Microtubules are reversibly depolymerized in response to changing gaseous microenvironments within Aspergillus nidulans biofilms

PubMed Central

Shukla, Nandini; Osmani, Aysha H.; Osmani, Stephen A.

2017-01-01

How microtubules (MTs) are regulated during fungal biofilm formation is unknown. By tracking MT +end–binding proteins (+TIPS) in Aspergillus nidulans, we find that MTs are regulated to depolymerize within forming fungal biofilms. During this process, EB1, dynein, and ClipA form transient fibrous and then bar-like structures, novel configurations for +TIPS. Cells also respond in an autonomous manner, with cells separated by a septum able to maintain different MT dynamics. Surprisingly, all cells with depolymerized MTs rapidly repolymerize their MTs after air exchange above the static culture medium of biofilms. Although the specific gasotransmitter for this biofilm response is not known, we find that addition of hydrogen sulfide gas to growing cells recapitulates all aspects of reversible MT depolymerization and transient formation of +TIPs bars. However, as biofilms mature, physical removal of part of the biofilm is required to promote MT repolymerization, which occurs at the new biofilm edge. We further show MT depolymerization within biofilms is regulated by the SrbA hypoxic transcription factor and that without SrbA, MTs are maintained as biofilms form. This reveals a new mode of MT regulation in response to changing gaseous biofilm microenvironments, which could contribute to the unique characteristics of fungal biofilms in medical and industrial settings. PMID:28057761

Leadership in multiteam systems.

PubMed

DeChurch, Leslie A; Marks, Michelle A

2006-03-01

This study examined 2 leader functions likely to be instrumental in synchronizing large systems of teams (i.e., multiteam systems [MTSs]). Leader strategizing and coordinating were manipulated through training, and effects on functional leadership, interteam coordination, and MTS performance were examined. Three hundred eighty-four undergraduate students participated in a laboratory simulation modeling a 3-team MTS performing an F-22 battle simulation task (N = 64 MTSs). Results indicate that both leader training manipulations improved functional leadership and interteam coordination and that functional leader behavior was positively related to MTS-level performance. Functional leadership mediated the effects of both types of training on interteam coordination, and interteam coordination fully mediated the effect of MTS leadership on MTS performance.

Shared leadership in multiteam systems: how cockpit and cabin crews lead each other to safety.

PubMed

Bienefeld, Nadine; Grote, Gudela

2014-03-01

In this study, we aimed to examine the effect of shared leadership within and across teams in multiteam systems (MTS) on team goal attainment and MTS success. Due to different and sometimes competing goals in MTS, leadership is required within and across teams. Shared leadership, the effectiveness of which has been proven in single teams, may be an effective strategy to cope with these challenges. We observed leadership in 84 cockpit and cabin crews that collaborated in the form of six-member MTS aircrews (N = 504) during standardized simulations of an in-flight emergency. Leadership was coded by three trained observers using a structured observation system. Team goal attainment was assessed by two subject matter experts using a checklist-based rating tool. MTS goal attainment was measured objectively on the basis of the outcome of the simulated flights. In successful MTS aircrews, formal leaders and team members displayed significantly more leadership behaviors, shared leadership by pursers and flight attendants predicted team goal attainment, and pursers' shared leadership across team boundaries predicted cross-team goal attainment. In cockpit crews, leadership was not shared and captains' vertical leadership predicted team goal attainment regardless of MTS success. The results indicate that in general, shared leadership positively relates to team goal attainment and MTS success,whereby boundary spanners' dual leadership role is key. Leadership training in MTS should address shared rather than merely vertical forms of leadership, and component teams in MTS should be trained together with emphasis on boundary spanners' dual leadership role. Furthermore, team members should be empowered to engage in leadership processes when required.

[Current states and future aspects of graduate schools for adult graduate students: experiences of the master's course as a medical technologist].

PubMed

Obara, Takehiro; Suwabe, Akira

2012-12-01

The educational system for medical technologists (MTs) has gradually shifted from a three-year technical school system to a four-year university system. It is worthwhile for MTs to advance to a graduate school, in order to improve their routine-work skills, performances, and also to advance their own research as well as to learn how to direct younger MTs. Recently, MTs who advance to the graduate school as adult graduate students are increasing. In this article, the current states and future aspects of the graduate school of Iwate Medical University are reported. In our Department of Central Clinical Laboratory in Iwate Medical University Hospital, three of my colleagues have completed the master's course of the graduate school as adult graduate students, and three are currently attending the school. Nevertheless, none of them has advanced to the doctor's course yet. The primary reason why they do not advance is the heavy burden on any adult graduate students physically, mentally, and financially to study in the graduate school and carry out routine duties at the same time. Thus, in order to encourage MTs to go or to graduate school education, it is important to arrange systems which will enable MTs to advance to the graduate school as adult graduate students. I believe there are three key elements to make this possible. Firstly, prepare easier access to curriculums for MTs to study special fields and learn special skills. Secondly, arrange an increase in the salary scheme depending on the degree attained from the graduate school. Thirdly, provide financial support for graduate school expenses. In conclusion, it is expected that a large number of MTs will advance to the graduate school if these changes for a better educational environment are made.

A Muon Tomography Station with GEM Detectors for Nuclear Threat Detection

NASA Astrophysics Data System (ADS)

Staib, Michael; Gnanvo, Kondo; Grasso, Leonard; Hohlmann, Marcus; Locke, Judson; Costa, Filippo; Martoiu, Sorin; Muller, Hans

2011-10-01

Muon tomography for homeland security aims at detecting well-shielded nuclear contraband in cargo and imaging it in 3D. The technique exploits multiple scattering of atmospheric cosmic ray muons, which is stronger in dense, high-Z nuclear materials, e.g. enriched uranium, than in low-Z and medium-Z shielding materials. We have constructed and operated a compact Muon Tomography Station (MTS) that tracks muons with six to ten 30 cm x 30 cm Triple Gas Electron Multiplier (GEM) detectors placed on the sides of a 27-liter cubic imaging volume. The 2D strip readouts of the GEMs achieve a spatial resolution of ˜130 μm in both dimensions and the station is operated at a muon trigger rate of ˜20 Hz. The 1,536 strips per GEM detector are read out with the first medium-size implementation of the Scalable Readout System (SRS) developed specifically for Micro-Pattern Gas Detectors by the RD51 collaboration at CERN. We discuss the performance of this MTS prototype and present experimental results on tomographic imaging of high-Z objects with and without shielding.

A CRISPR/molecular beacon hybrid system for live-cell genomic imaging.

PubMed

Wu, Xiaotian; Mao, Shiqi; Yang, Yantao; Rushdi, Muaz N; Krueger, Christopher J; Chen, Antony K

2018-04-30

The clustered regularly interspersed short palindromic repeat (CRISPR) gene-editing system has been repurposed for live-cell genomic imaging, but existing approaches rely on fluorescent protein reporters, making sensitive and continuous imaging difficult. Here, we present a fluorophore-based live-cell genomic imaging system that consists of a nuclease-deactivated mutant of the Cas9 protein (dCas9), a molecular beacon (MB), and an engineered single-guide RNA (sgRNA) harboring a unique MB target sequence (sgRNA-MTS), termed CRISPR/MB. Specifically, dCas9 and sgRNA-MTS are first co-expressed to target a specific locus in cells, followed by delivery of MBs that can then hybridize to MTS to illuminate the target locus. We demonstrated the feasibility of this approach for quantifying genomic loci, for monitoring chromatin dynamics, and for dual-color imaging when using two orthogonal MB/MTS pairs. With flexibility in selecting different combinations of fluorophore/quencher pairs and MB/MTS sequences, our CRISPR/MB hybrid system could be a promising platform for investigating chromatin activities.

A method to track rotational motion for use in single-molecule biophysics.

PubMed

Lipfert, Jan; Kerssemakers, Jacob J W; Rojer, Maylon; Dekker, Nynke H

2011-10-01

The double helical nature of DNA links many cellular processes such as DNA replication, transcription, and repair to rotational motion and the accumulation of torsional strain. Magnetic tweezers (MTs) are a single-molecule technique that enables the application of precisely calibrated stretching forces to nucleic acid tethers and to control their rotational motion. However, conventional magnetic tweezers do not directly monitor rotation or measure torque. Here, we describe a method to directly measure rotational motion of particles in MT. The method relies on attaching small, non-magnetic beads to the magnetic beads to act as fiducial markers for rotational tracking. CCD images of the beads are analyzed with a tracking algorithm specifically designed to minimize crosstalk between translational and rotational motion: first, the in-plane center position of the magnetic bead is determined with a kernel-based tracker, while subsequently the height and rotation angle of the bead are determined via correlation-based algorithms. Evaluation of the tracking algorithm using both simulated images and recorded images of surface-immobilized beads demonstrates a rotational resolution of 0.1°, while maintaining a translational resolution of 1-2 nm. Example traces of the rotational fluctuations exhibited by DNA-tethered beads confined in magnetic potentials of varying stiffness demonstrate the robustness of the method and the potential for simultaneous tracking of multiple beads. Our rotation tracking algorithm enables the extension of MTs to magnetic torque tweezers (MTT) to directly measure the torque in single molecules. In addition, we envision uses of the algorithm in a range of biophysical measurements, including further extensions of MT, tethered particle motion, and optical trapping measurements.

Microtubules are reversibly depolymerized in response to changing gaseous microenvironments within Aspergillus nidulans biofilms.

PubMed

Shukla, Nandini; Osmani, Aysha H; Osmani, Stephen A

2017-03-01

How microtubules (MTs) are regulated during fungal biofilm formation is unknown. By tracking MT +end-binding proteins (+TIPS) in Aspergillus nidulans , we find that MTs are regulated to depolymerize within forming fungal biofilms. During this process, EB1, dynein, and ClipA form transient fibrous and then bar-like structures, novel configurations for +TIPS. Cells also respond in an autonomous manner, with cells separated by a septum able to maintain different MT dynamics. Surprisingly, all cells with depolymerized MTs rapidly repolymerize their MTs after air exchange above the static culture medium of biofilms. Although the specific gasotransmitter for this biofilm response is not known, we find that addition of hydrogen sulfide gas to growing cells recapitulates all aspects of reversible MT depolymerization and transient formation of +TIPs bars. However, as biofilms mature, physical removal of part of the biofilm is required to promote MT repolymerization, which occurs at the new biofilm edge. We further show MT depolymerization within biofilms is regulated by the SrbA hypoxic transcription factor and that without SrbA, MTs are maintained as biofilms form. This reveals a new mode of MT regulation in response to changing gaseous biofilm microenvironments, which could contribute to the unique characteristics of fungal biofilms in medical and industrial settings. © 2017 Shukla et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Can urgency classification of the Manchester triage system predict serious bacterial infections in febrile children?

PubMed

Nijman, Ruud G; Zwinkels, Rob L J; van Veen, Mirjam; Steyerberg, Ewout W; van der Lei, Johan; Moll, Henriëtte A; Oostenbrink, Rianne

2011-08-01

To evaluate the discriminative ability of the Manchester triage system (MTS) to identify serious bacterial infections (SBIs) in children with fever in the emergency department (ED) and to study the association between predictors of SBI and discriminators of MTS urgency of care. This prospective observational study included 1255 children with fever (1 month-16 years) attending the ED of the Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands in 2008-9. Triage urgency was determined with the MTS (urgency (U) level 1-5). The relationship between triage urgency and SBI was assessed with multivariable logistic regression, including effects of age, sex and temperature. Discriminative ability was assessed by receiver operating characteristic curve analysis. SBI prevalence was 11% (n=131, 95% CI 9% to 12%). The discriminative value of the MTS for predicting SBI was 0.57 (95% CI 0.52 to 0.62), and the MTS did not contribute to a model including age, sex and temperature. The sensitivity of the MTS (U1-2 vs U3-5) to detect SBI was 0.42 (95% CI 0.33 to 0.51) and specificity was 0.69 (95% CI 0.66 to 0.72). MTS high urgency discriminators include several known predictors of SBI, such as fever, work of breathing, meningism and oxygen saturation, but apply to non-SBI children as well. The MTS has poor discriminative ability to predict the presence of SBIs in children presenting with fever to the paediatric ED. Important predictors of SBI are represented within the MTS, but are used in a different way to classify urgency.

Development of a novel Global Trauma System Evaluation Tool and initial results of implementation in the Republic of South Sudan.

PubMed

Remick, Kyle N; Wong, Evan G; Chuot Chep, Chep; Morton, Richard T; Monsour, Abdullah; Fisher, Dane; Oh, John S; Wilson, Ramey; Malone, Debra L; Branas, Charles; Elster, Eric; Gross, Kirby R; Kushner, Adam L

2014-11-01

Trauma remains a leading cause of death and disability in the world, and trauma systems decrease mortality from trauma. We developed the Global Trauma System Evaluation Tool (G-TSET) specifically for use in low- and middle-income countries (LMICs). The Sudan People's Liberation Army (SPLA) in the Republic of South Sudan (RSS) desires a military trauma system (MTS) which allowed us to pilot the G-TSET. The G-TSET was developed by modifying key components of a trauma system applicable to LMICs. We partnered with the SPLA Medical Corps using clinical collaboration, direct observation, and discussion groups. Benchmarks and indicators were scored with 5 indicating "full capability" and 1 meaning "not present" and were used to develop a SPLA MTS plan. The overall MTS score was 1.15 indicating an urgent need for system development. The assessment highlighted the need for SPLA Command support. Battlefield care, transport to a trauma facility, and inter-facility communication were identified for improvement. After essential battlefield care, consisting primarily of bandaging and splinting, transport times for injured SPLA soldiers were 12h to 3 days by truck. Based on our findings, we collaborated with SPLA medical leadership to develop a plan to develop a formal MTS. We piloted a novel trauma system assessment tool for the MTS in the RSS. Qualitatively, we identified gaps in the MTS and provided the medical leadership with a plan for improvement. We anticipate a short-term follow-up to quantify improvement, and we seek to validate this tool for use in other countries. Published by Elsevier Ltd.

Evolution of stimulants to treat ADHD: transdermal methylphenidate

PubMed Central

Patrick, Kennerly S.; Straughn, Arthur B.; Perkins, Jeb S.; González, Mario A.

2009-01-01

Objective The following comprehensive review describes the evolution of stimulant drug formulations used in the treatment of attention-deficit/hyperactivity disorder (ADHD). Emphasis is placed on the basic and clinical pharmacology of the dl-methylphenidate (MPH) transdermal system (MTS). Methods The pharmacokinetic and pharmacodynamic literature pertaining to MPH and amphetamine enantiomers was reviewed in the context of ADHD therapy and MTS as a treatment option. Results MTS incorporates MPH into an adhesive monolithic matrix, using the free base form of the drug to facilitate transdermal absorption. MTS technology minimizes contact dermatitis by eliminating to need for percutaneous penetration enhancers. After a lag time of approximately 2 h, plasma concentrations of the therapeutic d-MPH isomer become detectable, then continuously rise over the course of the recommended 9 h wear time. Concentrations of l-MPH typically attain 40−50% that of d-MPH (vs. 1−2% following oral MPH). Unauthorized MTS removal poses some misuse liability and over 50% of MTS drug content remains in the discarded system. Conclusions While liquid or chewable MPH formulations overcome potential swallowing difficulties, as do sprinkled once-daily extended-release (ER) MPH products, only MTS addresses swallowing difficulties while also offering a flexible individualized MPH exposure time in a once-daily MPH regimen. PMID:19051222

Differential exhumation at eastern margin of the Tibetan Plateau, from apatite fission-track thermochronology

NASA Astrophysics Data System (ADS)

Deng, Bin; Liu, Shu-gen; Li, Zhi-wu; Jansa, Luba F.; Liu, Shun; Wang, Guo-zhi; Sun, Wei

2013-04-01

New apatite fission-track (AFT) ages from Mesozoic sediments in the Sichuan basin, combined with previous fission-track data, demonstrate differential uplift and exhumation across the basin. Particularly significant change in exhumation (at least ~ 2000 m) was found across the Huaying Mts. Modeled temperature-time histories and the Boomerang plot of AFT dataset across the basin suggest rapid cooling and exhumation events during 120-80 Ma and at 20-10 Ma. They reflect the start of the basin-scale differential uplift and exhumation which effected the eastern growth of Tibetan Plateau. In particular, nested old-age center separated by Huaying Mts. was found in the center-to-northwest part of the Sichuan basin. A simplified one-dimensional, steady-state solution model was developed to calculate the mean exhumation rate, which is 0.05-0.2 mm/yr in most parts of the basin. It suggests a slow exhumation across much of the basin. The regional pattern of AFT age, length and erosion rate supports a progressive change from the nested old-age center towards the southwest. This pattern supports the idea of a prolonged, steady-state uplift and exhumation process across the basin, controlled by cratonic basin structure. The eastern growth of the Tibetan Plateau has exerted a significant effect on the rapid exhumation of the southwestern part of the Sichuan basin, but not on all of the basin during the Late Cenozoic.

A Pilot Investigation Comparing Instructional Packages for MTS Training: "Manual Alone" vs. "Manual-Plus-Computer-Aided Personalized System of Instruction"

ERIC Educational Resources Information Center

Oliveira, Marileide; Goyos, Celso; Pear, Joseph

2012-01-01

Matching-to-sample (MTS) training consists of presenting a stimulus as a sample followed by stimuli called comparisons from which a subject makes a choice. This study presents results of a pilot investigation comparing two packages for teaching university students to conduct MTS training. Two groups--control and experimental--with 2 participants…

Augmented reality guidance system for peripheral nerve blocks

NASA Astrophysics Data System (ADS)

Wedlake, Chris; Moore, John; Rachinsky, Maxim; Bainbridge, Daniel; Wiles, Andrew D.; Peters, Terry M.

2010-02-01

Peripheral nerve block treatments are ubiquitous in hospitals and pain clinics worldwide. State of the art techniques use ultrasound (US) guidance and/or electrical stimulation to verify needle tip location. However, problems such as needle-US beam alignment, poor echogenicity of block needles and US beam thickness can make it difficult for the anesthetist to know the exact needle tip location. Inaccurate therapy delivery raises obvious safety and efficacy issues. We have developed and evaluated a needle guidance system that makes use of a magnetic tracking system (MTS) to provide an augmented reality (AR) guidance platform to accurately localize the needle tip as well as its projected trajectory. Five anesthetists and five novices performed simulated nerve block deliveries in a polyvinyl alcohol phantom to compare needle guidance under US alone to US placed in our AR environment. Our phantom study demonstrated a decrease in targeting attempts, decrease in contacting of critical structures, and an increase in accuracy of 0.68 mm compared to 1.34mm RMS in US guidance alone. Currently, the MTS uses 18 and 21 gauge hypodermic needles with a 5 degree of freedom sensor located at the needle tip. These needles can only be sterilized using an ethylene oxide process. In the interest of providing clinicians with a simple and efficient guidance system, we also evaluated attaching the sensor at the needle hub as a simple clip-on device. To do this, we simultaneously performed a needle bending study to assess the reliability of a hub-based sensor.

Maritime trade & transportation 2002

DOT National Transportation Integrated Search

2002-01-01

The Marine Transportation System (MTS) contributes to U.S. economic growth, enhances U.S. global competitiveness, and supports national security objectives. The MTS consists of an extensive network of waterways, ports, and their intermodal connectors...

Monoterpenes released from fruit, plant, and vegetable systems.

PubMed

Iqbal, Mohammad Asif; Kim, Ki-Hyun; Ahn, Jeong Hyeon

2014-09-29

To quantify the emission rate of monoterpenes (MTs) from diverse natural sources, the sorbent tube (ST)-thermal desorption (TD) method was employed to conduct the collection and subsequent detection of MTs by gas chromatography. The calibration of MTs, when made by both mass spectrometric (MS) and flame ionization detector (FID), consistently exhibited high coefficient of determination values (R2 > 0.99). This approach was employed to measure their emission rate from different fruit/plant/vegetable (F/P/V) samples with the aid of an impinger-based dynamic headspace sampling system. The results obtained from 10 samples (consisting of carrot, pine needle (P. sylvestris), tangerine, tangerine peel, strawberry, sepals of strawberry, plum, apple, apple peel, and orange juice) marked α-pinene, β-pinene, myrcene, α-terpinene, R-limonene, γ-terpinene, and p-cymene as the most common MTs. R-limonene was the major species emitted from citrus fruits and beverages with its abundance exceeding 90%. In contrast, α-pinene was the most abundant MT (37%) for carrot, while it was myrcene (31%) for pine needle. The overall results for F/P/V samples confirmed α-pinene, β-pinene, myrcene, α-terpinene, and γ-terpinene as common MTs. Nonetheless, the types and magnitude of MTs released from fruits were distinguished from those of vegetables and plants.

Mechanisms for focusing mitotic spindle poles by minus end-directed motor proteins.

PubMed

Goshima, Gohta; Nédélec, François; Vale, Ronald D

2005-10-24

During the formation of the metaphase spindle in animal somatic cells, kinetochore microtubule bundles (K fibers) are often disconnected from centrosomes, because they are released from centrosomes or directly generated from chromosomes. To create the tightly focused, diamond-shaped appearance of the bipolar spindle, K fibers need to be interconnected with centrosomal microtubules (C-MTs) by minus end-directed motor proteins. Here, we have characterized the roles of two minus end-directed motors, dynein and Ncd, in such processes in Drosophila S2 cells using RNA interference and high resolution microscopy. Even though these two motors have overlapping functions, we show that Ncd is primarily responsible for focusing K fibers, whereas dynein has a dominant function in transporting K fibers to the centrosomes. We also report a novel localization of Ncd to the growing tips of C-MTs, which we show is mediated by the plus end-tracking protein, EB1. Computer modeling of the K fiber focusing process suggests that the plus end localization of Ncd could facilitate the capture and transport of K fibers along C-MTs. From these results and simulations, we propose a model on how two minus end-directed motors cooperate to ensure spindle pole coalescence during mitosis.

Short-term predictive capacity of two different triage systems in patients with acute heart failure: TRICA-EAHFE study.

PubMed

Miró, Òscar; Tost, Josep; Herrero, Pablo; Jacob, Javier; Martín-Sánchez, Francisco Javier; Gil, Víctor; Fernández-Pérez, Cristina; Escoda, Rosa; Llorens, Pere

2016-12-01

To evaluate whether prioritization of patients with acute heart failure (AHF) in the Andorran Triage Model/Spanish Triage System (MAT/SET) and the Manchester Triage System (MTS) also allows the identification of different profiles of outcome and prognosis and determine whether either system has a better predictive capacity of outcomes. Patients with AHF included in the Spanish EAHFE registry from hospitals using the MAT/SET or MTS were selected and divided according to the triage system used. Outcome variables included hospital admission, length of stay, death during admission, 3, 7, and 30-day all-cause mortality, and emergency department (ED) reconsultation at 30 days. The results were compared according to the level of priority and the triage system used. We included 3837 patients (MAT/SET=2474; MTS=1363) classified as follows: 4.0% level 1; 34.7% level 2; 55.1% level 3; and 6.3% levels 4-5. Both systems associated greater priority with higher rates of admission and mortality; the MTS associated greater priority with greater ED reconsultation and the MAT/SET found greater priority to be associated with less ED reconsultation. The discriminative capacity of the two scales for adverse outcomes was statistically significant, albeit poor, for almost all the outcome events and it was of scarce clinical relevance (Area under the curve of the receiver operating characteristic between 0.458 and 0.661). The prediction of the outcome of patients with AHF determined with the MAT/SET or MTS showed scarce differences between the two systems, and their discriminative capacity does not seem to be clinically relevant.

Metallothionein Induction as Indicator of Low Level Metal Exposure to Aquatic Macroinvertebrates from a Relatively Unimpacted River System in South Africa.

PubMed

Kemp, M; Wepener, V; de Kock, K N; Wolmarans, C T

2017-12-01

The Marico River is relatively unaffected by anthropogenic activities. However, metal concentrations-mainly from natural sources-occasionally exceed environmental quality guidelines. Macroinvertebrates are capable to react to these metals through processes such as the induction of metallothioneins (MTs). The aims of this study were to determine whether the induction of MTs can be used as indicator of natural metal exposure in not anthropogenically impacted systems and whether there are relationships between metal concentrations in water, sediment and macroinvertebrates and concomitant MT levels. Positive correlations were found between metals in sediment and macroinvertebrates, while there were no correlations between metal concentrations in water and macroinvertebrates. Even in a not anthropogenically impacted system, a positive correlation existed between trace metal bioaccumulation (e.g. Ni, Pb, Zn) in macroinvertebrates and the induction of MTs. There were, however, no correlations between MTs and bioaccumulation of earth metals (e.g. Al, Fe, Mn, Ti).

Transdermal and oral dl-methylphenidate-ethanol interactions in C57BL/6J mice: transesterification to ethylphenidate and elevation of d-methylphenidate concentrations.

PubMed

Bell, Guinevere H; Novak, Andrew J; Griffin, William C; Patrick, Kennerly S

2011-07-01

We tested the hypothesis that C57BL/6J mice will model human metabolic interactions between dl-methylphenidate (MPH) and ethanol, placing an emphasis on the MPH transdermal system (MTS). Specifically, we asked: (1) will ethanol increase d-MPH biological concentrations, (2) will MTS facilitate the systemic bioavailability of l-MPH, and (3) will l-MPH enantioselectively interact with ethanol to yield l-ethylphenidate (l-EPH)? Mice were dosed with MTS (¼ of a 12.5 cm(2) patch on shaved skin) or a comparable oral dl-MPH dose (7.5 mg/kg), with or without ethanol (3.0 g/kg), and then placed in metabolic cages for 3 h. MPH and EPH isomer concentrations in blood, brain, and urine were analyzed by gas chromatographic-mass spectrometry monitoring of N-(S)-prolylpiperidyl fragments. As in humans, MTS greatly facilitated the absorption of l-MPH in this mouse strain. Similarly, ethanol led to the enantioselective formation of l-EPH and to an elevation in d-MPH concentrations with both MTS and oral MPH. Although only guarded comparisons between MTS and oral MPH can be made due to route-dependent drug absorption rate differences, MTS was associated with significant MPH-ethanol interactions. Ethanol-mediated increases in circulating concentrations of d-MPH carry toxicological and abuse liability implications should this animal model hold for ethanol-consuming attention-deficit hyperactivity disorder patients or coabusers. Copyright © 2011 Wiley-Liss, Inc. and the American Pharmacists Association

Evaluation of atomic pressure in the multiple time-step integration algorithm.

PubMed

Andoh, Yoshimichi; Yoshii, Noriyuki; Yamada, Atsushi; Okazaki, Susumu

2017-04-15

In molecular dynamics (MD) calculations, reduction in calculation time per MD loop is essential. A multiple time-step (MTS) integration algorithm, the RESPA (Tuckerman and Berne, J. Chem. Phys. 1992, 97, 1990-2001), enables reductions in calculation time by decreasing the frequency of time-consuming long-range interaction calculations. However, the RESPA MTS algorithm involves uncertainties in evaluating the atomic interaction-based pressure (i.e., atomic pressure) of systems with and without holonomic constraints. It is not clear which intermediate forces and constraint forces in the MTS integration procedure should be used to calculate the atomic pressure. In this article, we propose a series of equations to evaluate the atomic pressure in the RESPA MTS integration procedure on the basis of its equivalence to the Velocity-Verlet integration procedure with a single time step (STS). The equations guarantee time-reversibility even for the system with holonomic constrants. Furthermore, we generalize the equations to both (i) arbitrary number of inner time steps and (ii) arbitrary number of force components (RESPA levels). The atomic pressure calculated by our equations with the MTS integration shows excellent agreement with the reference value with the STS, whereas pressures calculated using the conventional ad hoc equations deviated from it. Our equations can be extended straightforwardly to the MTS integration algorithm for the isothermal NVT and isothermal-isobaric NPT ensembles. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Emerging roles for microtubules in angiosperm pollen tube growth highlight new research cues

PubMed Central

Onelli, Elisabetta; Idilli, Aurora I.; Moscatelli, Alessandra

2015-01-01

In plants, actin filaments have an important role in organelle movement and cytoplasmic streaming. Otherwise microtubules (MTs) have a role in restricting organelles to specific areas of the cell and in maintaining organelle morphology. In somatic plant cells, MTs also participate in cell division and morphogenesis, allowing cells to take their definitive shape in order to perform specific functions. In the latter case, MTs influence assembly of the cell wall, controlling the delivery of enzymes involved in cellulose synthesis and of wall modulation material to the proper sites. In angiosperm pollen tubes, organelle movement is generally attributed to the acto-myosin system, the main role of which is in distributing organelles in the cytoplasm and in carrying secretory vesicles to the apex for polarized growth. Recent data on membrane trafficking suggests a role of MTs in fine delivery and repositioning of vesicles to sustain pollen tube growth. This review examines the role of MTs in secretion and endocytosis, highlighting new research cues regarding cell wall construction and pollen tube-pistil crosstalk, that help unravel the role of MTs in polarized growth. PMID:25713579

Fast Multivariate Search on Large Aviation Datasets

NASA Technical Reports Server (NTRS)

Bhaduri, Kanishka; Zhu, Qiang; Oza, Nikunj C.; Srivastava, Ashok N.

2010-01-01

Multivariate Time-Series (MTS) are ubiquitous, and are generated in areas as disparate as sensor recordings in aerospace systems, music and video streams, medical monitoring, and financial systems. Domain experts are often interested in searching for interesting multivariate patterns from these MTS databases which can contain up to several gigabytes of data. Surprisingly, research on MTS search is very limited. Most existing work only supports queries with the same length of data, or queries on a fixed set of variables. In this paper, we propose an efficient and flexible subsequence search framework for massive MTS databases, that, for the first time, enables querying on any subset of variables with arbitrary time delays between them. We propose two provably correct algorithms to solve this problem (1) an R-tree Based Search (RBS) which uses Minimum Bounding Rectangles (MBR) to organize the subsequences, and (2) a List Based Search (LBS) algorithm which uses sorted lists for indexing. We demonstrate the performance of these algorithms using two large MTS databases from the aviation domain, each containing several millions of observations Both these tests show that our algorithms have very high prune rates (>95%) thus needing actual

Multiple-time-stepping generalized hybrid Monte Carlo methods

DOE Office of Scientific and Technical Information (OSTI.GOV)

Escribano, Bruno, E-mail: bescribano@bcamath.org; Akhmatskaya, Elena; IKERBASQUE, Basque Foundation for Science, E-48013 Bilbao

2015-01-01

Performance of the generalized shadow hybrid Monte Carlo (GSHMC) method [1], which proved to be superior in sampling efficiency over its predecessors [2–4], molecular dynamics and hybrid Monte Carlo, can be further improved by combining it with multi-time-stepping (MTS) and mollification of slow forces. We demonstrate that the comparatively simple modifications of the method not only lead to better performance of GSHMC itself but also allow for beating the best performed methods, which use the similar force splitting schemes. In addition we show that the same ideas can be successfully applied to the conventional generalized hybrid Monte Carlo method (GHMC).more » The resulting methods, MTS-GHMC and MTS-GSHMC, provide accurate reproduction of thermodynamic and dynamical properties, exact temperature control during simulation and computational robustness and efficiency. MTS-GHMC uses a generalized momentum update to achieve weak stochastic stabilization to the molecular dynamics (MD) integrator. MTS-GSHMC adds the use of a shadow (modified) Hamiltonian to filter the MD trajectories in the HMC scheme. We introduce a new shadow Hamiltonian formulation adapted to force-splitting methods. The use of such Hamiltonians improves the acceptance rate of trajectories and has a strong impact on the sampling efficiency of the method. Both methods were implemented in the open-source MD package ProtoMol and were tested on a water and a protein systems. Results were compared to those obtained using a Langevin Molly (LM) method [5] on the same systems. The test results demonstrate the superiority of the new methods over LM in terms of stability, accuracy and sampling efficiency. This suggests that putting the MTS approach in the framework of hybrid Monte Carlo and using the natural stochasticity offered by the generalized hybrid Monte Carlo lead to improving stability of MTS and allow for achieving larger step sizes in the simulation of complex systems.« less

The German Version of the Manchester Triage System and Its Quality Criteria – First Assessment of Validity and Reliability

PubMed Central

Gräff, Ingo; Goldschmidt, Bernd; Glien, Procula; Bogdanow, Manuela; Fimmers, Rolf; Hoeft, Andreas; Kim, Se-Chan; Grigutsch, Daniel

2014-01-01

Background The German Version of the Manchester Triage System (MTS) has found widespread use in EDs across German-speaking Europe. Studies about the quality criteria validity and reliability of the MTS currently only exist for the English-language version. Most importantly, the content of the German version differs from the English version with respect to presentation diagrams and change indicators, which have a significant impact on the category assigned. This investigation offers a preliminary assessment in terms of validity and inter-rater reliability of the German MTS. Methods Construct validity of assigned MTS level was assessed based on comparisons to hospitalization (general / intensive care), mortality, ED and hospital length of stay, level of prehospital care and number of invasive diagnostics. A sample of 45,469 patients was used. Inter-rater agreement between an expert and triage nurses (reliability) was calculated separately for a subset group of 167 emergency patients. Results For general hospital admission the area under the curve (AUC) of the receiver operating characteristic was 0.749; for admission to ICU it was 0.871. An examination of MTS-level and number of deceased patients showed that the higher the priority derived from MTS, the higher the number of deaths (p<0.0001 / χ2 Test). There was a substantial difference in the 30-day survival among the 5 MTS categories (p<0.0001 / log-rank test).The AUC for the predict 30-day mortality was 0.613. Categories orange and red had the highest numbers of heart catheter and endoscopy. Category red and orange were mostly accompanied by an emergency physician, whereas categories blue and green were walk-in patients. Inter-rater agreement between expert triage nurses was almost perfect (κ = 0.954). Conclusion The German version of the MTS is a reliable and valid instrument for a first assessment of emergency patients in the emergency department. PMID:24586477

Long-Term Effects of Methylphenidate Transdermal Delivery System Treatment of ADHD on Growth

ERIC Educational Resources Information Center

Faraone, Stephen V.; Giefer, Eldred E.

2007-01-01

Objective: To examine the long-term effects of the methylphenidate transdermal system (MTS) on the growth of children being treated for attention-deficit/hyperactivity disorder. Method: Height, weight, and body mass index (BMI) were measured in 127 children ages 6 to 12 at longitudinal assessments for up to 36 months of treatment with MTS. These…

Assessment of a Rotating Time Sampling Procedure: Implications for Interobserver Agreement and Response Measurement

ERIC Educational Resources Information Center

Becraft, Jessica L.; Borrero, John C.; Davis, Barbara J.; Mendres-Smith, Amber E.

2016-01-01

The current study was designed to evaluate a rotating momentary time sampling (MTS) data collection system. A rotating MTS system has been used to measure activity preferences of preschoolers but not to collect data on responses that vary in duration and frequency (e.g., talking). We collected data on talking for 10 preschoolers using a 5-s MTS…

Modified Mahalanobis Taguchi System for Imbalance Data Classification

PubMed Central

2017-01-01

The Mahalanobis Taguchi System (MTS) is considered one of the most promising binary classification algorithms to handle imbalance data. Unfortunately, MTS lacks a method for determining an efficient threshold for the binary classification. In this paper, a nonlinear optimization model is formulated based on minimizing the distance between MTS Receiver Operating Characteristics (ROC) curve and the theoretical optimal point named Modified Mahalanobis Taguchi System (MMTS). To validate the MMTS classification efficacy, it has been benchmarked with Support Vector Machines (SVMs), Naive Bayes (NB), Probabilistic Mahalanobis Taguchi Systems (PTM), Synthetic Minority Oversampling Technique (SMOTE), Adaptive Conformal Transformation (ACT), Kernel Boundary Alignment (KBA), Hidden Naive Bayes (HNB), and other improved Naive Bayes algorithms. MMTS outperforms the benchmarked algorithms especially when the imbalance ratio is greater than 400. A real life case study on manufacturing sector is used to demonstrate the applicability of the proposed model and to compare its performance with Mahalanobis Genetic Algorithm (MGA). PMID:28811820

Switching from oral extended-release methylphenidate to the methylphenidate transdermal system: continued ADHD symptom control and tolerability after abrupt conversion

PubMed Central

Arnold, L. E.; Hodgkins, P.; McKay, M.; Beckett-Thurman, L.; Greenbaum, M.; Bukstein, O.; Patel, A.; Bozzolo, D. R.

2013-01-01

Objective To evaluate symptom control and tolerability after abrupt conversion from oral extended-release methylphenidate (ER-MPH) to methylphenidate transdermal system (MTS) via a dose-transition schedule in children with attention-deficit/hyperactivity disorder (ADHD). Methods In a 4-week, prospective, multisite, open-label study, 171 children (164 intent-to-treat) with diagnosed ADHD aged 6–12 years abruptly switched from a stable dose of oral ER-MPH to MTS in nominal dosages of 10, 15, 20, and 30 mg using a predefined dose-transition schedule. After the first week on the scheduled dose, the dose was titrated to optimal effect. The primary effectiveness outcome was the change from baseline (while taking ER-MPH) to week 4 in ADHD-Rating Scale-IV (ADHD-RS-IV) total scores. Adverse events (AEs) were assessed throughout the study. Results Most subjects (58%) remained on the initial MTS dose defined by the dose-transition schedule; 38% increased and 4% decreased their MTS dose for optimization. MTS dose optimization resulted in significantly better ADHD-RS-IV total (mean ± SD) scores at week 4 than at baseline (9.9±7.47 vs 14.1±7.48; p<0.0001). The most commonly reported AEs included headache, decreased appetite, insomnia, and upper abdominal pain. Four subjects (2.3%) discontinued because of application site reactions and 3 discontinued because of other AEs. Conclusions Abrupt conversion from a stable dose of oral ER-MPH to MTS was accomplished using a predefined dose-transition schedule without loss of symptom control; however, careful titration to optimal dose is recommended. Most AEs were mild to moderate and, with the exception of application site reactions, were similar to AEs typically observed with oral MPH. Limitations of this study included its open-label sequential design without placebo, which could result in spurious attribution of improvement to the study treatment and precluded superiority determinations of MTS over baseline ER-MPH treatment. The apparent superiority of MTS was likely due to more careful titration and clinical monitoring rather than the product itself. NCT NCT00151983 PMID:19916704

Oral immunization of Carassius auratus with modified recombinant A-layer proteins entrapped in alginate beads.

PubMed

Maurice, Sarah; Nussinovitch, Amos; Jaffe, Nicole; Shoseyov, Oded; Gertler, Arieh

2004-12-09

This study was focused on the utilization of a recombinant expression system to produce a unique modified subunit vaccine possessing a self-contained delivery system which could potentially improve the uptake and delivery of vaccine products as well their immunogenic potential. For this purpose the A-layer protein (At-R) associated with the fish pathogen atypical Aeromonas salmonicida was cloned and modified by the genetic fusion of the protein transduction domain (MTS) derived from Kaposi fibroblast growth factor (At-MTS). The potential for these proteins to be employed as antigens for oral immunization of goldfish was examined by encapsulation of At-R, At-MTS and the control, BSA, into biodegradable alginate gel macrospheres which were fed to goldfish in place of standard pellet fish feed. The bead physical properties were modified only in the presence of At-R and the temporal release of proteins was significantly less when At-MTS was employed. Western blot analysis of serum samples collected from fish following intubation with the recombinant proteins determined that the rate of protein uptake from the digestive tract into the blood system improved considerably when MTS was fused to At-R. Experimental fish were fed one of three protein-alginate formulae on a schedule of 3 days/week or 5 days/month for a period of 2 months. After 1 month, animals fed on the 5-day protocol demonstrated increased serum antibody titers while following an additional month of feeding this level decreased and titers were found to be higher in fish maintained on the 3-day regime. Fish fed At-MTS maintained the highest titer at the end of 2-month period. To determine whether the diminished antibody titers were a result of oral tolerance fish were injected intraperitoneally with the At-R antigen. Only experimental groups which had been fed At-R or At-MTS demonstrated increased antibody titers which paralleled a typical secondary humoral response. In spite of the presence of an increased titer to A-protein, vaccinated fish did not demonstrate resistance to infection with atypical A. salmonicida.

The impact of metabolic syndrome on the responsiveness to α1-blocker in men with BPH/LUTS.

PubMed

Lee, Y-C; Liu, C-C; Juan, Y-S; Wu, W-J; Li, W-M; Yeh, H-C; Wang, C-J; Huang, C-N; Huang, C-H; Huang, S-P

2013-04-01

Increasing evidence has proposed the components of metabolic syndrome (MtS) as risk factors for the development of benign prostate hyperplasia (BPH); therefore, it is thought that MtS may play a role in lower urinary tract symptoms related to BPH (BPH/LUTS) aetiology. Considering the closed relationships between MtS and BPH/LUTS, it is possible that patients with MtS might have different drug responsiveness in men with BPH/LUTS. We prospectively investigated the impact of MtS on responsiveness to α1-blocker in men with BPH/LUTS. We enrolled a total of 109 patients with a mean (SD) age of 59.8 (9.0) years, having a prostate volume of 20 cm(3) or greater with moderate to severe LUTS. All patients received doxazosin GITS (gastrointestinal therapeutic system) 4 mg once daily for a 12-week period of treatment. The efficacy measurement was assessed by the changes from baseline in the total IPSS, maximum urinary flow rate and postvoid residual urine volume. The drug responders were defined as those who had a total IPSS decrease of more than 4 points from baseline after 12 weeks of treatment. Using multiple logistic regression analysis, our results showed that MtS was an independent factor for drug non-responder (OR = 4.26, p = 0.002). The rate of drug responder and total IPSS improvements in patients with MtS significantly decreased as the number of MtS components increased (p = 0.012 and p = 0.026). Among the MtS components, abnormal fasting blood glucose (FBG) was the most significantly independent factor for drug non-responder (OR = 3.17, p = 0.020). This study suggested that the presence of MtS had a significantly negative impact on the responsiveness to α1-blocker in men with BPH/LUTS. Our results are important for BPH/LUTS patients who did not initially respond to α1-blocker or who strive to reduce these metabolic risk factors. © 2013 Blackwell Publishing Ltd.

Solar Power Satellite system in formation on a common geostationary orbit

NASA Astrophysics Data System (ADS)

Salazar, F. J. T.; Winter, O. C.

2017-10-01

The diurnal day-night cycle severely limits the Terrestrial solar power. To overcome this limitation, a Solar Power Satellite (SPS) system, consisting of a sunlight reflector and a microwave energy generator-transmitter in formation, is presented in this work. The microwave transmitting satellite (MTS) is placed on a common geostationary orbit (GEO) in the Earth’s equatorial plane, and the sunlight reflector uses the solar radiation pressure to achieve quasi-periodic orbits about the MTS, so that the sunlight is always redirected to the MTS, which converts the solar energy in electromagnetic power and transmits it by microwaves to an Earth-receiving antenna. Assuming the sun line direction constant at dierent seasons (i.e. autumn/spring equinoxes and winter and summer solstices), previous studies have shown the existence of a family of displaced ecliptic orbits above or below the equatorial plane of the Earth around a GEO. In this study, the position of the Sun is assumed on the ecliptic plane with a mean obliquity (inclination of Earth’s equator with respect to the ecliptic) of 23.5◦. A linear solution as an initial condition for the full equations of motions about a GEO, which yields bounded orbit for the sunlight reflector about the MTS in the Earth-satellite two-body problem with solar radiation pressure. To redirect the sunlight to the MTS, the law of reflection is satisfied by the space mirror attitude.

A Regularized Linear Dynamical System Framework for Multivariate Time Series Analysis.

PubMed

Liu, Zitao; Hauskrecht, Milos

2015-01-01

Linear Dynamical System (LDS) is an elegant mathematical framework for modeling and learning Multivariate Time Series (MTS). However, in general, it is difficult to set the dimension of an LDS's hidden state space. A small number of hidden states may not be able to model the complexities of a MTS, while a large number of hidden states can lead to overfitting. In this paper, we study learning methods that impose various regularization penalties on the transition matrix of the LDS model and propose a regularized LDS learning framework (rLDS) which aims to (1) automatically shut down LDSs' spurious and unnecessary dimensions, and consequently, address the problem of choosing the optimal number of hidden states; (2) prevent the overfitting problem given a small amount of MTS data; and (3) support accurate MTS forecasting. To learn the regularized LDS from data we incorporate a second order cone program and a generalized gradient descent method into the Maximum a Posteriori framework and use Expectation Maximization to obtain a low-rank transition matrix of the LDS model. We propose two priors for modeling the matrix which lead to two instances of our rLDS. We show that our rLDS is able to recover well the intrinsic dimensionality of the time series dynamics and it improves the predictive performance when compared to baselines on both synthetic and real-world MTS datasets.

Development of the network architecture of the Canadian MSAT system

NASA Technical Reports Server (NTRS)

Davies, N. George; Shoamanesh, Alireza; Leung, Victor C. M.

1988-01-01

A description is given of the present concept for the Canadian Mobile Satellite (MSAT) System and the development of the network architecture which will accommodate the planned family of three categories of service: a mobile radio service (MRS), a mobile telephone service (MTS), and a mobile data service (MDS). The MSAT satellite will have cross-strapped L-band and Ku-band transponders to provide communications services between L-band mobile terminals and fixed base stations supporting dispatcher-type MRS, gateway stations supporting MTS interconnections to the public telephone network, data hub stations supporting the MDS, and the network control center. The currently perceived centralized architecture with demand assignment multiple access for the circuit switched MRS, MTS and permanently assigned channels for the packet switched MDS is discussed.

Development of the network architecture of the Canadian MSAT system

NASA Astrophysics Data System (ADS)

Davies, N. George; Shoamanesh, Alireza; Leung, Victor C. M.

1988-05-01

A description is given of the present concept for the Canadian Mobile Satellite (MSAT) System and the development of the network architecture which will accommodate the planned family of three categories of service: a mobile radio service (MRS), a mobile telephone service (MTS), and a mobile data service (MDS). The MSAT satellite will have cross-strapped L-band and Ku-band transponders to provide communications services between L-band mobile terminals and fixed base stations supporting dispatcher-type MRS, gateway stations supporting MTS interconnections to the public telephone network, data hub stations supporting the MDS, and the network control center. The currently perceived centralized architecture with demand assignment multiple access for the circuit switched MRS, MTS and permanently assigned channels for the packet switched MDS is discussed.

The robotic ENT microsurgery system: A novel robotic platform for microvascular surgery.

PubMed

Feng, Allen L; Razavi, Christopher R; Lakshminarayanan, Pranav; Ashai, Zaid; Olds, Kevin; Balicki, Marcin; Gooi, Zhen; Day, Andrew T; Taylor, Russell H; Richmon, Jeremy D

2017-11-01

Assess the feasibility of a novel robotic platform for use in microvascular surgery. Prospective feasibility study. Robotics laboratory. The Robotic ENT (Ear, Nose, and Throat) Microsurgery System (REMS) (Galen Robotics, Inc., Sunnyvale, CA) is a robotic arm that stabilizes a surgeon's instrument, allowing precise, tremor-free movement. Six microvascular naïve medical students and one microvascular expert performed microvascular anastomosis of a chicken ischiatic artery, with and without the REMS. Trials were blindly graded by seven microvascular surgeons using a microvascular tremor scale (MTS) based on instrument tip movement as a function of vessel width. Time to completion (TTC) was measured, and an exit survey assessed participants' experience. The interrater reliability of the MTS was calculated. For microvascular-naïve participants, the mean MTS score for REMS-assisted trials was 0.72 (95% confidence interval [CI] 0.64-1.07) and 2.40 (95% CI 2.12-2.69) for freehand (P < 0.001). The mean TTC was 1,265 seconds for REMS-assisted trials and 1,320 seconds for freehand (P > 0.05). For the microvascular expert, the mean REMS-assisted MTS score was 0.71 (95% CI 0.15-1.27) and 0.86 (95% CI 0.35-1.37) for freehand (P > 0.05). TTC was 353 seconds for the REMS-assisted trial and 299 seconds for freehand. All participants thought the REMS was more accurate and improved instrument handling and stability. The intraclass correlation coefficient for MTS ratings was 0.914 (95% CI 0.823-0.968) for consistency and 0.901 (95% CI 0.795-0.963) for absolute value. The REMS is a feasible adjunct for microvascular surgery and a potential teaching tool capable of reducing tremor in novice users. Furthermore, the MTS is a feasible grading system for assessing microvascular tremor. NA. Laryngoscope, 127:2495-2500, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Fast and Flexible Multivariate Time Series Subsequence Search

NASA Technical Reports Server (NTRS)

Bhaduri, Kanishka; Oza, Nikunj C.; Zhu, Qiang; Srivastava, Ashok N.

2010-01-01

Multivariate Time-Series (MTS) are ubiquitous, and are generated in areas as disparate as sensor recordings in aerospace systems, music and video streams, medical monitoring, and financial systems. Domain experts are often interested in searching for interesting multivariate patterns from these MTS databases which often contain several gigabytes of data. Surprisingly, research on MTS search is very limited. Most of the existing work only supports queries with the same length of data, or queries on a fixed set of variables. In this paper, we propose an efficient and flexible subsequence search framework for massive MTS databases, that, for the first time, enables querying on any subset of variables with arbitrary time delays between them. We propose two algorithms to solve this problem (1) a List Based Search (LBS) algorithm which uses sorted lists for indexing, and (2) a R*-tree Based Search (RBS) which uses Minimum Bounding Rectangles (MBR) to organize the subsequences. Both algorithms guarantee that all matching patterns within the specified thresholds will be returned (no false dismissals). The very few false alarms can be removed by a post-processing step. Since our framework is also capable of Univariate Time-Series (UTS) subsequence search, we first demonstrate the efficiency of our algorithms on several UTS datasets previously used in the literature. We follow this up with experiments using two large MTS databases from the aviation domain, each containing several millions of observations. Both these tests show that our algorithms have very high prune rates (>99%) thus needing actual disk access for only less than 1% of the observations. To the best of our knowledge, MTS subsequence search has never been attempted on datasets of the size we have used in this paper.

TIP maker and TIP marker; EB1 as a master controller of microtubule plus ends.

PubMed

Vaughan, Kevin T

2005-10-24

The EB1 protein is a member of the exciting and enigmatic family of microtubule (MT) tip-tracking proteins. EB1 acts as an exquisite marker of dynamic MT plus ends in some cases, whereas in others EB1 is thought to directly dictate the behavior of the plus ends. How EB1 differentiates between these two roles remains unclear; however, a growing list of interactions between EB1 and other MT binding proteins suggests there may be a single mechanism. Adding another layer of complexity to these interactions, two studies published in this issue implicate EB1 in cross-talk between mitotic MTs and between MTs and actin filaments (Goshima et al., p. 229; Wu et al., p. 201). These results raise the possibility that EB1 is a central player in MT-based transport, and that the activity of MT-binding proteins depends on their ability or inability to interact with EB1.

Distinct molecular cues ensure a robust microtubule-dependent nuclear positioning in the Drosophila oocyte

PubMed Central

Tissot, Nicolas; Lepesant, Jean-Antoine; Bernard, Fred; Legent, Kevin; Bosveld, Floris; Martin, Charlotte; Faklaris, Orestis; Bellaïche, Yohanns; Coppey, Maïté; Guichet, Antoine

2017-01-01

Controlling nucleus localization is crucial for a variety of cellular functions. In the Drosophila oocyte, nuclear asymmetric positioning is essential for the reorganization of the microtubule (MT) network that controls the polarized transport of axis determinants. A combination of quantitative three-dimensional live imaging and laser ablation-mediated force analysis reveal that nuclear positioning is ensured with an unexpected level of robustness. We show that the nucleus is pushed to the oocyte antero-dorsal cortex by MTs and that its migration can proceed through distinct tracks. Centrosome-associated MTs favour one migratory route. In addition, the MT-associated protein Mud/NuMA that is asymmetrically localized in an Asp-dependent manner at the nuclear envelope hemisphere where MT nucleation is higher promotes a separate route. Our results demonstrate that centrosomes do not provide an obligatory driving force for nuclear movement, but together with Mud, contribute to the mechanisms that ensure the robustness of asymmetric nuclear positioning. PMID:28447612

Optical Quantification of Intracellular pH in Drosophila melanogaster Malpighian Tubule Epithelia with a Fluorescent Genetically-encoded pH Indicator.

PubMed

Rossano, Adam J; Romero, Michael F

2017-08-11

Epithelial ion transport is vital to systemic ion homeostasis as well as maintenance of essential cellular electrochemical gradients. Intracellular pH (pHi) is influenced by many ion transporters and thus monitoring pHi is a useful tool for assessing transporter activity. Modern Genetically Encoded pH-Indicators (GEpHIs) provide optical quantification of pHi in intact cells on a cellular and subcellular scale. This protocol describes real-time quantification of cellular pHi regulation in Malpighian Tubules (MTs) of Drosophila melanogaster through ex vivo live-imaging of pHerry, a pseudo-ratiometric GEpHI with a pKa well-suited to track pH changes in the cytosol. Extracted adult fly MTs are composed of morphologically and functionally distinct sections of single-cell layer epithelia, and can serve as an accessible and genetically tractable model for investigation of epithelial transport. GEpHIs offer several advantages over conventional pH-sensitive fluorescent dyes and ion-selective electrodes. GEpHIs can label distinct cell populations provided appropriate promoter elements are available. This labeling is particularly useful in ex vivo, in vivo, and in situ preparations, which are inherently heterogeneous. GEpHIs also permit quantification of pHi in intact tissues over time without need for repeated dye treatment or tissue externalization. The primary drawback of current GEpHIs is the tendency to aggregate in cytosolic inclusions in response to tissue damage and construct over-expression. These shortcomings, their solutions, and the inherent advantages of GEpHIs are demonstrated in this protocol through assessment of basolateral proton (H + ) transport in functionally distinct principal and stellate cells of extracted fly MTs. The techniques and analysis described are readily adaptable to a wide variety of vertebrate and invertebrate preparations, and the sophistication of the assay can be scaled from teaching labs to intricate determination of ion flux via specific transporters.

Clustering analysis of moving target signatures

NASA Astrophysics Data System (ADS)

Martone, Anthony; Ranney, Kenneth; Innocenti, Roberto

2010-04-01

Previously, we developed a moving target indication (MTI) processing approach to detect and track slow-moving targets inside buildings, which successfully detected moving targets (MTs) from data collected by a low-frequency, ultra-wideband radar. Our MTI algorithms include change detection, automatic target detection (ATD), clustering, and tracking. The MTI algorithms can be implemented in a real-time or near-real-time system; however, a person-in-the-loop is needed to select input parameters for the clustering algorithm. Specifically, the number of clusters to input into the cluster algorithm is unknown and requires manual selection. A critical need exists to automate all aspects of the MTI processing formulation. In this paper, we investigate two techniques that automatically determine the number of clusters: the adaptive knee-point (KP) algorithm and the recursive pixel finding (RPF) algorithm. The KP algorithm is based on a well-known heuristic approach for determining the number of clusters. The RPF algorithm is analogous to the image processing, pixel labeling procedure. Both algorithms are used to analyze the false alarm and detection rates of three operational scenarios of personnel walking inside wood and cinderblock buildings.

Thermodynamic design of a high temperature chemical vapor deposition process to synthesize α-SiC in Si-C-H and Si-C-H-Cl systems

NASA Astrophysics Data System (ADS)

Kang, Yura; Yoo, Chang-Hyoung; Nam, Deok-Hui; Lee, Myung-Hyun; Seo, Won-Seon; Hong, Suklyun; Jeong, Seong-Min

2018-03-01

In this study, we thermodynamically reviewed the suitable growth process conditions of α-SiC in the Si-C-H system using tetramethylsilane (TMS) and in the Si-C-H-Cl system using methyltrichlorosilane (MTS). In the Si-C-H-Cl system, pure solid SiC was obtained at high temperatures under a larger range of hydrogen dilution ratios than that tolerated in the Si-C-H system. X-ray diffraction and micro-Raman analysis of the products obtained at 1900, 2000, and 2100 °C showed that the α-SiC becomes more dominant with increasing temperature in the Si-C-H-Cl system. While TMS was unsuitable for high temperature processing due to its high C/Si ratio, MTS was found to be appropriate for growing α-SiC crystals at high temperatures under a range of conditions. These results indicate that a novel method to grow α-SiC single crystals through HTCVD using MTS as a precursor could be established.

Microtubule-dependent path to the cell cortex for cytoplasmic dynein in mitotic spindle orientation

PubMed Central

Markus, Steven M.; Lee, Wei-Lih

2011-01-01

During animal development, microtubules (MTs) play a major role in directing cellular and subcellular patterning, impacting cell polarization and subcellular organization, thereby affecting cell fate determination and tissue architecture. In particular, when progenitor cells divide asymmetrically along an anterior-posterior or apical-basal axis, MTs must coordinate the position of the mitotic spindle with the site of cell division to ensure normal distribution of cell fate determinants and equal sequestration of genetic material into the two daughter cells. Emerging data from diverse model systems have led to the prevailing view that, during mitotic spindle positioning, polarity cues at the cell cortex signal for the recruitment of NuMA and the minus-end directed MT motor cytoplasmic dynein.1 The NuMA/dynein complex is believed to connect, in turn, to the mitotic spindle via astral MTs, thus aligning and tethering the spindle, but how this connection is achieved faithfully is unclear. Do astral MTs need to search for and then capture cortical NuMA/dynein? How does dynein capture the astral MTs emanating from the correct spindle pole? Recently, using the classical model of asymmetric cell division—budding yeast S. cerevisiae—we successfully demonstrated that astral MTs assume an active role in cortical dynein targeting, in that astral MTs utilize their distal plus ends to deliver dynein to the daughter cell cortex, the site where dynein activity is needed to perform its spindle alignment function. This observation introduced the novel idea that, during mitotic spindle orientation processes, polarity cues at the cell cortex may actually signal to prime the cortical receptors for MT-dependent dynein delivery. This model is consistent with the observation that dynein/dynactin accumulate prominently at the astral MT plus ends during metaphase in a wide range of cultured mammalian cells. PMID:22754610

Predictive value of hippocampal MR imaging-based high-dimensional mapping in mesial temporal epilepsy: preliminary findings.

PubMed

Hogan, R E; Wang, L; Bertrand, M E; Willmore, L J; Bucholz, R D; Nassif, A S; Csernansky, J G

2006-01-01

We objectively assessed surface structural changes of the hippocampus in mesial temporal sclerosis (MTS) and assessed the ability of large-deformation high-dimensional mapping (HDM-LD) to demonstrate hippocampal surface symmetry and predict group classification of MTS in right and left MTS groups compared with control subjects. Using eigenvector field analysis of HDM-LD segmentations of the hippocampus, we compared the symmetry of changes in the right and left MTS groups with a group of 15 matched controls. To assess the ability of HDM-LD to predict group classification, eigenvectors were selected by a logistic regression procedure when comparing the MTS group with control subjects. Multivariate analysis of variance on the coefficients from the first 9 eigenvectors accounted for 75% of the total variance between groups. The first 3 eigenvectors showed the largest differences between the control group and each of the MTS groups, but with eigenvector 2 showing the greatest difference in the MTS groups. Reconstruction of the hippocampal deformation vector fields due solely to eigenvector 2 shows symmetrical patterns in the right and left MTS groups. A "leave-one-out" (jackknife) procedure correctly predicted group classification in 14 of 15 (93.3%) left MTS subjects and all 15 right MTS subjects. Analysis of principal dimensions of hippocampal shape change suggests that MTS, after accounting for normal right-left asymmetries, affects the right and left hippocampal surface structure very symmetrically. Preliminary analysis using HDM-LD shows it can predict group classification of MTS and control hippocampi in this well-defined population of patients with MTS and mesial temporal lobe epilepsy (MTLE).

Tomato linalool synthase is induced in trichomes by jasmonic acid

PubMed Central

van Schie, Chris C. N.; Haring, Michel A.

2007-01-01

Tomato (Lycopersicon esculentum) plants emit a blend of volatile organic compounds, which mainly consists of terpenes. Upon herbivory or wounding, the emission of several terpenes increases. We have identified and characterized the first two tomato monoterpene synthases, LeMTS1 and LeMTS2. Although these proteins were highly homologous, recombinant LeMTS1 protein produced (R)-linalool from geranyl diphosphate (GPP) and (E)-nerolidol from farnesyl diphosphate (FPP), while recombinant LeMTS2 produced β-phellandrene, β-myrcene, and sabinene from GPP. In addition, these genes were expressed in different tissues: LeMTS1 was expressed in flowers, young leaves, stems, and petioles, while LeMTS2 was strongest expressed in stems and roots. LeMTS1 expression in leaves was induced by spider mite-infestation, wounding and jasmonic acid (JA)-treatment, while LeMTS2 did not respond to these stimuli. The expression of LeMTS1 in stems and petioles was predominantly detected in trichomes and could be induced by JA. Because JA treatment strongly induced emission of linalool and overexpression of LeMTS1 in tomato resulted in increased production of linalool, we propose that LeMTS1 is a genuine linalool synthase. Our results underline the importance of trichomes in JA-induced terpene emission in tomato. PMID:17440821

Anaphase B

PubMed Central

Scholey, Jonathan M.; Civelekoglu-Scholey, Gul; Brust-Mascher, Ingrid

2016-01-01

Anaphase B spindle elongation is characterized by the sliding apart of overlapping antiparallel interpolar (ip) microtubules (MTs) as the two opposite spindle poles separate, pulling along disjoined sister chromatids, thereby contributing to chromosome segregation and the propagation of all cellular life. The major biochemical “modules” that cooperate to mediate pole–pole separation include: (i) midzone pushing or (ii) braking by MT crosslinkers, such as kinesin-5 motors, which facilitate or restrict the outward sliding of antiparallel interpolar MTs (ipMTs); (iii) cortical pulling by disassembling astral MTs (aMTs) and/or dynein motors that pull aMTs outwards; (iv) ipMT plus end dynamics, notably net polymerization; and (v) ipMT minus end depolymerization manifest as poleward flux. The differential combination of these modules in different cell types produces diversity in the anaphase B mechanism. Combinations of antagonist modules can create a force balance that maintains the dynamic pre-anaphase B spindle at constant length. Tipping such a force balance at anaphase B onset can initiate and control the rate of spindle elongation. The activities of the basic motor filament components of the anaphase B machinery are controlled by a network of non-motor MT-associated proteins (MAPs), for example the key MT cross-linker, Ase1p/PRC1, and various cell-cycle kinases, phosphatases, and proteases. This review focuses on the molecular mechanisms of anaphase B spindle elongation in eukaryotic cells and briefly mentions bacterial DNA segregation systems that operate by spindle elongation. PMID:27941648

Involvement of microtubules in rhizoid differentiation of Spirogyra species.

PubMed

Yoshida, K; Inoue, N; Sonobe, S; Shimmen, T

2003-06-01

Some species of Spirogyra form rosette-shaped or rod-shaped rhizoids in the terminal cell of the filaments. In the present study, we analyzed an involvement of microtubules (MTs) in rhizoid differentiation. Before rhizoid differentiation, cortical MTs were arranged transversely to the long axis of cylindrical cells, reflecting the diffuse growth. At the beginning of rhizoid differentiation, MTs were absent from the extreme tip of the terminal cell. In the other area of the cell, however, MTs were arranged transversely to the long axis of the cell. In the fully differentiated rosette-shaped rhizoid, MTs were randomly organized. However, at a younger stage of rosette-shaped rhizoids, MTs were sometimes arranged almost transversely in the lobes of the rosette. In the rod-shaped rhizoid, MTs were arranged almost transversely. MT-destabilizing drugs (oryzalin and propyzamide) induced swelling of rhizoids, and neither rosette-shaped nor rod-shaped rhizoids were formed. The role of MTs in rhizoid differentiation was discussed.

Metal dealing at the origin of the Chordata phylum: the metallothionein system and metal overload response in amphioxus.

PubMed

Guirola, Maria; Pérez-Rafael, Sílvia; Capdevila, Mercè; Palacios, Oscar; Atrian, Sílvia

2012-01-01

Non-vertebrate chordates, specifically amphioxus, are considered of the utmost interest for gaining insight into the evolutionary trends, i.e. differentiation and specialization, of gene/protein systems. In this work, MTs (metallothioneins), the most important metal binding proteins, are characterized for the first time in the cephalochordate subphylum at both gene and protein level, together with the main features defining the amphioxus response to cadmium and copper overload. Two MT genes (BfMT1 and BfMT2) have been identified in a contiguous region of the genome, as well as several ARE (antioxidant response element) and MRE (metal response element) located upstream the transcribed region. Their corresponding cDNAs exhibit identical sequence in the two lancelet species (B. floridae and B. lanceolatum), BfMT2 cDNA resulting from an alternative splicing event. BfMT1 is a polyvalent metal binding peptide that coordinates any of the studied metal ions (Zn, Cd or Cu) rendering complexes stable enough to last in physiological environments, which is fully concordant with the constitutive expression of its gene, and therefore, with a metal homeostasis housekeeping role. On the contrary, BfMT2 exhibits a clear ability to coordinate Cd(II) ions, while it is absolutely unable to fold into stable Cu (I) complexes, even as mixed species. This identifies it as an essential detoxification agent, which is consequently only induced in emergency situations. The cephalochordate MTs are not directly related to vertebrate MTs, neither by gene structure, protein similarity nor metal-binding behavior of the encoded peptides. The closest relative is the echinoderm MT, which confirm proposed phylogenetic relationships between these two groups. The current findings support the existence in most organisms of two types of MTs as for their metal binding preferences, devoted to different biological functions: multivalent MTs for housekeeping roles, and specialized MTs that evolve either as Cd-thioneins or Cu-thioneins, according to the ecophysiological needs of each kind of organisms.

Metal Dealing at the Origin of the Chordata Phylum: The Metallothionein System and Metal Overload Response in Amphioxus

PubMed Central

Capdevila, Mercè; Palacios, Òscar; Atrian, Sílvia

2012-01-01

Non-vertebrate chordates, specifically amphioxus, are considered of the utmost interest for gaining insight into the evolutionary trends, i.e. differentiation and specialization, of gene/protein systems. In this work, MTs (metallothioneins), the most important metal binding proteins, are characterized for the first time in the cephalochordate subphylum at both gene and protein level, together with the main features defining the amphioxus response to cadmium and copper overload. Two MT genes (BfMT1 and BfMT2) have been identified in a contiguous region of the genome, as well as several ARE (antioxidant response element) and MRE (metal response element) located upstream the transcribed region. Their corresponding cDNAs exhibit identical sequence in the two lancelet species (B. floridae and B. lanceolatum), BfMT2 cDNA resulting from an alternative splicing event. BfMT1 is a polyvalent metal binding peptide that coordinates any of the studied metal ions (Zn, Cd or Cu) rendering complexes stable enough to last in physiological environments, which is fully concordant with the constitutive expression of its gene, and therefore, with a metal homeostasis housekeeping role. On the contrary, BfMT2 exhibits a clear ability to coordinate Cd(II) ions, while it is absolutely unable to fold into stable Cu (I) complexes, even as mixed species. This identifies it as an essential detoxification agent, which is consequently only induced in emergency situations. The cephalochordate MTs are not directly related to vertebrate MTs, neither by gene structure, protein similarity nor metal-binding behavior of the encoded peptides. The closest relative is the echinoderm MT, which confirm proposed phylogenetic relationships between these two groups. The current findings support the existence in most organisms of two types of MTs as for their metal binding preferences, devoted to different biological functions: multivalent MTs for housekeeping roles, and specialized MTs that evolve either as Cd-thioneins or Cu-thioneins, according to the ecophysiological needs of each kind of organisms. PMID:22905252

Regulation of microtubule-based transport by MAP4

PubMed Central

Semenova, Irina; Ikeda, Kazuho; Resaul, Karim; Kraikivski, Pavel; Aguiar, Mike; Gygi, Steven; Zaliapin, Ilya; Cowan, Ann; Rodionov, Vladimir

2014-01-01

Microtubule (MT)-based transport of organelles driven by the opposing MT motors kinesins and dynein is tightly regulated in cells, but the underlying molecular mechanisms remain largely unknown. Here we tested the regulation of MT transport by the ubiquitous protein MAP4 using Xenopus melanophores as an experimental system. In these cells, pigment granules (melanosomes) move along MTs to the cell center (aggregation) or to the periphery (dispersion) by means of cytoplasmic dynein and kinesin-2, respectively. We found that aggregation signals induced phosphorylation of threonine residues in the MT-binding domain of the Xenopus MAP4 (XMAP4), thus decreasing binding of this protein to MTs. Overexpression of XMAP4 inhibited pigment aggregation by shortening dynein-dependent MT runs of melanosomes, whereas removal of XMAP4 from MTs reduced the length of kinesin-2–dependent runs and suppressed pigment dispersion. We hypothesize that binding of XMAP4 to MTs negatively regulates dynein-dependent movement of melanosomes and positively regulates kinesin-2–based movement. Phosphorylation during pigment aggregation reduces binding of XMAP4 to MTs, thus increasing dynein-dependent and decreasing kinesin-2–dependent motility of melanosomes, which stimulates their accumulation in the cell center, whereas dephosphorylation of XMAP4 during dispersion has an opposite effect. PMID:25143402

Marine Transportation System Performance Measures Research

DTIC Science & Technology

2016-06-01

A. Protopapas, D. Bierling, L. E . Olson, B. Wang, and M. Khodakarami. 2014. Integrating MTS commerce data with multimodal freight transportation...suggests using ob- served data to develop models that explore a wide range of future scenar- ios and provide insight into potential effects on MTS...sources were the FT920 – U.S. Merchandise Trade: Selected Highlights (for total, water and air data , published by U.S. Department of Commerce , U.S

Collective behavior of minus-ended motors in mitotic microtubule asters gliding toward DNA

NASA Astrophysics Data System (ADS)

Athale, Chaitanya A.; Dinarina, Ana; Nedelec, Francois; Karsenti, Eric

2014-02-01

Microtubules (MTs) nucleated by centrosomes form star-shaped structures referred to as asters. Aster motility and dynamics is vital for genome stability, cell division, polarization and differentiation. Asters move either toward the cell center or away from it. Here, we focus on the centering mechanism in a membrane independent system of Xenopus cytoplasmic egg extracts. Using live microscopy and single particle tracking, we find that asters move toward chromatinized DNA structures. The velocity and directionality profiles suggest a random-walk with drift directed toward DNA. We have developed a theoretical model that can explain this movement as a result of a gradient of MT length dynamics and MT gliding on immobilized dynein motors. In simulations, the antagonistic action of the motor species on the radial array of MTs leads to a tug-of-war purely due to geometric considerations and aster motility resembles a directed random-walk. Additionally, our model predicts that aster velocities do not change greatly with varying initial distance from DNA. The movement of asymmetric asters becomes increasingly super-diffusive with increasing motor density, but for symmetric asters it becomes less super-diffusive. The transition of symmetric asters from superdiffusive to diffusive mobility is the result of number fluctuations in bound motors in the tug-of-war. Overall, our model is in good agreement with experimental data in Xenopus cytoplasmic extracts and predicts novel features of the collective effects of motor-MT interactions.

Assessing sensitivity and specificity of the Manchester Triage System in the evaluation of acute coronary syndrome in adult patients in emergency care: a systematic review protocol.

PubMed

Nishi, Fernanda Ayache; de Motta Maia, Flávia Oliveira; de Lopes Monteiro da Cruz, Dina Almeida

2015-11-01

The objective of this review is to assess the sensitivity and specificity of the Manchester Triage System in the evaluation of adult patients with acute coronary syndrome in emergency departments. Acute coronary syndrome (ACS) is a group of clinical conditions that include myocardial infarction with or without elevation of the ST segment and unstable angina. The term acute myocardial infarction (AMI) can be applied when there is evidence of myocardium necrosis with a clinical sign compatible with myocardial ischaemia. Acute myocardial infarction can be identified using clinical methods including electrocardiography (ECG), elevation in myocardium necrosis biomarkers, and imaging. Acute myocardial infarction is one of the leading causes of death and disability worldwide, and may be the first manifestation of coronary artery disease.Estimating the prevalence of coronary diseases in the general population is quite a complex task. In 2010, the prevalence of coronary diseases was reported as 6.4% among the general population in the United States.One of the main manifestations of ACS is chest pain. However, even in the presence of this typical symptom, early diagnosis of ACS is a challenge for health care professionals who initially attend to these patients. Several authors have indicated the importance and difficulty of recognizing chest pain of cardiac origin, where immediate medical attention is required.Triage, or risk classification, is a clinical management tool used in emergency services to guide patient flow when the need for medical attention exceeds that available. The Manchester Triage Group was developed in 1994 in the United Kingdom. The aim was to establish a consensus among physicians and nurses in the emergency room by creating a triage pattern focused on the development of the following:Thus, the Manchester Triage System (MTS) was created. The MTS simplifies the clinical management of each patient, and consequently, the whole service, by utilizing a system that defines the clinical priority for adults and children. The assessment of clinical priority needs to be fast; therefore, it is separated from the process of medical diagnosis. Restricting the time allocated for patient classification prevents an attempt to make a medical diagnosis at the time of classification.The main goal of the MTS is to set a time limit for each patient to be attended to safely, that is, with no risk to the patient's health. One of the main principles of the system is the higher the perceived risk to the patient's health, the shorter the waiting time for medical attendance. The MTS comprises a scale of five priority levels ().(Table is included in full-text article.)The MTS is composed of 52 distinct flowcharts that "guide" the triage decision-making process. Based on the main presenting symptom of the patient seeking emergency care, the health care professional must choose one of the 52 flowcharts in order to proceed with evaluation. Classification into one of the five clinical priority levels is set for each patient using the selected flowchart.The lack of a risk classification system within an emergency room implies attendance on a first-come, first-served basis, which in many cases may jeopardize a patient's safety, as patients whose health status is more unstable or severe are not prioritized.The MTS is a tool that aims to define the degree of severity and associated safe waiting time for patients in the emergency department, establishing an order of priority for medical care. It determines the clinical priority of every patient who comes to the emergency department. It is possible to evaluate the sensitivity and specificity of the MTS by calculating the frequency of appropriately assigned clinical priority levels to patients presenting at the emergency department.A "diagnostic test" can be understood as a laboratory or imaging test: however, the concepts related to "test" also apply to clinical information from other findings, such as physical examination and patient history. The sensitivity of a test is understood as the capacity of the test to detect individuals who present with a particular condition, or the proportion of individuals with a particular condition who have been tested positive for this condition (true positive). Highly sensitive tests can be used at the beginning of the diagnostic process, when a great number of possibilities are being considered, with the intention of excluding as many options as possible. The specificity of a test is defined as the capacity of the test to identify individuals who do not have a particular medical condition, or the proportion of individuals without the condition who have a negative test (true negative). A triage system that presents a good sensitivity can minimize the occurrence of undertriage, the same way, systems with suitable specificity can avoid the occurrence of overtriage.The assessment of patients with ACS suspected using the MTS, can occur through different flow charts, since the patient does not always have typical symptoms and concerns such as chest pain as the main complaint. For this reason, in addition to the flowchart "chest pain", other flowcharts, including "shortness of breath in adults", "unwell adult", "collapsed adult", and "palpitations", enable distinguishing chest pain and other urgent conditions from non-urgent conditions, and can assist the appraiser to establish the highest priority level to treat patients with these urgent conditions.According to the algorithm from the American Heart Association, every patient who presents symptoms of chest discomfort suggestive of ischaemia must receive medical attention within 10 minutes. Therefore, in order to recognize patients in those conditions, the health care professional applying MTS must establish priority levels of "red" or "orange", thereby setting a safe waiting time for these patients.Although there are well-established criteria for the prioritization of patients with suspected ACS, several studies have reported the difficulties of evaluating patients with these conditions. Various factors can interfere with the outcome of this process, such as atypical presentation of symptoms, AMI classification, patient age, and professional skill.Primary studies have addressed the issue from different perspectives. Studies have been conducted to evaluate the ability of nurses using MTS to detect high-risk patients with chest pain, the impact of MTS on short-term mortality in AMI, and the sensitivity and specificity of MTS for patients with ACS, and to assess whether the MTS was used effectively in patients admitted to the hospital with a diagnosis of acute coronary syndrome.These studies concluded that use of the MTS by nurses is a sensitive method for identifying high risk cardiac chest pain, but further studies are required to assess whether additional training can improve the sensitivity of MTS. The MTS safeguards patients with typical AMI presentation and ST elevation during myocardial infarction, and who are under 70 years of age. The MTS has a high sensitivity in prioritization (immediate/very urgent) of patients with ACS. Additionally, most patients admitted for ACS are initially triaged as "orange" or "yellow", an indication for prompt assessment in the emergency department. This has a positive effect on time to first medical assessment, but has no effect on time to hospital admission.A systematic review addressing a similar theme was published. The review evaluated the efficacy of MTS for all groups of patients and included studies that evaluated the MTS in relation to different outcomes. This proposed review is different as it will include primary studies with a specific sub-population (patients with ACS). Another important difference lies in the fact that the published review did not include critical appraisal of the primary studies included in review. A systematic review that synthesizes the available evidence on the sensitivity of MTS to evaluate patients with an ACS medical diagnosis is necessary to guide decisions related to the use or adoption of the instrument, as well as providing data that can contribute to improvements to the system.

Creating integrative work: a qualitative study of how massage therapists work with existing clients.

PubMed

Fortune, Luann Drolc; Hymel, Glenn M

2015-01-01

As one of the most often used complementary treatments, massage is increasingly positioned as an essential component of integrative medicine. Recent studies evaluate the clinical efficacy of massage therapy, but few studies explore how massage therapists (MTs) execute their work and exercise clinical reasoning in natural settings. To gain foundational knowledge about clinical reasoning and applied knowledge, this study examined how 10 MTs executed an entire session with established clients. Results support translational research design and inform educators. Ethnomethodology and phenomenology informed the qualitative design. Data were collected by videotaping actual sessions and interviewing the participants immediately afterward while viewing the videos. Computer-aided analysis identified data patterns for thematic interpretation. The MTs shared tacit knowledge that directed their work: a) maintaining a primarily biomechanical focus, b) prerequisite safe touch, c) multitasking not allowed, d) MTs assume physical risk, and e) the work affects multiple bodily systems. The MTs sensed effectiveness experientially by adopting common tactics: a) visualizing the manual engagement points, b) assuming the client controlled the physiological release, and c) educating the client. Within these commonalities, they operationalized their work in complex and singular ways, with the particular client relationship critical to structuring the session and evaluating the outcome. MTs viewed their work primarily as a biomechanical intervention, but understood therapeutic massage as serving multiple functions. Process-oriented clinical reasoning mirrored models found in psychotherapy and was informed by experience, intuition, and training, which resulted in an intentionally holistic approach. Copyright © 2014 Elsevier Ltd. All rights reserved.

A biopolymer transistor: electrical amplification by microtubules.

PubMed

Priel, Avner; Ramos, Arnolt J; Tuszynski, Jack A; Cantiello, Horacio F

2006-06-15

Microtubules (MTs) are important cytoskeletal structures engaged in a number of specific cellular activities, including vesicular traffic, cell cyto-architecture and motility, cell division, and information processing within neuronal processes. MTs have also been implicated in higher neuronal functions, including memory and the emergence of "consciousness". How MTs handle and process electrical information, however, is heretofore unknown. Here we show new electrodynamic properties of MTs. Isolated, taxol-stabilized MTs behave as biomolecular transistors capable of amplifying electrical information. Electrical amplification by MTs can lead to the enhancement of dynamic information, and processivity in neurons can be conceptualized as an "ionic-based" transistor, which may affect, among other known functions, neuronal computational capabilities.

Assessing sensitivity and specificity of the Manchester Triage System in the evaluation of acute coronary syndrome in adult patients in emergency care: a systematic review.

PubMed

Nishi, Fernanda Ayache; de Oliveira Motta Maia, Flávia; de Souza Santos, Itamar; de Almeida Lopes Monteiro da Cruz, Dina

2017-06-01

Triage is the first assessment and sorting process used to prioritize patients arriving in the emergency department (ED). As a triage tool, the Manchester Triage System (MTS) must have a high sensitivity to minimize the occurrence of under-triage, but must not compromise specificity to avoid the occurrence of overtriage. Sensitivity and specificity of the MTS can be calculated using the frequency of appropriately assigned clinical priority levels for patients presenting to the ED. However, although there are well established criteria for the prioritization of patients with suspected acute coronary syndrome (ACS), several studies have reported difficulties when evaluating patients with this condition. The objective of this review was to synthesize the best available evidence on assessing the sensitivity and specificity of the MTS for screening high-level priority adult patients presenting to the ED with ACS. The current review considered studies that evaluated the use of the MTS in the risk classification of adult patients in the ED. In this review, studies that investigated the priority level, as established by the MTS to screen patients under suspicion of ACS or the sensitivity and specificity of the MTS, for screening patients before the medical diagnosis of ACS were included. This review included both experimental and epidemiological study designs. The results were presented in a narrative synthesis. Six studies were appraised by the independent reviewers. All appraised studies enrolled a consecutive or random sample of patients and presented an overall moderate methodological quality, and all of them were included in this review. A total of 54,176 participants were included in the six studies. All studies were retrospective. Studies included in this review varied in content and data reporting. Only two studies reported sensitivity and specificity values or all the necessary data to calculate sensitivity and specificity. The remaining four studies presented either a sensitivity analysis or the number of true positives and false negatives. However, these four studies were conducted considering only data from patients diagnosed with ACS. Sensitivity values were relatively uniform among the studies: 0.70-0.80. A specificity of 0.59 was reported in the study including only patients with non-traumatic chest pain. On the other hand, in the study that included patients with any complaint, the specificity of MTS to screen patients with ACS was 0.97. The current review demonstrates that the MTS has a moderate sensitivity to evaluate patients with ACS. This may compromise time to treatment in the ED, an important variable in the prognosis of ACS. Atypical presentation of ACS, or high specificity, may also explain the moderate sensitivity demonstrated in this review. However, because of minimal data, it is not possible to confirm this hypothesis. It is difficult to determine the acceptable level of sensitivity or specificity to ensure that a certain triage system is safe.

