Inquiries Network, Iowa City

Engineering, nutrient removal, and feedstock conversion evaluations of four corn stover harvest scenarios

Crop residue has been identified as a near-term source of biomass for renewable fuel, heat, power, chemicals and other bio-materials. A prototype one-pass harvest system was used to collect residue samples from a corn (Zea mays L.) field near Ames, IA. Four harvest scenarios (low cut, high-cut top, high-cut bottom, and normal cut) were evaluated and are expressed as collected stover harvest indices (CSHI). High-cut top and high-cut bottom samples were obtained from the same plot in separate operations. Chemical composition, dilute acid pretreatment response, ethanol conversion yield and efficiency, and thermochemical conversion for each scenario were determined. Mean grain yield in this study (10.1 Mg ha−1 dry weight) was representative of the average yield (10.0 Mg ha−1) for the area (Story County, IA) and year (2005). The four harvest scenarios removed 6.7, 4.9, 1.7, and 5.1 Mg ha−1 of dry matter, respectively, or 0.60 for low cut, 0.66 for normal cut, and 0.61 for the total high-cut (top+bottom) scenarios when expressed as CSHI values. The macro-nutrient replacement value for the normal harvest scenario was $57.36 ha−1 or$11.27 Mg−1. Harvesting stalk bottoms increased stover water content, risk of combine damage, estimated transportation costs, and left insufficient soil cover, while also producing a problematic feedstock. These preliminary results indicate harvesting stover (including the cobs) at a height of approximately 40 cm would be best for farmers and ethanol producers because of faster harvest speed and higher quality ethanol feedstock

Multimessenger parameter inference of gravitational-wave and electromagnetic observations of white dwarf binaries

The upcoming Laser Interferometer Space Antenna (LISA) will detect a large gravitational-wave foreground of Galactic white dwarf binaries. These sources are exceptional for their probable detection at electromagnetic wavelengths, some long before LISA flies. Studies in both gravitational and electromagnetic waves will yield strong constraints on system parameters not achievable through measurements of one messenger alone. In this work, we present a Bayesian inference pipeline and simulation suite in which we study potential constraints on binaries in a variety of configurations. We show how using LISA detections and parameter estimation can significantly improve constraints on system parameters when used as a prior for the electromagnetic analyses. We also provide rules of thumb for how current measurements will benefit from LISA measurements in the future.Comment: 8 pages, 5 figures, accepted to MNRA

Radar absorption, basal reflection, thickness and polarization measurements from the Ross Ice Shelf, Antarctica

Radio-glaciological parameters from the Moore’s Bay region of the Ross Ice Shelf, Antarctica, have been measured. The thickness of the ice shelf in Moore’s Bay was measured from reflection times of radio-frequency pulses propagating vertically through the shelf and reflecting from the ocean, and is found to be 576 ± 8 m. Introducing a baseline of 543 ± 7m between radio transmitter and receiver allowed the computation of the basal reflection coefficient, R, separately from englacial loss. The depth-averaged attenuation length of the ice column, 〈L〉 is shown to depend linearly on frequency. The best fit (95% confidence level) is 〈L(ν)〉= (460±20) − (180±40)ν m (20 dB km−1), for the frequencies ν = [0.100–0.850] GHz, assuming no reflection loss. The mean electric-field reflection coefficient is (1.7 dB reflection loss) across [0.100–0.850] GHz, and is used to correct the attenuation length. Finally, the reflected power rotated into the orthogonal antenna polarization i

In vivo assessment of diet-induced rat hepatic steatosis development by percutaneous single-fiber spectroscopy detects scattering spectral changes due to fatty infiltration

This study explores percutaneous single-fiber spectroscopy (SfS) of rat livers undergoing fatty infiltration. Eight test rats were fed a methionine-choline-deficient (MCD) diet, and four control rats were fed a normal diet. Two test rats and one control rat were euthanized on days 12, 28, 49, and 77 following initiation of the diet, after percutaneous SfS of the liver under transabdominal ultrasound guidance. Histology of each set of the two euthanized test rats showed mild and mild hepatic lipid accumulations on day 12, moderate and severe on day 28, severe and mild on day 49, and moderate and mild on day 77. Livers with moderate or higher lipid accumulation generally presented higher spectral reflectance intensity when compared to lean livers. Livers of the eight test rats on day 12, two of which had mild lipid accumulation, revealed an average scattering power of 0.37±0.14 in comparison to 0.07±0.14 for the four control rats (p<0.01). When livers of the test rats with various levels of fatty infiltration were combined, the average scattering power was 0.36±0.15 in comparison to 0.14±0.24 of the control rats (0.05<p<0.1). Increasing lipid accumulation in concentration and size seemed to cause an increase of the scattering power prior to increasing total spectral reflectance.Electrical and Computer EngineeringVeterinary Clinical Science

In vivo percutaneous reflectance spectroscopy of fatty liver development in rats suggests that the elevation of the scattering power is an early indicator of hepatic steatosis

This study assessed whether there was a scattering spectral marker quantifiable by reflectance measurements that could indicate early development of hepatic steatosis in rats for potential applications to pre-procurement organ evaluation. Sixteen rats were fed a methionine-choline-deficient (MCD) diet and eight rats were fed a normal diet. Direct assessment of the liver parenchyma of rats in vivo was performed by percutaneous reflectance spectroscopy using a single fiber probe at the beginning of diet-intake and arbitrary post-diet-intake times up to 11 weeks to render longitudinal comparison. Histological sampling of the liver over the duration of diet administration was performed on two MCD-diet treated rats and one control rat euthanized after reflectance spectroscopy measurement. The images of hematoxylin/eosin-stained liver specimens were analyzed morphometrically to evaluate the lipid size changes associated with the level of steatosis. The MCD-diet-treated group (n=16) had mild steatosis in seven rats, moderate in three rats, severe in six rats, and no other significant pathology. No control rats (n=8) developed hepatic steatosis. Among the parameters retrieved from per-SfS, only the scattering power (can be either positive or negative) appeared to be statistically different between MCD-treated and control livers. The scattering power for the 16 MCD-diet-treated livers at the time of euthanasia and presenting various levels of steatosis was 0.33±0.21, in comparison to 0.036±0.25 of the eight control livers (p=0.0189). When evaluated at days 12 and 13 combined, the scattering power of the 16 MCD-diet-treated livers was 0.32±0.17, in comparison to 0.10±0.11 of the eight control livers (p=0.0017). All of four MCD-treated livers harvested at days 12 and 13 presented mild steatosis with sub-micron size lipid droplets, even though none of the MCD-treated livers were sonographically remarkable for fatty changes. The elevation of the scattering power may be a valuable marker indicating early hepatic steatosis before the steatosis is sonographically detectable.Electrical and Computer EngineeringVeterinary Clinical Science