[Arms racing between human beings and pathogens: NDM-1 and superbugs].

Science.gov (United States)

Sun, Mingwei; Zheng, Beiwen; Gao, George F; Zhu, Baoli

2010-11-01

Throughout human history, pandemic bacterial diseases such as the plague and tuberculosis have posed an enormous threat to human beings. The discovery of antibiotics has provided us with powerful arsenal for the defense against bacterial infections. However, bacteria are acquiring more and more resistance genes to shield off antibiotics through mutation and horizontal gene transfer. Therefore, novel antibiotics must be produced and the arms race between bacterial pathogens and antibiotics is becoming increasingly intense. Recently, researchers have found that plasmids carrying a new metallo-beta-lactamase gene, blaNDM-1, and many other antibiotics resistance genes can easily spread through bacterial populations and confer recipient stains resistance to nearly all of the current antibiotics. It is a threat to the human health and a great challenge for our medical science, which we are facing. We need to find new ways to fight and win this arms racing.

Mitigating humanitarian crises during non-international armed conflicts: the role of human rights and ceasefire agreements

OpenAIRE

Lane, Lottie

2016-01-01

Situations of humanitarian crisis are often caused by armed conflicts. Given the prevalence of non-international armed conflicts today, ways of ameliorating these situations are at the forefront of concerns. The international humanitarian law rules governing non-international armed conflict remain much less developed than those for international armed conflicts. This is exacerbated by the lack of direct human rights obligations for non-state armed groups, which makes governing the behaviour o...

Human arm stiffness and equilibrium-point trajectory during multi-joint movement.

Science.gov (United States)

Gomi, H; Kawato, M

1997-03-01

By using a newly designed high-performance manipulandum and a new estimation algorithm, we measured human multi-joint arm stiffness parameters during multi-joint point-to-point movements on a horizontal plane. This manipulandum allows us to apply a sufficient perturbation to subject's arm within a brief period during movement. Arm stiffness parameters were reliably estimated using a new algorithm, in which all unknown structural parameters could be estimated independent of arm posture (i.e., constant values under any arm posture). Arm stiffness during transverse movement was considerably greater than that during corresponding posture, but not during a longitudinal movement. Although the ratios of elbow, shoulder, and double-joint stiffness were varied in time, the orientation of stiffness ellipses during the movement did not change much. Equilibrium-point trajectories that were predicted from measured stiffness parameters and actual trajectories were slightly sinusoidally curved in Cartesian space and their velocity profiles were quite different from the velocity profiles of actual hand trajectories. This result contradicts the hypothesis that the brain does not take the dynamics into account in movement control depending on the neuromuscular servo mechanism; rather, it implies that the brain needs to acquire some internal models of controlled objects.

The Arms Trade and States' Duty to Ensure Respect for Humanitarian and Human Rights Law

DEFF Research Database (Denmark)

Brehm, Maya

2007-01-01

transfers has traditionally been treated as a question of arms control law, but in the recent debate about legal restrictions on states' liberty to transfer arms, norms of international humanitarian and human rights law have frequently been invoked. This article surveys the existing international legal......The unregulated international trade in conventional arms, especially in small arms and light weapons, has come to be viewed as an exacerbating factor in armed conflict, violent crime and internal repression. Concern about the negative humanitarian, development and security impact of this trade has...... been growing over the last decade. Against this backdrop, the UN General Assembly invited states in December 2006 to consider the feasibility of an instrument establishing common international standards for conventional arms transfers-also known as the ‘Arms Trade Treaty' (ATT). The legality of arms...

LRRC6 mutation causes primary ciliary dyskinesia with dynein arm defects.

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Amjad Horani

Full Text Available Despite recent progress in defining the ciliome, the genetic basis for many cases of primary ciliary dyskinesia (PCD remains elusive. We evaluated five children from two unrelated, consanguineous Palestinian families who had PCD with typical clinical features, reduced nasal nitric oxide concentrations, and absent dynein arms. Linkage analyses revealed a single common homozygous region on chromosome 8 and one candidate was conserved in organisms with motile cilia. Sequencing revealed a single novel mutation in LRRC6 (Leucine-rich repeat containing protein 6 that fit the model of autosomal recessive genetic transmission, leading to a change of a highly conserved amino acid from aspartic acid to histidine (Asp146His. LRRC6 was localized to the cytoplasm and was up-regulated during ciliogenesis in human airway epithelial cells in a Foxj1-dependent fashion. Nasal epithelial cells isolated from affected individuals and shRNA-mediated silencing in human airway epithelial cells, showed reduced LRRC6 expression, absent dynein arms, and slowed cilia beat frequency. Dynein arm proteins were either absent or mislocalized to the cytoplasm in airway epithelial cells from a primary ciliary dyskinesia subject. These findings suggest that LRRC6 plays a role in dynein arm assembly or trafficking and when mutated leads to primary ciliary dyskinesia with laterality defects.

Octopuses use a human-like strategy to control precise point-to-point arm movements.

Science.gov (United States)

Sumbre, Germán; Fiorito, Graziano; Flash, Tamar; Hochner, Binyamin

2006-04-18

One of the key problems in motor control is mastering or reducing the number of degrees of freedom (DOFs) through coordination. This problem is especially prominent with hyper-redundant limbs such as the extremely flexible arm of the octopus. Several strategies for simplifying these control problems have been suggested for human point-to-point arm movements. Despite the evolutionary gap and morphological differences, humans and octopuses evolved similar strategies when fetching food to the mouth. To achieve this precise point-to-point-task, octopus arms generate a quasi-articulated structure based on three dynamic joints. A rotational movement around these joints brings the object to the mouth . Here, we describe a peripheral neural mechanism-two waves of muscle activation propagate toward each other, and their collision point sets the medial-joint location. This is a remarkably simple mechanism for adjusting the length of the segments according to where the object is grasped. Furthermore, similar to certain human arm movements, kinematic invariants were observed at the joint level rather than at the end-effector level, suggesting intrinsic control coordination. The evolutionary convergence to similar geometrical and kinematic features suggests that a kinematically constrained articulated limb controlled at the level of joint space is the optimal solution for precise point-to-point movements.

Locomotor-like leg movements evoked by rhythmic arm movements in humans.

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Francesca Sylos-Labini

Full Text Available Motion of the upper limbs is often coupled to that of the lower limbs in human bipedal locomotion. It is unclear, however, whether the functional coupling between upper and lower limbs is bi-directional, i.e. whether arm movements can affect the lumbosacral locomotor circuitry. Here we tested the effects of voluntary rhythmic arm movements on the lower limbs. Participants lay horizontally on their side with each leg suspended in an unloading exoskeleton. They moved their arms on an overhead treadmill as if they walked on their hands. Hand-walking in the antero-posterior direction resulted in significant locomotor-like movements of the legs in 58% of the participants. We further investigated quantitatively the responses in a subset of the responsive subjects. We found that the electromyographic (EMG activity of proximal leg muscles was modulated over each cycle with a timing similar to that of normal locomotion. The frequency of kinematic and EMG oscillations in the legs typically differed from that of arm oscillations. The effect of hand-walking was direction specific since medio-lateral arm movements did not evoke appreciably leg air-stepping. Using externally imposed trunk movements and biomechanical modelling, we ruled out that the leg movements associated with hand-walking were mainly due to the mechanical transmission of trunk oscillations. EMG activity in hamstring muscles associated with hand-walking often continued when the leg movements were transiently blocked by the experimenter or following the termination of arm movements. The present results reinforce the idea that there exists a functional neural coupling between arm and legs.

STRATEGIC MANAGEMENT OF HUMAN RESOURCE AND THE SLOVAK ARMED FORCES

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Jaroslav NEKORANEC

2014-04-01

Full Text Available Human resource management is an important area of strategic management of the organization which focuses on everything that concerns people. The main role of human resource management is to contribute to organizational performance and its continuous improvement. In order to fulfill the aims and objectives of the organization, it is necessary that organization top management has a clear-cut view of human resource management strategies that would work in practice. One of the most important and most challenging aspects of human resource management can be applied also in organizations characterized by specific features such as the Armed Forces of the Slovak Republic.

PTPN13, a Fas-associated protein tyrosine phosphatase, is located on the long arm of chromosome 4 at band q21.3

Energy Technology Data Exchange (ETDEWEB)

Inazawa, Johji; Ariyama, Takeshi; Abe, Tatsuo [Kyoto Prefectural Univ. of Medicine (Japan)] [and others

1996-01-15

PTPN13 is a protein tyrosine phosphatase that associates with the C-terminal negative regulatory domain in the Fas (APO-1/CD95) receptor. The PTPN13 protein contains six GLGF repeats that have been found in the rat postsynaptic density protein (PSD-95) and the Drosophila tumor suppressor protein, lethal-(1)-disclarge-1 (dlg-1). The localization of the PTPN13 gene to human chromosome 4q21.3 was determined by both FISH and PCR analysis of somatic cell hybrids. This 4q21.3 chromosomal region contains a gene for autosomal dominant polycystic kidney disease as well as the region frequently deleted in liver and ovarian cancers, suggesting that PTPN13 is a candidate for one of the putative tumor suppressor genes on the long arm of chromosome 4. 21 refs., 1 fig.

The amyloid precursor-like protein (APLP) gene maps to the long arm of human chromosome 19

Energy Technology Data Exchange (ETDEWEB)

Wasco, W.; Tanzi, R.E. (Harvard Medical School, Boston, MA (United States)); Brook, J.D. (Center for Medical Genetics, Nottingham (United Kingdom))

1993-01-01

We have recently isolated a cDNA from a mouse brain library that encodes a protein whose predicted amino acid sequence is 42% identical and 64% similar to that of the amyloid [beta] protein precursor (APP; 16). This 653-amino-acid amyloid precursor-like protein (APLP) is similar to APP in overall structure as well as amino acid sequence. The amino acid homologies are particularly strong in three distinct regions of the proteins where the identities are 47, 54, and 56% (16). All three of these regions are also conserved in the Drosophila APP-like gene, APPL (11). Notably, 12 cysteine residues and a N -glyco-sylation site are conserved in the extracellular portion of APLP and APP, and a clathrin-binding domain is conserved in the cytoplasmic domain. The cytoplasmic domain is also conserved in a partial CDNA reported to encode an APP-like gene in rat testes (17), These data suggest that APLP and APP are members of a highly conserved gene family. A panel of DNAs from 31 human-rodent somatic cell lines of known karyotype was digested with EcoR1. These DNAs were then probed with the human APLP cDNA clone and the hybridization pattern was consistent with the assignment of the APLP locus to chromosome 19. 17 refs., 1 fig.

CRISPR/Cas9-Mediated Fluorescent Tagging of Endogenous Proteins in Human Pluripotent Stem Cells.

Science.gov (United States)

Sharma, Arun; Toepfer, Christopher N; Ward, Tarsha; Wasson, Lauren; Agarwal, Radhika; Conner, David A; Hu, Johnny H; Seidman, Christine E

2018-01-24

Human induced pluripotent stem cells (hiPSCs) can be used to mass produce surrogates of human tissues, enabling new advances in drug screening, disease modeling, and cell therapy. Recent developments in clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 genome editing technology use homology-directed repair (HDR) to efficiently generate custom hiPSC lines harboring a variety of genomic insertions and deletions. Thus, hiPSCs that encode an endogenous protein fused to a fluorescent reporter protein can be rapidly created by employing CRISPR/Cas9 genome editing, enhancing HDR efficiency and optimizing homology arm length. These fluorescently tagged hiPSCs can be used to visualize protein function and dynamics in real time as cells proliferate and differentiate. Given that nearly any intracellular protein can be fluorescently tagged, this system serves as a powerful tool to facilitate new discoveries across many biological disciplines. In this unit, we present protocols for the design, generation, and monoclonal expansion of genetically customized hiPSCs encoding fluorescently tagged endogenous proteins. © 2018 by John Wiley & Sons, Inc. Copyright © 2018 John Wiley & Sons, Inc.

Evolution of robotic arms.

Science.gov (United States)

Moran, Michael E

2007-01-01

The foundation of surgical robotics is in the development of the robotic arm. This is a thorough review of the literature on the nature and development of this device with emphasis on surgical applications. We have reviewed the published literature and classified robotic arms by their application: show, industrial application, medical application, etc. There is a definite trend in the manufacture of robotic arms toward more dextrous devices, more degrees-of-freedom, and capabilities beyond the human arm. da Vinci designed the first sophisticated robotic arm in 1495 with four degrees-of-freedom and an analog on-board controller supplying power and programmability. von Kemplen's chess-playing automaton left arm was quite sophisticated. Unimate introduced the first industrial robotic arm in 1961, it has subsequently evolved into the PUMA arm. In 1963 the Rancho arm was designed; Minsky's Tentacle arm appeared in 1968, Scheinman's Stanford arm in 1969, and MIT's Silver arm in 1974. Aird became the first cyborg human with a robotic arm in 1993. In 2000 Miguel Nicolalis redefined possible man-machine capacity in his work on cerebral implantation in owl-monkeys directly interfacing with robotic arms both locally and at a distance. The robotic arm is the end-effector of robotic systems and currently is the hallmark feature of the da Vinci Surgical System making its entrance into surgical application. But, despite the potential advantages of this computer-controlled master-slave system, robotic arms have definite limitations. Ongoing work in robotics has many potential solutions to the drawbacks of current robotic surgical systems.

Interaction of C-terminal truncated human alphaA-crystallins with target proteins.