Cell prestress. II. Contribution of microtubules

NASA Technical Reports Server (NTRS)

Stamenovic, Dimitrije; Mijailovich, Srboljub M.; Tolic-Norrelykke, Iva Marija; Chen, Jianxin; Wang, Ning; Ingber, D. E. (Principal Investigator)

2002-01-01

The tensegrity model hypothesizes that cytoskeleton-based microtubules (MTs) carry compression as they balance a portion of cell contractile stress. To test this hypothesis, we used traction force microscopy to measure traction at the interface of adhering human airway smooth muscle cells and a flexible polyacrylamide gel substrate. The prediction is that if MTs balance a portion of contractile stress, then, upon their disruption, the portion of stress balanced by MTs would shift to the substrate, thereby causing an increase in traction. Measurements were done first in maximally activated cells (10 microM histamine) and then again after MTs had been disrupted (1 microM colchicine). We found that after disruption of MTs, traction increased on average by approximately 13%. Because in activated cells colchicine induced neither an increase in intracellular Ca(2+) nor an increase in myosin light chain phosphorylation as shown previously, we concluded that the observed increase in traction was a result of load shift from MTs to the substrate. In addition, energy stored in the flexible substrate was calculated as work done by traction on the deformation of the substrate. This result was then utilized in an energetic analysis. We assumed that cytoskeleton-based MTs are slender elastic rods supported laterally by intermediate filaments and that MTs buckle as the cell contracts. Using the post-buckling equilibrium theory of Euler struts, we found that energy stored during buckling of MTs was quantitatively consistent with the measured increase in substrate energy after disruption of MTs. This is further evidence supporting the idea that MTs are intracellular compression-bearing elements.

A MAD Explanation for the Correlation between Bulk Lorentz Factor and Minimum Variability Timescale

NASA Astrophysics Data System (ADS)

Lloyd-Ronning, Nicole; Lei, Wei-hua; Xie, Wei

2018-04-01

We offer an explanation for the anti-correlation between the minimum variability timescale (MTS) in the prompt emission light curve of gamma-ray bursts (GRBs) and the estimated bulk Lorentz factor of these GRBs, in the context of a magnetically arrested disk (MAD) model. In particular, we show that previously derived limits on the maximum available energy per baryon in a Blandford-Znajek jet leads to a relationship between the characteristic MAD timescale in GRBs and the maximum bulk Lorentz factor: tMAD∝Γ-6, somewhat steeper than (although within the error bars of) the fitted relationship found in the GRB data. Similarly, the MAD model also naturally accounts for the observed anti-correlation between MTS and gamma-ray luminosity L in the GRB data, and we estimate the accretion rates of the GRB disk (given these luminosities) in the context of this model. Both of these correlations (MTS - Γ and MTS - L) are also observed in the AGN data, and we discuss the implications of our results in the context of both GRB and blazar systems.

A mitral annulus tracking approach for navigation of off-pump beating heart mitral valve repair.

PubMed

Li, Feng P; Rajchl, Martin; Moore, John; Peters, Terry M

2015-01-01

To develop and validate a real-time mitral valve annulus (MVA) tracking approach based on biplane transesophageal echocardiogram (TEE) data and magnetic tracking systems (MTS) to be used in minimally invasive off-pump beating heart mitral valve repair (MVR). The authors' guidance system consists of three major components: TEE, magnetic tracking system, and an image guidance software platform. TEE provides real-time intraoperative images to show the cardiac motion and intracardiac surgical tools. The magnetic tracking system tracks the TEE probe and the surgical tools. The software platform integrates the TEE image planes and the virtual model of the tools and the MVA model on the screen. The authors' MVA tracking approach, which aims to update the MVA model in near real-time, comprises of three steps: image based gating, predictive reinitialization, and registration based MVA tracking. The image based gating step uses a small patch centered at each MVA point in the TEE images to identify images at optimal cardiac phases for updating the position of the MVA. The predictive reinitialization step uses the position and orientation of the TEE probe provided by the magnetic tracking system to predict the position of the MVA points in the TEE images and uses them for the initialization of the registration component. The registration based MVA tracking step aims to locate the MVA points in the images selected by the image based gating component by performing image based registration. The validation of the MVA tracking approach was performed in a phantom study and a retrospective study on porcine data. In the phantom study, controlled translations were applied to the phantom and the tracked MVA was compared to its "true" position estimated based on a magnetic sensor attached to the phantom. The MVA tracking accuracy was 1.29 ± 0.58 mm when the translation distance is about 1 cm, and increased to 2.85 ± 1.19 mm when the translation distance is about 3 cm. In the study on porcine data, the authors compared the tracked MVA to a manually segmented MVA. The overall accuracy is 2.37 ± 1.67 mm for single plane images and 2.35 ± 1.55 mm for biplane images. The interoperator variation in manual segmentation was 2.32 ± 1.24 mm for single plane images and 1.73 ± 1.18 mm for biplane images. The computational efficiency of the algorithm on a desktop computer with an Intel(®) Xeon(®) CPU @3.47 GHz and an NVIDIA GeForce 690 graphic card is such that the time required for registering four MVA points was about 60 ms. The authors developed a rapid MVA tracking algorithm for use in the guidance of off-pump beating heart transapical mitral valve repair. This approach uses 2D biplane TEE images and was tested on a dynamic heart phantom and interventional porcine image data. Results regarding the accuracy and efficiency of the authors' MVA tracking algorithm are promising, and fulfill the requirements for surgical navigation.

A minimal model for kinetochore-microtubule dynamics

NASA Astrophysics Data System (ADS)

Liu, Andrea

2014-03-01

During mitosis, chromosome pairs align at the center of a bipolar microtubule (MT) spindle and oscillate as MTs attaching them to the cell poles polymerize and depolymerize. The cell fixes misaligned pairs by a tension-sensing mechanism. Pairs later separate as shrinking MTs pull each chromosome toward its respective cell pole. We present a minimal model for these processes based on properties of MT kinetics. We apply the measured tension-dependence of single MT kinetics to a stochastic many MT model, which we solve numerically and with master equations. We find that the force-velocity curve for the single chromosome system is bistable and hysteretic. Above some threshold load, tension fluctuations induce MTs to spontaneously switch from a pulling state into a growing, pushing state. To recover pulling from the pushing state, the load must be reduced far below the threshold. This leads to oscillations in the two-chromosome system. Our minimal model quantitatively captures several aspects of kinetochore dynamics observed experimentally. This work was supported by NSF-DMR-1104637.

Synergistic effects and related bioactive mechanisms of Potentilla fruticosa Linn. leaves combined with green tea polyphenols studied with microbial test system (MTS).

PubMed

Liu, Ze-Hua; Luo, Zi-Wen; Li, Deng-Wu; Wang, Dong-Mei; Ji, Xia

2018-06-01

Previous research found Potentilla fruticosa leaf extracts (PFE) combined with green tea polyphenols (GTP) showed obvious synergistic effects based on chemical mechanisms. This study further confirmed the synergy of PFE + GTP viewed from bioactivities using the microbial test system (MTS). The MTS antioxidant activity results showed the combination of PFE + GTP exhibited synergistic effect and the ratio 3:1 showed the strongest synergy, which were in accordance with the results in H 2 O 2 production rate. The combination of PFE + GTP promoted CAT and SOD enzyme activity and their gene expression especially at the ratio 3:1. Therefore, the synergism of PFE + GTP may be due to the promotion of CAT and SOD genes expression which enhanced the CAT and SOD enzyme activities. These results confirmed the synergy of PFE + GTP and could provide theoretical basis to produce a compounded tea made of a mixture of leaves from Potentilla species.

A novel strategy for dual-channel detection of metallothioneins and mercury based on the conformational switching of functional chimera aptamer.

PubMed

Tang, Xian; Wang, Yong-Sheng; Xue, Jin-Hua; Zhou, Bin; Cao, Jin-Xiu; Chen, Si-Han; Li, Ming-Hui; Wang, Xiao-Feng; Zhu, Yu-Feng; Huang, Yan-Qin

2015-03-25

A novel strategy for dual-channel detection of metallothioneins (MTs) and Hg(2+) has been proposed. In the absence of Hg(2+), the functional chimera aptamer (FCA) designed can form an intact G-quadruplex with flexibility, which was demonstrated to have peroxidase-like activities upon hemin binding. In the presence of Hg(2+), the formation of T-Hg(2+)-T complex results in the conformational switching of FCA, which lost the peroxidase-like activities and cannot catalyze the oxidation of ABTS by H2O2. Upon addition of MTs in this solution, MTs could interact with Hg(2+) to form a MTs-Hg(2+) complex, leading to the recovery of the G-quadruplex DNAzyme. The color and absorbance of the sensing system were also changed accordingly. In the optimizing condition, ΔA was directly proportional to the concentration ranging from 8.84 nM to 1.0 μM for Hg(2+), and 7.82 nM to 0.462 μM for MTs with the detection limits of 2.65 nM and 2.34 nM, respectively. The proposed dual-channel method avoids the label steps in common methods, and allows direct analysis of the samples without costly instruments, and is reliable, inexpensive and sensitive. Copyright © 2015 Elsevier B.V. All rights reserved.

Microtubule-based nanomaterials: Exploiting nature's dynamic biopolymers

DOE PAGES

Bachand, George D.; Stevens, Mark J.; Spoerke, Erik David

2015-04-09

For more than a decade now, biomolecular systems have served as an inspiration for the development of synthetic nanomaterials and systems that are capable of reproducing many of unique and emergent behaviors of living systems. In addition, one intriguing element of such systems may be found in a specialized class of proteins known as biomolecular motors that are capable of performing useful work across multiple length scales through the efficient conversion of chemical energy. Microtubule (MT) filaments may be considered within this context as their dynamic assembly and disassembly dissipate energy, and perform work within the cell. MTs are onemore » of three cytoskeletal filaments in eukaryotic cells, and play critical roles in a range of cellular processes including mitosis and vesicular trafficking. Based on their function, physical attributes, and unique dynamics, MTs also serve as a powerful archetype of a supramolecular filament that underlies and drives multiscale emergent behaviors. In this review, we briefly summarize recent efforts to generate hybrid and composite nanomaterials using MTs as biomolecular scaffolds, as well as computational and synthetic approaches to develop synthetic one-dimensional nanostructures that display the enviable attributes of the natural filaments.« less

Biased Brownian motion as a mechanism to facilitate nanometer-scale exploration of the microtubule plus end by a kinesin-8.

PubMed

Shin, Yongdae; Du, Yaqing; Collier, Scott E; Ohi, Melanie D; Lang, Matthew J; Ohi, Ryoma

2015-07-21

Kinesin-8s are plus-end-directed motors that negatively regulate microtubule (MT) length. Well-characterized members of this subfamily (Kip3, Kif18A) exhibit two important properties: (i) They are "ultraprocessive," a feature enabled by a second MT-binding site that tethers the motors to a MT track, and (ii) they dissociate infrequently from the plus end. Together, these characteristics combined with their plus-end motility cause Kip3 and Kif18A to enrich preferentially at the plus ends of long MTs, promoting MT catastrophes or pausing. Kif18B, an understudied human kinesin-8, also limits MT growth during mitosis. In contrast to Kif18A and Kip3, localization of Kif18B to plus ends relies on binding to the plus-end tracking protein EB1, making the relationship between its potential plus-end-directed motility and plus-end accumulation unclear. Using single-molecule assays, we show that Kif18B is only modestly processive and that the motor switches frequently between directed and diffusive modes of motility. Diffusion is promoted by the tail domain, which also contains a second MT-binding site that decreases the off rate of the motor from the MT lattice. In cells, Kif18B concentrates at the extreme tip of a subset of MTs, superseding EB1. Our data demonstrate that kinesin-8 motors use diverse design principles to target MT plus ends, which likely target them to the plus ends of distinct MT subpopulations in the mitotic spindle.

Biased Brownian motion as a mechanism to facilitate nanometer-scale exploration of the microtubule plus end by a kinesin-8

PubMed Central

Shin, Yongdae; Du, Yaqing; Collier, Scott E.; Ohi, Melanie D.; Lang, Matthew J.; Ohi, Ryoma

2015-01-01

Kinesin-8s are plus-end–directed motors that negatively regulate microtubule (MT) length. Well-characterized members of this subfamily (Kip3, Kif18A) exhibit two important properties: (i) They are “ultraprocessive,” a feature enabled by a second MT-binding site that tethers the motors to a MT track, and (ii) they dissociate infrequently from the plus end. Together, these characteristics combined with their plus-end motility cause Kip3 and Kif18A to enrich preferentially at the plus ends of long MTs, promoting MT catastrophes or pausing. Kif18B, an understudied human kinesin-8, also limits MT growth during mitosis. In contrast to Kif18A and Kip3, localization of Kif18B to plus ends relies on binding to the plus-end tracking protein EB1, making the relationship between its potential plus-end–directed motility and plus-end accumulation unclear. Using single-molecule assays, we show that Kif18B is only modestly processive and that the motor switches frequently between directed and diffusive modes of motility. Diffusion is promoted by the tail domain, which also contains a second MT-binding site that decreases the off rate of the motor from the MT lattice. In cells, Kif18B concentrates at the extreme tip of a subset of MTs, superseding EB1. Our data demonstrate that kinesin-8 motors use diverse design principles to target MT plus ends, which likely target them to the plus ends of distinct MT subpopulations in the mitotic spindle. PMID:26150501

Methoxsalen supplementation attenuates bone loss and inflammatory response in ovariectomized mice.

PubMed

Ham, Ju Ri; Choi, Ra-Yeong; Yee, Sung-Tae; Hwang, Yun-Ho; Kim, Myung-Joo; Lee, Mi-Kyung

2017-12-25

Methoxsalen (MTS) is a natural bioactive compound found in a variety of plants that has many known biofunctions; however, its effects on osteoporosis and related mechanisms are not clear. This study examined whether MTS exhibited preventive effects against postmenopausal osteoporosis. Female C3H/HeN mice were divided into four groups: Sham, ovariectomy (OVX), OVX with MTS (0.02% in diet), and OVX with estradiol (0.03 μg/day, s.c). After 6 weeks, MTS supplementation significantly increased femur bone mineral density and bone surface along with bone surface/total volume. MTS significantly elevated the levels of serum formation markers (estradiol, osteocalcin and bone-alkaline phosphatase) such as estradiol in OVX mice. Tartrate resistant acid phosphatase staining revealed that MTS suppressed osteoclast numbers and formation in femur tissues compared with the OVX group. Supplementation of MTS slightly up-regulated osteoblastogenesis-related genes (Runx-2, osterix, osteocalcin, and Alp) expression, whereas it significantly down-regulated inflammatory genes (Nfκb and Il6) expression in femur tissue compared with the OVX group. These results indicate that MTS supplementation effectively prevented OVX-induced osteoporosis via enhancement of bone formation and suppression of inflammatory response in OVX mice. Our study provides valid scientific information regarding the development and application of MTS as a food ingredient, a food supplement or an alternative agent for preventing postmenopausal osteoporosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Thematic Matching as Remedial Teaching for Symbolic Matching for Individuals with Autism Spectrum Disorder

PubMed Central

Lionello-DeNolf, Karen M.; Farber, Rachel; Jones, B. Max; Dube, William V.

2014-01-01

Matching-to-sample (MTS) is often used to teach symbolic relationships between spoken or printed words and their referents to children with intellectual and developmental disabilities. However, many children have difficulty learning symbolic matching, even though they may demonstrate generalized identity matching. The current study investigated whether training on symbolic MTS tasks in which the stimuli are physically dissimilar but members of familiar categories (i.e., thematic matching) can remediate an individual’s difficulty learning symbolic MTS tasks involving non-representative stimuli. Three adolescent males diagnosed with autism spectrum disorder were first trained on symbolic MTS tasks with unfamiliar, non-representative form stimuli. Thematic matching was introduced after the participants failed to learn 0, 2 or 4 symbolic MTS tasks and before additional symbolic MTS tasks were introduced. After exposure to thematic matching, accuracy on symbolic MTS tasks with novel stimuli increased to above chance for all participants. For two participants, high accuracy (> 90%) was achieved on a majority of these sessions. Thus, thematic matching may be an effective intervention for students with limited verbal repertoires and who have difficulty learning symbolic MTS tasks. Possible explanations for the facilitative effect of thematic matching are considered and warrant further investigation. PMID:24634695

SLI Complex Curvature Friction Stir Weld Risk Reduction Program

NASA Technical Reports Server (NTRS)

Hartley, Paula J.; Schneider, Jules; Jones, Chip; Lawless, Kirby; Russell, Carolyn

2003-01-01

The Space Launch Initiative Program (SLI) in conjunction with the National Center for Advanced Manufacturing (NCAM) will demonstrate the ability to produce large-scale complex curvature hardware using the self-reacting friction stir welding process. This multi-phased risk reduction program includes friction stir welding process development and manufacture of a 22-ft diameter quarter dome using a conventional tooling approach; it culminates in a 27.5-ft diameter quarter dome demonstration performed on a 5-axis Universal Weld System. The design, fabrication, and installation of the Universal Weld System is made possible through a collaboration between the State of Louisiana, NASA, and the University of New Orleans. The Universal Weld System, manufactured by MTS Systems Corporation, will be installed at the Michoud Assembly Facility in New Orleans, Louisiana, and will be capable of manufacturing domes up to 30 ft in diameter. All welding will be accomplished using the Adaptable Adjustable Pin Tool (AdAPT) weld head and controller manufactured by MTS. Weld parameters will be developed for an aluminum alloy in gauges ranging from 0.320 to 0.400 in. thick. Weld quality will be verified through radiography, mechanical property testing at ambient and LN2 temperatures, and metallurgical analysis. The AdAPT weld head will then be mounted on a 22-ft diameter dome tool, which will be modified to include a welding track and drive system for moving the AdAPT weld head along the weld joint. This tool will then be used to manufacture a 22-ft diameter dome of an aluminum alloy, with 0.320-in. constant thickness joints, consisting of three individual gore panels. Finally, the 27.5-ft diameter quarter dome will be welded on the Universal Weld System. The quarter dome will consist of three individual gore panels with weld lands tapering from 0.320 to 0.360 in. in thickness. With the demonstration of these welds, the ability to manufacture large diameter domes using the friction stir weld process in conjunction with a universal weld system provides a low risk approach to the fabrication of aluminum tanks for future launch vehicle applications.

Are metallothioneins equally good biomarkers of metal and oxidative stress?

PubMed

Figueira, Etelvina; Branco, Diana; Antunes, Sara C; Gonçalves, Fernando; Freitas, Rosa

2012-10-01

Several researchers investigated the induction of metallothioneins (MTs) in the presence of metals, namely Cadmium (Cd). Fewer studies observed the induction of MTs due to oxidizing agents, and literature comparing the sensitivity of MTs to different stressors is even more scarce or even nonexistent. The role of MTs in metal and oxidative stress and thus their use as a stress biomarker, remains to be clearly elucidated. To better understand the role of MTs as a biomarker in Cerastoderma edule, a bivalve widely used as bioindicator, a laboratory assay was conducted aiming to assess the sensitivity of MTs to metal and oxidative stressors. For this purpose, Cd was used to induce metal stress, whereas hydrogen peroxide (H2O2), being an oxidizing compound, was used to impose oxidative stress. Results showed that induction of MTs occurred at very different levels in metal and oxidative stress. In the presence of the oxidizing agent (H2O2), MTs only increased significantly when the degree of oxidative stress was very high, and mortality rates were higher than 50 percent. On the contrary, C. edule survived to all Cd concentrations used and significant MTs increases, compared to the control, were observed in all Cd exposures. The present work also revealed that the number of ions and the metal bound to MTs varied with the exposure conditions. In the absence of disturbance, MTs bound most (60-70 percent) of the essential metals (Zn and Cu) in solution. In stressful situations, such as the exposure to Cd and H2O2, MTs did not bind to Cu and bound less to Zn. When organisms were exposed to Cd, the total number of ions bound per MT molecule did not change, compared to control. However the sort of ions bound per MT molecule differed; part of the Zn and all Cu ions where displaced by Cd ions. For organisms exposed to H2O2, each MT molecule bound less than half of the ions compared to control and Cd conditions, which indicates a partial oxidation of thiol groups in the cysteine residues through ROS scavenging. The present results suggest that MTs are excellent markers of metal stress, but not of oxidative stress. Copyright © 2012 Elsevier Inc. All rights reserved.

Examining the specific contributions of individual Arabidopsis metallothioneins to copper distribution and metal tolerance.

PubMed

Guo, Woei-Jiun; Meetam, Metha; Goldsbrough, Peter B

2008-04-01

Metallothioneins (MTs) are small cysteine-rich proteins found in various eukaryotes. Plant MTs are classified into four types based on the arrangement of cysteine residues. To determine whether all four types of plant MTs function as metal chelators, six Arabidopsis (Arabidopsis thaliana) MTs (MT1a, MT2a, MT2b, MT3, MT4a, and MT4b) were expressed in the copper (Cu)- and zinc (Zn)-sensitive yeast mutants, Deltacup1 and Deltazrc1 Deltacot1, respectively. All four types of Arabidopsis MTs provided similar levels of Cu tolerance and accumulation to the Deltacup1 mutant. The type-4 MTs (MT4a and MT4b) conferred greater Zn tolerance and higher accumulation of Zn than other MTs to the Deltazrc1 Deltacot1 mutant. To examine the functions of MTs in plants, we studied Arabidopsis plants that lack MT1a and MT2b, two MTs that are expressed in phloem. The lack of MT1a, but not MT2b, led to a 30% decrease in Cu accumulation in roots of plants exposed to 30 mum CuSO(4). Ectopic expression of MT1a RNA in the mt1a-2 mt2b-1 mutant restored Cu accumulation in roots. The mt1a-2 mt2b-1 mutant had normal metal tolerance. However, when MT deficiency was combined with phytochelatin deficiency, growth of the mt1a-2 mt2b-1 cad1-3 triple mutant was more sensitive to Cu and cadmium compared to the cad1-3 mutant. Together these results provide direct evidence for functional contributions of MTs to plant metal homeostasis. MT1a, in particular, plays a role in Cu homeostasis in the roots under elevated Cu. Moreover, MTs and phytochelatins function cooperatively to protect plants from Cu and cadmium toxicity.

A framework for implementing data services in multi-service mobile satellite systems

NASA Technical Reports Server (NTRS)

Ali, Mohammed O.; Leung, Victor C. M.; Spolsky, Andrew I.

1988-01-01

Mobile satellite systems being planned for introduction in the early 1990s are expected to be invariably of the multi-service type. Mobile Telephone Service (MTS), Mobile Radio Service (MRS), and Mobile Data Service (MDS) are the major classifications used to categorize the many user applications to be supported. The MTS and MRS services encompass circuit-switched voice communication applications, and may be efficiently implemented using a centralized Demand-Assigned Multiple Access (DAMA) scheme. Applications under the MDS category are, on the other hand, message-oriented and expected to vary widely in characteristics; from simplex mode short messaging applications to long duration, full-duplex interactive data communication and large file transfer applications. For some applications under this service category, the conventional circuit-based DAMA scheme may prove highly inefficient due to the long time required to set up and establish communication links relative to the actual message transmission time. It is proposed that by defining a set of basic bearer services to be supported in MDS and optimizing their transmission and access schemes independent of the MTS and MRS services, the MDS applications can be more efficiently integrated into the multi-service design of mobile satellite systems.

A framework for implementing data services in multi-service mobile satellite systems

NASA Astrophysics Data System (ADS)

Ali, Mohammed O.; Leung, Victor C. M.; Spolsky, Andrew I.

1988-05-01

Mobile satellite systems being planned for introduction in the early 1990s are expected to be invariably of the multi-service type. Mobile Telephone Service (MTS), Mobile Radio Service (MRS), and Mobile Data Service (MDS) are the major classifications used to categorize the many user applications to be supported. The MTS and MRS services encompass circuit-switched voice communication applications, and may be efficiently implemented using a centralized Demand-Assigned Multiple Access (DAMA) scheme. Applications under the MDS category are, on the other hand, message-oriented and expected to vary widely in characteristics; from simplex mode short messaging applications to long duration, full-duplex interactive data communication and large file transfer applications. For some applications under this service category, the conventional circuit-based DAMA scheme may prove highly inefficient due to the long time required to set up and establish communication links relative to the actual message transmission time. It is proposed that by defining a set of basic bearer services to be supported in MDS and optimizing their transmission and access schemes independent of the MTS and MRS services, the MDS applications can be more efficiently integrated into the multi-service design of mobile satellite systems.

Raman spectroscopic and microthermometric studies of authigenic quartz (the Pepper Mts., Central Poland) as an indicator of fluids circulation

NASA Astrophysics Data System (ADS)

Naglik, Beata; Toboła, Tomasz; Natkaniec-Nowak, Lucyna; Luptáková, Jarmila; Milovská, Stanislava

2017-02-01

Differently colored authigenic quartz crystals were found as the druses compound within mudstone heteroliths from the Pepper Mts. Shale Formation (Cambrian unit of the Holy Cross Mts., Central Poland). The genesis of this mineral was established on the basis of fluid inclusion study. Raman microspectroscopy was the key instrumental technique to identify the nature of the compounds trapped in the fluid inclusions. Methane (2917 cm- 1) or water vapor (broad band 2500-3000 cm- 1) occur within two-phased primary inclusion assemblages, while nitrogen (2329 cm- 1) associated with methane and trace amount of carbon dioxide (1285, 1388 cm- 1) occur within secondary fluid inclusion assemblage. Temperatures of homogenization of primary fluid inclusions was obtained on the basis of heating experiments and ranged from 171° to 266 °C. These values are much higher than expected for the diagenetic system without metamorphic changes what may imply hydrothermal origin of quartz crystals. The source of fluids is uncertain as in the Holy Cross Mts. there was no volcanic activity to the end of Late Devonian. However, fluids originated in metamorphic basin could use deep faults as the migration paths.

Dual-mode enhancement of metallothionein protein with cell transduction and retention peptide fusion.

PubMed

Lim, Kwang Suk; Lim, Myoung-Hwa; Won, Young-Wook; Kim, Jang Kyoung; Kang, Young Cheol; Park, Eun Jeong; Chae, Ji-Won; Kim, So-Mi; Ryu, Seong-Eon; Pak, Youngmi Kim; Kim, Yong-Hee

2013-10-28

Protein transduction domains (PTDs), also known as cell-penetrating peptides (CPPs), have been developed as effective systems for delivering bio-active cargos such as proteins, genes and particles. Further improvements on cell-specific targeting, intracellular organelle targeting and intracellular retention are still necessary to enhance the therapeutic effect of PTD fusion proteins. In order to enhance the cell transduction and retention of anti-oxidative metallothionein protein (MT), MT was recombinantly fused with transcriptional activator (Tat) with or without a short peptide (sMTS) derived from mitochondria malate dehydrogenase (mMDH). Cellular uptake and retention time of fusion protein were significantly increased in the H9c2 cell by sMTS. The Tat-sMTS-MT (TMM) fusion protein protected H9c2 cells more effectively against hypoxia, hyperglycemia and combination compared with Tat-MT (TM) by reducing intracellular ROS level. It maintained the normal blood glucose level over an extended period of time in a streptozotocin-induced diabetic mouse model. PTD-sMTS-MT fusion protein has a potential to be used as a therapeutic protein for the treatment or prevention of diabetes and diabetic complications. © 2013.

Evaluation of the ease of taking mini-tablets compared with other tablet formulations in healthy volunteers.

PubMed

Hayakawa, Yoshiyuki; Uchida, Shinya; Namiki, Noriyuki

2016-03-10

"Mini-tablets" (MTs) are tablets of diameter≤3mm and have been widely studied and developed. However, reports comparing MTs with other tablet formulations are few. We wished to evaluate the ease of taking a MT quantitatively in comparison with an orally disintegrating mini-tablet (ODMT), conventional tablet (CT) and conventional orally disintegrating tablet (ODT). Four types of tablets were prepared. We prepared tablets of two diameters (3mm for MTs and ODMTs vs. 8mm for CTs and ODTs) and two formulations (MTs and CTs vs. ODMTs and ODTs). Our randomized crossover trial in 18 healthy volunteers (8 men and 10 women; mean age, 22.5years) indicated that the visual analog scale (VAS) score for the ease and amount of water required for intake of MTs was significantly lower than those of CTs. An ODMT required the least amount of water and smallest VAS score for the ease of taking a tablet. Our results showed that the advantage of MTs with regard to the ease of taking and decreased amount of water required was exerted for a unit of dosing comprising <5 tablets. These data suggested the usefulness of MTs and the importance of the number of MTs for comfortable consumption by patients. Copyright © 2015. Published by Elsevier B.V.

Dephosphorylation of microtubule-binding sites at the neurofilament-H tail domain by alkaline, acid, and protein phosphatases.

PubMed

Hisanaga, S; Yasugawa, S; Yamakawa, T; Miyamoto, E; Ikebe, M; Uchiyama, M; Kishimoto, T

1993-06-01

The dephosphorylation-induced interaction of neurofilaments (NFs) with microtubules (MTs) was investigated by using several phosphatases. Escherichia coli alkaline and wheat germ acid phosphatases increased the electrophoretic mobility of NF-H and NF-M by dephosphorylation, and induced the binding of NF-H to MTs. The binding of NFs to MTs was observed only after the electrophoretic mobility of NF-H approached the exhaustively dephosphorylated level when alkaline phosphatase was used. The number of phosphate remaining when NF-H began to bind to MTs was estimated by measuring phosphate bound to NF-H. NF-H did not bind to MTs even when about 40 phosphates from the total of 51 had been removed by alkaline phosphatase. The removal of 6 further phosphates finally resulted in the association of NF-H with MTs. A similar finding, that the restricted phosphorylation sites in the NF-H tail domain, but not the total amount of phosphates, were important for binding to MTs, was also obtained with acid phosphatases. In contrast to alkaline and acid phosphatases, four classes of protein phosphatases (protein phosphatases 1, 2A, 2B, and 2C) were ineffective for shifting the electrophoretic mobility of NF proteins and for inducing the association of NFs to MTs.

A Multiscale Material Testing System for In Situ Optical and Electron Microscopes and Its Application

PubMed Central

Ye, Xuan; Cui, Zhiguo; Fang, Huajun; Li, Xide

2017-01-01

We report a novel material testing system (MTS) that uses hierarchical designs for in-situ mechanical characterization of multiscale materials. This MTS is adaptable for use in optical microscopes (OMs) and scanning electron microscopes (SEMs). The system consists of a microscale material testing module (m-MTM) and a nanoscale material testing module (n-MTM). The MTS can measure mechanical properties of materials with characteristic lengths ranging from millimeters to tens of nanometers, while load capacity can vary from several hundred micronewtons to several nanonewtons. The m-MTM is integrated using piezoelectric motors and piezoelectric stacks/tubes to form coarse and fine testing modules, with specimen length from millimeters to several micrometers, and displacement distances of 12 mm with 0.2 µm resolution for coarse level and 8 µm with 1 nm resolution for fine level. The n-MTM is fabricated using microelectromechanical system technology to form active and passive components and realizes material testing for specimen lengths ranging from several hundred micrometers to tens of nanometers. The system’s capabilities are demonstrated by in-situ OM and SEM testing of the system’s performance and mechanical properties measurements of carbon fibers and metallic microwires. In-situ multiscale deformation tests of Bacillus subtilis filaments are also presented. PMID:28777341

Intravenous flurbiprofen axetil can stabilize the hemodynamic instability due to mesenteric traction syndrome--evaluation with continuous measurement of the systemic vascular resistance index using a FloTrac® sensor.

PubMed

Takada, Motoshi; Taruishi, Chieko; Sudani, Tomoko; Suzuki, Akira; Iida, Hiroki

2013-08-01

Evaluation of the stabilizing effect of intravenous flurbiprofen axetil against hemodynamic instability due to mesenteric traction syndrome (MTS) by continuous measurement of systemic vascular resistance index (SVRI) using a FloTrac(®) sensor was evaluated. Prospective randomized trial. A single-center study performed in an educational hospital. Two prospective studies were carried out, each with 40 patients scheduled for elective open abdominal surgery. Twenty patients received 50 mg of flurbiprofen axetil after the recognition of MTS by the anesthesiologist (group FT). The remaining patients served as controls (groups CP and CT). SVRI data was collected every 20 seconds for 1 hour after starting the laparotomy. The average SVRI prior to skin incision was taken as the baseline. Following 3 values were devised to evaluate MTS: the S-value (sum total of changes in SVRI from baseline), the T-value (period during which SVRI remained 20% or more below baseline), and the M-value (maximum change in SVRI from baseline). In group FP, decrease in SVRI was smaller than in group CP, and statistical differences in the 3 values were found. In group FT, SVRI recovered earlier than in group CT, and statistical differences were found in S-value and T-value. However, the M-value had no statistical differences. Intravenous flurbiprofen axetil can stabilize the hemodynamic instability due to MTS. Copyright © 2013 Elsevier Inc. All rights reserved.

Dose distribution of secondary radiation in a water phantom for a proton pencil beam-EURADOS WG9 intercomparison exercise.

PubMed

Stolarczyk, L; Trinkl, S; Romero-Expósito, M; Mojżeszek, N; Ambrozova, I; Domingo, C; Davídková, M; Farah, J; Kłodowska, M; Knežević, Ž; Liszka, M; Majer, M; Miljanić, S; Ploc, O; Schwarz, M; Harrison, R M; Olko, P

2018-04-19

Systematic 3D mapping of out-of-field doses induced by a therapeutic proton pencil scanning beam in a 300  ×  300  ×  600 mm 3 water phantom was performed using a set of thermoluminescence detectors (TLDs): MTS-7 ( 7 LiF:Mg,Ti), MTS-6 ( 6 LiF:Mg,Ti), MTS-N ( nat LiF:Mg,Ti) and TLD-700 ( 7 LiF:Mg,Ti), radiophotoluminescent (RPL) detectors GD-352M and GD-302M, and polyallyldiglycol carbonate (PADC)-based (C 12 H 18 O 7 ) track-etched detectors. Neutron and gamma-ray doses, as well as linear energy transfer distributions, were experimentally determined at 200 points within the phantom. In parallel, the Geant4 Monte Carlo code was applied to calculate neutron and gamma radiation spectra at the position of each detector. For the cubic proton target volume of 100  ×  100  ×  100 mm 3 (spread out Bragg peak with a modulation of 100 mm) the scattered photon doses along the main axis of the phantom perpendicular to the primary beam were approximately 0.5 mGy Gy -1 at a distance of 100 mm and 0.02 mGy Gy -1 at 300 mm from the center of the target. For the neutrons, the corresponding values of dose equivalent were found to be ~0.7 and ~0.06 mSv Gy -1 , respectively. The measured neutron doses were comparable with the out-of-field neutron doses from a similar experiment with 20 MV x-rays, whereas photon doses for the scanning proton beam were up to three orders of magnitude lower.

Dose distribution of secondary radiation in a water phantom for a proton pencil beam—EURADOS WG9 intercomparison exercise

NASA Astrophysics Data System (ADS)

Stolarczyk, L.; Trinkl, S.; Romero-Expósito, M.; Mojżeszek, N.; Ambrozova, I.; Domingo, C.; Davídková, M.; Farah, J.; Kłodowska, M.; Knežević, Ž.; Liszka, M.; Majer, M.; Miljanić, S.; Ploc, O.; Schwarz, M.; Harrison, R. M.; Olko, P.

2018-04-01

Systematic 3D mapping of out-of-field doses induced by a therapeutic proton pencil scanning beam in a 300  ×  300  ×  600 mm3 water phantom was performed using a set of thermoluminescence detectors (TLDs): MTS-7 (7LiF:Mg,Ti), MTS-6 (6LiF:Mg,Ti), MTS-N (natLiF:Mg,Ti) and TLD-700 (7LiF:Mg,Ti), radiophotoluminescent (RPL) detectors GD-352M and GD-302M, and polyallyldiglycol carbonate (PADC)-based (C12H18O7) track-etched detectors. Neutron and gamma-ray doses, as well as linear energy transfer distributions, were experimentally determined at 200 points within the phantom. In parallel, the Geant4 Monte Carlo code was applied to calculate neutron and gamma radiation spectra at the position of each detector. For the cubic proton target volume of 100  ×  100  ×  100 mm3 (spread out Bragg peak with a modulation of 100 mm) the scattered photon doses along the main axis of the phantom perpendicular to the primary beam were approximately 0.5 mGy Gy‑1 at a distance of 100 mm and 0.02 mGy Gy‑1 at 300 mm from the center of the target. For the neutrons, the corresponding values of dose equivalent were found to be ~0.7 and ~0.06 mSv Gy‑1, respectively. The measured neutron doses were comparable with the out-of-field neutron doses from a similar experiment with 20 MV x-rays, whereas photon doses for the scanning proton beam were up to three orders of magnitude lower.

Miura-type transformations for lattice equations and Lie group actions associated with Darboux-Lax representations

NASA Astrophysics Data System (ADS)

Berkeley, George; Igonin, Sergei

2016-07-01

Miura-type transformations (MTs) are an essential tool in the theory of integrable nonlinear partial differential and difference equations. We present a geometric method to construct MTs for differential-difference (lattice) equations from Darboux-Lax representations (DLRs) of such equations. The method is applicable to parameter-dependent DLRs satisfying certain conditions. We construct MTs and modified lattice equations from invariants of some Lie group actions on manifolds associated with such DLRs. Using this construction, from a given suitable DLR one can obtain many MTs of different orders. The main idea behind this method is closely related to the results of Drinfeld and Sokolov on MTs for the partial differential KdV equation. Considered examples include the Volterra, Narita-Itoh-Bogoyavlensky, Toda, and Adler-Postnikov lattices. Some of the constructed MTs and modified lattice equations seem to be new.

Hsp90 binds microtubules and is involved in the reorganization of the microtubular network in angiosperms.

PubMed

Krtková, Jana; Zimmermann, Aleksandra; Schwarzerová, Kateřina; Nick, Peter

2012-09-15

Microtubules (MTs) are essential for many processes in plant cells. MT-associated proteins (MAPs) influence MT polymerization dynamics and enable them to perform their functions. The molecular chaperone Hsp90 has been shown to associate with MTs in animal and plant cells. However, the role of Hsp90-MT binding in plants has not yet been investigated. Here, we show that Hsp90 associates with cortical MTs in tobacco cells and decorates MTs in the phragmoplast. Further, we show that tobacco Hsp90_MT binds directly to polymerized MTs in vitro. The inhibition of Hsp90 by geldanamycin (GDA) severely impairs MT re-assembly after cold-induced de-polymerization. Our results indicate that the plant Hsp90 interaction with MTs plays a key role in cellular events, where MT re-organization is needed. Copyright © 2012 Elsevier GmbH. All rights reserved.

Undertriage in the Manchester triage system: an assessment of severity and options for improvement.

PubMed

Seiger, N; van Veen, M; Steyerberg, E W; Ruige, M; van Meurs, A H J; Moll, H A

2011-07-01

The Manchester Triage System (MTS) determines an inappropriately low level of urgency (undertriage) to a minority of children. The aim of the study was to assess the clinical severity of undertriaged patients in the MTS and to define the determinants of undertriage. Patients who had attended the emergency department (ED) were triaged according to the MTS. Undertriage was defined as a 'low urgent' classification (levels 3, 4 and 5) under the MTS; as a 'high urgent' classification (levels 1 and 2) under an independent reference standard based on abnormal vital signs (level 1), potentially life-threatening conditions (level 2), and a combination of resource use, hospitalisation, and follow-up for the three lowest urgency levels. In an expert meeting, three experienced paediatricians used a standardised format to determine the clinical severity. The clinical severity had been expressed by possible consequences of treatment delay caused by undertriage, such as the use of more interventions and diagnostics, longer hospitalisation, complications, morbidity, and mortality. In a prospective observational study we used logistic regression analysis to assess predictors for undertriage. In total, 0.9% (119/13,408) of the patients were undertriaged. In 53% (63/119) of these patients, experts considered undertriage as clinically severe. In 89% (56/63) of these patients the high reference urgency was determined on the basis of abnormal vital signs. The prospective observational study showed undertriage was more likely in infants (especially those younger than three months), and in children assigned to the MTS 'unwell child' flowchart (adjusted OR<3 months 4.2, 95% CI 2.3 to 7.7 and adjusted ORunwell child 11.1, 95% CI 5.5 to 22.3). Undertriage is infrequent, but can have serious clinical consequences. To reduce significant undertriage, the authors recommend a systematic assessment of vital signs in all children.

Copper-induced overexpression of genes encoding antioxidant system enzymes and metallothioneins involve the activation of CaMs, CDPKs and MEK1/2 in the marine alga Ulva compressa.

PubMed

Laporte, Daniel; Valdés, Natalia; González, Alberto; Sáez, Claudio A; Zúñiga, Antonio; Navarrete, Axel; Meneses, Claudio; Moenne, Alejandra

2016-08-01

Transcriptomic analyses were performed in the green macroalga Ulva compressa cultivated with 10μM copper for 24h. Nucleotide sequences encoding antioxidant enzymes, ascorbate peroxidase (ap), dehydroascorbate reductase (dhar) and glutathione reductase (gr), enzymes involved in ascorbate (ASC) synthesis l-galactose dehydrogenase (l-gdh) and l-galactono lactone dehydrogenase (l-gldh), in glutathione (GSH) synthesis, γ-glutamate-cysteine ligase (γ-gcl) and glutathione synthase (gs), and metal-chelating proteins metallothioneins (mt) were identified. Amino acid sequences encoded by transcripts identified in U. compressa corresponding to antioxidant system enzymes showed homology mainly to plant and green alga enzymes but those corresponding to MTs displayed homology to animal and plant MTs. Level of transcripts encoding the latter proteins were quantified in the alga cultivated with 10μM copper for 0-12 days. Transcripts encoding enzymes of the antioxidant system increased with maximal levels at day 7, 9 or 12, and for MTs at day 3, 7 or 12. In addition, the involvement of calmodulins (CaMs), calcium-dependent protein kinases (CDPKs), and the mitogen-activated protein kinase kinase (MEK1/2) in the increase of the level of the latter transcripts was analyzed using inhibitors. Transcript levels decreased with inhibitors of CaMs, CDPKs and MEK1/2. Thus, copper induces overexpression of genes encoding antioxidant enzymes, enzymes involved in ASC and GSH syntheses and MTs. The increase in transcript levels may involve the activation of CaMs, CDPKs and MEK1/2 in U. compressa. Copyright © 2016 Elsevier B.V. All rights reserved.

Methylphenidate Transdermal System: A Multisite, Open-Label Study of Dermal Reactions in Pediatric Patients Diagnosed With ADHD

PubMed Central

Squires, Liza; Li, Yunfeng; Civil, Richard; Paller, Amy S.

2010-01-01

Objective: To characterize dermal reactions and examine methylphenidate (MPH) sensitization in subjects receiving methylphenidate transdermal system (MTS). Method: This multicenter, open-label, dose-optimization study utilized MTS doses of 10, 15, 20, and 30 mg in children aged 6 to 12 years, inclusive (N = 305), with a DSM-IV-TR primary diagnosis of attention-deficit/hyperactivity disorder. The study was conducted between January 8, 2007, and August 23, 2007. Subjects wore MTS on their hips for 9 hours per day, alternating sides daily for a total of 7 weeks. Assessments included the Experience of Discomfort scale, Transdermal System Adherence scale, and Dermal Response Scale (DRS; 0 = no irritation, 7 = strong reaction). On-study reevaluations were conducted to characterize DRS scores ≥ 4. Epicutaneous allergy patch testing was conducted for DRS scores ≥ 6, persistent DRS scores ≥ 4, DRS score increase following an assessment of ≥ 4, or DRS scores of 4 or 5 following elective discontinuation. Results: Approximately half of subjects experienced definite erythema at the patch site that generally dissipated within 24 hours. Four subjects experienced a DRS score of 4 (1%): erythema in 1 subject resolved on study treatment, 2 cases resolved poststudy and subjects tolerated oral MPH, and 1 subject discontinued treatment. The latter subject was referred for patch testing and was diagnosed with allergic contact sensitization to MPH. Conclusions: Few severe dermal effects were seen with MTS treatment. Dermal reactions were characterized as contact dermatitis and dissipated rapidly. On patch testing, 1 subject (0.3%) manifested sensitization to MPH. Trial Registration: clinicaltrials.gov Identifier: NCT00434213 PMID:21494336

Effect of naturally mouldy wheat or fungi administration on metallothioneins level in brain tissues of rats.

PubMed

Vasatkova, Anna; Krizova, Sarka; Krystofova, Olga; Adam, Vojtech; Zeman, Ladislav; Beklova, Miroslava; Kizek, Rene

2009-01-01

The aim of this study is to determine level of metallothioneins (MTs) in brain tissues of rats administered by feed mixtures with different content of mouldy wheat or fungi. Selected male laboratory rats of Wistar albino at age of 28 days were used in our experiments. The rats were administered by feed mixtures with different content of vitamins, naturally mouldy wheat or fungi for 28 days. At the very end of the experiment, the animals were put to death and brains were sampled. MT level was determined by differential pulse voltammetry Brdicka reaction. We found that MTs' level in brain tissues from rats administered by standard feed mixtures was significantly higher compared to the level of MTs in rats supplemented by vitamins. Further we studied the effect of supplementation of naturally mouldy wheat on MTs level in rats. In mouldy wheat we detected the presence of following fungi species: Mucor spp., Absidia spp., Penicillium spp., Aspergillus spp. and Fusarium spp. Moreover we also identified and quantified following mycotoxins - deoxynivalenol, zearalenone, T2-toxin and aflatoxins. Level of MTs determined in rats treated with 33 or 66% of mouldy wheat was significantly lower compared to control ones. On the other hand rats treated with 100% of mouldy wheat had less MTs but not significantly. Supplementation of vitamins to rats fed by mouldy wheat had adverse effect on MTs level compared to rats with no other supplementation by vitamins. Moreover vitamins supplementation has no effect on MTs level in brain tissues of rats treated or non-treated with Ganoderma lucidum L. Both mycotoxins and vitamins have considerable effect on level of MTs in brain tissues. It can be assumed that the administered substances markedly influence redox metabolism, which could negatively influence numerous biochemical pathways including those closely related with MTs.

Cytoplasmic flows as signatures for the mechanics of mitotic positioning

PubMed Central

Nazockdast, Ehssan; Rahimian, Abtin; Needleman, Daniel; Shelley, Michael

2017-01-01

The proper positioning of mitotic spindle in the single-cell Caenorhabditis elegans embryo is achieved initially by the migration and rotation of the pronuclear complex (PNC) and its two associated astral microtubules (MTs). Pronuclear migration produces global cytoplasmic flows that couple the mechanics of all MTs, the PNC, and the cell periphery with each other through their hydrodynamic interactions (HIs). We present the first computational study that explicitly accounts for detailed HIs between the cytoskeletal components and demonstrate the key consequences of HIs for the mechanics of pronuclear migration. First, we show that, because of HIs between the MTs, the cytoplasm-filled astral MTs behave like a porous medium, with its permeability decreasing with increasing the number of MTs. We then directly study the dynamics of PNC migration under various force-transduction models, including the pushing or pulling of MTs at the cortex and the pulling of MTs by cytoplasmically bound force generators. Although achieving proper position and orientation on reasonable time scales does not uniquely choose a model, we find that each model produces a different signature in its induced cytoplasmic flow. We suggest that cytoplasmic flows can be used to differentiate between mechanisms. PMID:28331070

From proto-mitosis to mitosis — An alternative hypothesis on the origin and evolution of the mitotic spindle

NASA Astrophysics Data System (ADS)

Roos, U.-P.

1984-03-01

Based on the assumption that the ancestral proto-eukaryote evolved from an ameboid prokarybte I propose the hypothesis that nuclear division of the proto-eukaryote was effected by the same system of contractile filaments it used for ameboid movement and cytosis. When the nuclear membranes evolved from the cell membrane, contractile filaments remained associated with them. The attachment site of the genome in the nuclear envelope was linked to the cell membrane by specialized contractile filaments. During protomitosis, i.e., nuclear and cell division of the proto-eukaryote, these filaments performed segregation of the chromosomes, whereas others constricted and cleaved the nucleus and the mother cell. When microtubules (MTs) had evolved in the cytoplasm, they also became engaged in nuclear division. Initially, an extranuolear bundle of MTs assisted chromosome segregation by establishing a defined axis. The evolutionary tendency then was towards an increasingly important role for MTs. Spindle pole bodies (SPBs) developed from the chromosomal attachment sites in the nuclear envelope and organized an extranuclear central spindle. The chromosomes remained attached to the SPBs during nuclear division. In a subsequent step the spindle became permanently lodged inside the nucleus. Chromosomes detached from the SPBs and acquired kinetochores and kinetochore-MTs. At first, this spindle segregated chromosomes by elongation, the kinetochore-MTs playing the role of static anchors. Later, spindle elongation was supplemented by poleward movement of the chromosomes. When dissolution of the nuclear envelope at the beginning of mitosis became a permanent feature, the open spindle of higher eukaryotes was born.

In-hospital delay in ST-segment-elevation myocardial infarction after Manchester Triage.

PubMed

Trigo, Joana; Gago, Paula; Mimoso, Jorge; Santos, Walter; Marques, Nuno; Gomes, Veloso

2008-10-01

In ST-segment elevation myocardial infarction (STEMI), time to reperfusion influences morbidity and mortality, and reducing in-hospital delay (IHD) continues to be important. Doubts have been expressed whether the Manchester Triage System (MTS) contributes to this objective. To evaluate the effectiveness of the MTS in classifying STEMI patients and its effect on IHD. We analyzed 278 patients with STEMI admitted to the Coronary Care Unit through the Emergency Department between January 13 2005 and November 26 2006. The patients were divided into two groups according to their MTS classification: Group A--emergent and very urgent patients; Group B--urgent and standard patients. The two groups were compared in terms of clinical and demographic characteristics, pre-hospital delay (PHD), IHD and door-to-needle (DNT) and door-to-balloon (DBT) times. The mean age of the patients studied was 68 +/- 14 years, and 184 patients (65.7%) were male. Group A comprised 220 patients (79%) and Group B 58 patients (21%). There were no significant differences between the two groups in clinical or demographic characteristics or in PHD. IHD, DNT and DBT were significantly longer in Group B. 1) Although the majority of STEMI patients were classified as emergent or very urgent, the percentage not classified as such by the MTS was excessively high. 2) This could not be explained by clinical characteristics or by PHD. 3) The incorrect classification by the MTS of patients with STEMI resulted in significantly increased IHD in a large proportion of patients, limiting prompt access to reperfusion therapy.

Electron tomography of the microtubule cytoskeleton in multinucleated hyphae of Ashbya gossypii.

PubMed

Gibeaux, Romain; Lang, Claudia; Politi, Antonio Z; Jaspersen, Sue L; Philippsen, Peter; Antony, Claude

2012-12-01

We report the mechanistic basis guiding the migration pattern of multiple nuclei in hyphae of Ashbya gossypii. Using electron tomography, we reconstructed the cytoplasmic microtubule (cMT) cytoskeleton in three tip regions with a total of 13 nuclei and also the spindle microtubules of four mitotic nuclei. Each spindle pole body (SPB) nucleates three cMTs and most cMTs above a certain length grow according to their plus-end structure. Long cMTs closely align for several microns along the cortex, presumably marking regions where dynein generates pulling forces on nuclei. Close proximity between cMTs emanating from adjacent nuclei was not observed. The majority of nuclei carry duplicated side-by-side SPBs, which together emanate an average of six cMTs, in most cases in opposite orientation with respect to the hyphal growth axis. Such cMT arrays explain why many nuclei undergo short-range back and forth movements. Only occasionally do all six cMTs orient in one direction, a precondition for long-range nuclear bypassing. Following mitosis, daughter nuclei carry a single SPB with three cMTs. The increased probability that all three cMTs orient in one direction explains the high rate of nuclear bypassing observed in these nuclei. The A. gossypii mitotic spindle was found to be structurally similar to that of Saccharomyces cerevisiae in terms of nuclear microtubule (nMT) number, length distribution and three-dimensional organization even though the two organisms differ significantly in chromosome number. Our results suggest that two nMTs attach to each kinetochore in A. gossypii and not only one nMT like in S. cerevisiae.

Cell division in two large pennate diatoms Hantzschia and Nitzschia III. A new proposal for kinetochore function during prometaphase

PubMed Central

1980-01-01

Prometaphase in two large species of diatoms is examined, using the following techniques: (a) time-lapse cinematography of chromosome movements in vivo; (b) electron microscopy of corresponding stages: (c) reconstruction of the microtubules (MTs) in the kinetochore fiber of chromosomes attached to the spindle. In vivo, the chromosomes independently commence oscillations back and forth to one pole. The kinetochore is usually at the leading edge of such chromosome movements; a variable time later both kinetochores undergo such oscillations but toward opposite poles and soon stretch poleward to establish stable bipolar attachment. Electron microscopy of early prometaphase shows that the kinetochores usually laterally associate with MTs that have one end attached to the spindle pole. At late prometaphase, most chromosomes are fully attached to the spindle, but the kinetochores on unattached chromosomes are bare of MTs. Reconstruction of the kinetochore fiber demonstrates that most of its MTs (96%) extend past the kinetochore and are thus apparently not nucleated there. At least one MT terminates at each kinetochore analyzed. Our interpretation is that the conventional view of kinetochore function cannot apply to diatoms. The kinetochore fiber in diatoms appears to be primarily composed of MTs from the poles, in contrast to the conventional view that many MTs of the kinetochore fiber are nucleated by the kinetochore. Similarly, chromosomes appear to initially orient their kinetochores to opposite poles by moving along MTs attached to the poles, instead of orientation effected by kinetochore MTs laterally associating with other MTs in the spindle. The function of the kinetochore in diatoms and other cell types is discussed. PMID:7400213

Electrochemical and spectroscopic characterization of surface sol-gel processes.

PubMed

Chen, Xiaohong; Wilson, George S

2004-09-28

(3-Mercaptopropyl)trimethoxysilane (MTS) forms a unique film on a platinum substrate by self-assembly and sol-gel cross-linking. The gelating and drying states of the self-assembled MTS sol-gel films were probed by use of electrochemical and spectroscopic methods. The thiol moiety was the only active group within the sol-gel network. Gold nanoparticles were employed to detect the availability of the thiol group and their interaction further indicated the physicochemical states of the sol-gel inner structure. It was found that the thiol groups in the open porous MTS aerogel matrix were accessible to the gold nanoparticles while thiol groups in the compact MTS xerogel network were not accessible to the gold nanoparticles. The characteristics of the sol-gel matrix change with time because of its own irreversible gelating and drying process. The present work provides direct evidence of gold nanoparticle binding with thiol groups within the sol-gel structures and explains the different permeability of "aerogel" and "xerogel" films of MTS on the basis of electrochemical and spectroscopic results. Two endogenous species, hydrogen peroxide and ascorbic acid, were used to test the permeability of the self-assembled sol-gel film in different states. The MTS xerogel film on the platinum electrode was extremely selective against ascorbic acid while maintaining high sensitivity to hydrogen peroxide in contrast to the relatively high permeability of ascorbic acid in the MTS aerogel film. This study showed the potential of the MTS sol-gel film as a nanoporous material in biosensor development.

Semen quality, antioxidant status and reproductive performance of rabbits bucks fed milk thistle seeds and rosemary leaves.

PubMed

Attia, Youssef A; Hamed, Rawia S; Bovera, Fulvia; Abd El-Hamid, Abd El-Hamid E; Al-Harthi, Mohammed A; Shahba, Hossam A

2017-09-01

The study aimed to investigate the effects of milk thistle seeds (MTS) and rosemary leaves (RL) both at 5 and 10g/kg diet on reproductive performance, semen quality and blood metabolites of rabbit bucks. A total of 35 rabbit bucks were randomly distributed into five experimental groups (7 bucks/group). All the groups were fed the same basal diet. The 1st group (control) did not have MTS and RL in its basal diet. The 2nd and 3rd groups were supplemented with MTS at 5 and 10g/kg, respectively. The 4th and 5th groups were fed the basal diet supplemented with RL at 5 and 10g/kg, respectively. The sperm concentration (SC), total sperm output (TSO), live sperm (LS), total live sperm (TLS) and total motile sperm (TMS) were significantly greater in the bucks fed MTS at 10 and RL at 5g/kg diet than the control group. Bucks fed MTS at 10g/kg diet had higher fertility than the control. Also, RL 5g/kg group showed higher testosterone and fertility than the control, but the MTS 10g/kg group showed the highest value for both parameters. In conclusion, MTS and RL at 10 and 5g/kg, respectively, significantly improved the semen quality and the fertility and MTS also increased the economic efficiency of rabbit bucks. Copyright © 2017 Elsevier B.V. All rights reserved.

Protein expression changes during human triple negative breast cancer cell line progression to lymph node metastasis in a xenografted model in nude mice

PubMed Central

Roberti, María Paula; Arriaga, Juan Martín; Bianchini, Michele; Quintá, Héctor Ramiro; Bravo, Alicia Inés; Levy, Estrella Mariel; Mordoh, José; Barrio, María Marcela

2012-01-01

Triple negative breast cancers (TNBC) lacking hormone receptors and HER-2 amplification are very aggressive tumors. Since relevant differences between primary tumors and metastases could arise during tumor progression as evidenced by phenotypic discordances reported for hormonal receptors or HER-2 expression, in this analysis we studied changes that occurred in our TNBC model IIB-BR-G throughout the development of IIB-BR-G-MTS6 metastasis to the lymph nodes (LN) in nude mice, using an antibody-based protein array to characterize their expression profile. We also analyzed their growth kinetics, migration, invasiveness and cytoskeleton structure in vitro and in vivo. In vitro IIB-BR-G-MTS6 cells grew slower but showed higher anchorage independent growth. In vivo IIB-BR-G-MTS6 tumors grew significantly faster and showed a 100% incidence of LN metastasis after s.c. inoculation, although no metastasis was observed for IIB-BR-G. CCL3, IL1β, CXCL1, CSF2, CSF3, IGFBP1, IL1α, IL6, IL8, CCL20, PLAUR, PlGF and VEGF were strongly upregulated in IIB-BR-G-MTS6 while CCL4, ICAM3, CXCL12, TNFRSF18, FIGF were the most downregulated proteins in the metastatic cell line. IIB-BR-G-MTS6 protein expression profile could reflect a higher NFκB activation in these cells. In vitro, IIB-BR-G displayed higher migration but IIB-BR-G-MTS6 had more elevated matrigel invasion ability. In agreement with that observation, IIB-BR-G-MTS6 had an upregulated expression of MMP1, MMP9, MMP13, PLAUR and HGF. IIB-BR-G-MTS6 tumors presented also higher local lymphatic invasion than IIB-BR-G but similar lymphatic vessel densities. VEGFC and VEGFA/B expression were higher both in vitro and in vivo for IIB-BR-G-MTS6. IIB-BR-G-MTS6 expressed more vimentin than IB-BR-G cells, which was mainly localized in the cellular extremities and both cell lines are E-cadherin negative. Our results suggest that IIB-BR-G-MTS6 cells have acquired a pronounced epithelial-to-mesenchymal transition phenotype. Protein expression changes observed between primary tumor-derived IIB-BR-G and metastatic IIB-BR-G-MTS6 TNBC cells suggest potential targets involved in the control of metastasis. PMID:22825326

Reversible Morphological Control of Tubulin-Encapsulating Giant Liposomes by Hydrostatic Pressure.

PubMed

Hayashi, Masahito; Nishiyama, Masayoshi; Kazayama, Yuki; Toyota, Taro; Harada, Yoshie; Takiguchi, Kingo

2016-04-19

Liposomes encapsulating cytoskeletons have drawn much recent attention to develop an artificial cell-like chemical-machinery; however, as far as we know, there has been no report showing isothermally reversible morphological changes of liposomes containing cytoskeletons because the sets of various regulatory factors, that is, their interacting proteins, are required to control the state of every reaction system of cytoskeletons. Here we focused on hydrostatic pressure to control the polymerization state of microtubules (MTs) within cell-sized giant liposomes (diameters ∼10 μm). MT is the cytoskeleton formed by the polymerization of tubulin, and cytoskeletal systems consisting of MTs are very dynamic and play many important roles in living cells, such as the morphogenesis of nerve cells and formation of the spindle apparatus during mitosis. Using real-time imaging with a high-pressure microscope, we examined the effects of hydrostatic pressure on the morphology of tubulin-encapsulating giant liposomes. At ambient pressure (0.1 MPa), many liposomes formed protrusions due to tubulin polymerization within them. When high pressure (60 MPa) was applied, the protrusions shrank within several tens of seconds. This process was repeatedly inducible (around three times), and after the pressure was released, the protrusions regenerated within several minutes. These deformation rates of the liposomes are close to the velocities of migrating or shape-changing living cells rather than the shortening and elongation rates of the single MTs, which have been previously measured. These results demonstrate that the elongation and shortening of protrusions of giant liposomes is repeatedly controllable by regulating the polymerization state of MTs within them by applying and releasing hydrostatic pressure.

Maximal venous outflow velocity: an index for iliac vein obstruction.

PubMed

Jones, T Matthew; Cassada, David C; Heidel, R Eric; Grandas, Oscar G; Stevens, Scott L; Freeman, Michael B; Edmondson, James D; Goldman, Mitchell H

2012-11-01

Leg swelling is a common cause for vascular surgical evaluation, and iliocaval obstruction due to May-Thurner syndrome (MTS) can be difficult to diagnose. Physical examination and planar radiographic imaging give anatomic information but may miss the fundamental pathophysiology of MTS. Similarly, duplex ultrasonographic examination of the legs gives little information about central impedance of venous return above the inguinal ligament. We have modified the technique of duplex ultrasonography to evaluate the flow characteristics of the leg after tourniquet-induced venous engorgement, with the objective of revealing iliocaval obstruction characteristic of MTS. Twelve patients with signs and symptoms of MTS were compared with healthy control subjects for duplex-derived maximal venous outflow velocity (MVOV) after tourniquet-induced venous engorgement of the leg. The data for healthy control subjects were obtained from a previous study of asymptomatic volunteers using the same MVOV maneuvers. The tourniquet-induced venous engorgement mimics that caused during vigorous exercise. A right-to-left ratio of MVOV was generated for patient comparisons. Patients with clinical evidence of MTS had a mean right-to-left MVOV ratio of 2.0, asymptomatic control subjects had a mean ratio of 1.3, and MTS patients who had undergone endovascular treatment had a poststent mean ratio of 1.2 (P = 0.011). Interestingly, computed tomography and magnetic resonance imaging results, when available, were interpreted as positive in only 53% of the patients with MTS according to both our MVOV criteria and confirmatory venography. After intervention, the right-to-left MVOV ratio in the MTS patients was found to be reduced similar to asymptomatic control subjects, indicating a relief of central venous obstruction by stenting the compressive MTS anatomy. Duplex-derived MVOV measurements are helpful for detection of iliocaval venous obstruction, such as MTS. Right-to-left MVOV ratios and postengorgement spectral analysis are helpful adjuncts to duplex imaging for leg swelling. The MVOV maneuvers are well tolerated by patients and yields physiological data regarding central venous obstruction that computed tomography and magnetic resonance imaging fail to detect. Copyright © 2012 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.

Effects of milk thistle seed against aflatoxin B1 in broiler model.

PubMed

Amiridumari, Halimeh; Sarir, Hadi; Afzali, Nazar; Fanimakki, Omid

2013-09-01

Consumption of aflatoxin B1 (AFB1) contaminated products can pose a risk of development of various diseases in human and animals due to radical production. The scope of this work is to evaluate the efficacy of milk thistle seed (MTS), as a radical scavenger, on serum biochemistry, lipid profile and liver enzymes against AFB1 in broiler chickens contaminated with AFB1. The effect of nine experimental treatments (3 × 3 factorial design) was assessed using 216 one-d-old Ross 308 male broiler chicks in a randomized complete design with four replicates of six birds for each dietary treatments: Control (T1), 250 ppb AFB1 (T2), 500 ppb AFB1 (T3), 0.5% MTS (T4), 0.5% MTS Plus 250 ppb AFB1 (T5), 0.5% MTS Plus 500 ppb AFB1 (T6), 1.0% MTS (T7), 1.0% MTS Plus 250 ppb AFB1 (T8), and 1.0% MTS Plus 500 ppb AFB1 (T9). The individual and combined effects of dietary AFB1 and MTS on serum biochemistry factors (Glucose, Calcium, Phosphorus, Iron, Creatinine, and Uric acid), lipid profile (Triglyceride, Cholesterol, Low density lipoprotein (LDL), and High density lipoprotein (HDL)) and liver enzymes aspartate amino-transferase and alanine amino-transaminase (ALT) in broilers were evaluated at 21 days of age. Also, statistical packages Macros-1.002 (2010) were used to perform the above analysis on computer. Consumption of 500 ppb AFB1 in to the diet significantly decreased HDL (58.13 ± 2.65), Calcium (7.11 ± 0.13), and Glucose (197.1 ± 7.42) compared to the control group (85.12 ± 1.95, 9.45 ± 0.17 and 223.1 ± 6.61, respectively), (P < 0.05). In contrast, it significantly increased creatinine (2.25 ± 0.011) and AST (244.51 ± 4.91). Using MTS together with AFB1 significantly reduced the effect of AFB1 on the above parameters. MTS can provide protection against the negative effects of AFB1 on broiler chicks.

Mercury and metallothioneins in blood fractions and tissues of captive Morelet's crocodiles in Quintana Roo, Mexico.

PubMed

Buenfil-Rojas, A M; Alvarez-Legorreta, T; Cedeño-Vázquez, J R

2018-05-01

Even though studies of heavy metals and their relation with metallothioneins (MTs) in reptile tissues have been conducted, research on heavy metals and MTs in organs and blood fractions of crocodylians is limited. To date there are no studies on the distribution of MTs in organs and their relation with mercury (Hg), or the concentration of MTs in plasma and erythrocytes of crocodylians. In order to understand the role of MTs in crocodiles, our aim was to assess the detoxification mechanisms for exposure to metals in Morelet's crocodile (Crocodylus moreletii) by using two biomarkers (Hg and MTs) in blood fractions and tissues, and comparing them with concentrations between two populations of crocodiles, one previously wild and currently captive (Theme Park) and another raised in a Wildlife Management Unit (WMU). The caudal scutes from the Theme Park showed higher concentrations of Hg than those from the skin in the WMU samples, and significant negative relationships were observed between the total length (TL) and Hg in the scutes. The significant negative relationship between Hg and hemoglobin (Hb) may be due to disorders in the oxidation process and even denature of this protein, while the positive trend observed between MTs and Hb is consistent with the detoxifying functions and the protection against oxidative damage. This study is the first to report Hg in the erythrocytes of crocodylians and the use of MTs for testing the potential of these biomarkers as a tool to assess Hg exposure in crocodile's habitats. Copyright © 2018 Elsevier Ltd. All rights reserved.

TAT-MTS-MCM fusion proteins reduce MMA levels and improve mitochondrial activity and liver function in MCM-deficient cells.

PubMed

Erlich-Hadad, Tal; Hadad, Rita; Feldman, Anat; Greif, Hagar; Lictenstein, Michal; Lorberboum-Galski, Haya

2018-03-01

Methylmalonic aciduria (MMA) is a disorder of organic acid metabolism resulting from a functional defect of the mitochondrial enzyme, methylmalonyl-CoA mutase (MCM). The main treatments for MMA patients are dietary restriction of propiogenic amino acids and carnitine supplementation. Liver or combined liver/kidney transplantation has been used to treat those with the most severe clinical manifestations. Thus, therapies are necessary to help improve quality of life and prevent liver, renal and neurological complications. Previously, we successfully used the TAT-MTS-Protein approach for replacing a number of mitochondrial-mutated proteins. In this targeted system, TAT, an 11 a.a peptide, which rapidly and efficiently can cross biological membranes, is fused to a mitochondrial targeting sequence (MTS), followed by the mitochondrial mature protein which sends the protein into the mitochondria. In the mitochondria, the TAT-MTS is cleaved off and the native protein integrates into its natural complexes and is fully functional. In this study, we used heterologous MTSs of human, nuclear-encoded mitochondrial proteins, to target the human MCM protein into the mitochondria. All fusion proteins reached the mitochondria and successfully underwent processing. Treatment of MMA patient fibroblasts with these fusion proteins restored mitochondrial activity such as ATP production, mitochondrial membrane potential and oxygen consumption, indicating the importance of mitochondrial function in this disease. Treatment with the fusion proteins enhanced cell viability and most importantly reduced MMA levels. Treatment also enhanced albumin and urea secretion in a CRISPR/Cas9-engineered HepG2 MUT (-/-) liver cell line. Therefore, we suggest using this TAT-MTS-Protein approach for the treatment of MMA. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

47 CFR 69.113 - Non-premium charges for MTS-WATS equivalent services.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 3 2014-10-01 2014-10-01 false Non-premium charges for MTS-WATS equivalent... CARRIER SERVICES (CONTINUED) ACCESS CHARGES Computation of Charges § 69.113 Non-premium charges for MTS-WATS equivalent services. (a) Charges that are computed in accordance with this section shall be...

47 CFR 69.113 - Non-premium charges for MTS-WATS equivalent services.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 3 2011-10-01 2011-10-01 false Non-premium charges for MTS-WATS equivalent... CARRIER SERVICES (CONTINUED) ACCESS CHARGES Computation of Charges § 69.113 Non-premium charges for MTS-WATS equivalent services. (a) Charges that are computed in accordance with this section shall be...

47 CFR 69.113 - Non-premium charges for MTS-WATS equivalent services.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 3 2012-10-01 2012-10-01 false Non-premium charges for MTS-WATS equivalent... CARRIER SERVICES (CONTINUED) ACCESS CHARGES Computation of Charges § 69.113 Non-premium charges for MTS-WATS equivalent services. (a) Charges that are computed in accordance with this section shall be...

47 CFR 69.113 - Non-premium charges for MTS-WATS equivalent services.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 3 2010-10-01 2010-10-01 false Non-premium charges for MTS-WATS equivalent... CARRIER SERVICES (CONTINUED) ACCESS CHARGES Computation of Charges § 69.113 Non-premium charges for MTS-WATS equivalent services. (a) Charges that are computed in accordance with this section shall be...

47 CFR 69.113 - Non-premium charges for MTS-WATS equivalent services.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 3 2013-10-01 2013-10-01 false Non-premium charges for MTS-WATS equivalent... CARRIER SERVICES (CONTINUED) ACCESS CHARGES Computation of Charges § 69.113 Non-premium charges for MTS-WATS equivalent services. (a) Charges that are computed in accordance with this section shall be...

Learning a Mahalanobis Distance-Based Dynamic Time Warping Measure for Multivariate Time Series Classification.

PubMed

Mei, Jiangyuan; Liu, Meizhu; Wang, Yuan-Fang; Gao, Huijun

2016-06-01

Multivariate time series (MTS) datasets broadly exist in numerous fields, including health care, multimedia, finance, and biometrics. How to classify MTS accurately has become a hot research topic since it is an important element in many computer vision and pattern recognition applications. In this paper, we propose a Mahalanobis distance-based dynamic time warping (DTW) measure for MTS classification. The Mahalanobis distance builds an accurate relationship between each variable and its corresponding category. It is utilized to calculate the local distance between vectors in MTS. Then we use DTW to align those MTS which are out of synchronization or with different lengths. After that, how to learn an accurate Mahalanobis distance function becomes another key problem. This paper establishes a LogDet divergence-based metric learning with triplet constraint model which can learn Mahalanobis matrix with high precision and robustness. Furthermore, the proposed method is applied on nine MTS datasets selected from the University of California, Irvine machine learning repository and Robert T. Olszewski's homepage, and the results demonstrate the improved performance of the proposed approach.

Engineered tug-of-war between kinesin and dynein controls direction of microtubule transport in vivo

PubMed Central

Rezaul, Karim; Gupta, Dipika; Semenova, Irina; Ikeda, Kazuho; Kraikivski, Pavel; Yu, Ji; Cowan, Ann; Zaliapin, Ilya; Rodionov, Vladimir

2017-01-01

Bidirectional transport of membrane organelles along microtubules (MTs) is driven by plus-end directed kinesins and minus-end directed dynein bound to the same cargo. Activities of opposing MT motors produce bidirectional movement of membrane organelles and cytoplasmic particles along MT transport tracks. Directionality of MT-based transport might be controlled by a protein complex that determines which motor type is active at any given moment of time, or determined by the outcome of a tug-of-war between MT motors dragging cargo organelles in opposite directions. However, evidence in support of each mechanisms of regulation is based mostly on the results of theoretical analyses or indirect experimental data. Here, we test whether the direction of movement of membrane organelles in vivo can be controlled by the tug-of-war between opposing MT motors alone, by attaching large number of kinesin-1 motors to organelles transported by dynein to minus-ends of MTs. We find that recruitment of kinesin significantly reduces the length and velocity of minus-end-directed dynein-dependent MT runs, leading to a reversal of the overall direction of dynein-driven organelles in vivo. Therefore in the absence of external regulators tug-of-war between opposing MT motors alone is sufficient to determine the directionality of MT transport in vivo. PMID:26843027

Leadership in Multiteam Systems

ERIC Educational Resources Information Center

DeChurch, Leslie A.; Marks, Michelle A.

2006-01-01

This study examined 2 leader functions likely to be instrumental in synchronizing large systems of teams (i.e., multiteam systems [MTSs]). Leader strategizing and coordinating were manipulated through training, and effects on functional leadership, interteam coordination, and MTS performance were examined. Three hundred eighty-four undergraduate…

Dynamics of multiple nuclei in Ashbya gossypii hyphae depend on the control of cytoplasmic microtubules length by Bik1, Kip2, Kip3, and not on a capture/shrinkage mechanism.

PubMed

Grava, Sandrine; Philippsen, Peter

2010-11-01

Ashbya gossypii has a budding yeast-like genome but grows exclusively as multinucleated hyphae. In contrast to budding yeast where positioning of nuclei at the bud neck is a major function of cytoplasmic microtubules (cMTs), A. gossypii nuclei are constantly in motion and positioning is not an issue. To investigate the role of cMTs in nuclear oscillation and bypassing, we constructed mutants potentially affecting cMT lengths. Hyphae lacking the plus (+)end marker Bik1 or the kinesin Kip2 cannot polymerize long cMTs and lose wild-type nuclear movements. Interestingly, hyphae lacking the kinesin Kip3 display longer cMTs concomitant with increased nuclear oscillation and bypassing. Polymerization and depolymerization rates of cMTs are 3 times higher in A. gossypii than in budding yeast and cMT catastrophes are rare. Growing cMTs slide along the hyphal cortex and exert pulling forces on nuclei. Surprisingly, a capture/shrinkage mechanism seems to be absent in A. gossypii. cMTs reaching a hyphal tip do not shrink, and cMT +ends accumulate in hyphal tips. Thus, differences in cMT dynamics and length control between budding yeast and A. gossypii are key elements in the adaptation of the cMT cytoskeleton to much longer cells and much higher degrees of nuclear mobilities.

Cognitive consequences of coexisting temporal lobe developmental malformations and hippocampal sclerosis.

PubMed

Martin, R; Dowler, R; Gilliam, F; Faught, E; Morawetz, R; Kuzniecky, R

1999-09-11

To characterize patterns of cognitive functioning in a well-defined group of patients with MRI-identified coexisting left temporal lobe developmental malformations (TLDM) and mesial temporal sclerosis (MTS), and to examine neuropsychological outcome in this dual-pathology group following epilepsy surgery. Cognitive functioning in patients with left TLDM and MTS (n = 15) was compared with patients with isolated left MTS (n = 40). TLDM and MTS were identified by high-quality MRI protocol. Patients were administered a battery of neuropsychology tests as part of their presurgical workup for possible epilepsy surgery. Unilateral temporal lobe resection was performed on 10 of the dual-pathology patients and 34 of the isolated MTS patients. Postoperative cognitive performance was also assessed. Both groups displayed impairments in verbal and visual memory, language, and academic achievement. Performance on measures of psychometric intelligence, executive function, and attention were not impaired and were similar between groups. Presence of dual pathology was associated with a significantly less efficient verbal encoding strategy on the word list learning task. Postoperatively, declines were noted for both groups across tasks of verbal memory and language. Groups were not different significantly in terms of neuropsychological outcome after surgery. Patients with coexisting TLDM and MTS have impaired cognitive functioning similar to MTS patients-in particular, with regard to episodic memory and language deficits. Temporal lobe resection produces similar cognitive changes in both groups.

A Chimeric Kinesin-1 Head/Kinesin-5 Tail Motor Switches between Diffusive and Processive Motility

PubMed Central

Thiede, Christina; Lakämper, Stefan; Wessel, Alok D.; Kramer, Stefanie; Schmidt, Christoph F.

2013-01-01

Homotetrameric kinesin-5 motors are essential for chromosome separation and assembly of the mitotic spindle. These kinesins bind between two microtubules (MTs) and slide them apart, toward the spindle poles. This process must be tightly regulated in mitosis. In in vitro assays, Eg5 moves diffusively on single MTs and switches to a directed mode between MTs. How allosteric communication between opposing motor domains works remains unclear, but kinesin-5 tail domains may be involved. Here we present a single-molecule fluorescence study of a tetrameric kinesin-1 head/kinesin-5 tail chimera, DK4mer. This motor exhibited fast processive motility on single MTs interrupted by pauses. Like Eg5, DK4mer diffused along MTs with ADP, and slid antiparallel MTs apart with ATP. In contrast to Eg5, diffusive and processive periods were clearly distinguishable. This allowed us to measure transition rates among states and for unbinding as a function of buffer ionic strength. These data, together with results from controls using tail-less dimers, indicate that there are two modes of interaction with MTs, separated by an energy barrier. This result suggests a scheme of motor regulation that involves switching between two bound states, possibly allosterically controlled by the opposing tetramer end. Such a scheme is likely to be relevant for the regulation of native kinesin-5 motors. PMID:23442865

Therapeutic effects of flurbiprofen axetil on mesenteric traction syndrome: randomized clinical trial.

PubMed

Takahashi, Hidemasa; Shida, Dai; Tagawa, Kyoko; Iwamoto, Ryo; Arita, Makoto; Arai, Hiroyuki; Suzuki, Takeo

2017-08-11

This study aimed to reveal the appropriate timing for the intravenous administration of flurbiprofen axetil for preventing mesenteric traction syndrome (MTS), caused by prostacyclin release. In this prospective, randomized, clinical study, forty-five patients who were undergoing elective surgery for colorectal cancer via laparotomy were enrolled. Patients were randomly divided into 3 groups: a preoperative group (n = 16) receiving flurbiprofen axetil directly before surgery; a post-MTS group (n = 14) receiving following MTS onset; and a control group (n = 15) who were not administered flurbiprofen axetil. 6-keto-PGF1α, a stable metabolite of prostacyclin, levels were measured and mean blood pressures were recorded. In the preoperative group, 6-keto-PGF1α levels did not increase, blood pressure levels did not decrease, and no facial flushing was observed. In both the post-MTS and control groups, 6-keto-PGF1α levels increased markedly after mesenteric traction and blood pressure decreased significantly. The post-MTS group exhibited a faster decreasing trend in 6-keto-PGF1α levels and quick restore of the mean blood pressure, and the use of vasopressors and phenylephrine were lower than that in the control group. Even therapeutic administration of flurbiprofen axetil after the onset of MTS has also effects on MTS by suppressing prostacyclin production. Clinical trial number: UMIN000009111 . (Registered 14 October 2012).

What Is Learned when Concept Learning Fails?--A Theory of Restricted-Domain Relational Learning

ERIC Educational Resources Information Center

Wright, Anthony A.; Lickteig, Mark T.

2010-01-01

Two matching-to-sample (MTS) and four same/different (S/D) experiments employed tests to distinguish between item-specific learning and relational learning. One MTS experiment showed item-specific learning when concept learning failed (i.e., no novel-stimulus transfer). Another MTS experiment showed item-specific learning when pigeons'…

Decreasing Errors in Reading-Related Matching to Sample Using a Delayed-Sample Procedure

ERIC Educational Resources Information Center

Doughty, Adam H.; Saunders, Kathryn J.

2009-01-01

Two men with intellectual disabilities initially demonstrated intermediate accuracy in two-choice matching-to-sample (MTS) procedures. A printed-letter identity MTS procedure was used with 1 participant, and a spoken-to-printed-word MTS procedure was used with the other participant. Errors decreased substantially under a delayed-sample procedure,…

Interrelationships among mediators of cellular zinc homeostasis in healthy and type 2 diabetes mellitus populations.

PubMed

Chu, Anna; Foster, Meika; Hancock, Dale; Petocz, Peter; Samman, Samir

2017-04-01

The involvement of zinc in multiple physiological systems requires tight control of cellular zinc concentration. This study aims to explore the relationships among selected mediators of cellular zinc homeostasis in an apparently healthy (AH) population and a cohort with type 2 diabetes mellitus (T2DM). Baseline data of three trials forming two cohorts, AH (n = 70) and T2DM (n = 42), were used for multivariate analyses to identify groupings within ten zinc transporter and metallothionein (MT) gene expressions, stratified by health status. Multiple regression models were used to explore relationships among zinc transporter/MT groupings and plasma zinc. Gene expression of zinc transporters and MTs, with the exception of ZnT6, were significantly lower in the T2DM cohort (p < 0.01). Cluster analysis showed that the groupings of zinc transporters and MTs were largely similar between the two cohorts, with the exception for ZnT1 and ZIP7. Zinc transporters and MTs were significant determinants of plasma zinc (r 2 = 0.48, p = 0.001) in the AH cohort, but not in the T2DM cohort. The current study suggests altered cellular zinc homeostasis in T2DM and supports the use of multiple zinc transporters and MTs groupings to further understand zinc homeostasis in health and T2DM. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Insights into RpoB clinical mutants in mediating rifampicin resistance in Mycobacterium tuberculosis.

PubMed

Nusrath Unissa, Ameeruddin; Hassan, Sameer; Indira Kumari, Venkatesan; Revathy, Ravi; Hanna, Luke Elizabeth

2016-06-01

Rifampicin (RIF) an essential first-line anti-tuberculosis (TB) drug, resistance to RIF is a potential threat to TB control program and widely considered as surrogate marker for detection of multi-drug resistant-TB (MDR-TB), molecular understanding of which is the utmost need of the hour. Mutations at RIF resistance-determining region (RRDR) of 81-bp in the rpoB gene coding for β subunit or RpoB protein is the major cause of RIF resistance in Mycobacterium tuberculosis (MTB). Mutation at positions 526 and 531 are generally associated with high-level RIF resistance and at codons 516, 521 and 533 with low-level resistance. Thus, in order to understand the interactions between the clinical mutants (MTs) of RpoB and RIF which are responsible for mediating both levels of RIF resistance from MTB. In the present study, models of wild type (WT) and seven MTs (D516V, L521M, H526D, H526R, H526Y, S531L and L533P) of RpoB from MTB were generated using crystal structure of 2A68 and 4KBM as templates, for deducing 3 domains structure. Molecular docking between RpoB proteins and RIF was carried out, which showed higher values for WT compared to MTs. The high score in WT may be due to the presence of favorable interactions with RIF and MT-L521M which lacks in other MTs. Molecular dynamics (MD) simulation was performed for over 10 nanoseconds, which suggest the root mean square deviation (RMSD) was more and root mean square fluctuation (RMSF) was less in WT compared to MTs. The ligand RMSD exhibited very unique deviation with the MT-D516V compared to other MTs and WT. The RMSF for MTs such as H526R-H526D, L521M and D516V were higher for residues such as 152, 265, 352, 402, 513, 552, and 577 compared to WT. Hydrogen bond interactions at RIF binding site after MD simulations were found comparatively lower in WT than MTs. Similarly, the binding energy of WT was observed to be lesser in comparison to MTs. All MTs demonstrated certain (2Å) degree of structural deviation from the WT. Overall, these results suggest that RIF binding ability shows differences between WT and MTs, which could be because of different substitutions affecting the conformation of the MT proteins, leading to changes in binding interactions with RIF, eventually to the cause of RIF resistance. Copyright © 2016 Elsevier Inc. All rights reserved.

Innocent until proven guilty? Stable coexistence of alien rainbow trout and native marble trout in a Slovenian stream

NASA Astrophysics Data System (ADS)

Vincenzi, Simone; Crivelli, Alain J.; Jesensek, Dusan; Rossi, Gianluigi; de Leo, Giulio A.

2011-01-01

To understand the consequences of the invasion of the nonnative rainbow trout Oncorhynchus mykiss on the native marble trout Salmo marmoratus, we compared two distinct headwater sectors where marble trout occur in allopatry (MTa) or sympatry (MTs) with rainbow trout (RTs) in the Idrijca River (Slovenia). Using data from field surveys from 2002 to 2009, with biannual (June and September) sampling and tagging from June 2004 onwards, we analyzed body growth and survival probabilities of marble trout in each stream sector. Density of age-0 in September over the study period was greater for MTs than MTa and very similar between MTs and RTs, while density of trout ≥age-1 was similar for MTa and MTs and greater than density of RTs. Monthly apparent survival probabilities were slightly higher in MTa than in MTs, while RTs showed a lower survival than MTs. Mean weight of marble and rainbow trout aged 0+ in September was negatively related to cohort density for both marble and rainbow trout, but the relationship was not significantly different between MTs and MTa. No clear depression of body growth of sympatric marble trout between sampling intervals was observed. Despite a later emergence, mean weight of RTs cohorts at age 0+ in September was significantly higher than weight of both MTs and MTa. The establishment of a self-sustaining population of rainbow trout does not have a significant impact on body growth and survival probabilities of sympatric marble trout. The numerical dominance of rainbow trout in streams at lower altitudes seem to suggest that while the low summer flow pattern of Slovenian streams is favorable for rainbow trout invasion, the adaptation of marble trout to headwater environments may limit the invasion success of rainbow trout in headwaters.

Age at onset in patients with medically refractory temporal lobe epilepsy and mesial temporal sclerosis: impact on clinical manifestations and postsurgical outcome.

PubMed

Asadi-Pooya, Ali A; Sperling, Michael R

2015-08-01

To evaluate the demographic and clinical manifestations and postsurgical outcome of childhood-onset mesial temporal sclerosis and temporal lobe epilepsy (MTS-TLE) and establishing the potential differences as compared to the patients with adult-onset MTS-TLE. In this retrospective study all patients with a clinical diagnosis of medically refractory TLE due to mesial temporal sclerosis, who underwent epilepsy surgery at Jefferson comprehensive epilepsy center, were recruited. Patients were prospectively registered in a database from 1986 through 2014. Postsurgical outcome was classified into two groups; seizure-free or relapsed. Clinical manifestations and outcome were compared between patients with childhood-onset MTS-TLE (i.e., age at onset of the first afebrile habitual seizure below 10 years) and those with adult-onset MTS-TLE (i.e., age at onset of the first afebrile habitual seizure 20 years or above). One hundred and twelve patients had childhood-onset MTS-TLE and 76 had adult-onset MTS-TLE. Demographic, clinical, EEG and MRI characteristics of these two groups were similar. Postoperative outcome was not statistically different between these two groups of patients (P=0.9). Temporal lobe epilepsy due to mesial temporal sclerosis is a common cause of epilepsy that can start from early childhood to late adulthood. The etiology of MTS-TLE may be different in various age groups, but it seems that when mesial temporal sclerosis is the pathological substrate of TLE, clinical manifestations and response to surgical treatment of patients are very similar in patients with childhood-onset MTS-TLE compared to those with adult-onset disease. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Septal membrane localization by C-terminal amphipathic α-helices of MinD in Bacillus subtilis mutant cells lacking MinJ or DivIVA.

PubMed

Ishikawa, Kazuki; Matsuoka, Satoshi; Hara, Hiroshi; Matsumoto, Kouji

2017-10-18

The Min system, which inhibits assembly of the cytokinetic protein FtsZ, is largely responsible for positioning the division site in rod-shaped bacteria. It has been reported that MinJ, which bridges DivIVA and MinD, is targeted to the cell poles by an interaction with DivIVA, and that MinJ in turn recruits MinCD to the cell poles. MinC, however, is located primarily at active division sites at mid-cell when expressed from its native promoter. Surprisingly, we found that Bacillus subtilis MinD is located at nascent septal membranes and at an asymmetric site on lateral membranes between nascent septal membranes in filamentous cells lacking MinJ or DivIVA. Bacillus subtilis MinD has two amphipathic α-helices rich in basic amino acid residues at its C-terminus; one of these, named MTS1 here, is the counterpart of the membrane targeting sequence (MTS) in Escherichia coli MinD while the other, named MTS-like sequence (MTSL), is the nearest helix to MTS1. These amphipathic helices were located independently at nascent septal membranes in cells lacking MinJ or DivIVA, whereas elimination of the helices from the wild type protein reduced its localization considerably. MinD variants with altered MTS1 and MTSL, in which basic amino acid residues were replaced with proline or acidic residues, were not located at nascent septal membranes, indicating that the binding to the nascent septal membranes requires basic residues and a helical structure. The septal localization of MTSL, but not of MTS1, was dependent on host cell MinD. These results suggest that MinD is targeted to nascent septal membranes via its C-terminal amphipathic α-helices in B. subtilis cells lacking MinJ or DivIVA. Moreover, the diffuse distribution of MinD lacking both MTSs suggests that only a small fraction of MinD depends on MinJ for its localization to nascent septal membranes.

Birefringence of single and bundled microtubules.

PubMed

Oldenbourg, R; Salmon, E D; Tran, P T

1998-01-01

We have measured the birefringence of microtubules (MTs) and of MT-based macromolecular assemblies in vitro and in living cells by using the new Pol-Scope. A single microtubule in aqueous suspension and imaged with a numerical aperture of 1.4 had a peak retardance of 0.07 nm. The peak retardance of a small bundle increased linearly with the number of MTs in the bundle. Axonemes (prepared from sea urchin sperm) had a peak retardance 20 times higher than that of single MTs, in accordance with the nine doublets and two singlets arrangement of parallel MTs in the axoneme. Measured filament retardance decreased when the filament was defocused or the numerical aperture of the imaging system was decreased. However, the retardance "area," which we defined as the image retardance integrated along a line perpendicular to the filament axis, proved to be independent of focus and of numerical aperture. These results are in good agreement with a theory that we developed for measuring retardances with imaging optics. Our theoretical concept is based on Wiener's theory of mixed dielectrics, which is well established for nonimaging applications. We extend its use to imaging systems by considering the coherence region defined by the optical set-up. Light scattered from within that region interferes coherently in the image point. The presence of a filament in the coherence region leads to a polarization dependent scattering cross section and to a finite retardance measured in the image point. Similar to resolution measurements, the linear dimension of the coherence region for retardance measurements is on the order lambda/(2 NA), where lambda is the wavelength of light and NA is the numerical aperture of the illumination and imaging lenses.

Birefringence of single and bundled microtubules.

PubMed Central

Oldenbourg, R; Salmon, E D; Tran, P T

1998-01-01

We have measured the birefringence of microtubules (MTs) and of MT-based macromolecular assemblies in vitro and in living cells by using the new Pol-Scope. A single microtubule in aqueous suspension and imaged with a numerical aperture of 1.4 had a peak retardance of 0.07 nm. The peak retardance of a small bundle increased linearly with the number of MTs in the bundle. Axonemes (prepared from sea urchin sperm) had a peak retardance 20 times higher than that of single MTs, in accordance with the nine doublets and two singlets arrangement of parallel MTs in the axoneme. Measured filament retardance decreased when the filament was defocused or the numerical aperture of the imaging system was decreased. However, the retardance "area," which we defined as the image retardance integrated along a line perpendicular to the filament axis, proved to be independent of focus and of numerical aperture. These results are in good agreement with a theory that we developed for measuring retardances with imaging optics. Our theoretical concept is based on Wiener's theory of mixed dielectrics, which is well established for nonimaging applications. We extend its use to imaging systems by considering the coherence region defined by the optical set-up. Light scattered from within that region interferes coherently in the image point. The presence of a filament in the coherence region leads to a polarization dependent scattering cross section and to a finite retardance measured in the image point. Similar to resolution measurements, the linear dimension of the coherence region for retardance measurements is on the order lambda/(2 NA), where lambda is the wavelength of light and NA is the numerical aperture of the illumination and imaging lenses. PMID:9449366

Contributions of microtubule rotation and dynamic instability to kinetochore capture

NASA Astrophysics Data System (ADS)

Sweezy-Schindler, Oliver; Edelmaier, Christopher; Blackwell, Robert; Glaser, Matt; Betterton, Meredith

2014-03-01

The capture of lost kinetochores (KCs) by microtubules (MTs) is a crucial part of prometaphase during mitosis. Microtubule dynamic instability has been considered the primary mechanism of KC capture, but recent work discovered that lateral KC attachment to pivoting MTs enabled rapid capture even with significantly reduced MT dynamics. We aim to understand the relative contributions of MT rotational diffusion and dynamic instability to KC capture, as well as KC capture through end-on and/or lateral attachment. Our model consists of rigid MTs and a spherical KC, which are allowed to diffuse inside a spherical nuclear envelope consistent with the geometry of fission yeast. For simplicity, we include a single spindle pole body, which is anchored to the nuclear membrane, and its associated polar MTs. Brownian dynamics treats the diffusion of the MTs and KC and kinetic Monte Carlo models stochastic processes such as dynamic instability. NSF 1546021.

Why is the central area of the Alburni Mts in southern Italy so full of caves?

NASA Astrophysics Data System (ADS)

Cafaro, Simona; Gueguen, Erwan; Parise, Mario; Schiattarella, Marcello

2016-04-01

The Alburni Mts represent one of the most important karst area of southern Italy, with about 250 registered caves. Located in the southern Apennines, they constitute an impressive carbonate massif within the Mesozoic-Cenozoic Campania-Lucania platform. The study area is located inside the National Park of Cilento, Vallo di Diano and Alburni, and is bounded by two major rivers: the Calore and Tanagro rivers. This area has been repeatedly affected during Pleistocene by the activity of a regional, partly blind, NW-SE-striking fault system responsible for several huge earthquakes. The massif is limited to the north by an important normal fault zone (Alburni Line), whereas towards the E-SE it is bounded by a complex fault system linking the Alburni Mts to the Maddalena Mts across the Auletta basin and the Vallo di Diano valley. The entire massif is structured by NW-SE trending transtensional faults delimiting half-graben basins, and offset also by NE-SW trending faults. In particular, structural and geomorphological data have shown that the central area of the calcareous ridge is characterized by a relative structural low rhombic-shaped in planimetric view. Approximately 180 karst caves of the known 250, including some of the most significant from a speleological viewpoint, are located in this area. Is this simply due to repeated exploration activity in the last 25 years in this specific sector or might it be related to geological matter? New morphometric and structural data suggest that a relevant transversal structure, consisting of a complex NE-SW fault system, responsible for the genesis of the downthrown area in the central sector of the flat-topped ridge, was able to create the tectonic framework for the development of a great number of karst caves which present peculiar features and hydrological behaviour due to such structural controls. In this contribution we present and discuss these data, aimed at contributing to increase the knowledge on an area of sure karst and speleological interest.

Learner-Centered Mentoring: Building from Student Teachers' Individual Needs and Experiences as Novice Practitioners

ERIC Educational Resources Information Center

Kolman, Joni S.; Roegman, Rachel; Goodwin, A. Lin

2017-01-01

This exploratory study documents the practices of a group of mentor teachers (MTs) in high-need schools within a high-accountability district. These MTs support teacher candidates, called residents, in an urban teacher residency program. The primary research question--what are the mentoring practices of a group of strong MTs?--led the authors not…

"Atypical touch perception in MTS may derive from an abnormally plastic self-representation".

PubMed

Bufalari, Ilaria; Porciello, Giuseppina; Aglioti, Salvatore Maria

2015-01-01

Mirror Touch Synesthetes (MTSs) feel touch while they observe others being touched. According to the authors, two complementary theoretical frameworks, the Threshold Theory and the Self-Other Theory, explain Mirror Touch Synesthesia (MTS). Based on the behavioral evidence that in MTSs the mere observation of touch is sufficient to elicit self-other merging (i.e., self-representation changes), a condition that in non-MTSs just elicits self-other sharing (i.e., mirroring activity without self-other blurring), and on the rTPJ anatomical alterations in MTS, we argue that MTS may derive from an abnormally plastic self-representation and atypical multisensory integrative mechanisms.

The Abl-related gene (Arg) requires its F-actin-microtubule cross-linking activity to regulate lamellipodial dynamics during fibroblast adhesion.

PubMed

Miller, Ann L; Wang, Yinxiang; Mooseker, Mark S; Koleske, Anthony J

2004-05-10

Microtubules (MTs) help establish and maintain cell polarity by promoting actin-dependent membrane protrusion at the leading edge of the cell, but the molecular mechanisms that mediate cross-talk between actin and MTs during this process are unclear. We demonstrate that the Abl-related gene (Arg) nonreceptor tyrosine kinase is required for dynamic lamellipodial protrusions after adhesion to fibronectin. arg-/- fibroblasts exhibit reduced lamellipodial dynamics as compared with wild-type fibroblasts, and this defect can be rescued by reexpression of an Arg-yellow fluorescent protein fusion. We show that Arg can bind MTs with high affinity and cross-link filamentous actin (F-actin) bundles and MTs in vitro. MTs concentrate and insert into Arg-induced F-actin-rich cell protrusions. Arg requires both its F-actin-binding domains and its MT-binding domain to rescue the defects in lamellipodial dynamics of arg-/- fibroblasts. These findings demonstrate that Arg can mediate physical contact between F-actin and MTs at the cell periphery and that this cross-linking activity is required for Arg to regulate lamellipodial dynamics in fibroblasts. Copyright the Rockefeller University Press

Widespread extrahippocampal NAA/(Cr+Cho) abnormalities in TLE with and without mesial temporal sclerosis.

PubMed

Mueller, Susanne G; Ebel, Andreas; Barakos, Jerome; Scanlon, Cathy; Cheong, Ian; Finlay, Daniel; Garcia, Paul; Weiner, Michael W; Laxer, Kenneth D

2011-04-01

MR spectroscopy has demonstrated extrahippocampal NAA/(Cr+Cho) reductions in medial temporal lobe epilepsy with (TLE-MTS) and without (TLE-no) mesial temporal sclerosis. Because of the limited brain coverage of those previous studies, it was, however, not possible to assess differences in the distribution and extent of these abnormalities between TLE-MTS and TLE-no. This study used a 3D whole brain echoplanar spectroscopic imaging (EPSI) sequence to address the following questions: (1) Do TLE-MTS and TLE-no differ regarding severity and distribution of extrahippocampal NAA/(Cr+Cho) reductions? (2) Do extrahippocampal NAA/(Cr+Cho) reductions provide additional information for focus lateralization? Forty-three subjects (12 TLE-MTS, 13 TLE-no, 18 controls) were studied with 3D EPSI. Statistical parametric mapping (SPM2) was used to identify regions of significantly decreased NAA/(Cr+Cho) in TLE groups and in individual patients. TLE-MTS and TLE-no had widespread extrahippocampal NAA/(Cr+Cho) reductions. NAA/(Cr+Cho) reductions had a bilateral fronto-temporal distribution in TLE-MTS and a more diffuse, less well defined distribution in TLE-no. Extrahippocampal NAA/(Cr+Cho) decreases in the single subject analysis showed a large inter-individual variability and did not provide additional focus lateralizing information. Extrahippocampal NAA/(Cr+Cho) reductions in TLE-MTS and TLE-no are neither focal nor homogeneous. This reduces their value for focus lateralization and suggests a heterogeneous etiology of extrahippocampal spectroscopic metabolic abnormalities in TLE.

The Functions of Metamorphic Metallothioneins in Zinc and Copper Metabolism.

PubMed

Krężel, Artur; Maret, Wolfgang

2017-06-09

Recent discoveries in zinc biology provide a new platform for discussing the primary physiological functions of mammalian metallothioneins (MTs) and their exquisite zinc-dependent regulation. It is now understood that the control of cellular zinc homeostasis includes buffering of Zn 2+ ions at picomolar concentrations, extensive subcellular re-distribution of Zn 2+ , the loading of exocytotic vesicles with zinc species, and the control of Zn 2+ ion signalling. In parallel, characteristic features of human MTs became known: their graded affinities for Zn 2+ and the redox activity of their thiolate coordination environments. Unlike the single species that structural models of mammalian MTs describe with a set of seven divalent or eight to twelve monovalent metal ions, MTs are metamorphic. In vivo, they exist as many species differing in redox state and load with different metal ions. The functions of mammalian MTs should no longer be considered elusive or enigmatic because it is now evident that the reactivity and coordination dynamics of MTs with Zn 2+ and Cu⁺ match the biological requirements for controlling-binding and delivering-these cellular metal ions, thus completing a 60-year search for their functions. MT represents a unique biological principle for buffering the most competitive essential metal ions Zn 2+ and Cu⁺. How this knowledge translates to the function of other families of MTs awaits further insights into the specifics of how their properties relate to zinc and copper metabolism in other organisms.

DDA3 associates with microtubule plus ends and orchestrates microtubule dynamics and directional cell migration

PubMed Central

Zhang, Liangyu; Shao, Hengyi; Zhu, Tongge; Xia, Peng; Wang, Zhikai; Liu, Lifang; Yan, Maomao; Hill, Donald L.; Fang, Guowei; Chen, Zhengjun; Wang, Dongmei; Yao, Xuebiao

2013-01-01

Cell motility and adhesion involve orchestrated interaction of microtubules (MTs) with their plus-end tracking proteins (+TIPs). However, the mechanisms underlying regulations of MT dynamics and directional cell migration are still elusive. Here, we show that DDA3-EB1 interaction orchestrates MT plus-end dynamics and facilitates directional cell migration. Biochemical characterizations reveal that DDA3 interacts with EB1 via its SxIP motif within the C-terminal Pro/Ser-rich region. Time-lapse and total internal reflection fluorescence (TIRF) microscopic assays demonstrate that DDA3 exhibits EB1-dependent, MT plus-end loading and tracking. The EB1-based loading of DDA3 is responsible for MT plus-ends stabilization at the cell cortex, which in turn orchestrates directional cell migration. Interestingly, the DDA3-EB1 interaction is potentially regulated by EB1 acetylation, which may account for physiological regulation underlying EGF-elicited cell migration. Thus, the EB1-based function of DDA3 links MT dynamics to directional cell migration. PMID:23652583

ICS security in maritime transportation : a white paper examining the security and resiliency of critical transportation infrastructure

DOT National Transportation Integrated Search

2013-07-29

The John A. Volpe National Transportation Systems Center was asked by the Office of Security of the Maritime Administration to examine the issue of industrial control systems (ICS) security in the Maritime Transportation System (MTS), and to develop ...

Linking Late Miocene Magmatism and Exhumation of the Pamir-West Kunlun Mountains to Lithospheric Thinning

NASA Astrophysics Data System (ADS)

Cao, K.; Wang, G.; Zeng, Z.; Replumaz, A.

2016-12-01

In this study, we report newly-discovered potassic plutons emplaced at 11 Ma in the SE Pamir. Together with recently-reported volcanism at 12 Ma in the West Kunlun Mts. (Cao et al., 2015), it can be inferred that Late Miocene magmas extend from the north-central Tibet to the central Pamir. Furthermore, our new apatite fission-track analysis in the SE Pamir-West Kunlun Mountains present uniform ages clustering at 11-6 Ma. Forward and inverse modeling indicate Late Miocene ( 11-6 Ma) rapid exhumation of the SE Pamir-West Kunlun Mountains, concurrent with accelerated exhumation of the Shakhdara dome (Stübner et al., 2013), initial doming of the Muztagata massif (Robinson et al., 2007; Sobel et al., 2011; Cao et al., 2013), and thrusting of the front faults along Pamir-West Kunlun Mts. (Bershaw et al., 2012; Cao et al., 2013, 2015). The simultaneous doming and potassic magmatism could attributed to stress relaxation of the upper crust at that time, possibly driven by the thinning of lower lithosphere beneath Pamir-West Kunlun Mts.. Such plausible mechanisms could be responsible for Neogene magmatism, rock exhumation and plateau growth in northwestern Tibet. At the continental scale, our results support that the Tibetan Plateau underwent a Late Miocene phase of deformation and developed outward and upward since then (Molnar et al., 2012). Three representative models are proposed to account for Late Miocene magmatism and crustal deformation in northern Tibet, including 1) southward subduction of the Tarim lithosphere mantle (Matte et al., 1996; Wittlinger et al., 2004), 2) convective removal of lower lithosphere (Molnar et al., 1993; Turner et al., 1993, 1996), and 3) penetration of molten crust into Kunlun terrane (Le Pape et al., 2012; Wang et al., 2012). Our results allow to discuss these competing models in the western Tibet, to better understand the intracontinent orogenesis in central Asia, in which the lithospheric processes have led to upper crust deformation.

Microtubule Depolymerization as a Driver for Chromosome Motion

NASA Astrophysics Data System (ADS)

McIntosh, Richard

2014-03-01

Microtubules (MTs) are rigid polymers of the protein, tubulin, which function as intracellular struts. They are also tracks along which motor enzymes can run, carrying cargo to specific cellular locations. Most MTs are dynamic; they assemble and disassemble rapidly, particularly during cell division when the cell forms the ``mitotic spindle,'' a machine that organizes the duplicated chromosomes into a planar disk, then pulls the duplicate copies apart, moving them to opposite ends of the cell. This process is necessary for the daughter cells to have a full complement of DNA. The mitotic spindle is a labile framework that exerts several kinds of forces on the chromosomes to move them in well organized ways. It contains many motor enzymes that contribute to spindle formation, but genetic evidence shows that the motors that attach to chromosomes and might contribute to chromosome motion are dispensable for normal mitosis. Apparently MT dynamics can also serve as a motor and is an important source of force for chromosome motion. We have studied this process and find that MTs can be coupled to a load by specific spindle proteins so that MT depolymerization can exert substantial force. With the yeast protein, Dam1, a single MT can generate 30 pN, about 5-fold more than is generated by a motor enzyme like kinesin or myosin. The resulting motions are processive, so a depolymerizing MT can carry its load for many micrometers. However, Dam1 is found only in fungi. We have therefore sought other proteins that can serve as analogous couplers. Several MT-dependent motor enzymes can do the job in ways that do not require ATP, their normal source of energy. Some non-motor MT-associated proteins will also work, e.g., the kinetochore proteins NDC80 and CENP-F. Data will be presented that show the strengths and weaknesses of each coupler, allowing some generalization about how the mitotic machinery works. Supported by NIH GM033787.

Frequency stabilization of a 1083 nm fiber laser to {sup 4}He transition lines with optical heterodyne saturation spectroscopies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gong, W.; Peng, X., E-mail: xiangpeng@pku.edu.cn; Li, W.

2014-07-15

Two kinds of optical heterodyne saturation spectroscopies, namely, frequency modulation spectroscopy (FMS) and modulation transfer spectroscopy (MTS), are demonstrated for locking a fiber laser to the transition lines of metastable {sup 4}He atoms around 1083 nm. The servo-loop error signals of FMS and MTS for stabilizing laser frequency are optimized by studying the dependence of the peak-to-peak amplitude and slope on the optical power of pump and probe beams. A comparison of the stabilization performances of FMS/MTS and polarization spectroscopy (PS) is presented, which shows that MTS exhibits relatively superior performance with the least laser frequency fluctuation due to itsmore » flat-background dispersive signal, originated from the four-wave mixing process. The Allan deviation of the stabilized laser frequency is 5.4 × 10{sup −12}@100 s with MTS for data acquired in 1000 s, which is sufficiently applicable for fields like laser cooling, optical pumping, and optical magnetometry.« less

Centromere protein F includes two sites that couple efficiently to depolymerizing microtubules

PubMed Central

Volkov, Vladimir A.; Grissom, Paula M.; Arzhanik, Vladimir K.; Zaytsev, Anatoly V.; Renganathan, Kutralanathan; McClure-Begley, Tristan; Old, William M.; Ahn, Natalie

2015-01-01

Firm attachments between kinetochores and dynamic spindle microtubules (MTs) are important for accurate chromosome segregation. Centromere protein F (CENP-F) has been shown to include two MT-binding domains, so it may participate in this key mitotic process. Here, we show that the N-terminal MT-binding domain of CENP-F prefers curled oligomers of tubulin relative to MT walls by approximately fivefold, suggesting that it may contribute to the firm bonds between kinetochores and the flared plus ends of dynamic MTs. A polypeptide from CENP-F’s C terminus also bound MTs, and either protein fragment diffused on a stable MT wall. They also followed the ends of dynamic MTs as they shortened. When either fragment was coupled to a microbead, the force it could transduce from a shortening MT averaged 3–5 pN but could exceed 10 pN, identifying CENP-F as a highly effective coupler to shortening MTs. PMID:26101217

[Problems in career planning for novice medical technologists in Japanese national hospitals].

PubMed

Ogasawara, Shu; Tsutaya, Shoji; Akimoto, Hiroyuki; Kojima, Keiya; Yabaka, Hiroyuki

2012-12-01

Skills and knowledge regarding many different types of test are required for medical technologists (MTs) to provide accurate information to help doctors and other medical specialists. In order to become an efficient MT, specialized training programs are required. Certification in specialized areas of clinical laboratory sciences or a doctoral degree in medical sciences may help MTs to realize career advancement, a higher earning potential, and expand the options in their career. However, most young MTs in national university hospitals are employed as part-time workers on a three-year contract, which is too short to obtain certifications or a doctoral degree. We have to leave the hospital without expanding our future. We need to take control of our own development in order to enhance our employability within the period. As teaching and training hospitals, national university hospitals in Japan are facing a difficult dilemma in nurturing MTs. I hope, as a novice medical technologist, that at least university hospitals in Japan create an appropriate workplace environment for novice MTs.

An Unusual Endovascular Therapeutic Approach for a Rare Case of May-Thurner Syndrome.

PubMed

DaSilva-DeAbreu, Adrian; Masha, Luke; Peerbhai, Shareez

2017-03-06

BACKGROUND The etiology of deep venous thrombosis (DVT) may pose a significant diagnostic challenge because truly reversible causes of DVT are rare. In this regard, known pelvic anatomic abnormalities such as aortic and iliac aneurysms should be seriously considered as a complicating factor in patients presenting with acute DVT so as not to miss a potentially curable etiology of May-Thurner syndrome (MTS). CASE REPORT We report the case of a 69-year-old man with a known abdominal aortic aneurysm and bilateral iliac artery aneurysms who presented with an acute DVT. A computed tomography scan of the abdomen and pelvis showed increased dilation of his aneurysmal disease with new resultant compression of the left iliac vein representing acquired MTS. The patient underwent endovascular aneurysm repair of the infra-renal abdominal aortic aneurysm and right common iliac artery aneurysm with a Gore Excluder endoprosthesis in lieu of venous stenting, with resolution of symptoms. CONCLUSIONS Infra-renal aortic and iliac aneurysms causing MTS are extremely rare, and patients at risk for MTS through these mechanisms do not fit the classical demographics associated with this syndrome. Furthermore, this is the first case described in which MTS was treated by addressing the aneurysm through an endoprosthetic approach instead of venous stenting, which is the conventional intervention for MTS.

Thermal drift is enough to drive a single microtubule along its axis even in the absence of motor proteins.

PubMed Central

Nakata, T; Sato-Yoshitake, R; Okada, Y; Noda, Y; Hirokawa, N

1993-01-01

One-dimensional diffusion of microtubules (MTs), a back-and-forth motion of MTs due to thermal diffusion, was reported in dynein motility assay. The interaction between MTs and dynein that allows such motion was implicated in its importance in the force generating cycle of dynein ATPase cycle. However, it was not known whether the phenomenon is special to motor proteins. Here we show two independent examples of one-dimensional diffusion of MTs in the absence of motor proteins. Dynamin, a MT-activated GTPase, causes a nucleotide dependent back-and-forth movement of single MT up to 1 micron along the longitudinal axes, although the MT never showed unidirectional consistent movement. Quantitative analysis of the motion and its nucleotide condition indicates that the motion is due to a thermal driven diffusion, restricted to one dimension, under the weak interaction between MT and dynamin. However, specific protein-protein interaction is not essential for the motion, because similar back-and-forth movement of MT was achieved on coverslips coated with only 0.8% methylcellulose. Both cases demonstrate that thermal diffusion could provide a considerable sliding of MTs only if MTs are restricted on the surface appropriately. Images FIGURE 1 FIGURE 2 FIGURE 3 PMID:7906153

Report of the Nuclear Propulsion Mission Analysis, Figures of Merit Subpanel: Quantifiable figures of merit for nuclear thermal propulsion

NASA Technical Reports Server (NTRS)

Haynes, Davy A.

1991-01-01

The results of an inquiry by the Nuclear Propulsion Mission Analysis, Figures of Merit subpanel are given. The subpanel was tasked to consider the question of what are the appropriate and quantifiable parameters to be used in the definition of an overall figure of merit (FoM) for Mars transportation system (MTS) nuclear thermal rocket engines (NTR). Such a characterization is needed to resolve the NTR engine design trades by a logical and orderly means, and to provide a meaningful method for comparison of the various NTR engine concepts. The subpanel was specifically tasked to identify the quantifiable engine parameters which would be the most significant engine factors affecting an overall FoM for a MTS and was not tasked with determining 'acceptable' or 'recommended' values for the identified parameters. In addition, the subpanel was asked not to define an overall FoM for a MTS. Thus, the selection of a specific approach, applicable weighting factors, to any interrelationships, for establishing an overall numerical FoM were considered beyond the scope of the subpanel inquiry.

Localization of a microtubule organizing center by kinesin motors

NASA Astrophysics Data System (ADS)

Arita, Chikashi; Bosche, Jonas; Lück, Alexander; Santen, Ludger

2017-12-01

Molecular motors are proteins which bind to a polarized cytoskeletal filament and move steadily along it. Molecular motors of the kinesin family move along microtubules (MTs), which are a component of the cytoskeleton. A very processive kinesin motor Kip3p, is known to promote catastrophes and pausing of MT, in particular on cortical contact. These properties play an important role in positioning the mitotic spindle in budding yeast. We present a theoretical approach to positioning of MT networks under confinement. In order to explore a localization mechanism of a microtubule organizing center (MTOC), we introduce an idealized system of two MTs connected by a MTOC. The dynamics of Kip3p is modeled by interacting stochastic particles, which allows us to study the effects of motor-induced depolymerization in a finite volume. We find that localization in the middle of the cavity is realized in a parameter regime where the motor densities on the MTs are increasing with the distance from the MTOC. Localization at an asymmetric position is also possible by tuning model parameters.

Determination and uncertainty of moment tensors for microearthquakes at Okmok Volcano, Alaska

USGS Publications Warehouse

Pesicek, J.D.; Sileny, J.; Prejean, S.G.; Thurber, C.H.

2012-01-01

Efforts to determine general moment tensors (MTs) for microearthquakes in volcanic areas are often hampered by small seismic networks, which can lead to poorly constrained hypocentres and inadequate modelling of seismic velocity heterogeneity. In addition, noisy seismic signals can make it difficult to identify phase arrivals correctly for small magnitude events. However, small volcanic earthquakes can have source mechanisms that deviate from brittle double-couple shear failure due to magmatic and/or hydrothermal processes. Thus, determining reliable MTs in such conditions is a challenging but potentially rewarding pursuit. We pursued such a goal at Okmok Volcano, Alaska, which erupted recently in 1997 and in 2008. The Alaska Volcano Observatory operates a seismic network of 12 stations at Okmok and routinely catalogues recorded seismicity. Using these data, we have determined general MTs for seven microearthquakes recorded between 2004 and 2007 by inverting peak amplitude measurements of P and S phases. We computed Green's functions using precisely relocated hypocentres and a 3-D velocity model. We thoroughly assessed the quality of the solutions by computing formal uncertainty estimates, conducting a variety of synthetic and sensitivity tests, and by comparing the MTs to solutions obtained using alternative methods. The results show that MTs are sensitive to station distribution and errors in the data, velocity model and hypocentral parameters. Although each of the seven MTs contains a significant non-shear component, we judge several of the solutions to be unreliable. However, several reliable MTs are obtained for a group of previously identified repeating events, and are interpreted as compensated linear-vector dipole events.

Self-organization mechanisms in the assembly and maintenance of bipolar spindles

NASA Astrophysics Data System (ADS)

Burbank, Kendra Stewart

Anastral, meiotic spindles are thought to be organized differently from astral, mitotic spindles, but the field has lacked basic structural information required to describe and model them, including the location of microtubule nucleating sites and minus ends. How the various components of spindles act together to establish and maintain the dynamic bipolar structure of spindles is not understood. We measure the distributions of oriented microtubules (MTs) in metaphase anastral spindles in Xenopus extracts by fluorescence speckle microscopy and cross-correlation analysis. We localized plus ends by tubulin incorporation and combined this with the orientation data to infer the localization of minus ends. We find that minus ends are localized throughout the spindle, sparsely at the equator and at higher concentrations near the poles. This dads to the surprising conclusion that spindles contained many short MTs, not connected to the spindle poles. Based on these data, we propose a slide-and-cluster model based on four known molecular activities: MT nucleation near chromosomes, the sliding of MTs by a plus-enddirected motor, the clustering of their minus ends by a minus-end-directed motor, and the loss of MTs by dynamic instability. This work demonstrates how the interplay between two types of motors together with continual nucleation of MTs by chromosomes could organize the MTs into spindles. Our model applies to overlapping, nonkinetochore MTs in anastral spindles, and perhaps also to interpolar MTs in astral spindles. We show mathematically that the slide-and-cluster mechanism robustly forms bipolar spindles a stable steady-state length, sometimes with sharp poles. This model accounts for several experimental observations that were difficult to explain with existing models, and is the first self contained model for anastral spindle assembly, MT sliding (known as poleward flux), and spindle bistability. Our experimental results support the slide-and-cluster scenario; most significantly, we find that MT sliding slows near spindle poles, confirming the models primary prediction.

Wnt5a Evokes Cortical Axon Outgrowth and Repulsive Guidance by Tau Mediated Reorganization of Dynamic Microtubules

PubMed Central

Li, Li; Fothergill, Thomas; Hutchins, B Ian; Dent, Erik W; Kali, Katherine

2014-01-01

Wnt5a guides cortical axons in vivo by repulsion and in vitro evokes cortical axon outgrowth and repulsion by calcium signaling pathways. Here we examined the role of microtubule (MT) reorganization and dynamics in mediating effects of Wnt5a. Inhibiting MT dynamics with nocodazole and taxol abolished Wnt5a evoked axon outgrowth and repulsion of cultured hamster cortical neurons. EGFP-EB3 labeled dynamic MTs visualized in live cell imaging revealed that growth cone MTs align with the nascent axon. Wnt5a increased axon outgrowth by reorganization of dynamic MTs from a splayed to a bundled array oriented in the direction of axon extension, and Wnt5a gradients induced asymmetric redistribution of dynamic MTs toward the far side of the growth cone. Wnt5a gradients also evoked calcium transients that were highest on the far side of the growth cone. Calcium signaling and the reorganization of dynamic MTs could be linked by tau, a MT associated protein that stabilizes MTs. Tau is phosphorylated at the Ser 262 MT binding site by CaMKII, and is required for Wnt5a induced axon outgrowth and repulsive turning. Phosphorylation of tau at Ser262 is known to detach tau from MTs to increase their dynamics. Using transfection with tau constructs mutated at Ser262, we found that this site is required for the growth and guidance effects of Wnt5a by mediating reorganization of dynamic MTs in cortical growth cones. Moreover, CaMKII inhibition also prevents MT reorganization required for Wnt5a induced axon outgrowth, thus linking Wnt/calcium signaling to tau mediated MT reorganization during growth cone behaviors. © 2013 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc.Develop Neurobiol 74: 797–817, 2014 PMID:23818454

The Stoichiometric Transition from Zn6Cu1-Metallothionein to Zn7-Metallothionein Underlies the Up-regulation of Metallothionein (MT) Expression

PubMed Central

Alvarez, Lydia; Gonzalez-Iglesias, Hector; Garcia, Montserrat; Ghosh, Sikha; Sanz-Medel, Alfredo; Coca-Prados, Miguel

2012-01-01

We examined the profiling of gene expression of metallothioneins (MTs) in human tissues from cadaver eyes with microarray-based analysis. All MT1 isoforms, with the exception of MT1B, were abundantly expressed in lens and corneal tissue. Along with MT1B, MT4 was not detected in any tissues. Antibodies to MT1/2 labeled the corneal epithelial and endothelial cells, whereas MT3 label the retinal ganglion cells. We studied the effects of zinc and cytokines on the gene expression of MT isoforms in a corneal epithelial cell line (HCEsv). Zinc exerted an up-regulation of the expression of MT isoforms, and this effect was further potentiated in the presence of IL1α or TNFα. Zinc also elicited a strong down-regulation of the expression of inflammatory cytokines, and this effect was blocked in the presence of TNFα or IL1α. The concentration of MTs, bound zinc, and the metal stoichiometry of MTs in cultured HCEsv were determined by mass spectrometry. The total concentration of MTs was 0.24 ± 0.03 μm and, after 24 h of zinc exposure, increased to 0.96 ± 0.01 μm. The combination of zinc and IL1α further enhanced the level of MTs to 1.13 ± 0.03 μm. The average metal stoichiometry of MTs was Zn6Cu1-MT, and after exposure to the different treatments, it changed to Zn7-MT. Actinomycin D blocked transcription, and cycloheximide attenuated synthesis of MTs in the presence or absence of zinc, suggesting transcriptional regulation. Overall the data provide molecular and analytical evidence on the interplay between zinc, MTs, and proinflammatory cytokines in HCEsv cells, with potential implications on cell-based inflammatory eye diseases. PMID:22722935

The pyruvic acid analog 3-bromopyruvate interferes with the tetrazolium reagent MTS in the evaluation of cytotoxicity.

PubMed

Ganapathy-Kanniappan, Shanmugasundaram; Geschwind, Jean-Francois H; Kunjithapatham, Rani; Buijs, Manon; Syed, Labiq H; Rao, Pramod P; Ota, Shinichi; Vali, Mustafa

2010-04-01

3-Bromopyruvate (3BrPA) is a pyruvate analog known for its alkylating property. Recently, several reports have documented the antiglycolytic and anticancer effects of 3BrPA and its potential for therapeutic applications. 3BrPA-mediated cytotoxicity has been evaluated in vitro by various methods including tetrazolium salt (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide)-based assays such as MTT, MTS, and so on. However, growing body of evidences has shown that tetrazolium reagent may interfere with the test compounds. In this study, we investigated whether the tetrazolium reagent interferes with the assessment of 3BrPA cytotoxicity. The results of the tetrazolium-based MTS assay were compared with 3 distinct cell viability detection methods, that is, Trypan Blue staining, ATP depletion, and Annexin V staining in 2 different cell lines, Vx-2 and HepG2. The MTS assay data showed false positive results by indicating increased cell viability at 1 mM and 2 mM 3BrPA whereas the other cell viability assays demonstrated that both Vx-2 and HepG2 cells are not viable at the same treatment conditions. In order to validate the direct interaction of 3BrPA with MTS reagent, we tested cell-free media incubated with different concentrations of 3BrPA. The results of cell-free media showed an increase in absorbance in a dose-dependent manner confirming the interaction of MTS with 3BrPA. Thus, our data clearly demonstrate that 3BrPA interferes with the accuracy of MTS-based cytotoxicity evaluation. Hence, we suggest that employing multiple methods of biochemical as well as morphological cytotoxicity assays is critical to evaluate 3BrPA-mediated cell death.

Characteristics of multiple tropopauses in the tropics

NASA Astrophysics Data System (ADS)

Mehta, Sanjay Kumar; Ratnam Madineni, Venkat; Krishna Murthy, B. V.

The characteristics of multiple tropopauses (MTs) in the tropics are studied using radiosonde data from 5 stations (Truk,Rochambeau, Singapore, Seychelles and Darwin) in the tropical belt during 1999 to 2008 and COSMIC GPS RO data during 2006-2008. In this study we emphasized the limitations of the WMO criteria for identifying the MTs and evolved an alternative criterion to effectively delineate MTs over tropical region. The current method is based on cold point tropopause (CPT) and points of inflections in the temperature profile rather than lapse rate as in WMO criteria. The points of inflection can occur both below and above the CPT. The one which occurs below the CPT is designated as the lower tropopause (LT) and those occurring above the CPT as second tropopause (ST) and third tropopause (TT) according to their heights of occurrence with CPT as the first tropopause. The percentage occurrences (25-50) of MTs are observed to be higher using the current method than by the WMO criteria (10-30). There is significant seasonal variation in the LT, CPT and ST temperatures (heights) with lower (higher) values occurring in the Northern Hemisphere winter. While the CPT temperatures are lowest at the equator the CPT heights are not highest at the equator. The occurrences of MTs are higher over equator and decrease away towards higher latitudes in the tropics. Longitudinal variation of the MTs is observed with relatively high occurrences during NH summer season over placeIndian Ocean. The equatorial minimum in the CPT temperature is broader and colder in the eastern hemisphere than the western hemisphere It is found that MTs can either occur on consecutive days in groups or on isolated days. The plausible causative mechanisms will be presented in the conference.

Direct force measurements reveal that protein Tau confers short-range attractions and isoform-dependent steric stabilization to microtubules

PubMed Central

Chung, Peter J.; Choi, Myung Chul; Miller, Herbert P.; Feinstein, H. Eric; Raviv, Uri; Li, Youli; Wilson, Leslie; Feinstein, Stuart C.; Safinya, Cyrus R.

2015-01-01

Microtubules (MTs) are hollow cytoskeletal filaments assembled from αβ-tubulin heterodimers. Tau, an unstructured protein found in neuronal axons, binds to MTs and regulates their dynamics. Aberrant Tau behavior is associated with neurodegenerative dementias, including Alzheimer’s. Here, we report on a direct force measurement between paclitaxel-stabilized MTs coated with distinct Tau isoforms by synchrotron small-angle X-ray scattering (SAXS) of MT-Tau mixtures under osmotic pressure (P). In going from bare MTs to MTs with Tau coverage near the physiological submonolayer regime (Tau/tubulin-dimer molar ratio; ΦTau = 1/10), isoforms with longer N-terminal tails (NTTs) sterically stabilized MTs, preventing bundling up to PB ∼ 10,000–20,000 Pa, an order of magnitude larger than bare MTs. Tau with short NTTs showed little additional effect in suppressing the bundling pressure (PB ∼ 1,000–2,000 Pa) over the same range. Remarkably, the abrupt increase in PB observed for longer isoforms suggests a mushroom to brush transition occurring at 1/13 < ΦTau < 1/10, which corresponds to MT-bound Tau with NTTs that are considerably more extended than SAXS data for Tau in solution indicate. Modeling of Tau-mediated MT–MT interactions supports the hypothesis that longer NTTs transition to a polyelectrolyte brush at higher coverages. Higher pressures resulted in isoform-independent irreversible bundling because the polyampholytic nature of Tau leads to short-range attractions. These findings suggest an isoform-dependent biological role for regulation by Tau, with longer isoforms conferring MT steric stabilization against aggregation either with other biomacromolecules or into tight bundles, preventing loss of function in the crowded axon environment. PMID:26542680

Hexavalent chromium-induced differential disruption of cortical microtubules in some Fabaceae species is correlated with acetylation of α-tubulin.

PubMed

Eleftheriou, Eleftherios P; Adamakis, Ioannis-Dimosthenis S; Michalopoulou, Vasiliki A

2016-03-01

The effects of hexavalent chromium [Cr(VI)] on the cortical microtubules (MTs) of five species of the Fabaceae family (Vicia faba, Pisum sativum, Vigna sinensis, Vigna angularis, and Medicago sativa) were investigated by confocal laser scanning microscopy after immunolocalization of total tubulin with conventional immunofluorescence techniques and of acetylated α-tubulin with the specific 6-11B-1 monoclonal antibody. Moreover, total α-tubulin and acetylated α-tubulin were quantified by Western immunoblotting and scanning densitometry. Results showed the universality of Cr(VI) detrimental effects to cortical MTs, which proved to be a sensitive and reliable subcellular marker for monitoring Cr(VI) toxicity in plant cells. However, a species-specific response was recorded, and a correlation of MT disturbance with the acetylation status of α-tubulin was demonstrated. In V. faba, MTs were depolymerized at the gain of cytoplasmic tubulin background and displayed low α-tubulin acetylation, while in P. sativum, V. sinensis, V. angularis, and M. sativa, MTs became bundled and changed orientation from perpendicular to oblique or longitudinal. Bundled MTs were highly acetylated as determined by both immunofluorescence and Western immunoblotting. Tubulin acetylation in P. sativum and M. sativa preceded MT bundling; in V. sinensis it followed MT derangement, while in V. angularis the two phenomena coincided. Total α-tubulin remained constant in all treatments. Should acetylation be an indicator of MT stabilization, it is deduced that bundled MTs became stabilized, lost their dynamic properties, and were rendered inactive. Results of this report allow the conclusion that Cr(VI) toxicity disrupts MTs and deranges the MT-mediated functions either by depolymerizing or stabilizing them.

Phase retrieval from the phase-shift moiré fringe patterns in simultaneous dual-wavelength interferometry

NASA Astrophysics Data System (ADS)

Cheng, Jinlong; Gao, Zhishan; Bie, Shuyou; Dou, Yimeng; Ni, Ruihu; Yuan, Qun

2018-02-01

Simultaneous dual-wavelength interferometry (SDWI) could extend the measured range of each single-wavelength interferometry. The moiré fringe generated in SDWI indirectly represents the information of the measured long synthetic-wavelength ({λ }{{S}}) phase, thus the phase demodulation is rather arduous. To address this issue, we present a method to convert the moiré fringe pattern into a synthetic-wavelength interferogram (moiré to synthetic-wavelength, MTS). After the square of the moiré fringe pattern in the MTS method, the additive moiré pattern is turned into a multiplicative one. And the synthetic-wavelength interferogram could be obtained by a low-pass filtering in spectrum of the multiplicative moiré fringe pattern. Therefore, when the dual-wavelength interferometer is implemented with the π/2 phase shift at {λ }{{S}}, a sequence of synthetic-wavelength phase-shift interferograms with π/2 phase shift could be obtained after the MTS method processing on the captured moiré fringe patterns. And then the synthetic-wavelength phase could be retrieved by the conventional phase-shift algorithm. Compared with other methods in SDWI, the proposed MTS approach could reduce the restriction of the phase shift and frame numbers for the adoption of the conventional phase-shift algorithm. Following, numerical simulations are executed to evaluate the performance of the MTS method in processing time, frames of interferograms and the phase shift error compensation. And the necessary linear carrier for MTS method is less than 0.11 times of the traditional dual-wavelength spatial-domain Fourier transform method. Finally, the deviations for MTS method in experiment are 0.97% for a step with the height of 7.8 μm and 1.11% for a Fresnel lens with the step height of 6.2328 μm.

Automated volumetry of hippocampus is useful to confirm unilateral mesial temporal sclerosis in patients with radiologically positive findings.

PubMed

Silva, Guilherme; Martins, Cristina; Moreira da Silva, Nádia; Vieira, Duarte; Costa, Dias; Rego, Ricardo; Fonseca, José; Silva Cunha, João Paulo

2017-08-01

Background and purpose We evaluated two methods to identify mesial temporal sclerosis (MTS): visual inspection by experienced epilepsy neuroradiologists based on structural magnetic resonance imaging sequences and automated hippocampal volumetry provided by a processing pipeline based on the FMRIB Software Library. Methods This retrospective study included patients from the epilepsy monitoring unit database of our institution. All patients underwent brain magnetic resonance imaging in 1.5T and 3T scanners with protocols that included thin coronal T2, T1 and fluid-attenuated inversion recovery and isometric T1 acquisitions. Two neuroradiologists with experience in epilepsy and blinded to clinical data evaluated magnetic resonance images for the diagnosis of MTS. The diagnosis of MTS based on an automated method included the calculation of a volumetric asymmetry index between the two hippocampi of each patient and a threshold value to define the presence of MTS obtained through statistical tests (receiver operating characteristics curve). Hippocampi were segmented for volumetric quantification using the FIRST tool and fslstats from the FMRIB Software Library. Results The final cohort included 19 patients with unilateral MTS (14 left side): 14 women and a mean age of 43.4 ± 10.4 years. Neuroradiologists had a sensitivity of 100% and specificity of 73.3% to detect MTS (gold standard, k = 0.755). Automated hippocampal volumetry had a sensitivity of 84.2% and specificity of 86.7% (k = 0.704). Combined, these methods had a sensitivity of 84.2% and a specificity of 100% (k = 0.825). Conclusions Automated volumetry of the hippocampus could play an important role in temporal lobe epilepsy evaluation, namely on confirmation of unilateral MTS diagnosis in patients with radiological suggestive findings.

Oscillations of manometric tubular springs with rigid end

NASA Astrophysics Data System (ADS)

Cherentsov, D. A.; Pirogov, S. P.; Dorofeev, S. M.; Ryabova, Y. S.

2018-05-01

The paper presents a mathematical model of attenuating oscillations of manometric tubular springs (MTS) taking into account the rigid tip. The dynamic MTS model is presented in the form of a thin-walled curved rod oscillating in the plane of curvature of the central axis. Equations for MTS oscillations are obtained in accordance with the d’Alembert principle in projections onto the normal and tangential. The Bubnov-Galerkin method is used to solve the equations obtained.

A Modified Mechanical Threshold Stress Constitutive Model for Austenitic Stainless Steels

NASA Astrophysics Data System (ADS)

Prasad, K. Sajun; Gupta, Amit Kumar; Singh, Yashjeet; Singh, Swadesh Kumar

2016-12-01

This paper presents a modified mechanical threshold stress (m-MTS) constitutive model. The m-MTS model incorporates variable athermal and dynamic strain aging (DSA) Components to accurately predict the flow stress behavior of austenitic stainless steels (ASS)-316 and 304. Under strain rate variations between 0.01-0.0001 s-1, uniaxial tensile tests were conducted at temperatures ranging from 50-650 °C to evaluate the material constants of constitutive models. The test results revealed the high dependence of flow stress on strain, strain rate and temperature. In addition, it was observed that DSA occurred at elevated temperatures and very low strain rates, causing an increase in flow stress. While the original MTS model is capable of predicting the flow stress behavior for ASS, statistical parameters point out the inefficiency of the model when compared to other models such as Johnson Cook model, modified Zerilli-Armstrong (m-ZA) model, and modified Arrhenius-type equations (m-Arr). Therefore, in order to accurately model both the DSA and non-DSA regimes, the original MTS model was modified by incorporating variable athermal and DSA components. The suitability of the m-MTS model was assessed by comparing the statistical parameters. It was observed that the m-MTS model was highly accurate for the DSA regime when compared to the existing models. However, models like m-ZA and m-Arr showed better results for the non-DSA regime.

Effects of dual pathology on cognitive outcome following left anterior temporal lobectomy for treatment of epilepsy.

PubMed

Prayson, B E; Prayson, R A; Kubu, C S; Bingaman, W; Najm, I M; Busch, R M

2013-09-01

The objective of this retrospective study was to determine if dual pathology [DUAL - focal cortical dysplasia (FCD) and mesial temporal sclerosis (MTS)] in patients with left temporal lobe epilepsy is associated with greater risk for cognitive decline following temporal lobectomy than single pathology (MTS only). Sixty-three adults (Mage=36.5years, female: 52.4%) who underwent left anterior temporal lobectomy for treatment of epilepsy (MTS=28; DUAL=35) completed preoperative and postoperative neuropsychological evaluations. The base rate of dual pathology was 55.5%. Repeated measures ANOVAs yielded significant 2-way interactions (group×time) on most measures of language and memory with generally moderate effect sizes. Specifically, patients with MTS only demonstrated postoperative declines, while those with dual pathology remained unchanged or improved. Results suggest that dual pathology may be associated with better cognitive outcome following epilepsy surgery than MTS alone, possibly reflecting limited functionality of the resected tissue or intrahemispheric reorganization of function in the context of a developmental lesion. Copyright © 2013 Elsevier Inc. All rights reserved.

The attitude of risk taking Islamic junior high school (MTs) students in learning mathematics

NASA Astrophysics Data System (ADS)

Yuni, Y.; Darhim; Turmudi

2018-05-01

This study aims to determine the risk-taking attitude of students at Islamic Junior High School (MTs) in Bekasi towards learning mathematics. This is a preliminary research to get information about risk taking attitude in order to conduct next research. Data are obtained by providing questionnaires of 20 indicators, which includes be careful in act, having peace of mind, resolute in making decisions and confident in the act. Respondents are as many as 97 students of 7th grade students of MTs and taken with random techniques from two MTs in the city of Bekasi. The research instrument was adopted from DOSPERT developed, adapted to the ability of 7th grade students of MTs. The attitude of risk taking is part of the student's responsibility attitude to the learning of mathematics, either during preparation, process or after learning mathematics. The attitude of risk taking is important to know in order to be trained continuously. Because the trained attitude of risk taking will make students succeed in learning and working later.

Application of Multilayer Feedforward Neural Networks to Precipitation Cell-Top Altitude Estimation

NASA Technical Reports Server (NTRS)

Spina, Michelle S.; Schwartz, Michael J.; Staelin, David H.; Gasiewski, Albin J.

1998-01-01

The use of passive 118-GHz O2 observations of rain cells for precipitation cell-top altitude estimation is demonstrated by using a multilayer feed forward neural network retrieval system. Rain cell observations at 118 GHz were compared with estimates of the cell-top altitude obtained by optical stereoscopy. The observations were made with 2 4 km horizontal spatial resolution by using the Millimeter-wave Temperature Sounder (MTS) scanning spectrometer aboard the NASA ER-2 research aircraft during the Genesis of Atlantic Lows Experiment (GALE) and the COoperative Huntsville Meteorological EXperiment (COHMEX) in 1986. The neural network estimator applied to MTS spectral differences between clouds, and nearby clear air yielded an rms discrepancy of 1.76 km for a combined cumulus, mature, and dissipating cell set and 1.44 km for the cumulus-only set. An improvement in rms discrepancy to 1.36 km was achieved by including additional MTS information on the absolute atmospheric temperature profile. An incremental method for training neural networks was developed that yielded robust results, despite the use of as few as 56 training spectra. Comparison of these results with a nonlinear statistical estimator shows that superior results can be obtained with a neural network retrieval system. Imagery of estimated cell-top altitudes was created from 118-GHz spectral imagery gathered from CAMEX, September through October 1993, and from cyclone Oliver, February 7, 1993.

Dual-channel detection of metallothioneins and mercury based on a mercury-mediated aptamer beacon using thymidine-mercury-thymidine complex as a quencher.

PubMed

Chen, Si-Han; Wang, Yong-Sheng; Chen, Yun-Sheng; Tang, Xian; Cao, Jin-Xiu; Li, Ming-Hui; Wang, Xiao-Feng; Zhu, Yu-Feng; Huang, Yan-Qin

2015-01-01

A novel dual-channel strategy for the detection of metallothioneins (MTs) and Hg(2+) has been developed based on a mercury-mediated aptamer beacon (MAB) using thymidine-mercury-thymidine complex as a quencher for the first time. In the presence of Hg(2+), the T-rich oligonucleotide with a 6-carboxyfluorescein (TRO-FAM) can form an aptamer beacon via the formation of T-Hg(2+)-T base pairs, which results in a fluorescence quenching of the sensing system owing to the fluorescence resonance energy transfer (FRET) from the fluorophore of FAM to the terminated T-Hg(2+)-T base pair. The addition of MTs into this solution leads to the disruption of the T-Hg(2+)-T complex, resulting in an increase of the fluorescent signal of the system. In the optimizing condition, ΔF was directly proportional to the concentrations ranging from 5.63 nM to 0.275 μM for MTs, and 14.2 nM to 0.30 μM for Hg(2+) with the detection limits of 1.69 nM and 4.28 nM, respectively. The proposed dual-channel method avoids the label steps of a quencher in common molecular beacon strategies, without tedious procedure or the requirement of sophisticated equipment, and is rapid, inexpensive and sensitive. Copyright © 2015 Elsevier B.V. All rights reserved.

Methylphenidate Transdermal System in Adult ADHD and Impact on Emotional and Oppositional Symptoms

ERIC Educational Resources Information Center

Marchant, Barrie K.; Reimherr, Frederick W.; Robison, Reid J.; Olsen, John L.; Kondo, Douglas G.

2011-01-01

Objective: This trial evaluated the effect of methylphenidate transdermal system (MTS) on the full spectrum of adult symptoms (attention-disorganization, hyperactivity-impulsivity, emotional dysregulation [ED], and oppositional-defiant disorder [ODD]) found in this disorder. Method: This placebo-controlled, double-blind, flexible-dose, crossover…

Golgi as an MTOC: making microtubules for its own good

PubMed Central

Zhu, Xiaodong; Kaverina, Irina

2013-01-01

In cells, microtubules (MTs) are nucleated at MT-organizing centers (MTOCs). The centrosome-based MTOCs organize radial MT arrays which are often not optimal for polarized trafficking. A recently discovered subset of non-centrosomal MTs nucleated at the Golgi has proven to be indispensable for the Golgi organization, post-Golgi trafficking and cell polarity. Here, we summarize the history of this discovery, known molecular prerequisites of MT nucleation at the Golgi and unique functions of Golgi-derived MTs. PMID:23821162

One-Dimensional Brownian Motion of Charged Nanoparticles along Microtubules: A Model System for Weak Binding Interactions

PubMed Central

Minoura, Itsushi; Katayama, Eisaku; Sekimoto, Ken; Muto, Etsuko

2010-01-01

Abstract Various proteins are known to exhibit one-dimensional Brownian motion along charged rodlike polymers, such as microtubules (MTs), actin, and DNA. The electrostatic interaction between the proteins and the rodlike polymers appears to be crucial for one-dimensional Brownian motion, although the underlying mechanism has not been fully clarified. We examined the interactions of positively-charged nanoparticles composed of polyacrylamide gels with MTs. These hydrophilic nanoparticles bound to MTs and displayed one-dimensional Brownian motion in a charge-dependent manner, which indicates that nonspecific electrostatic interaction is sufficient for one-dimensional Brownian motion. The diffusion coefficient decreased exponentially with an increasing particle charge (with the exponent being 0.10 kBT per charge), whereas the duration of the interaction increased exponentially (exponent of 0.22 kBT per charge). These results can be explained semiquantitatively if one assumes that a particle repeats a cycle of binding to and movement along an MT until it finally dissociates from the MT. During the movement, a particle is still electrostatically constrained in the potential valley surrounding the MT. This entire process can be described by a three-state model analogous to the Michaelis-Menten scheme, in which the two parameters of the equilibrium constant between binding and movement, and the rate of dissociation from the MT, are derived as a function of the particle charge density. This study highlights the possibility that the weak binding interactions between proteins and rodlike polymers, e.g., MTs, are mediated by a similar, nonspecific charge-dependent mechanism. PMID:20409479

One-dimensional Brownian motion of charged nanoparticles along microtubules: a model system for weak binding interactions.

PubMed

Minoura, Itsushi; Katayama, Eisaku; Sekimoto, Ken; Muto, Etsuko

2010-04-21

Various proteins are known to exhibit one-dimensional Brownian motion along charged rodlike polymers, such as microtubules (MTs), actin, and DNA. The electrostatic interaction between the proteins and the rodlike polymers appears to be crucial for one-dimensional Brownian motion, although the underlying mechanism has not been fully clarified. We examined the interactions of positively-charged nanoparticles composed of polyacrylamide gels with MTs. These hydrophilic nanoparticles bound to MTs and displayed one-dimensional Brownian motion in a charge-dependent manner, which indicates that nonspecific electrostatic interaction is sufficient for one-dimensional Brownian motion. The diffusion coefficient decreased exponentially with an increasing particle charge (with the exponent being 0.10 kBT per charge), whereas the duration of the interaction increased exponentially (exponent of 0.22 kBT per charge). These results can be explained semiquantitatively if one assumes that a particle repeats a cycle of binding to and movement along an MT until it finally dissociates from the MT. During the movement, a particle is still electrostatically constrained in the potential valley surrounding the MT. This entire process can be described by a three-state model analogous to the Michaelis-Menten scheme, in which the two parameters of the equilibrium constant between binding and movement, and the rate of dissociation from the MT, are derived as a function of the particle charge density. This study highlights the possibility that the weak binding interactions between proteins and rodlike polymers, e.g., MTs, are mediated by a similar, nonspecific charge-dependent mechanism. Copyright 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Fluoxetine coupled with zinc in a chronic mild stress model of depression: Providing a reservoir for optimum zinc signaling and neuronal remodeling.

PubMed

Omar, Nesreen Nabil; Tash, Reham Fathy

2017-09-01

Recently, depression has been envisioned as more than an alteration in neurotransmitters centered around receptor signaling pathways. Consequently, the precise mechanisms of selective serotonin reuptake inhibitor (SSRI) antidepressant drugs such as fluoxetine are being revisited. Zinc is a trace element that has been long implicated in the psychopathology and therapy of depression. Zinc has been found to be sequestered and dispensed during stress and inflammation through a family of proteins called metallothioneins (MTs). In addition, MTs are well known for their antioxidant and therefore cytoprotective action. Changes in MTs, their upstream regulators and downstream effectors in response to fluoxetine have not been yet studied. The aim of the present study is to examine whether depression-induced changes in protein levels and mRNA levels of nuclear factor-erythroid 2-related factor 2 (Nrf2), MTs, antioxidant defensive enzyme heme oxygenase (HO-1), zinc-specific receptor GPR39 and brain derived neurotrophic factor (BDNF) in the hippocampus can be reversed by fluoxetine treatment, zinc supplementation or a combination of the two. The present study investigated the effect of chronic (4weeks) combined treatment with zinc hydroaspartate (15mg/kg) and fluoxetine (10mg/kg) on a chronic mild stress model (CMS) in male Sprague-Dawley rats. Hippocampal mRNA and protein levels of Nrf2, HO-1, MTs, GPR39 (protein level only) and BDNF were significantly higher in response to a combined therapy of fluoxetine and zinc than to either monotherapy. Additionally, HO-1 and MTs gene expression was correlated with that of Nrf2 in the FLX-only group. Fluoxetine therapy activated the expression of MTs and HO-1 through an Nrf2-dependent pathway. When FLX was escorted by zinc, activated MTs had a positive impact on BDNF through the zinc signaling receptor GPR39, resulting in general improvement in neuronal plasticity as well as reduction of neuronal atrophy and neuronal cell loss. Copyright © 2017 Elsevier Inc. All rights reserved.

Study of consensus-based time synchronization in wireless sensor networks.

PubMed

He, Jianping; Li, Hao; Chen, Jiming; Cheng, Peng

2014-03-01

Recently, various consensus-based protocols have been developed for time synchronization in wireless sensor networks. However, due to the uncertainties lying in both the hardware fabrication and network communication processes, it is not clear how most of the protocols will perform in real implementations. In order to reduce such gap, this paper investigates whether and how the typical consensus-based time synchronization protocols can tolerate the uncertainties in practical sensor networks through extensive testbed experiments. For two typical protocols, i.e., Average Time Synchronization (ATS) and Maximum Time Synchronization (MTS), we first analyze how the time synchronization accuracy will be affected by various uncertainties in the system. Then, we implement both protocols on our sensor network testbed consisted of Micaz nodes, and investigate the time synchronization performance and robustness under various network settings. Noticing that the synchronized clocks under MTS may be slightly faster than the desirable clock, by adopting both maximum consensus and minimum consensus, we propose a modified protocol, MMTS, which is able to drive the synchronized clocks closer to the desirable clock while maintaining the convergence rate and synchronization accuracy of MTS. © 2013 ISA. Published by ISA. All rights reserved.

Free vibration analysis of microtubules based on the molecular mechanics and continuum beam theory.

PubMed

Zhang, Jin; Wang, Chengyuan

2016-10-01

A molecular structural mechanics (MSM) method has been implemented to investigate the free vibration of microtubules (MTs). The emphasis is placed on the effects of the configuration and the imperfect boundaries of MTs. It is shown that the influence of protofilament number on the fundamental frequency is strong, while the effect of helix-start number is almost negligible. The fundamental frequency is also found to decrease as the number of the blocked filaments at boundaries decreases. Subsequently, the Euler-Bernoulli beam theory is employed to reveal the physics behind the simulation results. Fitting the Euler-Bernoulli beam into the MSM data leads to an explicit formula for the fundamental frequency of MTs with various configurations and identifies a possible correlation between the imperfect boundary conditions and the length-dependent bending stiffness of MTs reported in experiments.

Aurora-A regulates MCRS1 function during mitosis.

PubMed

Meunier, Sylvain; Timón, Krystal; Vernos, Isabelle

2016-07-02

The mitotic spindle is made of microtubules (MTs) nucleated through different pathways involving the centrosomes, the chromosomes or the walls of pre-existing MTs. MCRS1 is a RanGTP target that specifically associates with the chromosome-driven MTs protecting them from MT depolymerases. MCRS1 is also needed for the control of kinetochore fiber (K-fiber) MT minus-ends dynamics in metaphase. Here, we investigated the regulation of MCRS1 activity in M-phase. We show that MCRS1 is phosphorylated by the Aurora-A kinase in mitosis on Ser35/36. Although this phosphorylation has no role on MCRS1 localization to chromosomal MTs and K-fiber minus-ends, we show that it regulates MCRS1 activity in mitosis. We conclude that Aurora-A activity is particularly important in the tuning of K-fiber minus-ends dynamics in mitosis.

Effect of radio frequency waves of electromagnetic field on the tubulin.

PubMed

Taghi, Mousavi; Gholamhosein, Riazi; Saeed, Rezayi-Zarchi

2013-09-01

Microtubules (MTs) are macromolecular structures consisting of tubulin heterodimers and present in almost every eukaryotic cell. MTs fulfill all conditions for generation of electromagnetic field and are electrically polar due to the electrical polarity of a tubulin heterodimer. The calculated static electric dipole moment of about 1000 Debye makes them capable of being aligned parallel to the applied electromagnetic field direction. In the present study, the tubulin heterodimers were extracted and purified from the rat brains. MTs were obtained by polymerization in vitro. Samples of microtubules were adsorbed in the absence and in the presence of electromagnetic fields with radio frequency of 900 Hz. Our results demonstrate the effect of electromagnetic field with 900 Hz frequency to change the structure of MTs. In this paper, a related patent was used that will help to better understand the studied subject.

Evaluation of paper gradient concentration strips for antifungal combination testing of Candida spp.

PubMed

Siopi, Maria; Siafakas, Nikolaos; Zerva, Loukia; Meletiadis, Joseph

2015-11-01

In vitro combination testing with broth microdilution chequerboard (CHEQ) method is widely used although it is time-consuming, cumbersome and difficult to apply in routine setting of clinical microbiology laboratory. A new gradient concentration paper strip method, the Liofilchem(®) MIC test strips (MTS), provides an alternative easy and fast method enabling the simultaneous diffusion of both drugs in combination. We therefore tested a polyene+azole and an azole+echinocandin combination against 18 Candida isolates with the CHEQ method based on EUCAST guidelines and the MTS method in research and routine settings. Fractional inhibitory concentration (FIC) indices were calculated after 24 and 48 h of incubation based on complete and prominent (FIC-2) growth inhibition endpoints. Reproducibility and agreement within 1 twofold dilution was assessed. The FICs of the two methods were correlated quantitatively with t-test and Pearson analysis and qualitatively with Chi-squared test. The reproducibility of the CHEQ and MTS method was 88-100% and their agreement was 80% with 62-77% of MTS FICs being higher than the corresponding CHEQ FICs. A statistically significant Pearson correlation (r = 0.86, P = 0.0003) and association (χ(2) = 17.05, df = 4, P = 0.002) was found between MTS FIC and CHEQ FIC-2 after 24 h. Categorical agreement was 63% with no very major or major errors. All MTS synergistic interactions were also synergistic with the CHEQ method. © 2015 Blackwell Verlag GmbH.

Neuropsychological functioning in children with temporal lobe epilepsy and hippocampal atrophy without mesial temporal sclerosis: a distinct clinical entity?

PubMed

Schmidt, Charlotte S M; Lassonde, Maryse; Gagnon, Louise; Sauerwein, Catherine H; Carmant, Lionel; Major, Philippe; Paquette, Natacha; Lepore, Franco; Gallagher, Anne

2015-03-01

Unilateral hippocampal atrophy (HA) is considered as a precursor of mesial temporal sclerosis (MTS) in some patients with temporal lobe epilepsy. However, in other cases, it has been suggested that HA without MTS may constitute a distinct epileptic entity. Hippocampal atrophy without MTS was defined as HA without T2-weighted hyperintensity, loss of internal architecture, or associated lesion seen on the MRI data. To date, no study has focused on the cognitive pattern of children with epilepsy with HA without MTS. The objectives of the present study were to characterize the cognitive profile of these children and to investigate the presence (or the absence) of material-specific memory deficits in these young patients, as found in patients with MTS. Toward this end, 16 young patients with epilepsy with either left or right HA without MTS completed a set of neuropsychological tests, assessing overall intelligence, verbal memory and nonverbal memory, and some aspects of attention and executive functions. Results showed normal intellectual functioning without specific memory deficits in these patients. Furthermore, comparison between patients with left HA and patients with right HA failed to reveal a material-specific lateralized memory pattern. Instead, attention and executive functions were found to be impaired in most patients. These results suggest that HA may constitute a distinct epileptic entity, and this information may help health-care providers initiate appropriate and timely interventions. Copyright © 2014 Elsevier Inc. All rights reserved.

How well do vital signs identify children with serious infections in paediatric emergency care?

PubMed

Thompson, M; Coad, N; Harnden, A; Mayon-White, R; Perera, R; Mant, D

2009-11-01

To determine whether vital signs identify children with serious infections, and to compare their diagnostic value with that of the Manchester triage score (MTS) and National Institute for Health and Clinical Excellence (NICE) traffic light system of clinical risk factors. Prospective cohort of children presenting with suspected acute infection. We recorded vital signs, level of consciousness, activity level, respiratory distress, hydration and MTS category. Paediatric assessment unit at a teaching hospital in England. 700 children (median age 3 years), of whom 357 (51.0%) were referred from primary care, 198 (28.3%) self-referrals and 116 (16.6%) emergency ambulance transfers. Just over half (383 or 54.7%) were admitted. Severity of infection categorised as serious, intermediate, minor or not infection. Children with serious or intermediate infections (n = 313) were significantly more likely than those with minor or no infection (n = 387) to have a temperature >or=39 degrees C, tachycardia, saturations 2 seconds. Having one or more of temperature >or=39 degrees C, saturations

Steering microtubule shuttle transport with dynamically controlled magnetic fields

DOE PAGES

Mahajan, K. D.; Ruan, G.; Dorcéna, C. J.; ...

2016-03-23

Nanoscale control of matter is critical to the design of integrated nanosystems. Here, we describe a method to dynamically control directionality of microtubule (MT) motion using programmable magnetic fields. MTs are combined with magnetic quantum dots (i.e., MagDots) that are manipulated by external magnetic fields provided by magnetic nanowires. MT shuttles thus undergo both ATP-driven and externally-directed motion with a fluorescence component that permits simultaneous visualization of shuttle motion. This technology is used to alter the trajectory of MTs in motion and to pin MT motion. Ultimately, such an approach could be used to evaluate the MT-kinesin transport system andmore » could serve as the basis for improved lab-on-a-chip technologies based on MT transport.« less

Mislocalization of SLP-76 leads to aberrant inflammatory cytokine and autoantibody production.

PubMed

Sonnenberg, Gregory F; Mangan, Paul R; Bezman, Natalie A; Sekiguchi, Debora R; Luning Prak, Eline T; Erikson, Jan; Maltzman, Jonathan S; Jordan, Martha S; Koretzky, Gary A

2010-03-18

Central and peripheral tolerance is required to prevent immune responses to self-antigens. We now present a mouse model in which wild-type (WT) SH2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) has been constitutively targeted to the membrane, where CD4+ T cells become spontaneously dysregulated and develop an inflammatory phenotype. Mice bearing membrane-targeted SLP-76 (MTS) have a partial T-cell lymphopenia and impaired signaling though the mature T-cell receptor. The CD4+ T cells that develop in these mice possess an activated-like phenotype and are skewed toward the inflammatory T(H)1 and T(H)17 lineages. MTS mice also spontaneously develop autoantibodies at an early age. To rule out abnormal thymic selection as the sole cause of the MTS phenotype, we expressed WT SLP-76 along with the MTS followed by deletion of the WT allele in peripheral T cells. The peripheral MTS-expressing T cells demonstrate skewed cytokine responses when transferred into lymphopenic hosts. Thus, the abnormal effector T-cell phenotype still occurs in the presence of preserved central and peripheral tolerance, suggesting that diminished T-cell receptor signaling can promote skewed T-cell responses.

The effect of human microtubule-associated-protein tau on the assembly structure of microtubules and its ionic strength dependence

NASA Astrophysics Data System (ADS)

Choi, M. C.; Raviv, U.; Miller, H. P.; Gaylord, M. R.; Kiris, E.; Ventimiglia, D.; Needleman, D. J.; Chung, P. J.; Deek, J.; Lapointe, N.; Kim, M. W.; Wilson, L.; Feinstein, S. C.; Safinya, C. R.

2010-03-01

Microtubules (MTs), 25 nm protein nanotubes, are among the major filamentous elements of the eukaryotic cytoskeleton involved in intracellular trafficking, cell division and the establishment and maintenance of cell shape. Microtubule-associated-protein tau regulates tubulin assembly, MT dynamics and stability. Aberrant tau action has long been correlated with numerous neurodegenerative diseases, including Alzheimer's, and fronto-temporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) Using synchrotron small angle x-ray scattering (SAXS) and binding assay, we examine the effects of tau on the assembly structure of taxol-stabilized MTs. We find that tau regulates the distribution of protofilament numbers in MTs as reflected in the observed increase in the average radius of MTs with increasing the tau/tubulin molar ratio. Additionally, tau-MT interactions are mediated to a large extent via electrostatic interactions: the binding affinity of tau to MTs is ionic strength dependent. Supported by DOE-BES DE-FG02-06ER46314, NSF DMR-0803103, NIH NS35010, NIH NS13560. (Ref) M.C. Choi, S.C. Feinstein, and C.R. Safinya et al. Biophys. J. 97; 519 (2009).

Control of microtubule trajectory within an electric field by altering surface charge density

PubMed Central

Isozaki, Naoto; Ando, Suguru; Nakahara, Tasuku; Shintaku, Hirofumi; Kotera, Hidetoshi; Meyhöfer, Edgar; Yokokawa, Ryuji

2015-01-01

One of challenges for using microtubules (MTs) driven by kinesin motors in microfluidic environments is to control their direction of movement. Although applying physical biases to rectify MTs is prevalent, it has not been established as a design methodology in conjunction with microfluidic devices. In the future, the methodology is expected to achieve functional motor-driven nanosystems. Here, we propose a method to guide kinesin-propelled MTs in multiple directions under an electric field by designing a charged surface of MT minus ends labeled with dsDNA via a streptavidin-biotin interaction. MTs labeled with 20-bp or 50-bp dsDNA molecules showed significantly different trajectories according to the DNA length, which were in good agreement with values predicted from electrophoretic mobilities measured for their minus ends. Since the effective charge of labeled DNA molecules was equal to that of freely dispersed DNA molecules in a buffer solution, MT trajectory could be estimated by selecting labeling molecules with known charges. Moreover, the estimated trajectory enables to define geometrical sizes of a microfluidic device. This rational molecular design and prediction methodology allows MTs to be guided in multiple directions, demonstrating the feasibility of using molecular sorters driven by motor proteins. PMID:25567007

Control of microtubule trajectory within an electric field by altering surface charge density.

PubMed

Isozaki, Naoto; Ando, Suguru; Nakahara, Tasuku; Shintaku, Hirofumi; Kotera, Hidetoshi; Meyhöfer, Edgar; Yokokawa, Ryuji

2015-01-08

One of challenges for using microtubules (MTs) driven by kinesin motors in microfluidic environments is to control their direction of movement. Although applying physical biases to rectify MTs is prevalent, it has not been established as a design methodology in conjunction with microfluidic devices. In the future, the methodology is expected to achieve functional motor-driven nanosystems. Here, we propose a method to guide kinesin-propelled MTs in multiple directions under an electric field by designing a charged surface of MT minus ends labeled with dsDNA via a streptavidin-biotin interaction. MTs labeled with 20-bp or 50-bp dsDNA molecules showed significantly different trajectories according to the DNA length, which were in good agreement with values predicted from electrophoretic mobilities measured for their minus ends. Since the effective charge of labeled DNA molecules was equal to that of freely dispersed DNA molecules in a buffer solution, MT trajectory could be estimated by selecting labeling molecules with known charges. Moreover, the estimated trajectory enables to define geometrical sizes of a microfluidic device. This rational molecular design and prediction methodology allows MTs to be guided in multiple directions, demonstrating the feasibility of using molecular sorters driven by motor proteins.

Organization of cortical microtubules in graviresponding maize roots

NASA Technical Reports Server (NTRS)

Blancaflor, E. B.; Hasenstein, K. H.

1993-01-01

Immunofluorescence labeling of cortical microtubules (MTs) was used to investigate the relationship between MT arrangement and changes in growth rate of the upper and lower sides of horizontally placed roots of maize (Zea mays L. cv. Merit). Cap cells and cells of the elongation zone of roots grown vertically in light or darkness showed MT arrangements that were transverse (perpendicular) to the growth direction. Microtubules of cells basal to the elongation zone typically showed oblique orientation. Two hours after horizontal reorientation, cap cells of gravicompetent, light-grown and curving roots contained MTs parallel to the gravity vector. The MT arrangement on the upper side of the elongation zone remained transverse but the MTs of the outer four to five layers of cortical cells along the lower side of the elongation zone showed reorientation parallel to the axis of the root. The MTs of the lower epidermis retained their transverse orientation. Dark-grown roots did not curve and did not show reorientation of MTs in cells of the root cap or elongation zone. The data indicate that MT depolymerization and reorientation is correlated with reduction in growth rate, and that MT reorientation is one of the steps of growth control of graviresponding roots.

Genetic improvement of butanol tolerance in Escherichia coli by cell surface expression of fish metallothionein.

PubMed

Lin, Kuo Hsing; Chin, Wei Chih; Lee, Ang Hsuan; Huang, Chieh Chen

2011-01-01

Cysteine-rich metallothioneins (MTs) have been reported to possess the capacity to scavenge reactive oxygen species in vitro and in vivo. Recombinant strains of Escherichia coli expressing outer membrane protein C (OmpC) fused with MTs from human, mouse and tilapia displayed the ability for such surface-localized MTs to scavenge extracellular free radicals, but the benefits of the possible applications of this capacity have not yet been demonstrated. Because the intrinsic butanol tolerance of microbes has become an impediment for biological butanol production, we examined whether surface-displayed MTs could contribute to butanol tolerance. The results show that strains expressing OmpC-MT fusion proteins had higher butanol tolerance than strains with cytoplasmically expressed MTs. Furthermore, the OmpC-tilapia MT fusion protein enhanced butanol tolerance more strongly than other recombinant constructs. Although the enhanced level of tolerance was not as high as that provided by OmpC-tilapia MT, over-expression of OmpC was also found to contribute to butanol tolerance. These results suggest that free-radical scavenging by MT and OmpC-related osmoregulation enhance butanol tolerance. Our results shed new light on methods for engineering bacteria with higher butanol tolerance. © 2011 Landes Bioscience

Suppressor of cytokine signaling 1 (SOCS1) mitigates anterior uveitis and confers protection against ocular HSV-1 infection.

PubMed

Yu, Cheng-Rong; Hayashi, Kozaburo; Lee, Yun Sang; Mahdi, Rashid M; Shen, De Fen; Chan, Chi-Chao; Egwuagu, Charles E

2015-04-01

Immunological responses to pathogens are stringently regulated in the eye to prevent excessive inflammation that damage ocular tissues and compromise vision. Suppressors of cytokine signaling (SOCS) regulate intensity/duration of inflammatory responses. We have used SOCS1-deficient mice and retina-specific SOCS1 transgenic rats to investigate roles of SOCS1 in ocular herpes simplex virus (HSV-1) infection and non-infectious uveitis. We also genetically engineered cell-penetrating SOCS proteins (membrane-translocating sequence (MTS)-SOCS1, MTS-SOCS3) and examined whether they can be used to inhibit inflammatory cytokines. Overexpression of SOCS1 in transgenic rat eyes attenuated ocular HSV-1 infection while SOCS1-deficient mice developed severe non-infectious anterior uveitis, suggesting that SOCS1 may contribute to mechanism of ocular immune privilege by regulating trafficking of inflammatory cells into ocular tissues. Furthermore, MTS-SOCS1 inhibited IFN-γ-induced signal transducers and activators of transcription 1 (STAT1) activation by macrophages while MTS-SOCS3 suppressed expansion of pathogenic Th17 cells that mediate uveitis, indicating that MTS-SOCS proteins maybe used to treat ocular inflammatory diseases of infectious or autoimmune etiology.

Regulation of Intracellular Copper by Induction of Endogenous Metallothioneins Improves the Disease Course in a Mouse Model of Amyotrophic Lateral Sclerosis.