Directory of Open Access Journals (Sweden)

Anbarasu Kumarasamy

2008-09-01

Full Text Available Significant portion of alphaA-crystallin in human lenses exists as C-terminal residues cleaved at residues 172, 168, and 162. Chaperone activity, determined with alcohol dehydrogenase (ADH and betaL-crystallin as target proteins, was increased in alphaA(1-172 and decreased in alphaA(1-168 and alphaA(1-162. The purpose of this study was to show whether the absence of the C-terminal residues influences protein-protein interactions with target proteins.Our hypothesis is that the chaperone-target protein binding kinetics, otherwise termed subunit exchange rates, are expected to reflect the changes in chaperone activity. To study this, we have relied on fluorescence resonance energy transfer (FRET utilizing amine specific and cysteine specific fluorescent probes. The subunit exchange rate (k for ADH and alphaA(1-172 was nearly the same as that of ADH and alphaA-wt, alphaA(1-168 had lower and alphaA(1-162 had the lowest k values. When betaL-crystallin was used as the target protein, alphaA(1-172 had slightly higher k value than alphaA-wt and alphaA(1-168 and alphaA(1-162 had lower k values. As expected from earlier studies, the chaperone activity of alphaA(1-172 was slightly better than that of alphaA-wt, the chaperone activity of alphaA(1-168 was similar to that of alphaA-wt and alphaA(1-162 had substantially decreased chaperone activity.Cleavage of eleven C-terminal residues including Arg-163 and the C-terminal flexible arm significantly affects the interaction with target proteins. The predominantly hydrophilic flexible arm appears to be needed to keep the chaperone-target protein complex soluble.

Shaping of arm configuration space by prescription of non-Euclidean metrics with applications to human motor control

Science.gov (United States)

Biess, Armin

2013-01-01

The study of the kinematic and dynamic features of human arm movements provides insights into the computational strategies underlying human motor control. In this paper a differential geometric approach to movement control is taken by endowing arm configuration space with different non-Euclidean metric structures to study the predictions of the generalized minimum-jerk (MJ) model in the resulting Riemannian manifold for different types of human arm movements. For each metric space the solution of the generalized MJ model is given by reparametrized geodesic paths. This geodesic model is applied to a variety of motor tasks ranging from three-dimensional unconstrained movements of a four degree of freedom arm between pointlike targets to constrained movements where the hand location is confined to a surface (e.g., a sphere) or a curve (e.g., an ellipse). For the latter speed-curvature relations are derived depending on the boundary conditions imposed (periodic or nonperiodic) and the compatibility with the empirical one-third power law is shown. Based on these theoretical studies and recent experimental findings, I argue that geodesics may be an emergent property of the motor system and that the sensorimotor system may shape arm configuration space by learning metric structures through sensorimotor feedback.

CCDC103 mutations cause primary ciliary dyskinesia by disrupting assembly of ciliary dynein arms

Science.gov (United States)

Panizzi, Jennifer R.; Becker-Heck, Anita; Castleman, Victoria H.; Al-Mutairi, Dalal; Liu, Yan; Loges, Niki T.; Pathak, Narendra; Austin-Tse, Christina; Sheridan, Eamonn; Schmidts, Miriam; Olbrich, Heike; Werner, Claudius; Häffner, Karsten; Hellman, Nathan; Chodhari, Rahul; Gupta, Amar; Kramer-Zucker, Albrecht; Olale, Felix; Burdine, Rebecca D.; Schier, Alexander F.; O’Callaghan, Christopher; Chung, Eddie MK; Reinhardt, Richard; Mitchison, Hannah M.; King, Stephen M.; Omran, Heymut; Drummond, Iain A.

2012-01-01

Cilia are essential for fertilization, respiratory clearance, cerebrospinal fluid circulation, and to establish laterality1. Cilia motility defects cause Primary Ciliary Dyskinesia (PCD, MIM 242650), a disorder affecting 1:15-30,000 births. Cilia motility requires the assembly of multisubunit dynein arms that drive cilia bending2. Despite progress in understanding the genetic basis of PCD, mutations remain to be identified for several PCD linked loci3. Here we show that the zebrafish cilia paralysis mutant schmalhanstn222 (smh) mutant encodes the coiled-coil domain containing 103 protein (Ccdc103), a foxj1a regulated gene. Screening 146 unrelated PCD families identified patients in six families with reduced outer dynein arms, carrying mutations in CCDC103. Dynein arm assembly in smh mutant zebrafish was rescued by wild-type but not mutant human CCDC103. Chlamydomonas Ccdc103 functions as a tightly bound, axoneme-associated protein. The results identify Ccdc103 as a novel dynein arm attachment factor that when mutated causes Primary Ciliary Dyskinesia. PMID:22581229

Analysis of the role of homology arms in gene-targeting vectors in human cells.

Directory of Open Access Journals (Sweden)

Ayako Ishii

Full Text Available Random integration of targeting vectors into the genome is the primary obstacle in human somatic cell gene targeting. Non-homologous end-joining (NHEJ, a major pathway for repairing DNA double-strand breaks, is thought to be responsible for most random integration events; however, absence of DNA ligase IV (LIG4, the critical NHEJ ligase, does not significantly reduce random integration frequency of targeting vector in human cells, indicating robust integration events occurring via a LIG4-independent mechanism. To gain insights into the mechanism and robustness of LIG4-independent random integration, we employed various types of targeting vectors to examine their integration frequencies in LIG4-proficient and deficient human cell lines. We find that the integration frequency of targeting vector correlates well with the length of homology arms and with the amount of repetitive DNA sequences, especially SINEs, present in the arms. This correlation was prominent in LIG4-deficient cells, but was also seen in LIG4-proficient cells, thus providing evidence that LIG4-independent random integration occurs frequently even when NHEJ is functionally normal. Our results collectively suggest that random integration frequency of conventional targeting vectors is substantially influenced by homology arms, which typically harbor repetitive DNA sequences that serve to facilitate LIG4-independent random integration in human cells, regardless of the presence or absence of functional NHEJ.

On the Value of Estimating Human Arm Stiffness during Virtual Teleoperation with Robotic Manipulators.

Science.gov (United States)

Buzzi, Jacopo; Ferrigno, Giancarlo; Jansma, Joost M; De Momi, Elena

2017-01-01

Teleoperated robotic systems are widely spreading in multiple different fields, from hazardous environments exploration to surgery. In teleoperation, users directly manipulate a master device to achieve task execution at the slave robot side; this interaction is fundamental to guarantee both system stability and task execution performance. In this work, we propose a non-disruptive method to study the arm endpoint stiffness. We evaluate how users exploit the kinetic redundancy of the arm to achieve stability and precision during the execution of different tasks with different master devices. Four users were asked to perform two planar trajectories following virtual tasks using both a serial and a parallel link master device. Users' arm kinematics and muscular activation were acquired and combined with a user-specific musculoskeletal model to estimate the joint stiffness. Using the arm kinematic Jacobian, the arm end-point stiffness was derived. The proposed non-disruptive method is capable of estimating the arm endpoint stiffness during the execution of virtual teleoperated tasks. The obtained results are in accordance with the existing literature in human motor control and show, throughout the tested trajectory, a modulation of the arm endpoint stiffness that is affected by task characteristics and hand speed and acceleration.

On the Value of Estimating Human Arm Stiffness during Virtual Teleoperation with Robotic Manipulators

Directory of Open Access Journals (Sweden)

Jacopo Buzzi

2017-09-01

Full Text Available Teleoperated robotic systems are widely spreading in multiple different fields, from hazardous environments exploration to surgery. In teleoperation, users directly manipulate a master device to achieve task execution at the slave robot side; this interaction is fundamental to guarantee both system stability and task execution performance. In this work, we propose a non-disruptive method to study the arm endpoint stiffness. We evaluate how users exploit the kinetic redundancy of the arm to achieve stability and precision during the execution of different tasks with different master devices. Four users were asked to perform two planar trajectories following virtual tasks using both a serial and a parallel link master device. Users' arm kinematics and muscular activation were acquired and combined with a user-specific musculoskeletal model to estimate the joint stiffness. Using the arm kinematic Jacobian, the arm end-point stiffness was derived. The proposed non-disruptive method is capable of estimating the arm endpoint stiffness during the execution of virtual teleoperated tasks. The obtained results are in accordance with the existing literature in human motor control and show, throughout the tested trajectory, a modulation of the arm endpoint stiffness that is affected by task characteristics and hand speed and acceleration.

Estimation of Human Arm Joints Using Two Wireless Sensors in Robotic Rehabilitation Tasks

Directory of Open Access Journals (Sweden)

Arturo Bertomeu-Motos

2015-12-01

Full Text Available This paper presents a novel kinematic reconstruction of the human arm chain with five degrees of freedom and the estimation of the shoulder location during rehabilitation therapy assisted by end-effector robotic devices. This algorithm is based on the pseudoinverse of the Jacobian through the acceleration of the upper arm, measured using an accelerometer, and the orientation of the shoulder, estimated with a magnetic angular rate and gravity (MARG device. The results show a high accuracy in terms of arm joints and shoulder movement with respect to the real arm measured through an optoelectronic system. Furthermore, the range of motion (ROM of 50 healthy subjects is studied from two different trials, one trying to avoid shoulder movements and the second one forcing them. Moreover, the shoulder movement in the second trial is also estimated accurately. Besides the fact that the posture of the patient can be corrected during the exercise, the therapist could use the presented algorithm as an objective assessment tool. In conclusion, the joints’ estimation enables a better adjustment of the therapy, taking into account the needs of the patient, and consequently, the arm motion improves faster.

Tc-99m-Human Serum Albumin Transit Time as a Measure of Arm Breast Cancer-Related Lymphedema

DEFF Research Database (Denmark)

Toyserkani, Navid M; Hvidsten, Svend; Tabatabaeifar, Siavosh

2017-01-01

34-68 years, with unilateral arm lymphedema following breast cancer treatment underwent bilateral lymphoscintigraphy using intradermal injection in both hands of technetium-99m-labeled human serum albumin and sequential 5 min imaging for 5 hours. The mean transit time (MTT) in the arms was calculated...... based on time activity curves generated from injection site and arm regions. Visual lymphedema scoring was performed based on dermal backflow and lymph node presence. Excess arm volume was calculated from circumference measurements. RESULTS: The MTT (mean ± SD) was significantly longer in the lymphedema...

Kinematics design and human motion transfer for a humanoid service robot arm

CSIR Research Space (South Africa)

Dube, C

2009-11-01

Full Text Available . Philadelphia: Saunders Col- lege Publishing, 1982. [2] Hamill, J. and Knutzen, K. M., Biomechanical Basis of Human Motion, Baltimore: Williams and Wilkins, 1995. [3] Lenarcˇicˇ, J. and Klopcˇar, N.,“Positional kinematics of hu- manoid arms,” Robotica, vol...

Biomechanical Constraints Underlying Motor Primitives Derived from the Musculoskeletal Anatomy of the Human Arm.

Science.gov (United States)

Gritsenko, Valeriya; Hardesty, Russell L; Boots, Mathew T; Yakovenko, Sergiy

2016-01-01

Neural control of movement can only be realized though the interaction between the mechanical properties of the limb and the environment. Thus, a fundamental question is whether anatomy has evolved to simplify neural control by shaping these interactions in a beneficial way. This inductive data-driven study analyzed the patterns of muscle actions across multiple joints using the musculoskeletal model of the human upper limb. This model was used to calculate muscle lengths across the full range of motion of the arm and examined the correlations between these values between all pairs of muscles. Musculoskeletal coupling was quantified using hierarchical clustering analysis. Muscle lengths between multiple pairs of muscles across multiple postures were highly correlated. These correlations broadly formed two proximal and distal groups, where proximal muscles of the arm were correlated with each other and distal muscles of the arm and hand were correlated with each other, but not between groups. Using hierarchical clustering, between 11 and 14 reliable muscle groups were identified. This shows that musculoskeletal anatomy does indeed shape the mechanical interactions by grouping muscles into functional clusters that generally match the functional repertoire of the human arm. Together, these results support the idea that the structure of the musculoskeletal system is tuned to solve movement complexity problem by reducing the dimensionality of available solutions.

Expression of the Flp proteins by Haemophilus ducreyi is necessary for virulence in human volunteers

Directory of Open Access Journals (Sweden)

Zwickl Beth W

2011-09-01

Full Text Available Abstract Background Haemophilus ducreyi, the causative agent of the sexually transmitted disease chancroid, contains a flp (fimbria like protein operon that encodes proteins predicted to contribute to adherence and pathogenesis. H. ducreyi mutants that lack expression of Flp1 and Flp2 or TadA, which has homology to NTPases of type IV secretion systems, have decreased abilities to attach to and form microcolonies on human foreskin fibroblasts (HFF. A tadA mutant is attenuated in its ability to cause disease in human volunteers and in the temperature dependent rabbit model, but a flp1flp2 mutant is virulent in rabbits. Whether a flp deletion mutant would cause disease in humans is not clear. Results We constructed 35000HPΔflp1-3, a deletion mutant that lacks expression of all three Flp proteins but has an intact tad secretion system. 35000HPΔflp1-3 was impaired in its ability to form microcolonies and to attach to HFF in vitro when compared to its parent (35000HP. Complementation of the mutant with flp1-3 in trans restored the parental phenotype. To test whether expression of Flp1-3 was necessary for virulence in humans, ten healthy adult volunteers were experimentally infected with a fixed dose of 35000HP (ranging from 54 to 67 CFU on one arm and three doses of 35000HPΔflp1-3 (ranging from 63 to 961 CFU on the other arm. The overall papule formation rate for the parent was 80% (95% confidence interval, CI, 55.2%-99.9% and for the mutant was 70.0% (95% CI, 50.5%-89.5% (P = 0.52. Mutant papules were significantly smaller (mean, 11.2 mm2 than were parent papules (21.8 mm2 24 h after inoculation (P = 0.018. The overall pustule formation rates were 46.7% (95% CI 23.7-69.7% at 30 parent sites and 6.7% (95% CI, 0.1-19.1% at 30 mutant sites (P = 0.001. Conclusion These data suggest that production and secretion of the Flp proteins contributes to microcolony formation and attachment to HFF cells in vitro. Expression of flp1-3 is also necessary for H

Expression of the Flp proteins by Haemophilus ducreyi is necessary for virulence in human volunteers.