PubMed

Tokuda, Eiichi; Watanabe, Shunsuke; Okawa, Eriko; Ono, Shin-ichi

2015-04-01

Mutations in SOD1 cause amyotrophic lateral sclerosis (ALS), an incurable motor neuron disease. The pathogenesis of the disease is poorly understood, but intracellular copper dyshomeostasis has been implicated as a key process in the disease. We recently observed that metallothioneins (MTs) are an excellent target for the modification of copper dyshomeostasis in a mouse model of ALS (SOD1(G93A)). Here, we offer a therapeutic strategy designed to increase the level of endogenous MTs. The upregulation of endogenous MTs by dexamethasone, a synthetic glucocorticoid, significantly improved the disease course and rescued motor neurons in SOD1(G93A) mice, even if the induction was initiated when peak body weight had decreased by 10%. Neuroprotection was associated with the normalization of copper dyshomeostasis, as well as with decreased levels of SOD1(G93A) aggregates. Importantly, these benefits were clearly mediated in a MT-dependent manner, as dexamethasone did not provide any protection when endogenous MTs were abolished from SOD1(G93A) mice. In conclusion, the upregulation of endogenous MTs represents a promising strategy for the treatment of ALS linked to mutant SOD1.

An evaluation of four MTS recurrent training courses.

DOT National Transportation Integrated Search

1978-09-01

This study assessed the effectiveness of four recurrent training courses at the FAA Management Training School (MTS).The courses evaluated were Performance Improvement and Employee Appraisal (PIP/PER), Labor Relations for Management (LMR), Constructi...

A randomized, single-blind trial of 5% minoxidil foam once daily versus 2% minoxidil solution twice daily in the treatment of androgenetic alopecia in women.

PubMed

Blume-Peytavi, Ulrike; Hillmann, Kathrin; Dietz, Ekkehart; Canfield, Douglas; Garcia Bartels, Natalie

2011-12-01

Although twice-daily application of propylene glycol-containing 2% minoxidil topical solution (MTS) stimulates new hair growth, higher concentrations of minoxidil in a once-daily, propylene glycol-free formulation may improve efficacy and reduce unpleasant side effects. We sought to compare the efficacy, safety, and acceptability and to show noninferiority of once-daily 5% minoxidil topical foam (MTF) with twice-daily 2% MTS in women with androgenetic alopecia. A total of 113 women with androgenetic alopecia were randomized to 24 weeks of treatment with 5% MTF or 2% MTS. The primary efficacy parameter was change from baseline in nonvellus target area hair count at week 24. Secondary end points included change in nonvellus target area hair width, overall efficacy by global photographic review as assessed by treatment-blinded evaluators and the subject herself, adverse events, and participants' assessment of product aesthetics. After 24 weeks, women randomized to 5% MTF once daily showed noninferior target area hair count and target area hair width and experienced greater, but nonsignificant, improvements in target area hair count, target area hair width, and overall efficacy by global photographic review than those randomized to 2% MTS used twice daily. 5% MTF was significantly superior to 2% MTS in participants' agreement with "the treatment does not interfere with styling my hair" (P = .002). Women randomized to 5% MTF experienced significantly lower rates of local intolerance (P = .046) especially in pruritus and dandruff compared with 2% MTS. Because of differences in the formulations tested, study participants were not blinded to treatment. Once-daily 5% MTF is noninferior and as effective for stimulating hair growth as twice-daily 2% MTS in women with androgenetic alopecia and is associated with several aesthetic and practical advantages. Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Near-atomic model of microtubule-tau interactions.

PubMed

Kellogg, Elizabeth H; Hejab, Nisreen M A; Poepsel, Simon; Downing, Kenneth H; DiMaio, Frank; Nogales, Eva

2018-06-15

Tau is a developmentally regulated axonal protein that stabilizes and bundles microtubules (MTs). Its hyperphosphorylation is thought to cause detachment from MTs and subsequent aggregation into fibrils implicated in Alzheimer's disease. It is unclear which tau residues are crucial for tau-MT interactions, where tau binds on MTs, and how it stabilizes them. We used cryo-electron microscopy to visualize different tau constructs on MTs and computational approaches to generate atomic models of tau-tubulin interactions. The conserved tubulin-binding repeats within tau adopt similar extended structures along the crest of the protofilament, stabilizing the interface between tubulin dimers. Our structures explain the effect of phosphorylation on MT affinity and lead to a model of tau repeats binding in tandem along protofilaments, tethering together tubulin dimers and stabilizing polymerization interfaces. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Contralateral interictal and ictal EEG epileptiform activity accentuate memory impairment in unilateral mesial temporal sclerosis patients.

PubMed

Pinto, Lecio F; Adda, Carla C; Silva, Liliane C A; Banaskiwitz, Natalie H C; Passarelli, Valmir; Jorge, Carmen L; Valerio, Rosa M; Castro, Luiz H

2017-03-01

Memory impairment is a recognized complication of mesial temporal sclerosis (MTS). Epileptiform activity may negatively impact on cognition. We evaluated the impact of contralateral EEG involvement on memory in unilateral MTS (uMTS) patients. Retrospective review of 121 right-handed uMTS patients (69 left) evaluated with prolonged video-EEG and verbal and nonverbal memory tests (Rey Auditory Verbal Learning Test and Rey-Osterrieth Complex figure), with additional very delayed trials. Patients were classified according to ictal/interictal EEG findings and MTS side as left or right concordant or discordant. Thirty-nine normal individuals who underwent the same neuropsychological battery served as controls. Demographic, disease, and treatment features did not differ among groups. On the 7-day verbal memory free recall, left discordant performed significantly worse than controls and right concordant, recognized fewer words, and had more recognition errors than all other groups, including left concordant. For nonverbal memory, right discordant performed significantly worse than controls on delayed recall, and attained lower scores than other groups on immediate and 7-day recall, but this difference did not reach statistical significance. Left discordant had higher scores of memory complaints than controls and disclosed a trend toward accentuated memory impairment compared with the other groups over time. Our results suggest that contralateral electrographic involvement in uMTS was associated with more pronounced memory impairment for verbal material in left discordant patients, and to a lesser extent, for nonverbal material in right discordant patients. Left discordant group also had increased memory complaints. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Identification of two metallothionein genes and their roles in stress responses of Musca domestica toward hyperthermy and cadmium tolerance.

PubMed

Tang, Ting; Huang, Da-wei; Zhang, Di; Wu, Yin-jian; Murphy, Robert W; Liu, Feng-song

2011-10-01

Stress proteins such as metallothioneins (MTs) play a key role in cellular protection against environmental stressors. In nature, insects such as houseflies (Musca domestica) are commonly exposed to multiple stressors including heavy metals (e.g. Cadmium, Cd) and high temperatures. In this paper, we identify two novel MT genes from the cDNAs of M. domestica, MdMT1 and MdMT2, which putatively encode 40 and 42 amino acid residues respectively. Expression of the two MTs' mRNAs, which are examined in the fat body, gut, hemocyte, and the epidermis. From our study, we saw that the expression of MdMT1 and MdMT2 are enhanced by Cd and thermal stress. Levels of expression are highest at 10 mM Cd(2+) within a 24-h period, and expressions increase significantly with exposure to 10 mM Cd for 12h. Levels of the mRNAs are up-regulated after heat shock and that of MdMT2 reaches its maximum peak faster than MdMT1. Both of the MT genes might be involved in a transient systemic tolerance response to stressors and they may play important roles in heavy metal and high temperature tolerance in the housefly. To detect whether or not the MTs bind heavy metals, the target genes are cloned into the prokaryotic expression vector pET-DsbA to obtain fusion protein expressed in Escherichia coli BL21 (DE3). Recombinant DsbA-MdMT1 significantly increases tolerance of the host bacteria to Cd(2+), but DsbA-MdMT2 is absent. These differential characteristics will facilitate future investigations into the physiological functions of MTs. Copyright © 2011 Elsevier Inc. All rights reserved.

Modulation of nitric oxide-mediated metal release from metallothionein by the redox state of glutathione in vitro.

PubMed

Khatai, Leila; Goessler, Walter; Lorencova, Helena; Zangger, Klaus

2004-06-01

Metallothioneins (MTs) release bound metals when exposed to nitric oxide. At inflammatory sites, both metallothionein and inducible nitric oxide synthase (iNOS) are induced by the same factors and the zinc released from metallothionein by NO suppresses both the induction and activity of iNOS. In a search for a possible modulatory mechanism of this coexpression of counteracting proteins, we investigated the role of the glutathione redox state in vitro because the oxidation state of thiols is involved in the metal binding in Cd-S or Zn-S clusters found in metallothioneins, and NO also binds to reduced glutathione via S-nitrosation. Using a variety of techniques, we found that NO and also ONOO(-)-mediated metal release from purified MTs is suppressed by reduced glutathione (GSH), but not by oxidized glutathione. Considering the millimolar concentrations of GSH present in mammalian cells, the metal release from MTs by NO should play no role in living systems. Therefore, the fact that it has been observed in vivo points to a hitherto unknown mechanism or additional compound(s) being involved in this physiologically relevant reaction and as long as this additional factor is not found experimental results on the MT-NO interaction should be treated with caution. Contrary to the peroxynitrite-induced activation of guanylyl cyclase, where GSH is needed, we found that the metal release from metallothionein by peroxynitrite is not enhanced, but also suppressed by reduced glutathione. In addition, we show that zinc, the major natural metal ligand in mammalian MTs and suppressor of iNOS, is released more readily under the influence of NO than cadmium, but in contrast to the MT isoform 1, the amount of metal released from the beta-domain of MT-2 is comparable to that from the alpha-domain.

Biochemical activity and multiple locations of particulate guanylate cyclase in Rhyacophila dorsalis acutidens (Insecta: Trichoptera) provide insights into the cGMP signalling pathway in Malpighian tubules.

PubMed

Secca, T; Sciaccaluga, M; Marra, A; Barberini, L; Bicchierai, M C

2011-04-01

In insect renal physiology, cGMP and cAMP have important regulatory roles. In Drosophila melanogaster, considered a good model for molecular physiology studies, and in other insects, cGMP and cAMP act as signalling molecules in the Malpighian tubules (MTs). However, many questions related to cyclic nucleotide functions are unsolved in principal cells (PC) and stellate cells (SC), the two cell types that compose the MT. In PC, despite the large body of information available on soluble guanylate cyclase (sGC) in the cGMP pathway, the functional circuit of particulate guanylate cyclase (pGC) remains obscure. In SC, on the other side, the synthesis and physiological role of the cGMP are still unknown. Our biochemical data regarding the presence of cyclic nucleotides in the MTs of Rhyacophila dorsalis acutidens revealed a cGMP level above the 50%, in comparison with the cAMP. The specific activity values for the membrane-bound guanylate cyclase were also recorded, implying that, besides the sGC, pGC is a physiologically relevant source of cGMP in MTs. Cytochemical studies showed ultrastructurally that there was a great deal of pGC on the basolateral membranes of both the principal and stellate cells. In addition, pGC was also detected in the contact zone between the two cell types and in the apical microvillar region of the stellate cells bordering the tubule lumen. The pGC signal is so well represented in PC and, unexpectedly in SC of MTs, that it is possible to hypothesize the existence of still uncharacterized physiological processes regulated by the pGC-cGMP system. Copyright © 2011 Elsevier Ltd. All rights reserved.

National Early Warning Score (NEWS) as an emergency department predictor of disease severity and 90-day survival in the acutely dyspneic patient - a prospective observational study.

PubMed

Bilben, Bente; Grandal, Linda; Søvik, Signe

2016-06-02

National Early Warning Score (NEWS) was designed to detect deteriorating patients in hospital wards, specifically those at increased risk of ICU admission, cardiac arrest, or death within 24 h. NEWS is not validated for use in Emergency Departments (ED), but emerging data suggest it may be useful. A criticism of NEWS is that patients with chronic poor oxygenation, e.g. severe chronic obstructive pulmonary disease (COPD), will have elevated NEWS also in the absence of acute deterioration, possibly reducing the predictive power of NEWS in this subgroup. We wanted to prospectively evaluate the usefulness of NEWS in unselected adult patients emergently presenting in a Norwegian ED with respiratory distress as main symptom. In respiratory distressed patients, NEWS was calculated on ED arrival, after 2-4 h, and the next day. Manchester Triage Scale (MTS) category, age, gender, comorbidity (ASA score), ICU-admission, ventilatory support, and discharge diagnoses were noted. Survival status was tracked for >90 days through the Population Registry. Data are medians (25-75th percentiles). Factors predicting 90-day survival were analysed with multiple logistic regression. We included 246 patients; 71 years old (60-80), 89 % home-dwelling, 74 % ASA 3-4, 72 % MTS 1-2, 88 % admitted to hospital. NEWS on arrival was 5 (3-7). NEWS correlated closely with MTS category and maximum in-hospital level of care (ED, ward, high-dependency unit, ICU). Sixteen patients died in-hospital, 26 died after discharge within 90 days. Controlled for age, ASA score, and COPD, a higher NEWS on ED arrival predicted poorer 90-day survival. Increased NEWS also correlated with decreased 30-day- and in-hospital survival and a decreased probability for home-dwelling patients to be discharged directly home. In respiratory distressed patients, NEWS on ED arrival correlated closely with triage category and need of ICU admission and predicted long-term out-of-hospital survival controlled for age, comorbidity, and COPD. NEWS should be explored in the ED setting to determine its role in clinical decision-making and in communication along the acute care chain.

Modified fused silicide coatings for tantalum (Ta-10W) reentry heat shields

NASA Technical Reports Server (NTRS)

Packer, C. M.; Perkins, R. A.

1973-01-01

Results are presented of a program of research to develop a reliable, high performance, fused slurry silicide coating for the Ta-10W alloy. The effort was directed toward developing new and improved formulations for use at 2600 to 2800 F (1700 to 1811 K) in an atmospheric reentry thermal protection system with a 100-mission capability. Based on a thorough characterization of isothermal and cyclic oxidation behavior, bend transition temperatures, room- and elevated-temperature tensile properties, and creep behavior, a 2.5 Mn-33Ti-64.5Si coating (designated MTS) provides excellent protection for the Ta-10W alloy in simulated reentry environments. An extensive analysis of the oxidation behavior and characteristics of the MTS coating in terms of fundamental mechanisms also is presented.

A novel function of the cell polarity-regulating kinase PAR-1/MARK in dendritic spines

PubMed Central

Hayashi, Kenji; Suzuki, Atsushi; Ohno, Shigeo

2011-01-01

Dendritic spines are postsynaptic structures that receive excitatory synaptic signals from presynaptic terminals in neurons. Because the morphology of spines has been considered to be a crucial factor for the efficiency of synaptic transmission, understanding the mechanisms regulating their morphology is important for neuroscience. Actin filaments and their regulatory proteins are known to actively maintain spine morphology; recent studies have also shown an essential role of microtubules (MTs). Live imaging of the plus-ends of MTs in mature neurons revealed that MTs stochastically enter spines and mediate accumulation of p140Cap, which regulates reorganization of actin filaments. However, the molecular mechanism by which MT dynamics is controlled has remained largely unknown. A cell polarity-regulating serine/threonine kinase, partitioning-defective 1 (PAR-1), phosphorylates classical MAPs and inhibits their binding to MTs. Because the interaction of MAPs with MTs can decrease MT dynamic instability, PAR-1 is supposed to activate MT dynamics through its MAP/MT affinity-regulating kinase (MARK) activity, although there is not yet any direct evidence for this. Here, we review recent findings on the localization of PAR-1b in the dendrites of mouse hippocampal neurons, and its novel function in the maintenance of mature spine morphology by regulating MT dynamics. PMID:22545177

A novel function of the cell polarity-regulating kinase PAR-1/MARK in dendritic spines.

PubMed

Hayashi, Kenji; Suzuki, Atsushi; Ohno, Shigeo

2011-11-01

Dendritic spines are postsynaptic structures that receive excitatory synaptic signals from presynaptic terminals in neurons. Because the morphology of spines has been considered to be a crucial factor for the efficiency of synaptic transmission, understanding the mechanisms regulating their morphology is important for neuroscience. Actin filaments and their regulatory proteins are known to actively maintain spine morphology; recent studies have also shown an essential role of microtubules (MTs). Live imaging of the plus-ends of MTs in mature neurons revealed that MTs stochastically enter spines and mediate accumulation of p140Cap, which regulates reorganization of actin filaments. However, the molecular mechanism by which MT dynamics is controlled has remained largely unknown. A cell polarity-regulating serine/threonine kinase, partitioning-defective 1 (PAR-1), phosphorylates classical MAPs and inhibits their binding to MTs. Because the interaction of MAPs with MTs can decrease MT dynamic instability, PAR-1 is supposed to activate MT dynamics through its MAP/MT affinity-regulating kinase (MARK) activity, although there is not yet any direct evidence for this. Here, we review recent findings on the localization of PAR-1b in the dendrites of mouse hippocampal neurons, and its novel function in the maintenance of mature spine morphology by regulating MT dynamics.

Single microfilaments mediate the early steps of microtubule bundling during preprophase band formation in onion cotyledon epidermal cells

PubMed Central

Takeuchi, Miyuki; Karahara, Ichirou; Kajimura, Naoko; Takaoka, Akio; Murata, Kazuyoshi; Misaki, Kazuyo; Yonemura, Shigenobu; Staehelin, L. Andrew; Mineyuki, Yoshinobu

2016-01-01

The preprophase band (PPB) is a cytokinetic apparatus that determines the site of cell division in plants. It originates as a broad band of microtubules (MTs) in G2 and narrows to demarcate the future division site during late prophase. Studies with fluorescent probes have shown that PPBs contain F-actin during early stages of their development but become actin depleted in late prophase. Although this suggests that actins contribute to the early stages of PPB formation, how actins contribute to PPB-MT organization remains unsolved. To address this question, we used electron tomography to investigate the spatial relationship between microfilaments (MFs) and MTs at different stages of PPB assembly in onion cotyledon epidermal cells. We demonstrate that the PPB actins observed by fluorescence microscopy correspond to short, single MFs. A majority of the MFs are bound to MTs, with a subset forming MT-MF-MT bridging structures. During the later stages of PPB assembly, the MF-mediated links between MTs are displaced by MT-MT linkers as the PPB MT arrays mature into tightly packed MT bundles. On the basis of these observations, we propose that the primary function of actins during PPB formation is to mediate the initial bundling of the PPB MTs. PMID:27053663

Cell cycle phase dependent emergence of thymidylate synthase studied by monoclonal antibody (M-TS-4).

PubMed

Shibui, S; Hoshino, T; Iwasaki, K; Nomura, K; Jastreboff, M M

1989-05-01

A method of identifying thymidylate synthase (TS) at the cellular level was developed using anti-TS monoclonal antibody (M-TS-4), a monoclonal antibody created against purified TS from a HeLa cell line. In HeLa cells and four human glioma cell lines (U-251, U-87, 343-MGA, and SF-188), TS was identified primarily in the cytoplasm. Autoradiographic and flow cytometric studies showed that TS appeared mainly in the G1 phase and subsided early in the S phase; thus, the G1 phase can be divided into TS-positive and -negative fractions. Nuclear TS was not demonstrated unequivocally with M-TS-4, and the relationship between nuclear TS and DNA synthesis could not be determined. Although the percentage of TS-positive cells was larger than the S-phase fraction measured by autoradiography after a pulse of tritiated thymidine or by the immunoperoxidase method using BUdR, the ratios were within a similar range (1.2-1.4) in all cell lines studied. Therefore, the S-phase fraction can be estimated indirectly from the percentage of TS-positive cells measured by M-TS-4. Because the emergence of TS detected by our method is cell cycle dependent, M-TS-4 may be useful for biochemical studies of TS and for cytokinetic analysis.

Characterization of the microtubule binding domain of microtubule actin crosslinking factor (MACF): identification of a novel group of microtubule associated proteins.

PubMed

Sun, D; Leung, C L; Liem, R K

2001-01-01

MACF (microtubule actin cross-linking factor) is a large, 608-kDa protein that can associate with both actin microfilaments and microtubules (MTs). Structurally, MACF can be divided into 3 domains: an N-terminal domain that contains both a calponin type actin-binding domain and a plakin domain; a rod domain that is composed of 23 dystrophin-like spectrin repeats; and a C-terminal domain that includes two EF-hand calcium-binding motifs, as well as a region that is homologous to two related proteins, GAR22 and Gas2. We have previously demonstrated that the C-terminal domain of MACF binds to MTs, although no homology was observed between this domain and other known microtubule-binding proteins. In this report, we describe the characterization of this microtubule-binding domain of MACF by transient transfection studies and in vitro binding assays. We found that the C-terminus of MACF contains at least two microtubule-binding regions, a GAR domain and a domain containing glycine-serine-arginine (GSR) repeats. In transfected cells, the GAR domain bound to and partially stabilized MTs to depolymerization by nocodazole. The GSR-containing domain caused MTs to form bundles that are still sensitive to nocodazole-induced depolymerization. When present together, these two domains acted in concert to bundle MTs and render them stable to nocodazole treatment. Recently, a study has shown that the N-terminal half of the plakin domain (called the M1 domain) of MACF also binds MTs. We therefore examined the microtubule binding ability of the M1 domain in the context of the entire plakin domain with and without the remaining N-terminal regions of two different MACF isoforms. Interestingly, in the presence of the surrounding sequences, the M1 domain did not bind MTs. In addition to MACF, cDNA sequences encoding the GAR and GSR-containing domains are also found in the partial human EST clone KIAA0728, which has high sequence homology to the 3' end of the MACF cDNA; hence, we refer to it as MACF2. The C-terminal domain of mouse MACF2 was cloned and characterized. The microtubule-binding properties of MACF2 C-terminal domain are similar to that of MACF. The GAR domain was originally found in Gas 2 protein and here we show that it can associate with MTs in transfected cells. Plectin and desmoplakin have GSR-containing domains at their C-termini and we further demonstrate that the GSR-containing domain of plectin, but not desmoplakin, can bind to MTs in vivo.

Methylphenidate Transdermal System in Adults with Past Stimulant Misuse: An Open-Label Trial

ERIC Educational Resources Information Center

McRae-Clark, Aimee L.; Brady, Kathleen T.; Hartwell, Karen J.; White, Kathleen; Carter, Rickey E.

2011-01-01

Objective: This 8-week, open-label trial assessed the efficacy of methylphenidate transdermal system (MTS) in 14 adult individuals diagnosed with ADHD and with a history of stimulant misuse, abuse, or dependence. Method: The primary efficacy endpoint was the Wender-Reimherr Adult ADHD Scale (WRAADS), and secondary efficacy endpoints included the…

An evaluation of the effectiveness of the FAA Management Training School.

DOT National Transportation Integrated Search

1975-01-01

This report covers two aspects of an agency-wide assessment of the FAA Management Training School (MTS) program. The first part of the report considers the evaluation of MTS by approximately 10% of the Supervisory and Managerial Training Course gradu...

NOAA’s Physical Oceanographic Real-Time Systems (PORTS(Registered))

DTIC Science & Technology

2010-06-01

1 NOAA’s Physical Oceanographic Real - Time Systems (PORTS®) Darren Wright and Robert Bassett National Oceanic and Atmospheric Administration...operation of several Physical Oceanographic Real - Time Systems (PORTS®). 0-933957-38-1 ©2009 MTS Report Documentation Page Form ApprovedOMB No. 0704-0188...TITLE AND SUBTITLE NOAAs Physical Oceanographic Real - Time Systems (PORTS®) 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6

It's about Time: Theorizing the Antecedents and Outcomes of Dynamic Processes in Teams and Multiteam Systems

ERIC Educational Resources Information Center

Schecter, Aaron Mitchell

2017-01-01

Multiteam systems (MTS) are an organizational form comprised of two or more independent teams which share at least one common goal. These "teams of teams" can be found in all areas of life, from business to medicine, science to the military. Accordingly, it is of great interest to determine how these systems function, and what makes a…

Metal ion release from metallothioneins: proteolysis as an alternative to oxidation.

PubMed

Peroza, Estevão A; dos Santos Cabral, Augusto; Wan, Xiaoqiong; Freisinger, Eva

2013-09-01

Metallothioneins (MTs) are among others involved in the cellular regulation of essential Zn(II) and Cu(I) ions. However, the high binding affinity of these proteins requires additional factors to promote metal ion release under physiological conditions. The mechanisms and efficiencies of these processes leave many open questions. We report here a comprehensive analysis of the Zn(II)-release properties of various MTs with special focus on members of the four main subfamilies of plant MTs. Zn(II) competition experiments with the metal ion chelator 4-(2-pyridylazo)resorcinol (PAR) in the presence of the cellular redox pair glutathione (GSH)/glutathione disulfide (GSSG) show that plant MTs from the subfamilies MT1, MT2, and MT3 are remarkably more affected by oxidative stress than those from the Ec subfamily and the well-characterized human MT2 form. In addition, we evaluated proteolytic digestion with trypsin and proteinase K as an alternative mechanism for selective promotion of metal ion release from MTs. Also here the observed percentage of liberated metal ions depends strongly on the MT form evaluated. Closer evaluation of the data additionally allowed deducing the thermodynamic and kinetic properties of the Zn(II) release processes. The Cu(I)-form of chickpea MT2 was used to exemplify that both oxidation and proteolysis are also effective ways to increase the transfer of copper ions to other molecules. Zn(II) release experiments with the individual metal-binding domains of Ec-1 from wheat grain reveal distinct differences from the full-length protein. This triggers the question about the roles of the long cysteine-free peptide stretches typical for plant MTs.

An Unusual Endovascular Therapeutic Approach for a Rare Case of May-Thurner Syndrome

PubMed Central

DaSilva-DeAbreu, Adrian; Masha, Luke; Peerbhai, Shareez

2017-01-01

Patient: Male, 69 Final Diagnosis: May-Thurner syndrome secondary to left common iliac artery aneurysm Symptoms: Left lower extremity edema • left lower extremity erythema • left lower extremity pain Medication: — Clinical Procedure: Endovascular aneurysm repair (EVAR) of the infra-renal abdominal aorta aneurysm and right common iliac artery aneurysm Specialty: Cardiology Objective: Unknown ethiology Background: The etiology of deep venous thrombosis (DVT) may pose a significant diagnostic challenge because truly reversible causes of DVT are rare. In this regard, known pelvic anatomic abnormalities such as aortic and iliac aneurysms should be seriously considered as a complicating factor in patients presenting with acute DVT so as not to miss a potentially curable etiology of May-Thurner syndrome (MTS). Case Report: We report the case of a 69-year-old man with a known abdominal aortic aneurysm and bilateral iliac artery aneurysms who presented with an acute DVT. A computed tomography scan of the abdomen and pelvis showed increased dilation of his aneurysmal disease with new resultant compression of the left iliac vein representing acquired MTS. The patient underwent endovascular aneurysm repair of the infra-renal abdominal aortic aneurysm and right common iliac artery aneurysm with a Gore Excluder endoprosthesis in lieu of venous stenting, with resolution of symptoms. Conclusions: Infra-renal aortic and iliac aneurysms causing MTS are extremely rare, and patients at risk for MTS through these mechanisms do not fit the classical demographics associated with this syndrome. Furthermore, this is the first case described in which MTS was treated by addressing the aneurysm through an endoprosthetic approach instead of venous stenting, which is the conventional intervention for MTS. PMID:28260745

Synthesis of mesoporous TS-1 using a hybrid SiO{sub 2}–TiO{sub 2} xerogel for catalytic oxidative desulfurization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Seung-Tae; Jeong, Kwang-Eun; Jeong, Soon-Yong

2012-12-15

Graphical abstract: Display Omitted Highlights: ► Meso-TS-1 catalyst was synthesized using a SiO{sub 2}–TiO{sub 2} xerogel with an organosilane precursor. ► Hierarchical pore structure was confirmed by characterization of the materials. ► Catalytic activity was tested using oxidative desulfurization of the model sulfur compounds. ► Meso-TS-1 demonstrated significantly improved catalytic activity than TS-1. -- Abstract: Mesoporous TS-1 (M-TS-1) was synthesized using a hybrid SiO{sub 2}–TiO{sub 2} xerogel combined with an organosilane precursor. Prepared samples were characterized by XRD, UV–vis spectroscopy, SEM, and N{sub 2} adsorption–desorption measurement. M-TS-1, prepared in 2 days, showed high crystallinity and the best textural properties amongmore » the samples. The N{sub 2} adsorption–desorption isotherms of M-TS-1 exhibited a hysteresis loop at pressure higher than P/P{sub 0} = 0.4, clearly indicating the existence of mesopores. M-TS-1 has significantly larger mesopore volume (0.48 cm{sup 3}/g) than that of conventional TS-1 (0.07 cm{sup 3}/g), and showed a narrow peak centered at ca. 6.3 nm. In the oxidative desulfurization reaction, M-TS-1 was more active than conventional TS-1 at the same Ti-loading; M-TS-1 produced a dibenzothiophene (DBT) conversion of 96%, whereas conventional TS-1 produced a final DBT conversion of 5.6% after a reaction time of 180 min. Oxidative desulfurization over TS-1 was influenced both by electron density and steric hindrance in the sulfur compounds tested.« less

A Summer Health Program for African-American High School Students in Baltimore, Maryland: Community Partnership for Integrative Health.

PubMed

Pierce, Beverly; Bowden, Brandin; McCullagh, Molly; Diehl, Alica; Chissell, Zachary; Rodriguez, Rebecca; Berman, Brian M; D Adamo, Christopher R

Physical inactivity, poor nutrition, and chronic stress threaten the health of African-American youth in urban environments. Conditions often worsen in summer with diminished access to healthy foods and safe venues for physical activity. A public-private partnership was formed to develop and evaluate an integrative health intervention entitled "Mission Thrive Summer" (MTS). The MTS setting was an urban farm and adjacent school in a low-income community in Baltimore, Maryland. The intervention included farming, nutrition education, cooking, physical activity, yoga, mindfulness, and employment. Mixed-methods outcomes evaluation was conducted. Quantitative measures included accelerometry and self-reported health behaviors, using the Child and Adolescent Mindfulness Measure, Perceived Stress Scale, Physical Activity Questionnaire for Adolescents (PAQA), CDC Youth Risk Behavior Survey, and Block Kids Food Screener (BKFS). Outcomes were compared pre- and post-intervention using paired t-tests. Qualitative evaluation was based on participant and parent interviews. In total, 36 African-American 9th- and 10th-grade students joined MTS (17 in 2013, 26 in 2014, and 7 participating both years). In total, 88% of participants completed MTS. Accelerometry revealed that participants took 7158 steps and burned 544 calories per day during MTS. Participants experienced statistically significant improvements in self-reported physical activity (PAQA) and dietary habits (BKFS). Surveys did not detect changes in stress or mindfulness (P > .05). Qualitative data demonstrated new knowledge and skills, increased self-efficacy, health behavior change, and program enjoyment. MTS was feasible among African-American high school students in Baltimore. Mixed-methods outcomes evaluation provided preliminary evidence of health behavior change during the summer and at follow-up. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Diagnosis of malignancy of adult mediastinal tumors by conventional and transesophageal echocardiography.

PubMed

Zhou, Wei-Wei; Wang, Hong-Wei; Liu, Nan-Nan; Li, Jing-Jing; Yuan, Wei; Zhao, Rui; Xiang, Liang-Bi; Qi, Miao

2015-04-20

Transesophageal echocardiography (TEE) is a well-established method for detecting and diagnosing heart tumors. In contrast, its role in assessing the presence, growth and evidence of malignant tumors originating from mediastinal sites remains unclear. The aim of this study was to compare the diagnostic impact of TEE and transthoracic echocardiography (TTE) for determining the localization, growth and malignancy of adult mediastinal tumors (MTs). In a prospective and investigator-blinded study, we evaluated 144 consecutive patients with MT lesions to assess the diagnostic impact of TEE and TTE for detecting the presence of tumors spreading both inside and outside of the heart and for determining infiltration and invasion using pathological examination results as a reference. All tumor lesions were diagnosed and carefully evaluated by biopsy. Biopsy revealed malignant tumors in 79 patients and benign tumors in 65 patients. When compared to histological findings, TEE predicted malignancy from the presence of tumors spreading both inside and outside of the heart and from infiltration and invasion in 49/79 patients (62.0%). TTE predicted malignancy in only 8/79 patients (10.1%, P < 0.005). TEE visualized tumor lesions in 130 patients (90.3%) while the TTE visualized tumor lesions in 110 patients (76.4%) and was less effective at detecting MT lesions (P < 0.001). TTE and TEE could detect anterior MTs and adequately verified MTs (P > 0.05); TEE detected medium MTs better than TTE (P < 0.001). TEE is effective and superior to TTE for predicting the localization and growth of MTs as well as for accessing evidence of tumor malignancy. TTE and TEE were able to detect anterior MTs; TEE was able to detect medium MT better than TTE.

Diagnosis of Malignancy of Adult Mediastinal Tumors by Conventional and Transesophageal Echocardiography

PubMed Central

Zhou, Wei-Wei; Wang, Hong-Wei; Liu, Nan-Nan; Li, Jing-Jing; Yuan, Wei; Zhao, Rui; Xiang, Liang-Bi; Qi, Miao

2015-01-01

Background: Transesophageal echocardiography (TEE) is a well-established method for detecting and diagnosing heart tumors. In contrast, its role in assessing the presence, growth and evidence of malignant tumors originating from mediastinal sites remains unclear. The aim of this study was to compare the diagnostic impact of TEE and transthoracic echocardiography (TTE) for determining the localization, growth and malignancy of adult mediastinal tumors (MTs). Methods: In a prospective and investigator-blinded study, we evaluated 144 consecutive patients with MT lesions to assess the diagnostic impact of TEE and TTE for detecting the presence of tumors spreading both inside and outside of the heart and for determining infiltration and invasion using pathological examination results as a reference. Results: All tumor lesions were diagnosed and carefully evaluated by biopsy. Biopsy revealed malignant tumors in 79 patients and benign tumors in 65 patients. When compared to histological findings, TEE predicted malignancy from the presence of tumors spreading both inside and outside of the heart and from infiltration and invasion in 49/79 patients (62.0%). TTE predicted malignancy in only 8/79 patients (10.1%, P < 0.005). TEE visualized tumor lesions in 130 patients (90.3%) while the TTE visualized tumor lesions in 110 patients (76.4%) and was less effective at detecting MT lesions (P < 0.001). TTE and TEE could detect anterior MTs and adequately verified MTs (P > 0.05); TEE detected medium MTs better than TTE (P < 0.001). Conclusions: TEE is effective and superior to TTE for predicting the localization and growth of MTs as well as for accessing evidence of tumor malignancy. TTE and TEE were able to detect anterior MTs; TEE was able to detect medium MT better than TTE. PMID:25881598

Poleward force at the kinetochore in metaphase depends on the number of kinetochore microtubules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hays, T.S.; Salmon, E.D.

1990-02-01

To examine the dependence of poleward force at a kinetochore on the number of kinetochore microtubules (kMTs), we altered the normal balance in the number of microtubules at opposing homologous kinetochores in meiosis I grasshopper spermatocytes at metaphase with a focused laser microbeam. Observations were made with light and electron microscopy. Irradiations that partially damaged one homologous kinetochore caused the bivalent chromosome to shift to a new equilibrium position closer to the pole to which the unirradiated kinetochore was tethered; the greater the dose of irradiation, the farther the chromosome moved. The number of kMTs on the irradiated kinetochore decreasedmore » with severity of irradiation, while the number of kMTs on the unirradiated kinetochore remained constant and independent of chromosome-to-pole distance. Assuming a balance of forces on the chromosome at congression equilibrium, our results demonstrate that the net poleward force on a chromosome depends on the number of kMTs and the distance from the pole. In contrast, the velocity of chromosome movement showed little dependence on the number of kMTs. Possible mechanisms which explain the relationship between the poleward force at a kinetochore, the number of kinetochore microtubules, and the lengths of the kinetochore fibers at congression equilibrium include a traction fiber model in which poleward force producers are distributed along the length of the kinetochore fibers, or a kinetochore motor-polar ejection model in which force producers located at or near the kinetochore pull the chromosomes poleward along the kMTs and against an ejection force that is produced by the polar microtubule array and increases in strength toward the pole.« less

Heterologous mitochondrial targeting sequences can deliver functional proteins into mitochondria.

PubMed

Marcus, Dana; Lichtenstein, Michal; Cohen, Natali; Hadad, Rita; Erlich-Hadad, Tal; Greif, Hagar; Lorberboum-Galski, Haya

2016-12-01

Mitochondrial Targeting Sequences (MTSs) are responsible for trafficking nuclear-encoded proteins into mitochondria. Once entering the mitochondria, the MTS is recognized and cleaved off. Some MTSs are long and undergo two-step processing, as in the case of the human frataxin (FXN) protein (80aa), implicated in Friedreich's ataxia (FA). Therefore, we chose the FXN protein to examine whether nuclear-encoded mitochondrial proteins can efficiently be targeted via a heterologous MTS (hMTS) and deliver a functional protein into mitochondria. We examined three hMTSs; that of citrate synthase (cs), lipoamide deydrogenase (LAD) and C6ORF66 (ORF), as classically MTS sequences, known to be removed by one-step processing, to deliver FXN into mitochondria, in the form of fusion proteins. We demonstrate that using hMTSs for delivering FXN results in the production of 4-5-fold larger amounts of the fusion proteins, and at 4-5-fold higher concentrations. Moreover, hMTSs delivered a functional FXN protein into the mitochondria even more efficiently than the native MTSfxn, as evidenced by the rescue of FA patients' cells from oxidative stress; demonstrating a 18%-54% increase in cell survival; and a 13%-33% increase in ATP levels, as compared to the fusion protein carrying the native MTS. One fusion protein with MTScs increased aconitase activity within patients' cells, by 400-fold. The implications form our studies are of vast importance for both basic and translational research of mitochondrial proteins as any mitochondrial protein can be delivered efficiently by an hMTS. Moreover, effective targeting of functional proteins is important for restoration of mitochondrial function and treatment of related disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Physical strain-mediated microtubule reorientation in the epidermis of gravitropically or phototropically stimulated maize coleoptiles.

PubMed

Fischer, K; Schopfer, P

1998-07-01

During gravitropic and phototropic curvature of the maize coleoptile, the cortical microtubules (MTs) adjacent to the outer epidermal cell wall assume opposite orientations at the two sides of the organ. Starting from a uniformly random pattern during straight growth in darkness, the MTs reorientate perpendicularly to the organ axis at the outer (faster growing) side and parallel to the organ axis at the inner (slower growing) side. As similar reorientations can be induced during straight growth by increasing or decreasing the effective auxin concentration, it has been proposed that these reorientations may be used as a diagnostic test for assessing the auxin status of the epidermal cells during tropic curvature. This idea was tested by determining the MT orientations in the coleoptile of intact maize seedlings in which the gravitropic or phototropic curvature was prevented or inversed by an appropriate mechanical counterforce. Forces that just prevented the coleoptile from curving in a gravity or light field prevented reorientations of the MTs. Forces strong enough to overcompensate the tropic stimuli by enforcing curvature in the opposite direction induced reorientations of the MTs opposite to those produced by tropic stimulation. These results show that the MTs at the outer surface of the coleoptile respond to changes in mechanical tissue strain rather than to gravitropic or phototropic stimuli and associated changes at the level of auxin or any other element in the signal transduction chain between perception of tropic stimuli and asymmetric growth response. It is proposed that cortical MTs can act as strain gauges in a positive feed-back regulatory circle utilized for amplification and stabilization of environmentally induced changes in the direction of elongation growth.

Buckling analysis of orthotropic protein microtubules under axial and radial compression based on couple stress theory.

PubMed

Beni, Yaghoub Tadi; Zeverdejani, M Karimi; Mehralian, Fahimeh

2017-10-01

Protein microtubules (MTs) are one of the important intercellular components and have a vital role in the stability and strength of the cells. Due to applied external loads, protein microtubules may be involved buckling phenomenon. Due to impact of protein microtubules in cell reactions, it is important to determine their critical buckling load. Considering nature of protein microtubules, various parameters are effective on microtubules buckling. The small size of microtubules and also lack of uniformity of MTs properties in different directions caused the necessity of accuracy in the analysis of these bio-structure. In fact, microtubules must be considered as a size dependent cylinder, which behave as an orthotropic material. Hence, in the present work using first-order shear deformation model (FSDT), the buckling equations of anisotropic MTs are derived based on new modified couple stress theory (NMCST). After solving the stability equations, the influences of various parameters are measured on the MTs critical buckling load. Copyright © 2017 Elsevier Inc. All rights reserved.

Near-atomic cryo-EM structure of PRC1 bound to the microtubule.

PubMed

Kellogg, Elizabeth H; Howes, Stuart; Ti, Shih-Chieh; Ramírez-Aportela, Erney; Kapoor, Tarun M; Chacón, Pablo; Nogales, Eva

2016-08-23

Proteins that associate with microtubules (MTs) are crucial to generate MT arrays and establish different cellular architectures. One example is PRC1 (protein regulator of cytokinesis 1), which cross-links antiparallel MTs and is essential for the completion of mitosis and cytokinesis. Here we describe a 4-Å-resolution cryo-EM structure of monomeric PRC1 bound to MTs. Residues in the spectrin domain of PRC1 contacting the MT are highly conserved and interact with the same pocket recognized by kinesin. We additionally found that PRC1 promotes MT assembly even in the presence of the MT stabilizer taxol. Interestingly, the angle of the spectrin domain on the MT surface corresponds to the previously observed cross-bridge angle between MTs cross-linked by full-length, dimeric PRC1. This finding, together with molecular dynamic simulations describing the intrinsic flexibility of PRC1, suggests that the MT-spectrin domain interface determines the geometry of the MT arrays cross-linked by PRC1.

Near-atomic cryo-EM structure of PRC1 bound to the microtubule

PubMed Central

Kellogg, Elizabeth H.; Howes, Stuart; Ti, Shih-Chieh; Ramírez-Aportela, Erney; Kapoor, Tarun M.; Chacón, Pablo; Nogales, Eva

2016-01-01

Proteins that associate with microtubules (MTs) are crucial to generate MT arrays and establish different cellular architectures. One example is PRC1 (protein regulator of cytokinesis 1), which cross-links antiparallel MTs and is essential for the completion of mitosis and cytokinesis. Here we describe a 4-Å–resolution cryo-EM structure of monomeric PRC1 bound to MTs. Residues in the spectrin domain of PRC1 contacting the MT are highly conserved and interact with the same pocket recognized by kinesin. We additionally found that PRC1 promotes MT assembly even in the presence of the MT stabilizer taxol. Interestingly, the angle of the spectrin domain on the MT surface corresponds to the previously observed cross-bridge angle between MTs cross-linked by full-length, dimeric PRC1. This finding, together with molecular dynamic simulations describing the intrinsic flexibility of PRC1, suggests that the MT–spectrin domain interface determines the geometry of the MT arrays cross-linked by PRC1. PMID:27493215

Microtubule minus end motors kinesin-14 and dynein drive nuclear congression in parallel pathways

PubMed Central

Scheffler, Kathleen; Minnes, Refael; Fraisier, Vincent; Paoletti, Anne

2015-01-01

Microtubules (MTs) and associated motors play a central role in nuclear migration, which is crucial for diverse biological functions including cell division, polarity, and sexual reproduction. In this paper, we report a dual mechanism underlying nuclear congression during fission yeast karyogamy upon mating of haploid cells. Using microfluidic chambers for long-term imaging, we captured the precise timing of nuclear congression and identified two minus end–directed motors operating in parallel in this process. Kinesin-14 Klp2 associated with MTs may cross-link and slide antiparallel MTs emanating from the two nuclei, whereas dynein accumulating at spindle pole bodies (SPBs) may pull MTs nucleated from the opposite SPB. Klp2-dependent nuclear congression proceeds at constant speed, whereas dynein accumulation results in an increase of nuclear velocity over time. Surprisingly, the light intermediate chain Dli1, but not dynactin, is required for this previously unknown function of dynein. We conclude that efficient nuclear congression depends on the cooperation of two minus end–directed motors. PMID:25869666

Mirror-touch synaesthesia: Difficulties inhibiting the other.

PubMed

Santiesteban, Idalmis; Bird, Geoffrey; Tew, Oliver; Cioffi, Maria Cristina; Banissy, Michael J

2015-10-01

Individuals with mirror touch synaesthesia (MTS) experience touch on their own body when observing others being touched. A recent account proposes that such rare experiences could be linked to impairment in self-other representations. Here we tested participants with MTS on a battery of social cognition tests and found that compared to non-synaesthete controls, the MTS group showed impairment in imitation-inhibition but not in visual perspective taking or theory of mind. Although all of these socio-cognitive abilities rely on the control of self-other representations, they differ as to whether the self, or the other, should be preferentially represented. For imitation-inhibition, representations of the other should be inhibited and self-representations should be enhanced, whereas the opposite is true for visual perspective taking and theory of mind. These findings suggest that MTS is associated with a specific deficit in inhibiting representation of other individuals and shed light on the fractionability of processes underlying typical social cognition. Copyright © 2015 Elsevier Ltd. All rights reserved.

Theory of meiotic spindle assembly

NASA Astrophysics Data System (ADS)

Furthauer, Sebastian; Foster, Peter; Needleman, Daniel; Shelley, Michael

2016-11-01

The meiotic spindle is a biological structure that self assembles from the intracellular medium to separate chromosomes during meiosis. It consists of filamentous microtubule (MT) proteins that interact through the fluid in which they are suspended and via the associated molecules that orchestrate their behavior. We aim to understand how the interplay between fluid medium, MTs, and regulatory proteins allows this material to self-organize into the spindle's highly stereotyped shape. To this end we develop a continuum model that treats the spindle as an active liquid crystal with MT turnover. In this active material, molecular motors, such as dyneins which collect MT minus ends and kinesins which slide MTs past each other, generate active fluid and material stresses. Moreover nucleator proteins that are advected with and transported along MTs control the nucleation and depolymerization of MTs. This theory captures the growth process of meiotic spindles, their shapes, and the essential features of many perturbation experiments. It thus provides a framework to think about the physics of this complex biological suspension.

Copper metallothioneins.

PubMed

Calvo, Jenifer; Jung, Hunmin; Meloni, Gabriele

2017-04-01

Metallothioneins (MTs) are a class of low molecular weight and cysteine-rich metal binding proteins present in all the branches of the tree of life. MTs efficiently bind with high affinity several essential and toxic divalent and monovalent transition metals by forming characteristic polynuclear metal-thiolate clusters within their structure. MTs fulfil multiple biological functions related to their metal binding properties, with essential roles in both Zn(II) and Cu(I) homeostasis as well as metal detoxification. Depending on the organism considered, the primary sequence, and the specific physiological and metabolic status, Cu(I)-bound MT isoforms have been isolated, and their chemistry and biology characterized. Besides the recognized role in the biochemistry of divalent metals, it is becoming evident that unique biological functions in selectively controlling copper levels, its reactivity as well as copper-mediated biochemical processes have evolved in some members of the MT superfamily. Selected examples are reviewed to highlight the peculiar chemical properties and biological functions of copper MTs. © 2016 IUBMB Life, 69(4):236-245, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Observations of white-light flares in NOAA active region 11515: high occurrence rate and relationship with magnetic transients

NASA Astrophysics Data System (ADS)

Song, Y. L.; Tian, H.; Zhang, M.; Ding, M. D.

2018-06-01

Aims: There are two goals in this study. One is to investigate how frequently white-light flares (WLFs) occur in a flare-productive active region (NOAA active region 11515). The other is to investigate the relationship between WLFs and magnetic transients (MTs). Methods: We used the high-cadence (45 s) full-disk continuum filtergrams and line-of-sight magnetograms taken by the Helioseismic and Magnetic Imager (HMI) on board the Solar Dynamics Observatory (SDO) to identify WLFs and MTs, respectively. Images taken by the Atmospheric Imaging Assembly (AIA) on board SDO were also used to show the flare morphology in the upper atmosphere. Results: We found at least 20 WLFs out of a total of 70 flares above C class (28.6%) in NOAA active region 11515 during its passage across the solar disk (E45°-W45°). Each of these WLFs occurred in a small region, with a short duration of about 5 min. The enhancement of the white-light continuum intensity is usually small, with an average enhancement of 8.1%. The 20 WLFs we observed were found along an unusual configuration of the magnetic field that was characterized by a narrow ribbon of negative field. Furthermore, the WLFs were found to be accompanied by MTs, with radical changes in magnetic field strength (or even a sign reversal) observed during the flare. In contrast, there is no obvious signature of MTs in the 50 flares without white-light enhancements. Conclusions: Our results suggest that WLFs occur much more frequently than previously thought, with most WLFs being fairly weak enhancements. This may explain why WLFs are reported rarely. Our observations also suggest that MTs and WLFs are closely related and appear cospatial and cotemporal, when considering HMI data. A greater enhancement of WL emission is often accompanied by a greater change in the line-of-sight component of the unsigned magnetic field. Considering the close relationship between MTs and WLFs, many previously reported flares with MTs may be WLFs. The movie is available at http://www.aanda.org

Heuristic consequences of a load of oxygen in microtubules.

PubMed

Denis, Pierre A

2014-04-01

The current cell oxygen paradigm shows some major gaps that have not yet been resolved. Something seems to be lacking for the comprehensive statement of the oxygen distribution in the cell, especially the low cytoplasmic oxygen level. The entrapment of oxygen in microtubules (MTs) resolves the latter observation, as well as the occurrence of an extensive cytoplasmic foam formation. It leads to a novel oxygen paradigm for cells. During the steady-state treadmilling, the mobile cavity would absorb oxygenated cytoplasm forward, entrap gas nuclei and concentrate them. A fluorescence method is described to confirm the in vitro load of oxygen in MTs during their periodic growths and shrinkages. The latter operating mechanism is called the gas dynamic instability (GDI) of MTs. Several known biosystems could rest on the GDI. (1) The GTP-cap is linked with the gas meniscus encountered in a tube filled with gas. The GTP hydrolysis is linked to the conformational change of the GTPase domain according to the bubble pressure, and to the shaking of protofilaments with gas particles (soliton-like waves). (2) The GDI provides a free energy water pump because water molecules have to escape from MT pores when foam concentrates within the MT. Beside ATP hydrolysis in motor proteins, the GDI provides an additional driving force in intracellular transport of cargo. The water streams flowing from the MT through slits organize themselves as water layers between the cargo and the MT surface, and break ionic bridges. It makes the cargo glide over a water rail. (3) The GDI provides a universal motor for chromosome segregation because the depolymerization of kinetochorial MTs is expected to generate a strong cytoplasmic foam. Chromosomes are sucked up according to the pressure difference (or density difference) applied to opposite sides of the kinetochore, which is in agreement with Archimedes' principle of buoyancy. Non-kinetochorial MTs reabsorb foam during GDI. Last, the mitotic spindle is imagined as a gas recycler. (4) The luminal particles within MTs (called MIPs) are imagined as a foam organizer, the luminal proteins being part of the borders and edges of identical bubbles. (5) Last, volatile anesthetics could destabilize MTs through anesthetic-induced bubble nucleation between protofilaments, and therefore causing shear stress and the opening of MT. The load of oxygen in MTs might provide a major advance in this area of research. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Effects of cadmium and zinc on solar-simulated light-irradiated cells: potential role of zinc-metallothionein in zinc-induced genoprotection.

PubMed

Jourdan, Eric; Emonet-Piccardi, Nathalie; Didier, Christine; Beani, Jean-Claude; Favier, Alain; Richard, Marie-Jeanne

2002-09-15

Zinc is an essential oligoelement for cell growth and cell survival and has been demonstrated to protect cells from oxidative stress induced by UVA or from genotoxic stress due to UVB. In a recent work we demonstrated that the antioxidant role of zinc could be related to its ability to induce metallothioneins (MTs). In this study we identified the mechanism of zinc protection against solar-simulated light (SSL) injury. Cultured human keratinocytes (HaCaT) were used to examine MTs expression and localization in response to solar-simulated radiation. We found translocation to the nucleus, with overexpression of MTs in irradiated cells, a novel observation. The genoprotective effect of zinc was dependent on time and protein synthesis. DNA damage was significantly decreased after 48 h of ZnCl(2) (100 microM) treatment and is inhibited by actinomycin D. ZnCl(2) treatment (100 microM) led to an intense induction, redistribution, and accumulation of MT in the nucleus of irradiated cells. MT expression correlated with the time period of ZnCl(2) treatment. CdCl(2), a potent MT inducer, did not show any genoprotection, although the MTs were expressed in the nucleus. Overall our findings demonstrate that MTs could be a good candidate for explaining the genoprotection mediated by zinc on irradiated cells.

Centrosome centering and decentering by microtubule network rearrangement

PubMed Central

Letort, Gaëlle; Nedelec, Francois; Blanchoin, Laurent; Théry, Manuel

2016-01-01

The centrosome is positioned at the cell center by pushing and pulling forces transmitted by microtubules (MTs). Centrosome decentering is often considered to result from asymmetric, cortical pulling forces exerted in particular by molecular motors on MTs and controlled by external cues affecting the cell cortex locally. Here we used numerical simulations to investigate the possibility that it could equally result from the redistribution of pushing forces due to a reorientation of MTs. We first showed that MT gliding along cell edges and pivoting around the centrosome regulate MT rearrangement and thereby direct the spatial distribution of pushing forces, whereas the number, dynamics, and stiffness of MTs determine the magnitude of these forces. By modulating these parameters, we identified different regimes, involving both pushing and pulling forces, characterized by robust centrosome centering, robust off-centering, or “reactive” positioning. In the last-named conditions, weak asymmetric cues can induce a misbalance of pushing and pulling forces, resulting in an abrupt transition from a centered to an off-centered position. Taken together, these results point to the central role played by the configuration of the MTs on the distribution of pushing forces that position the centrosome. We suggest that asymmetric external cues should not be seen as direct driver of centrosome decentering and cell polarization but instead as inducers of an effective reorganization of the MT network, fostering centrosome motion to the cell periphery. PMID:27440925

Comparative analysis of the tubulin cytoskeleton organization in nodules of Medicago truncatula and Pisum sativum: bacterial release and bacteroid positioning correlate with characteristic microtubule rearrangements.

PubMed

Kitaeva, Anna B; Demchenko, Kirill N; Tikhonovich, Igor A; Timmers, Antonius C J; Tsyganov, Viktor E

2016-04-01

In this study we analyzed and compared the organization of the tubulin cytoskeleton in nodules of Medicago truncatula and Pisum sativum. We combined antibody labeling and green fluorescent protein tagging with laser confocal microscopy to observe microtubules (MTs) in nodules of both wild-type (WT) plants and symbiotic plant mutants blocked at different steps of nodule development. The 3D MT organization of each histological nodule zone in both M. truncatula and P. sativum is correlated to specific developmental processes. Endoplasmic MTs appear to support infection thread growth, infection droplet formation and bacterial release into the host cytoplasm in nodules of both species. No differences in the organization of the MT cytoskeleton between WT and bacterial release mutants were apparent, suggesting both that the phenotype is not linked to a defect in MT organization and that the growth of hypertrophied infection threads is supported by MTs. Strikingly, bacterial release coincides with a change in the organization of cortical MTs from parallel arrays into an irregular, crisscross arrangement. After release, the organization of endoplasmic MTs is linked to the distribution of symbiosomes. The 3D MT organization of each nodule histological zone in M. truncatula and P. sativum was analyzed and linked to specific developmental processes. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

In Vitro Reconstitution of Microtubule Plus End-directed, GTPγS-sensitive Motility of Golgi MembranesV⃞

PubMed Central

Fullerton, Aaron T.; Bau, Mu-Yeh; Conrad, Patricia A.; Bloom, George S.

1998-01-01

Purified Golgi membranes were mixed with cytosol and microtubules (MTs) and observed by video enhanced light microscopy. Initially, the membranes appeared as vesicles that moved along MTs. As time progressed, vesicles formed aggregates from which membrane tubules emerged, traveled along MTs, and eventually generated extensive reticular networks. Membrane motility required ATP, occurred mainly toward MT plus ends, and was inhibited almost completely by the H1 monoclonal antibody to kinesin heavy chain, 5′-adenylylimidodiphosphate, and 100 μM but not 20 μM vanadate. Motility was also blocked by GTPγS or AlF4− but was insensitive to AlCl3, NaF, staurosporin, or okadaic acid. The targets for GTPγS and AlF4− were evidently of cytosolic origin, did not include kinesin or MTs, and were insensitive to several probes for trimeric G proteins. Transport of Golgi membranes along MTs mediated by a kinesin has thus been reconstituted in vitro. The motility is regulated by one or more cytosolic GTPases but not by protein kinases or phosphatases that are inhibited by staurosporin or okadaic acid, respectively. The pertinent GTPases are likely to be small G proteins or possibly dynamin. The in vitro motility may correspond to Golgi-to-ER or Golgi-to-cell surface transport in vivo. PMID:9763438

Relationship between the nonlinear ferroelectric and liquid crystal models for microtubules

NASA Astrophysics Data System (ADS)

Satarić, M. V.; Tuszyński, J. A.

2003-01-01

Microtubules (MTs), which are the main components of the cytoskeleton, are important in a variety of cellular activities, but some physical properties underlying the most important features of their behavior are still lacking satisfactory explanation. One of the essential enigmas regarding the energy balance in MTs is the hydrolysis of the exchangable guanosine 5'-triphosphate bound to the β monomer of the molecule. The energy released in the hydrolysis process amounts to 6.25×10-20 J and has been the subject of many attempts to answer the questions of its utilization. Earlier, we put forward a hypothesis that this energy can cause a local conformational distortion of the dimer. This distortion should have nonlinear character and could lead to the formation of a traveling kink soliton. In this paper we use the formalism of the liquid crystal theory to consider the nonlinear dynamics of MTs. We demonstrate that this new model is formally equivalent to our earlier ferroelectric model which was widely exploited in an attempt to elucidate some important dynamical activities in MTs. We also study the stability of kink solitons against small perturbations and their unusual mutual interactions as well as the interactions with structural inhomogenities of MTs. Our new approach based on liquid crystal properties of microtubules has been recently corroborated by new insights gained from the electrostatic properties of tubulin and microtubules.

Impact of examinees' stereopsis and near visual acuity on laparoscopic virtual reality performance.

PubMed

Hoffmann, Henry; Ruiz-Schirinzi, Rebecca; Goldblum, David; Dell-Kuster, Salome; Oertli, Daniel; Hahnloser, Dieter; Rosenthal, Rachel

2015-10-01

Laparoscopic surgery represents specific challenges, such as the reduction of a three-dimensional anatomic environment to two dimensions. The aim of this study was to investigate the impact of the loss of the third dimension on laparoscopic virtual reality (VR) performance. We compared a group of examinees with impaired stereopsis (group 1, n = 28) to a group with accurate stereopsis (group 2, n = 29). The primary outcome was the difference between the mean total score (MTS) of all tasks taken together and the performance in task 3 (eye-hand coordination), which was a priori considered to be the most dependent on intact stereopsis. The MTS and performance in task 3 tended to be slightly, but not significantly, better in group 2 than in group 1 [MTS: -0.12 (95 % CI -0.32, 0.08; p = 0.234); task 3: -0.09 (95 % CI -0.29, 0.11; p = 0.385)]. The difference of MTS between simulated impaired stereopsis between group 2 (by attaching an eye patch on the adominant eye in the 2nd run) and the first run of group 1 was not significant (MTS: p = 0.981; task 3: p = 0.527). We were unable to demonstrate an impact of impaired examinees' stereopsis on laparoscopic VR performance. Individuals with accurate stereopsis seem to be able to compensate for the loss of the third dimension in laparoscopic VR simulations.

Shark (Scyliorhinus torazame) metallothionein: cDNA cloning, genomic sequence, and expression analysis.

PubMed

Cho, Young Sun; Choi, Buyl Nim; Ha, En-Mi; Kim, Ki Hong; Kim, Sung Koo; Kim, Dong Soo; Nam, Yoon Kwon

2005-01-01

Novel metallothionein (MT) complementary DNA and genomic sequences were isolated from a cartilaginous shark species, Scyliorhinus torazame. The full-length open reading frame (ORF) of shark MT cDNA encoded 68 amino acids with a high cysteine content (29%). The genomic ORF sequence (932 bp) of shark MT isolated by polymerase chain reaction (PCR) comprised 3 exons with 2 interventing introns. Shark MT sequence shared many conserved features with other vertebrate MTs: overall amino acid identities of shark MT ranged from 47% to 57% with fish MTs, and 41% to 62% with mammalian MTs. However, in addition to these conserved characteristics, shark MT sequence exhibited some unique characteristics. It contained 4 extra amino acids (Lys-Ala-Gly-Arg) at the end of the beta-domain, which have not been reported in any other vertebrate MTs. The last amino acid residue at the C-terminus was Ser, which also has not been reported in fish and mammalian MTs. The MT messenger RNA levels in shark liver and kidney, assessed by semiquantitative reverse transcriptase PCR and RNA blot hybridization, were significantly affected by experimental exposures to heavy metals (cadmium, copper, and zinc). Generally, the transcriptional activation of shark MT gene was dependent on the dose (0-10 mg/kg body weight for injection and 0-20 microM for immersion) and duration (1-10 days); zinc was a more potent inducer than copper and cadmium.

A Randomized, Double-Blind, Placebo-Controlled, Laboratory Classroom Assessment of Methylphenidate Transdermal System in Children with ADHD

ERIC Educational Resources Information Center

McGough, James J.; Wigal, Sharon B.; Abikoff, Howard; Turnbow, John M.; Posner, Kelly; Moon, Eliot

2006-01-01

Objective: This study evaluates the efficacy, duration of action, and tolerability of methylphenidate transdermal system (MTS) in children with ADHD. Method: Participants were dose optimized over 5 weeks utilizing patch doses of 10, 16, 20, and 27 mg applied in the morning and worn for 9 hours. Following optimization, 80 participants were…

'We didn't know anything, it was a mess!' Emergent structures and the effectiveness of a rescue operation multi-team system.

PubMed

Fleştea, Alina Maria; Fodor, Oana Cătălina; Curşeu, Petru Lucian; Miclea, Mircea

2017-01-01

Multi-team systems (MTS) are used to tackle unpredictable events and to respond effectively to fast-changing environmental contingencies. Their effectiveness is influenced by within as well as between team processes (i.e. communication, coordination) and emergent phenomena (i.e. situational awareness). The present case study explores the way in which the emergent structures and the involvement of bystanders intertwine with the dynamics of processes and emergent states both within and between the component teams. Our findings show that inefficient transition process and the ambiguous leadership generated poor coordination and hindered the development of emergent phenomena within the whole system. Emergent structures and bystanders substituted leadership functions and provided a pool of critical resources for the MTS. Their involvement fostered the emergence of situational awareness and facilitated contingency planning processes. However, bystander involvement impaired the emergence of cross-understandings and interfered with coordination processes between the component teams. Practitioner Summary: Based on a real emergency situation, the present research provides important theoretical and practical insights about the role of bystander involvement in the dynamics of multi-team systems composed to tackle complex tasks and respond to fast changing and unpredictable environmental contingencies.

Microtubules in Plant Cells: Strategies and Methods for Immunofluorescence, Transmission Electron Microscopy and Live Cell Imaging

PubMed Central

Celler, Katherine; Fujita, Miki; Kawamura, Eiko; Ambrose, Chris; Herburger, Klaus; Wasteneys, Geoffrey O.

2016-01-01

Microtubules are required throughout plant development for a wide variety of processes, and different strategies have evolved to visualize and analyze them. This chapter provides specific methods that can be used to analyze microtubule organization and dynamic properties in plant systems and summarizes the advantages and limitations for each technique. We outline basic methods for preparing samples for immunofluorescence labelling, including an enzyme-based permeabilization method, and a freeze-shattering method, which generates microfractures in the cell wall to provide antibodies access to cells in cuticle-laden aerial organs such as leaves. We discuss current options for live cell imaging of MTs with fluorescently tagged proteins (FPs), and provide chemical fixation, high pressure freezing/freeze substitution, and post-fixation staining protocols for preserving MTs for transmission electron microscopy and tomography. PMID:26498784

Fission yeast Alp14 is a dose-dependent plus end–tracking microtubule polymerase

PubMed Central

Al-Bassam, Jawdat; Kim, Hwajin; Flor-Parra, Ignacio; Lal, Neeraj; Velji, Hamida; Chang, Fred

2012-01-01

XMAP215/Dis1 proteins are conserved tubulin-binding TOG-domain proteins that regulate microtubule (MT) plus-end dynamics. Here we show that Alp14, a XMAP215 orthologue in fission yeast, Schizosaccharomyces pombe, has properties of a MT polymerase. In vivo, Alp14 localizes to growing MT plus ends in a manner independent of Mal3 (EB1). alp14-null mutants display short interphase MTs with twofold slower assembly rate and frequent pauses. Alp14 is a homodimer that binds a single tubulin dimer. In vitro, purified Alp14 molecules track growing MT plus ends and accelerate MT assembly threefold. TOG-domain mutants demonstrate that tubulin binding is critical for function and plus end localization. Overexpression of Alp14 or only its TOG domains causes complete MT loss in vivo, and high Alp14 concentration inhibits MT assembly in vitro. These inhibitory effects may arise from Alp14 sequestration of tubulin and effects on the MT. Our studies suggest that Alp14 regulates the polymerization state of tubulin by cycling between a tubulin dimer–bound cytoplasmic state and a MT polymerase state that promotes rapid MT assembly. PMID:22696680

Stimulation of microtubule-based transport by nucleation of microtubules on pigment granules

PubMed Central

Semenova, Irina; Gupta, Dipika; Usui, Takeo; Hayakawa, Ichiro; Cowan, Ann; Rodionov, Vladimir

2017-01-01

Microtubule (MT)-based transport can be regulated through changes in organization of MT transport tracks, but the mechanisms that regulate these changes are poorly understood. In Xenopus melanophores, aggregation of pigment granules in the cell center involves their capture by the tips of MTs growing toward the cell periphery, and granule aggregation signals facilitate capture by increasing the number of growing MT tips. This increase could be explained by stimulation of MT nucleation either on the centrosome or on the aggregate of pigment granules that gradually forms in the cell center. We blocked movement of pigment granules to the cell center and compared the MT-nucleation activity of the centrosome in the same cells in two signaling states. We found that granule aggregation signals did not stimulate MT nucleation on the centrosome but did increase MT nucleation activity of pigment granules. Elevation of MT-nucleation activity correlated with the recruitment to pigment granules of a major component of MT-nucleation templates, γ-tubulin, and was suppressed by γ-tubulin inhibitors. We conclude that generation of new MT transport tracks by concentration of the leading pigment granules provides a positive feedback loop that enhances delivery of trailing granules to the cell center. PMID:28381426

Deep low-frequency earthquake activities during the failed magmatic eruptions of Mts. Iwate and Fuji, Japan

NASA Astrophysics Data System (ADS)

Nakamichi, H.; Hamaguchi, H.; Ukawa, M.; Tanaka, S.; Ueki, S.; Nishimura, T.

2008-12-01

I review deep low-frequency earthquake (DLF) activities during the failed magmatic eruptions of Mts. Iwate and Fuji, Japan. Volcanic unrests at Mts. Iwate and Fuji were observed in 1998-1999 and 2000-2001, respectively. Several hundred DLFs occurred during the unrest at Mt. Iwate; the number of DLFs in a normal year is less than or equal to 10. The DLF activity at Mt. Fuji increased sharply during the period from September 2000 to May 2001. The frequency of DLFs at Mt. Fuji during the DLF swarm was 20 times higher than that during normal activity. The DLFs of Mts. Iwate and Fuji show non-DC source mechanisms and suggest fluid motion at the focal regions. The DLF hypocenters of Mt. Fuji defined an ellipsoid with a diameter of 5 km; their focal depths are 11-16 km. The ellipsoid was centered 3 km northeast of the summit, and its major axis was directed in the northwest-southeast direction. The center of the ellipsoid gradually migrated upward, and 2-3 km in the northwest direction during 1998-2001. The migration of the DLFs reflects the volcanic fluid migration associated with a northwest-southeast-oriented dike beneath Mt. Fuji. The DLFs of Mt. Iwate were located at intermediate depths (5-12 km) beneath the summit and at deep depths (31-37 km) in the regions located 10 km south and 10 km northeast of the summit. In April 1998, the frequency of DLFs increased five days before an increase in the occurrence of shallow volcanic earthquakes at Mt. Iwate. Hypocenter migration of the DLFs at intermediate depths was observed from April 1998 to September 1998. New fumarole activity in the western region of Mt. Iwate commenced in 1999. These observations indicate that DLFs at Mts. Fuji and Iwate have common features in their activities and source mechanisms. But, shallow volcanic activities at these two volcanoes were much different: strong shallow seismic activity and volcano inflations as well as a new formation of fumarolic area were observed at Mt. Iwate, while such shallow activities were not detected at Mt. Fuji. Although it is still unknown what mechanisms control their magma supply systems, we may say that activation of DLF beneath active volcanoes does not always accompany magma intrusions in the shallow volcano edifice.

Oppositional Defiant Disorder in Adults with ADHD

ERIC Educational Resources Information Center

Reimherr, Frederick W.; Marchant, Barrie K.; Olsen, John L.; Wender, Paul H.; Robison, Reid J.

2013-01-01

Objective: Oppositional defiant disorder (ODD) is the most common comorbid condition in childhood ADHD. This trial was prospectively designed to explore ODD symptoms in ADHD adults. Method: A total of 86 patients in this placebo-controlled, double-blind trial of methylphenidate transdermal system (MTS) were categorized based on the presence of ODD…

Community College Faculty Members' Perceived Multicultural Teaching Competence and Attitudes Regarding Cultural Diversity

ERIC Educational Resources Information Center

Fittz, Mia Web

2015-01-01

This study utilized the Survey of Community College Faculty (SCCF), a combined survey of the Multicultural Teaching Scale (MTS) and Pluralism and Diversity Attitude Assessment (PADAA) that framed the research. The MTS assessed self-reported cultural competencies categorized into five dimensions: (a) Content Integration, (b) Knowledge Construction,…

Teaching Ambition: A Case Study of High School Music Students

ERIC Educational Resources Information Center

Draves, Tami

2012-01-01

Music teacher socialisation (MTS) has received increased attention in music education research, but few researchers have explored MTS with students during their primary socialisation, or pre-college, years. The purpose of this qualitative multiple case study was to examine the perspectives of high school music students who plan to pursue a music…

The Model Technology School: Toward Literacy through Technology. Technology.

ERIC Educational Resources Information Center

Schneider, Raymond J.

This paper describes one Florida school's experience with the Model Technology Schools (MTS) pilot program, and proposes a poetry curriculum for K-12 education that incorporates laserdisc technology for student presentations. Webster Elementary School in St. Augustine was the smallest of five schools chosen for the MTS program to demonstrate the…

Over-Selectivity as a Learned Response

ERIC Educational Resources Information Center

Reed, Phil; Petrina, Neysa; McHugh, Louise

2011-01-01

An experiment investigated the effects of different levels of task complexity in pre-training on over-selectivity in a subsequent match-to-sample (MTS) task. Twenty human participants were divided into two groups; exposed either to a 3-element, or a 9-element, compound stimulus as a sample during MTS training. After the completion of training,…

The potential roles of metallothionein as a therapeutic target for cerebral ischemia and retinal diseases.

PubMed

Ito, Yasushi; Tanaka, Hirotaka; Hara, Hideaki

2013-01-01

Methallothionein (MT) is a low molecular weight cysteine rich metalloprotein. In mammals, there are four isoforms (MT-1, -2, -3, and -4) and they have multiple roles, such as the detoxification of heavy metals, regulating essential metal homeostasis, and protecting against oxidative stress. Recently, accumulating studies have suggested that MTs (especially MT-1, -2, and -3) are an important neuroprotective substance for cerebral ischemia and retinal diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP), that are characterized by a progressive retinal degeneration. Oxidative stress and/or zinc toxicity has been implicated as part of the common pathway in these diseases. Studying the expression patterns and functions of MTs may broaden our understanding of the endogenous molecular responses that these diseases trigger, and may help us to develop new therapeutic strategies to treat them. However, the precise roles of MTs within the brain and retina are not fully understood in terms of neuropathological conditions. In this review, we discuss the recent findings focusing on MTs' functions following cerebral ischemia, AMD, and RP.

Microtubule minus end motors kinesin-14 and dynein drive nuclear congression in parallel pathways.

PubMed

Scheffler, Kathleen; Minnes, Refael; Fraisier, Vincent; Paoletti, Anne; Tran, Phong T

2015-04-13

Microtubules (MTs) and associated motors play a central role in nuclear migration, which is crucial for diverse biological functions including cell division, polarity, and sexual reproduction. In this paper, we report a dual mechanism underlying nuclear congression during fission yeast karyogamy upon mating of haploid cells. Using microfluidic chambers for long-term imaging, we captured the precise timing of nuclear congression and identified two minus end-directed motors operating in parallel in this process. Kinesin-14 Klp2 associated with MTs may cross-link and slide antiparallel MTs emanating from the two nuclei, whereas dynein accumulating at spindle pole bodies (SPBs) may pull MTs nucleated from the opposite SPB. Klp2-dependent nuclear congression proceeds at constant speed, whereas dynein accumulation results in an increase of nuclear velocity over time. Surprisingly, the light intermediate chain Dli1, but not dynactin, is required for this previously unknown function of dynein. We conclude that efficient nuclear congression depends on the cooperation of two minus end-directed motors. © 2015 Scheffler et al.

Reactional mechanisms of the chemical vapour deposition of SiC-based ceramics from {CH3SiCl3}/{H2} gas precursor

NASA Astrophysics Data System (ADS)

Loumagne, F.; Langlais, F.; Naslain, R.

1995-10-01

The kinetics of SiC-based ceramics deposition from CH 3SiCl 3{( MTS) }/{H2} gas precursor has been investigated over a range of reduced pressure and low temperature, where kinetics are controlled by chemical reactions. Overall kinetic laws have been determined from the measurement of the apparent activation energy and the influence of MTS, H 2, CH 4 and HCl. The kinetics of SiC deposition highly depends on both the dilution ratio α = {P H2}/{P MTS} and the total pressure. For 3 ≤ α ≤ 10 and T = 825°C, the reaction order with respect to MTS equals 2. At T = 925°C, it becomes nil in the low pressure range and 1 for P ≥ 10 kPa, whereas at 825 and 925°C, PH 2 has no influence on the growth rate. The apparent reaction orders are explained on the basis of a Langmuir-Hinshelwood model. The limiting step is evidenced as being HCl elimination by both SiCl and CH bonds breaking.

Structural analysis of the role of TPX2 in branching microtubule nucleation

PubMed Central

Thawani, Akanksha

2017-01-01

The mitotic spindle consists of microtubules (MTs), which are nucleated by the γ-tubulin ring complex (γ-TuRC). How the γ-TuRC gets activated at the right time and location remains elusive. Recently, it was uncovered that MTs nucleate from preexisting MTs within the mitotic spindle, which requires the protein TPX2, but the mechanism basis for TPX2 action is unknown. Here, we investigate the role of TPX2 in branching MT nucleation. We establish the domain organization of Xenopus laevis TPX2 and define the minimal TPX2 version that stimulates branching MT nucleation, which we find is unrelated to TPX2’s ability to nucleate MTs in vitro. Several domains of TPX2 contribute to its MT-binding and bundling activities. However, the property necessary for TPX2 to induce branching MT nucleation is contained within newly identified γ-TuRC nucleation activator motifs. Separation-of-function mutations leave the binding of TPX2 to γ-TuRC intact, whereas branching MT nucleation is abolished, suggesting that TPX2 may activate γ-TuRC to promote branching MT nucleation. PMID:28264915

Isolation and functional effects of monoclonal antibodies binding to thymidylate synthase.

PubMed

Jastreboff, M M; Todd, M B; Malech, H L; Bertino, J R

1985-01-29

Monoclonal antibodies against electrophoretically pure thymidylate synthase from HeLa cells have been produced. Antibodies (M-TS-4 and M-TS-9) from hybridoma clones were shown by enzyme-linked immunoassay to recognize thymidylate synthase from a variety of human cell lines, but they did not bind to thymidylate synthase from mouse cell lines. The strongest binding of antibodies was observed to enzyme from HeLa cells. These two monoclonal antibodies bind simultaneously to different antigenic sites on thymidylate synthase purified from HeLa cells, as reflected by a high additivity index and results of cross-linked radioimmunoassay. Both monoclonal antibodies inhibit the activity of thymidylate synthase from human cell lines. The strongest inhibition was observed with thymidylate synthase from HeLa cells. Monoclonal antibody M-TS-9 (IgM subclass) decreased the rate of binding of [3H]FdUMP to thymidylate synthase in the presence of 5,10-methylenetetrahydrofolate while M-TS-4 (IgG1) did not change the rate of ternary complex formation. These data indicate that the antibodies recognize different epitopes on the enzyme molecule.

Dynein-mediated pulling forces drive rapid mitotic spindle elongation in Ustilago maydis

PubMed Central

Fink, Gero; Schuchardt, Isabel; Colombelli, Julien; Stelzer, Ernst; Steinberg, Gero

2006-01-01

Spindle elongation segregates chromosomes and occurs in anaphase, an essential step in mitosis. Dynein-mediated pulling forces position the spindle, but their role in anaphase is a matter of debate. Here, we demonstrate that dynein is responsible for rapid spindle elongation in the model fungus Ustilago maydis. We show that initial slow elongation is supported by kinesin-5, which is located in the spindle mid-zone. When the spindle reaches ∼2 μm in length, the elongation rate increases four-fold. This coincides with the appearance of long and less-dynamic microtubules (MTs) at each pole that accumulate dynein at their tips. Laser-mediated nanosurgery revealed that these MTs exert pulling forces in control cells, but not in dynein mutants. In addition, dynein mutants undergo initial slow anaphase, but fail to establish less-dynamic MTs and do not perform rapid spindle elongation, suggesting that dynein drives anaphase B. This is most likely mediated by cortical sliding of astral MTs along stationary dynein, which is off-loaded from the MT plus-end to the cortex. PMID:17024185

Identifying Issues and Concerns with the Use of Interval-Based Systems in Single Case Research Using a Pilot Simulation Study

ERIC Educational Resources Information Center

Ledford, Jennifer R.; Ayres, Kevin M.; Lane, Justin D.; Lam, Man Fung

2015-01-01

Momentary time sampling (MTS), whole interval recording (WIR), and partial interval recording (PIR) are commonly used in applied research. We discuss potential difficulties with analyzing data when these systems are used and present results from a pilot simulation study designed to determine the extent to which these issues are likely to be…

Rapid Intradermal Delivery of Liquid Formulations Using a Hollow Microstructured Array

PubMed Central

Burton, Scott A.; Ng, Chin-Yee; Simmers, Ryan; Moeckly, Craig; Brandwein, David; Gilbert, Tom; Johnson, Nathan; Brown, Ken; Alston, Tesha; Prochnow, Gayatri; Siebenaler, Kris

2010-01-01

ABSTRACT Purpose The purpose of this work is to demonstrate rapid intradermal delivery of up to 1.5 mL of formulation using a hollow microneedle delivery device designed for self-application. Methods 3M’s hollow Microstructured Transdermal System (hMTS) was applied to domestic swine to demonstrate delivery of a variety of formulations including small molecule salts and proteins. Blood samples were collected after delivery and analyzed via HPLC or ELISA to provide a PK profile for the delivered drug. Site evaluations were conducted post delivery to determine skin tolerability. Results Up to 1.5 mL of formulation was infused into swine at a max rate of approximately 0.25 mL/min. A red blotch, the size of the hMTS array, was observed immediately after patch removal, but had faded so as to be almost indistinguishable 10 min post-patch removal. One-mL deliveries of commercial formulations of naloxone hydrochloride and human growth hormone and a formulation of equine anti-tetanus toxin were completed in swine. With few notable differences, the resulting PK profiles were similar to those achieved following subcutaneous injection of these formulations. Conclusions 3M’s hMTS can provide rapid, intradermal delivery of 300–1,500 µL of liquid formulations of small molecules salts and proteins, compounds not typically compatible with passive transdermal delivery. PMID:20582455

Kinesin-5–dependent Poleward Flux and Spindle Length Control in Drosophila Embryo Mitosis

PubMed Central

Brust-Mascher, Ingrid; Sommi, Patrizia; Cheerambathur, Dhanya K.

2009-01-01

We used antibody microinjection and genetic manipulations to dissect the various roles of the homotetrameric kinesin-5, KLP61F, in astral, centrosome-controlled Drosophila embryo spindles and to test the hypothesis that it slides apart interpolar (ip) microtubules (MT), thereby controlling poleward flux and spindle length. In wild-type and Ncd null mutant embryos, anti-KLP61F dissociated the motor from spindles, producing a spatial gradient in the KLP61F content of different spindles, which was visible in KLP61F-GFP transgenic embryos. The resulting mitotic defects, supported by gene dosage experiments and time-lapse microscopy of living klp61f mutants, reveal that, after NEB, KLP61F drives persistent MT bundling and the outward sliding of antiparallel MTs, thereby contributing to several processes that all appear insensitive to cortical disruption. KLP61F activity contributes to the poleward flux of both ipMTs and kinetochore MTs and to the length of the metaphase spindle. KLP61F activity maintains the prometaphase spindle by antagonizing Ncd and another unknown force-generator and drives anaphase B, although the rate of spindle elongation is relatively insensitive to the motor's concentration. Finally, KLP61F activity contributes to normal chromosome congression, kinetochore spacing, and anaphase A rates. Thus, a KLP61F-driven sliding filament mechanism contributes to multiple aspects of mitosis in this system. PMID:19158379

Multidrug resistance characterization in multicellular tumour spheroids from two human lung cancer cell lines.

PubMed

Barrera-Rodríguez, Raúl; Fuentes, Jorge Morales

2015-01-01

Most of the knowledge about the mechanisms of multidrug resistance in lung cancer has been achieved through the use of cell lines isolated from tumours cultivated either in suspensions of isolated cells or in monolayers and following exposition to different cytostatic agents. However, tumour cell lines growing as multicellular tumour spheroids (MTS) frequently develop multicellular resistance in a drug-independent form. The aim of this study was to characterize the phenotypic and functional differences between two human NSCLC cell lines (INER-37 and INER-51) grown as traditional monolayer cultures versus as MTS. After 72 hours treatment with anticancer drugs, chemosensitivity in monolayers and tumour spheroids cultures was assessed using MTT assay. Reverse transcription-polymerase chain reaction was employed to detect the mRNAs of multidrug resistance-related genes. The expression of P-gp was analyzed by immunohistochemical staining and cell cycle profiles were analyzed using FACS. The results indicate that when grown as MTS each lung cancer cell line had different morphologies as well as and abrogation of cell proliferation with decrease of the G2/M phase. Also, MTS acquired multicellular resistance to several chemotherapeutic agents in only a few days of culture which were accomplished by significant changes in the expression of MDR-related genes. Overall, the MTS culture changed the cellular response to drugs nevertheless each of the cell lines studied seems to implement different mechanisms to acquire multicellular resistance.