Science.gov (United States)

Janowicz, Diane M; Cooney, Sean A; Walsh, Jessica; Baker, Beth; Katz, Barry P; Fortney, Kate R; Zwickl, Beth W; Ellinger, Sheila; Munson, Robert S

2011-09-22

Haemophilus ducreyi, the causative agent of the sexually transmitted disease chancroid, contains a flp (fimbria like protein) operon that encodes proteins predicted to contribute to adherence and pathogenesis. H. ducreyi mutants that lack expression of Flp1 and Flp2 or TadA, which has homology to NTPases of type IV secretion systems, have decreased abilities to attach to and form microcolonies on human foreskin fibroblasts (HFF). A tadA mutant is attenuated in its ability to cause disease in human volunteers and in the temperature dependent rabbit model, but a flp1flp2 mutant is virulent in rabbits. Whether a flp deletion mutant would cause disease in humans is not clear. We constructed 35000HPΔflp1-3, a deletion mutant that lacks expression of all three Flp proteins but has an intact tad secretion system. 35000HPΔflp1-3 was impaired in its ability to form microcolonies and to attach to HFF in vitro when compared to its parent (35000HP). Complementation of the mutant with flp1-3 in trans restored the parental phenotype. To test whether expression of Flp1-3 was necessary for virulence in humans, ten healthy adult volunteers were experimentally infected with a fixed dose of 35000HP (ranging from 54 to 67 CFU) on one arm and three doses of 35000HPΔflp1-3 (ranging from 63 to 961 CFU) on the other arm. The overall papule formation rate for the parent was 80% (95% confidence interval, CI, 55.2%-99.9%) and for the mutant was 70.0% (95% CI, 50.5%-89.5%) (P = 0.52). Mutant papules were significantly smaller (mean, 11.2 mm2) than were parent papules (21.8 mm2) 24 h after inoculation (P = 0.018). The overall pustule formation rates were 46.7% (95% CI 23.7-69.7%) at 30 parent sites and 6.7% (95% CI, 0.1-19.1%) at 30 mutant sites (P = 0.001). These data suggest that production and secretion of the Flp proteins contributes to microcolony formation and attachment to HFF cells in vitro. Expression of flp1-3 is also necessary for H. ducreyi to initiate disease and progress to

A scored human protein-protein interaction network to catalyze genomic interpretation

DEFF Research Database (Denmark)

Li, Taibo; Wernersson, Rasmus; Hansen, Rasmus B

2017-01-01

Genome-scale human protein-protein interaction networks are critical to understanding cell biology and interpreting genomic data, but challenging to produce experimentally. Through data integration and quality control, we provide a scored human protein-protein interaction network (InWeb_InBioMap,......Genome-scale human protein-protein interaction networks are critical to understanding cell biology and interpreting genomic data, but challenging to produce experimentally. Through data integration and quality control, we provide a scored human protein-protein interaction network (In...

Molecular cloning and chromosome mapping of the human gene encoding protein phosphotyrosyl phosphatase 1B

International Nuclear Information System (INIS)

Brown-Shimer, S.; Johnson, K.A.; Bruskin, A.; Green, N.R.; Hill, D.E.; Lawrence, J.B.; Johnson, C.

1990-01-01

The inactivation of growth suppressor genes appears to play a major role in the malignant process. To assess whether protein phosphotyrosyl phosphatases function as growth suppressors, the authors have isolated a cDNA clone encoding human protein phosphotyrosyl phosphatase 1B for structural and functional characterization. The translation product deduced from the 1,305-nucleotide open reading frame predicts a protein containing 435 amino acids and having a molecular mass of 49,966 Da. The amino-terminal 321 amino acids deduced from the cDNA sequence are identical to the empirically determined sequence of protein phosphotyrosyl phosphatase 1B. A genomic clone has been isolated and used in an in situ hybridization to banded metaphase chromosomes to determine that the gene encoding protein phosphotyrosyl phosphatase 1B maps as a single-copy gene to the long arm of chromosome 20 in the region q13.1-q13.2

Learning robotic eye-arm-hand coordination from human demonstration: a coupled dynamical systems approach.

Science.gov (United States)

Lukic, Luka; Santos-Victor, José; Billard, Aude

2014-04-01

We investigate the role of obstacle avoidance in visually guided reaching and grasping movements. We report on a human study in which subjects performed prehensile motion with obstacle avoidance where the position of the obstacle was systematically varied across trials. These experiments suggest that reaching with obstacle avoidance is organized in a sequential manner, where the obstacle acts as an intermediary target. Furthermore, we demonstrate that the notion of workspace travelled by the hand is embedded explicitly in a forward planning scheme, which is actively involved in detecting obstacles on the way when performing reaching. We find that the gaze proactively coordinates the pattern of eye-arm motion during obstacle avoidance. This study provides also a quantitative assessment of the coupling between the eye-arm-hand motion. We show that the coupling follows regular phase dependencies and is unaltered during obstacle avoidance. These observations provide a basis for the design of a computational model. Our controller extends the coupled dynamical systems framework and provides fast and synchronous control of the eyes, the arm and the hand within a single and compact framework, mimicking similar control system found in humans. We validate our model for visuomotor control of a humanoid robot.

Highly sensitive detection of individual HEAT and ARM repeats with HHpred and COACH.

Science.gov (United States)

Kippert, Fred; Gerloff, Dietlind L

2009-09-24

HEAT and ARM repeats occur in a large number of eukaryotic proteins. As these repeats are often highly diverged, the prediction of HEAT or ARM domains can be challenging. Except for the most clear-cut cases, identification at the individual repeat level is indispensable, in particular for determining domain boundaries. However, methods using single sequence queries do not have the sensitivity required to deal with more divergent repeats and, when applied to proteins with known structures, in some cases failed to detect a single repeat. Testing algorithms which use multiple sequence alignments as queries, we found two of them, HHpred and COACH, to detect HEAT and ARM repeats with greatly enhanced sensitivity. Calibration against experimentally determined structures suggests the use of three score classes with increasing confidence in the prediction, and prediction thresholds for each method. When we applied a new protocol using both HHpred and COACH to these structures, it detected 82% of HEAT repeats and 90% of ARM repeats, with the minimum for a given protein of 57% for HEAT repeats and 60% for ARM repeats. Application to bona fide HEAT and ARM proteins or domains indicated that similar numbers can be expected for the full complement of HEAT/ARM proteins. A systematic screen of the Protein Data Bank for false positive hits revealed their number to be low, in particular for ARM repeats. Double false positive hits for a given protein were rare for HEAT and not at all observed for ARM repeats. In combination with fold prediction and consistency checking (multiple sequence alignments, secondary structure prediction, and position analysis), repeat prediction with the new HHpred/COACH protocol dramatically improves prediction in the twilight zone of fold prediction methods, as well as the delineation of HEAT/ARM domain boundaries. A protocol is presented for the identification of individual HEAT or ARM repeats which is straightforward to implement. It provides high

Validity of mid arm circumference to detect protein energy malnutrition among 8-11 months old infants in a rural medical college of West Bengal.

Science.gov (United States)

Sadhukhan, Sanjoy Kr; Chatterjee, Chitra; Shrivastava, Prabha; Sardar, Jadav Chandra; Joardar, Gautam Kr; Lahiri, Saibendu

2010-09-01

This institution-based cross-sectional observational validation study was conducted in the immunisation clinic of North Bengal Medical College and Hospital, Sushrutanagar. The objective was to identify the validity characteristics of mid arm circumference to detect protein energy malnutrition among 8-11 months infants and to find out a suitable cut-off value if any. Study variables were age, sex, body weight and mid arm circumference. Mid arm circumference was validated against weight for age criteria (gold standard) of malnutrition. The mean mid arm circumference of the infants was found to be almost constant with only about 2.22% change over 4 months, signifying that single cut-off point can be used to detect protein energy malnutrition. Mid arm circumference values from 13.0 to 12.5 cm were found to have the highest accuracy to detect protein energy malnutrition (about 86%). The cut-off values of 12.5 and 12.6 cm were noted to have a sensitivity and specificity of about 52% and 96% respectively, a false negativity of 48% but a false positivity of only 4%. Receiver operating characteristics curve detected 12.5(12.6) cm as the best diagnostic cut-off point which can detect more than 50% of the malnourished babies with very little false positivity/misdiagnosis (only 4%). A simple measuring tape with some reorientation of the health workers can detect the beginning of childhood malnutrition.

Viral Organization of Human Proteins

Science.gov (United States)

Wuchty, Stefan; Siwo, Geoffrey; Ferdig, Michael T.

2010-01-01

Although maps of intracellular interactions are increasingly well characterized, little is known about large-scale maps of host-pathogen protein interactions. The investigation of host-pathogen interactions can reveal features of pathogenesis and provide a foundation for the development of drugs and disease prevention strategies. A compilation of experimentally verified interactions between HIV-1 and human proteins and a set of HIV-dependency factors (HDF) allowed insights into the topology and intricate interplay between viral and host proteins on a large scale. We found that targeted and HDF proteins appear predominantly in rich-clubs, groups of human proteins that are strongly intertwined among each other. These assemblies of proteins may serve as an infection gateway, allowing the virus to take control of the human host by reaching protein pathways and diversified cellular functions in a pronounced and focused way. Particular transcription factors and protein kinases facilitate indirect interactions between HDFs and viral proteins. Discerning the entanglement of directly targeted and indirectly interacting proteins may uncover molecular and functional sites that can provide novel perspectives on the progression of HIV infection and highlight new avenues to fight this virus. PMID:20827298

Combined short-arm centrifuge and aerobic exercise training improves cardiovascular function and physical working capacity in humans.

Science.gov (United States)

Yang, Chang-Bin; Zhang, Shu; Zhang, Yu; Wang, Bing; Yao, Yong-Jie; Wang, Yong-Chun; Wu, Yan-Hong; Liang, Wen-Bin; Sun, Xi-Qing

2010-12-01

Musculoskeletal and cardiovascular deconditioning occurring in long-term spaceflight gives rise to the needs to develop new strategies to counteract these adverse effects. Short-arm centrifuge combined with ergometer has been proposed as a strategy to counteract adverse effects of microgravity. This study sought to investigate whether the combination of short-arm centrifuge and aerobic exercise training have advantages over short-arm centrifuge or aerobic exercise training alone. One week training was conducted by 24 healthy men. They were randomly divided into 3 groups: (1) short-arm centrifuge training, (2) aerobic exercise training, 40 W, and (3) combined short-arm centrifuge and aerobic exercise training. Before and after training, the cardiac pump function represented by stroke volume, cardiac output, left ventricular ejection time, and total peripheral resistance was evaluated. Variability of heart rate and systolic blood pressure were determined by spectral analysis. Physical working capacity was surveyed by near maximal physical working capacity test. The 1-week combined short-arm centrifuge and aerobic exercise training remarkably ameliorated the cardiac pump function and enhanced vasomotor sympathetic nerve modulation and improved physical working capacity by 10.9% (Pcentrifuge nor the aerobic exercise group showed improvements in these functions. These results demonstrate that combined short-arm centrifuge and aerobic exercise training has advantages over short-arm centrifuge or aerobic exercise training alone in influencing several physiologically important cardiovascular functions in humans. The combination of short-arm centrifuge and aerobic exercise offers a promising countermeasure to microgravity.

21 CFR 890.3640 - Arm sling.

Science.gov (United States)

2010-04-01

... arm sling is a device intended for medical purposes to immobilize the arm, by means of a fabric band... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Arm sling. 890.3640 Section 890.3640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES...

Human conglutinin-like protein

DEFF Research Database (Denmark)

Jensenius, J C; Thiel, S; Baatrup, G

1985-01-01

The presence in human plasma of a molecule homologous to bovine conglutinin is indicated by the results of biological and immunochemical analysis. The human conglutinin-like protein shows calcium-dependent binding to complement-treated solid phase IgG and immunological cross-reaction with chicken...... anti-bovine conglutinin. The binding of the human protein to complement-treated IgG was inhibited by N-acetyl-D-glucosamine but not by other sugars. Analysis by SDS-PAGE and Western blotting showed reaction of anti-conglutinin with molecules of similar mobility to the monomer and hexamer of bovine...

Inferring high-confidence human protein-protein interactions

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Yu Xueping

2012-05-01

Full Text Available Abstract Background As numerous experimental factors drive the acquisition, identification, and interpretation of protein-protein interactions (PPIs, aggregated assemblies of human PPI data invariably contain experiment-dependent noise. Ascertaining the reliability of PPIs collected from these diverse studies and scoring them to infer high-confidence networks is a non-trivial task. Moreover, a large number of PPIs share the same number of reported occurrences, making it impossible to distinguish the reliability of these PPIs and rank-order them. For example, for the data analyzed here, we found that the majority (>83% of currently available human PPIs have been reported only once. Results In this work, we proposed an unsupervised statistical approach to score a set of diverse, experimentally identified PPIs from nine primary databases to create subsets of high-confidence human PPI networks. We evaluated this ranking method by comparing it with other methods and assessing their ability to retrieve protein associations from a number of diverse and independent reference sets. These reference sets contain known biological data that are either directly or indirectly linked to interactions between proteins. We quantified the average effect of using ranked protein interaction data to retrieve this information and showed that, when compared to randomly ranked interaction data sets, the proposed method created a larger enrichment (~134% than either ranking based on the hypergeometric test (~109% or occurrence ranking (~46%. Conclusions From our evaluations, it was clear that ranked interactions were always of value because higher-ranked PPIs had a higher likelihood of retrieving high-confidence experimental data. Reducing the noise inherent in aggregated experimental PPIs via our ranking scheme further increased the accuracy and enrichment of PPIs derived from a number of biologically relevant data sets. These results suggest that using our high

Validation Studies of the Human Movement Analysis Panel for Hand/Arm Performance

OpenAIRE

Smith, Charles D.; Walton, Ashley; Slevin, John T.; Gerhardt, Greg A.; Umberger, Gloria; Smoot, Kyle; Schulze, Emily; Gash, Don

2007-01-01

The human movement analysis panel (HMAP) measures separable components of arm motion and simple and complex finger coordination. HMAP testing takes 30 minutes to administer. In separate experiments we have validated the HMAP against the standard grooved pegboard and measures of gait speed, and demonstrated important learning effects over both short durations of days, and longer intervals of months to years in normal subjects of different ages. Stepwise regression demonstrated the strongest co...