Microtube strip heat exchanger

NASA Astrophysics Data System (ADS)

Doty, F. D.

1990-12-01

Doty Scientific (DSI) believes their microtube-strip heat exchanger will contribute significantly to the following: (1) the closed Brayton cycles being pursued at MIT, NASA, and elsewhere; (2) reverse Brayton cycle cryocoolers, currently being investigated by NASA for space missions, being applied to MRI superconducting magnets; and (3) high-efficiency cryogenic gas separation schemes for CO2 removal from exhaust stacks. The goal of this current study is to show the potential for substantial progress in high-effectiveness, low-cost, gas-to-gas heat exchangers for diverse applications at temperatures from below 100 K to above 1000 K. To date, the highest effectiveness measured is about 98 percent and relative pressure drops below 0.1 percent with a specific conductance of about 45 W/kgK are reported. During the pre-award period DSI built and tested a 3-module heat exchanger bank using 103-tube microtube strip (MTS) modules. To add to their analytical capabilities, DSI has acquired computational fluid dynamics (CFD) software. This report describes the pre-award work and the status of the ten tasks of the current project, which are: analyze flow distribution and thermal stresses within individual modules; design a heat exchanger bank of ten modules with 400 microtube per module; obtain production quality tubestrip die and AISI 304 tubestrips; obtain production quality microtubing; construct revised MTS heat exchanger; construct dies and fixtures for prototype heat exchanger; construct 100 MTS modules; assemble 8 to 10 prototype MTS heat exchangers; test prototype MTS heat exchanger; and verify test through independent means.

Monolayer to MTS: using SEM, HIM, TEM and SERS to compare morphology, nanosensor uptake and redox potential in MCF7 cells

NASA Astrophysics Data System (ADS)

Jamieson, L. E.; Bell, A. P.; Harrison, D. J.; Campbell, C. J.

2015-06-01

Cellular redox potential is important for the control and regulation of a vast number of processes occurring in cells. When the fine redox potential balance within cells is disturbed it can have serious consequences such as the initiation or progression of disease. It is thought that a redox gradient develops in cancer tumours where the peripheral regions are well oxygenated and internal regions, further from vascular blood supply, become starved of oxygen and hypoxic. This makes treatment of these areas more challenging as, for example, radiotherapy relies on the presence of oxygen. Currently techniques for quantitative analysis of redox gradients are limited. Surface enhanced Raman scattering (SERS) nanosensors (NS) have been used to detect redox potential in a quantitative manner in monolayer cultured cells with many advantages over other techniques. This technique has considerable potential for use in multicellular tumour spheroids (MTS) - a three dimensional (3D) cell model which better mimics the tumour environment and gradients that develop. MTS are a more realistic model of the in vivo cellular morphology and environment and are becoming an increasingly popular in vitro model, replacing traditional monolayer culture. Imaging techniques such as transmission electron microscopy (TEM), scanning electron microscopy (SEM) and helium ion microscopy (HIM) were used to investigate differences in morphology and NS uptake in monolayer culture compared to MTS. After confirming NS uptake, the first SERS measurements revealing quantitative information on redox potential in MTS were performed.

Metals and metallothioneins in Morelet's crocodile (Crocodylus moreletii) from a transboundary river between Mexico and Belize.

PubMed

Buenfil-Rojas, A M; Álvarez-Legorreta, T; Cedeño-Vázquez, J R

2015-02-01

The aim of this study was to determine concentrations of heavy metals (cadmium [Cd] and mercury [Hg]) and metallothioneins (MTs) in blood plasma and caudal scutes of Morelet's crocodile (Crocodylus moreletii) from Rio Hondo, a river and natural border between Mexico and Belize. Three transects of the river (approximately 20 km each) were surveyed in September 2012 and April 2013, and samples were collected from 24 crocodiles from these areas. In blood plasma, Cd (7.6 ± 9.6 ng/ml) was detected in 69 % of samples (n = 9); Hg (12.2 ± 9.2 ng/ml) was detected in 46 % of samples (n = 6); and MTs (10,900 ± 9,400 ng/ml) were detected in 92 % of samples (n = 12). In caudal scutes samples, Cd (31.7 ± 39.4 ng/g) was detected in 84 % of samples (n = 12) and Hg (374.1 ± 429.4 ng/g) in 83 % of samples (n = 20). No MTs were detected in caudal scutes. Hg concentrations in scutes from the Rio Hondo were 2- to 5-fold greater than those previously reported in scutes from other localities in northern Belize. In blood plasma, a significant positive relationship between Hg and body size was observed. Mean concentrations of Cd and MTs in size classes suggest that MTs may be related to Cd exposure. This is the first report of MT presence in crocodile blood.

A refined reaction-diffusion model of tau-microtubule dynamics and its application in FDAP analysis.

PubMed

Igaev, Maxim; Janning, Dennis; Sündermann, Frederik; Niewidok, Benedikt; Brandt, Roland; Junge, Wolfgang

2014-12-02

Fluorescence decay after photoactivation (FDAP) and fluorescence recovery after photobleaching (FRAP) are well established approaches for studying the interaction of the microtubule (MT)-associated protein tau with MTs in neuronal cells. Previous interpretations of FDAP/FRAP data have revealed dwell times of tau on MTs in the range of several seconds. However, this is difficult to reconcile with a dwell time recently measured by single-molecule analysis in neuronal processes that was shorter by two orders of magnitude. Questioning the validity of previously used phenomenological interpretations of FDAP/FRAP data, we have generalized the standard two-state reaction-diffusion equations by 1), accounting for the parallel and discrete arrangement of MTs in cell processes (i.e., homogeneous versus heterogeneous distribution of tau-binding sites); and 2), explicitly considering both active (diffusion upon MTs) and passive (piggybacking upon MTs at rates of slow axonal transport) motion of bound tau. For some idealized cases, analytical solutions were derived. By comparing them with the full numerical solution and Monte Carlo simulations, the respective validity domains were mapped. Interpretation of our FDAP data (from processes of neuronally differentiated PC12 cells) in light of the heterogeneous formalism yielded independent estimates for the association (∼2 ms) and dwell (∼100 ms) times of tau to/on a single MT rather than in an MT array. The dwell time was shorter by orders of magnitude than that in a previous report where a homogeneous topology of MTs was assumed. We found that the diffusion of bound tau was negligible in vivo, in contrast to an earlier report that tau diffuses along the MT lattice in vitro. Methodologically, our results demonstrate that the heterogeneity of binding sites cannot be ignored when dealing with reaction-diffusion of cytoskeleton-associated proteins. Physiologically, the results reveal the behavior of tau in cellular processes, which is noticeably different from that in vitro. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

MSH-2 and MLH-1 Protein Expression in Muir Torre Syndrome-Related and Sporadic Sebaceous Neoplasms

PubMed Central

Morales-Burgos, Adisbeth; Sánchez, Jorge L.; Figueroa, Luz D.; De Jesús-Monge, Wilfredo E.; Cruz-Correa, Marcia R.; González-Keelan, Carmen; Nazario, Cruz María

2009-01-01

Background Muir-Torre Syndrome (MTS) is a rare autosomal-dominant disorder characterized by the predisposition to both sebaceous neoplasm and internal malignancies. MTS-associated sebaceous neoplasms reveal mutations in DNA mismatch repair (MMR) genes and microsatellite instability. A significant part of MTS patients represents a phenotypic variant, the hereditary nonpolyposis colorectal cancer (HNPCC). A strong correlation between microsatellite instability and immunostaining has been demonstrated. The early recognition of sebaceous neoplasm as part of MTS, and their differentiation from sporadic sebaceous neoplasm may have an important application in a clinical setting. The absence of MLH-1 or MSH-2 expression by immunostaining identifies tumors with mismatch repair deficiency. Objectives Our aim is to determine whether an immunohistochemical approach, targeting DNA repair proteins MSH-2 and MLH-1 in MTS-related sebaceous neoplasm and their sporadic counterparts, can be used for their identification. Methods We examined 15 sebaceous neoplasms (including 6 internal malignancy- associated sebaceous neoplasms and 8 sporadic sebaceous neoplasms) from 11 patients for the expression of MSH-2 and MLH-1 by immunohistochemistry. Results Four of 5 internal malignancy-associated sebaceous neoplasms showed loss of expression of MSH-2 or MLH-1. Correlation of the immunostaining pattern of the sebaceous neoplasms and the patients’ positive history of colon carcinoma was 80%. Seven of 8 sporadic sebaceous neoplasms showed a positive expression of MSH-2 and MLH-1. The prevalence for loss of expression of MMR proteins in sebaceous neoplasms was 38.5%. MMR immunostaining had 87.5% specificity and 80% sensitivity. Limitations This study is limited by a small sample size, and by bias selection due to the use of non nationwide data-base as the resource of cases. Conclusions Our findings demonstrate that immunohistochemical testing for internal malignancy-associated sebaceous neoplasms is a practical approach to confirm a suspected inherited MMR gene defect, and an accurate method to distinguish between sporadic and MTS-associated sebaceous lesions. PMID:19069357

Defining when to initiate massive transfusion: a validation study of individual massive transfusion triggers in PROMMTT patients.

PubMed

Callcut, Rachael A; Cotton, Bryan A; Muskat, Peter; Fox, Erin E; Wade, Charles E; Holcomb, John B; Schreiber, Martin A; Rahbar, Mohammad H; Cohen, Mitchell J; Knudson, M Margaret; Brasel, Karen J; Bulger, Eileen M; Del Junco, Deborah J; Myers, John G; Alarcon, Louis H; Robinson, Bryce R H

2013-01-01

Early predictors of massive transfusion (MT) would prevent undertriage of patients likely to require MT. This study validates triggers using the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study. All enrolled patients in PROMMTT were analyzed. The initial emergency department value for each trigger (international normalized ratio [INR], systolic blood pressure, hemoglobin, base deficit, positive result for Focused Assessment for the Sonography of Trauma examination, heart rate, temperature, and penetrating injury mechanism) was compared for patients receiving MT (≥ 10 U of packed red blood cells in 24 hours) versus no MT. Adjusted odds ratios (ORs) for MT are reported using multiple logistic regression. If all triggers were known, a Massive Transfusion Score (MTS) was created, with 1 point assigned for each met trigger. A total of 1,245 patients were prospectively enrolled with 297 receiving an MT. Data were available for all triggers in 66% of the patients including 67% of the MTs (199 of 297). INR was known in 87% (1,081 of 1,245). All triggers except penetrating injury mechanism and heart rate were valid individual predictors of MT, with INR as the most predictive (adjusted OR, 2.5; 95% confidence interval, 1.7-3.7). For those with all triggers known, a positive INR trigger was seen in 49% receiving MT. Patients with an MTS of less than 2 were unlikely to receive MT (negative predictive value, 89%). If any two triggers were present (MTS ≥ 2), sensitivity for predicting MT was 85%. MT was present in 33% with an MTS of 2 greater compared with 11% of those with MTS of less than 2 (OR, 3.9; 95% confidence interval, 2.6-5.8; p < 0.0005). Parameters that can be obtained early in the initial emergency department evaluation are valid predictors for determining the likelihood of MT. Diagnostic, level II.

The use of hippocampal volumetric measurements to improve diagnostic accuracy in pediatric patients with mesial temporal sclerosis.

PubMed

Guzmán Pérez-Carrillo, Gloria J; Owen, Christopher; Schwetye, Katherine E; McFarlane, Spencer; Vellimana, Ananth K; Mar, Soe; Miller-Thomas, Michelle M; Shimony, Joshua S; Smyth, Matthew D; Benzinger, Tammie L S

2017-06-01

OBJECTIVE Many patients with medically intractable epilepsy have mesial temporal sclerosis (MTS), which significantly affects their quality of life. The surgical excision of MTS lesions can result in marked improvement or even complete resolution of the epileptic episodes. Reliable radiological diagnosis of MTS is a clinical challenge. The purpose of this study was to evaluate the utility of volumetric mapping of the hippocampi for the identification of MTS in a case-controlled series of pediatric patients who underwent resection for medically refractory epilepsy, using pathology as a gold standard. METHODS A cohort of 57 pediatric patients who underwent resection for medically intractable epilepsy between 2005 and 2015 was evaluated. On pathological investigation, this group included 24 patients with MTS and 33 patients with non-MTS findings. Retrospective quantitative volumetric measurements of the hippocampi were acquired for 37 of these 57 patients. Two neuroradiologists with more than 10 years of experience who were blinded to the patients' MTS status performed the retrospective review of MR images. To produce the volumetric data, MR scans were parcellated and segmented using the FreeSurfer software suite. Hippocampal regions of interest were compared against an age-weighted local regression curve generated with data from the pediatric normal cohort. Standard deviations and percentiles of specific subjects were calculated. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined for the original clinical read and the expert readers. Receiver operating characteristic curves were generated for the methods of classification to compare results from the readers with the authors' results, and an optimal threshold was determined. From that threshold the sensitivity, specificity, PPV, and NPV were calculated for the volumetric analysis. RESULTS With the use of quantitative volumetry, a sensitivity of 72%, a specificity of 95%, a PPV of 93%, an NPV of 78%, and an area under the curve of 0.84 were obtained using a percentage difference of normalized hippocampal volume. The resulting specificity (95%) and PPV (93%) are superior to the original clinical read and to Reader A and Reader B's findings (range for specificity 74%-86% and for PPV 64%-71%). The sensitivity (72%) and NPV (78%) are comparable to Reader A's findings (73% and 81%, respectively) and are better than those of the original clinical read and of Reader B (sensitivity 45% and 63% and NPV 71% and 70%, respectively). CONCLUSIONS Volumetric measurement of the hippocampi outperforms expert readers in specificity and PPV, and it demonstrates comparable to superior sensitivity and NPV. Volumetric measurements can complement anatomical imaging for the identification of MTS, much like a computer-aided detection tool would. The implementation of this approach in the daily clinical workflow could significantly improve diagnostic accuracy.

Mechanical splitting of microtubules into protofilament bundles by surface-bound kinesin-1

DOE PAGES

VanDelinder, Virginia; Adams, Peter G.; Bachand, George D.

2016-12-21

The fundamental biophysics of gliding microtubule (MT) motility by surface-tethered kinesin-1 motor proteins has been widely studied, as well as applied to capture and transport analytes in bioanalytical microdevices. In these systems, phenomena such as molecular wear and fracture into shorter MTs have been reported due the mechanical forces applied on the MT during transport. In the present work, we show that MTs can be split longitudinally into protofilament bundles (PFBs) by the work performed by surface-bound kinesin motors. We examine the properties of these PFBs using several techniques (e.g., fluorescence microscopy, SEM, AFM), and show that the PFBs continuemore » to be mobile on the surface and display very high curvature compared to MT. Further, higher surface density of kinesin motors and shorter kinesin-surface tethers promote PFB formation, whereas modifying MT with GMPCPP or higher paclitaxel concentrations did not affect PFB formation.« less

Multiple time scale analysis of pressure oscillations in solid rocket motors

NASA Astrophysics Data System (ADS)

Ahmed, Waqas; Maqsood, Adnan; Riaz, Rizwan

2018-03-01

In this study, acoustic pressure oscillations for single and coupled longitudinal acoustic modes in Solid Rocket Motor (SRM) are investigated using Multiple Time Scales (MTS) method. Two independent time scales are introduced. The oscillations occur on fast time scale whereas the amplitude and phase changes on slow time scale. Hopf bifurcation is employed to investigate the properties of the solution. The supercritical bifurcation phenomenon is observed for linearly unstable system. The amplitude of the oscillations result from equal energy gain and loss rates of longitudinal acoustic modes. The effect of linear instability and frequency of longitudinal modes on amplitude and phase of oscillations are determined for both single and coupled modes. For both cases, the maximum amplitude of oscillations decreases with the frequency of acoustic mode and linear instability of SRM. The comparison of analytical MTS results and numerical simulations demonstrate an excellent agreement.

Teamwork situated in multiteam systems: Key lessons learned and future opportunities.

PubMed

Shuffler, Marissa L; Carter, Dorothy R

2018-01-01

Many important contexts requiring teamwork, including health care, space exploration, national defense, and scientific discovery, present important challenges that cannot be addressed by a single team working independently. Instead, the complex goals these contexts present often require effectively coordinated efforts of multiple specialized teams working together as a multiteam system (MTS). For almost 2 decades, researchers have endeavored to understand the novelties and nuances for teamwork and collaboration that ensue when teams operate together as "component teams" in these interdependent systems. In this special issue on the settings of teamwork, we aim to synthesize what is known thus far regarding teamwork situated in MTS contexts and offer new directions and considerations for developing, maintaining, and sustaining effective collaboration in MTSs. Our review of extant research on MTSs reveals 7 key lessons learned regarding teamwork situated in MTSs, but also reveals that much is left to learn about the science and practice of ensuring effective multiteam functioning. We elaborate these lessons and delineate 4 major opportunities for advancing the science of MTSs as a critical embedding context for collaboration and teamwork, now and in the future. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

A Further Assessment of Momentary Time-Sampling across Extended Interval Lengths

ERIC Educational Resources Information Center

Alvero, Alicia M.; Rappaport, Eva; Taylor, Matthew A.

2011-01-01

The current study compared the estimation of momentary time-sampling (MTS) to actual safety performance of three ergonomic responses: back, shoulder, and feet. Actual safety performance was established for the five participants by measuring the target responses with a continuous procedure. MTS 90, 105, 120, 135, 150, 165, 180, 195, 210, 240, and…

A Comparison of Momentary Time Sampling and Partial-Interval Recording for Assessment of Effects of Social Skills Training

ERIC Educational Resources Information Center

Radley, Keith C.; O'Handley, Roderick D.; Labrot, Zachary C.

2015-01-01

Assessment in social skills training often utilizes procedures such as partial-interval recording (PIR) and momentary time sampling (MTS) to estimate changes in duration in social engagements due to intervention. Although previous research suggests PIR to be more inaccurate than MTS in estimating levels of behavior, treatment analysis decisions…

The Use of Problem-Based Learning Model to Improve Quality Learning Students Morals

ERIC Educational Resources Information Center

Nurzaman

2017-01-01

Model of moral cultivation in MTsN Bangunharja done using three methods, classical cultivation methods, extra-curricular activities in the form of religious activities, scouting, sports, and Islamic art, and habituation of morals. Problem base learning models in MTsN Bangunharja applied using the following steps: find the problem, define the…

Warfighting Concepts to Future Weapon System Designs (WARCON)

DTIC Science & Technology

2003-09-12

34* Software design documents rise to litigation. "* A Material List "Cost information that may support, or may * Final Engineering Process Maps be...document may include design the system as derived from the engineering design, software development, SRD. MTS Technologies, Inc. 26 FOR OFFICIAL USE...document, early in the development phase. It is software engineers produce the vision of important to establish a standard, formal the design effort. As

Targeting N-RAS as a Therapeutic Approach for Melanoma

DTIC Science & Technology

2013-10-01

Labs (Woburn, MA), Sigma-Aldrich (St. Louis, MO) and Fisher Scientific (Pittsburgh, PA), respectively. Z-VAD-FMK was purchased from R&D Systems ...proliferation assays (MTS assay) and caspase assays were performed with CellTiter 96 AQueous Non-Radioactive Cell Proliferation Assay kit and Caspase-Glo 3...7 Assay Systems (Promega [Madison, WI]) according to the manufacturers’ protocols. Briefly, for the assays employing inhibitors, cells were plated

Variations of biomarkers response in mussels Mytilus galloprovincialis to low, moderate and high concentrations of organic chemicals and metals.

PubMed

Perić, Lorena; Nerlović, Vedrana; Žurga, Paula; Žilić, Luka; Ramšak, Andreja

2017-05-01

The changes of acetylcholinesterase activity (AChE), metallothioneins content (MTs), catalase activity (CAT) and lipid peroxidation (LPO) were assessed after 4 days exposure of mussels Mytilus galloprovincialis to a wide range of sublethal concentrations of chlorpyrifos (CHP, 0.03-100 μg/L), benzo(a)pyrene (B(a)P, 0.01-100 μg/L), cadmium (Cd, 0.2-200 μg/L) and copper (Cu, 0.2-100 μg/L). The activity of AChE in the gills decreased after exposure to CHP and Cu, whereas no change of activity was detected after exposure to B(a)P and Cd. Both induction and decrease of MTs content in digestive gland occurred after exposure to CHP and B(a)P, while a marked increase was evident at highest exposure concentrations of Cd. The content of MTs progressively decreased of MTs with increasing concentration of Cu. CAT activity and LPO in the gills did not change after exposure to any of the chemicals. The results demonstrate different response profile in relation to the type of chemical compound, and highlight the potential implications for evaluation of biological effect of contaminants in marine environment. Furthermore, the AChE activity in the gills and MTs content in the digestive gland could be modulated by CHP and Cu at environmentally relevant concentrations indicating the potential risks of short-term transient mussels exposure that may occur due to run-off from land or accidental releases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Induction, regulation, degradation, and biological significance of mammalian metallothioneins.

PubMed

Miles, A T; Hawksworth, G M; Beattie, J H; Rodilla, V

2000-01-01

MTs are small cysteine-rich metal-binding proteins found in many species and, although there are differences between them, it is of note that they have a great deal of sequence and structural homology. Mammalian MTs are 61 or 62 amino acid polypeptides containing 20 conserved cysteine residues that underpin the binding of metals. The existence of MT across species is indicative of its biological demand, while the conservation of cysteines indicates that these are undoubtedly central to the function of this protein. Four MT isoforms have been found so far, MT-1, MT-2, MT-3, and MT-4, but these also have subtypes with 17 MT genes identified in man, of which 10 are known to be functional. Different cells express different MT isoforms with varying levels of expression perhaps as a result of the different function of each isoform. Even different metals induce and bind to MTs to different extents. Over 40 years of research into MT have yielded much information on this protein, but have failed to assign to it a definitive biological role. The fact that multiple MT isoforms exist, and the great variety of substances and agents that act as inducers, further complicates the search for the biological role of MTs. This article reviews the current knowledge on the biochemistry, induction, regulation, and degradation of this protein in mammals, with a particular emphasis on human MTs. It also considers the possible biological roles of this protein, which include participation in cell proliferation and apoptosis, homeostasis of essential metals, cellular free radical scavenging, and metal detoxification.

Investigations of Photovoltaic Ferroelectric-Semiconductor Nonvolatile Memory.

DTIC Science & Technology

1981-03-01

HEWLETT-PACKARD BOX 3310 100 MARKET ST APT 1 3404 EAST HARMONY RD2U ATTN J. M. KIRSCH, MTS ATTN R. SCHAEFER ATTN L. W. JAMES, MTS FULLERTON, CA 92633...RADIO SYS SPERRY UNICORN 1300 S ROGERS 367 ORCHARD STREET 52-21 65 PL AT’rN J. F. PRATHER, MGR CEN ATTN I. A. PAULL, ES ATTN W. BURSTEIN, ENGR

Self-Assembled Superparamagnetic Iron Oxide Nanoclusters for Universal Cell Labeling and MRI

NASA Astrophysics Data System (ADS)

Chen, Shuzhen; Zhang, Jun; Jiang, Shengwei; Lin, Gan; Luo, Bing; Yao, Huan; Lin, Yuchun; He, Chengyong; Liu, Gang; Lin, Zhongning

2016-05-01

Superparamagnetic iron oxide (SPIO) nanoparticles have been widely used in a variety of biomedical applications, especially as contrast agents for magnetic resonance imaging (MRI) and cell labeling. In this study, SPIO nanoparticles were stabilized with amphiphilic low molecular weight polyethylenimine (PEI) in an aqueous phase to form monodispersed nanocomposites with a controlled clustering structure. The iron-based nanoclusters with a size of 115.3 ± 40.23 nm showed excellent performance on cellular uptake and cell labeling in different types of cells, moreover, which could be tracked by MRI with high sensitivity. The SPIO nanoclusters presented negligible cytotoxicity in various types of cells as detected using MTS, LDH, and flow cytometry assays. Significantly, we found that ferritin protein played an essential role in protecting stress from SPIO nanoclusters. Taken together, the self-assembly of SPIO nanoclusters with good magnetic properties provides a safe and efficient method for universal cell labeling with noninvasive MRI monitoring capability.

A PAR-1–dependent orientation gradient of dynamic microtubules directs posterior cargo transport in the Drosophila oocyte

PubMed Central

Parton, Richard M.; Hamilton, Russell S.; Ball, Graeme; Yang, Lei; Cullen, C. Fiona; Lu, Weiping; Ohkura, Hiroyuki

2011-01-01

Cytoskeletal organization is central to establishing cell polarity in various cellular contexts, including during messenger ribonucleic acid sorting in Drosophila melanogaster oocytes by microtubule (MT)-dependent molecular motors. However, MT organization and dynamics remain controversial in the oocyte. In this paper, we use rapid multichannel live-cell imaging with novel image analysis, tracking, and visualization tools to characterize MT polarity and dynamics while imaging posterior cargo transport. We found that all MTs in the oocyte were highly dynamic and were organized with a biased random polarity that increased toward the posterior. This organization originated through MT nucleation at the oocyte nucleus and cortex, except at the posterior end of the oocyte, where PAR-1 suppressed nucleation. Our findings explain the biased random posterior cargo movements in the oocyte that establish the germline and posterior. PMID:21746854

Preparation of BFV Gag antiserum and preliminary study on cellular distribution of BFV.

PubMed

Wang, Jian; Guo, Hong-yan; Jia, Rui; Xu, Xuan; Tan, Juan; Geng, Yun-qi; Qiao, Wen-tao

2010-04-01

Viruses (e.g. Human immunodeficiency virus, Human simplex virus and Prototype foamy virus) are obligate intracellular parasites and therefore depend on the cellular machinery for cellular trafficking. Bovine foamy virus (BFV) is a member of the Spumaretrovirinae subfamily of Retroviruses, however, details of its cellular trafficking remain unknown. In this study, we cloned the BFV gag gene into prokaryotic expression vector pET28a and purified the denaturalized Gag protein. The protein was used to immunize BALB/c mouse to produce antiserum, which could specifically recognize the BFV Gag protein in BFV-infected cells through western blot assay. Additionally, these results demonstrated that both the optimal and suboptimal cleavage of Gag protein occur in BFV-infected cells. Subsequently, the Gag antiserum was used to investigate subcellular localization of BFV. In immunofluorescence microscopy assays, colocalization microtubules (MTs) and assembling viral particles were clearly observed, which implied that BFV may transport along cellular MTs in host cells. Furthermore, MTs-depolymerizing assay indicated MTs were required for the efficient replication of BFV. In conclusion, our study suggests that BFV has evolved the mechanism to hijack the cellular cytoskeleton for its replication.

Dynamic microtubules drive circuit rewiring in the absence of neurite remodeling

PubMed Central

Kurup, Naina; Yan, Dong; Goncharov, Alexandr; Jin, Yishi

2015-01-01

A striking neuronal connectivity change in C. elegans involves the coordinated elimination of existing synapses and formation of synapses at new locations, without altering neuronal morphology. Here, we investigate the tripartite interaction between dynamic microtubules (MTs), kinesin-1, and vesicular cargo during this synapse remodeling. We find that a reduction in the dynamic MT population in motor neuron axons, resulting from genetic interaction between loss of function in the conserved MAPKKK dlk-1 and an α-tubulin mutation, specifically blocks synapse remodeling. Using live imaging and pharmacological modulation of the MT cytoskeleton, we show that dynamic MTs are increased at the onset of remodeling and are critical for new synapse formation. DLK-1 acts during synapse remodeling, and its function involves MT catastrophe factors including kinesin-13/KLP-7 and spastin/SPAS-1. Through a forward genetic screen, we identify gain-of-function mutations in kinesin-1 that can compensate for reduced dynamic MTs to promote synaptic vesicle transport during remodeling. Our data provide in vivo evidence supporting the requirement of dynamic MTs for kinesin-1 dependent axonal transport and shed insight on the role of the MT cytoskeleton in facilitating neural circuit plasticity. PMID:26051896

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xie, Wei; Lei, Wei-Hua; Wang, Ding-Xiong, E-mail: leiwh@hust.edu.cn

Recently, two empirical correlations related to the minimum variability timescale (MTS) of the light curves are discovered in gamma-ray bursts (GRBs). One is the anti-correlation between MTS and Lorentz factor Γ, and the other is the anti-correlation between the MTS and gamma-ray luminosity L {sub γ}. Both of the two correlations might be used to explore the activity of the central engine of GRBs. In this paper, we try to understand these empirical correlations by combining two popular black hole central engine models (namely, the Blandford and Znajek mechanism (BZ) and the neutrino-dominated accretion flow (NDAF)). By taking the MTSmore » as the timescale of viscous instability of the NDAF, we find that these correlations favor the scenario in which the jet is driven by the BZ mechanism.« less

Geographic information systems for mapping the National Exam Result of Junior High School in 2014 at West Java Province

NASA Astrophysics Data System (ADS)

Setiawan Abdullah, Atje; Nurani Ruchjana, Budi; Rejito, Juli; Rosadi, Rudi; Candra Permana, Fahmi

2017-10-01

National Exam level of schooling is implemented by the Ministry of Education and Culture for the development of education in Indonesia. The national examinations are centrally evaluated by the National Education Standards Agency, and the expected implementation of the national exams can describe the successful implementation of education at the district, municipal, provincial, or national level. In this study, we evaluate, analyze, and explore the implementation of the national exam database of the results of the Junior High School in 2014, with the Junior High School (SMP/MTs) as the smallest unit of analysis at the district level. The method used in this study is a data mining approach using the methodology of Knowledge Discovery in Databases (KDD) using descriptive analysis and spatial mapping of national examinations. The results of the classification of the data mining process to national exams of Junior High School in 2014 using data 6,878 SMP/MTs in West Java showed that 81.01 % were at moderate levels. While the results of the spatial mapping for SMP/MTs in West Java can be explained 36,99 % at the unfavorable level. The evaluation results visualization in graphic is done using ArcGIS to provide position information quality of education in municipal, provincial or national level. The results of this study can be used by management to make decision to improve educational services based on the national exam database in West Java. Keywords: KDD, spatial mapping, national exam.

Multiplex Recurrence Networks

NASA Astrophysics Data System (ADS)

Eroglu, Deniz; Marwan, Norbert

2017-04-01

The complex nature of a variety of phenomena in physical, biological, or earth sciences is driven by a large number of degrees of freedom which are strongly interconnected. Although the evolution of such systems is described by multivariate time series (MTS), so far research mostly focuses on analyzing these components one by one. Recurrence based analyses are powerful methods to understand the underlying dynamics of a dynamical system and have been used for many successful applications including examples from earth science, economics, or chemical reactions. The backbone of these techniques is creating the phase space of the system. However, increasing the dimension of a system requires increasing the length of the time series in order get significant and reliable results. This requirement is one of the challenges in many disciplines, in particular in palaeoclimate, thus, it is not easy to create a phase space from measured MTS due to the limited number of available obervations (samples). To overcome this problem, we suggest to create recurrence networks from each component of the system and combine them into a multiplex network structure, the multiplex recurrence network (MRN). We test the MRN by using prototypical mathematical models and demonstrate its use by studying high-dimensional palaeoclimate dynamics derived from pollen data from the Bear Lake (Utah, US). By using the MRN, we can distinguish typical climate transition events, e.g., such between Marine Isotope Stages.

Through tissue imaging of a live breast cancer tumour model using handheld surface enhanced spatially offset resonance Raman spectroscopy (SESORRS).

PubMed

Nicolson, Fay; Jamieson, Lauren E; Mabbott, Samuel; Plakas, Konstantinos; Shand, Neil C; Detty, Michael R; Graham, Duncan; Faulds, Karen

2018-04-21

In order to improve patient survival and reduce the amount of unnecessary and traumatic biopsies, non-invasive detection of cancerous tumours is of imperative and urgent need. Multicellular tumour spheroids (MTS) can be used as an ex vivo cancer tumour model, to model in vivo nanoparticle (NP) uptake by the enhanced permeability and retention (EPR) effect. Surface enhanced spatially offset Raman spectroscopy (SESORS) combines both surface enhanced Raman spectroscopy (SERS) and spatially offset Raman spectroscopy (SORS) to yield enhanced Raman signals at much greater sub-surface levels. By utilizing a reporter that has an electronic transition in resonance with the laser frequency, surface enhanced resonance Raman scattering (SERRS) yields even greater enhancement in Raman signal. Using a handheld SORS spectrometer with back scattering optics, we demonstrate the detection of live breast cancer 3D MTS containing SERRS active NPs through 15 mm of porcine tissue. False color 2D heat intensity maps were used to determine tumour model location. In addition, we demonstrate the tracking of SERRS-active NPs through porcine tissue to depths of up to 25 mm. This unprecedented performance is due to the use of red-shifted chalcogenpyrylium-based Raman reporters to demonstrate the novel technique of surface enhanced spatially offset resonance Raman spectroscopy (SESORRS) for the first time. Our results demonstrate a significant step forward in the ability to detect vibrational fingerprints from a tumour model at depth through tissue. Such an approach offers significant promise for the translation of NPs into clinical applications for non-invasive disease diagnostics based on this new chemical principle of measurement.

Distributed Sensor Systems and Electromechanical Analog Facility

DTIC Science & Technology

1980-01-01

interfaces (parallel I/O, modems , etc.) real time operating systems (perhaps a short survey of what is available in the industry today), data...consists of a LSI-11 microprocessor, 56K bytes of memory, and serial and parallel I/O boards. 2.1.7 Disk controller The standard disk controller...with MTS via the modems connected to the LSI-lls. This pseudodevice cannot be reassigned. OSWIT I/O AND INTERRUPT STRUCTURE 137 OSWIT

Kinetochore Fiber Maturation in PtK1 Cells and Its Implications for the Mechanisms of Chromosome Congression and Anaphase Onset

PubMed Central

McEwen, Bruce F.; Heagle, Amy B.; Cassels, Grisel O.; Buttle, Karolyn F.; Rieder, Conly L.

1997-01-01

Kinetochore microtubules (kMts) are a subset of spindle microtubules that bind directly to the kinetochore to form the kinetochore fiber (K-fiber). The K-fiber in turn interacts with the kinetochore to produce chromosome motion toward the attached spindle pole. We have examined K-fiber maturation in PtK1 cells using same-cell video light microscopy/serial section EM. During congression, the kinetochore moving away from its spindle pole (i.e., the trailing kinetochore) and its leading, poleward moving sister both have variable numbers of kMts, but the trailing kinetochore always has at least twice as many kMts as the leading kinetochore. A comparison of Mt numbers on sister kinetochores of congressing chromosomes with their direction of motion, as well as distance from their associated spindle poles, reveals that the direction of motion is not determined by kMt number or total kMt length. The same result was observed for oscillating metaphase chromosomes. These data demonstrate that the tendency of a kinetochore to move poleward is not positively correlated with the kMt number. At late prometaphase, the average number of Mts on fully congressed kinetochores is 19.7 ± 6.7 (n = 94), at late metaphase 24.3 ± 4.9 (n = 62), and at early anaphase 27.8 ± 6.3 (n = 65). Differences between these distributions are statistically significant. The increased kMt number during early anaphase, relative to late metaphase, reflects the increased kMt stability at anaphase onset. Treatment of late metaphase cells with 1 μM taxol inhibits anaphase onset, but produces the same kMt distribution as in early anaphase: 28.7 ± 7.4 (n = 54). Thus, a full complement of kMts is not sufficient to induce anaphase onset. We also measured the time course for kMt acquisition and determined an initial rate of 1.9 kMts/min. This rate accelerates up to 10-fold during the course of K-fiber maturation, suggesting an increased concentration of Mt plus ends in the vicinity of the kinetochore at late metaphase and/or cooperativity for kMt acquisition. PMID:9199171

The predictive ability of triglycerides and waist (hypertriglyceridemic waist) in assessing metabolic triad change in obese children and adolescents.

PubMed

Hobkirk, James P; King, Roderick F; Gately, Paul; Pemberton, Philip; Smith, Alexander; Barth, Julian H; Harman, Nicola; Davies, Ian; Carroll, Sean

2013-10-01

The metabolic triad [fasting insulin, apolipoprotein B, and low-density lipoporotein (LDL) peak particle density] is characteristic of increased intra-abdominal adipose tissue and insulin resistance and can be predicted by the simple and adoptable screening tool, the hypertriglyceridemic waist. The associations between hypertriglyceridemic waist components [fasting triglycerides (TG) and waist circumference cut-points derived from a child-specific metabolic syndrome definition] with the metabolic triad were examined in obese youth before and after weight loss. A continuous metabolic triad score (MTS) was calculated as a cumulative and standardized residual score of fasting insulin, apolipoprotein B, and LDL peak particle density (z-scores of the metabolic triad variables regressed onto age and sex). The predictive ability of TG and waist in assessing metabolic triad change was undertaken in 75 clinically obese boys and girls, aged 8-18, body mass index (BMI) 34.2±6.4 kg/m(2) before and after weight loss. Fasting TG concentrations (r(2)=0.216, P<0.0001) and waist circumference (r(2)=0.049, P=0.019) were both significant independent predictors of the cumulative MTS, together accounting for 26.5% of its total variance. All cardiometabolic risk factors [except a reduction in high-density lipoprotein cholesterol (HDL-C)] were favorably modified following weight loss. Fasting TG change was the only significant predictor of the MTS change (r(2)=0.177, P<0.0001). Waist circumference was not a significant predictor of MTS change. The reduction in fasting TG concentration (but not waist circumference) was the only significant predictor of MTS change. Fasting TG may be the most important metabolic syndrome component to best characterize the metabolic heterogeneity in obese cohorts and the changes in metabolic risk in clinically obese youth.

Synthetic metabolic bypass for a metabolic toggle switch enhances acetyl-CoA supply for isopropanol production by Escherichia coli.

PubMed

Soma, Yuki; Yamaji, Taiki; Matsuda, Fumio; Hanai, Taizo

2017-05-01

Almost all synthetic pathways for biofuel production are designed to require endogenous metabolites in glycolysis, such as phosphoenolpyruvate, pyruvate, and acetyl-CoA. However, such metabolites are also required for bacterial cell growth. To reduce the metabolic imbalance between cell growth and target chemical production, we previously constructed a metabolic toggle switch (MTS) as a conditional flux redirection tool controlling metabolic flux of TCA cycle toward isopropanol production. This approach succeeded to improve the isopropanol production titer and yield while ensuring sufficient cell growth. However, excess accumulation of pyruvate, the precursor for acetyl-CoA synthesis, was also observed. In this study, for efficient conversation of pyruvate to acetyl-CoA (pyruvate oxidation), we designed a synthetic metabolic bypass composed of poxB and acs with the MTS for acetyl-CoA supply from the excess pyruvate. When this designed bypass was expressed at the appropriate expression level associated with the conditional metabolic flux redirection, pyruvate accumulation was prevented, and the isopropanol production titer and yield were improved. Final isopropanol production titer of strain harboring MTS with the synthetic metabolic bypass improved 4.4-fold compared with strain without metabolic flux regulation, and it was 1.3-fold higher than that of strain harboring the conventional MTS alone. Additionally, glucose consumption was also improved 1.7-fold compared with strain without metabolic flux regulation. On the other hand, introduction of the synthetic metabolic bypass alone showed no improvement in isopropanol production and glucose consumption. These results showed that the improvement in bio-production process caused by synergy between the MTS and the synthetic metabolic bypass. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Trends in HFE Methods and Tools and Their Applicability to Safety Reviews

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Hara, J.M.; Plott, C.; Milanski, J.

2009-09-30

The U.S. Nuclear Regulatory Commission's (NRC) conducts human factors engineering (HFE) safety reviews of applicant submittals for new plants and for changes to existing plants. The reviews include the evaluation of the methods and tools (M&T) used by applicants as part of their HFE program. The technology used to perform HFE activities has been rapidly evolving, resulting in a whole new generation of HFE M&Ts. The objectives of this research were to identify the current trends in HFE methods and tools, determine their applicability to NRC safety reviews, and identify topics for which the NRC may need additional guidance tomore » support the NRC's safety reviews. We conducted a survey that identified over 100 new HFE M&Ts. The M&Ts were assessed to identify general trends. Seven trends were identified: Computer Applications for Performing Traditional Analyses, Computer-Aided Design, Integration of HFE Methods and Tools, Rapid Development Engineering, Analysis of Cognitive Tasks, Use of Virtual Environments and Visualizations, and Application of Human Performance Models. We assessed each trend to determine its applicability to the NRC's review by considering (1) whether the nuclear industry is making use of M&Ts for each trend, and (2) whether M&Ts reflecting the trend can be reviewed using the current design review guidance. We concluded that M&T trends that are applicable to the commercial nuclear industry and are expected to impact safety reviews may be considered for review guidance development. Three trends fell into this category: Analysis of Cognitive Tasks, Use of Virtual Environments and Visualizations, and Application of Human Performance Models. The other trends do not need to be addressed at this time.« less

Deletion of the Tail Domain of the Kinesin-5 Cin8 Affects Its Directionality*

PubMed Central

Düselder, André; Fridman, Vladimir; Thiede, Christina; Wiesbaum, Alice; Goldstein, Alina; Klopfenstein, Dieter R.; Zaitseva, Olga; Janson, Marcel E.; Gheber, Larisa; Schmidt, Christoph F.

2015-01-01

The bipolar kinesin-5 motors are one of the major players that govern mitotic spindle dynamics. Their bipolar structure enables them to cross-link and slide apart antiparallel microtubules (MTs) emanating from the opposing spindle poles. The budding yeast kinesin-5 Cin8 was shown to switch from fast minus-end- to slow plus-end-directed motility upon binding between antiparallel MTs. This unexpected finding revealed a new dimension of cellular control of transport, the mechanism of which is unknown. Here we have examined the role of the C-terminal tail domain of Cin8 in regulating directionality. We first constructed a stable dimeric Cin8/kinesin-1 chimera (Cin8Kin), consisting of head and neck linker of Cin8 fused to the stalk of kinesin-1. As a single dimeric motor, Cin8Kin switched frequently between plus and minus directionality along single MTs, demonstrating that the Cin8 head domains are inherently bidirectional, but control over directionality was lost. We next examined the activity of a tetrameric Cin8 lacking only the tail domains (Cin8Δtail). In contrast to wild-type Cin8, the motility of single molecules of Cin8Δtail in high ionic strength was slow and bidirectional, with almost no directionality switches. Cin8Δtail showed only a weak ability to cross-link MTs in vitro. In vivo, Cin8Δtail exhibited bias toward the plus-end of the MTs and was unable to support viability of cells as the sole kinesin-5 motor. We conclude that the tail of Cin8 is not necessary for bidirectional processive motion, but is controlling the switch between plus- and minus-end-directed motility. PMID:25991727

Laser scan of the Grimming Mts. (Austria) with the latest LiDAR VZ-4000 equipment: preliminary results

NASA Astrophysics Data System (ADS)

Bauer, Harald; Hatzenbichler, Georg; Amon, Philipp; Fallah, Mohammad; Tari, Gabor; Grasemann, Bernhard

2013-04-01

As part of a cooperation project between OMV, RIEGL and the University of Vienna the new LiDAR (Light Detection and Ranging) VZ-4000 laser scanner was tested at the Grimming Mts. of the Eastern Alps in Austria. The prominent Grimming Mts. lies in the eastern part of the Dachstein Massif at the southern margin of the Northern Calcareous Alps. The Grimming, with a peak of 2,351 m above sea level, is one of the highest isolated mountains in Europe. Because of its spectacular topography, the Grimming has been used as an important surface reference mark since 1822. From a structural geology standpoint, the Grimming forms a huge antiform made up of dominantly well-bedded Triassic Dachstein Limestone. Because of the relatively well exposed bedrock surfaces above the tree-line and the fairly complex internal structure, the Grimming Mts. provides an ideal target for testing new high resolution laser scan techniques and devices. The maximum distance from the scanning positions on the nearby valley floor to the mountain face was about 4,500 m and the generated point cloud has an average resolution of 25 points per square meter. The purpose of this work was to test the latest version of the high resolution LiDAR laser equipment in a setting which falls beyond the capabilities of most existing LiDAR devices. The results of the pilot study include high-resolution spatial data on bedding planes, fault planes and the thickness variations of individual beds within the Dachstein Limestone. For the first time, the data obtained can be directly used to generate the proper 3D geometry of folds and faults observed on the Grimming Mts. This leads to a modern understanding of this prominent Alpine anticline in terms of structural geology.

Age-related changes of metallothionein 1/2 and metallothionein 3 expression in rat brain.

PubMed

Scudiero, Rosaria; Cigliano, Luisa; Verderame, Mariailaria

2017-01-01

Neurodegeneration is one of the main physiological consequences of aging on brain. Metallothioneins (MTs), low molecular weight, cysteine-rich proteins that bind heavy-metal ions and oxygen-free radicals, are commonly expressed in various tissues of mammals. MTs are involved in the regulation of cell proliferation and protection, and may be engaged in aging. Expression of the ubiquitous MTs (1 and 2) and the brain specific MT3 have been studied in many neurodegenerative disorders. The research results indicate that MTs may play important, although not yet fully known, roles in brain diseases; in addition, data lack the ability to identify the MT isoforms functionally involved. The aim of this study was to analyse the level of gene expression of selected MT isoforms during brain aging. By using real-time PCR analysis, we determined the MT1/2 and MT3 expression profiles in cerebral cortex and hippocampus of adolescent (2months), adult (4 and 8months), and middle-aged (16months) rats. We show that the relative abundance of all types of MT transcripts changes during aging in both hippocampus and cortex; the first effect is a generalized decrease in the content of MTs transcripts from 2- to 8-months-old rats. After passing middle age, at 16months, we observe a huge increase in MT3 transcripts in both cortical and hippocampal areas, while the MT1/2 mRNA content increases slightly, returning to the levels measured in adolescent rats. These findings demonstrate an age-related expression of the MT3 gene. A possible link between the increasing amount of MT3 in brain aging and its different metal-binding behaviour is discussed. Copyright © 2016 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Mesial Temporal Sclerosis: Accuracy of NeuroQuant versus Neuroradiologist.

PubMed

Azab, M; Carone, M; Ying, S H; Yousem, D M

2015-08-01

We sought to compare the accuracy of a volumetric fully automated computer assessment of hippocampal volume asymmetry versus neuroradiologists' interpretations of the temporal lobes for mesial temporal sclerosis. Detecting mesial temporal sclerosis (MTS) is important for the evaluation of patients with temporal lobe epilepsy as it often guides surgical intervention. One feature of MTS is hippocampal volume loss. Electronic medical record and researcher reports of scans of patients with proved mesial temporal sclerosis were compared with volumetric assessment with an FDA-approved software package, NeuroQuant, for detection of mesial temporal sclerosis in 63 patients. The degree of volumetric asymmetry was analyzed to determine the neuroradiologists' threshold for detecting right-left asymmetry in temporal lobe volumes. Thirty-six patients had left-lateralized MTS, 25 had right-lateralized MTS, and 2 had bilateral MTS. The estimated accuracy of the neuroradiologist was 72.6% with a κ statistic of 0.512 (95% CI, 0.315-0.710) [moderate agreement, P < 3 × 10(-6)]), whereas the estimated accuracy of NeuroQuant was 79.4% with a κ statistic of 0.588 (95% CI, 0.388-0.787) [moderate agreement, P < 2 × 10(-6)]). This discrepancy in accuracy was not statistically significant. When at least a 5%-10% volume discrepancy between temporal lobes was present, the neuroradiologists detected it 75%-80% of the time. As a stand-alone fully automated software program that can process temporal lobe volume in 5-10 minutes, NeuroQuant compares favorably with trained neuroradiologists in predicting the side of mesial temporal sclerosis. Neuroradiologists can often detect even small temporal lobe volumetric changes visually. © 2015 by American Journal of Neuroradiology.

Growth and FIB-SEM analyses of C60 microtubes vertically synthesized on porous alumina membranes

NASA Astrophysics Data System (ADS)

Miyazawa, Kun'ichi; Kuriyama, Ryota; Shimomura, Shuichi; Wakahara, Takatsugu; Tachibana, Masaru

2014-02-01

The vertical growth of C60 microtubes (C60MTs) on anodic aluminum oxide (AAO) membranes was investigated. The C60MT size dependence on isopropyl alcohol (IPA) injection rate, into C60-saturated toluene solutions through AAO membranes, was measured. A longitudinal section of the interface between a vertically grown C60MT (V-C60MT) and a membrane was prepared by focused ion beam processing, and observed with scanning electron microscopy. No cracking was observed along the interface, suggesting good bonding. V-C60MTs exhibited spiral growth. V-C60MT planar density, wall thickness and aspect ratio all decreased with increasing IPA injection rate. The relationships among length, inner and outer diameters of V-C60MTs were also investigated by varying IPA injection rate.

The Drosophila Microtubule-Associated Protein Mars Stabilizes Mitotic Spindles by Crosslinking Microtubules through Its N-Terminal Region

PubMed Central

Zhang, Gang; Beati, Hamze; Nilsson, Jakob; Wodarz, Andreas

2013-01-01

Correct segregation of genetic material relies on proper assembly and maintenance of the mitotic spindle. How the highly dynamic microtubules (MTs) are maintained in stable mitotic spindles is a key question to be answered. Motor and non-motor microtubule associated proteins (MAPs) have been reported to stabilize the dynamic spindle through crosslinking adjacent MTs. Mars, a novel MAP, is essential for the early development of Drosophila embryos. Previous studies showed that Mars is required for maintaining an intact mitotic spindle but did not provide a molecular mechanism for this function. Here we show that Mars is able to stabilize the mitotic spindle in vivo. Both in vivo and in vitro data reveal that the N-terminal region of Mars functions in the stabilization of the mitotic spindle by crosslinking adjacent MTs. PMID:23593258

Effects of air pollution and climatic factors on Norway spruce forests in the Orlicke hory Mts. (Czech Republic), 1979-2014

Treesearch

Stanislav Vacek; Iva Hunova; Zdenek Vacek; Pavla Hejcmanova; Vilem Podrazsky; Jan Kral; Tereza Putalova; W. Keith Moser

2015-01-01

The area of the Orlicke hory Mts. has been characterised by decline and disturbances of Norway spruce (Picea abies/L./Karst.) stands since the 1980s. Currently, only three permanent research plots have been preserved from the original sixteen established plots in this region. In the present study, the health status, as indicated by defoliation, mortality, and...

Is the Modified Tardieu Scale in Semi-Standing Position Better Associated with Knee Extension and Hamstring Activity in Terminal Swing than the Supine Tardieu?

ERIC Educational Resources Information Center

Faber, Irene R.; Nienhuis, Bart; Rijs, Nique P. A. M.; Geurts, Alexander C. H.; Duysens, Jacques

2008-01-01

The aim of this study was to investigate whether the modified Tardieu scale (MTS) in a semi-standing position, used for the assessment of hamstrings spasticity, was better associated with knee extension and hamstrings activity in terminal swing than the MTS in a supine position in children with cerebral palsy (CP). Seven children diagnosed with…

Metallothionein Gene Family in the Sea Urchin Paracentrotus lividus: Gene Structure, Differential Expression and Phylogenetic Analysis

PubMed Central

Ragusa, Maria Antonietta; Nicosia, Aldo; Costa, Salvatore; Cuttitta, Angela; Gianguzza, Fabrizio

2017-01-01

Metallothioneins (MT) are small and cysteine-rich proteins that bind metal ions such as zinc, copper, cadmium, and nickel. In order to shed some light on MT gene structure and evolution, we cloned seven Paracentrotus lividus MT genes, comparing them to Echinodermata and Chordata genes. Moreover, we performed a phylogenetic analysis of 32 MTs from different classes of echinoderms and 13 MTs from the most ancient chordates, highlighting the relationships between them. Since MTs have multiple roles in the cells, we performed RT-qPCR and in situ hybridization experiments to understand better MT functions in sea urchin embryos. Results showed that the expression of MTs is regulated throughout development in a cell type-specific manner and in response to various metals. The MT7 transcript is expressed in all tissues, especially in the stomach and in the intestine of the larva, but it is less metal-responsive. In contrast, MT8 is ectodermic and rises only at relatively high metal doses. MT5 and MT6 expression is highly stimulated by metals in the mesenchyme cells. Our results suggest that the P. lividus MT family originated after the speciation events by gene duplications, evolving developmental and environmental sub-functionalization. PMID:28417916

Dual peptide conjugation strategy for improved cellular uptake and mitochondria targeting.

PubMed

Lin, Ran; Zhang, Pengcheng; Cheetham, Andrew G; Walston, Jeremy; Abadir, Peter; Cui, Honggang

2015-01-21

Mitochondria are critical regulators of cellular function and survival. Delivery of therapeutic and diagnostic agents into mitochondria is a challenging task in modern pharmacology because the molecule to be delivered needs to first overcome the cell membrane barrier and then be able to actively target the intracellular organelle. Current strategy of conjugating either a cell penetrating peptide (CPP) or a subcellular targeting sequence to the molecule of interest only has limited success. We report here a dual peptide conjugation strategy to achieve effective delivery of a non-membrane-penetrating dye 5-carboxyfluorescein (5-FAM) into mitochondria through the incorporation of both a mitochondrial targeting sequence (MTS) and a CPP into one conjugated molecule. Notably, circular dichroism studies reveal that the combined use of α-helix and PPII-like secondary structures has an unexpected, synergistic contribution to the internalization of the conjugate. Our results suggest that although the use of positively charged MTS peptide allows for improved targeting of mitochondria, with MTS alone it showed poor cellular uptake. With further covalent linkage of the MTS-5-FAM conjugate to a CPP sequence (R8), the dually conjugated molecule was found to show both improved cellular uptake and effective mitochondria targeting. We believe these results offer important insight into the rational design of peptide conjugates for intracellular delivery.

Decreased necrotizing fasciitis capacity caused by a single nucleotide mutation that alters a multiple gene virulence axis

PubMed Central

Olsen, Randall J.; Sitkiewicz, Izabela; Ayeras, Ara A.; Gonulal, Vedia E.; Cantu, Concepcion; Beres, Stephen B.; Green, Nicole M.; Lei, Benfang; Humbird, Tammy; Greaver, Jamieson; Chang, Ellen; Ragasa, Willie P.; Montgomery, Charles A.; Cartwright, Joiner; McGeer, Allison; Low, Donald E.; Whitney, Adeline R.; Cagle, Philip T.; Blasdel, Terry L.; DeLeo, Frank R.; Musser, James M.

2010-01-01

Single-nucleotide changes are the most common cause of natural genetic variation among members of the same species, but there is remarkably little information bearing on how they alter bacterial virulence. We recently discovered a single-nucleotide mutation in the group A Streptococcus genome that is epidemiologically associated with decreased human necrotizing fasciitis (“flesh-eating disease”). Working from this clinical observation, we find that wild-type mtsR function is required for group A Streptococcus to cause necrotizing fasciitis in mice and nonhuman primates. Expression microarray analysis revealed that mtsR inactivation results in overexpression of PrsA, a chaperonin involved in posttranslational maturation of SpeB, an extracellular cysteine protease. Isogenic mutant strains that overexpress prsA or lack speB had decreased secreted protease activity in vivo and recapitulated the necrotizing fasciitis-negative phenotype of the ΔmtsR mutant strain in mice and monkeys. mtsR inactivation results in increased PrsA expression, which in turn causes decreased SpeB secreted protease activity and reduced necrotizing fasciitis capacity. Thus, a naturally occurring single-nucleotide mutation dramatically alters virulence by dysregulating a multiple gene virulence axis. Our discovery has broad implications for the confluence of population genomics and molecular pathogenesis research. PMID:20080771

Tumor spheroid model for the biologically targeted radiotherapy of neuroblastoma micrometastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walker, K.A.; Mairs, R.; Murray, T.

Neuroblastoma is a pediatric malignancy with a poor prognosis at least partly attributable to an early pattern of dissemination. New approaches to treatment of micrometastases include targeted radiotherapy using radiolabeled antibodies or molecules which are taken up preferentially by tumor cells. Multicellular tumor spheroids (MTS) resemble micrometastases during the avascular phase of their development. A human neuroblastoma cell line (NBl-G) was grown as MTS and incubated briefly with a radiolabeled monoclonal antibody ({sup 131}I-UJ13A) directed against neuroectodermal antigens. Spheroid response was evaluated in terms of regrowth delay or proportion sterilized. A dose-response relationship was demonstrated in terms of {sup 131}Imore » activity or duration of incubation. Control experiments using unlabeled UJ13A, radiolabeled nonspecific antibody (T2.10), radiolabeled human serum albumin, and radiolabeled sodium iodide showed these to be relatively ineffective compared to {sup 131}I-UJ13A. The cell line NBl-G grown as MTS has also been found to preferentially accumulate the radiolabeled catecholamine precursor molecule m-({sup 131}I)iodobenzylguanidine compared to cell lines derived from other tumor types. NBl-G cells grown as MTS provide a promising laboratory model for targeted radiotherapy of neuroblastoma micrometastases using radiolabeled antibodies or m-iodobenzylguanidine.« less

Separation and characterization of metallothionein in the liver of sea turtles by high performance liquid chromatographylinductively coupled plasma-mass spectrometry

NASA Astrophysics Data System (ADS)

Shinsuke, T.; Yasumi, A.; Takashi, K.

2003-05-01

To investigate whether trace metals bind to metallothioneins (MTs) in the hepatocytosol of green turtles (Chelonia mydas) and hawksbill turtles (Eretmochelys imbricata), MT fraction was obtained by ultracentrifugation and gel filtration methods. MTs separated from hepatocytosol were further purified and characterized by high performance liquid chromatography/inductively coupled plasma-mass spectrometry. In addition, the involvement of MTs in the accumulation of trace metals in the liver of sea turtle was examine. Gel filtration analysis showed that significant amounts of Cu, Zn, Ag and Cd were bound to MT in the cytosol of sea turtles, suggesting that such trace metals were primarily detoxified by interaction with MTs in the liver. Elution profiles of these trace metals by anion-exchange chromatography were different between green turtles and hawksbill turtles. These results suggest the presence of multiple isoforms of MT in the liver of both sea turtles; however, constituents of isoforms were different between green and hawksbill turtles. In both species, we observed the elevation of the height of a specific peak in elution profile with an increase in Cu concentration in hepatocytosol. This result suggests the presence of a novel MT isoform related to copper accumulation in the liver of sea turtles.

Efficacy of a Methylphenidate Transdermal System versus t.i.d. Methylphenidate in a Laboratory Setting

ERIC Educational Resources Information Center

Pelham, William E.; Waxmonsky, James G.; Schentag, Jerome; Ballow, Charles H.; Panahon, Carlos J.; Gnagy, Elizabeth M.; Hoffman, Martin T.; Burrows-MacLean, Lisa; Meichenbaum, David L.; Forehand, Gregory L.; Fabiano, Gregory A.; Tresco, Katy E.; Lopez-Williams, Andy; Coles, Erika K.; Gonzalez, Mario A.

2011-01-01

Objective: To test the efficacy and tolerability of the methylphenidate transdermal formulation (MTS) against immediate-release methylphenidate (IR MPH) and placebo in a 12-hr analog classroom setting. Method: A total of nine boys ages 6 to 9 years, medicated with MPH for ADHD, complete a within-subject, double-blind study. For the purpose of the…

MTS-MD of Biomolecules Steered with 3D-RISM-KH Mean Solvation Forces Accelerated with Generalized Solvation Force Extrapolation.

PubMed

Omelyan, Igor; Kovalenko, Andriy

2015-04-14

We developed a generalized solvation force extrapolation (GSFE) approach to speed up multiple time step molecular dynamics (MTS-MD) of biomolecules steered with mean solvation forces obtained from the 3D-RISM-KH molecular theory of solvation (three-dimensional reference interaction site model with the Kovalenko-Hirata closure). GSFE is based on a set of techniques including the non-Eckart-like transformation of coordinate space separately for each solute atom, extension of the force-coordinate pair basis set followed by selection of the best subset, balancing the normal equations by modified least-squares minimization of deviations, and incremental increase of outer time step in motion integration. Mean solvation forces acting on the biomolecule atoms in conformations at successive inner time steps are extrapolated using a relatively small number of best (closest) solute atomic coordinates and corresponding mean solvation forces obtained at previous outer time steps by converging the 3D-RISM-KH integral equations. The MTS-MD evolution steered with GSFE of 3D-RISM-KH mean solvation forces is efficiently stabilized with our optimized isokinetic Nosé-Hoover chain (OIN) thermostat. We validated the hybrid MTS-MD/OIN/GSFE/3D-RISM-KH integrator on solvated organic and biomolecules of different stiffness and complexity: asphaltene dimer in toluene solvent, hydrated alanine dipeptide, miniprotein 1L2Y, and protein G. The GSFE accuracy and the OIN efficiency allowed us to enlarge outer time steps up to huge values of 1-4 ps while accurately reproducing conformational properties. Quasidynamics steered with 3D-RISM-KH mean solvation forces achieves time scale compression of conformational changes coupled with solvent exchange, resulting in further significant acceleration of protein conformational sampling with respect to real time dynamics. Overall, this provided a 50- to 1000-fold effective speedup of conformational sampling for these systems, compared to conventional MD with explicit solvent. We have been able to fold the miniprotein from a fully denatured, extended state in about 60 ns of quasidynamics steered with 3D-RISM-KH mean solvation forces, compared to the average physical folding time of 4-9 μs observed in experiment.

S14 as a Therapeutic Target in Breast Cancer

DTIC Science & Technology

2005-08-01

dimethylthiazol-2yl)-5-(3-carboxymethyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay (Promega). Oxidation of MTS by viable mitochondria yields a...potential mediators of the observed superinduction. The amplified signal could not be attributed to progestin induction of PPAR Gamma Coactivator-113 (PGC-lf3...quantitation of siRNA transfection efficiency, verification of localization of the siRNA to the interior of the cells, using more than one siRNA, and the

Cutting edge: rescue of pre-TCR but not mature TCR signaling in mice expressing membrane-targeted SLP-76.

PubMed

Bezman, Natalie A; Baker, Rebecca G; Lenox, Laurie E; Jordan, Martha S; Koretzky, Gary A

2009-05-01

SLP-76 (Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa) organizes signaling from immunoreceptors, including the platelet collagen receptor, the pre-TCR, and the TCR, and is required for T cell development. In this study we examine a mouse in which wild-type SLP-76 is replaced with a mutant constitutively targeted to the cell membrane. Membrane-targeted SLP-76 (MTS) supports ITAM signaling in platelets and from the pre-TCR. Signaling from the mature TCR, however, is defective in MTS thymocytes, resulting in failed T cell differentiation. Defective thymic selection by MTS is not rescued by a SLP-76 mutant whose localization is restricted to the cytosol. Thus, fixed localization of SLP-76 reveals differential requirements for the subcellular localization of signaling complexes downstream of the pre-TCR vs mature TCR.

Shape Memory effect and Superelasticity in the [001] Single crystals of a FeNiCoAlTa Alloy with γ-α'-Thermoelastic Martensitic Transformations

NASA Astrophysics Data System (ADS)

Chumlyakov, Yu. I.; Kireeva, I. V.; Kretinina, I. V.; Keinikh, K. S.; Kuts, O. A.; Kirillov, V. A.; Karaman, I.; Maier, H.

2013-12-01

Using single crystals of a Fe - 28% Ni - 17% Co - 11.5% Al - 25% Ta (аt.%) alloy, oriented for tensile loading along the [001] direction, the shape-memory (SME) and superelasticity (SE) effects caused by reversible thermoelastic martensitic transformations (MTs) from a high-temperature fcc-phase into a bctmartensite are investigated. It is demonstrated that the conditions necessary for the thermoelastic MTs to occur are achieved by aging at 973 K within the time interval (t) from 0.5 to 7.0 hours, which is accompanied by precipitation of the γ'-phase particles, (FeNiCo)3(AlTa), whose d < 8-12 nm. When the size of the γ'-precipitates becomes as large as d ≥ 8-12 nm, the MT becomes partially reversible. The physical causes underlying the kinetics of thermoelstic reversible fcc-bct MTs are discussed.

Covalent Immobilization of Microtubules on Glass Surfaces for Molecular Motor Force Measurements and Other Single-Molecule Assays

PubMed Central

Nicholas, Matthew P.; Rao, Lu; Gennerich, Arne

2014-01-01

Rigid attachment of microtubules (MTs) to glass cover slip surfaces is a prerequisite for a variety of microscopy experiments in which MTs are used as substrates for MT-associated proteins, such as the molecular motors kinesin and cytoplasmic dynein. We present an MT-surface coupling protocol in which aminosilanized glass is formylated using the cross-linker glutaraldehyde, fluorescence-labeled MTs are covalently attached, and the surface is passivated with highly pure beta-casein. The technique presented here yields rigid MT immobilization while simultaneously blocking the remaining glass surface against nonspecific binding by polystyrene optical trapping microspheres. This surface chemistry is straightforward and relatively cheap and uses a minimum of specialized equipment or hazardous reagents. These methods provide a foundation for a variety of optical tweezers experiments with MT-associated molecular motors and may also be useful in other assays requiring surface-immobilized proteins. PMID:24633798

Metallothionein 2A affects the cell respiration by suppressing the expression of mitochondrial protein cytochrome c oxidase subunit II.

PubMed

Bragina, Olga; Gurjanova, Karina; Krishtal, Jekaterina; Kulp, Maria; Karro, Niina; Tõugu, Vello; Palumaa, Peep

2015-06-01

Metallothioneins (MT) are involved in a broad range of cellular processes and play a major role in protection of cells towards various stressors. Two functions of MTs, namely the maintaining of the homeostasis of transition metal ions and the redox balance, are directly linked to the functioning of mitochondria. Dyshomeostasis of MTs is often related with malfunctioning of mitochondria; however, the mechanism by which MTs affect the mitochondrial respiratory chain is still unknown. We demonstrated that overexpression of MT-2A in HEK cell line decreased the oxidative phosphorylation capacity of the cells. HEK cells overexpressing MT-2A demonstrated reduced oxygen consumption and lower cellular ATP levels. MT-2A did not affect the number of mitochondria, but reduced specifically the level of cytochrome c oxidase subunit II protein, which resulted in lower activity of the complex IV.

Crystal structure of lactose permease in complex with an affinity inactivator yields unique insight into sugar recognition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chaptal, Vincent; Kwon, Seunghyug; Sawaya, Michael R.

Lactose permease of Escherichia coli (LacY) with a single-Cys residue in place of A122 (helix IV) transports galactopyranosides and is specifically inactivated by methanethiosulfonyl-galactopyranosides (MTS-gal), which behave as unique suicide substrates. In order to study the mechanism of inactivation more precisely, we solved the structure of single-Cys122 LacY in complex with covalently bound MTS-gal. This structure exhibits an inward-facing conformation similar to that observed previously with a slight narrowing of the cytoplasmic cavity. MTS-gal is bound covalently, forming a disulfide bond with C122 and positioned between R144 and W151. E269, a residue essential for binding, coordinates the C-4 hydroxyl ofmore » the galactopyranoside moiety. The location of the sugar is in accord with many biochemical studies.« less

The Role of Hybrid Make-to-Stock (MTS) - Make-to-Order (MTO) and Economic Order Quantity (EOQ) Inventory Control Models in Food and Beverage Processing Industry

NASA Astrophysics Data System (ADS)

Najhan Mohd Nagib, Ahmad; Naufal Adnan, Ahmad; Ismail, Azianti; Halim, Nurul Hayati Abdul; Syuhadah Khusaini, Nurul

2016-11-01

The inventory model had been utilized since the early 1900s. The implementation of the inventory management model is generally to ensure that an organisation is able to fulfil customer's demand at the lowest possible cost to improve profitability. This paper focuses on reviewing previous published papers regarding inventory control model mainly in the food and beverage processing industry. The author discusses four inventory models, which are the make-to-stock (MTS), make-to-order (MTO), economic order quantity (EOQ), and hybrid of MTS-MTO models. The issues raised by the researchers on the above techniques as well as the elements need to be considered upon selection have been discussed in this paper. The main objective of the study is to highlight the important role played by these inventory control models in the food and beverage processing industry.

Studies on the in vivo sensitivity of spindle microtubules to calcium ions and evidence for a vesicular calcium-sequestering system

PubMed Central

1981-01-01

I microinjected calcium ions into echinoderm eggs during mitosis to determine the calcium sensitivity of microtubules (Mts) in vivo. Spindle birefringence (BR), a measure of the number of aligned Mts in the spindle, is locally, rapidly, and reversibly abolished by small volumes of microinjected CaCl2 (1 mM). Rapid return of BR is followed by anaphase, and subsequent divisions are normal. Similar doses of MgCl2, BaCl2, KCl, NaCl, pH buffers, distilled water, or vegetable oil have no effect on spindle BR, whereas large doses of such agents sometimes cause slow, uniform loss in BR over the course of a minute or more. Of the ions tested, only Sr++ causes effects comparable to Ca++. Ca-EGTA buffers, containing greater than micromolar free Ca++, abolishes BR in a manner similar to millimolar concentrations of injected CaCl2. Caffeine, a potent uncoupler of the Ca++-pump/ATPase of sarcoplasmic reticulum, causes a local, transient depression in spindle BR in the injected region. Finally, injection of potassium oxalate results in the formation of small, highly BR crystals, presumably CA- oxalate, in Triton-sensitive compartments in the cytoplasm. Taken together, these findings demonstrate that spindle Mts are sensitive to levels of free Ca++ in the physiological range, provide evidence for the existence of a strong cytoplasmic Ca++-sequestering system, and support the notion that Mt assembly and disassembly in local regions of the spindle may be orchestrated by local changes in the cytoplasmic free Ca++ concentration during mitosis. An appendix offers the design of a new chamber for immobilizing echinoderm eggs for injection, a new method for determining the volume of the injected solution, and a description of the microinjection technique, which was designed, but never fully described, by Hiramoto (Y. Hiramoto, Exp. Cell. Res., 1962, 27:416-426.). PMID:7194345

The Application of Curve Fitting on the Voltammograms of Various Isoforms of Metallothioneins–Metal Complexes

PubMed Central

Merlos Rodrigo, Miguel Angel; Molina-López, Jorge; Jimenez Jimenez, Ana Maria; Planells Del Pozo, Elena; Adam, Pavlina; Eckschlager, Tomas; Zitka, Ondrej; Richtera, Lukas; Adam, Vojtech

2017-01-01

The translation of metallothioneins (MTs) is one of the defense strategies by which organisms protect themselves from metal-induced toxicity. MTs belong to a family of proteins comprising MT-1, MT-2, MT-3, and MT-4 classes, with multiple isoforms within each class. The main aim of this study was to determine the behavior of MT in dependence on various externally modelled environments, using electrochemistry. In our study, the mass distribution of MTs was characterized using MALDI-TOF. After that, adsorptive transfer stripping technique with differential pulse voltammetry was selected for optimization of electrochemical detection of MTs with regard to accumulation time and pH effects. Our results show that utilization of 0.5 M NaCl, pH 6.4, as the supporting electrolyte provides a highly complicated fingerprint, showing a number of non-resolved voltammograms. Hence, we further resolved the voltammograms exhibiting the broad and overlapping signals using curve fitting. The separated signals were assigned to the electrochemical responses of several MT complexes with zinc(II), cadmium(II), and copper(II), respectively. Our results show that electrochemistry could serve as a great tool for metalloproteomic applications to determine the ratio of metal ion bonds within the target protein structure, however, it provides highly complicated signals, which require further resolution using a proper statistical method, such as curve fitting. PMID:28287470

Circadian Rhythm Regulates Development of Enamel in Mouse Mandibular First Molar

PubMed Central

Tao, Jiang; Zhai, Yue; Park, Hyun; Han, Junli; Dong, Jianhui; Xie, Ming; Gu, Ting; Lewi, Keidren; Ji, Fang; Jia, William

2016-01-01

Rhythmic incremental growth lines and the presence of melatonin receptors were discovered in tooth enamel, suggesting possible role of circadian rhythm. We therefore hypothesized that circadian rhythm may regulate enamel formation through melatonin receptors. To test this hypothesis, we examined expression of melatonin receptors (MTs) and amelogenin (AMELX), a maker of enamel formation, during tooth germ development in mouse. Using qRT-PCR and immunocytochemistry, we found that mRNA and protein levels of both MTs and AMELX in normal mandibular first molar tooth germs increased gradually after birth, peaked at 3 or 4 day postnatal, and then decreased. Expression of MTs and AMELX by immunocytochemistry was significantly delayed in neonatal mice raised in all-dark or all-light environment as well as the enamel development. Furthermore, development of tooth enamel was also delayed showing significant immature histology in those animals, especially for newborn mice raised in all daylight condition. Interestingly, disruption in circadian rhythm in pregnant mice also resulted in delayed enamel development in their babies. Treatment with melatonin receptor antagonist 4P-PDOT in pregnant mice caused underexpression of MTs and AMELX associated with long-lasting deficiency in baby enamel tissue. Electromicroscopic evidence demonstrated increased necrosis and poor enamel mineralization in ameloblasts. The above results suggest that circadian rhythm is important for normal enamel development at both pre- and postnatal stages. Melatonin receptors were partly responsible for the regulation. PMID:27494172

Historical Risk Factors Associated with Seizure Outcome After Surgery for Drug-Resistant Mesial Temporal Lobe Epilepsy.

PubMed

Asadi-Pooya, Ali A; Nei, Maromi; Sharan, Ashwini; Sperling, Michael R

2016-05-01

To investigate the possible influence of risk factors on seizure outcome after surgery for drug-resistant temporal lobe epilepsy (TLE) and mesial temporal sclerosis (MTS). This retrospective study recruited patients with drug-resistant MTS-TLE who underwent epilepsy surgery at Jefferson Comprehensive Epilepsy Center and were followed for a minimum of 1 year. Patients had been prospectively registered in a database from 1986 through 2014. After surgery outcome was classified into 2 groups: seizure-free or relapsed. The possible risk factors influencing long-term outcome after surgery were investigated. A total of 275 patients with MTS-TLE were studied. Two thirds of the patients had Engel's class 1 outcome and 48.4% of the patients had sustained seizure freedom, with no seizures since surgery. Patients with a history of tonic-clonic seizures in the year preceding surgery were more likely to experience seizure recurrence (odds ratio, 2.4; 95% confidence interval 1.19-4.80; P = 0.01). Gender, race, family history of epilepsy, history of febrile seizure, history of status epilepticus, duration of disease before surgery, intelligence quotient, and seizure frequency were not predictors of outcome. Many patients with drug-resistant MTS-TLE respond favorably to surgery. It is critical to distinguish among different types and etiologies of TLE when predicting outcome after surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

Circadian Rhythm Regulates Development of Enamel in Mouse Mandibular First Molar.

PubMed

Tao, Jiang; Zhai, Yue; Park, Hyun; Han, Junli; Dong, Jianhui; Xie, Ming; Gu, Ting; Lewi, Keidren; Ji, Fang; Jia, William

2016-01-01

Rhythmic incremental growth lines and the presence of melatonin receptors were discovered in tooth enamel, suggesting possible role of circadian rhythm. We therefore hypothesized that circadian rhythm may regulate enamel formation through melatonin receptors. To test this hypothesis, we examined expression of melatonin receptors (MTs) and amelogenin (AMELX), a maker of enamel formation, during tooth germ development in mouse. Using qRT-PCR and immunocytochemistry, we found that mRNA and protein levels of both MTs and AMELX in normal mandibular first molar tooth germs increased gradually after birth, peaked at 3 or 4 day postnatal, and then decreased. Expression of MTs and AMELX by immunocytochemistry was significantly delayed in neonatal mice raised in all-dark or all-light environment as well as the enamel development. Furthermore, development of tooth enamel was also delayed showing significant immature histology in those animals, especially for newborn mice raised in all daylight condition. Interestingly, disruption in circadian rhythm in pregnant mice also resulted in delayed enamel development in their babies. Treatment with melatonin receptor antagonist 4P-PDOT in pregnant mice caused underexpression of MTs and AMELX associated with long-lasting deficiency in baby enamel tissue. Electromicroscopic evidence demonstrated increased necrosis and poor enamel mineralization in ameloblasts. The above results suggest that circadian rhythm is important for normal enamel development at both pre- and postnatal stages. Melatonin receptors were partly responsible for the regulation.

Kinesins have a dual function in organizing microtubules during both tip growth and cytokinesis in Physcomitrella patens.

PubMed

Hiwatashi, Yuji; Sato, Yoshikatsu; Doonan, John H

2014-03-01

Microtubules (MTs) play a crucial role in the anisotropic deposition of cell wall material, thereby affecting the direction of growth. A wide range of tip-growing cells display highly polarized cell growth, and MTs have been implicated in regulating directionality and expansion. However, the molecular machinery underlying MT dynamics in tip-growing plant cells remains unclear. Here, we show that highly dynamic MT bundles form cyclically in the polarized expansion zone of the moss Physcomitrella patens caulonemal cells through the coalescence of growing MT plus ends. Furthermore, the plant-specific kinesins (KINID1) that are is essential for the proper MT organization at cytokinesis also regulate the turnover of the tip MT bundles as well as the directionality and rate of cell growth. The plus ends of MTs grow toward the expansion zone, and KINID1 is necessary for the stability of a single coherent focus of MTs in the center of the zone, whose formation coincides with the accumulation of KINID1. We propose that KINID-dependent MT bundling is essential for the correct directionality of growth as well as for promoting growth per se. Our findings indicate that two localized cell wall deposition processes, tip growth and cytokinesis, previously believed to be functionally and evolutionarily distinct, share common and plant-specific MT regulatory components.

Bidirectional motility of kinesin-5 motor proteins: structural determinants, cumulative functions and physiological roles.

PubMed

Singh, Sudhir Kumar; Pandey, Himanshu; Al-Bassam, Jawdat; Gheber, Larisa

2018-05-01

Mitotic kinesin-5 bipolar motor proteins perform essential functions in mitotic spindle dynamics by crosslinking and sliding antiparallel microtubules (MTs) apart within the mitotic spindle. Two recent studies have indicated that single molecules of Cin8, the Saccharomyces cerevisiae kinesin-5 homolog, are minus end-directed when moving on single MTs, yet switch directionality under certain experimental conditions (Gerson-Gurwitz et al., EMBO J 30:4942-4954, 2011; Roostalu et al., Science 332:94-99, 2011). This finding was unexpected since the Cin8 catalytic motor domain is located at the N-terminus of the protein, and such kinesins have been previously thought to be exclusively plus end-directed. In addition, the essential intracellular functions of kinesin-5 motors in separating spindle poles during mitosis can only be accomplished by plus end-directed motility during antiparallel sliding of the spindle MTs. Thus, the mechanism and possible physiological role of the minus end-directed motility of kinesin-5 motors remain unclear. Experimental and theoretical studies from several laboratories in recent years have identified additional kinesin-5 motors that are bidirectional, revealed structural determinants that regulate directionality, examined the possible mechanisms involved and have proposed physiological roles for the minus end-directed motility of kinesin-5 motors. Here, we summarize our current understanding of the remarkable ability of certain kinesin-5 motors to switch directionality when moving along MTs.

Persistence, Transmission, and Virulence Characteristics of Aeromonas Strains in a Duckweed Aquaculture-Based Hospital Sewage Water Recycling Plant in Bangladesh▿

PubMed Central

Rahman, Mokhlasur; Huys, Geert; Rahman, Motiur; Albert, M. John; Kühn, Inger; Möllby, Roland

2007-01-01

The persistence and transmission of Aeromonas in a duckweed aquaculture-based hospital sewage water treatment plant in Bangladesh was studied. A total of 670 samples from different sites of the hospital sewage water treatment plant, from feces of hospitalized children suffering from diarrhea, from environmental control ponds, and from feces of healthy humans were collected over a period of three years. In total, 1,315 presumptive Aeromonas isolates were biochemically typed by the PhenePlate rapid screening system (PhP-AE). A selection of 90 representative isolates was further analyzed with PhenePlate (PhP) extended typing (PhP-48), fatty acid methyl ester analysis, and amplified fragment length polymorphism (AFLP) fingerprinting. In addition, the prevalence of the putative virulence factors hemolysin and cytotoxin and the presence of the cytolytic enterotoxin gene (AHCYTOEN) were analyzed. Aeromonas was found at all sites of the treatment plant, in 40% of the samples from environmental control ponds, in 8.5% of the samples from hospitalized children suffering from diarrhea, and in 3.5% of samples from healthy humans. A significantly high number of Aeromonas bacteria was found in duckweed, which indicates that duckweed may serve as a reservoir for these bacteria. PhP-AE typing allowed identification of more than 192 distinct PhP types, of which 18 major PhP types (MTs) were found in multiple sites and during several occasions. AFLP fingerprinting revealed the prevalence of genotypically indistinguishable Aeromonas isolates among certain PhP MTs recovered from different sampling occasions and/or at multiple sites. Hemolytic and cytotoxic activities were observed in 43% of the tested strains, whereas 29% possessed the cytolytic enterotoxin gene AHCYTOEN. Collectively, two specific MTs associated with diarrhea were shown to exhibit high cytotoxicity. Furthermore, all tested isolates of these major types were positive for the cytolytic enterotoxin gene. In conclusion, our data indicate that certain phenotypically and genotypically stable clonal lineages of Aeromonas have persisted in the treatment system for a prolonged period and might spread from the hospitalized children suffering from diarrhea to fish produced for human consumption through the sewage water treatment system. PMID:17194839

HIV rapid diagnostic testing by lay providers in a key population-led health service programme in Thailand.