Lister vaccine strain of vaccinia virus armed with the endostatin-angiostatin fusion gene: an oncolytic virus superior to dl1520 (ONYX-015) for human head and neck cancer.

Science.gov (United States)

Tysome, James R; Wang, Pengju; Alusi, Ghassan; Briat, Arnaud; Gangeswaran, Rathi; Wang, Jiwei; Bhakta, Vipul; Fodor, Istvan; Lemoine, Nick R; Wang, Yaohe

2011-09-01

Oncolytic viral therapy represents a promising strategy for the treatment of head and neck squamous cell carcinoma (HNSCC), with dl1520 (ONYX-015) the most widely used oncolytic adenovirus in clinical trials. This study aimed to determine the effectiveness of the Lister vaccine strain of vaccinia virus as well as a vaccinia virus armed with the endostatin-angiostatin fusion gene (VVhEA) as a novel therapy for HNSCC and to compare them with dl1520. The potency and replication of the Lister strain and VVhEA and the expression and function of the fusion protein were determined in human HNSCC cells in vitro and in vivo. Finally, the efficacy of VVhEA was compared with dl1520 in vivo in a human HNSCC model. The Lister vaccine strain of vaccinia virus was more effective than the adenovirus against all HNSCC cell lines tested in vitro. Although the potency of VVhEA was attenuated in vitro, the expression and function of the endostatin-angiostatin fusion protein was confirmed in HNSCC models both in vitro and in vivo. This novel vaccinia virus (VVhEA) demonstrated superior antitumor potency in vivo compared with both dl1520 and the control vaccinia virus. This study suggests that the Lister strain vaccinia virus armed with an endostatin-angiostatin fusion gene may be a potential therapeutic agent for HNSCC.

A genetic linkage map of the chromosome 4 short arm

Energy Technology Data Exchange (ETDEWEB)

Locke, P.A.; MacDonald, M.E.; Srinidhi, J.; Tanzi, R.E.; Haines, J.L. (Massachusetts General Hospital, Boston (United States)); Gilliam, T.C. (Columbia Univ., New York, NY (United States)); Conneally, P.M. (Indiana Univ. Medical Center, Indianapolis (United States)); Wexler, N.S. (Columbia Univ., New York, NY (United States) Hereditary Disease Foundation, Santa Monica, CA (United States)); Gusella, J.F. (Massachusetts General Hospital, Boston (United States) Harvard Univ., Boston, MA (United States))

1993-01-01

The authors have generated an 18-interval contiguous genetic linkage map of human chromosome 4 spanning the entire short arm and proximal long arm. Fifty-seven polymorphisms, representing 42 loci, were analyzed in the Venezuelan reference pedigree. The markers included seven genes (ADRA2C, ALB, GABRB1, GC, HOX7, IDUA, QDPR), one pseudogene (RAF1P1), and 34 anonymous DNA loci. Four loci were represented by microsatellite polymorphisms and one (GC) was expressed as a protein polymorphism. The remainder were genotyped based on restriction fragment length polymorphism. The sex-averaged map covered 123 cM. Significant differences in sex-specific rates of recombination were observed only in the pericentromeric and proximal long arm regions, but these contributed to different overall map lengths of 115 cM in males and 138 cM in females. This map provides 19 reference points along chromosome 4 that will be particularly useful in anchoring and seeding physical mapping studies and in aiding in disease studies. 26 refs., 1 fig., 1 tab.

Therapeutic IgG4 antibodies engage in Fab-arm exchange with endogenous human IgG4 in vivo

NARCIS (Netherlands)

Labrijn, Aran F.; Buijsse, Antonio Ortiz; van den Bremer, Ewald T. J.; Verwilligen, Annemiek Y. W.; Bleeker, Wim K.; Thorpe, Susan J.; Killestein, Joep; Polman, Chris H.; Aalberse, Rob C.; Schuurman, Janine; van de Winkel, Jan G. J.; Parren, Paul W. H. I.

Two humanized IgG4 antibodies, natalizumab and gemtuzumab, are approved for human use, and several others, like TGN1412, are or have been in clinical development. Although IgG4 antibodies can dynamically exchange half-molecules(1), Fab-arm exchange with therapeutic antibodies has not been

Therapeutic IgG4 antibodies engage in Fab-arm exchange with endogenous human IgG4 in vivo

NARCIS (Netherlands)

Labrijn, Aran F.; Buijsse, Antonio Ortiz; van den Bremer, Ewald T. J.; Verwilligen, Annemiek Y. W.; Bleeker, Wim K.; Thorpe, Susan J.; Killestein, Joep; Polman, Chris H.; Aalberse, Rob C.; Schuurman, Janine; van de Winkel, Jan G. J.; Parren, Paul W. H. I.

2009-01-01

Two humanized IgG4 antibodies, natalizumab and gemtuzumab, are approved for human use, and several others, like TGN1412, are or have been in clinical development. Although IgG4 antibodies can dynamically exchange half-molecules, Fab-arm exchange with therapeutic antibodies has not been demonstrated

Protein phosphorylation systems in postmortem human brain

International Nuclear Information System (INIS)

Walaas, S.I.; Perdahl-Wallace, E.; Winblad, B.; Greengard, P.

1989-01-01

Protein phosphorylation systems regulated by cyclic adenosine 3',5'-monophosphate (cyclic AMP), or calcium in conjunction with calmodulin or phospholipid/diacylglycerol, have been studied by phosphorylation in vitro of particulate and soluble fractions from human postmortem brain samples. One-dimensional or two-dimensional gel electrophoretic protein separations were used for analysis. Protein phosphorylation catalyzed by cyclic AMP-dependent protein kinase was found to be highly active in both particulate and soluble preparations throughout the human CNS, with groups of both widely distributed and region-specific substrates being observed in different brain nuclei. Dopamine-innervated parts of the basal ganglia and cerebral cortex contained the phosphoproteins previously observed in rodent basal ganglia. In contrast, calcium/phospholipid-dependent and calcium/calmodulin-dependent protein phosphorylation systems were less prominent in human postmortem brain than in rodent brain, and only a few widely distributed substrates for these protein kinases were found. Protein staining indicated that postmortem proteolysis, particularly of high-molecular-mass proteins, was prominent in deeply located, subcortical regions in the human brain. Our results indicate that it is feasible to use human postmortem brain samples, when obtained under carefully controlled conditions, for qualitative studies on brain protein phosphorylation. Such studies should be of value in studies on human neurological and/or psychiatric disorders

Prediction of three-dimensional arm trajectories based on ECoG signals recorded from human sensorimotor cortex.

Directory of Open Access Journals (Sweden)

Yasuhiko Nakanishi

Full Text Available Brain-machine interface techniques have been applied in a number of studies to control neuromotor prostheses and for neurorehabilitation in the hopes of providing a means to restore lost motor function. Electrocorticography (ECoG has seen recent use in this regard because it offers a higher spatiotemporal resolution than non-invasive EEG and is less invasive than intracortical microelectrodes. Although several studies have already succeeded in the inference of computer cursor trajectories and finger flexions using human ECoG signals, precise three-dimensional (3D trajectory reconstruction for a human limb from ECoG has not yet been achieved. In this study, we predicted 3D arm trajectories in time series from ECoG signals in humans using a novel preprocessing method and a sparse linear regression. Average Pearson's correlation coefficients and normalized root-mean-square errors between predicted and actual trajectories were 0.44~0.73 and 0.18~0.42, respectively, confirming the feasibility of predicting 3D arm trajectories from ECoG. We foresee this method contributing to future advancements in neuroprosthesis and neurorehabilitation technology.

Variation of gunshot injury patterns in mortality associated with human rights abuses and armed conflict: an exploratory study.

Science.gov (United States)

Baraybar, Jose Pablo

2015-09-01

The analysis of the distribution of gunshot injuries in a sample of 777 sets of human remains of proven human rights abuse from Somaliland, the Balkans and Peru is compared to frequencies of injuries sustained by combatants in contemporary conflicts reported in the literature. Principal Component Analysis (PCA) reduced the data to three components accounting for 82.94% of the variance. The first component with 38.31% of variance shows segments Arms and thorax/abdomen to be positively correlated (0.887 and 0.662, respectively); the segment head/neck is strongly correlated (0.951) to the second component while the segment thorax/abdomen shows a low, negative correlation (-0.388). Finally in the third component only the legs are strongly correlated (0.991). Data was further subjected to a K-means cluster analysis to determine the likely groupings combining the four types of injuries. Each of the three clusters reproduced similar patterns observed in the PCA: Cluster 1 shows the prevalence of injuries to the thorax/abdomen and extremities in addition to injuries to the head/neck; Cluster 2 shows injuries to the head/neck and Cluster 3 injuries to the thorax/abdomen and a lower representation of the arms and legs. Most of the cases (70.5%), irrespective of geography and type of site (attack or detention), were grouped into Cluster 2. Such comparison shows that in human rights abuse, irrespective of their geography, gunshot injuries tend to follow a pattern favouring the head/neck and thorax/abdomen areas over the extremities, the reverse pattern observed in contemporary combat operations. In those settings gunshot wound trauma is the second cause of mortality/morbidity (after fragmenting ammunition) and its distribution concentrates on the extremities, thorax/abdomen and head; following the pattern of protective armour when it is used. Considering that human rights abuses are often presented as encounters between two armed groups in the context of counter

Establishment of one-axis vibration test system for measurement of biodynamic response of human hand-arm system.

Science.gov (United States)

Shibata, Nobuyuki; Hosoya, Naoki; Maeda, Setsuo

2008-12-01

Prolonged exposure to hand-arm vibration (HAV) due to use of hand-held power tools leads to an increased occurrence of symptoms of disorders in the vascular, neurological, and osteo-articular systems of the upper limbs called hand-arm vibration syndrome (HAVS). Biodynamic responses of the hand-arm system to vibration can be suggestive parameters that give us better assessment of exposure to HAV and fundamental data for design of low-vibration-exposure power tools. Recently, a single axis hand-arm vibration system has been installed in the Japan National Institute of Occupational Safety and Health (NIOSH). The aims of this study were to obtain the fundamental dynamic characteristics of an instrumented handle and to validate the performance and measurement accuracy of the system applied to dynamic response measurement. A pseudo-random vibration signal with a frequency range of 5-1,250 Hz and a power spectrum density of 1.0 (m/s2)2/Hz was used in this study. First the dynamic response of the instrumented handle without any weight was measured. After this measurement, the dynamic response measurement of the handle with weights mounted on the handle was performed. The apparent mass of a weight itself was obtained by using the mass cancellation method. The mass of the measuring cap on the instrumented handle was well compensated by using the mass cancellation method. Based on the 10% error tolerance, this handle can reliably measure the dynamic response represented by an apparent mass with a minimum weight of 2.0 g in a frequency range of 10.0 to 1,000 Hz. A marked increase in the AM magnitude of the weights of 15 g and 20 g in frequency ranges greater than 800 Hz is attributed not to the fundamental resonance frequency of the handle with weights, but to the fixation of the weight to the measuring cap. In this aspect, the peak of the AM magnitude can be reduced and hence should not be an obstacle to the biodynamic response measurement of the human hand-arm system. On the

Navigating to new frontiers in behavioral neuroscience: Traditional neuropsychological tests predict human performance on a rodent-inspired radial-arm maze

Directory of Open Access Journals (Sweden)

Sarah E. Mennenga

2014-09-01

Full Text Available We constructed an 11-arm, walk-through, human radial-arm maze (HRAM as a translational instrument to compare existing methodology in the areas of rodent and human learning and memory research. The HRAM, utilized here, serves as an intermediary test between the classic rat radial-arm maze (RAM and standard human neuropsychological and cognitive tests. We show that the HRAM is a useful instrument to examine working memory ability, explore the relationships between rodent and human memory and cognition models, and evaluate factors that contribute to human navigational ability. One-hundred-and-fifty-seven participants were tested on the HRAM, and scores were compared to performance on a standard cognitive battery focused on episodic memory, working memory capacity, and visuospatial ability. We found that errors on the HRAM increased as working memory demand became elevated, similar to the pattern typically seen in rodents, and that for this task, performance appears similar to Miller’s classic description of human working memory capacity of 7±2 items. Regression analysis revealed that measures of working memory capacity and visuospatial ability accounted for a large proportion of variance in HRAM scores, while measures of episodic memory and general intelligence did not serve as significant predictors of HRAM performance. We present the HRAM as a novel instrument for measuring navigational behavior in humans, as is traditionally done in basic science studies evaluating rodent learning and memory, thus providing a useful tool to help connect and translate between human and rodent models of cognitive functioning.

Induction of anchorage-independent growth of human embryonic fibroblasts with a deletion in the short arm of chromosome 11 by human papillomavirus type 16 DNA

International Nuclear Information System (INIS)

Smits, H.L.; Raadsheer, E.; Rood, I.; Mehendale, S.; Slater, R.M.; van der Noordaa, J.; Ter Schegget, J.

1988-01-01

Human embryonic fibroblasts with a large deletion (11p11.11p15.1) in the short arm of one chromosome 11 (del-11 cells) appeared to be susceptible to transformation by early human papillomavirus type 16 (HPV-16) DNA, whereas diploid human embryonic fibroblasts were not. This difference in susceptibility might be explained by the absence of a tumor suppressor gene located within the deleted part on the short arm of chromosome 11. The presence of abundant viral early-gene transcripts in transformed cells suggests that transformation was induced by an elevated level of an HPV-16 early-gene product(s). The low transcriptional activity of HPV-16 in diploid cells may indicate that cellular genes affect viral transcription. Interruption of the HPV-16 E2 early open reading frame is probably required for high-level HPV-16 early-gene expression driven from the homologous enhancer-promoter region

Robots testing robots: ALAN-Arm, a humanoid arm for the testing of robotic rehabilitation systems.