PubMed

Wongkanya, Rapeeporn; Pankam, Tippawan; Wolf, Shauna; Pattanachaiwit, Supanit; Jantarapakde, Jureeporn; Pengnongyang, Supabhorn; Thapwong, Prasopsuk; Udomjirasirichot, Apichat; Churattanakraisri, Yutthana; Prawepray, Nanthika; Paksornsit, Apiluk; Sitthipau, Thidadaow; Petchaithong, Sarayut; Jitsakulchaidejt, Raruay; Nookhai, Somboon; Lertpiriyasuwat, Cheewanan; Ongwandee, Sumet; Phanuphak, Praphan; Phanuphak, Nittaya

2018-01-01

Introduction:  Rapid diagnostic testing (RDT) for HIV has a quick turn-around time, which increases the proportion of people testing who receive their result. HIV RDT in Thailand has traditionally been performed only by medical technologists (MTs), which is a barrier to its being scaled up. We evaluated the performance of HIV RDT conducted by trained lay providers who were members of, or worked closely with, a group of men who have sex with men (MSM) and with transgender women (TG) communities, and compared it to tests conducted by MTs. Methods:  Lay providers received a 3-day intensive training course on how to perform a finger-prick blood collection and an HIV RDT as part of the Key Population-led Health Services (KPLHS) programme among MSM and TG. All the samples were tested by lay providers using Alere Determine HIV 1/2. HIV-reactive samples were confirmed by DoubleCheckGold Ultra HIV 1&2 and SD Bioline HIV 1/2. All HIV-positive and 10% of HIV-negative samples were re-tested by MTs using Serodia HIV 1/2. Results:  Of 1680 finger-prick blood samples collected and tested using HIV RDT by lay providers in six drop-in centres in Bangkok, Chiang Mai, Chonburi and Songkhla, 252 (15%) were HIV-positive. MTs re-tested these HIV-positive samples and 143 randomly selected HIV-negative samples with 100% concordant test results. Conclusion:  Lay providers in Thailand can be trained and empowered to perform HIV RDT as they were found to achieve comparable results in sample testing with MTs. Based on the task-shifting concept, this rapid HIV testing performed by lay providers as part of the KPLHS programme has great potential to enhance HIV prevention and treatment programmes among key at-risk populations.

Recruitment of EB1, a Master Regulator of Microtubule Dynamics, to the Surface of the Theileria annulata Schizont

PubMed Central

Woods, Kerry L.; Theiler, Romina; Mühlemann, Marcus; Segiser, Adrian; Huber, Sandra; Ansari, Hifzur R.; Pain, Arnab; Dobbelaere, Dirk A. E.

2013-01-01

The apicomplexan parasite Theileria annulata transforms infected host cells, inducing uncontrolled proliferation and clonal expansion of the parasitized cell population. Shortly after sporozoite entry into the target cell, the surrounding host cell membrane is dissolved and an array of host cell microtubules (MTs) surrounds the parasite, which develops into the transforming schizont. The latter does not egress to invade and transform other cells. Instead, it remains tethered to host cell MTs and, during mitosis and cytokinesis, engages the cell's astral and central spindle MTs to secure its distribution between the two daughter cells. The molecular mechanism by which the schizont recruits and stabilizes host cell MTs is not known. MT minus ends are mostly anchored in the MT organizing center, while the plus ends explore the cellular space, switching constantly between phases of growth and shrinkage (called dynamic instability). Assuming the plus ends of growing MTs provide the first point of contact with the parasite, we focused on the complex protein machinery associated with these structures. We now report how the schizont recruits end-binding protein 1 (EB1), a central component of the MT plus end protein interaction network and key regulator of host cell MT dynamics. Using a range of in vitro experiments, we demonstrate that T. annulata p104, a polymorphic antigen expressed on the schizont surface, functions as a genuine EB1-binding protein and can recruit EB1 in the absence of any other parasite proteins. Binding strictly depends on a consensus SxIP motif located in a highly disordered C-terminal region of p104. We further show that parasite interaction with host cell EB1 is cell cycle regulated. This is the first description of a pathogen-encoded protein to interact with EB1 via a bona-fide SxIP motif. Our findings provide important new insight into the mode of interaction between Theileria and the host cell cytoskeleton. PMID:23675298

10Be exposure age chronology of the last glaciation of the Roháčská Valley in the Western Tatra Mountains, central Europe

NASA Astrophysics Data System (ADS)

Engel, Zbyněk; Mentlík, Pavel; Braucher, Régis; Křížek, Marek; Pluháčková, Markéta; Arnold, Maurice; Aumaître, Georges; Bourlès, Didier; Keddadouche, Karim; Aster Team; Arnold, Maurice; Aumaître, Georges; Bourlès, Didier; Keddadouche, Karim

2017-09-01

10Be exposure ages from moraines and bedrock sites in the Roháčská Valley provide chronology of the last glaciation in the largest valley of the Western Tatra Mts., the Western Carpathians. The minimum apparent exposure age of 19.4 ± 2.1 ka obtained for the oldest sampled boulder and the mean age of 18.0 ± 0.8 ka calculated for the terminal moraine indicate that the oldest preserved moraine was probably deposited at the time of the global Last Glacial Maximum (LGM). The age of this moraine coincides with the termination of the maximum glacier expansion in other central European ranges, including the adjacent High Tatra Mts. and the Alps. The equilibrium line altitude (ELA) of the LGM glacier in the Roháčská Valley, estimated at 1400-1410 m a.s.l., was 50-80 m lower than in the eastern part of the range, indicating a positive ELA gradient from west to east among the north-facing glaciers in the Tatra Mts. Lateglacial glacier expansion occurred no later than 13.4 ± 0.5 ka and 11.9 ± 0.5 ka, as indicated by the mean exposure ages calculated for re-advance moraines. This timing is consistent with the exposure age chronology of the last Lateglacial re-advance in the High Tatra Mts., Alps and lower mountain ranges in central Europe. The ELA in the Roháčská Valley estimated at 1690-1770 m a.s.l. in this period was located 130-300 m lower than in the north-facing valleys in the High Tatra Mts. 10Be exposure ages obtained for a rock glacier constrains the timing of this landform stabilization in the Salatínska Valley and provides the first chronological evidence for the Lateglacial activity of rock glaciers in the Carpathians.

Recovery of microtubules on the blepharoplast of Ceratopteris spermatogenous cells after oryzalin treatment.

PubMed

Vaughn, Kevin C; Bowling, Andrew J

2008-11-01

Most land plants have ill-defined microtubule-organizing centers (MTOCs), consisting of sites on the nuclear envelope or even along microtubules (MTs). In contrast, the spermatogenous cells of the pteridophyte Ceratopteris richardii have a well-defined MTOC, the blepharoplast, which organizes MTs through the last two division cycles. This allows a rare opportunity to study the organization and workings of a structurally well-defined plant MTOC. In this study, antheridial plants were treated with levels of oryzalin that cause complete MT loss from the cells containing blepharoplasts. The oryzalin was then washed out and plants were allowed to recover for varying amounts of time. If the spermatogenous cells were fixed prior to washing out, the blepharoplasts had an unusual appearance. In the matrix (pericentriolar) material where MT ends are normally found, clear areas of about the diameter of MTs were seen embedded in a much deeper matrix, made more obvious in stereo pairs. Occasionally, the matrix material was highly distended, although the basal body template cylinder morphology appeared to be unaltered. The blepharoplasts often occurred as clusters of 2 or 4, indicating that blepharoplast reproduction is not affected by the lack of MTs, but that their movement to the poles is. Gamma (gamma) tubulin antibodies labeled the edge of the blepharoplast in areas where the pits are located, indicating that these might be sites for MT nucleation. After wash out, the new MTs always re-appeared on the blepharoplast and the recovery occurred within an hour of washout. MT lengths increased with increasing washout time and were indistinguishable from untreated blepharoplasts after 24 h of recovery. After washout, arrays formed in new sperm cells such as the spline and basal bodies were often malformed or present in multiple copies, as were the blepharoplasts in these cells prior to wash out. These data indicate that the blepharoplast serves as the site of MT nucleation and organization even after complete MT de-polymerization.

The evolution of epilepsy surgery between 1991 and 2011 in nine major epilepsy centers across the United States, Germany, and Australia

PubMed Central

Jehi, Lara; Friedman, Daniel; Carlson, Chad; Cascino, Gregory; Dewar, Sandra; Elger, Christian; Engel, Jerome; Knowlton, Robert; Kuzniecky, Ruben; McIntosh, Anne; O’Brien, Terence J.; Spencer, Dennis; Sperling, Michael R.; Worrell, Gregory; Bingaman, Bill; Gonzalez-Martinez, Jorge; Doyle, Werner; French, Jacqueline

2016-01-01

Summary Objective Epilepsy surgery is the most effective treatment for select patients with drug-resistant epilepsy. In this article, we aim to provide an accurate understanding of the current epidemiologic characteristics of this intervention, as this knowledge is critical for guiding educational, academic, and resource priorities. Methods We profile the practice of epilepsy surgery between 1991 and 2011 in nine major epilepsy surgery centers in the United States, Germany, and Australia. Clinical, imaging, surgical, and histopathologic data were derived from the surgical databases at various centers. Results Although five of the centers performed their highest number of surgeries for mesial temporal sclerosis (MTS) in 1991, and three had their highest number of MTS surgeries in 2001, only one center achieved its peak number of MTS surgeries in 2011. The most productive year for MTS surgeries varied then by center; overall, the nine centers surveyed performed 48% (95% confidence interval [CI] −27.3% to −67.4%) fewer such surgeries in 2011 compared to either 1991 or 2001, whichever was higher. There was a parallel increase in the performance of surgery for nonlesional epilepsy. Further analysis of 5/9 centers showed a yearly increase of 0.6 ± 0.07% in the performance of invasive electroencephalography (EEG) without subsequent resections. Overall, although MTS was the main surgical substrate in 1991 and 2001 (proportion of total surgeries in study centers ranging from 33.3% to 70.2%); it occupied only 33.6% of all resections in 2011 in the context of an overall stable total surgical volume. Significance These findings highlight the major aspects of the evolution of epilepsy surgery across the past two decades in a sample of well-established epilepsy surgery centers, and the critical current challenges of this treatment option in addressing complex epilepsy cases requiring detailed evaluations. Possible causes and implications of these findings are discussed. PMID:26250432

Patient perspectives of care in a regionalised trauma system: lessons from the Victorian State Trauma System.

PubMed

Gabbe, Belinda J; Sleney, Jude S; Gosling, Cameron M; Wilson, Krystle; Hart, Melissa J; Sutherland, Ann M; Christie, Nicola

2013-02-18

To explore injured patients' experiences of trauma care to identify areas for improvement in service delivery. Qualitative study using in-depth, semi-structured interviews, conducted from 1 April 2011 to 31 January 2012, with 120 trauma patients registered by the Victorian State Trauma Registry and the Victorian Orthopaedic Trauma Outcomes Registry and managed at the major adult trauma services (MTS) in Victoria. Emergent themes from patients' experiences of acute, rehabilitation and post-discharge care in the Victorian State Trauma System (VSTS). Patients perceived their acute hospital care as high quality, although 3s with communication and surgical management delays were common. Discharge from hospital was perceived as stressful, and many felt ill prepared for discharge. A consistent emerging theme was the sense of a lack of coordination of post-discharge care, and the absence of a consistent point of contact for ongoing management. Most patients' primary point of contact after discharge was outpatient clinics at the MTS, which were widely criticised because of substantial delays in receiving an appointment, prolonged waiting times, limited time with clinicians, lack of continuity of care and inability to see senior clinicians. This study highlights perceived 3s in the patient care pathway in the VSTS, especially those relating to communication, information provision and post-discharge care. Trauma patients perceived the need for a single point of contact for coordination of post-discharge care.

Eosinophil Cell Lines in a Tri-Cell Multicellular Tumor Spheroid (MTS)/Endothelium Complex: Down Regulation of Adhesion and Integrin Molecules-Implications of Metastasis Inhibition

DTIC Science & Technology

2003-10-01

Crohn disease . Scand J Gastroenterol 200136:190-195. prolonged survival, enhanced functional properties, and be- 54 Blandeima-Melo C, Sugiyama K...and are also prominent in other disease conditions such 7 growth in vitro. In this study MCF-7 multicellular tumor as cutaneous hypersensitive...disorders (8) and inflammatory spheroids (MTS) were developed to study the effect of bowel disease (9). Eosinophils have also been found in eosinophils and

Methods for Multiplex Template Sampling in Digital PCR Assays

PubMed Central

Petriv, Oleh I.; Heyries, Kevin A.; VanInsberghe, Michael; Walker, David; Hansen, Carl L.

2014-01-01

The efficient use of digital PCR (dPCR) for precision copy number analysis requires high concentrations of target molecules that may be difficult or impossible to obtain from clinical samples. To solve this problem we present a strategy, called Multiplex Template Sampling (MTS), that effectively increases template concentrations by detecting multiple regions of fragmented target molecules. Three alternative assay approaches are presented for implementing MTS analysis of chromosome 21, providing a 10-fold concentration enhancement while preserving assay precision. PMID:24854517

Methods for multiplex template sampling in digital PCR assays.

PubMed

Petriv, Oleh I; Heyries, Kevin A; VanInsberghe, Michael; Walker, David; Hansen, Carl L

2014-01-01

The efficient use of digital PCR (dPCR) for precision copy number analysis requires high concentrations of target molecules that may be difficult or impossible to obtain from clinical samples. To solve this problem we present a strategy, called Multiplex Template Sampling (MTS), that effectively increases template concentrations by detecting multiple regions of fragmented target molecules. Three alternative assay approaches are presented for implementing MTS analysis of chromosome 21, providing a 10-fold concentration enhancement while preserving assay precision.

Structural differences between yeast and mammalian microtubules revealed by cryo-EM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Howes, Stuart C.; Geyer, Elisabeth A.; LaFrance, Benjamin

Microtubules are polymers of αβ-tubulin heterodimers essential for all eukaryotes. Despite sequence conservation, there are significant structural differences between microtubules assembled in vitro from mammalian or budding yeast tubulin. Yeast MTs were not observed to undergo compaction at the interdimer interface as seen for mammalian microtubules upon GTP hydrolysis. Lack of compaction might reflect slower GTP hydrolysis or a different degree of allosteric coupling in the lattice. The microtubule plus end–tracking protein Bim1 binds yeast microtubules both between αβ-tubulin heterodimers, as seen for other organisms, and within tubulin dimers, but binds mammalian tubulin only at interdimer contacts. At the concentrationsmore » used in cryo-electron microscopy, Bim1 causes the compaction of yeast microtubules and induces their rapid disassembly. In conclusion, our studies demonstrate structural differences between yeast and mammalian microtubules that likely underlie their differing polymerization dynamics. These differences may reflect adaptations to the demands of different cell size or range of physiological growth temperatures.« less

A new method using insert-based systems (IBS) to improve cell behavior study on flexible and rigid biomaterials.

PubMed

Grenade, Charlotte; Moniotte, Nicolas; Rompen, Eric; Vanheusden, Alain; Mainjot, Amélie; De Pauw-Gillet, Marie-Claire

2016-12-01

In vitro studies about biomaterials biological properties are essential screening tests. Yet cell cultures encounter difficulties related to cell retention on material surface or to the observation of both faces of permeable materials. The objective of the present study was to develop a reliable in vitro method to study cell behavior on rigid and flexible/permeable biomaterials elaborating two specific insert-based systems (IBS-R and IBS-F respectively). IBS-R was designed as a specific cylindrical polytetrafluoroethylene (PTFE) system to evaluate attachment, proliferation and morphology of human gingival fibroblasts (HGFs) on grade V titanium and lithium disilicate glass-ceramic discs characteristics of dental prostheses. The number of cells, their covering on discs and their morphology were determined from MTS assays and microscopic fluorescent images after 24, 48 and 72 h. IBS-F was developed as a two components system to study HGFs behavior on guided bone regeneration polyester membranes. The viability and the membrane barrier effect were evaluated by metabolic MTS assays and by scanning electron microscopy. IBS-R and IBS-F were shown to promote (1) easy and rapid handling; (2) cell retention on biomaterial surface; (3) accurate evaluation of the cellular proliferation, spreading and viability; (4) use of non-toxic material. Moreover IBS-F allowed the study of the cell migration through degradable membranes, with an access to both faces of the biomaterial and to the bottom of culture wells for medium changing.

Nanomaterials Commercialization Center

DTIC Science & Technology

2013-02-01

turbine manufacturer). ln the wind energy area , customers clearly stated that the major short-tenn technical need for toughening is in the area of...interactions: • The wind energy composites market for turbine blades is an extremely high growth, high potential opportunity. Potential value ofnano...Wire Takeup System (MTS), with a winding pitch modified to meet the needs of the small diameter wire (- 100J.1m) produced in this reel-to-reelline

Episodic and semantic memory in children with mesial temporal sclerosis.

PubMed

Rzezak, Patricia; Guimarães, Catarina; Fuentes, Daniel; Guerreiro, Marilisa M; Valente, Kette Dualibi Ramos

2011-07-01

The aim of this study was to analyze semantic and episodic memory deficits in children with mesial temporal sclerosis (MTS) and their correlation with clinical epilepsy variables. For this purpose, 19 consecutive children and adolescents with MTS (8 to 16 years old) were evaluated and their performance on five episodic memory tests (short- and long-term memory and learning) and four semantic memory tests was compared with that of 28 healthy volunteers. Patients performed worse on tests of immediate and delayed verbal episodic memory, visual episodic memory, verbal and visual learning, mental scanning for semantic clues, object naming, word definition, and repetition of sentences. Clinical variables such as early age at seizure onset, severity of epilepsy, and polytherapy impaired distinct types of memory. These data confirm that children with MTS have episodic memory deficits and add new information on semantic memory. The data also demonstrate that clinical variables contribute differently to episodic and semantic memory performance. Copyright © 2011 Elsevier Inc. All rights reserved.

Dual circularly polarized broadside beam antenna based on metasurfaces

NASA Astrophysics Data System (ADS)

Tellechea, A.; Caminita, F.; Martini, E.; Ederra, I.; Teniente, J.; Iriarte, J. C.; Gonzalo, R.; Maci, S.

2018-02-01

Design details of a Ku band metasurface (MTS) antenna with dual circularly polarized (CP) broadside radiation is shown in this work. By means of the surface impedance tensor modulation, synchronized propagation of two transversal magnetic (TM) and transverse electric (TE) surface waves (SWs) is ensured in the structure, which contribute to the radiation in broadside direction by the generation of a CP leaky wave. The structure is implemented by elliptical subwavelength metallic elements with a cross-shaped aperture in the center, printed on top of a thin substrate with high permittivity (AD1000 with a thickness of λ0/17). For the experimental validation, the MTS prototype has been excited employing an orthomode transducer composed by a metallic stepped septum inside an air-filled waveguide. Two orthogonal TE11 modes excited with ±90° phase shift in the feed couple with the TM and TE SWs supported by the MTS and generate RHCP or LHCP broadside beam. Experimental results are compared with the simulation predictions. Finally, conclusions are drawn.

ACF7 regulates cytoskeletal-focal adhesion dynamics and migration and has ATPase activity.

PubMed

Wu, Xiaoyang; Kodama, Atsuko; Fuchs, Elaine

2008-10-03

Coordinated interactions between microtubule (MT) and actin cytoskeletons are involved in many polarized cellular processes. Spectraplakins are enormous (>500 kDa) proteins able to bind both MTs and actin filaments (F-actin) directly. To elucidate the physiological significance and functions of mammalian spectraplakin ACF7, we've conditionally targeted it in skin epidermis. Intriguingly, ACF7 deficiency compromises the targeting of microtubules along F-actin to focal adhesions (FAs), stabilizes FA-actin networks, and impairs epidermal migration. Exploring underlying mechanisms, we show that ACF7's binding domains for F-actin, MTs, and MT plus-end proteins are not sufficient to rescue the defects in FA-cytoskeletal dynamics and migration functions of ACF7 null keratinocytes. We've uncovered an intrinsic actin-regulated ATPase domain in ACF7 and demonstrate that it is both functional and essential for these roles. Our findings provide insight into the functions of this important cytoskeletal crosslinking protein in regulating dynamic interactions between MTs and F-actin to sustain directional cell movement.

Mechanics of kinetochore microtubules and their interactions with chromosomes during cell division

NASA Astrophysics Data System (ADS)

Nazockdast, Ehssan; Fürthauer, Sebastian; Redemann, Stephanie; Baumgart, Johannes; Lindow, Norbert; Kratz, Andrea; Prohaska, Steffen; Müller-Reichert, Thomas; Shelley, Michael

2016-11-01

The accurate segregation of chromosomes, and subsequent cell division, in Eukaryotic cells is achieved by the interactions of an assembly of microtubules (MTs) and motor-proteins, known as the mitotic spindle. We use a combination of our computational platform for simulating cytoskeletal assemblies and our structural data from high-resolution electron tomography of the mitotic spindle, to study the kinetics and mechanics of MTs in the spindle, and their interactions with chromosomes during chromosome segregation in the first cell division in C.elegans embryo. We focus on kinetochore MTs, or KMTs, which have one end attached to a chromosome. KMTs are thought to be a key mechanical component in chromosome segregation. Using exploratory simulations of MT growth, bending, hydrodynamic interactions, and attachment to chromosomes, we propose a mechanical model for KMT-chromosome interactions that reproduces observed KMT length and shape distributions from electron tomography. We find that including detailed hydrodynamic interactions between KMTs is essential for agreement with the experimental observations.

The genetic basis of Muir-Torre syndrome includes the hMLH1 locus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bapat, B.; Xia, L.; Mitri, A.

1996-09-01

Muir-Torre syndrome (MTS) (McKusick 158320) is an autosomal dominant disorder characterized by the development of sebaceous gland tumors and skin cancers, including keratoacanthomas and basal cell carcinomas. Affected family members may manifest a wide spectrum of internal malignancies, which include colorectal, endometrial, urologic, and upper gastrointestinal neoplasms. Sebaceous gland tumors, which are rare in the general population, are considered to be the hallmark of MTS and may arise prior to the development of other visceral cancers. Despite the high incidence of synchronous and metachronous tumors, prognosis is often favorable. Hereditary nonpolyposis colorectal cancer (HNPCC) is one of the most commonmore » autosomal dominantly inherited colorectal cancer susceptibility syndromes. In some HNPCC families, extracolonic tumors of the endometrium, ovary, small bowel, and renal and biliary tract occur at an increased frequency. On the basis of similarities in clinical symptoms of MTS and HNPCC, it is proposed that these two syndromes may have a common genetic basis. 24 refs., 2 figs.« less

Throwing speed and accuracy in baseball and cricket players.

PubMed

Freeston, Jonathan; Rooney, Kieron

2014-06-01

Throwing speed and accuracy are both critical to sports performance but cannot be optimized simultaneously. This speed-accuracy trade-off (SATO) is evident across a number of throwing groups but remains poorly understood. The goal was to describe the SATO in baseball and cricket players and determine the speed that optimizes accuracy. 20 grade-level baseball and cricket players performed 10 throws at 80% and 100% of maximal throwing speed (MTS) toward a cricket stump. Baseball players then performed a further 10 throws at 70%, 80%, 90%, and 100% of MTS toward a circular target. Baseball players threw faster with greater accuracy than cricket players at both speeds. Both groups demonstrated a significant SATO as vertical error increased with increases in speed; the trade-off was worse for cricketers than baseball players. Accuracy was optimized at 70% of MTS for baseballers. Throwing athletes should decrease speed when accuracy is critical. Cricket players could adopt baseball-training practices to improve throwing performance.

Absence of gender effect on amygdala volume in temporal lobe epilepsy.

PubMed

Silva, Ivaldo; Lin, Katia; Jackowski, Andrea P; Centeno, Ricardo da Silva; Pinto, Magali L; Carrete, Henrique; Yacubian, Elza M; Amado, Débora

2010-11-01

Sexual dimorphism has already been described in temporal lobe epilepsy with mesial temporal sclerosis (TLE-MTS). This study evaluated the effect of gender on amygdala volume in patients with TLE-MTS. One hundred twenty-four patients with refractory unilateral or bilateral TLE-MTS who were being considered for epilepsy surgery underwent a comprehensive presurgical evaluation and MRI. Amygdalas of 67 women (27 with right; 32 with left, and 8 with bilateral TLE) and 57 men (22 with right, 30 with left, and 5 with bilateral TLE) were manually segmented. Significant ipsilateral amygdala volume reduction was observed for patients with right and left TLE. No gender effect on amygdala volume was observed. Contralateral amygdalar asymmetry was observed for patients with right and left TLE. Although no gender effect was observed on amygdala volume, ipsilateral amygdala volume reductions in patients with TLE might be related to differential rates of cerebral maturation between hemispheres. Copyright © 2010 Elsevier Inc. All rights reserved.

Two Complementary Mechanisms Underpin Cell Wall Patterning during Xylem Vessel Development[OPEN

PubMed Central

Tang, Lu; Barkwill, Sarah; Lathe, Rahul; McFarlane, Heather E.

2017-01-01

The evolution of the plant vasculature was essential for the emergence of terrestrial life. Xylem vessels are solute-transporting elements in the vasculature that possess secondary wall thickenings deposited in intricate patterns. Evenly dispersed microtubule (MT) bands support the formation of these wall thickenings, but how the MTs direct cell wall synthesis during this process remains largely unknown. Cellulose is the major secondary wall constituent and is synthesized by plasma membrane-localized cellulose synthases (CesAs) whose catalytic activity propels them through the membrane. We show that the protein CELLULOSE SYNTHASE INTERACTING1 (CSI1)/POM2 is necessary to align the secondary wall CesAs and MTs during the initial phase of xylem vessel development in Arabidopsis thaliana and rice (Oryza sativa). Surprisingly, these MT-driven patterns successively become imprinted and sufficient to sustain the continued progression of wall thickening in the absence of MTs and CSI1/POM2 function. Hence, two complementary principles underpin wall patterning during xylem vessel development. PMID:28947492

Ase1/Prc1-dependent spindle elongation corrects merotely during anaphase in fission yeast

PubMed Central

Courtheoux, Thibault; Gay, Guillaume; Tournier, Sylvie

2009-01-01

Faithful segregation of sister chromatids requires the attachment of each kinetochore (Kt) to microtubules (MTs) that extend from opposite spindle poles. Merotelic Kt orientation is a Kt–MT misattachment in which a single Kt binds MTs from both spindle poles rather than just one. Genetic induction of merotelic Kt attachment during anaphase in fission yeast resulted in intra-Kt stretching followed by either correction or Kt disruption. Laser ablation of spindle MTs revealed that intra-Kt stretching and merotelic correction were dependent on MT forces. The presence of multiple merotelic chromosomes linearly antagonized the spindle elongation rate, and this phenomenon could be solved numerically using a simple force balance model. Based on the predictions of our mechanical model, we provide in vivo evidence that correction of merotelic attachment in anaphase is tension dependent and requires an Ase1/Prc1-dependent mechanism that prevents spindle collapse and thus asymmetric division and/or the appearance of the cut phenotype. PMID:19948483

[Retrospective calculation of the workload in emergency departments in case of a mass accident. An analysis of the Love Parade 2010].

PubMed

Ackermann, O; Heigel, U; Lazic, D; Vogel, T; Schofer, M D; Rülander, C

2012-04-01

For the clinical planning of mass events the emergency departments are of critical importance, but there are still no data available for the workload in these cases. As this is essential for an effective medical preparation, we calculated the workload based on the ICD codes of the vicitims at the Loveparade 2010 in Duisburg. Based on the patient data of the Loveparade 2010 we used a filter diagnosis to estimate the number of shock room patients, regular admittances, surgical wound treatments, applications of casts or splints, and diagnosis of drug abuse. In addition every patient was classified to a Manchester Triage System category. This resulted in a chronological and quantitative work-load profile of the emergency department, which was evaluated by the clinical experiences of the departmental medical staff. The workload profile as a whole displayed a realistic image of the real true situation on July 24, 2010. While only the number, diagnosis and chronology of medical surgical patients was realistic, the MTS classification was not. The emergency department had a maximum of 6 emergency room admittances, 6 regular admittances, 4-5 surgical wound treatments, 3 casts and 2 drug abuse patients per hour. The calculation of workload from the ICD data is a reasonable tool for retrospective estimation of the workload of an emergency department, the data can be used for future planning. The retrospective MTS grouping is at present not suitable for a realistic calculation. Retrospective measures in the MTS groups are at present not sufficiently suitable for valid data publication. © Georg Thieme Verlag KG Stuttgart · New York.

Atlas-based automatic measurements of the morphology of the tibiofemoral joint

NASA Astrophysics Data System (ADS)

Brehler, M.; Thawait, G.; Shyr, W.; Ramsay, J.; Siewerdsen, J. H.; Zbijewski, W.

2017-03-01

Purpose: Anatomical metrics of the tibiofemoral joint support assessment of joint stability and surgical planning. We propose an automated, atlas-based algorithm to streamline the measurements in 3D images of the joint and reduce userdependence of the metrics arising from manual identification of the anatomical landmarks. Methods: The method is initialized with coarse registrations of a set of atlas images to the fixed input image. The initial registrations are then refined separately for the tibia and femur and the best matching atlas is selected. Finally, the anatomical landmarks of the best matching atlas are transformed onto the input image by deforming a surface model of the atlas to fit the shape of the tibial plateau in the input image (a mesh-to-volume registration). We apply the method to weight-bearing volumetric images of the knee obtained from 23 subjects using an extremity cone-beam CT system. Results of the automated algorithm were compared to an expert radiologist for measurements of Static Alignment (SA), Medial Tibial Slope (MTS) and Lateral Tibial Slope (LTS). Results: Intra-reader variability as high as 10% for LTS and 7% for MTS (ratio of standard deviation to the mean in repeated measurements) was found for expert radiologist, illustrating the potential benefits of an automated approach in improving the precision of the metrics. The proposed method achieved excellent registration of the atlas mesh to the input volumes. The resulting automated measurements yielded high correlations with expert radiologist, as indicated by correlation coefficients of 0.72 for MTS, 0.8 for LTS, and 0.89 for SA. Conclusions: The automated method for measurement of anatomical metrics of the tibiofemoral joint achieves high correlation with expert radiologist without the need for time consuming and error prone manual selection of landmarks.

Atlas-based automatic measurements of the morphology of the tibiofemoral joint.

PubMed

Brehler, M; Thawait, G; Shyr, W; Ramsay, J; Siewerdsen, J H; Zbijewski, W

2017-02-11

Anatomical metrics of the tibiofemoral joint support assessment of joint stability and surgical planning. We propose an automated, atlas-based algorithm to streamline the measurements in 3D images of the joint and reduce user-dependence of the metrics arising from manual identification of the anatomical landmarks. The method is initialized with coarse registrations of a set of atlas images to the fixed input image. The initial registrations are then refined separately for the tibia and femur and the best matching atlas is selected. Finally, the anatomical landmarks of the best matching atlas are transformed onto the input image by deforming a surface model of the atlas to fit the shape of the tibial plateau in the input image (a mesh-to-volume registration). We apply the method to weight-bearing volumetric images of the knee obtained from 23 subjects using an extremity cone-beam CT system. Results of the automated algorithm were compared to an expert radiologist for measurements of Static Alignment (SA), Medial Tibial Slope (MTS) and Lateral Tibial Slope (LTS). Intra-reader variability as high as ~10% for LTS and 7% for MTS (ratio of standard deviation to the mean in repeated measurements) was found for expert radiologist, illustrating the potential benefits of an automated approach in improving the precision of the metrics. The proposed method achieved excellent registration of the atlas mesh to the input volumes. The resulting automated measurements yielded high correlations with expert radiologist, as indicated by correlation coefficients of 0.72 for MTS, 0.8 for LTS, and 0.89 for SA. The automated method for measurement of anatomical metrics of the tibiofemoral joint achieves high correlation with expert radiologist without the need for time consuming and error prone manual selection of landmarks.

Enhanced detoxification and degradation of herbicide atrazine by a group of O-methyltransferases in rice.

PubMed

Lu, Yi Chen; Luo, Fang; Pu, Zhong Ji; Zhang, Shuang; Huang, Meng Tian; Yang, Hong

2016-12-01

Atrazine (ATR) as a toxic herbicide has become one of the seriously environmental contaminants worldwide due to its long-term intensive use in crop production. This study identified novel methyltransferases (MTs) involved in detoxification and degradation of ATR residues in rice plants. From a subset of MTs differentially expressed in ATR-exposed rice, forty-four O-methyltransferase genes were investigated. Total activities were significantly enhanced by ATR in rice tissues. To prove detoxifying capacity of the MTs in rice plants, two rice O-MTs (LOC_Os04g09604 and LOC_Os11g15040) were selected and transformed into yeast cells (Pichia pastoris X-33). The positive transformants accumulated less ATR and showed less toxicity. Using UPLC-TOF-MS/MS, ATR-degraded products in rice and yeast cells were characterized. A novel O-methylated-modified metabolite (atraton) and six other ATR-derivatives were detected. The topological interaction between LOC_Os04g09604 enzyme and its substrate was specially analyzed by homology modeling programs, which was well confirmed by the molecular docking analysis. The significance of the study is to provide a better understanding of mechanisms for the specific detoxification and degradation of ATR residues in rice growing in environmentally relevant ATR-contaminated soils and may hold a potential engineering perspective for generating ATR-resistant rice that helps to minimize ATR residues in crops. Copyright © 2016 Elsevier Ltd. All rights reserved.

Identification of volatile and semivolatile compounds in chemical ionization GC-MS using a mass-to-structure (MTS) Search Engine with integral isotope pattern ranking.

PubMed

Liao, Wenta; Draper, William M

2013-02-21

The mass-to-structure or MTS Search Engine is an Access 2010 database containing theoretical molecular mass information for 19,438 compounds assembled from common sources such as the Merck Index, pesticide and pharmaceutical compilations, and chemical catalogues. This database, which contains no experimental mass spectral data, was developed as an aid to identification of compounds in atmospheric pressure ionization (API)-LC-MS. This paper describes a powerful upgrade to this database, a fully integrated utility for filtering or ranking candidates based on isotope ratios and patterns. The new MTS Search Engine is applied here to the identification of volatile and semivolatile compounds including pesticides, nitrosoamines and other pollutants. Methane and isobutane chemical ionization (CI) GC-MS spectra were obtained from unit mass resolution mass spectrometers to determine MH(+) masses and isotope ratios. Isotopes were measured accurately with errors of <4% and <6%, respectively, for A + 1 and A + 2 peaks. Deconvolution of interfering isotope clusters (e.g., M(+) and [M - H](+)) was required for accurate determination of the A + 1 isotope in halogenated compounds. Integrating the isotope data greatly improved the speed and accuracy of the database identifications. The database accurately identified unknowns from isobutane CI spectra in 100% of cases where as many as 40 candidates satisfied the mass tolerance. The paper describes the development and basic operation of the new MTS Search Engine and details performance testing with over 50 model compounds.

Anchoring plant metallothioneins to the inner face of the plasma membrane of Saccharomyces cerevisiae cells leads to heavy metal accumulation.

PubMed

Ruta, Lavinia Liliana; Lin, Ya-Fen; Kissen, Ralph; Nicolau, Ioana; Neagoe, Aurora Daniela; Ghenea, Simona; Bones, Atle M; Farcasanu, Ileana Cornelia

2017-01-01

In this study we engineered yeast cells armed for heavy metal accumulation by targeting plant metallothioneins to the inner face of the yeast plasma membrane. Metallothioneins (MTs) are cysteine-rich proteins involved in the buffering of excess metal ions, especially Cu(I), Zn(II) or Cd(II). The cDNAs of seven Arabidopsis thaliana MTs (AtMT1a, AtMT1c, AtMT2a, AtMT2b, AtMT3, AtMT4a and AtMT4b) and four Noccaea caerulescens MTs (NcMT1, NcMT2a, NcMT2b and NcMT3) were each translationally fused to the C-terminus of a myristoylation green fluorescent protein variant (myrGFP) and expressed in Saccharomyces cerevisiae cells. The myrGFP cassette introduced a yeast myristoylation sequence which allowed directional targeting to the cytosolic face of the plasma membrane along with direct monitoring of the intracellular localization of the recombinant protein by fluorescence microscopy. The yeast strains expressing plant MTs were investigated against an array of heavy metals in order to identify strains which exhibit the (hyper)accumulation phenotype without developing toxicity symptoms. Among the transgenic strains which could accumulate Cu(II), Zn(II) or Cd(II), but also non-canonical metal ions, such as Co(II), Mn(II) or Ni(II), myrGFP-NcMT3 qualified as the best candidate for bioremediation applications, thanks to the robust growth accompanied by significant accumulative capacity.

Phosphorylation of Mitochondrial Polyubiquitin by PINK1 Promotes Parkin Mitochondrial Tethering

PubMed Central

Shiba-Fukushima, Kahori; Arano, Taku; Matsumoto, Gen; Inoshita, Tsuyoshi; Yoshida, Shigeharu; Ishihama, Yasushi; Ryu, Kwon-Yul; Nukina, Nobuyuki; Hattori, Nobutaka; Imai, Yuzuru

2014-01-01

The kinase PINK1 and the E3 ubiquitin (Ub) ligase Parkin participate in mitochondrial quality control. The phosphorylation of Ser65 in Parkin's ubiquitin-like (UBl) domain by PINK1 stimulates Parkin activation and translocation to damaged mitochondria, which induces mitophagy generating polyUb chain. However, Parkin Ser65 phosphorylation is insufficient for Parkin mitochondrial translocation. Here we report that Ser65 in polyUb chain is also phosphorylated by PINK1, and that phosphorylated polyUb chain on mitochondria tethers Parkin at mitochondria. The expression of Tom70MTS-4xUb SE, which mimics phospho-Ser65 polyUb chains on the mitochondria, activated Parkin E3 activity and its mitochondrial translocation. An E3-dead form of Parkin translocated to mitochondria with reduced membrane potential in the presence of Tom70MTS-4xUb SE, whereas non-phospho-polyUb mutant Tom70MTS-4xUb SA abrogated Parkin translocation. Parkin binds to the phospho-polyUb chain through its RING1-In-Between-RING (IBR) domains, but its RING0-linker is also required for mitochondrial translocation. Moreover, the expression of Tom70MTS-4xUb SE improved mitochondrial degeneration in PINK1-deficient, but not Parkin-deficient, Drosophila. Our study suggests that the phosphorylation of mitochondrial polyUb by PINK1 is implicated in both Parkin activation and mitochondrial translocation, predicting a chain reaction mechanism of mitochondrial phospho-polyUb production by which rapid translocation of Parkin is achieved. PMID:25474007

Growth and microtubule orientation of Zea mays roots subjected to osmotic stress

NASA Technical Reports Server (NTRS)

Blancaflor, E. B.; Hasenstein, K. H.

1995-01-01

Previous work has shown that microtubule (MT) reorientation follows the onset of growth inhibition on the lower side of graviresponding roots, indicating that growth reduction can occur independently of MT reorientation. To test this observation further, we examined whether the reduction in growth in response to osmotic stress is correlated with MT reorientation. The distribution and rate of growth in maize roots exposed to 350 mOsm sorbitol and KCl or 5 mM Mes/Tris buffer were measured with a digitizer. After various times roots were processed for indirect immunofluorescence microscopy. Application of sorbitol or KCl had no effect on the organization of MTs in the apical 2 mm of the root but resulted in striking and different effects in the basal region of the root. Sorbitol treatment caused rapid appearance of oval to circular holes in the microtubular array that persisted for at least 9 h. Between 30 min and 4 h of submersion in KCl, MTs in cortical cells 4 mm and farther from the quiescent center began to reorient oblique to the longitudinal axis. After 9 h, the alignment of MTs had shifted to parallel to the root axis but MTs of the epidermal cells remained transverse. In KCl-treated roots MT reorientation appeared to follow a pattern of development similar to that in controls but without elongation. Our data provide additional evidence that MT reorientation is not the cause but a consequence of growth inhibition.

Sensitivity improvements of a resonance-based tactile sensor.

PubMed

Murayama, Yoshinobu; Lindahl, Olof A

2017-02-01

Resonance-based contact-impedance measurement refers to the application of resonance sensors based on the measurement of the changes in the resonance curve of an ultrasonic resonator in contact with a surface. The advantage of the resonance sensor is that it is very sensitive to small changes in the contact impedance. A sensitive micro tactile sensor (MTS) was developed, which measured the elasticity of soft living tissues at the single-cell level. In the present paper, we studied the method of improving the touch and stiffness sensitivity of the MTS. First, the dependence of touch sensitivity in relation to the resonator length was studied by calculating the sensitivity coefficient at each length ranging from 9 to 40 mm. The highest touch sensitivity was obtained with a 30-mm-long glass needle driven at a resonance frequency of 100 kHz. Next, the numerical calculation of contact impedance showed that the highest stiffness sensitivity was achieved when the driving frequency was 100 kHz and the contact-tip diameter of the MTS was 10 μm. The theoretical model was then confirmed experimentally using a phase-locked-loop-based digital feedback oscillation circuit. It was found that the developed MTS, whose resonant frequency was 97.030 kHz, performed with the highest sensitivity of 53.2 × 10 6  Hz/N at the driving frequency of 97.986 kHz, i.e. the highest sensitivity was achieved at 956 Hz above the resonant frequency.

Active and Dynamic Nanomaterials Based on Active Biomolecules

NASA Astrophysics Data System (ADS)

Koch, Steven J.; Rivera, Susan B.; Boal, Andrew K.; Edwards, J. Matthew; Bauer, Joseph M.; Manginell, Ronald P.; Liu, Jun; Bunker, Bruce C.; Bachand, George D.

2004-03-01

Living organisms have evolved dynamic and adaptable materials that fundamentally differ from synthetic materials. These biomaterials use chemical energy to drive non-equilibrium assembly processes, and to reconfigure in response to external stimuli or life cycle changes. Two striking examples are the diatom's active assembly of silica into a patterned cytoskeleton, and the chameleon's active transport of pigment particles to rapidly change skin color. Advances in molecular biology and nanoscale materials synthesis now present the opportunity for integrating biomolecules with synthetic components to produce new types of materials with novel assembly and adaptation capabilities. Our group has begun utilizing kinesin motor proteins and microtubules (MTs) to explore the construction of biomimetic materials. Initial work has focused on characterizing and engineering the properties of the biomolecules for robust performance in artificial systems. We have characterized the biochemical and biophysical properties of a kinesin motor protein from a thermostable fungus, and have evaluated strategies for stabilizing and functionalizing the MTs. We also have developed strategies for directed transport of MT shuttles, and for controlling the loading and unloading of nanoscale cargo.

Estimation of the geothermal potential of the Caldara di Manziana site in the Mts Sabatini Volcanic District (Central Italy) by integrating geochemical data and 3D-GIS modelling.

NASA Astrophysics Data System (ADS)

Ranaldi, Massimo; Lelli, Matteo; Tarchini, Luca; Carapezza, Maria Luisa; Patera, Antonio

2016-04-01

High-enthalpy geothermal fields of Central Italy are hosted in deeply fractured carbonate reservoirs occurring in thermally anomalous and seismically active zones. However, the Mts. Sabatini volcanic district, located north of Rome, has an interesting deep temperatures (T), but it is characterized by low to very low seismicity and permeability in the reservoir rocks (mostly because of hydrothermal self-sealing processes). Low PCO2 facilitates the complete sealing of the reservoir fractures, preventing hot fluids rising and, determining a low CO2 flux at the surface. Conversely, high CO2 flux generally reflects a high pressure of CO2, suggesting that an active geothermal reservoir is present at depth. In Mts. Sabatini district, the Caldara of Manziana (CM) is the only zone characterized by a very high CO2 flux (188 tons/day) from a surface of 0.15 km2) considering both the diffuse and viscous CO2 emission. This suggests the likely presence of an actively degassing geothermal reservoir at depth. Emitted gas is dominated by CO2 (>97 vol.%). Triangular irregular networks (TINs) have been used to represent the morphology of the bottom of the surficial volcanic deposits, the thickness of the impervious formation and the top of the geothermal reservoir. The TINs, integrated by T-gradient and deep well data, allowed to estimate the depth and the temperature of the top of the geothermal reservoir, respectively to ~-1000 m from the surface and to ~130°C. These estimations are fairly in agreement with those obtained by gas chemistry (818

Epothilone D prevents binge methamphetamine-mediated loss of striatal dopaminergic markers.

PubMed

Killinger, Bryan A; Moszczynska, Anna

2016-02-01

Exposure to binge methamphetamine (METH) can result in a permanent or transient loss of dopaminergic (DAergic) markers such as dopamine (DA), dopamine transporter, and tyrosine hydroxylase (TH) in the striatum. We hypothesized that the METH-induced loss of striatal DAergic markers was, in part, due to a destabilization of microtubules (MTs) in the nigrostriatal DA pathway that ultimately impedes anterograde axonal transport of these markers. To test this hypothesis, adult male Sprague-Dawley rats were treated with binge METH or saline in the presence or absence of epothilone D (EpoD), a MT-stabilizing compound, and assessed 3 days after the treatments for the levels of several DAergic markers as well as for the levels of tubulins and their post-translational modifications (PMTs). Binge METH induced a loss of stable long-lived MTs within the striatum but not within the substantia nigra pars compacta (SNpc). Treatment with a low dose of EpoD increased the levels of markers of stable MTs and prevented METH-mediated deficits in several DAergic markers in the striatum. In contrast, administration of a high dose of EpoD appeared to destabilize MTs and potentiated the METH-induced deficits in several DAergic markers. The low-dose EpoD also prevented the METH-induced increase in striatal DA turnover and increased behavioral stereotypy during METH treatment. Together, these results demonstrate that MT dynamics plays a role in the development of METH-induced losses of several DAergic markers in the striatum and may mediate METH-induced degeneration of terminals in the nigrostriatal DA pathway. Our study also demonstrates that MT-stabilizing drugs such as EpoD have a potential to serve as useful therapeutic agents to restore function of DAergic nerve terminals following METH exposure when administered at low doses. Administration of binge methamphetamine (METH) negatively impacts neurotransmission in the nigrostriatal dopamine (DA) system. The effects of METH include decreasing the levels of DAergic markers in the striatum. We have determined that high-dose METH destabilizes microtubules in this pathway, which is manifested by decreased levels of acetylated (Acetyl) and detyrosinated (Detyr) α-tubulin (I). A microtubule stabilizing agent epothilone D protects striatal microtubules form the METH-induced loss of DAergic markers (II). These findings provide a new strategy for protection form METH - restoration of proper axonal transport. © 2015 International Society for Neurochemistry.

Assessing generative braille responding following training in a matching-to-sample format.

PubMed

Putnam, Brittany C; Tiger, Jeffrey H

2016-12-01

We evaluated the effects of teaching sighted college students to select printed text letters given a braille sample stimulus in a matching-to-sample (MTS) format on the emergence of untrained (a) construction of print characters given braille samples, (b) construction of braille characters given print samples, (c) transcription of print characters given braille sample sentences, and (d) vocal reading given braille sample passages. The results demonstrated the generative development of these repertoires given MTS instruction. © 2016 Society for the Experimental Analysis of Behavior.

The Coast Guard Proceedings of the Marine Safety and Security Council. Volume 72, Number 2, Summer 2015

DTIC Science & Technology

2015-01-01

environ- mentally friendly power -producing and -saving technolo- gies on physical ATONs; using photovoltaic cells as supple- mental power sources, such...ATON positioning, solar power , and self-contained LED lanterns. And, as technological advancements have made accessing and transiting the MTS more...Atmospheric Administration (NOAA) charts up to date. However, with the vast increase in com- puting power and system interconnectivity, there is a rec

Chesapeake Inundation Prediction System (CIPS): A regional prototype for a national problem

USGS Publications Warehouse

Stamey, B.; Smith, W.; Carey, K.; Garbin, D.; Klein, F.; Wang, Hongfang; Shen, J.; Gong, W.; Cho, J.; Forrest, D.; Friedrichs, C.; Boicourt, W.; Li, M.; Koterba, M.; King, D.; Titlow, J.; Smith, E.; Siebers, A.; Billet, J.; Lee, J.; Manning, Douglas R.; Szatkowski, G.; Wilson, D.; Ahnert, P.; Ostrowski, J.

2007-01-01

Recent Hurricanes Katrina and Isabel, among others, not only demonstrated their immense destructive power, but also revealed the obvious, crucial need for improved storm surge forecasting and information delivery to save lives and property in future storms. Current operational methods and the storm surge and inundation products do not adequately meet requirements needed by Emergency Managers (EMs) at local, state, and federal levels to protect and inform our citizens. The Chesapeake Bay Inundation Prediction System (CIPS) is being developed to improve the accuracy, reliability, and capability of flooding forecasts for tropical cyclones and non-tropical wind systems such as nor'easters by modeling and visualizing expected on-land storm-surge inundation along the Chesapeake Bay and its tributaries. An initial prototype has been developed by a team of government, academic and industry partners through the Chesapeake Bay Observing System (CBOS) of the Mid-Atlantic Coastal Ocean Observing Regional Association (MACOORA) within the Integrated Ocean Observing System (IOOS). For demonstration purposes, this initial prototype was developed for the tidal Potomac River in the Washington, DC metropolitan area. The preliminary information from this prototype shows great potential as a mechanism by which NOAA National Weather Service (NWS) Forecast Offices (WFOs) can provide more specific and timely forecasts of likely inundation in individual localities from significant storm surge events. This prototype system has shown the potential to indicate flooding at the street level, at time intervals of an hour or less, and with vertical resolution of one foot or less. This information will significantly improve the ability of EMs and first responders to mitigate life and property loss and improve evacuation capabilities in individual communities. This paper provides an update and expansion of the initial prototype that was presented at the Oceans 2006 MTS/IEEE Conference in Boston, MA. ??2007 MTS.

Marble-hosted ruby deposits of the Morogoro Region, Tanzania

NASA Astrophysics Data System (ADS)

Balmer, Walter A.; Hauzenberger, Christoph A.; Fritz, Harald; Sutthirat, Chakkaphan

2017-10-01

The ruby deposits of the Uluguru and Mahenge Mts, Morogoro Region, are related to marbles which represent the cover sequence of the Eastern Granulites in Tanzania. In both localities the cover sequences define a tectonic unit which is present as a nappe structure thrusted onto the gneissic basement in a north-western direction. Based on structural geological observations the ruby deposits are bound to mica-rich boudins in fold hinges where fluids interacted with the marble-host rock in zones of higher permeability. Petrographic observations revealed that the Uluguru Mts deposits occur within calcite-dominated marbles whereas deposits in the Mahenge Mts are found in dolomite-dominated marbles. The mineral assemblage describing the marble-hosted ruby deposit in the Uluguru Mts is characterised by corundum-dolomite-phlogopite ± spinel, calcite, pargasite, scapolite, plagioclase, margarite, chlorite, tourmaline whereas the assemblage corundum-calcite-plagioclase-phlogopite ± dolomite, pargasite, sapphirine, titanite, tourmaline is present in samples from the Mahenge Mts. Although slightly different in mineral assemblage it was possible to draw a similar ruby formation history for both localities. Two ruby forming events were distinguished by textural differences, which could also be modeled by thermodynamic T-XCO2 calculations using non-ideal mixing models of essential minerals. A first formation of ruby appears to have taken place during the prograde path (M1) either by the breakdown of diaspore which was present in the original sedimentary precursor rock or by the breakdown of margarite to corundum and plagioclase. The conditions for M1 metamorphism was estimated at ∼750 °C at 10 kbar, which represents granulite facies conditions. A change in fluid composition towards a CO2 dominated fluid triggered a second ruby generation to form. Subsequently, the examined units underwent a late greenschist facies overprint. In the framework of the East African Orogen we assume that the prograde ruby formation occurred at the commonly observed metamorphic event around 620 Ma. At the peak or during beginning of retrogression the fluid composition changed triggering a second ruby generation. The late stage greenschist facies overprint could have occurred at the waning stage of this metamorphic episode which is in the range of ∼580 Ma.

Cost-effectiveness of precision medicine in the fourth-line treatment of metastatic lung adenocarcinoma: An early decision analytic model of multiplex targeted sequencing.

PubMed

Doble, Brett; John, Thomas; Thomas, David; Fellowes, Andrew; Fox, Stephen; Lorgelly, Paula

2017-05-01

To identify parameters that drive the cost-effectiveness of precision medicine by comparing the use of multiplex targeted sequencing (MTS) to select targeted therapy based on tumour genomic profiles to either no further testing with chemotherapy or no further testing with best supportive care in the fourth-line treatment of metastatic lung adenocarcinoma. A combined decision tree and Markov model to compare costs, life-years, and quality-adjusted life-years over a ten-year time horizon from an Australian healthcare payer perspective. Data sources included the published literature and a population-based molecular cohort study (Cancer 2015). Uncertainty was assessed using deterministic sensitivity analyses and quantified by estimating expected value of perfect/partial perfect information. Uncertainty due to technological/scientific advancement was assessed through a number of plausible future scenario analyses. Point estimate incremental cost-effective ratios indicate that MTS is not cost-effective for selecting fourth-line treatment of metastatic lung adenocarcinoma. Lower mortality rates during testing and for true positive patients, lower health state utility values for progressive disease, and targeted therapy resulting in reductions in inpatient visits, however, all resulted in more favourable cost-effectiveness estimates for MTS. The expected value to decision makers of removing all current decision uncertainty was estimated to be between AUD 5,962,843 and AUD 13,196,451, indicating that additional research to reduce uncertainty may be a worthwhile investment. Plausible future scenarios analyses revealed limited improvements in cost-effectiveness under scenarios of improved test performance, decreased costs of testing/interpretation, and no biopsy costs/adverse events. Reductions in off-label targeted therapy costs, when considered together with the other scenarios did, however, indicate more favourable cost-effectiveness of MTS. As more clinical evidence is generated for MTS, the model developed should be revisited and cost-effectiveness re-estimated under different testing scenarios to further understand the value of precision medicine and its potential impact on the overall health budget. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Predictors of spontaneous transient seizure remission in patients of medically refractory epilepsy due to mesial temporal sclerosis (MTS).

PubMed

Dhiman, Vikas; Sinha, Sanjib; Arimappamagan, Arivazhagan; Mahadevan, Anita; Bharath, Rose Dawn; Saini, Jitender; Rajeswaran, Jamuna; Rao, Malla Bhaskar; Shankar, Susrala K; Satishchandra, Parathasarthy

2015-02-01

To analyze the predictors of spontaneous transient seizure remission for ≥1 year in patients with drug-resistant epilepsy (DRE) due to mesial temporal sclerosis (MTS). This analysis included 38 patients with DRE (M:F = 20:18, age: 31.7 ± 10.9 years) diagnosed with unilateral MTS (right:left = 16:22). Group I ('remission' group) comprised of patients with seizure remission (M:F = 10:8, age: 32.8 ± 12.3 years, mean seizure free period: 2.2 ± 1.1 years; median: 2.1 years). Group II ('non-remission' group) comprised of age and gender matched 20 patients (M:F = 10:10, age: 30.7 ± 9.7 years) with unilateral MTS who never had seizure remission and subsequently underwent epilepsy surgery. Groups I and II were compared to find the predictors associated with transient seizure remission. The age at onset of seizures in group I was 13.2 ± 11.8 years and in group II was 12.0 ± 7.6 years. The duration of seizure was: group I - 19.7 ± 12.5 years and group II - 19.3 ± 7.7 years. Past history of seizure remissions (p < 0.001), frequent periods of remissions (p < 0.001), first remission within a year of onset of seizures (p = 0.04) and normal EEG (p = 0.04) were the important clinical predictors associated with seizure remission in this cohort. Fifteen patients in group I (83.3%) experienced remission following either change in AED (p ≤ 0.001) or increase in AED dosages (p < 0.001). There was no difference between the two groups regarding the type of semiology (partial vs. secondarily generalized) (p = 0.50), family history of seizures (p = 1.0), side of the lesion (p = 0.34), history of febrile seizures (p = 1.0) and the number of AEDs used (p = 0.53). The present study unfolds, some of the clinically relevant predictors associated with transient seizure remission in patients with DRE and MTS. Future molecular and network studies are required to understand its mechanism. Copyright © 2014 Elsevier B.V. All rights reserved.

Malachite green-conjugated microtubules as mobile bioprobes selective for malachite green aptamers with capturing/releasing ability.

PubMed

Hirabayashi, Miki; Taira, Shu; Kobayashi, Suzuko; Konishi, Kaoru; Katoh, Kaoru; Hiratsuka, Yuichi; Kodaka, Masato; Uyeda, Taro Q P; Yumoto, Noboru; Kubo, Tai

2006-06-20

We have developed a novel mobile bioprobe using a conjugate of a kinesin-driven microtubule (MT) and malachite green (MG) as a platform for capturing MG RNA aptamers. The fluorescence of MG increases when it is bound to an MG aptamer, allowing MT-MG conjugates to work as sensors of RNA transcripts containing the MG aptamer sequence. Kinesin motor proteins provide an effective driving force to create mobile bioprobes without any manipulation. Although the fluorescence of a small number of MG-binding aptamers is low, the self-organization of tubulins into MTs enables the microscopic observation of the bound aptamers by collecting them on MTs. We demonstrate that MT-MG conjugates can select target aptamers from a transcription mixture and transport them without losing their inherent motility. Because the MG aptamer binds MG in a reversible manner, MT-MG conjugates can conditionally load and unload the target aptamers. This is one advantage of this system over the molecular probes developed previously in which reversible unloading is impossible due to high-affinity binding, such as between avidin and biotin. Furthermore, an MT-MG conjugate can be used as a platform for other MG aptameric sensors with recognition regions for various target analytes optimized by further selection procedures. This is the first step to applying living systems to in vitro devices. This technique could provide a new paradigm of mobile bioprobes establishing high-throughput in vitro selection systems using microfluidic devices operating in parallel. 2006 Wiley Periodicals, Inc.

High-spatial-resolution passive microwave sounding systems

NASA Technical Reports Server (NTRS)

Staelin, D. H.; Rosenkranz, P. W.

1994-01-01

The principal contributions of this combined theoretical and experimental effort were to advance and demonstrate new and more accurate techniques for sounding atmospheric temperature, humidity, and precipitation profiles at millimeter wavelengths, and to improve the scientific basis for such soundings. Some of these techniques are being incorporated in both research and operational systems. Specific results include: (1) development of the MIT Microwave Temperature Sounder (MTS), a 118-GHz eight-channel imaging spectrometer plus a switched-frequency spectrometer near 53 GHz, for use on the NASA ER-2 high-altitude aircraft, (2) conduct of ER-2 MTS missions in multiple seasons and locations in combination with other instruments, mapping with unprecedented approximately 2-km lateral resolution atmospheric temperature and precipitation profiles, atmospheric transmittances (at both zenith and nadir), frontal systems, and hurricanes, (3) ground based 118-GHz 3-D spectral images of wavelike structure within clouds passing overhead, (4) development and analysis of approaches to ground- and space-based 5-mm wavelength sounding of the upper stratosphere and mesosphere, which supported the planning of improvements to operational weather satellites, (5) development of improved multidimensional and adaptive retrieval methods for atmospheric temperature and humidity profiles, (6) development of combined nonlinear and statistical retrieval techniques for 183-GHz humidity profile retrievals, (7) development of nonlinear statistical retrieval techniques for precipitation cell-top altitudes, and (8) numerical analyses of the impact of remote sensing data on the accuracy of numerical weather predictions; a 68-km gridded model was used to study the spectral properties of error growth.

Trunk-arm coordination in reaching for moving targets in people with Parkinson's disease: comparison between virtual and physical reality.

PubMed

Ma, Hui-Ing; Hwang, Wen-Juh; Wang, Ching-Yi; Fang, Jing-Jing; Leong, Iat-Fai; Wang, Tsui-Ying

2012-10-01

We used a trunk-assisted prehension task to examine the effect of task (reaching for stationary vs. moving targets) and environmental constraints (virtual reality [VR] vs. physical reality) on the temporal control of trunk and arm motions in people with Parkinson's disease (PD). Twenty-four participants with PD and 24 age-matched controls reached for and grasped a ball that was either stationary or moving along a ramp 120% of arm length away. In a similar VR task, participants reached for a virtual ball that was either stationary or moving. Movement speed was measured as trunk and arm movement times (MTs); trunk-arm coordination was measured as onset interval and offset interval between trunk and arm motions, as well as a summarized index-desynchrony score. In both VR and physical reality, the PD group had longer trunk and arm MTs than the control group when reaching for stationary balls (p<.001). When reaching for moving balls in VR and physical reality, however, the PD group had lower trunk and arm MTs, onset intervals, and desynchrony scores (p<.001). For the PD group, VR induced shorter trunk MTs, shorter offset intervals, and lower desynchrony scores than did physical reality when reaching for moving balls (p<.001). These findings suggest that using real moving targets in trunk-assisted prehension tasks improves the speed and synchronization of trunk and arm motions in people with PD, and that using virtual moving targets may induce a movement termination strategy different from that used in physical reality. Copyright © 2012 Elsevier B.V. All rights reserved.

Efficacy and Safety of Once-Daily Minoxidil Foam 5% Versus Twice-Daily Minoxidil Solution 2% in Female Pattern Hair Loss: A Phase III, Randomized, Investigator-Blinded Study.

PubMed

Blume-Peytavi, Ulrike; Shapiro, Jerry; Messenger, Andrew G; Hordinsky, Maria K; Zhang, Paul; Quiza, Carlos; Doshi, Uday; Olsen, Elise A

2016-07-01

A once-daily minoxidil topical foam (MTF) has been developed to treat female pattern hair loss.
Determine noninferiority of once-daily 5% MTF versus twice-daily 2% minoxidil topical solution (MTS) based on the change from baseline in target area hair count (TAHC) at 24 weeks. In a randomized, phase III trial, women with female pattern hair loss received once-daily 5% MTF (n=161) or twice-daily 2% MTS (n=161) for 52 weeks. Primary endpoint was change from baseline in TAHC at 24 weeks. Secondary endpoint was change from baseline in TAHC at 12 weeks. Exploratory endpoints included change in total unit area density and change in overall scalp coverage.
Once-daily 5% MTF increased TAHC from baseline (adjusted mean ± standard error) by 23.9 ± 2.1 hairs/cm² at week 24. Twice-daily 2% MTS increased TAHC 24.2 ± 2.1 hairs/cm² at week 24. The treatment difference was -0.3 hairs/cm² (95% CI = -6.0, 5.4). Since the lower bound of the 95% CI was less than -5.0, the prespecified noninferiority goal was not met. Both treatments were well tolerated.
Once-daily 5% MTF and twice-daily 2% MTS induced hair regrowth in female pattern hair loss, but prespecified noninferiority criteria were not met.
ClinicalTrials.gov identifier: NCT01145625

J Drugs Dermatol. 2016;15(7):883-889.

Expression of Metallothionein and Vascular Endothelial Growth Factor Isoforms in Breast Cancer Cells.

PubMed

Wierzowiecka, Barbara; Gomulkiewicz, Agnieszka; Cwynar-Zajac, Lucja; Olbromski, Mateusz; Grzegrzolka, Jedrzej; Kobierzycki, Christopher; Podhorska-Okolow, Marzenna; Dziegiel, Piotr

2016-01-01

Metallothioneins (MTs) are low-molecular-weight and cysteine-rich proteins that bind heavy metal ions and oxygen-free radicals. MTs are commonly expressed in various tissues of mammals and are involved in regulation of cell proliferation and differentiation, and may be engaged in angiogenesis. Expression of MTs has been studied in many cancer types, especially breast cancer. The research results indicate that MTs may play important, although not yet fully known, roles in cancer angiogenesis. The aim of this study was to analyze the level of gene expression of selected MT isoforms induced with zinc ions in correlation with vascular endothelial growth factor (VEGF) isoforms in in vitro models of breast cancer. The studies were carried out in three breast cancer cell lines (MCF-7, SK-BR-3, MDA-MB-231). An epithelial cell line derived from normal breast tissue (Me16c) was used as a control. The levels of expression of selected MT isoforms and selected genes involved in angiogenesis were studied with real-time PCR. Expression of different MT isoforms was induced by zinc ions to differing degrees in individual breast cancer cell lines. An increase in the expression of some MT isoforms was associated with a slight increase in the level of expression of VEGFA. The research results may indicate certain correlation between an increased expression of selected MT isoforms and a pro-angiogenic factor VEGF in specific types of breast cancer cells. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Quantitative immunodetection of metallothioneins in relation to metals concentration in spiders from variously polluted areas.

PubMed

Babczyńska, Agnieszka; Wilczek, Grażyna; Szulińska, Elżbieta; Franiel, Izabella

2011-09-01

Spiders inhabiting post industrial environments, such as waste heaps or ore-bearing areas, are exposed to high concentrations of metals, accumulated in the body of their prey and transferred along food chains. Therefore spiders are pressed to develop metal-neutralization strategies. Low-molecular, multifunction proteins: metallothioneins (MTs), often postulated as biomarkers of metal exposure, are known to bind metals and thus protect organisms against their toxic effects. Yet the proteins are still not well recognized in spiders. The aim of this study was to assess, by immunodetection method, ELISA, the concentration of metallothioneins in adult females of three web building spider species: Araneus diadematus (Araneidae), Agelena labyrinthica (Agelenidae) and Linyphia triangularis (Linyphiidae) from three variously polluted areas in southern Poland: Olkusz, ore-bearing post industrial site; Katowice-WeŁnowiec: post metallurgic waste heap, Pilica: the reference, rural, area. The concentration of metallothioneins has been analyzed in relation to the metal concentration in spiders body. The study gives the evidence that metallothioneins are reliably detectable by means of ELISA technique. The analysis of results obtained shows a strong species-dependence of the MTs level. Positive correlations between MTs concentration and metal body burden (mainly Zn and Pb) were found. This suggests that the proteins play an important role in the neutralization and regulation of metal ions in spiders. The same correlation indicate the possibility to consider MTs in spiders as biomarkers of metal exposure and effects. However, the species specificity as well as metal characteristics should be taken under account. Copyright © 2011 Elsevier Inc. All rights reserved.

Turbulence Modeling for the Simulation of Transition in Wall Shear Flows

NASA Technical Reports Server (NTRS)

Crawford, Michael E.

2007-01-01

Our research involves study of the behavior of k-epsilon turbulence models for simulation of bypass-level transition over flat surfaces and turbine blades. One facet of the research has been to assess the performance of a multitude of k-epsilon models in what we call "natural transition", i.e. no modifications to the k-e models. The study has been to ascertain what features in the dynamics of the model affect the start and end of the transition. Some of the findings are in keeping with those reported by others (e.g. ERCOFTAC). A second facet of the research has been to develop and benchmark a new multi-time scale k-epsilon model (MTS) for use in simulating bypass-level transition. This model has certain features of the published MTS models by Hanjalic, Launder, and Schiestel, and by Kim and his coworkers. The major new feature of our MTS model is that it can be used to compute wall shear flows as a low-turbulence Reynolds number type of model, i.e. there is no required partition with patching a one-equation k model in the near-wall region to a two-equation k-epsilon model in the outer part of the flow. Our MTS model has been studied extensively to understand its dynamics in predicting the onset of transition and the end-stage of the transition. Results to date indicate that it far superior to the standard unmodified k-epsilon models. The effects of protracted pressure gradients on the model behavior are currently being investigated.

Common Manual Therapy Practices in the Netherlands for Infants With Upper Cervical Dysfunction: A Prospective Cohort Study.

PubMed

Saedt, Eric R I C; Driehuis, Femke; Hoogeboom, Thomas J; van der Woude, Bé H; de Bie, Rob A; Nijhuis-van der Sanden, Maria W G

2018-01-01

The purpose of this study was to describe common clinical practices of manual therapists (MTs) in the Netherlands for infants with indications of upper cervical dysfunction (UCD). A prospective observational cohort study was conducted to gain insight into characteristics, reasons for seeking care, and common clinical practice for infants (<27 weeks) with indications of UCD, referred to MTs. Pre- and posttreatment self-reported questionnaires were used to collect data from parents and MTs. Parents reported on infant characteristics and perceived effect of treatment. Manual therapists reported on diagnostics, therapeutic procedures, and outcomes. Between 2006 and 2007, data regarding 307 referred infants (mean age: 11.2 weeks) were collected by parents and 42 MTs. The most frequent reasons for seeking care were positional preference, restlessness, and/or abnormal head position. Manual therapists observed active, spontaneous, and provoked mobility and passive upper cervical mobility. Of the 307 infants, 295 were diagnosed with UCD based on positive outcomes on the flexion-rotation test and/or lateral flexion test. After treatment with mobilization techniques, positive outcomes on the flexion-rotation test decreased from 78.8% to 6.8%. For the lateral flexion test, the positive outcomes decreased from 91.5% to 6.2%. All parents perceived positive treatment effects. No serious adverse events were reported during this study. This is the first study to describe common clinical practice for infants referred for manual therapy. Infants with UCD were treated mainly with upper cervical mobilization techniques, and the greatest perceived effect was observed after approximately 2 treatment sessions. Copyright © 2018. Published by Elsevier Inc.

The effect of a calcium phosphate mouth rinse on (chemo) radiation induced oral mucositis in head and neck cancer patients: a prospective study.

PubMed

Stokman, M A; Burlage, F R; Spijkervet, F K L

2012-08-01

Promising results of a calcium phosphate (CP) mouth rinse on reduced severity of oral mucositis have been reported. The aim of this study was to determine the effect of a CP mouth rinse on the frequency, duration and severity of (chemo) radiation induced oral mucositis in patients with head-neck cancer. patients with oral malignancies, treated with (chemo) radiotherapy, were included. Patients rinsed four times a day with a CP mouth rinse. Patients not willing to rinse with the CP mouth rinse served as control. Mucositis was scored according to the WHO score at baseline and twice a week during the full course of (chemo) radiotherapy. Patient's self-reported mouth-throat soreness (MTS) was evaluated at the same time interval using a diary in the CP mouth rinse group. The outcomes on MTS were compared with a historical control group. Fifty-two patients were analysed: 25 CP mouth rinse group, 11 control group and 16 historical group. There was no significant difference between the CP group and control group on development and severity of oral mucositis. No significant difference was found for subjective outcomes on MTS between the CP group and the historical group. The CP mouth rinse seems to have no influence on the frequency, duration and severity of oral mucositis during (chemo) radiation in patients with head and neck cancer. A trend to develop less MTS for drinking and eating was found when applying the CP mouth rinse. © 2012 John Wiley & Sons A/S.

Structure-property relation and relevance of beam theories for microtubules: a coupled molecular and continuum mechanics study.

PubMed

Li, Si; Wang, Chengyuan; Nithiarasu, Perumal

2018-04-01

Quasi-one-dimensional microtubules (MTs) in cells enjoy high axial rigidity but large transverse flexibility due to the inter-protofilament (PF) sliding. This study aims to explore the structure-property relation for MTs and examine the relevance of the beam theories to their unique features. A molecular structural mechanics (MSM) model was used to identify the origin of the inter-PF sliding and its role in bending and vibration of MTs. The beam models were then fitted to the MSM to reveal how they cope with the distinct mechanical responses induced by the inter-PF sliding. Clear evidence showed that the inter-PF sliding is due to the soft inter-PF bonds and leads to the length-dependent bending stiffness. The Euler beam theory is found to adequately describe MT deformation when the inter-PF sliding is largely prohibited. Nevertheless, neither shear deformation nor the nonlocal effect considered in the 'more accurate' beam theories can fully capture the effect of the inter-PF sliding. This reflects the distinct deformation mechanisms between an MT and its equivalent continuous body.

A MEMS Micro-Translation Stage with Long Linear Translation

NASA Technical Reports Server (NTRS)

Ferguson, Cynthia K.; English, J. M.; Nordin, G. P.; Ashley, P. R.; Abushagur, M. A. G.

2004-01-01

A MEMS Micro-Translation Stage (MTS) actuator concept has been developed that is capable of traveling long distances, while maintaining low power, low voltage, and accuracy as required by many applications, including optical coupling. The Micro-Translation Stage (MTS) uses capacitive electrostatic forces in a linear motor application, with stationary stators arranged linearly on both sides of a channel, and matching rotors on a moveable shuttle. This creates a force that allows the shuttle to be pulled along the channel. It is designed to carry 100 micron-sized elements on the top surface, and can travel back and forth in the channel, either in a stepping fashion allowing many interim stops, or it can maintain constant adjustable speeds for a controlled scanning motion. The MTS travel range is limited only by the size of the fabrication wafer. Analytical modeling and simulations were performed based on the fabrication process, to assure the stresses, friction and electrostatic forces were acceptable to allow successful operation of this device. The translation forces were analyzed to be near 0.5 micron N, with a 300 micron N stop-to-stop time of 11.8 ms.

Determination of self attenuation coefficient and relative TL efficiency of CaSO 4 :Dy, LiF:Mg,Cu,P and LiF:Mg,Ti TLDs - An alternate approach

NASA Astrophysics Data System (ADS)

Bakshi, A. K.; Chatterjee, S.; Palani Selvam, T.; Joshi, V. J.; Chougaonkar, M. P.

2011-10-01

Self attenuation of TL and relative TL efficiency of polytetra fluoro ethylene (PTFE) embedded CaSO 4:Dy disc, LiF:Mg,Ti (MTS) disc and LiF:Mg,Cu,P (MCP-N) chip were determined in the present study for photons of energy 10-34 keV. The relative TL efficiency was determined using an alternative approach in which ratio of experimental response and corrected theoretical response was used instead of measuring the absolute TL emission in photon counting mode. For CaSO 4:Dy disc, it was found that with increasing the proportion of CaSO 4:Dy phosphor in the disc, the light attenuation coefficient increases. The light attenuation coefficient of MTS disc and MCP-N chip was found to be 23.4 and 45.5 cm -1, respectively. The relative TL efficiency in the photon energy range of 10-34 keV for MTS discs and MCP-N chips, evaluated in the present study matches well with the reported values in the literature.

Microneurosurgical management of temporal lobe epilepsy by amygdalohippocampectomy (AH) plus standard anterior temporal lobectomy (ATL): a report of our initial five cases in Bangladesh

PubMed Central

Chowdhury, F H; Haque, M R; Islam, M S; Sarker, MH; Kawsar, KA; Sarker, AC

2010-01-01

Patient presenting as a case of Temporal Lobe Epilepsy (TLE) are usually resistant to antiepileptic drugs and surgery is the treatment of choice. This type of epilepsy may be due to Mesial Temporal Sclerosis (MTS), tumors [i.e. low grade glioma, Arterio-Venous Malformation (AVM) etc], trauma, infection (Tuberculosis) etc. Here we report five cases of surgically treated TLE that were due to a MTS, MTS with arachnoid cyst, low grade ganglioglioma, high grade ganglioglioma and a tuberculoma in the department of neurosurgery, Dhaka Medical College Hospital and Islami Bank Central Hospital, Dhaka, Bangladesh from August 2009 to February 2010. In all cases the only presenting symptoms was complex partial seizures (psychomotor epilepsy) for which all underwent scalp EEG (Electro Encephalogram) and MRI (Magnetic Resonance Imaging) of Brain. All patients were managed by amygdalohippocampectomy plus standard anterior lobectomy. One patient with high grade ganglioglioma recurred within two months of operation and expired within five months. The rest of the cases are seizure and disease free till the last follow up. PMID:22028754

GSK3 controls axon growth via CLASP-mediated regulation of growth cone microtubules

PubMed Central

Hur, Eun-Mi; Saijilafu; Lee, Byoung Dae; Kim, Seong-Jin; Xu, Wen-Lin; Zhou, Feng-Quan

2011-01-01

Suppression of glycogen synthase kinase 3 (GSK3) activity in neurons yields pleiotropic outcomes, causing both axon growth promotion and inhibition. Previous studies have suggested that specific GSK3 substrates, such as adenomatous polyposis coli (APC) and collapsin response mediator protein 2 (CRMP2), support axon growth by regulating the stability of axonal microtubules (MTs), but the substrate(s) and mechanisms conveying axon growth inhibition remain elusive. Here we show that CLIP (cytoplasmic linker protein)-associated protein (CLASP), originally identified as a MT plus end-binding protein, displays both plus end-binding and lattice-binding activities in nerve growth cones, and reveal that the two MT-binding activities regulate axon growth in an opposing manner: The lattice-binding activity mediates axon growth inhibition induced by suppression of GSK3 activity via preventing MT protrusion into the growth cone periphery, whereas the plus end-binding property supports axon extension via stabilizing the growing ends of axonal MTs. We propose a model in which CLASP transduces GSK3 activity levels to differentially control axon growth by coordinating the stability and configuration of growth cone MTs. PMID:21937714

The influence of physical therapy and anti-botulinum toxin antibody on the efficacy of botulinum toxin-A injections in children with spastic cerebral palsy.

PubMed

Jang, Dae-Hyun; Sung, In Young

2014-12-01

To identify factors associated with the efficacy of botulinum toxin-A (BoNT-A) injections. Thirty-eight children with spastic cerebral palsy (CP) received BoNT-A injections into the gastrocnemius. The baseline anti-botulinum antibodies were checked. The Static dorsiflexion range of motion (ROM), Modified Tardieu Scale (MTS) and Physician Rating Scale (PRS) were assessed at pre-injection as well as 4- and 12-week post-injection. No samples contained anti-botulinum antibodies. Greater baseline MTS dynamic range was associated with greater changes in MTS dynamic ranges at 4-week post-injection. More frequent physical therapy was associated with greater changes in static dorsiflexion ROM at 4-week post-injection and greater changes in PRS at 4- and 12-week post-injection. The improvement in PRS at 12-week post-injection was associated with the frequency of physical therapy. Therefore, intensive physical therapy programs may be necessary to maintain the beneficial effects of BoNT-A injections in children with CP.

Chirality of the cytoskeleton in the origins of cellular asymmetry

PubMed Central

2016-01-01

Self-assembly of two important components of the cytoskeleton of eukaryotic cells, actin microfilaments and microtubules (MTs) results in polar filaments of one chirality. As is true for bacterial flagella, in actin microfilaments, screw direction is important for assembly processes and motility. For MTs, polar orientation within the cell is paramount. The alignment of these elements in the cell cytoplasm gives rise to emergent properties, including the potential for cell differentiation and specialization. Complex MTs with a characteristic chirality are found in basal bodies and centrioles; this chirality is preserved in cilia. In motile cilia, it is reflected in the direction of the effective stroke. The positioning of the basal body or cilia on the cell surface depends on polarity proteins. In evolution, survival depends on global polarity information relayed to the cell in part by orientation of the MT and actin filament cytoskeletons and the chirality of the basal body to determine left and right coordinates within a defined anterior–posterior cell and tissue axis. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’. PMID:27821520

Organelle positioning in muscles requires cooperation between two KASH proteins and microtubules

PubMed Central

Elhanany-Tamir, Hadas; Yu, Yanxun V.; Shnayder, Miri; Jain, Ankit; Welte, Michael

2012-01-01

Striated muscle fibers are characterized by their tightly organized cytoplasm. Here, we show that the Drosophila melanogaster KASH proteins Klarsicht (Klar) and MSP-300 cooperate in promoting even myonuclear spacing by mediating a tight link between a newly discovered MSP-300 nuclear ring and a polarized network of astral microtubules (aMTs). In either klar or msp-300ΔKASH, or in klar and msp-300 double heterozygous mutants, the MSP-300 nuclear ring and the aMTs retracted from the nuclear envelope, abrogating this even nuclear spacing. Anchoring of the myonuclei to the core acto-myosin fibrillar compartment was mediated exclusively by MSP-300. This protein was also essential for promoting even distribution of the mitochondria and ER within the muscle fiber. Larval locomotion is impaired in both msp-300 and klar mutants, and the klar mutants were rescued by muscle-specific expression of Klar. Thus, our results describe a novel mechanism of nuclear spacing in striated muscles controlled by the cooperative activity of MSP-300, Klar, and astral MTs, and demonstrate its physiological significance. PMID:22927463

Two Complementary Mechanisms Underpin Cell Wall Patterning during Xylem Vessel Development.

PubMed

Schneider, Rene; Tang, Lu; Lampugnani, Edwin R; Barkwill, Sarah; Lathe, Rahul; Zhang, Yi; McFarlane, Heather E; Pesquet, Edouard; Niittyla, Totte; Mansfield, Shawn D; Zhou, Yihua; Persson, Staffan

2017-10-01

The evolution of the plant vasculature was essential for the emergence of terrestrial life. Xylem vessels are solute-transporting elements in the vasculature that possess secondary wall thickenings deposited in intricate patterns. Evenly dispersed microtubule (MT) bands support the formation of these wall thickenings, but how the MTs direct cell wall synthesis during this process remains largely unknown. Cellulose is the major secondary wall constituent and is synthesized by plasma membrane-localized cellulose synthases (CesAs) whose catalytic activity propels them through the membrane. We show that the protein CELLULOSE SYNTHASE INTERACTING1 (CSI1)/POM2 is necessary to align the secondary wall CesAs and MTs during the initial phase of xylem vessel development in Arabidopsis thaliana and rice ( Oryza sativa ). Surprisingly, these MT-driven patterns successively become imprinted and sufficient to sustain the continued progression of wall thickening in the absence of MTs and CSI1/POM2 function. Hence, two complementary principles underpin wall patterning during xylem vessel development. © 2017 American Society of Plant Biologists. All rights reserved.

Microtubules Enable the Planar Cell Polarity of Airway Cilia

PubMed Central

Vladar, Eszter K.; Bayly, Roy D.; Sangoram, Ashvin; Scott, Matthew P.; Axelrod, Jeffrey D.

2012-01-01

Summary Background Airway cilia must be physically oriented along the longitudinal tissue axis for concerted, directional motility that is essential for proper mucociliary clearance. Results We show that Planar Cell Polarity (PCP) signaling specifies directionality and orients respiratory cilia. Within all airway epithelial cells a conserved set of PCP proteins shows interdependent, asymmetric junctional localization; non-autonomous signaling coordinates polarization between cells; and a polarized microtubule (MT) network is likely required for asymmetric PCP protein localization. We find that basal bodies dock after polarity of PCP proteins is established, are polarized nearly simultaneously, and refinement of basal body/cilium orientation continues during airway epithelial development. Unique to mature multiciliated cells, we identify PCP-regulated, planar polarized MTs that originate from basal bodies and interact, via their plus ends, with membrane domains associated with the PCP proteins Frizzled and Dishevelled. Disruption of MTs leads to misoriented cilia. Conclusions A conserved PCP pathway orients airway cilia by communicating polarity information from asymmetric membrane domains at the apical junctions, through MTs, to orient the MT and actin based network of ciliary basal bodies below the apical surface. PMID:23122850

A Screen for Modifiers of Hedgehog Signaling in Drosophila melanogaster Identifies swm and mts

PubMed Central

Casso, David J.; Liu, Songmei; Iwaki, D. David; Ogden, Stacey K.; Kornberg, Thomas B.