Science.gov (United States)

Brookes, Jack; Kuznecovs, Maksims; Kanakis, Menelaos; Grigals, Arturs; Narvidas, Mazvydas; Gallagher, Justin; Levesley, Martin

2017-07-01

Robotics is increasing in popularity as a method of providing rich, personalized and cost-effective physiotherapy to individuals with some degree of upper limb paralysis, such as those who have suffered a stroke. These robotic rehabilitation systems are often high powered, and exoskeletal systems can attach to the person in a restrictive manner. Therefore, ensuring the mechanical safety of these devices before they come in contact with individuals is a priority. Additionally, rehabilitation systems may use novel sensor systems to measure current arm position. Used to capture and assess patient movements, these first need to be verified for accuracy by an external system. We present the ALAN-Arm, a humanoid robotic arm designed to be used for both accuracy benchmarking and safety testing of robotic rehabilitation systems. The system can be attached to a rehabilitation device and then replay generated or human movement trajectories, as well as autonomously play rehabilitation games or activities. Tests of the ALAN-Arm indicated it could recreate the path of a generated slow movement path with a maximum error of 14.2mm (mean = 5.8mm) and perform cyclic movements up to 0.6Hz with low gain (<1.5dB). Replaying human data trajectories showed the ability to largely preserve human movement characteristics with slightly higher path length and lower normalised jerk.

Early superoxide dismutase alterations during SV40-transformation of human fibroblasts.

Science.gov (United States)

Bravard, A; Hoffschir, F; Sabatier, L; Ricoul, M; Pinton, A; Cassingena, R; Estrade, S; Luccioni, C; Dutrillaux, B

1992-11-11

The expression of superoxide dismutases (SOD) 1 and 2 was studied in 4 clones of human fibroblasts after their infection by simian virus 40 (SV40), in parallel with the alterations of chromosomes 21 and chromosome 6q arms, carrying the genes that encode for SOD1 and SOD2 respectively. For all clones, a similar scheme with 2 main phases was observed for both chromosome and SOD variations. The first phase, defined as the pre-crisis phase, was characterized by chromosomal instability, but maintenance of normal numbers of chromosome 6q arms and chromosomes 21. The level of SOD2 mRNA was high, while SOD2 activity and immunoreactive protein were low. SOD1 protein and activity were decreased. In the second phase, defined as the post-crisis phase, the accumulation of clonal chromosomal rearrangements led to the loss of 6q arms, while the number of chromosomes 21 remained normal. SOD2 mRNA level was decreased and SOD2 immunoreactive protein and activity remained low. SOD1 protein and activity increased with passages, reaching values similar to those of control cells at late passages. As in established SV40-transformed human fibroblast cell lines, good correlation was found between SOD2 activity and the relative number of 6q arms. These results allow us to reconstruct the sequence of events leading to the decrease of SOD2, a possible tumor-suppressor gene, during the process of SV40-transformation of human fibroblasts.

Multi-muscle FES force control of the human arm for arbitrary goals.

Science.gov (United States)

Schearer, Eric M; Liao, Yu-Wei; Perreault, Eric J; Tresch, Matthew C; Memberg, William D; Kirsch, Robert F; Lynch, Kevin M

2014-05-01

We present a method for controlling a neuroprosthesis for a paralyzed human arm using functional electrical stimulation (FES) and characterize the errors of the controller. The subject has surgically implanted electrodes for stimulating muscles in her shoulder and arm. Using input/output data, a model mapping muscle stimulations to isometric endpoint forces measured at the subject's hand was identified. We inverted the model of this redundant and coupled multiple-input multiple-output system by minimizing muscle activations and used this inverse for feedforward control. The magnitude of the total root mean square error over a grid in the volume of achievable isometric endpoint force targets was 11% of the total range of achievable forces. Major sources of error were random error due to trial-to-trial variability and model bias due to nonstationary system properties. Because the muscles working collectively are the actuators of the skeletal system, the quantification of errors in force control guides designs of motion controllers for multi-joint, multi-muscle FES systems that can achieve arbitrary goals.

Recent advances in biodynamics of human hand-arm system.

Science.gov (United States)

Dong, Ren G; Wu, John Z; Welcome, Daniel E

2005-07-01

The biodynamics of human hand-arm system is one of the most important foundations for the measurement, evaluation, and risk assessment of hand-transmitted vibration (HTV) exposure. This paper presents a new conceptual model relating factors influencing cause-effect relationships for HTV exposure, a new study strategy, and a comprehensive review of the recent advances in the biodynamics closely associated with HTV exposure. The review covers the following five aspects: theoretical modeling of biodynamic responses, vibration transmissibility, driving-point biodynamic responses, evaluation of anti-vibration gloves, and applied forces. This review finds that some significant advances in each of these aspects have been achieved in the recent years. Several important issues and problems in the biodynamic measurement have been identified and resolved, which has significantly helped improve the reliability and accuracy of the experimental data. The results reported in recent years suggest that, from the point of view of biodynamics, the frequency weighting specified in ISO 5349-1 (2001) overestimates the low frequency effect but underestimates the high frequency effect on the fingers and hand. The major problems, issues, and topics for further studies are also outlined in this paper. It is anticipated that the further studies of the biodynamics of the system will eventually lead to establishment of a robust vibration exposure theory. Although this review focuses on the biodynamics of the hand-arm system, the fundamental concepts and some methodologies reviewed in this paper may also be applicable for the study of whole-body vibration exposure.

Visual Display of 5p-arm and 3p-arm miRNA Expression with a Mobile Application.

Science.gov (United States)

Pan, Chao-Yu; Kuo, Wei-Ting; Chiu, Chien-Yuan; Lin, Wen-Chang

2017-01-01

MicroRNAs (miRNAs) play important roles in human cancers. In previous studies, we have demonstrated that both 5p-arm and 3p-arm of mature miRNAs could be expressed from the same precursor and we further interrogated the 5p-arm and 3p-arm miRNA expression with a comprehensive arm feature annotation list. To assist biologists to visualize the differential 5p-arm and 3p-arm miRNA expression patterns, we utilized a user-friendly mobile App to display. The Cancer Genome Atlas (TCGA) miRNA-Seq expression information. We have collected over 4,500 miRNA-Seq datasets from 15 TCGA cancer types and further processed them with the 5p-arm and 3p-arm annotation analysis pipeline. In order to be displayed with the RNA-Seq Viewer App, annotated 5p-arm and 3p-arm miRNA expression information and miRNA gene loci information were converted into SQLite tables. In this distinct application, for any given miRNA gene, 5p-arm miRNA is illustrated on the top of chromosome ideogram and 3p-arm miRNA is illustrated on the bottom of chromosome ideogram. Users can then easily interrogate the differentially 5p-arm/3p-arm expressed miRNAs with their mobile devices. This study demonstrates the feasibility and utility of RNA-Seq Viewer App in addition to mRNA-Seq data visualization.

Visual Display of 5p-arm and 3p-arm miRNA Expression with a Mobile Application

Directory of Open Access Journals (Sweden)

Chao-Yu Pan

2017-01-01

Full Text Available MicroRNAs (miRNAs play important roles in human cancers. In previous studies, we have demonstrated that both 5p-arm and 3p-arm of mature miRNAs could be expressed from the same precursor and we further interrogated the 5p-arm and 3p-arm miRNA expression with a comprehensive arm feature annotation list. To assist biologists to visualize the differential 5p-arm and 3p-arm miRNA expression patterns, we utilized a user-friendly mobile App to display. The Cancer Genome Atlas (TCGA miRNA-Seq expression information. We have collected over 4,500 miRNA-Seq datasets from 15 TCGA cancer types and further processed them with the 5p-arm and 3p-arm annotation analysis pipeline. In order to be displayed with the RNA-Seq Viewer App, annotated 5p-arm and 3p-arm miRNA expression information and miRNA gene loci information were converted into SQLite tables. In this distinct application, for any given miRNA gene, 5p-arm miRNA is illustrated on the top of chromosome ideogram and 3p-arm miRNA is illustrated on the bottom of chromosome ideogram. Users can then easily interrogate the differentially 5p-arm/3p-arm expressed miRNAs with their mobile devices. This study demonstrates the feasibility and utility of RNA-Seq Viewer App in addition to mRNA-Seq data visualization.

Kidins220/ARMS as a functional mediator of multiple receptor signalling pathways.

Science.gov (United States)

Neubrand, Veronika E; Cesca, Fabrizia; Benfenati, Fabio; Schiavo, Giampietro

2012-04-15

An increasing body of evidence suggests that several membrane receptors--in addition to activating distinct signalling cascades--also engage in substantial crosstalk with each other, thereby adjusting their signalling outcome as a function of specific input information. However, little is known about the molecular mechanisms that control their coordination and integration of downstream signalling. A protein that is likely to have a role in this process is kinase-D-interacting substrate of 220 kDa [Kidins220, also known as ankyrin repeat-rich membrane spanning (ARMS), hereafter referred to as Kidins220/ARMS]. Kidins220/ARMS is a conserved membrane protein that is preferentially expressed in the nervous system and interacts with the microtubule and actin cytoskeleton. It interacts with neurotrophin, ephrin, vascular endothelial growth factor (VEGF) and glutamate receptors, and is a common downstream target of several trophic stimuli. Kidins220/ARMS is required for neuronal differentiation and survival, and its expression levels modulate synaptic plasticity. Kidins220/ARMS knockout mice show developmental defects mainly in the nervous and cardiovascular systems, suggesting a crucial role for this protein in modulating the cross talk between different signalling pathways. In this Commentary, we summarise existing knowledge regarding the physiological functions of Kidins220/ARMS, and highlight some interesting directions for future studies on the role of this protein in health and disease.

Arm-in-Arm Response Regulator Dimers Promote Intermolecular Signal Transduction

Energy Technology Data Exchange (ETDEWEB)

Baker, Anna W.; Satyshur, Kenneth A.; Morales, Neydis Moreno; Forest, Katrina T. (UW)

2016-02-01

Bacteriophytochrome photoreceptors (BphPs) and their cognate response regulators make up two-component signal transduction systems which direct bacteria to mount phenotypic responses to changes in environmental light quality. Most of these systems utilize single-domain response regulators to transduce signals through unknown pathways and mechanisms. Here we describe the photocycle and autophosphorylation kinetics of RtBphP1, a red light-regulated histidine kinase from the desert bacteriumRamlibacter tataouinensis. RtBphP1 undergoes red to far-red photoconversion with rapid thermal reversion to the dark state. RtBphP1 is autophosphorylated in the dark; this activity is inhibited under red light. The RtBphP1 cognate response regulator, theR. tataouinensisbacteriophytochrome response regulator (RtBRR), and a homolog, AtBRR fromAgrobacterium tumefaciens, crystallize unexpectedly as arm-in-arm dimers, reliant on a conserved hydrophobic motif, hFWAhL (where h is a hydrophobic M, V, L, or I residue). RtBRR and AtBRR dimerize distinctly from four structurally characterized phytochrome response regulators found in photosynthetic organisms and from all other receiver domain homodimers in the Protein Data Bank. A unique cacodylate-zinc-histidine tag metal organic framework yielded single-wavelength anomalous diffraction phases and may be of general interest. Examination of the effect of the BRR stoichiometry on signal transduction showed that phosphorylated RtBRR is accumulated more efficiently than the engineered monomeric RtBRR (RtBRR_mon) in phosphotransfer reactions. Thus, we conclude that arm-in-arm dimers are a relevant signaling intermediate in this class of two-component regulatory systems.

An integrated physical map of 210 markers assigned to the short arm of human chromosome 11

NARCIS (Netherlands)

Redeker, E.; Hoovers, J. M.; Alders, M.; van Moorsel, C. J.; Ivens, A. C.; Gregory, S.; Kalikin, L.; Bliek, J.; de Galan, L.; van den Bogaard, R.; Visser, J.; van der Voort, R.; Feinberg, A. P.; Little, P. F. R.; Westerveld, A.; Mannens, M.

1994-01-01

Using a panel of patient cell lines with chromosomal breakpoints, we constructed a physical map for the short arm of human chromosome 11. We focused on 11p15, a chromosome band harboring at least 25 known genes and associated with the Beckwith-Wiedemann syndrome, several childhood tumors, and

Use it and improve it or lose it: interactions between arm function and use in humans post-stroke.

Directory of Open Access Journals (Sweden)

Yukikazu Hidaka

2012-02-01

Full Text Available "Use it and improve it, or lose it" is one of the axioms of motor therapy after stroke. There is, however, little understanding of the interactions between arm function and use in humans post-stroke. Here, we explored putative non-linear interactions between upper extremity function and use by developing a first-order dynamical model of stroke recovery with longitudinal data from participants receiving constraint induced movement therapy (CIMT in the EXCITE clinical trial. Using a Bayesian regression framework, we systematically compared this model with competitive models that included, or not, interactions between function and use. Model comparisons showed that the model with the predicted interactions between arm function and use was the best fitting model. Furthermore, by comparing the model parameters before and after CIMT intervention in participants receiving the intervention one year after randomization, we found that therapy increased the parameter that controls the effect of arm function on arm use. Increase in this parameter, which can be thought of as the confidence to use the arm for a given level of function, lead to increase in spontaneous use after therapy compared to before therapy.

Sensory-Feedback Exoskeletal Arm Controller

Science.gov (United States)

An, Bin; Massie, Thomas H.; Vayner, Vladimir

2004-01-01

An electromechanical exoskeletal arm apparatus has been designed for use in controlling a remote robotic manipulator arm. The apparatus, called a force-feedback exoskeleton arm master (F-EAM) is comfortable to wear and easy to don and doff. It provides control signals from the wearer s arm to a robot arm or a computer simulator (e.g., a virtual-reality system); it also provides force and torque feedback from sensors on the robot arm or from the computer simulator to the wearer s arm. The F-EAM enables the wearer to make the robot arm gently touch objects and finely manipulate them without exerting excessive forces. The F-EAM features a lightweight design in which the motors and gear heads that generate force and torque feedback are made smaller than they ordinarily would be: this is achieved by driving the motors to power levels greater than would ordinarily be used in order to obtain higher torques, and by providing active liquid cooling of the motors to prevent overheating at the high drive levels. The F-EAM (see figure) includes an assembly that resembles a backpack and is worn like a backpack, plus an exoskeletal arm mechanism. The FEAM has five degrees of freedom (DOFs) that correspond to those of the human arm: 1. The first DOF is that of the side-to-side rotation of the upper arm about the shoulder (rotation about axis 1). The reflected torque for this DOF is provided by motor 1 via drum 1 and a planar four-bar linkage. 2. The second DOF is that of the up-and-down rotation of the arm about the shoulder. The reflected torque for this DOF is provided by motor 2 via drum 2. 3. The third DOF is that of twisting of the upper arm about its longitudinal axis. This DOF is implemented in a cable remote-center mechanism (CRCM). The reflected torque for this DOF is provided by motor 3, which drives the upper-arm cuff and the mechanism below it. A bladder inflatable by gas or liquid is placed between the cuff and the wearer s upper arm to compensate for misalignment

Kinematic feedback control laws for generating natural arm movements

International Nuclear Information System (INIS)

Kim, Donghyun; Jang, Cheongjae; Park, Frank C

2014-01-01

We propose a stochastic optimal feedback control law for generating natural robot arm motions. Our approach, inspired by the minimum variance principle of Harris and Wolpert (1998 Nature 394 780–4) and the optimal feedback control principles put forth by Todorov and Jordan (2002 Nature Neurosci. 5 1226–35) for explaining human movements, differs in two crucial respects: (i) the endpoint variance is minimized in joint space rather than Cartesian hand space, and (ii) we ignore the dynamics and instead consider only the second-order differential kinematics. The feedback control law generating the motions can be straightforwardly obtained by backward integration of a set of ordinary differential equations; these equations are obtained exactly, without any linear–quadratic approximations. The only parameters to be determined a priori are the variance scale factors, and for both the two-DOF planar arm and the seven-DOF spatial arm, a table of values is constructed based on the given initial and final arm configurations; these values are determined via an optimal fitting procedure, and consistent with existing findings about neuromuscular motor noise levels of human arm muscles. Experiments conducted with a two-link planar arm and a seven-DOF spatial arm verify that the trajectories generated by our feedback control law closely resemble human arm motions, in the sense of producing nearly straight-line hand trajectories, having bell-shaped velocity profiles, and satisfying Fitts Law. (paper)

Human Cementum Protein 1 induces expression of bone and cementum proteins by human gingival fibroblasts

International Nuclear Information System (INIS)

Carmona-Rodriguez, Bruno; Alvarez-Perez, Marco Antonio; Narayanan, A. Sampath; Zeichner-David, Margarita; Reyes-Gasga, Jose; Molina-Guarneros, Juan; Garcia-Hernandez, Ana Lilia; Suarez-Franco, Jose Luis; Chavarria, Ivet Gil; Villarreal-Ramirez, Eduardo; Arzate, Higinio

2007-01-01

We recently presented evidence showing that a human cementoblastoma-derived protein, named Cementum Protein 1 (CEMP1) may play a role as a local regulator of cementoblast differentiation and cementum-matrix mineralization. This protein was shown to be expressed by cementoblasts and progenitor cells localized in the periodontal ligament. In this study we demonstrate that transfection of CEMP1 into human gingival fibroblasts (HGF) induces mineralization and expression of bone and cementum-matrix proteins. The transfected HGF cells had higher alkaline phosphatase activity and proliferation rate and they expressed genes for alkaline phosphatase, bone sialoprotein, osteocalcin, osteopontin, the transcription factor Runx2/Cbfa1, and cementum attachment protein (CAP). They also produced biological-type hydroxyapatite. These findings indicate that the CEMP1 might participate in differentiation and mineralization of nonosteogenic cells, and that it might have a potential function in cementum and bone formation

Phosphorylation of human link proteins

International Nuclear Information System (INIS)

Oester, D.A.; Caterson, B.; Schwartz, E.R.

1986-01-01

Three link proteins of 48, 44 and 40 kDa were purified from human articular cartilage and identified with monoclonal anti-link protein antibody 8-A-4. Two sets of lower molecular weight proteins of 30-31 kDa and 24-26 kDa also contained link protein epitopes recognized by the monoclonal antibody and were most likely degradative products of the intact link proteins. The link proteins of 48 and 40 kDa were identified as phosphoproteins while the 44 kDa link protein did not contain 32 P. The phosphorylated 48 and 40 kDa link proteins contained approximately 2 moles PO 4 /mole link protein

A human protein interaction network shows conservation of aging processes between human and invertebrate species.

Directory of Open Access Journals (Sweden)

Russell Bell

2009-03-01

Full Text Available We have mapped a protein interaction network of human homologs of proteins that modify longevity in invertebrate species. This network is derived from a proteome-scale human protein interaction Core Network generated through unbiased high-throughput yeast two-hybrid searches. The longevity network is composed of 175 human homologs of proteins known to confer increased longevity through loss of function in yeast, nematode, or fly, and 2,163 additional human proteins that interact with these homologs. Overall, the network consists of 3,271 binary interactions among 2,338 unique proteins. A comparison of the average node degree of the human longevity homologs with random sets of proteins in the Core Network indicates that human homologs of longevity proteins are highly connected hubs with a mean node degree of 18.8 partners. Shortest path length analysis shows that proteins in this network are significantly more connected than would be expected by chance. To examine the relationship of this network to human aging phenotypes, we compared the genes encoding longevity network proteins to genes known to be changed transcriptionally during aging in human muscle. In the case of both the longevity protein homologs and their interactors, we observed enrichments for differentially expressed genes in the network. To determine whether homologs of human longevity interacting proteins can modulate life span in invertebrates, homologs of 18 human FRAP1 interacting proteins showing significant changes in human aging muscle were tested for effects on nematode life span using RNAi. Of 18 genes tested, 33% extended life span when knocked-down in Caenorhabditis elegans. These observations indicate that a broad class of longevity genes identified in invertebrate models of aging have relevance to human aging. They also indicate that the longevity protein interaction network presented here is enriched for novel conserved longevity proteins.

A human-specific de novo protein-coding gene associated with human brain functions.

Directory of Open Access Journals (Sweden)

Chuan-Yun Li

2010-03-01

Full Text Available To understand whether any human-specific new genes may be associated with human brain functions, we computationally screened the genetic vulnerable factors identified through Genome-Wide Association Studies and linkage analyses of nicotine addiction and found one human-specific de novo protein-coding gene, FLJ33706 (alternative gene symbol C20orf203. Cross-species analysis revealed interesting evolutionary paths of how this gene had originated from noncoding DNA sequences: insertion of repeat elements especially Alu contributed to the formation of the first coding exon and six standard splice junctions on the branch leading to humans and chimpanzees, and two subsequent substitutions in the human lineage escaped two stop codons and created an open reading frame of 194 amino acids. We experimentally verified FLJ33706's mRNA and protein expression in the brain. Real-Time PCR in multiple tissues demonstrated that FLJ33706 was most abundantly expressed in brain. Human polymorphism data suggested that FLJ33706 encodes a protein under purifying selection. A specifically designed antibody detected its protein expression across human cortex, cerebellum and midbrain. Immunohistochemistry study in normal human brain cortex revealed the localization of FLJ33706 protein in neurons. Elevated expressions of FLJ33706 were detected in Alzheimer's brain samples, suggesting the role of this novel gene in human-specific pathogenesis of Alzheimer's disease. FLJ33706 provided the strongest evidence so far that human-specific de novo genes can have protein-coding potential and differential protein expression, and be involved in human brain functions.

Human-specific protein isoforms produced by novel splice sites in the human genome after the human-chimpanzee divergence

Directory of Open Access Journals (Sweden)

Kim Dong Seon

2012-11-01

Full Text Available Abstract Background Evolution of splice sites is a well-known phenomenon that results in transcript diversity during human evolution. Many novel splice sites are derived from repetitive elements and may not contribute to protein products. Here, we analyzed annotated human protein-coding exons and identified human-specific splice sites that arose after the human-chimpanzee divergence. Results We analyzed multiple alignments of the annotated human protein-coding exons and their respective orthologous mammalian genome sequences to identify 85 novel splice sites (50 splice acceptors and 35 donors in the human genome. The novel protein-coding exons, which are expressed either constitutively or alternatively, produce novel protein isoforms by insertion, deletion, or frameshift. We found three cases in which the human-specific isoform conferred novel molecular function in the human cells: the human-specific IMUP protein isoform induces apoptosis of the trophoblast and is implicated in pre-eclampsia; the intronization of a part of SMOX gene exon produces inactive spermine oxidase; the human-specific NUB1 isoform shows reduced interaction with ubiquitin-like proteins, possibly affecting ubiquitin pathways. Conclusions Although the generation of novel protein isoforms does not equate to adaptive evolution, we propose that these cases are useful candidates for a molecular functional study to identify proteomic changes that might bring about novel phenotypes during human evolution.

Protein leverage effects of beef protein on energy intake in humans.

Science.gov (United States)

Martens, Eveline A; Tan, Sze-Yen; Dunlop, Mandy V; Mattes, Richard D; Westerterp-Plantenga, Margriet S

2014-06-01

The protein leverage hypothesis requires specific evidence that protein intake is regulated more strongly than energy intake. The objective was to determine ad libitum energy intake, body weight changes, appetite profile, and nitrogen balance in response to 3 diets with different protein-to-carbohydrate + fat ratios over 12 consecutive days, with beef as a source of protein. A 3-arm, 12-d randomized crossover study was performed in 30 men and 28 women [mean ± SD age: 33 ± 16 y; body mass index (in kg/m²): 24.4 ± 4.0] with the use of diets containing 5%, 15%, and 30% of energy (En%) from protein, predominantly from beef. Energy intake was significantly lower in the 30En%-protein condition (8.73 ± 1.93 MJ/d) than in the 5En%-protein (9.48 ± 1.67 MJ/d) and 15En%-protein (9.30 ± 1.62 MJ/d) conditions (P = 0.001), stemming largely from lower energy intake during meals (P = 0.001). Hunger (P = 0.001) and desire to eat (P = 0.001) ratings were higher and fullness ratings were lower (P = 0.001) in the 5En%-protein condition than in the 15En%-protein and 30En%-protein conditions. Nitrogen excretion was lower in the 5En%-protein condition (4.7 ± 1.5 g/24 h; P = 0.001) and was higher in the 30En%-protein condition (15.3 ± 8.7 g/24 h; P = 0.001) compared with the 15En%-protein condition (10.0 ± 5.2 g/24 h). Nitrogen balance was maintained in the 5En%-protein condition and was positive in the 15En%- and 30En%-protein conditions (P = 0.001). Complete protein leverage did not occur because subjects did not consume to a common protein amount at the expense of energy balance. Individuals did underconsume relative to energy requirements from high-protein diets. The lack of support for protein leverage effects on a low-protein diet may stem from the fact that protein intake was sufficient to maintain nitrogen balance over the 12-d trial. © 2014 American Society for Nutrition.

Nuclear pore complex protein mediated nuclear localization of dicer protein in human cells.

Directory of Open Access Journals (Sweden)

Yoshinari Ando

Full Text Available Human DICER1 protein cleaves double-stranded RNA into small sizes, a crucial step in production of single-stranded RNAs which are mediating factors of cytoplasmic RNA interference. Here, we clearly demonstrate that human DICER1 protein localizes not only to the cytoplasm but also to the nucleoplasm. We also find that human DICER1 protein associates with the NUP153 protein, one component of the nuclear pore complex. This association is detected predominantly in the cytoplasm but is also clearly distinguishable at the nuclear periphery. Additional characterization of the NUP153-DICER1 association suggests NUP153 plays a crucial role in the nuclear localization of the DICER1 protein.

Dynamics of Inter-heavy Chain Interactions in Human Immunoglobulin G (IgG) Subclasses Studied by Kinetic Fab Arm Exchange

NARCIS (Netherlands)

Rispens, Theo; Davies, Anna M.; Ooijevaar-de Heer, Pleuni; Absalah, Samira; Bende, Onno; Sutton, Brian J.; Vidarsson, Gestur; Aalberse, Rob C.

2014-01-01

Background: Fab arm exchange requires weak interactions between CH3 domains, such as in human IgG4. Results: CH3-CH3 interactions differ >1,000,000-fold between human subclasses and allotypes due to variations Lys/Asn-392, Val/Met-397, and Lys/Arg-409. Conclusion: For IgG2 and IgG3, but not IgG1,

Shedding lights on the flexible-armed porphyrins: Human telomeric G4 DNA interaction and cell photocytotoxicity research.

Science.gov (United States)

Sun, Xiang-Yu; Zhao, Ping; Jin, Shu-Fang; Liu, Min-Chao; Wang, Xia-Hong; Huang, Yu-Min; Cheng, Zhen-Feng; Yan, Si-Qi; Li, Yan-Yu; Chen, Ya-Qing; Zhong, Yan-Mei

2017-08-01

DNA polymorphism exerts a fascination on a large scientific community. Without crystallographic structural data, clarification of the binding modes between G-quadruplex (G4) and ligand (complex) is a challenging job. In the present work, three porphyrin compounds with different flexible carbon chains (arms) were designed, synthesized and characterized. Their binding, folding and stabilizing abilities to human telomeric G4 DNA structures were comparatively researched. Positive charges at the end of the flexible carbon chains seem to be favorable for the DNA-porphyrin interactions, which were evidenced by the spectral results and further confirmed by the molecular docking calculations. Biological function analysis demonstrated that these porphyrins show no substantial inhibition to Hela, A549 and BEL 7402 cancer cell lines under dark while exhibit broad inhibition under visible light. This significantly enhanced photocytotoxicity relative to the dark control is an essential property of photochemotherapeutic agents. The feature of the flexible arms emerges as critical influencing factors in the cell photocytotoxicity. Moreover, an ROS-mediated mitochondrial dysfunction pathway was suggested for the cell apoptosis induced by these flexible-armed porphyrins. It is found that the porphyrins with positive charges located at the end of the flexible arms represent an exciting opportunity for photochemotherapeutic anti-cancer drug design. Copyright © 2017. Published by Elsevier B.V.