2008-01-01

Signaling by Hedgehog (Hh) proteins shapes most tissues and organs in both vertebrates and invertebrates, and its misregulation has been implicated in many human diseases. Although components of the signaling pathway have been identified, key aspects of the signaling mechanism and downstream targets remain to be elucidated. We performed an enhancer/suppressor screen in Drosophila to identify novel components of the pathway and identified 26 autosomal regions that modify a phenotypic readout of Hh signaling. Three of the regions include genes that contribute constituents to the pathway—patched, engrailed, and hh. One of the other regions includes the gene microtubule star (mts) that encodes a subunit of protein phosphatase 2A. We show that mts is necessary for full activation of Hh signaling. A second region includes the gene second mitotic wave missing (swm). swm is recessive lethal and is predicted to encode an evolutionarily conserved protein with RNA binding and Zn+ finger domains. Characterization of newly isolated alleles indicates that swm is a negative regulator of Hh signaling and is essential for cell polarity. PMID:18245841

Quadrennial Review of Military Compensation (7th). Allowances. Major Topical Summary (MTS) 3

DTIC Science & Technology

1992-08-01

Colonel D. Cragin Shelton, ANG Compensation Analyst Major Daniel J. Arena, USA Compensation Analyst QRMC SUPPORT Mr. William H. Warnock Director xviii...of living in the 84 randomly selected areas, in rank order. The QRMC also had Runzheimer survey what were ’ William H. Albright, Benjamin R. Baker...Directorate of Plans, Programs and Analysis, 1990. Albright, William H. et al., A Reference Guide to the 1984 Military Health Services System Beneficiary

Quadrennial Review of Military Compensation (7th). Compensation Structure. Major Topical Summary (MTS) 1

DTIC Science & Technology

1992-08-01

professional sports franchises , fast food restaurants , or a widget factory as well as the uniformed services. The 7’ QRMC identified two additional...1990 ................. C-8 Figure C-7. Basic Pay as a Percentage of RMC, by Grade, 1991 ................... C-11 Figure C-8. Current Enlisted BAS vs ... independent survey. "* A separate but simplified system of special and incentive pays. "* Expense reimbursements. "* Other allowances and so-called fringe

An Evaluation of Four MTS Recurrent Training Courses,

DTIC Science & Technology

1978-09-01

management—by— objectives and team action . The evaluation of each of these four recurrent training courses follows the general approach taken in the earlier...D AU bI 519 FEant AVIATION ADMINISTRATION IflHINSTON 0 C OFFICE—ETC P/S 5/9AN EVALUATION Of FOJR MIS RECURRENT TRAIN ING C OURSES. (U)SEP 78 R C S M...Sep -~-__ L.__ T)78 ~. L I AN E VALUAT ION OF FOUR MTS RE CURRE NT TRAINING COURSESi —fl. - -— .-.~~. ..~~~~~~~ ‘ ) 6. erfo,a,~ng OrgoniZotro~I Cod

MCAK and Stathmin Upregulation in Breast Cancer Cells: Etiology and Response to Pharmacologic Reagents

DTIC Science & Technology

2004-07-01

and the affinity for MTs are cells (Maney et al., 2001). Finally, the neck domain is not molecular refinements that adapt motile kinesins for specific...1,500 nM taxol-stabilized MTs in 80 p.I of BRB80 (80 mM molecular motor. Nature. 389:93-96. Pipes, pH 6.8, 1 mM EGTA, and 1 mM MgCI2), 12.5 p.M taxol, 1...summarizes the biological functions and examines the possible molecular the r egio immeiatel iete mt core mechanisms of Kin C and Kin I unconventional

The Effects of Listener Training on the Emergence of Tact and Mand Signs by Individuals with Intellectual Disabilities

PubMed Central

Ribeiro, Daniela M; Elias, Nassim C; Goyos, Celso; Miguel, Caio F

2010-01-01

The purpose of the current study was to assess whether individuals with intellectual disabilities would emit untrained speaker responses (i.e., signed tacts and mands) after being taught listener behaviors. Listener relations were trained via an automated matching-to-sample (MTS) procedure. Following mastery, the emergence of signed tacts, generalized tacts, and mands was tested. All participants met criterion in listener relations training and showed the emergence of almost all relations. Results suggest that teaching listener relations first, through MTS tasks, is a viable way to produce emergence of speaker relations. PMID:22477464

Three new species and one new subspecies of Deserticossus Yakovlev, 2006 (Lepidoptera: Cossidae) from Kazakhstan, Kyrgyzstan and Russia, with world catalogue of the genus.

PubMed

Yakovlev, Roman V; Witt, Thomas J

2017-05-23

Three new species and one new subspecies of the genus Deserticossus Yakovlev, 2006 are described: Deserticossus doroshkini Yakovlev & Witt sp. nov. from eastern Kazakhstan (Tarbagatai Mts.), D. selevini Yakovlev & Witt sp. nov. from southeastern Kazakhstan (Malye Boguty Mts.), D. kamelini Yakovlev & Witt sp. nov. from Kyrgyzstan (Fergana Valley), and D. tsingtauana didenkoi Yakovlev & Witt subsp. nov. from Russia (Southern Siberia, Buryatia Republic). The described species and subspecies of Deserticossus are listed, with notes on the type material, synonymies, and distribution for each taxon.

Properties of self-assembled diluted magnetic semiconductor nanostructures =

NASA Astrophysics Data System (ADS)

Ankiewicz, Amelia Olga Goncalves

Este trabalho centra-se na investigacao da possibilidade de se conseguir um semicondutor magnetico diluido (SMD) baseado em ZnO. Foi levado a cabo um estudo detalhado das propriedades magneticas e estruturais de estruturas de ZnO, nomeadamente nanofios (NFs), nanocristais (NCs) e filmes finos, dopadas com metais de transicao (MTs). Foram usadas varias tecnicas experimentais para caracterizar estas estruturas, designadamente difraccao de raios-X, microscopia electronica de varrimento, ressonancia magnetica, SQUID, e medidas de transporte. Foram incorporados substitucionalmente nos sitios do Zn ioes de Mn2+ e Co2+ em ambos os NFs e NCs de ZnO. Revelou-se para ambos os ioes dopantes, que a incorporacao e heterogenea, uma vez que parte do sinal de ressonancia paramagnetica electronica (RPE) vem de ioes de MTs em ambientes distorcidos ou enriquecidos com MTs. A partir das intensidades relativas dos espectros de RPE e de modificacoes da superficie, demonstra-se ainda que os NCs exibem uma estrutura core-shell. Os resultados, evidenciam que, com o aumento da concentracao de MTs, a dimensao dos NCs diminui e aumentam as distorcoes da rede. Finalmente, no caso dos NCs dopados com Mn, obteve-se o resultado singular de que a espessura da shell e da ordem de 0.3 nm e de que existe uma acumulacao de Mn na mesma. Com o objectivo de esclarecer o papel dos portadores de carga na medicao das interaccoes ferromagneticas, foram co-dopados filmes de ZnO com Mn e Al ou com Co e Al. Os filmes dopados com Mn, revelaram-se simplesmente paramagneticos, com os ioes de Mn substitucionais nos sitios do Zn. Por outro lado, os filmes dopados com Co exibem ferromagnetismo fraco nao intrinseco, provavelmente devido a decomposicao spinodal. Foram ainda efectuados estudos comparativos com filmes de ligas de Zn1-xFexO. Como era de esperar, detectaram-se segundas fases de espinela e de oxido de ferro nestas ligas; todas as amostras exibiam curvas de histerese a 300 K. Estes resultados suportam a hipotese de que as segundas fases sao responsaveis pelo comportamento magnetico observado em muitos sistemas baseados em ZnO. Nao se observou nenhuma evidencia de ferromagnetismo mediado por portadores de carga. As experiencias mostram que a analise de RPE permite demonstrar directamente se e onde estao incorporados os ioes de MTs e evidenciam a importancia dos efeitos de superficie para dimensoes menores que 15 nm, para as quais se formam estruturas core-shell. As investigacoes realizadas no ambito desta tese demonstram que nenhuma das amostras de ZnO estudadas exibiram propriedades de um SMD intrinseco e que, no futuro, sao necessarios estudos teoricos e experimentais detalhados das interaccoes de troca entre os ioes de MTs e os atomos do ZnO para determinar a origem das propriedades magneticas observadas.

Kinetic energy definition in velocity Verlet integration for accurate pressure evaluation

NASA Astrophysics Data System (ADS)

Jung, Jaewoon; Kobayashi, Chigusa; Sugita, Yuji

2018-04-01

In molecular dynamics (MD) simulations, a proper definition of kinetic energy is essential for controlling pressure as well as temperature in the isothermal-isobaric condition. The virial theorem provides an equation that connects the average kinetic energy with the product of particle coordinate and force. In this paper, we show that the theorem is satisfied in MD simulations with a larger time step and holonomic constraints of bonds, only when a proper definition of kinetic energy is used. We provide a novel definition of kinetic energy, which is calculated from velocities at the half-time steps (t - Δt/2 and t + Δt/2) in the velocity Verlet integration method. MD simulations of a 1,2-dispalmitoyl-sn-phosphatidylcholine (DPPC) lipid bilayer and a water box using the kinetic energy definition could reproduce the physical properties in the isothermal-isobaric condition properly. We also develop a multiple time step (MTS) integration scheme with the kinetic energy definition. MD simulations with the MTS integration for the DPPC and water box systems provided the same quantities as the velocity Verlet integration method, even when the thermostat and barostat are updated less frequently.

Microtubule release from the centrosome in migrating cells

PubMed Central

Abal, Miguel; Piel, Matthieu; Bouckson-Castaing, Veronique; Mogensen, Mette; Sibarita, Jean-Baptiste; Bornens, Michel

2002-01-01

In migrating cells, force production relies essentially on a polarized actomyosin system, whereas the spatial regulation of actomyosin contraction and substrate contact turnover involves a complex cooperation between the microtubule (MT) and the actin filament networks (Goode, B.L., D.G. Drubin, and G. Barnes. 2000. Curr. Opin. Cell Biol., 12:63–71). Targeting and capture of MT plus ends at the cell periphery has been described, but whether or not the minus ends of these MTs are anchored at the centrosome is not known. Here, we show that release of short MTs from the centrosome is frequent in migrating cells and that their transport toward the cell periphery is blocked when dynein activity is impaired. We further show that MT release, but not MT nucleation or polymerization dynamics, is abolished by overexpression of the centrosomal MT-anchoring protein ninein. In addition, a dramatic inhibition of cell migration was observed; but, contrary to cells treated by drugs inhibiting MT dynamics, polarized membrane ruffling activity was not affected in ninein overexpressing cells. We thus propose that the balance between MT minus-end capture and release from the centrosome is critical for efficient cell migration. PMID:12473683

Kinetic energy definition in velocity Verlet integration for accurate pressure evaluation.

PubMed

Jung, Jaewoon; Kobayashi, Chigusa; Sugita, Yuji

2018-04-28

In molecular dynamics (MD) simulations, a proper definition of kinetic energy is essential for controlling pressure as well as temperature in the isothermal-isobaric condition. The virial theorem provides an equation that connects the average kinetic energy with the product of particle coordinate and force. In this paper, we show that the theorem is satisfied in MD simulations with a larger time step and holonomic constraints of bonds, only when a proper definition of kinetic energy is used. We provide a novel definition of kinetic energy, which is calculated from velocities at the half-time steps (t - Δt/2 and t + Δt/2) in the velocity Verlet integration method. MD simulations of a 1,2-dispalmitoyl-sn-phosphatidylcholine (DPPC) lipid bilayer and a water box using the kinetic energy definition could reproduce the physical properties in the isothermal-isobaric condition properly. We also develop a multiple time step (MTS) integration scheme with the kinetic energy definition. MD simulations with the MTS integration for the DPPC and water box systems provided the same quantities as the velocity Verlet integration method, even when the thermostat and barostat are updated less frequently.

Transient gibberellin application promotes Arabidopsis thaliana hypocotyl cell elongation without maintaining transverse orientation of microtubules on the outer tangential wall of epidermal cells.

PubMed

Sauret-Güeto, Susanna; Calder, Grant; Harberd, Nicholas P

2012-02-01

The phytohormone gibberellin (GA) promotes plant growth by stimulating cellular expansion. Whilst it is known that GA acts by opposing the growth-repressing effects of DELLA proteins, it is not known how these events promote cellular expansion. Here we present a time-lapse analysis of the effects of a single pulse of GA on the growth of Arabidopsis hypocotyls. Our analyses permit kinetic resolution of the transient growth effects of GA on expanding cells. We show that pulsed application of GA to the relatively slowly growing cells of the unexpanded light-grown Arabidopsis hypocotyl results in a transient burst of anisotropic cellular growth. This burst, and the subsequent restoration of initial cellular elongation rates, occurred respectively following the degradation and subsequent reappearance of a GFP-tagged DELLA (GFP-RGA). In addition, we used a GFP-tagged α-tubulin 6 (GFP-TUA6) to visualise the behaviour of microtubules (MTs) on the outer tangential wall (OTW) of epidermal cells. In contrast to some current hypotheses concerning the effect of GA on MTs, we show that the GA-induced boost of hypocotyl cell elongation rate is not dependent upon the maintenance of transverse orientation of the OTW MTs. This confirms that transverse alignment of outer face MTs is not necessary to maintain rapid elongation rates of light-grown hypocotyls. Together with future studies on MT dynamics in other faces of epidermal cells and in cells deeper within the hypocotyl, our observations advance understanding of the mechanisms by which GA promotes plant cell and organ growth. © 2011 The Authors. The Plant Journal © 2011 Blackwell Publishing Ltd.

Microtubule dynamics in nerve cells: analysis using microinjection of biotinylated tubulin into PC12 cells

PubMed Central

1988-01-01

To study microtubule (MT) dynamics in nerve cells, we microinjected biotin-labeled tubulin into the cell body of chemically fused and differentiated PC12 cells and performed the immunofluorescence or immunogold procedure using an anti-biotin antibody followed by secondary antibodies coupled to fluorescent dye or colloidal gold. Incorporation of labeled subunits into the cytoskeleton of neurites was observed within minutes after microinjection. Serial electron microscopic reconstruction revealed that existing MTs in PC12 neurites incorporated labeled subunits mainly at their distal ends and the elongation rate of labeled segments was estimated to be less than 0.3 micron/min. Overall organization of MTs in the nerve cells was different from that in undifferentiated cells such as fibroblasts. Namely, we have not identified any MT-organizing centers from which labeled MTs are emanating in the cell bodies of the injected cells. Stereo electron microscopy revealed that some fully labeled segments seemed to start in the close vicinity of electron dense material within the neurites. This suggests new nucleation off some structures in the neurites. We have also studied the overall pattern of the incorporation of labeled subunits which extended progressively from the proximal part of the neurites toward their tips. To characterize the mechanism of tubulin incorporation, we have measured mean density of gold labeling per unit length of labeled segments at different parts of the neurites. The results indicate access of free tubulin subunits into the neurites and local incorporation into the neurite cytoskeleton. Our results lead to the conclusion that MTs are not static polymers but dynamic structures that continue to elongate even within the differentiated nerve cell processes. PMID:3047145

Active mechanical stabilization of the viscoplastic intracellular space of Dictyostelia cells by microtubule-actin crosstalk.

PubMed

Heinrich, Doris; Sackmann, Erich

2006-11-01

The micro-viscoelasticity of the intracellular space of Dictyostelium discoideum cells is studied by evaluating the intracellular transport of magnetic force probes and their viscoelastic responses to force pulses of 20-700 pN. The role of the actin cortex, the microtubule (MT) aster and their crosstalk is explored by comparing the behaviour of wild-type cells, myosin II null mutants, latrunculin A and benomyl treated cells. The MT coupled beads perform irregular local and long range directed motions which are characterized by measuring their velocity distributions (P(v)). The correlated motion of the MT and the centrosome are evaluated by microfluorescence of GFP-labelled MTs. P(v) can be represented by log-normal distributions with long tails and it is determined by random sweeping motions (v approximately 0.5 microm/s) of the MTs (caused by tangential forces on the filament ends coupled to the actin cortex) and by intermittent bead transports parallel to the MTs (v(max) approximately 1.5 microm/s). The tails are due to spontaneous filament deflections (with speeds up to 10 microm/s) attributed to pre-stressing of the MT by local cortical tensions, generated by dynactin motors generating plus-end directed forces in the MTs. The viscoelastic responses are strongly non-linear and are mostly directed opposite or perpendicular to the force, showing that the cytoplasm behaves as an active viscoplastic body with time and force dependent drag coefficients. Nano-Newton loads exerted on the soft MT are balanced by traction forces arising at the MT ends coupled to the actin cortex and the centrosome, respectively. The mechanical coupling between the soft microtubules and the viscoelastic actin cortex provides cells with high mechanical stability despite the softness of the cytoplasm.

The presence of polyglucosan bodies in temporal lobe epilepsy: its role and significance.

PubMed

Abubakr, Abuhuziefa; Wambacq, Ilse; Donahue, John E; Zappulla, Rosario

2005-11-01

Mesial temporal sclerosis (MTS) is an important pathology in temporal lobe epilepsy (TLE) and often associated with good surgical outcome, however prognostic factors for surgical outcome are conflicting. The authors examine seizure outcome after surgery for TLE due to MTS, with focus on the presence of polyglucosan bodies (PGBs), and its relation to the epileptogenic process. Records of 44 consecutive patients with intractable TLE who underwent anterior temporal lobectomy (ATL) at JFK medical center between 1994-2001 were reviewed. Details of clinical, electrophysiological evaluation, and outcome were collected. All slides were reviewed for the presence of MTS. In twenty-one patients with MTS, detailed histology of surgical specimens was reviewed and relative concentration of PGBs was assessed. The postoperative follow-up duration ranges between 28-74 months. Surgical outcome was evaluated according to Engel's classification. Data of fourteen females (mean age 32.8 years) and 7 males (mean age 34.2) were analyzed. PBGs were identified in 10 patients (8 females and 2 males). All 10 patients had good surgical outcome, with 6 patients (60%) being seizure free (class 1) and 4 patients as class 2. While 11 patients (6 males and 5 females) with absent PGB, 72.8% had good surgical outcome. Of these, 7 (63.8%) had class 1, 1 patient had class 2, and 3 patients had class 3&4. Assessing several risk factors, the only significant difference between the two groups was epilepsy duration, which was significantly longer in patients with PGBs (P = 0.011). The histological presence of PGB is associated with long duration of epilepsy and could be the consequence of epilepsy. Despite prolonged duration of epilepsy, the surgical outcome in PGBs +ve is similar to PGBs -ve patients.

Effects of the chromatic defocus caused by interchange of two monochromatic lights on refraction and ocular dimension in guinea pigs.

PubMed

Qian, Yi-Feng; Dai, Jin-Hui; Liu, Rui; Chen, Min-Jie; Zhou, Xing-Tao; Chu, Ren-Yuan

2013-01-01

To investigate refractive and axial responses to the shift of focal plane resulting from the interchange of two monochromatic lights separately corresponding to the peak wavelengths of the cones absorption spectrum in retina, fifty 2-week-old pigmented guinea pigs were randomly assigned to five groups based on the mode of illumination: short-wavelength light (SL), middle-wavelength light (ML) and broad-band white light (BL) for 20 weeks, SL for 10 weeks followed by ML for 10 weeks (STM), as well as ML for 10 weeks followed by SL for 10 weeks (MTS). Biometric and refractive measurements were then performed every 2 weeks. After 10 weeks, SL and STM groups became more hyperopic and had less vitreous elongation than BL group. However, ML and MTS groups became more myopic and had more vitreous elongation. After interchange of the monochromatic light, the refractive error decreased rapidly by about 1.93D and the vitreous length increased by 0.14 mm in STM group from 10 to 12 weeks. After that, there were no significant intergroup differences between STM and BL groups. The interchange from ML to SL quickly increased the refractive error by about 1.53D and decreased the vitreous length by about 0.13 mm in MTS group after two weeks. At this time, there were also no significant intergroup differences between MTS and BL groups. The guinea pig eye can accurately detect the shift in focal plane caused by interchange of two monochromatic lights and rapidly generate refractive and axial responses. However, an excessive compensation was induced. Some properties of photoreceptors or retina may be changed by the monochromatic light to influence the following refractive development.

Pilot randomized trial on mindfulness training for smokers in young adult binge drinkers.

PubMed

Davis, James M; Mills, David M; Stankevitz, Kristin A; Manley, Alison R; Majeskie, Matthew R; Smith, Stevens S

2013-09-03

We report results of a pilot study designed to test a novel smoking cessation intervention, Mindfulness Training for Smokers (MTS), in smokers age 18-29 years with regular episodes of binge drinking. Mindfulness is a cognitive skill of applying close moment-to-moment attention to experience with a mental posture of acceptance and non-reactivity. The MTS intervention consisted of six weekly classes that provided instruction on how to use mindfulness to manage known precursors of smoking relapse including smoking triggers, strong emotions, stressful situations, addictive thoughts, urges, and withdrawal symptoms. The MTS intervention was compared to Interactive Learning for Smokers (ILS), a time/intensity matched control group using daily non-directed walking instead of mindfulness meditation. Recruitment was conducted primarily at local technical colleges. Primary outcome measures included biochemically-confirmed smoking abstinence and reduction in alcohol use at the end of treatment (2-weeks post-quit attempt). The sample (N = 55) was 70.9% male, with a mean age of 21.9 years, and a mean of 11.76 alcoholic drinks consumed per week. Intent-to-treat analysis showed biochemically-confirmed 7-day point prevalence abstinence rates at 2-weeks post-quit for MTS = 20.0% and ILS = 4.0%, p = .08. Secondary analysis showed number of drinks per week in the first 2-weeks post-quit correlated with smoking relapse at 2-weeks post-quit (p < .01). This pilot study demonstrated that Mindfulness Training for Smokers shows promise for smoking cessation and alcohol use reduction in treating young adult smokers with alcohol abuse. Results suggest the need for a study with larger sample size and methods that reduce attrition. ClnicalTrial.gov, NCT01679236.

Epothilone D Prevents Binge Methamphetamine-Mediated Loss of Striatal Dopaminergic Markers

PubMed Central

Killinger, Bryan A.; Moszczynska, Anna

2016-01-01

Exposure to binge methamphetamine (METH) can result in a permanent or transient loss of dopaminergic (DAergic) markers such as dopamine (DA), dopamine transporter (DAT), and tyrosine hydroxylase (TH) in the striatum. We hypothesized that the METH-induced loss of striatal DAergic markers was, in part, due to destabilization of microtubules (MTs) in the nigrostriatal DA pathway that ultimately impedes anterograde axonal transport of these markers. To test this hypothesis, adult male Sprague Dawley rats were treated with binge METH or saline in the presence or absence of epothilone D (EpoD), a MT-stabilizing compound, and assessed for the levels of several DAergic markers as well as for the levels of tubulins and their posttranslational modifications (PMTs) at 3 days after the treatments. Binge METH induced a loss of stable long-lived MTs within the striatum but not within the SNpc. Treatment with a low dose of EpoD increased the levels of markers of stable MTs and prevented METH-mediated deficits in several DAergic markers in the striatum. By contrast, administration of a high dose of EpoD appeared to destabilize MTs and potentiated the METH-induced deficits in several DAergic markers. The low-dose EpoD also prevented the METH-induced increase in striatal DA turnover and increased behavioral stereotypy during METH treatment. Together, these results demonstrate that MT dynamics plays a role in the development of METH-induced losses of several DAergic markers in the striatum and may mediate METH-induced degeneration of terminals in the nigrostriatal DA pathway. Our study also demonstrates that MT-stabilizing drugs, such as EpoD have a potential to serve as useful therapeutic agents to restore function of DAergic nerve terminals following METH exposure when administered at low doses. PMID:26465779

BRAF/KRAS gene sequencing of sebaceous neoplasms after mismatch repair protein analysis.

PubMed

Cornejo, Kristine M; Hutchinson, Lloyd; Deng, April; Tomaszewicz, Keith; Welch, Matthew; Lyle, Stephen; Dresser, Karen; Cosar, Ediz F

2014-06-01

Sebaceous neoplasms are cutaneous markers for the autosomal-dominant Muir-Torre syndrome (MTS). This phenotypic variant of Lynch syndrome (LS) is caused by germline mutations in DNA mismatch repair (MMR) genes. Microsatellite instability or loss of protein expression suggests a mutation or promoter hypermethylation in 1 of the MMR genes. BRAF gene sequencing may help to distinguish between patients with sporadic and LS-associated colorectal carcinomas with loss of MLH1 expression. LS-associated carcinomas are virtually negative for BRAF mutations, but a subset harbors KRAS mutations. The aim of our study was to test sebaceous neoplasms for V600E BRAF or KRAS mutations to determine if these mutations are associated with somatic or germline MMR defects, analogous to colorectal carcinomas. Over a 4-year period, 32 cases comprising 21 sebaceous adenomas, 3 sebaceomas, and 8 sebaceous carcinomas with sufficient material for testing were collected. MMR immunohistochemistry showed that 7 neoplasms had combined loss of MLH1-PMS2, 16 neoplasms had combined loss of MSH2-MSH6, 2 neoplasms had solitary loss of MSH6, and 7 sebaceous neoplasms had intact protein expression. BRAF/KRAS testing revealed all sebaceous neoplasms contained a wild-type BRAF gene. Two (15%) of 13 patients with MTS were found to harbor a KRAS mutation and loss of MLH1 expression. We conclude that a V600E BRAF mutation may not be helpful in distinguishing sporadic from MTS-associated sebaceous neoplasms. Further studies are needed to determine if KRAS mutations are restricted to patients with MTS or are also present in sporadic sebaceous neoplasms. Copyright © 2014 Elsevier Inc. All rights reserved.

Hyperforin changes the zinc-storage capacities of brain cells.

PubMed

Gibon, Julien; Richaud, Pierre; Bouron, Alexandre

2011-12-01

In vitro and in vivo experiments were carried out to investigate the consequences on brain cells of a chronic treatment with hyperforin, a plant extract known to dissipate the mitochondrial membrane potential and to release Zn(2+) and Ca(2+) from these organelles. Dissociated cortical neurons were grown in a culture medium supplemented with 1 μM hyperforin. Live-cell imaging experiments with the fluorescent probes FluoZin-3 and Fluo-4 show that a 3 day-hyperforin treatment diminishes the size of the hyperforin-sensitive pools of Ca(2+) and Zn(2+) whereas it increases the size of the DTDP-sensitive pool of Zn(2+) without affecting the ionomycin-sensitive pool of Ca(2+). When assayed by quantitative PCR the levels of mRNA coding for metallothioneins (MTs) I, II and III were increased in cortical neurons after a 3 day-hyperforin treatment. This was prevented by the zinc chelator TPEN, indicating that the plant extract controls the expression of MTs in a zinc-dependent manner. Brains of adult mice who received a daily injection (i.p.) of hyperforin (4 mg/kg/day) for 4 weeks had a higher sulphur content than control animals. They also exhibited an enhanced expression of the genes coding for MTs. However, the long-term treatment did not affect the brain levels of calcium and zinc. Based on these results showing that hyperforin influences the size of the internal pools of Zn(2+), the expression of MTs and the brain cellular sulphur content, it is proposed that hyperforin changes the Zn-storage capacity of brain cells and interferes with their thiol status. Copyright © 2011 Elsevier Ltd. All rights reserved.

Early Adoption of a Multi-target Stool DNA Test for Colorectal Cancer Screening

PubMed Central

Finney Rutten, Lila J.; Jacobson, Robert M.; Wilson, Patrick M.; Jacobson, Debra J.; Fan, Chun; Kisiel, John B.; Sweetser, Seth R.; Tulledge-Scheitel, Sidna M.; St. Sauver, Jennifer L.

2017-01-01

Objective To characterize early adoption of a novelmulti-target stool deoxyribonucleic acid (MTsDNA) screening test for colorectal cancer (CRC) and test the hypothesis that adoption differs by demographic characteristics, prior CRC screening behavior, and proceeds predictably over time. Patients and Methods We used the Rochester Epidemiology Project infrastructure to assess MTsDNA screening test use among adults aged 50–75 years, and identified 27,147 individuals eligible/due for screening colonoscopy from November 1, 2014 through November 30, 2015, and living in Olmsted County, Minnesota in2014. We used electronic Current Procedure Terminology and Health Care Common Procedure codes to evaluate early adoption of MTsDNA screening test in this population and to test whether early adoption varies by age, sex, race, and prior screening behavior. Results Overall, 2,193 (8.1%) and 974 (3.6%) of individuals were screened by colonoscopy and MT-sDNA, respectively. Age, sex, race, and prior screening were significantly and independently associated with MT-sDNA screening use compared to colonoscopy use after adjustment for all other variables. Rates of adoption of MTsDNA screening increased over time and were highest among those aged 50–54 years, females, whites, and had a prior history of screening. MT-sDNA screening use varied predictably by insurance coverage. Rates of colonoscopy decreased over time, while overall CRC screening rates remained steady. Conclusion Our results are generally consistent with predictions derived from prior research and Diffusion of Innovation framework, pointing to increasing use of the new screening test over time, and early adoption by younger patients, females, whites and those with prior CRC screening. PMID:28473037

Application of T2 relaxometry in lateralization and localization of mesial temporal lobe epilepsy and corresponding comparison with MR volumetry.

PubMed

Chen, Hui; Yu, Guilian; Wang, Jiangtao; Li, Feng; Li, Guangming

2016-09-01

Magnetic resonance (MR) volumetry is insensitive to subtle mesial temporal sclerosis (MTS), while T2 relaxometry is potential useful in detecting MTS, especially MTS in early course. To explore and compare the feasibility of T2 relaxometry and MR volumetry in evaluation of mesial temporal lobe epilepsy (MTLE) and lateralization of the epileptogenic zone, so as to optimize and enhance lesion depiction. For the 17 unilateral MTLE patients and 14 normal participants, the hippocampus and amygdala were contoured on axial T2-weighted (T2W) images and then co-registered onto T2 relaxation maps. Abnormal is defined as an elevated asymmetric ratio of larger than 2 SD. Visual and quantitative volumetric assessment were combined as outcomes of MR volumetry to distinguish MR-positive and MR-negative lesions. Operative and pathological findings were used as gold standard. T2 values of lesions were significantly elevated. In lateralizing the epileptogenic zones, T2 relaxometry yielded an overall accuracy of 94.1% (sensitivity 92.6%, specificity 100%), and MR volumetry yielded an overall accuracy of 82.4% (sensitivity 88.9%, specificity 57.1%), meaning a better performance of T2 relaxometry (P < 0.001, by chi-square test). For pathologically sclerotic structures, most (25/27) were recognized by T2 relaxometry, while 24 of 27 sclerotic structures were detected via MR volumetry. MR volumetry wrongly discerned three normal regions as MTS, while one MR-negative sclerotic hippocampus was detected by T2 relaxometry. T2 relaxometry is feasible in non-invasive lateralization of epileptogenic zone, and more advantaged than MR volumetry in detecting MR-negative lesions, facilitating prompt diagnosis and longitudinal disease monitoring. © The Foundation Acta Radiologica 2015.

Mechanical Properties and Fatigue Behavior of Unitized Composite Airframe Structures at Elevated Temperature

DTIC Science & Technology

2014-03-27

created using a hammer and a punch tool provided by Material Test Systems (MTS) and were kept to a minimal depth to avoid fracture initiation at the...temperature. 76 be seen that the modulus remains relatively constant until near failure. There was no apparent correlation between modulus loss and...Normalized modulus vs. fatigue cycles of all ±45° specimens can be seen in Figure 56. There is not an evident correlation between number of cycles and

A Study of the Time Dependence in Fracture Processes Relating to Service Life Prediction of Adhesive Joints and Advanced Composites.

DTIC Science & Technology

1981-04-30

fluid temperature should exceed 145°F. The flow control module contains all the hydraulic circuit elements necessary for both the pressure line to and...are contained in three basic modules : 1) the hydraulic power supply, 2) a flow control module containing valving, accumulators and filters, and 3) the...hydraulic transient overpressures, is located in the flow control module , as are the high and low pressure filters. The load frame (MTS Systems Corp

Establishing Baseline Subsurface Light Fields for the Flower Garden Banks National Marine Sancturay

DTIC Science & Technology

2011-04-12

Code 1226 Office of Counsel,Code 1008.3 ADOR/Director NCST E. R. Franchi , 7000 Public Affairs (Unclassified/ Unlimited Only). Code 7030 4...deRada et al., 2009), which receives boundary information from the operational Global NCOM system (Kara et al., 2006; http://www7320.nrlssc.navy.mil...Gulf of Mexico. OCEANS 2009, MTS/IEEE Biloxi - Marine Technology for Our Future: Global and Local Challenges, ISBN: 978-1-4244-4960-6, pp. 1-7, 26-29

Experimental Investigation of Mechanical Behavior of an Oxide/Oxide Ceramic Composite in Interlaminar Shear and under Combined Tension-Torsion Loading

DTIC Science & Technology

2014-03-27

testing machine was warmed up for at least 30 min using a cyclic command with a sine waveform in displacement control . Gripping sections of each test...the test specimen was inserted into the susceptor. Then the testing machine is placed in displacement control and the top portion of the specimen...the MTS software also triggered the operation of the high speed cameras. 31 The testing system was placed in displacement /rotation control and the

Predictive Software Cost Model Study. Volume II. Software Package Detailed Data.

DTIC Science & Technology

1980-06-01

will not be limited to: a. ASN-91 NWDS Computer b. Armament System Control Unit ( ASCU ) c. AN/ASN-90 IMS 6. CONFIGURATION CONTROL. OFP/OTP...planned approach. 3. Detailed analysis and study; impacts on hardware, manuals, data, AGE , etc; alternatives with pros and cons; cost estimates; ECP...WAIT UNTIL RESOURCE REQUEST FOR * : HAG TAPE HAS BEEN FULFILLED )MTS 0 RI * Ae* NESDIIRCE MAG TAPE (SHORT FORM)I:TST IN I" . TEST " AG TAPE RESOURCE

Validation of different pediatric triage systems in the emergency department

PubMed Central

Aeimchanbanjong, Kanokwan; Pandee, Uthen

2017-01-01

BACKGROUND: Triage system in children seems to be more challenging compared to adults because of their different response to physiological and psychosocial stressors. This study aimed to determine the best triage system in the pediatric emergency department. METHODS: This was a prospective observational study. This study was divided into two phases. The first phase determined the inter-rater reliability of five triage systems: Manchester Triage System (MTS), Emergency Severity Index (ESI) version 4, Pediatric Canadian Triage and Acuity Scale (CTAS), Australasian Triage Scale (ATS), and Ramathibodi Triage System (RTS) by triage nurses and pediatric residents. In the second phase, to analyze the validity of each triage system, patients were categorized as two groups, i.e., high acuity patients (triage level 1, 2) and low acuity patients (triage level 3, 4, and 5). Then we compared the triage acuity with actual admission. RESULTS: In phase I, RTS illustrated almost perfect inter-rater reliability with kappa of 1.0 (P<0.01). ESI and CTAS illustrated good inter-rater reliability with kappa of 0.8–0.9 (P<0.01). Meanwhile, ATS and MTS illustrated moderate to good inter-rater reliability with kappa of 0.5–0.7 (P<0.01). In phase II, we included 1 041 participants with average age of 4.7±4.2 years, of which 55% were male and 45% were female. In addition 32% of the participants had underlying diseases, and 123 (11.8%) patients were admitted. We found that ESI illustrated the most appropriate predicting ability for admission with sensitivity of 52%, specificity of 81%, and AUC 0.78 (95%CI 0.74–0.81). CONCLUSION: RTS illustrated almost perfect inter-rater reliability. Meanwhile, ESI and CTAS illustrated good inter-rater reliability. Finally, ESI illustrated the appropriate validity for triage system. PMID:28680520

Rho GTPases at the crossroad of signaling networks in mammals

PubMed Central

Wojnacki, José; Quassollo, Gonzalo; Marzolo, María-Paz; Cáceres, Alfredo

2014-01-01

Microtubule (MT) organization and dynamics downstream of external cues is crucial for maintaining cellular architecture and the generation of cell asymmetries. In interphase cells RhoA, Rac, and Cdc42, conspicuous members of the family of small Rho GTPases, have major roles in modulating MT stability, and hence polarized cell behaviors. However, MTs are not mere targets of Rho GTPases, but also serve as signaling platforms coupling MT dynamics to Rho GTPase activation in a variety of cellular conditions. In this article, we review some of the key studies describing the reciprocal relationship between small Rho-GTPases and MTs during migration and polarization. PMID:24691223

Radiosurgery for Medial Temporal Lobe Epilepsy Resulting from Mesial Temporal Sclerosis.

PubMed

Gianaris, Thomas; Witt, Thomas; Barbaro, Nicholas M

2016-01-01

Medial temporal lobe epilepsy associated with mesial temporal sclerosis (MTS) is perhaps the most well-defined epilepsy syndrome that is responsive to structural interventions such as surgery. Several minimally invasive techniques have arisen that provide additional options for the treatment of MTS while potentially avoiding many of open surgery's associated risks. By evading these risks, they also open up treatment options to patients who otherwise are poor surgical candidates. Radiosurgery is one of the most intensively studied of these alternatives and has found a growing role in the treatment of medial temporal lobe epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Inoceramid and foraminiferal record and biozonation of the Turonian and Coniacian (Upper Cretaceous) of the Mangyshlak Mts., western Kazakhstan

NASA Astrophysics Data System (ADS)

Walaszczyk, Ireneusz; Kopaevich, Ludmila F.; Beniamovski, Vladimir N.

2013-12-01

Walaszczyk, I., Kopaevich, L.F. and Beniamovski, V.N. 2013. Inoceramid and foraminiferal record and biozonation of the Turonian and Coniacian (Upper Cretaceous) of the Mangyshlak Mts., western Kazakhstan. Acta Geologica Polonica, 63 (4), 469-487. Warszawa. The Turonian and Coniacian (Upper Cretaceous) of the Mangyshlak Mts., western Kazakhstan, yielded a rich and relatively complete inoceramid bivalve record. The faunas and their succession correspond to those known from central and eastern Europe, allowing the zonation established in the latter areas to be applied in a virtually identical form. The gaps in the record of the group in Mangyshlak stem from the regional hiatuses in the geological record in the area and do not reflect any biogeographical differences between eastern and central-western Europe. Planktonic foraminifera are rare. Four successive interval range zones can be distinguished: in ascending stratigraphic order, the Helvetoglobotrunaca helvetica, Marginotruncaca pseudolinneiana, Marginotruncana coronata, and Concavotruncana concavata zones. Their correlation with the inoceramid zonation and, consequently, with the chronostratigraphic scheme, is demonstrated. The zonation and chronostratigraphic subdivision as applied in Mangyshlak may easily be applied to other areas of the peri-Caspian region (Caucasus, Tuarkyr, Kopet-Dagh, SE margin of the East-European Craton).

Halogenated auxins affect microtubules and root elongation in Lactuca sativa

NASA Technical Reports Server (NTRS)

Zhang, N.; Hasenstein, K. H.

2000-01-01

We studied the effect of 4,4,4-trifluoro-3-(indole-3-)butyric acid (TFIBA), a recently described root growth stimulator, and 5,6-dichloro-indole-3-acetic acid (DCIAA) on growth and microtubule (MT) organization in roots of Lactuca sativa L. DCIAA and indole-3-butyric acid (IBA) inhibited root elongation and depolymerized MTs in the cortex of the elongation zone, inhibited the elongation of stele cells, and promoted xylem maturation. Both auxins caused the plane of cell division to shift from anticlinal to periclinal. In contrast, TFIBA (100 micromolar) promoted elongation of primary roots by 40% and stimulated the elongation of lateral roots, even in the presence of IBA, the microtubular inhibitors oryzalin and taxol, or the auxin transport inhibitor naphthylphthalamic acid. However, TFIBA inhibited the formation of lateral root primordia. Immunostaining showed that TFIBA stabilized MTs orientation perpendicular to the root axis, doubled the cortical cell length, but delayed xylem maturation. The data indicate that the auxin-induced inhibition of elongation and swelling of roots results from reoriented phragmoplasts, the destabilization of MTs in elongating cells, and promotion of vessel formation. In contrast, TFIBA induced promotion of root elongation by enhancing cell length, prolonging transverse MT orientation, delaying cell and xylem maturation.

Vibration, buckling and smart control of microtubules using piezoelectric nanoshells under electric voltage in thermal environment

NASA Astrophysics Data System (ADS)

Farajpour, A.; Rastgoo, A.; Mohammadi, M.

2017-03-01

Piezoelectric nanomaterials such as zinc oxide (ZnO) are of low toxicity and have many biomedical applications including optical imaging, drug delivery, biosensing and harvesting biomechanical energy using hybrid nanogenerators. In this paper, the vibration, buckling and smart control of microtubules (MTs) embedded in an elastic medium in thermal environment using a piezoelectric nanoshell (PNS) are investigated. The MT and PNS are considered to be coupled by a filament network. The PNS is subjected to thermal loads and an external electric voltage which operates to control the mechanical behavior of the MT. Using the nonlocal continuum mechanics, the governing differential equations are derived. An exact solution is presented for simply supported boundary conditions. The differential quadrature method is also used to solve the governing equations for other boundary conditions. A detailed parametric study is conducted to investigate the effects of the elastic constants of surrounding medium and internal filament matrix, scale coefficient, electric voltage, the radius-to-thickness ratio of PNSs and temperature change on the smart control of MTs. It is found that the applied electric voltage can be used as an effective controlling parameter for the vibration and buckling of MTs.

Medical geochemistry research in Spissko-Gemerské rudohorie Mts., Slovakia.

PubMed

Rapant, S; Cvecková, V; Dietzová, Z; Khun, M; Letkovicová, M

2009-02-01

This study presents an assessment of the potential impact of geological contamination of the environment on the health of the population in Spissko-Gemerské rudohorie Mts. (SGR Mts.). The concentration levels of potentially toxic elements (mainly As, Cd, Cu, Hg, Pb, Sb, and Zn) were determined in soils, groundwater, surface water, and stream sediments as well as in the food chain (locally grown vegetables). A medical study included some 30 health indicators for all 98 municipalities of the study area. The As and Sb contents in human fluids and tissues were analyzed in one municipality identified to be at the highest risk. Based on element content, environmental and health risks were calculated for respective municipalities. Out of 98 municipalities 14 were characterized with extremely high environmental risk and 10 were characterized with very high carcinogenic risk from arsenic (groundwater). Extensive statistical analysis of geochemical data (element contents in soils, groundwater, surface water, and stream sediments) and health indicators was performed. Significant correlations between element contents in the geological environment and health indicators, mainly cancer and cardiovascular diseases, were identified. Biological monitoring has confirmed the transfer of elements from the geological environment to human fluids and tissues as well as to the local food chain.

Fully automated two-step assay for detection of metallothionein through magnetic isolation using functionalized γ-Fe2O3 particles.

PubMed

Merlos Rodrigo, Miguel Angel; Krejcova, Ludmila; Kudr, Jiri; Cernei, Natalia; Kopel, Pavel; Richtera, Lukas; Moulick, Amitava; Hynek, David; Adam, Vojtech; Stiborova, Marie; Eckschlager, Tomas; Heger, Zbynek; Zitka, Ondrej

2016-12-15

Metallothioneins (MTs) are involved in heavy metal detoxification in a wide range of living organisms. Currently, it is well known that MTs play substantial role in many pathophysiological processes, including carcinogenesis, and they can serve as diagnostic biomarkers. In order to increase the applicability of MT in cancer diagnostics, an easy-to-use and rapid method for its detection is required. Hence, the aim of this study was to develop a fully automated and high-throughput assay for the estimation of MT levels. Here, we report the optimal conditions for the isolation of MTs from rabbit liver and their characterization using MALDI-TOF MS. In addition, we described a two-step assay, which started with an isolation of the protein using functionalized paramagnetic particles and finished with their electrochemical analysis. The designed easy-to-use, cost-effective, error-free and fully automated procedure for the isolation of MT coupled with a simple analytical detection method can provide a prototype for the construction of a diagnostic instrument, which would be appropriate for the monitoring of carcinogenesis or MT-related chemoresistance of tumors. Copyright © 2016 Elsevier B.V. All rights reserved.

Oligocene shoshonitic rocks of the Rogozna Mts. (Central Balkan Peninsula): Evidence of petrogenetic links to the formation of Pb-Zn-Ag ore deposits

NASA Astrophysics Data System (ADS)

Borojević Šoštarić, S.; Cvetković, V.; Neubauer, F.; Palinkaš, L. A.; Bernroider, M.; Genser, J.

2012-09-01

This study focuses on age and evolution of the Oligocene quartz latite of the Rogozna Mts. (Central Balkan Peninsula), in order to better understand the link between magmatism and formation of Pb-Zn ± Ag mineralization. New 40Ar/39Ar biotite and amphibole plateau ages suggest that the Rogozna Mts. quartz latite originated through a continuous volcanic episode from 27.3 ± 0.1 to 29.5 ± 0.1 Ma which was immediately followed by a hydrothermal phase. The quartz latites are hypocrystalline porphyritic with phenocrysts and microphenocrysts (~ 60 vol.%) of plagioclase (An37-49), biotite Mg# [100 × Mg / (Mg + Fetot)] < 50, calcic amphibole, quartz, sanidine clinopyroxene and phlogopite (Mg# = 79 to 84). The rocks display numerous disequilibrium textures, such as: sieved plagioclase phenocrysts, dissolution effects on quartz, phlogopitized biotite and amphibole crystals, and phlogopite microphenocrysts showing effects of incomplete growth (or dissolution?) and biotitization. The Rogozna Mts. quartz latites are shoshonitic in character with Na2O/K2O < 1, high LILE/HFSE ratios, strong depletions at Nb and Ti and K, Pb and U peaks on primitive mantle-normalized diagrams. They are similar to other potassic/ultrapotassic rocks in this region, in particular to those of Veliki Majdan and Rudnik (West Serbia), which are also related to Pb-Zn deposits. The evolution of the Rogozna Mts. quartz latite is modeled using a trace element binary mixing model adopting a lamproite magma and a dacite-like calc-alkaline melt as end-members. The model implies that a fractionating magma chamber (~ 4.5-9.5 km) undergoes cooling in the range of > 850 °C-~720 °C and injection of lamproite-like melts. The injection causes an increase of temperature and a decrease of viscosity of the resulting hybrid magma, facilitating its upwelling and triggering pyroclastic eruptions. The addition of new volatiles by lamproitic melts most probably established the conditions for a hydrothermal phase above the magma chamber that was previously degassed explosively. This implies that magma mixing processes can be of great importance for the formation of Pb-Zn deposits. Similar processes are likely to have occurred in other areas with economically significant Pb-Zn-Ag ± other metal mineralization in the region of the Central Balkan Peninsula (Veliki Majdan, Rudnik, Golija, Kopaonik, Avala, etc.).

Measuring collective transport by defined numbers of processive and nonprocessive kinesin motors.

PubMed

Furuta, Ken'ya; Furuta, Akane; Toyoshima, Yoko Y; Amino, Misako; Oiwa, Kazuhiro; Kojima, Hiroaki

2013-01-08

Intracellular transport is thought to be achieved by teams of motor proteins bound to a cargo. However, the coordination within a team remains poorly understood as a result of the experimental difficulty in controlling the number and composition of motors. Here, we developed an experimental system that links together defined numbers of motors with defined spacing on a DNA scaffold. By using this system, we linked multiple molecules of two different types of kinesin motors, processive kinesin-1 or nonprocessive Ncd (kinesin-14), in vitro. Both types of kinesins markedly increased their processivities with motor number. Remarkably, despite the poor processivity of individual Ncd motors, the coupling of two Ncd motors enables processive movement for more than 1 μm along microtubules (MTs). This improvement was further enhanced with decreasing spacing between motors. Force measurements revealed that the force generated by groups of Ncd is additive when two to four Ncd motors work together, which is much larger than that generated by single motors. By contrast, the force of multiple kinesin-1s depends only weakly on motor number. Numerical simulations and single-molecule unbinding measurements suggest that this additive nature of the force exerted by Ncd relies on fast MT binding kinetics and the large drag force of individual Ncd motors. These features would enable small groups of Ncd motors to crosslink MTs while rapidly modulating their force by forming clusters. Thus, our experimental system may provide a platform to study the collective behavior of motor proteins from the bottom up.

How tectonics controlled post-collisional magmatism within the Dinarides: Inferences based on study of tectono-magmatic events in the Kopaonik Mts. (Southern Serbia)

NASA Astrophysics Data System (ADS)

Mladenović, Ana; Trivić, Branislav; Cvetković, Vladica

2015-04-01

In this study, we report evidence about coupling between tectonic and magmatic processes in a complex orogenic system. The study focuses on the Kopaonik Mts. situated between the Dinarides and the Carpatho-Balkanides (Southern Serbia), and a perfect area for investigating tectono-magmatic evolution. We combine a new data set on tectonic paleostress tensors with the existing information on Cenozoic magmatic rocks in the wider Kopaonik Mts. area. The paleostress study revealed the presence of four brittle deformational phases. The established link between fault mechanism and igneous processes suggests that two large tectono-magmatic events occurred in this area. The Late Eocene-Early Miocene tectono-magmatic event was generally characterized by transpressional tectonics that provided conditions for formation of basaltic underplating and subsequent lower crustal melting and generation of I-type magmas. Due to predominant compression in the first half of this event, these magmas could not reach the upper crustal levels. Later on, limited extensional pulses that occurred before the end of this event opened pathways for newly formed mantle melts to reach shallower crustal levels and mix with the evolving I-type magmas. The second event is Middle-Late Miocene in age. It was first associated with clear extensional conditions that caused advancing of basaltic melts to mid-crustal levels. This, in turn, induced the elevation of geotherms, melting of shallow crust and S-type granite formation. This event terminated with transpression that produced small volumes of basaltic melts and finally closed the igneous scene in this part of the Balkan Peninsula. Although we agree that the growth of igneous bodies is usually internally controlled and can be independent from the ambient structural pattern, we have strong reasons to believe that the integration of regional scale observations of fault kinematics with crucial petrogenetic information can be used for establishing spatial-temporal relationships between brittle tectonics and magmatism.

Crystal structure of SAM-dependent methyltransferase from Pyrococcus horikoshii.

PubMed

Pampa, K J; Madan Kumar, S; Hema, M K; Kumara, Karthik; Naveen, S; Kunishima, Naoki; Lokanath, N K

2017-12-01

Methyltransferases (MTs) are enzymes involved in methylation that are needed to perform cellular processes such as biosynthesis, metabolism, gene expression, protein trafficking and signal transduction. The cofactor S-adenosyl-L-methionine (SAM) is used for catalysis by SAM-dependent methyltransferases (SAM-MTs). The crystal structure of Pyrococcus horikoshii SAM-MT was determined to a resolution of 2.1 Å using X-ray diffraction. The monomeric structure consists of a Rossmann-like fold (domain I) and a substrate-binding domain (domain II). The cofactor (SAM) molecule binds at the interface between adjacent subunits, presumably near to the active site(s) of the enzyme. The observed dimeric state might be important for the catalytic function of the enzyme.

Rho GTPases at the crossroad of signaling networks in mammals: impact of Rho-GTPases on microtubule organization and dynamics.

PubMed

Wojnacki, José; Quassollo, Gonzalo; Marzolo, María-Paz; Cáceres, Alfredo

2014-01-01

Microtubule (MT) organization and dynamics downstream of external cues is crucial for maintaining cellular architecture and the generation of cell asymmetries. In interphase cells RhoA, Rac, and Cdc42, conspicuous members of the family of small Rho GTPases, have major roles in modulating MT stability, and hence polarized cell behaviors. However, MTs are not mere targets of Rho GTPases, but also serve as signaling platforms coupling MT dynamics to Rho GTPase activation in a variety of cellular conditions. In this article, we review some of the key studies describing the reciprocal relationship between small Rho-GTPases and MTs during migration and polarization.

Stability of the prosthetic screws of three types of craniofacial prostheses retention systems

PubMed Central

2016-01-01

Objectives This study aimed to evaluate the stability of prosthetic screws from three types of craniofacial prostheses retention systems (bar-clip, ball/O-ring, and magnet) when submitted to mechanical cycling. Materials and Methods Twelve models of acrylic resin were used with implants placed 20 mm from each other and separated into three groups: (1) bar-clip (Sistema INP, São Paulo, Brazil), (2) ball/O-ring (Sistema INP), and (3) magnet (Metalmag, São Paulo, Brazil), with four samples in each group. Each sample underwent a mechanical cycling removal and insertion test (f=0.5 Hz) to determine the torque and the detorque values of the retention screws. A servo-hydraulic MTS machine (810-Flextest 40; MTS Systems, Eden Prairie, MN, USA) was used to perform the cycling with 2.5 mm and a displacement of 10 mm/s. The screws of the retention systems received an initial torque of 30 Ncm and the torque values required for loosening the screw values were obtained in three cycles (1,080, 2,160, and 3,240). The screws were retorqued to 30 Ncm before each new cycle. Results The sample was composed of 24 screws grouped as follows: bar-clip (n=8), ball/O-ring (n=8), and magnet (n=8). There were significant differences between the groups, with greater detorque values observed in the ball/O-ring group when compared to the bar-clip and magnet groups for the first cycle. However, the detorque value was greater in the bar-clip group for the second cycle. Conclusion The results of this study indicate that all prosthetic screws will loosen slightly after an initial tightening torque, also the bar-clip retention system demonstrated greater loosening of the screws when compared with ball/O-ring and magnet retention systems. PMID:28053905

Aspects of remote maintenance in an FRG reprocessing plant from the manufacturer's viewpoint

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zeitzchel, G.; Tennie, M.; Saal, G.

In April 1986 a consortium led by Kraftwerk Union AG was commissioned by the German society for nuclear fuel reprocessing (DWK) to build the first West German commercial reprocessing plant for spent fuel assemblies. The main result of the planning efforts regarding remote maintenance operations inside the main process building was the introduction of FEMO technology (FEMO is an acronym based on German for remote handling modular technique). According to this technology the two cells in which the actual reprocessing (which is based on the PUREX technique) takes place are provided with frames to accommodate the process components (tanks, pumps,more » agitators, etc.), each frame together with the components which it supports forming one module. The two cells are inaccessible and windowless. For handling operations each cell is equipped with an overhead crane and a crane-like manipulator carrier system (MTS) with power manipulator. Viewing of the operations from outside the cells is made possible by television (TV) cameras installed at the crane, the MTS, and the manipulator. This paper addresses some examples of problems that still need to be solved in connection with FEMO handling. In particular, the need for close cooperation between the equipment operator, the component designer, the process engineer, the planning engineer, and the licensing authorities will be demonstrated.« less

Losses, Expansions, and Novel Subunit Discovery of Adaptor Protein Complexes in Haptophyte Algae.

PubMed

Lee, Laura J Y; Klute, Mary J; Herman, Emily K; Read, Betsy; Dacks, Joel B

2015-11-01

The phylum Haptophyta (Diaphoratickes) contains marine algae that perform biomineralization, extruding large, distinctive calcium carbonate scales (coccoliths) that completely cover the cell. Coccolith production is an important part of global carbon cycling; however, the membrane trafficking pathway by which they are secreted has not yet been elucidated. In most eukaryotes, post-Golgi membrane trafficking involves five heterotetrameric adaptor protein (AP) complexes, which impart cargo selection specificity. To better understand coccolith secretion, we performed comparative genomic, phylogenetic, and transcriptomic analyses of the AP complexes in Emiliania huxleyi strains 92A, Van556, EH2, and CCMP1516, and related haptophytes Gephyrocapsa oceanica and Isochrysis galbana; the latter has lost the ability to biomineralize. We show that haptophytes have a modified membrane trafficking system (MTS), as we found both AP subunit losses and duplications. Additionally, we identified a single conserved subunit of the AP-related TSET complex, whose expression suggests a functional role in membrane trafficking. Finally, we detected novel alpha adaptin ear and gamma adaptin ear proteins, the first of their kind to be described outside of opisthokonts. These novel ear proteins and the sculpting of the MTS may support the capacity for biomineralization in haptophytes, enhancing their ability to perform this highly specialized form of secretion. Copyright © 2015 Elsevier GmbH. All rights reserved.

Late Pleistocene deglaciation and paleo-environment in the Retezat Mountains, Southern Carpathians

NASA Astrophysics Data System (ADS)

Ruszkiczay-Rüdiger, Zsófia; Madarász, Balázs; Kern, Zoltán; Urdea, Petru; Braucher, Régis; Aster Team

2017-04-01

This study aims to use in situ produced 10Be based Cosmic Ray Exposure (CRE) ages to reconstruct glacier evolution in the Retezat Mts, the Southern Carpathians most glaciated area with peak elevations up to 2509 m asl. In the study area currently devoid of glaciers, the calculated theoretical ELA is at ˜2860 m asl. The paleo-Equilibrium Line Altitudes (ELAs) were calculated over the ˜21 to ˜13 ka time period based on the reconstructed glacial stillstands or re-advances geometries using the ssAAR method [1, 2]. Regarding the Northern side of the Retezat Mts, new and re-evaluated 10Be CRE ages (n=34) [3] were used while regarding the Southern side, they all result from a new sampling (n=25). According to the data, the most extended glaciation occurred during the LGM, down to ˜1050 m asl. on both sides of the Retezat Mts with most probable 10Be CRE ages of 21.0 -1.5+0.8 ka and 20.7 -1.0+0.9 ka. The reconstructed ELA depression in the North was ˜1010 m while it was ˜1190 m, in the South where the valleys glacial system (Lăpuşnicu - Judele) was significantly larger with longer glacier tongues. At the beginning of the Lateglacial (˜17-18 ka) the glaciers withdrew and the North-South difference between the ELA depression was decreased (˜885 m and ˜945 m, respectively). The ELA differences further reduced and vanished for the ˜15.3 ka glacial event - the last cold stage before the abrupt Bölling/Alleröd warming - with ELA depressions of ˜728 m and ˜712 m, respectively. The last glacial phase in the area characterized by small cirque glaciers occurred at 13.5 -0.6+0.6 ka in the North and 13.9 -0.4+0.9 ka in the South. By this time, the ELA depression was reduced to ˜660-680 m. Due to the small glacier size this value may have been influenced by local topoclimatic factors. So far, no data support Younger Dryas or Holocene glaciation of the Retezat Mts. The elevation difference of the ELAs suggests more precipitation on the Southern side of the Retezat Mts during the LGM. This may indicate a southerly wind regime at this part of Europe, which subsequently gave place to the westerly winds during the warming climate of the Lateglacial. Using a Chironomidae-based summer temperature (T) reconstruction from the area [4], T and mean annual precipitation (P) at the ELA were calculated for the ˜15.3 ka stage. Based on Ohmura et al. [5] a ˜4.5-4.9 ˚ C decrease of T and a ˜10-15% increase of P compared to the present values were calculated. Thanks to OTKA PD83610, PD104899; NKM-96/2014, NKM-31/2015; OMAA 90öu17; LP2012-27/2012, INSU/CNRS, the ANR through the program "EQUIPEX Investissement d'Avenir", IRD and CEA. References: [1] Pellitero et al. 2015 Computers & Gerosciences 82: 55-62 [2] Kern and László, 2010. Quat. Sci. Rev. 29, 2781-2787. [3] Ruszkiczay-Rüdiger et al. 2016 Quat. Int. 415. 216-229. [4] Tóth et al., 2012. Quat. Res. 77. 122-131. [5] Ohmura et al. 1992. J. of Glaciology, 38. 397-411.

Mitochondrial tRNA cleavage by tRNA-targeting ribonuclease causes mitochondrial dysfunction observed in mitochondrial disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ogawa, Tetsuhiro, E-mail: atetsu@mail.ecc.u-tokyo.ac.jp; Shimizu, Ayano; Takahashi, Kazutoshi

2014-08-15

Highlights: • MTS-tagged ribonuclease was translocated successfully to the mitochondrial matrix. • MTS-tagged ribonuclease cleaved mt tRNA and reduced COX activity. • Easy and reproducible method of inducing mt tRNA dysfunction. - Abstract: Mitochondrial DNA (mtDNA) is a genome possessed by mitochondria. Since reactive oxygen species (ROS) are generated during aerobic respiration in mitochondria, mtDNA is commonly exposed to the risk of DNA damage. Mitochondrial disease is caused by mitochondrial dysfunction, and mutations or deletions on mitochondrial tRNA (mt tRNA) genes are often observed in mtDNA of patients with the disease. Hence, the correlation between mt tRNA activity and mitochondrialmore » dysfunction has been assessed. Then, cybrid cells, which are constructed by the fusion of an enucleated cell harboring altered mtDNA with a ρ{sup 0} cell, have long been used for the analysis due to difficulty in mtDNA manipulation. Here, we propose a new method that involves mt tRNA cleavage by a bacterial tRNA-specific ribonuclease. The ribonuclease tagged with a mitochondrial-targeting sequence (MTS) was successfully translocated to the mitochondrial matrix. Additionally, mt tRNA cleavage, which resulted in the decrease of cytochrome c oxidase (COX) activity, was observed.« less

Time course and auxin sensitivity of cortical microtubule reorientation in maize roots

NASA Technical Reports Server (NTRS)

Blancaflor, E. B.; Hasenstein, K. H.

1995-01-01

The kinetics of MT [microtubule] reorientation in primary roots of Zea mays cv. Merit, were examined 15, 30, 45, and 60 min after horizontal positioning. Confocal microscopy of longitudinal tissue sections showed no change in MT orientation 15 and 30 min after horizontal placement. However, after 45 and 60 min, MTs of the outer 4-5 cortical cell layers along the lower side were reoriented. In order to test whether MT reorientation during graviresponse is caused by an auxin gradient, we examined the organization of MTs in roots that were incubated for 1 h in solutions containing 10(-9) to 10(-6) M IAA. IAA treatment at 10(-8) M or less showed no major or consistent changes but 10(-7) M IAA resulted in MT reorientation in the cortex. The auxin effect does not appear to be acid-induced since benzoic acid (10(-5) M) did not cause MT reorientation. The region closest to the maturation zone was most sensitive to IAA. The data indicate that early stages of gravity induced curvature occur in the absence of MT reorientation but sustained curvature leads to reoriented MTs in the outer cortex. Growth inhibition along the lower side of graviresponding roots appears to result from asymmetric distribution of auxin following gravistimulation.

PKCzeta is required for microtubule-based motility of vesicles containing the ntcp transporter.

PubMed

Sarkar, Souvik; Bananis, Eustratios; Nath, Sangeeta; Anwer, M Sawkat; Wolkoff, Allan W; Murray, John W

2006-08-01

Intracellular trafficking regulates the abundance and therefore activity of transporters present at the plasma membrane. The transporter, Na+-taurocholate co-transporting polypeptide (ntcp), is increased at the plasma membrane upon treatment of cells with cAMP, for which microtubules (MTs) are required and the PI3K pathway and PKCzeta have been implicated. However, trafficking of ntcp on MTs has not been demonstrated directly and the regulation and intracellular localization of ntcp is not well understood. Here, we utilize in vitro and whole-cell immunofluorescence microscopy assays to demonstrate that ntcp is present on intracellular vesicles that bind MTs and move bidirectionally, using kinesin-1 and dynein. These vesicles co-localize with markers for recycling endosomes and early but not late endosomes. They frequently undergo fission, providing a mechanism for the exclusion of ntcp from late endosomes. PI(3,4,5)P3 activates PKCzeta and enhances motility of the ntcp vesicles and overcomes the partial inhibition produced by a PI3-kinase inhibitor. Specific inhibition of PKCzeta blocks the motility of ntcp-containing vesicles but has no effect on late vesicles as shown both in vitro and in living cells transfected with ntcp-GFP. These data indicate that PKCzeta is required specifically for the intracellular movement of vesicles that contain the ntcp transporter.

Distinct effects of tubulin isotype mutations on neurite growth in Caenorhabditis elegans

PubMed Central

Zheng, Chaogu; Diaz-Cuadros, Margarete; Nguyen, Ken C. Q.; Hall, David H.; Chalfie, Martin

2017-01-01

Tubulins, the building block of microtubules (MTs), play a critical role in both supporting and regulating neurite growth. Eukaryotic genomes contain multiple tubulin isotypes, and their missense mutations cause a range of neurodevelopmental defects. Using the Caenorhabditis elegans touch receptor neurons, we analyzed the effects of 67 tubulin missense mutations on neurite growth. Three types of mutations emerged: 1) loss-of-function mutations, which cause mild defects in neurite growth; 2) antimorphic mutations, which map to the GTP binding site and intradimer and interdimer interfaces, significantly reduce MT stability, and cause severe neurite growth defects; and 3) neomorphic mutations, which map to the exterior surface, increase MT stability, and cause ectopic neurite growth. Structure-function analysis reveals a causal relationship between tubulin structure and MT stability. This stability affects neuronal morphogenesis. As part of this analysis, we engineered several disease-associated human tubulin mutations into C. elegans genes and examined their impact on neuronal development at the cellular level. We also discovered an α-tubulin (TBA-7) that appears to destabilize MTs. Loss of TBA-7 led to the formation of hyperstable MTs and the generation of ectopic neurites; the lack of potential sites for polyamination and polyglutamination on TBA-7 may be responsible for this destabilization. PMID:28835377

Decreased necrotizing fasciitis capacity caused by a single nucleotide mutation that alters a multiple gene virulence axis.

PubMed

Olsen, Randall J; Sitkiewicz, Izabela; Ayeras, Ara A; Gonulal, Vedia E; Cantu, Concepcion; Beres, Stephen B; Green, Nicole M; Lei, Benfang; Humbird, Tammy; Greaver, Jamieson; Chang, Ellen; Ragasa, Willie P; Montgomery, Charles A; Cartwright, Joiner; McGeer, Allison; Low, Donald E; Whitney, Adeline R; Cagle, Philip T; Blasdel, Terry L; DeLeo, Frank R; Musser, James M

2010-01-12

Single-nucleotide changes are the most common cause of natural genetic variation among members of the same species, but there is remarkably little information bearing on how they alter bacterial virulence. We recently discovered a single-nucleotide mutation in the group A Streptococcus genome that is epidemiologically associated with decreased human necrotizing fasciitis ("flesh-eating disease"). Working from this clinical observation, we find that wild-type mtsR function is required for group A Streptococcus to cause necrotizing fasciitis in mice and nonhuman primates. Expression microarray analysis revealed that mtsR inactivation results in overexpression of PrsA, a chaperonin involved in posttranslational maturation of SpeB, an extracellular cysteine protease. Isogenic mutant strains that overexpress prsA or lack speB had decreased secreted protease activity in vivo and recapitulated the necrotizing fasciitis-negative phenotype of the DeltamtsR mutant strain in mice and monkeys. mtsR inactivation results in increased PrsA expression, which in turn causes decreased SpeB secreted protease activity and reduced necrotizing fasciitis capacity. Thus, a naturally occurring single-nucleotide mutation dramatically alters virulence by dysregulating a multiple gene virulence axis. Our discovery has broad implications for the confluence of population genomics and molecular pathogenesis research.

Tumor suppressors Sav/Scrib and oncogene Ras regulate stem cell transformation in adult Drosophila Malpighian Tubules

PubMed Central

Zeng, Xiankun; Singh, Shree Ram; Hou, David; Hou, Steven X.

2012-01-01

An increasing body of evidence suggests that tumors might originate from a few transformed cells that share many properties with normal stem cells. However, it remains unclear how normal stem cells are transformed into cancer stem cells. Here, we demonstrated that mutations causing the loss of tumor suppressor Sav or Scrib or activation of the oncogene Ras transform normal stem cells into cancer stem cells through a multistep process in the adult Drosophila Malpighian Tubules (MTs). In wild-type MTs, each stem cell generates one self-renewing and one differentiating daughter cell. However, in flies with loss-of-function sav or scrib or gain-of-function Ras mutations, both daughter cells grew and behaved like stem cells, leading to the formation of tumors in MTs. Ras functioned downstream of Sav and Scrib in regulating the stem cell transformation. The Ras-transformed stem cells exhibited many of the hallmarks of cancer, such as increased proliferation, reduced cell death, and failure to differentiate. We further demonstrated that several signal transduction pathways (including MEK/MAPK, RhoA, PKA, and TOR) mediate Rasṕ function in the stem cell transformation. Therefore, we have identified a molecular mechanism that regulates stem cell transformation, and this finding may lead to strategies for preventing tumor formation in certain organs. PMID:20432470

Influence of volume magnetostriction on the thermodynamic properties of Ni-Mn-Ga shape memory alloys

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kosogor, Anna; Institute of Magnetism, 36-b, Vernadsky Str., Kyiv 03142; Donetsk Institute for Physics and Engineering, Kyiv 03028

2015-10-07

In the present article, the thermodynamic properties of Ni-Mn-Ga ferromagnetic shape memory alloys exhibiting the martensitic transformations (MTs) above and below Curie temperature are compared. It is shown that when MT goes below Curie temperature, the elastic and thermal properties of alloy noticeably depend on magnetization value due to spontaneous volume magnetostriction. However, the separation of magnetic parts from the basic characteristics of MT is a difficult task, because the volume magnetostriction does not qualitatively change the transformational behaviour of alloy. This problem is solved for several Ni-Mn-Ga alloys by means of the quantitative theoretical analysis of experimental data obtainedmore » in the course of stress-strain tests. For each alloy, the entropy change and the transformation heat evolved in the course of MT are evaluated, first, from the results of stress-strain tests and, second, from differential scanning calorimetry data. For all alloys, a quantitative agreement between the values obtained in two different ways is observed. It is shown that the magnetic part of transformation heat exceeds the non-magnetic one for the Ni-Mn-Ga alloys undergoing MTs in ferromagnetic state, while the elevated values of transformation heat measured for the alloys undergoing MTs in paramagnetic state are caused by large MT strains.« less

Cytoplasmic Nucleation and Atypical Branching Nucleation Generate Endoplasmic Microtubules in Physcomitrella patens[OPEN

PubMed Central

Nakaoka, Yuki; Kimura, Akatsuki; Tani, Tomomi; Goshima, Gohta

2015-01-01

The mechanism underlying microtubule (MT) generation in plants has been primarily studied using the cortical MT array, in which fixed-angled branching nucleation and katanin-dependent MT severing predominate. However, little is known about MT generation in the endoplasm. Here, we explored the mechanism of endoplasmic MT generation in protonemal cells of Physcomitrella patens. We developed an assay that utilizes flow cell and oblique illumination fluorescence microscopy, which allowed visualization and quantification of individual MT dynamics. MT severing was infrequently observed, and disruption of katanin did not severely affect MT generation. Branching nucleation was observed, but it showed markedly variable branch angles and was occasionally accompanied by the transport of nucleated MTs. Cytoplasmic nucleation at seemingly random locations was most frequently observed and predominated when depolymerized MTs were regrown. The MT nucleator γ-tubulin was detected at the majority of the nucleation sites, at which a single MT was generated in random directions. When γ-tubulin was knocked down, MT generation was significantly delayed in the regrowth assay. However, nucleation occurred at a normal frequency in steady state, suggesting the presence of a γ-tubulin-independent backup mechanism. Thus, endoplasmic MTs in this cell type are generated in a less ordered manner, showing a broader spectrum of nucleation mechanisms in plants. PMID:25616870

Influence of volume magnetostriction on the thermodynamic properties of Ni-Mn-Ga shape memory alloys

NASA Astrophysics Data System (ADS)

Kosogor, Anna; L'vov, Victor A.; Cesari, Eduard

2015-10-01

In the present article, the thermodynamic properties of Ni-Mn-Ga ferromagnetic shape memory alloys exhibiting the martensitic transformations (MTs) above and below Curie temperature are compared. It is shown that when MT goes below Curie temperature, the elastic and thermal properties of alloy noticeably depend on magnetization value due to spontaneous volume magnetostriction. However, the separation of magnetic parts from the basic characteristics of MT is a difficult task, because the volume magnetostriction does not qualitatively change the transformational behaviour of alloy. This problem is solved for several Ni-Mn-Ga alloys by means of the quantitative theoretical analysis of experimental data obtained in the course of stress-strain tests. For each alloy, the entropy change and the transformation heat evolved in the course of MT are evaluated, first, from the results of stress-strain tests and, second, from differential scanning calorimetry data. For all alloys, a quantitative agreement between the values obtained in two different ways is observed. It is shown that the magnetic part of transformation heat exceeds the non-magnetic one for the Ni-Mn-Ga alloys undergoing MTs in ferromagnetic state, while the elevated values of transformation heat measured for the alloys undergoing MTs in paramagnetic state are caused by large MT strains.

Late Permian volcanic dykes in the crystalline basement of the Považský Inovec Mts. (Western Carpathians): U-Th-Pb zircon SHRIMP and monazite chemical dating

NASA Astrophysics Data System (ADS)

Pelech, Ondrej; Vozárová, Anna; Uher, Pavel; Petrík, Igor; Plašienka, Dušan; Šarinová, Katarína; Rodionov, Nikolay

2017-08-01

This paper presents geochronological data for the volcanic dykes located in the northern Považský Inovec Mts. The dykes are up to 5 m thick and tens to hundreds of metres long. They comprise variously inclined and oriented lenses, composed of strongly altered grey-green alkali basalts. Their age was variously interpreted and discussed in the past. Dykes were emplaced into the Tatricum metamorphic rocks, mostly consisting of mica schists and gneisses of the Variscan (early Carboniferous) age. Two different methods, zircon SHRIMP and monazite chemical dating, were applied to determine the age of these dykes. U-Pb SHRIMP dating of magmatic zircons yielded the concordia age of 260.2 ± 1.4 Ma. The Th-U-Pb monazite dating of the same dyke gave the CHIME age of 259 ± 3Ma. Both ages confirm the magmatic crystallization at the boundary of the latest Middle Permian to the Late Permian. Dyke emplacement was coeval with development of the Late Paleozoic sedimentary basin known in the northern Považský Inovec Mts. and could be correlated with other pre-Mesozoic Tethyan regions especially in the Southern Alps.

Kinetochore fiber formation in animal somatic cells: dueling mechanisms come to a draw

PubMed Central

2008-01-01

The attachment to and movement of a chromosome on the mitotic spindle are mediated by the formation of a bundle of microtubules (MTs) that tethers the kinetochore on the chromosome to a spindle pole. The origin of these “kinetochore fibers” (K fibers) has been investigated for over 125 years. As noted in 1944 by Schrader [Mitosis, Columbia University Press, New York, 110 pp.], there are three possible ways to form a K fiber: (a) it grows from the pole until it contacts the kinetochore, (b) it grows directly from the kinetochore, or (c) it forms as a result of an interaction between the pole and the chromosome. Since Schrader's time, it has been firmly established that K fibers in centrosome-containing animal somatic cells form as kinetochores capture MTs growing from the spindle pole (route a). It is now similarly clear that in cells lacking centrosomes, including higher plants and many animal oocytes, K fibers “self-assemble” from MTs generated by the chromosomes (route b). Can animal somatic cells form K fibers in the absence of centrosomes by the “self-assembly” pathway? In 2000, the answer to this question was shown to be a resounding “yes.” With this result, the next question became whether the presence of a centrosome normally suppresses K fiber self-assembly or if this route works concurrently with centrosome-mediated K-fiber formation. This question, too, has recently been answered: observations on untreated live animal cells expressing green fluorescent protein-tagged tubulin clearly show that kinetochores can nucleate the formation of their associated MTs in a unique manner in the presence of functional centrosomes. The concurrent operation of these two “dueling” routes for forming K fibers in animal cells helps explain why the attachment of kinetochores and the maturation of K fibers occur as quickly as they do on all chromosomes within a cell. PMID:16270218

The Characteristics, Experiences and Perceptions of Registered Massage Therapists in New Zealand: Results from a National Survey of Practitioners.

PubMed

Cottingham, Phillip; Adams, Jon; Vempati, Ram; Dunn, Jill; Sibbritt, David

2018-06-01

Massage therapy is widely recognized as offering many health benefits, with a growing number of studies finding it has value in stress management, pain reduction, and overcoming physical limitations. However, there are few studies of massage therapists practices and perceptions in New Zealand and internationally. This paper reports the findings from the first national survey examining the characteristics, perceptions, and experiences of New Zealand-based massage therapists on a range of aspects related to their role and practices. This study sought to ascertain the characteristics, experiences, and perceptions of massage therapists in New Zealand, particularly in the aspects of: integration of health care; attitudes and practices related to research; and evidence and attitudes to registration. Massage practice in New Zealand (nationwide survey). Members of Massage New Zealand (a massage practitioners association). Massage practitioners were surveyed online, using a 65-part questionnaire, on a range of characteristics of their practices and their attitudes to research, integration, and registration. Statistical analysis was performed using STATA. Statistical significance was set at 0.05. Four hundred massage therapists (MTs) were invited to participate and 115 responded, providing a response rate of 29%. MTs valued research (95%) and perceived that it had an impact for their practices (88%). Significant correlations were found for research value and: mean case-load ( p = .009) and level of academic qualification ( p = .004). The majority of MTs (79%) supported integration with conventional practitioners, and 83% referred clients to general practitioners, with 75% receiving referrals from general practitioners. Ninety-three percent of MTs supported registration, with 67% of those supporting statutory registration. Massage practitioners perceive that they make a significant contribution to health care, but area of practice, such as research, and referral and integration into mainstream health care require more in-depth investigation.

Oxidation of the N-terminal domain of the wheat metallothionein Ec -1 leads to the formation of three distinct disulfide bridges.

PubMed

Tarasava, Katsiaryna; Chesnov, Serge; Freisinger, Eva

2016-05-01

Metallothioneins (MTs) are low molecular weight proteins, characterized by a high cysteine content and the ability to coordinate large amounts of d(10) metal ions, for example, Zn(II), Cd(II), and Cu(I), in form of metal-thiolate clusters. Depending on intracellular conditions such as redox potential or metal ion concentrations, MTs can occur in various states ranging from the fully metal-loaded holo- to the metal-free apo-form. The Cys thiolate groups in the apo-form can be either reduced or be involved in disulfide bridges. Although oxidation-mediated Zn(II) release might be a possible mechanism for the regulation of Zn(II) availability by MTs, no concise information regarding the associated pathways and the structure of oxidized apo-MT forms is available. Using the well-studied Zn2 γ-Ec -1 domain of the wheat Zn6 Ec -1 MT we attempt here to answer several question regarding the structure and biophysical properties of oxidized MT forms, such as: (1) does disulfide bond formation increase the stability against proteolysis, (2) is the overall peptide backbone fold similar for the holo- and the oxidized apo-MT form, and (3) are disulfide bridges specifically or randomly formed? Our investigations show that oxidation leads to three distinct disulfide bridges independently of the applied oxidation conditions and of the initial species used for oxidation, that is, the apo- or the holo-form. In addition, the oxidized apo-form is as stable against proteolysis as Zn2 γ-Ec -1, rendering the currently assumed degradation of oxidized MTs unlikely and suggesting a role of the oxidation process for the extension of protein lifetime in absence of sufficient amounts of metal ions. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 295-308, 2016. © 2016 Wiley Periodicals, Inc.

New insights into the parametrization of temperature and light responses of mono - and sesquiterpene emissions from Aleppo pine and rosemary

NASA Astrophysics Data System (ADS)

Staudt, M.; Bourgeois, I.; Al Halabi, R.; Song, W.; Williams, J.

2017-03-01

Phytogenic emission of large volatile organic compounds (VOCs) such as monoterpenes (MTs) and sesquiterpenes (SQTs) are key precursors to the formation and growth of atmospheric particles. However, controlled environment studies to elucidate emission responses to temperature and light are still sparse. In this study, the volatile contents and emission responses of Aleppo pine and Rosemary have been investigated. These two common Mediterranean species store semivolatiles inside (resin ducts) and outside (trichomes) their foliage tissues respectively. Both species emitted mainly MTs with basal emission rates of around 5 (Rosemary) and 10 (pine) μg g-1 h-1 and SQTs about one order of magnitude lower. In Aleppo pine, two volatile sources could be clearly distinguished: 1) de-novo synthesized emission of (E)-β-ocimene and linalool, which accounted for about 70% of the total VOC release, were not found in foliar VOC extracts and expressed light dependency (LD) and temperature responses typical for enzyme driven emissions; and 2) storage-derived emissions of various MTs and SQTs whose emissions increased exponentially with temperature, showed no light dependency and were all present in leaf extracts. In Rosemary, all emitted MTs and SQTs including many oxygenated compounds, showed responses typical for stored volatiles and were all found in leaf extracts. The emissions of individual volatiles or volatile classes could be well described with the commonly applied empirical algorithms developed for LD or non LD emissions. However, the shapes of the temperature responses, and hence the deduced coefficient values, were significantly different between oxygenated and non-oxygenated compounds. They also differed between the storage-derived emissions of the two plant species, for individual VOCs or VOC classes. We address the possible reasons for this variation in temperature responses and argue that they are mostly due to molecular interactions along the species specific leaf-internal diffusion paths including the build-up of transient VOC pools and degradation.

Association of Aurora-A (STK15) Kinase Polymorphisms With Clinical Outcome of Esophageal Cancer Treated With Preoperative Chemoradiation

PubMed Central

Pan, Jennifer Y.; Ajani, Jaffer A.; Gu, Jian; Gong, Yubo; Quin, Angel; Hung, Maosheng; Wu, Xifeng; Izzo, Julie G.

2013-01-01

BACKGROUND: Aurora-A/STK15 is a serine/threonine kinase critical for regulated chromosome segregation and cytokinesis. We investigated the association between 2 nonsynonymous single nucleotide polymorphisms in the coding region of STK15, T91A (Phe31Ile) and G169A (Val57Ile), and clinical outcome of esophageal cancer treated with preoperative chemoradiation. METHODS: Genotypes at Phe31Ile and Val57Ile were assessed from peripheral blood lymphocytes of 190 esophageal cancer patients and were correlated to response to treatment, recurrence rate, risk of death, disease-free survival (DFS) and median survival time (MTS). RESULTS: All patients had resectable esophageal or gastroesophageal junction cancer and received preoperative chemoradiation followed by esophagectomy. The heterozygous variant Phe31/Ile variant was significantly associated with tumor recurrence (odds ratio [OR] = 4.39; 95% confidence interval [CI], 2.12-8.94; P < .001), shorter DFS (P = .0001), and shorter MTS (P = .012). For patients receiving cisplatin-based therapy, only the variant Phe31/Ile had an adverse effect on response (OR = 2.8; 95% CI, 1.01-5.17; P = .048) and MTS (P = .026). The variant 91A-169G haplotype carried a significant risk for lack of complete response (OR = 2.54; 95% CI, 1.15-5.54) and higher rate of recurrence (OR = 2.73; 95%CI, 1.00-7.29). The presence of at least 1 variant allele at each locus further increased the risk of recurrence (adjusted OR = 6.21; 95% CI, 2.28-17.11; P = <.001), and was associated significantly shorter DFS (P = .003). CONCLUSIONS: Our study shows that functional SNPs in the STK15 gene are associated with higher rate of recurrence, higher likelihood of chemoratiotherapy-resistance, shorter DFS, and shorter MTS. Confirmation of our data and understanding the mechanisms through which STK15 functional SNPs mediate resistance to chemoradiotherapy are warranted. PMID:22213102

Characterization of the rubber tree metallothionein family reveals a role in mitigating the effects of reactive oxygen species associated with physiological stress.