Using Human Gestures and Generic Skills to Instruct a Mobile Robot Arm in a Feeder Filling Scenario

DEFF Research Database (Denmark)

Pedersen, Mikkel Rath; Høilund, Carsten; Krüger, Volker

2012-01-01

Mobile robots that have the ability to cooperate with humans are able to provide new possibilities to manufac- turing industries. In this paper, we discuss our mobile robot arm that a) can provide assistance at different locations in a factory and b) that can be programmed using complex human...... actions such as pointing in Take this object. In this paper, we discuss the use of the mobile robot for a feeding scenario where a human operator specifies the parts and the feeders through pointing gestures. The system is partially built using generic robotic skills. Through extensive experiments, we...

Human-Like Behavior of Robot Arms: General Considerations and the Handwriting Task-Part I: Mathematical Description of Human-Like Motion: Distributed Positioning and Virtual Fatigue

NARCIS (Netherlands)

Potkonjak, V.; Tzafestas, S.; Kostic, D.; Djordjevic, G.

2001-01-01

This two-part paper is concerned with the analysis and achievement of human-like behavior by robot arms (manipulators). The analysis involves three issues: (i) the resolution of the inverse kinematics problem of redundant robots, (ii) the separation of the end-effector's motion into two components,

Kinematics analysis on hinges of robot arm gripper for harmful chemical handling

Science.gov (United States)

Razali, Zol Bahri; Kader, Mohamed Mydin M. Abdul; Mustafa, Nurul Fahimah; Daud, Mohd Hisam

2017-09-01

The development of manufacturing industry is booming the application of industrial robot, and proportional to the use of robot arm. Some of the purpose of robot arm gripper is to sort things and place to the proper place. And some of the things are harmful to human, such as harmful chemical. By using robot arm to do picking and placing, it is expected to replace human tasks, as well as to reduce human from the harmful job. The problem of the robot arm gripper, most likely the problem of hinge, thus the analysis on the hinges of robot arm gripper to prevent claw is essential. By using robot arm, instead of human, is labored to do the harmful tasks and unexpected accident happen, costs and expenses in handling injured employee due to the harmful chemicals can be minimized. Thus the objective of this project is to make a kinematics analysis on the hinges of the robot arm gripper. Suitable material such as steel structure has also been selected for the construction of this hinges. This material has properties associated with compressive strength, fire resistance, corrosion and has a shape that is easy to move. Solid Works and ANSYS software is used to create animated movement on the design model and to detect deficiencies in the hinges. Detail methodology is described in this paper.

The Asteroid Redirect Mission (ARM)

Science.gov (United States)

Abell, Paul; Gates, Michele; Johnson, Lindley; Chodas, Paul; Mazanek, Dan; Reeves, David; Ticker, Ronald

2016-07-01

To achieve its long-term goal of sending humans to Mars, the National Aeronautics and Space Administration (NASA) plans to proceed in a series of incrementally more complex human spaceflight missions. Today, human flight experience extends only to Low-Earth Orbit (LEO), and should problems arise during a mission, the crew can return to Earth in a matter of minutes to hours. The next logical step for human spaceflight is to gain flight experience in the vicinity of the Moon. These cis-lunar missions provide a "proving ground" for the testing of systems and operations while still accommodating an emergency return path to the Earth that would last only several days. Cis-lunar mission experience will be essential for more ambitious human missions beyond the Earth-Moon system, which will require weeks, months, or even years of transit time. In addition, NASA has been given a Grand Challenge to find all asteroid threats to human populations and know what to do about them. Obtaining knowledge of asteroid physical properties combined with performing technology demonstrations for planetary defense provide much needed information to address the issue of future asteroid impacts on Earth. Hence the combined objectives of human exploration and planetary defense give a rationale for the Asteroid Re-direct Mission (ARM). Mission Description: NASA's ARM consists of two mission segments: 1) the Asteroid Redirect Robotic Mission (ARRM), the first robotic mission to visit a large (greater than ~100 m diameter) near-Earth asteroid (NEA), collect a multi-ton boulder from its surface along with regolith samples, demonstrate a planetary defense technique, and return the asteroidal material to a stable orbit around the Moon; and 2) the Asteroid Redirect Crewed Mission (ARCM), in which astronauts will take the Orion capsule to rendezvous and dock with the robotic vehicle, conduct multiple extravehicular activities to explore the boulder, and return to Earth with samples. NASA's proposed

A Physical Interaction Network of Dengue Virus and Human Proteins*

Science.gov (United States)

Khadka, Sudip; Vangeloff, Abbey D.; Zhang, Chaoying; Siddavatam, Prasad; Heaton, Nicholas S.; Wang, Ling; Sengupta, Ranjan; Sahasrabudhe, Sudhir; Randall, Glenn; Gribskov, Michael; Kuhn, Richard J.; Perera, Rushika; LaCount, Douglas J.

2011-01-01

Dengue virus (DENV), an emerging mosquito-transmitted pathogen capable of causing severe disease in humans, interacts with host cell factors to create a more favorable environment for replication. However, few interactions between DENV and human proteins have been reported to date. To identify DENV-human protein interactions, we used high-throughput yeast two-hybrid assays to screen the 10 DENV proteins against a human liver activation domain library. From 45 DNA-binding domain clones containing either full-length viral genes or partially overlapping gene fragments, we identified 139 interactions between DENV and human proteins, the vast majority of which are novel. These interactions involved 105 human proteins, including six previously implicated in DENV infection and 45 linked to the replication of other viruses. Human proteins with functions related to the complement and coagulation cascade, the centrosome, and the cytoskeleton were enriched among the DENV interaction partners. To determine if the cellular proteins were required for DENV infection, we used small interfering RNAs to inhibit their expression. Six of 12 proteins targeted (CALR, DDX3X, ERC1, GOLGA2, TRIP11, and UBE2I) caused a significant decrease in the replication of a DENV replicon. We further showed that calreticulin colocalized with viral dsRNA and with the viral NS3 and NS5 proteins in DENV-infected cells, consistent with a direct role for calreticulin in DENV replication. Human proteins that interacted with DENV had significantly higher average degree and betweenness than expected by chance, which provides additional support for the hypothesis that viruses preferentially target cellular proteins that occupy central position in the human protein interaction network. This study provides a valuable starting point for additional investigations into the roles of human proteins in DENV infection. PMID:21911577

A physical interaction network of dengue virus and human proteins.

Science.gov (United States)

Khadka, Sudip; Vangeloff, Abbey D; Zhang, Chaoying; Siddavatam, Prasad; Heaton, Nicholas S; Wang, Ling; Sengupta, Ranjan; Sahasrabudhe, Sudhir; Randall, Glenn; Gribskov, Michael; Kuhn, Richard J; Perera, Rushika; LaCount, Douglas J

2011-12-01

Dengue virus (DENV), an emerging mosquito-transmitted pathogen capable of causing severe disease in humans, interacts with host cell factors to create a more favorable environment for replication. However, few interactions between DENV and human proteins have been reported to date. To identify DENV-human protein interactions, we used high-throughput yeast two-hybrid assays to screen the 10 DENV proteins against a human liver activation domain library. From 45 DNA-binding domain clones containing either full-length viral genes or partially overlapping gene fragments, we identified 139 interactions between DENV and human proteins, the vast majority of which are novel. These interactions involved 105 human proteins, including six previously implicated in DENV infection and 45 linked to the replication of other viruses. Human proteins with functions related to the complement and coagulation cascade, the centrosome, and the cytoskeleton were enriched among the DENV interaction partners. To determine if the cellular proteins were required for DENV infection, we used small interfering RNAs to inhibit their expression. Six of 12 proteins targeted (CALR, DDX3X, ERC1, GOLGA2, TRIP11, and UBE2I) caused a significant decrease in the replication of a DENV replicon. We further showed that calreticulin colocalized with viral dsRNA and with the viral NS3 and NS5 proteins in DENV-infected cells, consistent with a direct role for calreticulin in DENV replication. Human proteins that interacted with DENV had significantly higher average degree and betweenness than expected by chance, which provides additional support for the hypothesis that viruses preferentially target cellular proteins that occupy central position in the human protein interaction network. This study provides a valuable starting point for additional investigations into the roles of human proteins in DENV infection.

ProNormz--an integrated approach for human proteins and protein kinases normalization.

Science.gov (United States)

Subramani, Suresh; Raja, Kalpana; Natarajan, Jeyakumar

2014-02-01

The task of recognizing and normalizing protein name mentions in biomedical literature is a challenging task and important for text mining applications such as protein-protein interactions, pathway reconstruction and many more. In this paper, we present ProNormz, an integrated approach for human proteins (HPs) tagging and normalization. In Homo sapiens, a greater number of biological processes are regulated by a large human gene family called protein kinases by post translational phosphorylation. Recognition and normalization of human protein kinases (HPKs) is considered to be important for the extraction of the underlying information on its regulatory mechanism from biomedical literature. ProNormz distinguishes HPKs from other HPs besides tagging and normalization. To our knowledge, ProNormz is the first normalization system available to distinguish HPKs from other HPs in addition to gene normalization task. ProNormz incorporates a specialized synonyms dictionary for human proteins and protein kinases, a set of 15 string matching rules and a disambiguation module to achieve the normalization. Experimental results on benchmark BioCreative II training and test datasets show that our integrated approach achieve a fairly good performance and outperforms more sophisticated semantic similarity and disambiguation systems presented in BioCreative II GN task. As a freely available web tool, ProNormz is useful to developers as extensible gene normalization implementation, to researchers as a standard for comparing their innovative techniques, and to biologists for normalization and categorization of HPs and HPKs mentions in biomedical literature. URL: http://www.biominingbu.org/pronormz. Copyright © 2013 Elsevier Inc. All rights reserved.

Dataset of protein species from human liver

Directory of Open Access Journals (Sweden)

Stanislav Naryzhny

2017-06-01

Full Text Available This article contains data related to the research article entitled “Zipf׳s law in proteomics” (Naryzhny et al., 2017 [1]. The protein composition in the human liver or hepatocarcinoma (HepG2 cells extracts was estimated using a filter-aided sample preparation (FASP protocol. The protein species/proteoform composition in the human liver was determined by two-dimensional electrophoresis (2-DE followed by Electrospray Ionization Liquid Chromatography-Tandem Mass Spectrometry (ESI LC-MS/MS. In the case of two-dimensional electrophoresis (2-DE, the gel was stained with Coomassie Brilliant Blue R350, and image analysis was performed with ImageMaster 2D Platinum software (GE Healthcare. The 96 sections in the 2D gel were selected and cut for subsequent ESI LC-MS/MS and protein identification. If the same protein was detected in different sections, it was considered to exist as different protein species/proteoforms. A list of human liver proteoforms detected in this way is presented.

Human cancer protein-protein interaction network: a structural perspective.

Directory of Open Access Journals (Sweden)

Gozde Kar

2009-12-01

Full Text Available Protein-protein interaction networks provide a global picture of cellular function and biological processes. Some proteins act as hub proteins, highly connected to others, whereas some others have few interactions. The dysfunction of some interactions causes many diseases, including cancer. Proteins interact through their interfaces. Therefore, studying the interface properties of cancer-related proteins will help explain their role in the interaction networks. Similar or overlapping binding sites should be used repeatedly in single interface hub proteins, making them promiscuous. Alternatively, multi-interface hub proteins make use of several distinct binding sites to bind to different partners. We propose a methodology to integrate protein interfaces into cancer interaction networks (ciSPIN, cancer structural protein interface network. The interactions in the human protein interaction network are replaced by interfaces, coming from either known or predicted complexes. We provide a detailed analysis of cancer related human protein-protein interfaces and the topological properties of the cancer network. The results reveal that cancer-related proteins have smaller, more planar, more charged and less hydrophobic binding sites than non-cancer proteins, which may indicate low affinity and high specificity of the cancer-related interactions. We also classified the genes in ciSPIN according to phenotypes. Within phenotypes, for breast cancer, colorectal cancer and leukemia, interface properties were found to be discriminating from non-cancer interfaces with an accuracy of 71%, 67%, 61%, respectively. In addition, cancer-related proteins tend to interact with their partners through distinct interfaces, corresponding mostly to multi-interface hubs, which comprise 56% of cancer-related proteins, and constituting the nodes with higher essentiality in the network (76%. We illustrate the interface related affinity properties of two cancer-related hub

Identification of Interferon-Stimulated Gene Proteins That Inhibit Human Parainfluenza Virus Type 3.