PubMed

Huang, Yacheng; Fang, Yongjun; Long, Xiangyu; Liu, Linya; Wang, Jia; Zhu, Jinheng; Ma, Yanyan; Qin, Yunxia; Qi, Jiyan; Hu, Xinwen; Tang, Chaorong

2018-06-01

Metallothioneins (MTs) as reactive oxygen species (ROS) scavengers play important roles in stress response and heavy metal homeostasis. In Hevea brasiliensis (the para rubber tree that is the source of commercial natural rubber) and in other trees, the functions of MTs are not well understood. Latex exudes when the rubber tree is tapped. The flow of latex and its regeneration can be enhanced by tapping, wounding and ethylene treatment, all of which produce ROS as a by-product. Here, we show the presence of four MT genes in H. brasiliensis, comprising three Type 2 (HbMT2, -2a and -2b) and one Type 3 (HbMT3L) isoforms, representing one of the smallest MT gene families among angiosperms. The four HbMTs exhibited distinct tissue expression patterns: HbMT2 and HbMT3L mainly in leaves, HbMT2a specifically in flowers and HbMT2b in diverse tissues. The expression of HbMT2b, an isoform present in latex, decreased significantly in the latex following the stress-inducing treatments of tapping, wounding and ethephon (an ethylene generator). The expressions of the leaf-abundant isoforms, HbMT2 and -3L were up-regulated following pathogenic fungus infection and high-temperature stress, but down-regulated by low-temperature stress. These reactions were consistent with multiple defense- and hormone-responsive cis-acting elements in the HbMT promoters. Nine transcription factors were shown to implicate in the high-temperature responsiveness of HbMT2 and -3L in leaves. Overexpression of HbMT2 in Escherichia coli enhanced the bacterium's tolerance to heavy metals and ROS, consistent with its predicted role as an ROS scavenger. Taken together, our results, along with other relevant studies, suggest an important role of HbMTs in latex regeneration as well as species adaptation via the regulation of ROS homeostasis.

Ankle Joint Angle and Lower Leg Musculotendinous Unit Responses to Cryotherapy.

PubMed

Akehi, Kazuma; Long, Blaine C; Warren, Aric J; Goad, Carla L

2016-09-01

Akehi, K, Long, BC, Warren, AJ, and Goad, CL. Ankle joint angle and lower leg musculotendinous unit responses to cryotherapy. J Strength Cond Res 30(9): 2482-2492, 2016-The use of cold application has been debated for its influence on joint range of motion (ROM) and stiffness. The purpose of this study was to determine whether a 30-minute ice bag application to the plantarflexor muscles or ankle influences passive ankle dorsiflexion ROM and lower leg musculotendinous stiffness (MTS). Thirty-five recreationally active college-aged individuals with no history of lower leg injury 6 months before data collection volunteered. On each testing day, we measured maximum passive ankle dorsiflexion ROM (°) and plantarflexor torque (N·m) on an isokinetic dynamometer to calculate the passive plantarflexor MTS (N·m per degree) at 4 joint angles before, during, and after a treatment. Surface electromyography amplitudes (μV), and skin surface and ambient air temperature (°C) were also measured. Subjects received an ice bag to the posterior lower leg, ankle joint, or nothing for 30 minutes in different days. Ice bag application to the lower leg and ankle did not influence passive ROM (F(12,396) = 0.67, p = 0.78). Passive torque increased after ice bag application to the lower leg (F(12,396) = 2.21, p = 0.011). Passive MTS at the initial joint angle increased after ice bag application to the lower leg (F(12,396) = 2.14, p = 0.014) but not at the other joint angles (p > 0.05). Surface electromyography amplitudes for gastrocnemius and soleus muscles increased after ice application to the lower leg (F(2,66) = 5.61, p = 0.006; F(12,396) = 3.60, p < 0.001). Ice bag application to the lower leg and ankle joint does not alter passive dorsiflexion ROM but increases passive ankle plantarflexor torque in addition to passive ankle plantarflexor MTS at the initial joint angle.

Energy intake and diet selection during buffet consumption in women classified by the 6-n-propylthiouracil bitter taste phenotype.

PubMed

Shafaie, Yasmine; Koelliker, Yvonne; Hoffman, Daniel J; Tepper, Beverly J

2013-12-01

Exposure to a variety of energy-dense foods promotes increased energy intake and adiposity. Taste blindness to the bitterness of 6-n-propylthiouracil (PROP) has been associated with increased adiposity in women and might be linked to an increased energy intake and greater selection of dietary fat. We investigated whether PROP nontaster (NT) women would consume more fat and energy in a buffet setting than medium taster (MT) or supertaster (ST) women. Seventy-five non-diet-restrained, lean, young women [mean ± SEM BMI (in kg/m²): 21.5 ± 0.6; age: 26.1 ± 1.3 y) ate lunch and dinner in the laboratory for 3 consecutive days under the following 2 conditions: ad libitum control meals (CONTs) or high-variety buffet meals (BUFFs). A standard breakfast was consumed each day of the study (4 - d washout between conditions). NTs and MTs consumed more energy and fat (as the percentage of energy) from BUFFs than did STs (P < 0.01), which contributed to higher daily energy intakes in these 2 groups of women during BUFFs (2149 ± 49 kcal/d for NTs and 2209 ± 48 kcal/d for MTs compared with 1933 ± 50 kcal/d for STs; P < 0.01). Together, NTs and MTs consumed an extra 246 kcal/d during BUFFs than during CONTs. In addition, compared with STs, NTs and MTs consumed more added fats and sweets (servings/d; P < 0.003) and more energy from snacks (P < 0.01) across all study days. NT and MT women consume more daily energy than do ST women when eating in a buffet setting, which is a common type of dietary exposure. This increase in energy intake over time could contribute to a positive energy balance and increased adiposity previously reported in these women.

MTS-6 detectors calibration by using ²³⁹Pu-Be neutron source.

PubMed

Wrzesień, Małgorzata; Albiniak, Łukasz; Al-Hameed, Hiba

2017-10-17

Thermoluminescent detectors, type MTS-6, containing isotope ⁶Li (lithium) are sensitive in the range of thermal neutron energy; the ²³⁹Pu-Be (plutonium-and-beryllium) source emits neutrons in the energy range from 1 to 11 MeV. These seemingly contradictory elements may be combined by using the paraffin moderator, a determined density of thermal neutrons in the paraffin block and a conversion coefficient neutron flux to kerma, not forgetting the simultaneous registration of the photon radiation inseparable from the companion neutron radiation. The main aim of this work is to present the idea of calibration of thermoluminescent detectors that consist of a ⁶Li isotope, by using ²³⁹Pu-Be neutron radiation source. In this work, MTS-6 and MTS-7 thermoluminescent detectors and a plutonium-and-beryllium (²³⁹Pu-Be) neutron source were used. Paraffin wax fills the block, acting as a moderator. The calibration idea was based on the determination of dose equivalent rate based on the average kerma rate calculated taking into account the empirically determined function describing the density of thermal neutron flux in the paraffin block and a conversion coefficient neutron flux to kerma. The calculated value of the thermal neutron flux density was 1817.5 neutrons/cm²/s and the average value of kerma rate determined on this basis amounted to 244 μGy/h, and the dose equivalent rate 610 μSv/h. The calculated value allowed for the assessment of the length of time of exposure of the detectors directly in the paraffin block. The calibration coefficient for the used batch of detectors is (6.80±0.42)×10^-7 Sv/impulse. Med Pr 2017;68(6):705-710. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Reticulated acanthoma with sebaceous differentiation: another sebaceous neoplasm associated with Muir-Torre syndrome?

PubMed

Shon, Wonwoo; Wolz, Michael M; Newman, Catherine C; Bridges, Alina G

2014-11-01

Reticulated acanthoma with sebaceous differentiation (RASD) represents a rare benign cutaneous epithelial neoplasm with sebaceous differentiation. There has been much speculation about the relationship between RASD and Muir-Torre syndrome (MTS). We report a 53 year-old man who presented with RASD in addition to a prior history of sebaceous adenomas. Immunohistochemically, the tumour cells in the RASD and sebaceous adenomas showed a significantly reduced MSH6 protein expression, whereas there was no loss of MLH1, MSH2 and PMS2. This benign neoplasm, which can be mistaken for various other cutaneous lesions with sebaceous differentiation, deserves wider recognition for its possible association with MTS. © 2013 The Authors. Australasian Journal of Dermatology © 2013 The Australasian College of Dermatologists.

The microtube-strip heat exchanger - Space power applications for ultra-high conductance gas-gas exchangers

NASA Astrophysics Data System (ADS)

Doty, F. D.; Hosford, Gregory S.; Spitzmesser, Jonathan B.

New developments in manufacturing automation permit the use of large, parallel arrays of very small diameter tubing for greatly increased performance in both spacecraft radiators and recuperators. Micro-tube strip (MTS) recuperators with normalized specific conductance above 1000 W/kgK (20 times the current state of the art) and pressure drops below 1 percent are shown to be realistic long-term goals. The same technology also promises an order of magnitude improvement in radiator specific mass. Some significant space power applications, including the Closed Brayton Cycle and Reverse Brayton Cycle, are discussed. A detailed analysis of the MTS recuperator is presented along with experimental results from prototypes, and some manufacturing considerations are mentioned.

Micromechanics of composite laminate compression failure

NASA Technical Reports Server (NTRS)

Guynn, E. Gail; Bradley, Walter L.

1986-01-01

The Dugdale analysis for metals loaded in tension was adapted to model the failure of notched composite laminates loaded in compression. Compression testing details, MTS alignment verification, and equipment needs were resolved. Thus far, only 2 ductile material systems, HST7 and F155, were selected for study. A Wild M8 Zoom Stereomicroscope and necessary attachments for video taping and 35 mm pictures were purchased. Currently, this compression test system is fully operational. A specimen is loaded in compression, and load vs shear-crippling zone size is monitored and recorded. Data from initial compression tests indicate that the Dugdale model does not accurately predict the load vs damage zone size relationship of notched composite specimens loaded in compression.

Genetic Interaction Mapping in Schizosaccharomyces pombe Using the Pombe Epistasis Mapper (PEM) System and a ROTOR HDA Colony Replicating Robot in a 1536 Array Format.

PubMed

Roguev, Assen; Xu, Jiewei; Krogan, Nevan

2018-02-01

This protocol describes an optimized high-throughput procedure for generating double deletion mutants in Schizosaccharomyces pombe using the colony replicating robot ROTOR HDA and the PEM (pombe epistasis mapper) system. The method is based on generating high-density colony arrays (1536 colonies per agar plate) and passaging them through a series of antidiploid and mating-type selection (ADS-MTS) and double-mutant selection (DMS) steps. Detailed program parameters for each individual replication step are provided. Using this procedure, batches of 25 or more screens can be routinely performed. © 2018 Cold Spring Harbor Laboratory Press.

A Heme-based Redox Sensor in the Methanogenic Archaeon Methanosarcina acetivorans*

PubMed Central

Molitor, Bastian; Stassen, Marc; Modi, Anuja; El-Mashtoly, Samir F.; Laurich, Christoph; Lubitz, Wolfgang; Dawson, John H.; Rother, Michael; Frankenberg-Dinkel, Nicole

2013-01-01

Based on a bioinformatics study, the protein MA4561 from the methanogenic archaeon Methanosarcina acetivorans was originally predicted to be a multidomain phytochrome-like photosensory kinase possibly binding open-chain tetrapyrroles. Although we were able to show that recombinantly produced and purified protein does not bind any known phytochrome chromophores, UV-visible spectroscopy revealed the presence of a heme tetrapyrrole cofactor. In contrast to many other known cytoplasmic heme-containing proteins, the heme was covalently attached via one vinyl side chain to cysteine 656 in the second GAF domain. This GAF domain by itself is sufficient for covalent attachment. Resonance Raman and magnetic circular dichroism data support a model of a six-coordinate heme species with additional features of a five-coordination structure. The heme cofactor is redox-active and able to coordinate various ligands like imidazole, dimethyl sulfide, and carbon monoxide depending on the redox state. Interestingly, the redox state of the heme cofactor has a substantial influence on autophosphorylation activity. Although reduced protein does not autophosphorylate, oxidized protein gives a strong autophosphorylation signal independent from bound external ligands. Based on its genomic localization, MA4561 is most likely a sensor kinase of a two-component system effecting regulation of the Mts system, a set of three homologous corrinoid/methyltransferase fusion protein isoforms involved in methyl sulfide metabolism. Consistent with this prediction, an M. acetivorans mutant devoid of MA4561 constitutively synthesized MtsF. On the basis of our results, we postulate a heme-based redox/dimethyl sulfide sensory function of MA4561 and propose to designate it MsmS (methyl sulfide methyltransferase-associated sensor). PMID:23661702

A test bed for investigating and evaluating the use of biometric-encoded driver licenses and their impact on law enforcement

NASA Astrophysics Data System (ADS)

Messner, Richard A.; Hludik, Frank; Crowley, Todd A.; Vidacic, Dragan; Stetson, Barrett; Nadel, Lawrence D.; Nichols, Linda J.; Harris, Carol

2004-08-01

This paper describes the results of a collaborative effort between the University of New Hampshire (UNH) and the Mitretek Systems (MTS) Center for Criminal Justice Technology (CCJT). Mitretek conducted an investigation into the impact of anticipated biometrically encoded driver licenses (DLs) on law enforcement. As part of this activity, Mitretek teamed with UNH to leverage the results of UNH's Project54 and develop a pilot Driver License Interoperability Test Bed to explore both implementation and operational aspects associated with reading and authenticating biometrically encoded DLs in law enforcement scenarios. The test bed enables the exploration of new methods, techniques (both hardware and software), and standards in a structured fashion. Spearheaded by the American Association of Motor Vehicle Administrators (AAMVA) and the International Committee for Information Technology Standards Technical Group M1 (INCITS-M1) initiatives, standards involving both DLs and biometrics, respectively, are evolving at a rapid pace. In order to ensure that the proposed standards will provide for interstate interoperability and proper functionality for the law enforcement community, it is critical to investigate the implementation and deployment issues surrounding biometrically encoded DLs. The test bed described in this paper addresses this and will provide valuable feedback to the standards organizations, the states, and law enforcement officials with respect to implementation and functional issues that are exposed through exploration of actual test systems. The knowledge gained was incorporated into a report prepared by MTS to describe the anticipated impact of biometrically encoded DLs on law enforcement practice.

Role of CLASP2 in microtubule stabilization and the regulation of persistent motility.

PubMed

Drabek, Ksenija; van Ham, Marco; Stepanova, Tatiana; Draegestein, Katharina; van Horssen, Remco; Sayas, Carmen Laura; Akhmanova, Anna; Ten Hagen, Timo; Smits, Ron; Fodde, Riccardo; Grosveld, Frank; Galjart, Niels

2006-11-21

In motile fibroblasts, stable microtubules (MTs) are oriented toward the leading edge of cells. How these polarized MT arrays are established and maintained, and the cellular processes they control, have been the subject of many investigations. Several MT "plus-end-tracking proteins," or +TIPs, have been proposed to regulate selective MT stabilization, including the CLASPs, a complex of CLIP-170, IQGAP1, activated Cdc42 or Rac1, a complex of APC, EB1, and mDia1, and the actin-MT crosslinking factor ACF7. By using mouse embryonic fibroblasts (MEFs) in a wound-healing assay, we show here that CLASP2 is required for the formation of a stable, polarized MT array but that CLIP-170 and an APC-EB1 interaction are not essential. Persistent motility is also hampered in CLASP2-deficient MEFs. We find that ACF7 regulates cortical CLASP localization in HeLa cells, indicating it acts upstream of CLASP2. Fluorescence-based approaches show that GFP-CLASP2 is immobilized in a bimodal manner in regions near cell edges. Our results suggest that the regional immobilization of CLASP2 allows MT stabilization and promotes directionally persistent motility in fibroblasts.

A defect in the CLIP1 gene (CLIP-170) can cause autosomal recessive intellectual disability.

PubMed

Larti, Farzaneh; Kahrizi, Kimia; Musante, Luciana; Hu, Hao; Papari, Elahe; Fattahi, Zohreh; Bazazzadegan, Niloofar; Liu, Zhe; Banan, Mehdi; Garshasbi, Masoud; Wienker, Thomas F; Ropers, H Hilger; Galjart, Niels; Najmabadi, Hossein

2015-03-01

In the context of a comprehensive research project, investigating novel autosomal recessive intellectual disability (ARID) genes, linkage analysis based on autozygosity mapping helped identify an intellectual disability locus on Chr.12q24, in an Iranian family (LOD score = 3.7). Next-generation sequencing (NGS) following exon enrichment in this novel interval, detected a nonsense mutation (p.Q1010*) in the CLIP1 gene. CLIP1 encodes a member of microtubule (MT) plus-end tracking proteins, which specifically associates with the ends of growing MTs. These proteins regulate MT dynamic behavior and are important for MT-mediated transport over the length of axons and dendrites. As such, CLIP1 may have a role in neuronal development. We studied lymphoblastoid and skin fibroblast cell lines established from healthy and affected patients. RT-PCR and western blot analyses showed the absence of CLIP1 transcript and protein in lymphoblastoid cells derived from affected patients. Furthermore, immunofluorescence analyses showed MT plus-end staining only in fibroblasts containing the wild-type (and not the mutant) CLIP1 protein. Collectively, our data suggest that defects in CLIP1 may lead to ARID.

A defect in the CLIP1 gene (CLIP-170) can cause autosomal recessive intellectual disability

PubMed Central

Larti, Farzaneh; Kahrizi, Kimia; Musante, Luciana; Hu, Hao; Papari, Elahe; Fattahi, Zohreh; Bazazzadegan, Niloofar; Liu, Zhe; Banan, Mehdi; Garshasbi, Masoud; Wienker, Thomas F; Ropers, H Hilger; Galjart, Niels; Najmabadi, Hossein

2015-01-01

In the context of a comprehensive research project, investigating novel autosomal recessive intellectual disability (ARID) genes, linkage analysis based on autozygosity mapping helped identify an intellectual disability locus on Chr.12q24, in an Iranian family (LOD score=3.7). Next-generation sequencing (NGS) following exon enrichment in this novel interval, detected a nonsense mutation (p.Q1010*) in the CLIP1 gene. CLIP1 encodes a member of microtubule (MT) plus-end tracking proteins, which specifically associates with the ends of growing MTs. These proteins regulate MT dynamic behavior and are important for MT-mediated transport over the length of axons and dendrites. As such, CLIP1 may have a role in neuronal development. We studied lymphoblastoid and skin fibroblast cell lines established from healthy and affected patients. RT-PCR and western blot analyses showed the absence of CLIP1 transcript and protein in lymphoblastoid cells derived from affected patients. Furthermore, immunofluorescence analyses showed MT plus-end staining only in fibroblasts containing the wild-type (and not the mutant) CLIP1 protein. Collectively, our data suggest that defects in CLIP1 may lead to ARID. PMID:24569606

Characteristics and source identification of dissolved trace elements in the Jinshui River of the South Qinling Mts., China.

PubMed

Bu, Hongmei; Wang, Weibo; Song, Xianfang; Zhang, Quanfa

2015-09-01

Dissolved trace elements and physiochemical parameters were analyzed to investigate their physicochemical characteristics and identify their sources at 12 sampling sites of the Jinshui River in the South Qinling Mts., China from October 2006 to November 2008. The two-factor ANOVA indicated significant temporal variations of the dissolved Cu, Fe, Sr, Si, and V (p < 0.001 or p < 0.05). With the exception of Sr (p < 0.001), no significant spatial variations were found. Distributions and concentrations of the dissolved trace elements displayed that dissolved Cu, Fe, Sr, Si, V, and Cr were originated from chemical weathering and leaching from the soil and bedrock. Dissolved Cu, Fe, Sr, As, and Si were also from anthropogenic inputs (farming and domestic effluents). Correlation and regression analysis showed that the chemical and physical processes of dissolved Cu was influenced by water temperature and dissolved oxygen (DO) to some degree. Dissolved Fe and Sr were affected by colloid destabilization or sedimentary inputs. Concentrations of dissolved Si were slightly controlled by biological uptake. Principal component analysis confirmed that Fe, Sr, and V resulted from domestic effluents, agricultural runoff, and confluence, whereas As, Cu, and Si were from agricultural activities, and Cr and Zn through natural processes. The research results provide a reference for ecological restoration and protection of the river environment in the Qinling Mts., China.

The susceptibility of soil enzymes to inhibition by leaf litter tannins is dependent on the tannin chemistry, enzyme class and vegetation history.

PubMed

Triebwasser, Daniella J; Tharayil, Nishanth; Preston, Caroline M; Gerard, Patrick D

2012-12-01

By inhibiting soil enzymes, tannins play an important role in soil carbon (C) and nitrogen (N) mineralization. The role of tannin chemistry in this inhibitory process, in conjunction with enzyme classes and isoforms, is less well understood. Here, we compared the inhibition efficiencies of mixed tannins (MTs, mostly limited to angiosperms) and condensed tannins (CTs, produced mostly by gymnosperms) against the potential activity of β-glucosidase (BG), N-acetyl-glucosaminidase (NAG), and peroxidase in two soils that differed in their vegetation histories. Compared with CTs, MTs exhibited 50% more inhibition of almond (Prunus dulcis) BG activity and greater inhibition of the potential NAG activity in the gymnosperm-acclimatized soils. CTs exhibited lower BG inhibition in the angiosperm-acclimated soils, whereas both types of tannins exhibited higher peroxidase inhibition in the angiosperm soils than in gymnosperm soils. At all of the tested tannin concentrations, irrespective of the tannin type and site history, the potential peroxidase activity was inhibited two-fold more than the hydrolase activity and was positively associated with the redox-buffering efficiency of tannins. Our finding that the inhibitory activities and mechanisms of MTs and CTs are dependent on the vegetative history and enzyme class is novel and furthers our understanding of the role of tannins and soil isoenzymes in decomposition. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

NUCLEAR HEATING IN LIF DOSEMETERS IN A FUSION NEUTRON FIELD, TRIAL OF DIRECT COMPARISON OF EXPERIMENTAL AND SIMULATED RESULTS.

PubMed

Pohorecki, Wladyslaw; Obryk, Barbara

2017-09-29

The results of nuclear heating measured by means of thermoluminescent dosemeters (TLD-LiF) in a Cu block irradiated by 14 MeV neutrons are presented. The integral Cu experiment relevant for verification of copper nuclear data at neutron energies characteristic for fusion facilities was performed in the ENEA FNG Laboratory at Frascati. Five types of TLDs were used: highly photon sensitive LiF:Mg,Cu,P (MCP-N), 7LiF:Mg,Cu,P (MCP-7) and standard, lower sensitivity LiF:Mg,Ti (MTS-N), 7LiF:Mg,Ti (MTS-7) and 6LiF:Mg,Ti (MTS-6). Calibration of the detectors was performed with gamma rays in terms of air-kerma (10 mGy of 137Cs air-kerma). Nuclear heating in the Cu block was also calculated with the use of MCNP transport code Nuclear heating in Cu and air in TLD's positions was calculated as well. The nuclear heating contribution from all simulated by MCNP6 code particles including protons, deuterons, alphas tritons and heavier ions produced by the neutron interactions were calculated. A trial of the direct comparison between experimental results and results of simulation was performed. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Characterization of tub4P287L, a β‐tubulin mutant, revealed new aspects of microtubule regulation in shade

PubMed Central

Yu, Jie; Qiu, Hong; Liu, Xin; Wang, Meiling; Gao, Yongli; Chory, Joanne

2015-01-01

Abstract When sun plants, such as Arabidopsis thaliana, are under canopy shade, elongation of stems/petioles will be induced as one of the most prominent responses. Plant hormones mediate the elongation growth. However, how environmental and hormonal signals are translated into cell expansion activity that leads to the elongation growth remains elusive. Through forward genetic study, we identified shade avoidance2 (sav2) mutant, which contains a P287L mutation in β‐TUBULIN 4. Cortical microtubules (cMTs) play a key role in anisotropic cell growth. Hypocotyls of sav2 are wild type‐like in white light, but are short and highly swollen in shade and dark. We showed that shade not only induces cMT rearrangement, but also affects cMT stability and dynamics of plus ends. Even though auxin and brassinosteroids are required for shade‐induced hypocotyl elongation, they had little effect on shade‐induced rearrangement of cMTs. Blocking auxin transport suppressed dark phenotypes of sav2, while overexpressing EB1b‐GFP, a microtubule plus‐end binding protein, rescued sav2 in both shade and dark, suggesting that tub4P287L represents a unique type of tubulin mutation that does not affect cMT function in supporting cell elongation, but may affect the ability of cMTs to respond properly to growth promoting stimuli. PMID:25899068

Effects of intermittent theta burst stimulation on spasticity after stroke.

PubMed

Kim, Dae Hyun; Shin, Ji Cheol; Jung, Seungsoo; Jung, Tae-Min; Kim, Deog Young

2015-07-08

Spasticity is a common cause of long-term disability in poststroke hemiplegic patients. We investigated whether intermittent theta burst stimulation (iTBS) could reduce upper-limb spasticity after a stroke. Fifteen hemiplegic stroke patients were recruited for a double-blind sham-controlled cross-over design study. A single session of iTBS or sham stimulation was delivered on the motor hotspot of the affected flexor carpi radialis muscle in a random and counterbalanced order with a 1-week interval. Modified Ashworth scale (MAS), modified Tardieu scale (MTS), H-wave/M-wave amplitude ratio, peak torque (PT), peak torque angle (PTA), work of affected wrist flexor, and rectified integrated electromyographic activity of the flexor carpi radialis muscle were measured before, immediately after, 30 min after, and 1 week after iTBS or sham stimulation. Repeated-measures analysis of variance showed a significant interaction between time and intervention for the MAS, MTS, PT, PTA, and rectified integrated electromyographic activity (P<0.05), indicating that these parameters were significantly improved by iTBS compared with sham stimulation. However, the H-wave/M-wave amplitude ratio and work were not affected. MAS and MTS significantly improved for at least 30 min after iTBS, but the other parameters only improved immediately after iTBS (P<0.05). In conclusion, iTBS on the affected hemisphere may help to reduce poststroke spasticity transiently.

Screening for Muir-Torre syndrome using mismatch repair protein immunohistochemistry of sebaceous neoplasms.

PubMed

Roberts, Maegan E; Riegert-Johnson, Douglas L; Thomas, Brittany C; Thomas, Colleen S; Heckman, Michael G; Krishna, Murli; DiCaudo, David J; Bridges, Alina G; Hunt, Katherine S; Rumilla, Kandelaria M; Cappel, Mark A

2013-06-01

Screening for the Muir-Torre variant of Lynch Syndrome (LS) using Mismatch Repair (MMR) gene immunohistochemistry (IHC) on sebaceous neoplasms (SNs) is technically feasible. To date, research into the clinical utility of MMR IHC for this indication is limited. We conducted a retrospective chart review of 90 patients with MMR IHC completed on at least one SN from January 2005 to May 2010. SNs included were adenomas, epitheliomas, carcinomas and basal and squamous cell carcinomas with sebaceous differentiation. Of the 90 patients, 13 (14 %) had genetically confirmed or fulfilled clinical criteria for a diagnosis of MTS and 51 patients (57 %) presented with an abnormal MMR IHC result (loss of one or more MMR proteins) on at least one SN. Abnormal IHC had a sensitivity of 85 %, specificity of 48 %, positive predictive value (PPV) of 22 % and negative predictive value (NPV) of 95 % when evaluating for MTS. When personal or family history of colorectal cancer (≥2 family members with a history of colorectal cancer) was taken into consideration, ignoring IHC results, sensitivity was 92 %, specificity was 99 %, PPV was 92 % and NPV was 99 %. MMR IHC on SNs when used to screen for MTS has poor diagnostic utility. We recommend that MMR IHC not be performed routinely on SNs when the patient does not have either personal or family history of colorectal cancer.

Mitotic Kinesin CENP-E Promotes Microtubule Plus-End Elongation

PubMed Central

Sardar, Harjinder S.; Luczak, Vincent G.; Lopez, Maria M.; Lister, Bradford C.; Gilbert, Susan P.

2010-01-01

Summary Centromere protein CENP-E is a dimeric kinesin (Kinesin-7 family) with critical roles in mitosis including establishment of microtubule (MT)-chromosome linkage and movement of monooriented chromosomes on kinetochore microtubules (kMTs) for proper alignment at metaphase [1-9]. We performed studies to test the hypothesis that CENP-E promotes MT elongation at the MT plus-ends. A human CENP-E construct was engineered, expressed, and purified which yielded the CENP-E-6His dimeric motor protein. The results show that CENP-E promotes MT plus-end directed MT gliding at 11 nm/s. The results from real-time microscopy assays indicate that 60.3% of polarity marked MTs exhibited CENP-E promoted MT plus-end elongation. The MT extension required ATP turnover, and MT plus-end elongation occurred at 1.48 μm/30 min. Immunolocalization studies revealed that 80.8% of plus-end elongated MTs showed CENP-E at the MT plus-end. The time dependence of CENP-E promoted MT elongation in solution best fit a single exponential function (kobs = 5.1 s−1), which is indicative of a mechanism in which α,β-tubulin subunit addition is tightly coupled to ATP turnover. Based on these results, we propose that CENP-E as part of its function in chromosome kinetochore-MT linkage plays a direct role in MT elongation. PMID:20797864

Caution is required in interpretation of mutations in the voltage sensing domain of voltage gated channels as evidence for gating mechanisms.

PubMed

Kariev, Alisher M; Green, Michael E

2015-01-12

The gating mechanism of voltage sensitive ion channels is generally considered to be the motion of the S4 transmembrane segment of the voltage sensing domains (VSD). The primary supporting evidence came from R → C mutations on the S4 transmembrane segment of the VSD, followed by reaction with a methanethiosulfonate (MTS) reagent. The cys side chain is -SH (reactive form -S-); the arginine side chain is much larger, leaving space big enough to accommodate the MTS sulfonate head group. The cavity created by the mutation has space for up to seven more water molecules than were present in wild type, which could be displaced irreversibly by the MTS reagent. Our quantum calculations show there is major reorientation of three aromatic residues that face into the cavity in response to proton displacement within the VSD. Two phenylalanines reorient sufficiently to shield/unshield the cysteine from the intracellular and extracellular ends, depending on the proton positions, and a tyrosine forms a hydrogen bond to the cysteine sulfur with its side chain -OH. These could produce the results of the experiments that have been interpreted as evidence for physical motion of the S4 segment, without physical motion of the S4 backbone. The computations strongly suggest that the interpretation of cysteine substitution reaction experiments be re-examined in the light of these considerations.

Early gene Broad complex plays a key role in regulating the immune response triggered by ecdysone in the Malpighian tubules of Drosophila melanogaster.

PubMed

Verma, Puja; Tapadia, Madhu G

2015-08-01

In insects, humoral response to injury is accomplished by the production of antimicrobial peptides (AMPs) which are secreted in the hemolymph to eliminate the pathogen. Drosophila Malpighian tubules (MTs), however, are unique immune organs that show constitutive expression of AMPs even in unchallenged conditions and the onset of immune response is developmental stage dependent. Earlier reports have shown ecdysone positively regulates immune response after pathogenic challenge however, a robust response requires prior potentiation by the hormone. Here we provide evidence to show that MTs do not require prior potentiation with ecdysone hormone for expression of AMPs and they respond to ecdysone very fast even without immune challenge, although the different AMPs Diptericin, Cecropin, Attacin, Drosocin show differential expression in response to ecdysone. We show that early gene Broad complex (BR-C) could be regulating the IMD pathway by activating Relish and physically interacting with it to activate AMPs expression. BR-C depletion from Malpighian tubules renders the flies susceptible to infection. We also show that in MTs ecdysone signaling is transduced by EcR-B1 and B2. In the absence of ecdysone signaling the IMD pathway associated genes are down regulated and activation and translocation of transcription factor Relish is also affected. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of the herbicide isoproturon on metallothioneins, growth, and antioxidative defenses in the aquatic worm Tubifex tubifex (Oligochaeta, Tubificidae).

PubMed

Mosleh, Yahia Y; Paris-Palacios, Séverine; Couderchet, Michel; Biagianti-Risbourg, Sylvie; Vernet, Guy

2005-07-01

Metallothioneins (MTs) are low molecular weight proteins, mainly implicated in metal ion detoxification. Increase in MT contents is considered to be a specific biomarker of metal exposure. Recently it has been demonstrated that MTs participate in several cellular functions such as regulation of growth, and antioxidative defenses. Therefore, the induction of MTs as biomarkers of exposure to the pesticide isoproturon has been investigated in the aquatic worms Tubifex tubifex. MT levels in exposed worms increased significantly (p < 0.05) after 2, 4, and 7 days of exposure to different concentrations of isoproturon (maximum increase compared to unexposed controls: +148.56% for 10 mg l(-1) after 4 days of exposure). In response to isoproturon, the activity of glutathione-S-transferase (max. +52%), glutathione-reductase (max. +100%), and catalase (max. +117%) increased, demonstrating the occurrence of an oxidative stress response to the herbicide. Thus, the increase in MT contents caused by isoproturon was interpreted as a defense response towards increased oxidative stress generated by the herbicide. Residues of isoproturon and its metabolites, 1-(4-isopropylphenyl)-3-methylurea, 1-(4-isopropylphenyl) urea, and 4-isopropylanilin were detected in the worm growth medium. Half-life of the herbicide was shorter at a low (0.1 mg l(-1)) initial concentration. The herbicide accumulated in T. tubifex but no metabolite could be detected.

Determination of dietary cadmium-induced metallothioneins in rabbit kidneys and cadmium in metallothioneins by anion-exchange high-performance liquid chromatography coupled with graphite furnace atomic absorption spectrometry.

PubMed

Peng, S; Shan, X Q; Zheng, Y; Jin, L Z; Xu, W B

1991-12-06

A rapid method is described for the determination of dietary cadmium-induced metallothioneins (MTs) in rabbit kidneys by anion-exchange high-performance liquid chromatography. Rabbit kidney MT-I and MT-II were eluted at ca. 15.0 and 18.8 min, respectively, from a DEAE-5PW anion-exchange column with a Tris-HCl buffer (0.01-0.25 M, pH 8.6) and detected by ultraviolet absorbance at 254 nm. A standard calibration curve was constructed using purified standard MT isoforms, which demonstrated an excellent linear correlation between UV absorbance peak heights and the amounts of MT isoforms. Feeding a dose of cadmium for some days resulted in an increase in MT concentrations in rabbit kidneys, but not in the livers. The cadmium concentrations in MT-I and MT-II elutions were determined by graphite furnace atomic absorption spectrometry. MT-I and MT-II showed some differences associated with the oral intake of cadmium. Dietary cadmium also caused zinc to accumulate in kidneys to some extent. The effects of dietary oleic acid on the synthesis of MTs were also studied. Based on the method of standard additions, the recovery of MTs exceeded 93% and replicated injection of samples yielded a relative standard deviation of 2.4% at an MT level of 280 micrograms/g.

Reconstitution of Contractile FtsZ Rings in Liposomes

PubMed Central

Osawa, Masaki; Anderson, David E.; Erickson, Harold P.

2009-01-01

FtsZ is a tubulin homolog and the major cytoskeletal protein in bacterial cell division. It assembles into the Z ring, which contains FtsZ and a dozen other division proteins, and constricts to divide the cell. We have constructed a membrane-targeted FtsZ (FtsZ-mts) by splicing an amphipathic helix to its C terminus. When mixed with lipid vesicles, FtsZ-mts was incorporated into the interior of some tubular vesicles. There it formed multiple Z rings that could move laterally in both directions along the length of the liposome and coalesce into brighter Z rings. Brighter Z rings produced visible constrictions in the liposome, suggesting that FtsZ itself can assemble the Z ring and generate a force. No other proteins were needed for assembly and force generation. PMID:18420899

Comparative analysis of Homo sapiens and Mus musculus cyclin-dependent kinase (CDK) inhibitor genes p16 (MTS1) and p15 (MTS2).

PubMed

Jiang, P; Stone, S; Wagner, R; Wang, S; Dayananth, P; Kozak, C A; Wold, B; Kamb, A

1995-12-01

Cyclin-dependent kinase inhibitors are a growing family of molecules that regulate important transitions in the cell cycle. At least one of these molecules, p16, has been implicated in human tumorigenesis while its close homolog, p15, is induced by cell contact and transforming growth factor-beta (TGF-beta). To investigate the evolutionary and functional features of p15 and p16, we have isolated mouse (Mus musculus) homologs of each gene. Comparative analysis of these sequences provides evidence that the genes have similar functions in mouse and human. In addition, the comparison suggests that a gene conversion event is part of the evolution of the human p15 and p16 genes.

End-binding protein 1 controls signal propagation from the T cell receptor

PubMed Central

Martín-Cófreces, Noa B; Baixauli, Francesc; López, María J; Gil, Diana; Monjas, Alicia; Alarcón, Balbino; Sánchez-Madrid, Francisco

2012-01-01

The role of microtubules (MTs) in the control and dynamics of the immune synapse (IS) remains unresolved. Here, we show that T cell activation requires the growth of MTs mediated by the plus-end specific protein end-binding 1 (EB1). A direct interaction of the T cell receptor (TCR) complex with EB1 provides the molecular basis for EB1 activity promoting TCR encounter with signalling vesicles at the IS. EB1 knockdown alters TCR dynamics at the IS and prevents propagation of the TCR activation signal to LAT, thus inhibiting activation of PLCγ1 and its localization to the IS. These results identify a role for EB1 interaction with the TCR in controlling TCR sorting and its connection with the LAT/PLCγ1 signalosome. PMID:22922463

MetaTracker: integration and abstraction of 3D motion tracking data from multiple hardware systems

NASA Astrophysics Data System (ADS)

Kopecky, Ken; Winer, Eliot

2014-06-01

Motion tracking has long been one of the primary challenges in mixed reality (MR), augmented reality (AR), and virtual reality (VR). Military and defense training can provide particularly difficult challenges for motion tracking, such as in the case of Military Operations in Urban Terrain (MOUT) and other dismounted, close quarters simulations. These simulations can take place across multiple rooms, with many fast-moving objects that need to be tracked with a high degree of accuracy and low latency. Many tracking technologies exist, such as optical, inertial, ultrasonic, and magnetic. Some tracking systems even combine these technologies to complement each other. However, there are no systems that provide a high-resolution, flexible, wide-area solution that is resistant to occlusion. While frameworks exist that simplify the use of tracking systems and other input devices, none allow data from multiple tracking systems to be combined, as if from a single system. In this paper, we introduce a method for compensating for the weaknesses of individual tracking systems by combining data from multiple sources and presenting it as a single tracking system. Individual tracked objects are identified by name, and their data is provided to simulation applications through a server program. This allows tracked objects to transition seamlessly from the area of one tracking system to another. Furthermore, it abstracts away the individual drivers, APIs, and data formats for each system, providing a simplified API that can be used to receive data from any of the available tracking systems. Finally, when single-piece tracking systems are used, those systems can themselves be tracked, allowing for real-time adjustment of the trackable area. This allows simulation operators to leverage limited resources in more effective ways, improving the quality of training.

NASA Design Strengthens Welds

NASA Technical Reports Server (NTRS)

2008-01-01

Friction Stir Welding (FSW) is a solid-state joining process-a combination of extruding and forging-ideal for use when the original metal characteristics must remain as unchanged as possible. While exploring methods to improve the use of FSW in manufacturing, engineers at Marshall Space Flight Center created technologies to address the method's shortcomings. MTS Systems Corporation, of Eden Prairie, Minnesota, discovered the NASA-developed technology and then signed a co-exclusive license agreement to commercialize Marshall's design for use in high-strength structural alloys. The resulting process offers the added bonuses of being cost-competitive, efficient, and most importantly, versatile.

Frequency-Unspecific Effects of θ-tACS Related to a Visuospatial Working Memory Task

PubMed Central

Kleinert, Maria-Lisa; Szymanski, Caroline; Müller, Viktor

2017-01-01

Working memory (WM) is crucial for intelligent cognitive functioning, and synchronization phenomena in the fronto-parietal network have been suggested as an underlying neural mechanism. In an attempt to provide causal evidence for this assumption, we applied transcranial alternating current stimulation (tACS) at theta frequency over fronto-parietal sites during a visuospatial match-to-sample (MtS) task. Depending on the stimulation protocol, i.e., in-phase, anti-phase or sham, we anticipated a differential impact of tACS on behavioral WM performance as well as on the EEG (electroencephalography) during resting state before and after stimulation. We hypothesized that in-phase tACS of the fronto-parietal theta network (stimulation frequency: 5 Hz; intensity: 1 mA peak-to-peak) would result in performance enhancement, whereas anti-phase tACS would cause performance impairment. Eighteen participants (nine female) received in-phase, anti-phase, and sham stimulation in balanced order. While being stimulated, subjects performed the MtS task, which varied in executive demand (two levels: low and high). EEG analysis of power peaks within the delta (0.5–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), and beta (12–30 Hz) frequency bands was carried out. No significant differences were observed between in-phase and anti-phase stimulation regarding both behavioral and EEG measurements. Yet, with regard to the alpha frequency band, we observed a statistically significant drop of peak power from pre to post in the sham condition, whereas alpha power remained on a similar level in the actively stimulated conditions. Our results indicate a frequency-unspecific modulation of neuronal oscillations by tACS. However, the closer participants’ individual theta peak frequencies were to the stimulation frequency of 5 Hz after anti-phase tACS, the faster they responded in the MtS task. This effect did not reach statistical significance during in-phase tACS and was not present during sham. A lack of statistically significant behavioral results in the MtS task and frequency-unspecific effects on the electrophysiological level question the effectiveness of tACS in modulating cortical oscillations in a frequency-specific manner. PMID:28747881

On the suitability of ultrathin detectors for absorbed dose assessment in the presence of high-density heterogeneities.

PubMed

Bueno, M; Carrasco, P; Jornet, N; Muñoz-Montplet, C; Duch, M A

2014-08-01

The aim of this study was to evaluate the suitability of several detectors for the determination of absorbed dose in bone. Three types of ultrathin LiF-based thermoluminescent dosimeters (TLDs)-two LiF:Mg,Cu,P-based (MCP-Ns and TLD-2000F) and a (7)Li-enriched LiF:Mg,Ti-based (MTS-7s)-as well as EBT2 Gafchromic films were used to measure percentage depth-dose distributions (PDDs) in a water-equivalent phantom with a bone-equivalent heterogeneity for 6 and 18 MV and a set of field sizes ranging from 5 x 5 cm2 to 20 x 20 cm2. MCP-Ns, TLD-2000F, MTS-7s, and EBT2 have active layers of 50, 20, 50, and 30 μm, respectively. Monte Carlo (MC) dose calculations (PENELOPE code) were used as the reference and helped to understand the experimental results and to evaluate the potential perturbation of the fluence in bone caused by the presence of the detectors. The energy dependence and linearity of the TLDs' response was evaluated. TLDs exhibited flat energy responses (within 2.5%) and linearity with dose (within 1.1%) within the range of interest for the selected beams. The results revealed that all considered detectors perturb the electron fluence with respect to the energy inside the bone-equivalent material. MCP-Ns and MTS-7s underestimated the absorbed dose in bone by 4%-5%. EBT2 exhibited comparable accuracy to MTS-7s and MCP-Ns. TLD-2000F was able to determine the dose within 2% accuracy. No dependence on the beam energy or field size was observed. The MC calculations showed that a[Formula: see text] thick detector can provide reliable dose estimations in bone regardless of whether it is made of LiF, water or EBT's active layer material. TLD-2000F was found to be suitable for providing reliable absorbed dose measurements in the presence of bone for high-energy x-ray beams.

Aberration of mitosis by hexavalent chromium in some Fabaceae members is mediated by species-specific microtubule disruption.

PubMed

Eleftheriou, Eleftherios P; Michalopoulou, Vasiliki A; Adamakis, Ioannis-Dimosthenis S

2015-05-01

Because the detrimental effects of chromium (Cr) to higher plants have been poorly investigated, the present study was undertaken to verify the toxic attributes of hexavalent chromium [Cr(VI)] to plant mitotic microtubules (MTs), to determine any differential disruption of MTs during mitosis of taxonomically related species and to clarify the relationship between the visualized chromosomal aberrations and the Cr(VI)-induced MT disturbance. For this purpose, 5-day-old uniform seedlings of Vicia faba, Pisum sativum, Vigna sinensis and Vigna angularis, all belonging to the Fabaceae family, were exposed to 250 μM Cr(VI) supplied as potassium dichromate (K₂Cr₂O₇) for 24, 72 and 120 h and others in distilled water serving as controls. Root tip samples were processed for tubulin immunolabelling (for MT visualization) and DNA fluorescent staining (for chromosomal visualization). Microscopic preparations of cell squashes were then examined and photographed by confocal laser scanning microscopy (CLSM). Cr(VI) halted seedling growth turning roots brown and necrotic. Severe chromosomal abnormalities and differential disturbance of the corresponding MT arrays were found in all mitotic phases. In particular, in V. faba MTs were primarily depolymerized and replaced by atypical tubulin conformations, whereas in P. sativum, V. sinensis and V. angularis they became bundled in a time-dependent manner. In P. sativum, the effects were milder compared to those of the other species, but in all cases MT disturbance adversely affected the proper aggregation of chromosomes on the metaphase plate, their segregation at anaphase and organization of the new nuclei at telophase. Cr(VI) is very toxic to seedling growth. The particular effect depends on the exact stage the cell is found at the time of Cr(VI) entrance and is species-specific. Mitotic MT arrays are differentially deranged by Cr(VI) in the different species examined, even if they are taxonomically related, while their disturbance underlies chromosomal abnormalities. Results furthermore support the view that MTs may constitute a reliable, sensitive and universal subcellular marker for monitoring heavy metal toxicity.

Radiogenomic analysis of hypoxia pathway reveals computerized MRI descriptors predictive of overall survival in glioblastoma

NASA Astrophysics Data System (ADS)

Beig, Niha; Patel, Jay; Prasanna, Prateek; Partovi, Sasan; Varadan, Vinay; Madabhushi, Anant; Tiwari, Pallavi

2017-03-01

Glioblastoma Multiforme (GBM) is a highly aggressive brain tumor with a median survival of 14 months. Hypoxia is a hallmark trait in GBM that is known to be associated with angiogenesis, tumor growth, and resistance to conventional therapy, thereby limiting treatment options for GBM patients. There is thus an urgent clinical need for non-invasively capturing tumor hypoxia in GBM towards identifying a subset of patients who would likely benefit from anti-angiogenic therapies (bevacizumab) in the adjuvant setting. In this study, we employed radiomic descriptors to (a) capture molecular variations of tumor hypoxia on routine MRI that are otherwise not appreciable; and (b) employ the radiomic correlates of hypoxia to discriminate patients with short-term survival (STS, overall survival (OS) < 7 months), mid-term survival (MTS) (7 months16 months). A total of 97 studies (25 STS, 36 MTS, 36 LTS) with Gadolinium T1-contrast (Gd-T1c), T2w, and FLAIR protocols with their corresponding gene expression profiles were obtained from the cancer genome atlas (TCGA) database. For each MRI study, necrotic, enhancing tumor, and edematous regions were segmented by an expert. A total of 30 radiomic descriptors (i.e. Haralick, Laws energy, Gabor) were extracted from every region across all three MRI protocols. By performing unsupervised clustering of the expression profile of hypoxia associated genes, a "low", "medium", or "high" index was defined for every study. Spearman correlation was then used to identify the most significantly correlated MRI features with the hypoxia index for every study. These features were further used to categorize each study as STS, MTS, and LTS using Kaplan-Meier (KM) analysis. Our results revealed that the most significant features (p < 0.05) were identified as Laws energy and Haralick features that capture image heterogeneity on FLAIR and Gd-T1w sequences. We also found these radiomic features to be significantly associated with survival, distinguishing MTS from LTS (p=.005) and STS from LTS (p=.0008).

Delineation and Diagnostic Criteria of Oral-Facial-Digital Syndrome Type VI

PubMed Central

2012-01-01

Oral-Facial-Digital Syndrome type VI (OFD VI) represents a rare phenotypic subtype of Joubert syndrome and related disorders (JSRD). In the original report polydactyly, oral findings, intellectual disability, and absence of the cerebellar vermis at post-mortem characterized the syndrome. Subsequently, the molar tooth sign (MTS) has been found in patients with OFD VI, prompting the inclusion of OFD VI in JSRD. We studied the clinical, neurodevelopmental, neuroimaging, and genetic findings in a cohort of 16 patients with OFD VI. We derived the following inclusion criteria from the literature: 1) MTS and one oral finding and polydactyly, or 2) MTS and more than one typical oral finding. The OFD VI neuroimaging pattern was found to be more severe than in other JSRD subgroups and includes severe hypoplasia of the cerebellar vermis, hypoplastic and dysplastic cerebellar hemispheres, marked enlargement of the posterior fossa, increased retrocerebellar collection of cerebrospinal fluid, abnormal brainstem, and frequently supratentorial abnormalities that occasionally include characteristic hypothalamic hamartomas. Additionally, two new JSRD neuroimaging findings (ascending superior cerebellar peduncles and fused thalami) have been identified. Tongue hamartomas, additional frenula, upper lip notch, and mesoaxial polydactyly are specific findings in OFD VI, while cleft lip/palate and other types of polydactyly of hands and feet are not specific. Involvement of other organs may include ocular findings, particularly colobomas. The majority of the patients have absent motor development and profound cognitive impairment. In OFD VI, normal cognitive functions are possible, but exceptional. Sequencing of known JSRD genes in most patients failed to detect pathogenetic mutations, therefore the genetic basis of OFD VI remains unknown. Compared with other JSRD subgroups, the neurological findings and impairment of motor development and cognitive functions in OFD VI are significantly worse, suggesting a correlation with the more severe neuroimaging findings. Based on the literature and this study we suggest as diagnostic criteria for OFD VI: MTS and one or more of the following: 1) tongue hamartoma(s) and/or additional frenula and/or upper lip notch; 2) mesoaxial polydactyly of one or more hands or feet; 3) hypothalamic hamartoma. PMID:22236771

Plants' healthiness assessment as part of the environmental monitoring of protected mountainous area in the example of Karkonosze (Giant) Mts. (SW Poland).

PubMed

Pusz, Wojciech

2015-10-01

The aim of phytopathological monitoring is to check the healthiness of plants and observe the changes that occur in their populations. In the vast majority, these types of observations are conducted in agriculture and forestry. An interesting aspect of phytopathological monitoring is the assessment of the origin of the plant species. The research of fungal communities (including pathogens) in plants may, for example, indicate the relic nature of the plant species. Reduction of the occurrence or disappearance of fungi species associated with its host plant can evidence slow decline of their habitats. This applies mainly to arctic-alpine fungal species. On the other hand, for some plant hosts, colonization of their organs by polyphagous fungi is being recorded. One such example is the downy willow, on which six species of fungi were found in the Karkonosze Mts. In 2014, there were no fungi found on this plant. However, comparing the species composition of fungi associated with downy willow given by Schroeter (1908) to the contemporary one and to the study results of other researchers, a decrease in the number of fungi species is clearly visible. This may be related to the environmental pollution, which took place in the Sudetes in the second half of the twentieth century. For instance, the species of the genus Rhytisma colonize the leaves of trees and shrubs and are particularly sensitive to the concentration of SO2 in the air, but nobody has looked for this fungus on this host in the past. Yet, presently, we were able to find Rhytisma fungus in Karkonosze Mts. Phytopathological monitoring was conducted in the years of 2014-2015 in the sub-alpine zone of the Karkonosze (Giant) Mts. It has been shown that, compared to similar studies conducted in the 1990s of the twentieth century, the species composition of fungi infesting Rubus chamaemorus and Betula carpactica has changed. Is this the beginning of changes that will occur in populations of plants?

40 CFR 97.52 - NOX Allowance Tracking System responsibilities of NOX authorized account representative.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 21 2011-07-01 2011-07-01 false NOX Allowance Tracking System... NOX AND SO2 TRADING PROGRAMS NOX Allowance Tracking System § 97.52 NOX Allowance Tracking System... Tracking System account, all submissions to the Administrator pertaining to the account, including, but not...

40 CFR 97.52 - NOX Allowance Tracking System responsibilities of NOX authorized account representative.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false NOX Allowance Tracking System... NOX AND SO2 TRADING PROGRAMS NOX Allowance Tracking System § 97.52 NOX Allowance Tracking System... Tracking System account, all submissions to the Administrator pertaining to the account, including, but not...

Current Development at the Southern California Earthquake Data Center (SCEDC)

NASA Astrophysics Data System (ADS)

Appel, V. L.; Clayton, R. W.

2005-12-01

Over the past year, the SCEDC completed or is near completion of three featured projects: Station Information System (SIS) Development: The SIS will provide users with an interface into complete and accurate station metadata for all current and historic data at the SCEDC. The goal of this project is to develop a system that can interact with a single database source to enter, update and retrieve station metadata easily and efficiently. The system will provide accurate station/channel information for active stations to the SCSN real-time processing system, as will as station/channel information for stations that have parametric data at the SCEDC i.e., for users retrieving data via STP. Additionally, the SIS will supply information required to generate dataless SEED and COSMOS V0 volumes and allow stations to be added to the system with a minimum, but incomplete set of information using predefined defaults that can be easily updated as more information becomes available. Finally, the system will facilitate statewide metadata exchange for both real-time processing and provide a common approach to CISN historic station metadata. Moment Tensor Solutions: The SCEDC is currently archiving and delivering Moment Magnitudes and Moment Tensor Solutions (MTS) produced by the SCSN in real-time and post-processing solutions for events spanning back to 1999. The automatic MTS runs on all local events with magnitudes > 3.0, and all regional events > 3.5. The distributed solution automatically creates links from all USGS Simpson Maps to a text e-mail summary solution, creates a .gif image of the solution, and updates the moment tensor database tables at the SCEDC. Searchable Scanned Waveforms Site: The Caltech Seismological Lab has made available 12,223 scanned images of pre-digital analog recordings of major earthquakes recorded in Southern California between 1962 and 1992 at http://www.data.scec.org/research/scans/. The SCEDC has developed a searchable web interface that allows users to search the available files, select multiple files for download and then retrieve a zipped file containing the results. Scanned images of paper records for M>3.5 southern California earthquakes and several significant teleseisms are available for download via the SCEDC through this search tool.

Portable Catapult Launcher For Small Aircraft

NASA Technical Reports Server (NTRS)

Rosenbaum, Bernard J. (Inventor); Petter, George E. (Inventor); Gessler, Joseph A. (Inventor); Hughes, Michael G. (Inventor)

2005-01-01

An apparatus for launching an aircraft having a multiplicity of interconnected elongated tracks of rigid material forming a track system and wherein each elongated track has a predetermined elongated track cross-sectional design, a winch system connected to the track system wherein the winch system has a variable mechanical advantage, one or more elongated elastic members wherein one end of each of the one or more elongated elastic members is adjustably connected to the track system, and a carrier slidably mounted to the track system wherein the canier is connected to the winch system and to the other end of each of the one or more elongated elastic members.

Portable catapult launcher for small aircraft

NASA Technical Reports Server (NTRS)

Rosenbaum, Bernard J. (Inventor); Petter, George E. (Inventor); Gessler, Joseph A. (Inventor); Hughes, Michael G. (Inventor)

2005-01-01

An apparatus for launching an aircraft having a multiplicity of interconnected elongated tracks of rigid material forming a track system and wherein each elongated track has a predetermined elongated track cross-sectional design, a winch system connected to the track system wherein the winch system has a variable mechanical advantage, one or more elongated elastic members wherein one end of each of the one or more elongated elastic members is adjustably connected to the track system, and a carrier slidably mounted to the track system wherein the carrier is connected to the winch system and to the other end of each of the one or more elongated elastic members.

Track analysis of laser-illuminated etched track detectors using an opto-digital imaging system

NASA Astrophysics Data System (ADS)

Eghan, Moses J.; Buah-Bassuah, Paul K.; Oppon, Osborne C.

2007-11-01

An opto-digital imaging system for counting and analysing tracks on a LR-115 detector is described. One batch of LR-115 track detectors was irradiated with Am-241 for a determined period and distance for linearity test and another batch was exposed to radon gas. The laser-illuminated etched track detector area was imaged, digitized and analysed by the system. The tracks that were counted on the opto-digital system with the aid of media cybernetics software as well as spark gap counter showed comparable track density results ranging between 1500 and 2750 tracks cm-2 and 65 tracks cm-2 in the two different batch detector samples with 0.5% and 1% track counts, respectively. Track sizes of the incident alpha particles from the radon gas on the LR-115 detector demonstrating different track energies are statistically and graphically represented. The opto-digital imaging system counts and measures other track parameters at an average process time of 3-5 s.

An instrumented pendulum system for measuring energy absorption during fracture insult to large animal joints in vivo.

PubMed

Diestelmeier, B W; Rudert, M J; Tochigi, Y; Baer, T E; Fredericks, D C; Brown, T D

2014-06-01

For systematic laboratory studies of bone fractures in general and intra-articular fractures in particular, it is often necessary to control for injury severity. Quantitatively, a parameter of primary interest in that regard is the energy absorbed during the injury event. For this purpose, a novel technique has been developed to measure energy absorption in experimental impaction. The specific application is for fracture insult to porcine hock (tibiotalar) joints in vivo, for which illustrative intra-operative data are reported. The instrumentation allowed for the measurement of the delivered kinetic energy and of the energy passed through the specimen during impaction. The energy absorbed by the specimen was calculated as the difference between those two values. A foam specimen validation study was first performed to compare the energy absorption measurements from the pendulum instrumentation versus the work of indentation performed by an MTS machine. Following validation, the pendulum apparatus was used to measure the energy absorbed during intra-articular fractures created in 14 minipig hock joints in vivo. The foam validation study showed close correspondence between the pendulum-measured energy absorption and MTS-performed work of indentation. In the survival animal series, the energy delivered ranged from 31.5 to 48.3 Js (41.3±4.0, mean±s.d.) and the proportion of energy absorbed to energy delivered ranged from 44.2% to 64.7% (53.6%±4.5%). The foam validation results support the reliability of the energy absorption measure provided by the instrumented pendulum system. Given that a very substantial proportion of delivered energy passed--unabsorbed--through the specimens, the energy absorption measure provided by this novel technique arguably provides better characterization of injury severity than is provided simply by energy delivery.

Acupuncture inhibits the decrease in brain catecholamine contents and the impairment of passive avoidance task in ovariectomized mice.

PubMed

Toriizuka, K; Okumura, M; Iijima, K; Haruyama, K; Cyong, J C

1999-01-01

The effects of acupuncture on the disorders elicited by abnormalities of endocrine system were investigated in ovariectomized mice. Female mice (strain; C57BL/6) were ovariectomized (OVX) and acupuncture points, Shenshu ([Japanese pictograph see text] : BL23) on both side of the back were continuously stimulated by subcutaneous needles for 20 days. After completion of experimental sessions, animals were sacrificed and specific brain regions were assayed for catecholamine contents by high performance liquid chromatography with electro chemical detector (ECD-HPLC). The mitogenic activities of splenic lymphocytes were measured by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTS) assay and alkaline phosphatase (ALP) assay. Furthermore, the effects of needle stimulation on learning and memory ability were studied by the step-through type passive avoidance test. Norepinephrine and dopamine contents in the frontoparietal cerebral cortex, ventral hippocampus and olfactory bulb were decreased in the OVX group, and both MTS activity and ALP activity were decreased 20 days after ovariectomy. The mean latent period was also shortened in the passive avoidance test in the OVX group. However, applying needle stimulation increased norepinephrine and dopamine contents in the brain regions, and enhanced mitogenic activities of splenic lymphocytes. The stimulation also improved memory-related behavior. It was concluded from this study that after mice were stimulated by subcutaneous needle insertion, overall changes were observed in central nervous system (including retention of memory) and immune functions. The study suggests that acupuncture improves the memory loss and decrease of immune responses accompanying aging and/or menopause, and the that it may have an important role in medical care for the elderly.

Strain of implants depending on occlusion types in mandibular implant-supported fixed prostheses

PubMed Central

Sohn, Byoung-Sup; Heo, Seong-Joo; Koak, Jai-Young; Kim, Seong-Kyun

2011-01-01

PURPOSE This study investigated the strain of implants using a chewing simulator with strain gauges in mandibular implant-supported fixed prostheses under various dynamic loads. MATERIALS AND METHODS Three implant-supported 5-unit fixed prostheses were fabricated with three different occlusion types (Group I: Canine protected occlusion, Group II: Unilaterally balanced occlusion, Group III: Bilaterally balanced occlusion). Two strain gauges were attached to each implant abutment. The programmed dynamic loads (0 - 300 N) were applied using a chewing simulator (MTS 858 Mini Bionix II systems, MTS systems corp., Minn, USA) and the strains were monitored. The statistical analyses were performed using the paired t-test and the ANOVA. RESULTS The mean strain values (MSV) for the working sides were 151.83 µε, 176.23 µε, and 131.07 µε for Group I, Group II, and Group III, respectively. There was a significant difference between Group II and Group III (P < .05). Also, the MSV for non-working side were 58.29 µε, 72.64 µε, and 98.93 µε for Group I, Group II, and Group III, respectively. One was significantly different from the others with a 95% confidence interval (P < .05). CONCLUSION The MSV for the working side of Groups I and II were significantly different from that for the non-working side (Group I: t = 7.58, Group II: t = 6.25). The MSV for the working side of Group II showed significantly larger than that of Group III (P < .01). Lastly, the MSV for the non-working side of Group III showed significantly larger than those of Group I or Group II (P < .01). PMID:21503186

Resource Sharing via Planed Relay for [InlineEquation not available: see fulltext.

NASA Astrophysics Data System (ADS)

Shen, Chong; Rea, Susan; Pesch, Dirk

2008-12-01

We present an improved version of adaptive distributed cross-layer routing algorithm (ADCR) for hybrid wireless network with dedicated relay stations ([InlineEquation not available: see fulltext.]) in this paper. A mobile terminal (MT) may borrow radio resources that are available thousands mile away via secure multihop RNs, where RNs are placed at pre-engineered locations in the network. In rural places such as mountain areas, an MT may also communicate with the core network, when intermediate MTs act as relay node with mobility. To address cross-layer network layers routing issues, the cascaded ADCR establishes routing paths across MTs, RNs, and cellular base stations (BSs) and provides appropriate quality of service (QoS). We verify the routing performance benefits of [InlineEquation not available: see fulltext.] over other networks by intensive simulation.

High- and Mid-temperature Superconducting Sensors for Far IR/Sub-mm Applications in Space

NASA Technical Reports Server (NTRS)

Lakew, Brook; Brasunas, J. C.

2004-01-01

In this review paper an overview of the potential applications of high Tc (approx. 90 K) superconductors (HTS) and mid-Tc (approx. 39 K) superconductors (MTS) thin films in far IR/Sub-mm thermal detectors is presented. HTSs (YBCO, GdBCO etc.) were discovered in the late 80s while superconductivity in MgB2, an MTS, was discovered in 2001. The sharp transition in transport properties of HTS has allowed the fabrication of composite infrared thermal detectors (bolometers) with better figures of merit than thermopile detectors - thermopiles are currently on board the CIRS instrument on the Cassini mission to Saturn. The potential for developing even more sensitive sensors for IR/Sub-mm applications using MgB2 thin films is assessed. Current MgB2 thin film deposition techniques and film quality are reviewed.

The functions of the cytoskeleton and associated proteins during mitosis and cytokinesis in plant cells

PubMed Central

Li, Shanwei; Sun, Tiantian; Ren, Haiyun

2015-01-01

In higher plants, microtubule (MT)-based, and actin filament (AF)-based structures play important roles in mitosis and cytokinesis. Besides the mitotic spindle, the evolution of a band comprising cortical MTs and AFs, namely, the preprophase band (PPB), is evident in plant cells. This band forecasts a specific division plane before the initiation of mitosis. During cytokinesis, another plant-specific cytoskeletal structure called the phragmoplast guides vesicles in the creation of a new cell wall. In addition, a number of cytoskeleton-associated proteins are reportedly involved in the formation and function of the PPB, mitotic spindle, and phragmoplast. This review summarizes current knowledge on the cytoskeleton-associated proteins that mediate the cytoskeletal arrays during mitosis and cytokinesis in plant cells and discusses the interaction between MTs and AFs involved in mitosis and cytokinesis. PMID:25964792

Polyaromatic hydrocarbon (PAH) degradation potential of a new acid tolerant, diazotrophic P-solubilizing and heavy metal resistant bacterium Cupriavidus sp. MTS-7 isolated from long-term mixed contaminated soil.

PubMed

Kuppusamy, Saranya; Thavamani, Palanisami; Megharaj, Mallavarapu; Lee, Yong Bok; Naidu, Ravi

2016-11-01

An isolate of Cupriavidus (strain MTS-7) was identified from a long-term PAHs and heavy metals mixed contaminated soil with the potential to biodegrade both LMW and HMW PAHs with added unique traits of acid and alkali tolerance, heavy metal tolerance, self-nutrient assimilation by N fixation and P solubilization. This strain completely degraded the model 3 (150 mg L(-1) Phe), 4 (150 mg L(-1) Pyr) and 5 (50 mg L(-1) BaP) ring PAHs in 4, 20 and 30 days, respectively. It could mineralize 90-100% of PAHs (200 mg L(-1) of Phe and Pyr) within 15 days across pH ranging from 5 to 8 and even in the presence of toxic metal contaminations. During biodegradation, the minimum inhibitory concentrations were 5 (Cu(2+)) and 3 (Cd(2+), Pb(2+), Zn(2+)) mg L(-1) of the potentially bioavailable metal ions and over 17 mg L(-1) metal levels was lethal for the microbe. Further, it could fix 217-274 μg mL(-1) of N and solubilize 79-135 μg mL(-1) of P while PAHs degradation. MTS-7 as a superior candidate could be thus used in the enhanced bioaugmentation and/or phytoremediation of long-term mixed contaminated sites. Copyright © 2016 Elsevier Ltd. All rights reserved.

Caution Is Required in Interpretation of Mutations in the Voltage Sensing Domain of Voltage Gated Channels as Evidence for Gating Mechanisms

PubMed Central

Kariev, Alisher M.; Green, Michael E.

2015-01-01

The gating mechanism of voltage sensitive ion channels is generally considered to be the motion of the S4 transmembrane segment of the voltage sensing domains (VSD). The primary supporting evidence came from R→C mutations on the S4 transmembrane segment of the VSD, followed by reaction with a methanethiosulfonate (MTS) reagent. The cys side chain is –SH (reactive form –S−); the arginine side chain is much larger, leaving space big enough to accommodate the MTS sulfonate head group. The cavity created by the mutation has space for up to seven more water molecules than were present in wild type, which could be displaced irreversibly by the MTS reagent. Our quantum calculations show there is major reorientation of three aromatic residues that face into the cavity in response to proton displacement within the VSD. Two phenylalanines reorient sufficiently to shield/unshield the cysteine from the intracellular and extracellular ends, depending on the proton positions, and a tyrosine forms a hydrogen bond to the cysteine sulfur with its side chain –OH. These could produce the results of the experiments that have been interpreted as evidence for physical motion of the S4 segment, without physical motion of the S4 backbone. The computations strongly suggest that the interpretation of cysteine substitution reaction experiments be re-examined in the light of these considerations. PMID:25588216

Intraflagellar transport velocity is governed by the number of active KIF17 and KIF3AB motors and their motility properties under load

PubMed Central

Milic, Bojan; Andreasson, Johan O. L.; Hogan, Daniel W.; Block, Steven M.

2017-01-01

Homodimeric KIF17 and heterotrimeric KIF3AB are processive, kinesin-2 family motors that act jointly to carry out anterograde intraflagellar transport (IFT), ferrying cargo along microtubules (MTs) toward the tips of cilia. How IFT trains attain speeds that exceed the unloaded rate of the slower, KIF3AB motor remains unknown. By characterizing the motility properties of kinesin-2 motors as a function of load we find that the increase in KIF3AB velocity, elicited by forward loads from KIF17 motors, cannot alone account for the speed of IFT trains in vivo. Instead, higher IFT velocities arise from an increased likelihood that KIF3AB motors dissociate from the MT, resulting in transport by KIF17 motors alone, unencumbered by opposition from KIF3AB. The rate of transport is therefore set by an equilibrium between a faster state, where only KIF17 motors move the train, and a slower state, where at least one KIF3AB motor on the train remains active in transport. The more frequently the faster state is accessed, the higher the overall velocity of the IFT train. We conclude that IFT velocity is governed by (i) the absolute numbers of each motor type on a given train, (ii) how prone KIF3AB is to dissociation from MTs relative to KIF17, and (iii) how prone both motors are to dissociation relative to binding MTs. PMID:28761002

Intraflagellar transport velocity is governed by the number of active KIF17 and KIF3AB motors and their motility properties under load.

PubMed

Milic, Bojan; Andreasson, Johan O L; Hogan, Daniel W; Block, Steven M

2017-08-15

Homodimeric KIF17 and heterotrimeric KIF3AB are processive, kinesin-2 family motors that act jointly to carry out anterograde intraflagellar transport (IFT), ferrying cargo along microtubules (MTs) toward the tips of cilia. How IFT trains attain speeds that exceed the unloaded rate of the slower, KIF3AB motor remains unknown. By characterizing the motility properties of kinesin-2 motors as a function of load we find that the increase in KIF3AB velocity, elicited by forward loads from KIF17 motors, cannot alone account for the speed of IFT trains in vivo. Instead, higher IFT velocities arise from an increased likelihood that KIF3AB motors dissociate from the MT, resulting in transport by KIF17 motors alone, unencumbered by opposition from KIF3AB. The rate of transport is therefore set by an equilibrium between a faster state, where only KIF17 motors move the train, and a slower state, where at least one KIF3AB motor on the train remains active in transport. The more frequently the faster state is accessed, the higher the overall velocity of the IFT train. We conclude that IFT velocity is governed by ( i ) the absolute numbers of each motor type on a given train, ( ii ) how prone KIF3AB is to dissociation from MTs relative to KIF17, and ( iii ) how prone both motors are to dissociation relative to binding MTs.

Validation of Shear Wave Elastography in Skeletal Muscle

PubMed Central

Eby, Sarah F.; Song, Pengfei; Chen, Shigao; Chen, Qingshan; Greenleaf, James F.; An, Kai-Nan

2013-01-01

Skeletal muscle is a very dynamic tissue, thus accurate quantification of skeletal muscle stiffness throughout its functional range is crucial to improve the physical functioning and independence following pathology. Shear wave elastography (SWE) is an ultrasound-based technique that characterizes tissue mechanical properties based on the propagation of remotely induced shear waves. The objective of this study is to validate SWE throughout the functional range of motion of skeletal muscle for three ultrasound transducer orientations. We hypothesized that combining traditional materials testing (MTS) techniques with SWE measurements will show increased stiffness measures with increasing tensile load, and will correlate well with each other for trials in which the transducer is parallel to underlying muscle fibers. To evaluate this hypothesis, we monitored the deformation throughout tensile loading of four porcine brachialis whole-muscle tissue specimens, while simultaneously making SWE measurements of the same specimen. We used regression to examine the correlation between Young's modulus from MTS and shear modulus from SWE for each of the transducer orientations. We applied a generalized linear model to account for repeated testing. Model parameters were estimated via generalized estimating equations. The regression coefficient was 0.1944, with a 95% confidence interval of (0.1463 – 0.2425) for parallel transducer trials. Shear waves did not propagate well for both the 45° and perpendicular transducer orientations. Both parallel SWE and MTS showed increased stiffness with increasing tensile load. This study provides the necessary first step for additional studies that can evaluate the distribution of stiffness throughout muscle. PMID:23953670

Hippocampal volumetry: Normative data in the Indian population.

PubMed

Mohandas, Aravind Narayan; Bharath, Rose Dawn; Prathyusha, Parthipulli Vasuki; Gupta, Arun K

2014-07-01

Mesial temporal sclerosis (MTS) is the most common cause of temporal lobe epilepsy. Quantitative analysis of the hippocampus using volumetry is commonly being used in the diagnosis of MTS and is being used as a marker in prognostication of seizure control. Although normative data for hippocampal volume (HV) is available for the western population, no such data is available for the Indian population. The aim of the study was to establish normative data for HV for the Indian population, which can aid in the accurate diagnosis of MTS. Magnetic resonance imaging (MRI) scans of 200 healthy volunteers were acquired using a 3 Tesla (3T) MRI scanner. Manual segmentation and volumetry was done using Siemens Syngo software. The data was analyzed using two tailed t-test to detect associations between HV and age, gender, and education. The data so obtained was also correlated with the data available from the rest of the world. A mean HV of 2.411 cm(3) (standard deviation -0.299) was found in the study, which was significantly smaller when compared to the data from the western population. The right hippocampus was larger than the left, with a mean volume of 2.424 cm(3) and 2.398 cm(3), respectively. HV was detected to be significantly higher in males. No association was found between HV and age and education. The values obtained in this study may be adopted as a standard in the evaluation of patients with intractable epilepsy.

Solar tracking system

DOEpatents

Okandan, Murat; Nielson, Gregory N.

2016-07-12

Solar tracking systems, as well as methods of using such solar tracking systems, are disclosed. More particularly, embodiments of the solar tracking systems include lateral supports horizontally positioned between uprights to support photovoltaic modules. The lateral supports may be raised and lowered along the uprights or translated to cause the photovoltaic modules to track the moving sun.

Ultra-Wideband Tracking System Design for Relative Navigation

NASA Technical Reports Server (NTRS)

Ni, Jianjun David; Arndt, Dickey; Bgo, Phong; Dekome, Kent; Dusl, John

2011-01-01

This presentation briefly discusses a design effort for a prototype ultra-wideband (UWB) time-difference-of-arrival (TDOA) tracking system that is currently under development at NASA Johnson Space Center (JSC). The system is being designed for use in localization and navigation of a rover in a GPS deprived environment for surface missions. In one application enabled by the UWB tracking, a robotic vehicle carrying equipments can autonomously follow a crewed rover from work site to work site such that resources can be carried from one landing mission to the next thereby saving up-mass. The UWB Systems Group at JSC has developed a UWB TDOA High Resolution Proximity Tracking System which can achieve sub-inch tracking accuracy of a target within the radius of the tracking baseline [1]. By extending the tracking capability beyond the radius of the tracking baseline, a tracking system is being designed to enable relative navigation between two vehicles for surface missions. A prototype UWB TDOA tracking system has been designed, implemented, tested, and proven feasible for relative navigation of robotic vehicles. Future work includes testing the system with the application code to increase the tracking update rate and evaluating the linear tracking baseline to improve the flexibility of antenna mounting on the following vehicle.

Model tracking system for low-level radioactive waste disposal facilities: License application interrogatories and responses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benbennick, M.E.; Broton, M.S.; Fuoto, J.S.

This report describes a model tracking system for a low-level radioactive waste (LLW) disposal facility license application. In particular, the model tracks interrogatories (questions, requests for information, comments) and responses. A set of requirements and desired features for the model tracking system was developed, including required structure and computer screens. Nine tracking systems were then reviewed against the model system requirements and only two were found to meet all requirements. Using Kepner-Tregoe decision analysis, a model tracking system was selected.

Ultra-Wideband Time-Difference-of-Arrival High Resolution 3D Proximity Tracking System

NASA Technical Reports Server (NTRS)

Ni, Jianjun; Arndt, Dickey; Ngo, Phong; Phan, Chau; Dekome, Kent; Dusl, John

2010-01-01

This paper describes a research and development effort for a prototype ultra-wideband (UWB) tracking system that is currently under development at NASA Johnson Space Center (JSC). The system is being studied for use in tracking of lunar./Mars rovers and astronauts during early exploration missions when satellite navigation systems are not available. U IATB impulse radio (UWB-IR) technology is exploited in the design and implementation of the prototype location and tracking system. A three-dimensional (3D) proximity tracking prototype design using commercially available UWB products is proposed to implement the Time-Difference- Of-Arrival (TDOA) tracking methodology in this research effort. The TDOA tracking algorithm is utilized for location estimation in the prototype system, not only to exploit the precise time resolution possible with UWB signals, but also to eliminate the need for synchronization between the transmitter and the receiver. Simulations show that the TDOA algorithm can achieve the fine tracking resolution with low noise TDOA estimates for close-in tracking. Field tests demonstrated that this prototype UWB TDOA High Resolution 3D Proximity Tracking System is feasible for providing positioning-awareness information in a 3D space to a robotic control system. This 3D tracking system is developed for a robotic control system in a facility called "Moonyard" at Honeywell Defense & System in Arizona under a Space Act Agreement.

Maintenance of head and neck tumor on-chip: gateway to personalized treatment?

PubMed Central

Bower, Ruth; Green, Victoria L; Kuvshinova, Elena; Kuvshinov, Dmitriy; Karsai, Laszlo; Crank, Stephen T; Stafford, Nicholas D; Greenman, John

2017-01-01

Aim: Head and neck squamous cell carcinomas (HNSCC) are solid tumors with low overall survival (40–60%). In a move toward personalized medicine, maintenance of tumor biopsies in microfluidic tissue culture devices is being developed. Methodology/results: HNSCC (n = 15) was dissected (5–10 mg) and either analyzed immediately or cultured in a microfluidic device (37°C) for 48 h. No difference was observed in morphology between pre- and postculture specimens. Dissociated samples were analyzed using trypan blue exclusion (viability), propidium iodide flow cytometry (death) and MTS assay (proliferation) with no significant difference observed highlighting tissue maintenance. Computational fluid dynamics showed laminar flow within the system. Conclusion: The microfluidic culture system successfully maintained HNSCC for 48 h, the culture system will allow testing of different treatment modalities with response monitoring. PMID:28670466

Tools for Tomorrow's Science and Technology Workforce: MATE's 2006 ROV Competition Sets Students' Sights on Ocean Observing Systems

NASA Technical Reports Server (NTRS)

Zande, Jill; Meeson, Blanche; Cook, Susan; Matsumoto, George

2006-01-01

Teams participating in the 2006 ROV competition organized by the Marine Advanced Technology Education (MATE) Center and the Marine Technology Society's (MTS) ROV Committee experienced first-hand the scientific and technical challenges that many ocean scientists, technicians, and engineers face every day. The competition tasked more than 1,000 middle and high school, college, and university students from Newfoundland to Hong Kong with designing and building ROVs to support the next generation of ocean observing systems. Teaming up with the National Office for Integrated and Sustained Ocean Observations, Ocean. US, and the Ocean Research Interactive Observatory Networks (ORION) Program, the competition highlighted ocean observing systems and the careers, organizations, and technologies associated with ocean observatories. The student teams were challenged to develop vehicles that can deploy, install, and maintain networks of instruments as well as to explore the practical applications and the research questions made possible by observing systems.

New device to measure dynamic intrusion/extrusion cycles of lyophobic heterogeneous systems.

PubMed

Guillemot, Ludivine; Galarneau, Anne; Vigier, Gérard; Abensur, Thierry; Charlaix, Élisabeth

2012-10-01

Lyophobic heterogeneous systems (LHS) are made of mesoporous materials immersed in a non-wetting liquid. One application of LHS is the nonlinear damping of high frequency vibrations. The behaviour of LHS is characterized by P - ΔV cycles, where P is the pressure applied to the system, and ΔV its volume change due to the intrusion of the liquid into the pores of the material, or its extrusion out of the pores. Very few dynamic studies of LHS have been performed until now. We describe here a new apparatus that allows us to carry out dynamic intrusion/extrusion cycles with various liquid/porous material systems, controlling the temperature from ambient to 120 °C and the frequency from 0.01 to 20 Hz. We show that for two LHS: water/MTS and Galinstan/CPG, the energy dissipated during one cycle depends very weakly on the cycle frequency, in strong contrast to conventional dampers.

Advanced tracking systems design and analysis

NASA Technical Reports Server (NTRS)

Potash, R.; Floyd, L.; Jacobsen, A.; Cunningham, K.; Kapoor, A.; Kwadrat, C.; Radel, J.; Mccarthy, J.

1989-01-01

The results of an assessment of several types of high-accuracy tracking systems proposed to track the spacecraft in the National Aeronautics and Space Administration (NASA) Advanced Tracking and Data Relay Satellite System (ATDRSS) are summarized. Tracking systems based on the use of interferometry and ranging are investigated. For each system, the top-level system design and operations concept are provided. A comparative system assessment is presented in terms of orbit determination performance, ATDRSS impacts, life-cycle cost, and technological risk.

Textual and shape-based feature extraction and neuro-fuzzy classifier for nuclear track recognition

NASA Astrophysics Data System (ADS)

Khayat, Omid; Afarideh, Hossein

2013-04-01

Track counting algorithms as one of the fundamental principles of nuclear science have been emphasized in the recent years. Accurate measurement of nuclear tracks on solid-state nuclear track detectors is the aim of track counting systems. Commonly track counting systems comprise a hardware system for the task of imaging and software for analysing the track images. In this paper, a track recognition algorithm based on 12 defined textual and shape-based features and a neuro-fuzzy classifier is proposed. Features are defined so as to discern the tracks from the background and small objects. Then, according to the defined features, tracks are detected using a trained neuro-fuzzy system. Features and the classifier are finally validated via 100 Alpha track images and 40 training samples. It is shown that principle textual and shape-based features concomitantly yield a high rate of track detection compared with the single-feature based methods.

Biological Interactions of Nanomaterials

DTIC Science & Technology

2008-12-01

reagent contains the tetrazolium compound MTS and an electron coupling reagent ( phenazine ethosulfate; PES). The quantity of formazan product as...PES Phenazine ethosulfate PS Polysaccharide RET Rearranged during transfection ROS Reactive oxygen species SD Standard deviation SEM Scanning