Science.gov (United States)

Rabbani, M A G; Ribaudo, Michael; Guo, Ju-Tao; Barik, Sailen

2016-12-15

A major arm of cellular innate immunity is type I interferon (IFN), represented by IFN-α and IFN-β. Type I IFN transcriptionally induces a large number of cellular genes, collectively known as IFN-stimulated gene (ISG) proteins, which act as antivirals. The IFIT (interferon-induced proteins with tetratricopeptide repeats) family proteins constitute a major subclass of ISG proteins and are characterized by multiple tetratricopeptide repeats (TPRs). In this study, we have interrogated IFIT proteins for the ability to inhibit the growth of human parainfluenza virus type 3 (PIV3), a nonsegmented negative-strand RNA virus of the Paramyxoviridae family and a major cause of respiratory disease in children. We found that IFIT1 significantly inhibited PIV3, whereas IFIT2, IFIT3, and IFIT5 were less effective or not at all. In further screening a set of ISG proteins we discovered that several other such proteins also inhibited PIV3, including IFITM1, IDO (indoleamine 2,3-dioxygenase), PKR (protein kinase, RNA activated), and viperin (virus inhibitory protein, endoplasmic reticulum associated, interferon inducible)/Cig5. The antiviral effect of IDO, the enzyme that catalyzes the first step of tryptophan degradation, could be counteracted by tryptophan. These results advance our knowledge of diverse ISG proteins functioning as antivirals and may provide novel approaches against PIV3. The innate immunity of the host, typified by interferon (IFN), is a major antiviral defense. IFN inhibits virus growth by inducing a large number of IFN-stimulated gene (ISG) proteins, several of which have been shown to have specific antiviral functions. Parainfluenza virus type 3 (PIV3) is major pathogen of children, and no reliable vaccine or specific antiviral against it currently exists. In this article, we report several ISG proteins that strongly inhibit PIV3 growth, the use of which may allow a better antiviral regimen targeting PIV3. Copyright © 2016, American Society for Microbiology

Prediction of protein-protein interactions between viruses and human by an SVM model

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Cui Guangyu

2012-05-01

Full Text Available Abstract Background Several computational methods have been developed to predict protein-protein interactions from amino acid sequences, but most of those methods are intended for the interactions within a species rather than for interactions across different species. Methods for predicting interactions between homogeneous proteins are not appropriate for finding those between heterogeneous proteins since they do not distinguish the interactions between proteins of the same species from those of different species. Results We developed a new method for representing a protein sequence of variable length in a frequency vector of fixed length, which encodes the relative frequency of three consecutive amino acids of a sequence. We built a support vector machine (SVM model to predict human proteins that interact with virus proteins. In two types of viruses, human papillomaviruses (HPV and hepatitis C virus (HCV, our SVM model achieved an average accuracy above 80%, which is higher than that of another SVM model with a different representation scheme. Using the SVM model and Gene Ontology (GO annotations of proteins, we predicted new interactions between virus proteins and human proteins. Conclusions Encoding the relative frequency of amino acid triplets of a protein sequence is a simple yet powerful representation method for predicting protein-protein interactions across different species. The representation method has several advantages: (1 it enables a prediction model to achieve a better performance than other representations, (2 it generates feature vectors of fixed length regardless of the sequence length, and (3 the same representation is applicable to different types of proteins.

Variable Thumb Moment Arm Modeling and Thumb-Tip Force Production of a Human-Like Robotic Hand.

Science.gov (United States)

Niehues, Taylor D; Deshpande, Ashish D

2017-10-01

The anatomically correct testbed (ACT) hand mechanically simulates the musculoskeletal structure of the fingers and thumb of the human hand. In this work, we analyze the muscle moment arms (MAs) and thumb-tip force vectors in the ACT thumb in order to compare the ACT thumb's mechanical structure to the human thumb. Motion data are used to determine joint angle-dependent MA models, and thumb-tip three-dimensional (3D) force vectors are experimentally analyzed when forces are applied to individual muscles. Results are presented for both a nominal ACT thumb model designed to match human MAs and an adjusted model that more closely replicates human-like thumb-tip forces. The results confirm that the ACT thumb is capable of faithfully representing human musculoskeletal structure and muscle functionality. Using the ACT hand as a physical simulation platform allows us to gain a better understanding of the underlying biomechanical and neuromuscular properties of the human hand to ultimately inform the design and control of robotic and prosthetic hands.

Two-Armed, Mobile, Sensate Research Robot

Science.gov (United States)

Engelberger, J. F.; Roberts, W. Nelson; Ryan, David J.; Silverthorne, Andrew

2004-01-01

The Anthropomorphic Robotic Testbed (ART) is an experimental prototype of a partly anthropomorphic, humanoid-size, mobile robot. The basic ART design concept provides for a combination of two-armed coordination, tactility, stereoscopic vision, mobility with navigation and avoidance of obstacles, and natural-language communication, so that the ART could emulate humans in many activities. The ART could be developed into a variety of highly capable robotic assistants for general or specific applications. There is especially great potential for the development of ART-based robots as substitutes for live-in health-care aides for home-bound persons who are aged, infirm, or physically handicapped; these robots could greatly reduce the cost of home health care and extend the term of independent living. The ART is a fully autonomous and untethered system. It includes a mobile base on which is mounted an extensible torso topped by a head, shoulders, and two arms. All subsystems of the ART are powered by a rechargeable, removable battery pack. The mobile base is a differentially- driven, nonholonomic vehicle capable of a speed >1 m/s and can handle a payload >100 kg. The base can be controlled manually, in forward/backward and/or simultaneous rotational motion, by use of a joystick. Alternatively, the motion of the base can be controlled autonomously by an onboard navigational computer. By retraction or extension of the torso, the head height of the ART can be adjusted from 5 ft (1.5 m) to 6 1/2 ft (2 m), so that the arms can reach either the floor or high shelves, or some ceilings. The arms are symmetrical. Each arm (including the wrist) has a total of six rotary axes like those of the human shoulder, elbow, and wrist joints. The arms are actuated by electric motors in combination with brakes and gas-spring assists on the shoulder and elbow joints. The arms are operated under closed-loop digital control. A receptacle for an end effector is mounted on the tip of the wrist and

Comparing human-Salmonella with plant-Salmonella protein-protein interaction predictions

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Sylvia eSchleker

2015-01-01

Full Text Available Salmonellosis is the most frequent food-borne disease world-wide and can be transmitted to humans by a variety of routes, especially via animal and plant products. Salmonella bacteria are believed to use not only animal and human but also plant hosts despite their evolutionary distance. This raises the question if Salmonella employs similar mechanisms in infection of these diverse hosts. Given that most of our understanding comes from its interaction with human hosts, we investigate here to what degree knowledge of Salmonella-human interactions can be transferred to the Salmonella-plant system. Reviewed are recent publications on analysis and prediction of Salmonella-host interactomes. Putative protein-protein interactions (PPIs between Salmonella and its human and Arabidopsis hosts were retrieved utilizing purely interolog-based approaches in which predictions were inferred based on available sequence and domain information of known PPIs, and machine learning approaches that integrate a larger set of useful information from different sources. Transfer learning is an especially suitable machine learning technique to predict plant host targets from the knowledge of human host targets. A comparison of the prediction results with transcriptomic data shows a clear overlap between the host proteins predicted to be targeted by PPIs and their gene ontology enrichment in both host species and regulation of gene expression. In particular, the cellular processes Salmonella interferes with in plants and humans are catabolic processes. The details of how these processes are targeted, however, are quite different between the two organisms, as expected based on their evolutionary and habitat differences. Possible implications of this observation on evolution of host-pathogen communication are discussed.

Deoxyribonucleic-binding homeobox proteins are augmented in human cancer

DEFF Research Database (Denmark)

Wewer, U M; Mercurio, A M; Chung, S Y

1990-01-01

Homeobox genes encode sequence-specific DNA-binding proteins that are involved in the regulation of gene expression during embryonic development. In this study, we examined the expression of homeobox proteins in human cancer. Antiserum was obtained against a synthetic peptide derived from...... was then isolated and used to elicit a rabbit antiserum. In immunostaining, both antisera reacted with the nuclei of cultured tumor cells. In tissue sections of human carcinoma, nuclear immunoreactivity was observed in the tumor cells in 40 of 42 cases examined. Adjacent normal epithelial tissue obtained from......, the presence of the homeobox transcript in human carcinoma was documented by in situ hybridization and RNase protection mapping. These results demonstrate that human cancer is associated with the expression of homeobox proteins. Such homeobox proteins, as well as other regulatory proteins, could be involved...

Effect of arm swing strategy on local dynamic stability of human gait

OpenAIRE

Punt, M.; Bruijn, S.M.; Wittink, H.; van Dieen, J.H.

2015-01-01

Introduction: Falling causes long term disability and can even lead to death. Most falls occur during gait. Therefore improving gait stability might be beneficial for people at risk of falling. Recently arm swing has been shown to influence gait stability. However at present it remains unknown which mode of arm swing creates the most stable gait. Aim: To examine how different modes of arm swing affect gait stability. Method: Ten healthy young male subjects volunteered for this study. All subj...

Efficient prediction of human protein-protein interactions at a global scale.

Science.gov (United States)

Schoenrock, Andrew; Samanfar, Bahram; Pitre, Sylvain; Hooshyar, Mohsen; Jin, Ke; Phillips, Charles A; Wang, Hui; Phanse, Sadhna; Omidi, Katayoun; Gui, Yuan; Alamgir, Md; Wong, Alex; Barrenäs, Fredrik; Babu, Mohan; Benson, Mikael; Langston, Michael A; Green, James R; Dehne, Frank; Golshani, Ashkan

2014-12-10

Our knowledge of global protein-protein interaction (PPI) networks in complex organisms such as humans is hindered by technical limitations of current methods. On the basis of short co-occurring polypeptide regions, we developed a tool called MP-PIPE capable of predicting a global human PPI network within 3 months. With a recall of 23% at a precision of 82.1%, we predicted 172,132 putative PPIs. We demonstrate the usefulness of these predictions through a range of experiments. The speed and accuracy associated with MP-PIPE can make this a potential tool to study individual human PPI networks (from genomic sequences alone) for personalized medicine.

Analysis of the protein-protein interactions between the human acidic ribosomal P-proteins: evaluation by the two hybrid system

DEFF Research Database (Denmark)

Tchórzewski, M; Boldyreff, B; Issinger, O

2000-01-01

The surface acidic ribosomal proteins (P-proteins), together with ribosomal core protein P0 form a multimeric lateral protuberance on the 60 S ribosomal subunit. This structure, also called stalk, is important for efficient translational activity of the ribosome. In order to shed more light...... forms the 60 S ribosomal stalk: P0-(P1/P2)(2). Additionally, mutual interactions among human and yeast P-proteins were analyzed. Heterodimer formation could be observed between human P2 and yeast P1 proteins....

Identification of novel human damage response proteins targeted through yeast orthology.

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J Peter Svensson

Full Text Available Studies in Saccharomyces cerevisiae show that many proteins influence cellular survival upon exposure to DNA damaging agents. We hypothesized that human orthologs of these S. cerevisiae proteins would also be required for cellular survival after treatment with DNA damaging agents. For this purpose, human homologs of S. cerevisiae proteins were identified and mapped onto the human protein-protein interaction network. The resulting human network was highly modular and a series of selection rules were implemented to identify 45 candidates for human toxicity-modulating proteins. The corresponding transcripts were targeted by RNA interference in human cells. The cell lines with depleted target expression were challenged with three DNA damaging agents: the alkylating agents MMS and 4-NQO, and the oxidizing agent t-BuOOH. A comparison of the survival revealed that the majority (74% of proteins conferred either sensitivity or resistance. The identified human toxicity-modulating proteins represent a variety of biological functions: autophagy, chromatin modifications, RNA and protein metabolism, and telomere maintenance. Further studies revealed that MMS-induced autophagy increase the survival of cells treated with DNA damaging agents. In summary, we show that damage recovery proteins in humans can be identified through homology to S. cerevisiae and that many of the same pathways are represented among the toxicity modulators.

Peptide Mimicrying Between SARS Coronavirus Spike Protein and Human Proteins Reacts with SARS Patient Serum

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K.-Y. Hwa

2008-01-01

Full Text Available Molecular mimicry, defined as similar structures shared by molecules from dissimilar genes or proteins, is a general strategy used by pathogens to infect host cells. Severe acute respiratory syndrome (SARS is a new human respiratory infectious disease caused by SARS coronavirus (SARS-CoV. The spike (S protein of SARS-CoV plays an important role in the virus entry into a cell. In this study, eleven synthetic peptides from the S protein were selected based on its sequence homology with human proteins. Two of the peptides D07 (residues 927–937 and D08 (residues 942–951 were recognized by the sera of SARS patients. Murine hyperimmune sera against these peptides bound to proteins of human lung epithelial cells A549. Another peptide D10 (residues 490–502 stimulated A549 to proliferate and secrete IL-8. The present results suggest that the selected S protein regions, which share sequence homology with human proteins, may play important roles in SARS-CoV infection.

Human serum protein and C-reactive protein levels among HIV ...

African Journals Online (AJOL)

Human serum protein and C-reactive protein levels were determined among HIV patients visiting St Camillus Hospital, Uromi, Edo State, Nigeria, between January to March, 2013. Fifty (50) HIV patients (20 males; 30 females) and 50 control subjects (24 males; 26 females) were enrolled for this study. The clinical status of ...

A Scintigraphic Method for Quantitation of Lymphatic Function in Arm Lymphedema

DEFF Research Database (Denmark)

Hvidsten, Svend; Toyserkani, Navid M; Sørensen, Jens A

2018-01-01

) measure of lymph fluid passing through the arm. METHODS AND RESULTS: Eleven patients, aged 34-68 years, with unilateral arm lymphedema following breast cancer treatment underwent simultaneous bilateral lymphoscintigraphy using intradermal injection of 99mTc-labeled human serum albumin (HSA). Imaging...... was performed at 30-45 minute intervals for 5 hours. Time activity curves from each injection site and each arm region were recorded. The input into the arm region was obtained as the (minus) time derivative of the injection site activity curve. In the proposed model the arm activity curve was considered...

A molecular arms race between host innate antiviral response and emerging human coronaviruses.

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Wong, Lok-Yin Roy; Lui, Pak-Yin; Jin, Dong-Yan

2016-02-01

Coronaviruses have been closely related with mankind for thousands of years. Community-acquired human coronaviruses have long been recognized to cause common cold. However, zoonotic coronaviruses are now becoming more a global concern with the discovery of highly pathogenic severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses causing severe respiratory diseases. Infections by these emerging human coronaviruses are characterized by less robust interferon production. Treatment of patients with recombinant interferon regimen promises beneficial outcomes, suggesting that compromised interferon expression might contribute at least partially to the severity of disease. The mechanisms by which coronaviruses evade host innate antiviral response are under intense investigations. This review focuses on the fierce arms race between host innate antiviral immunity and emerging human coronaviruses. Particularly, the host pathogen recognition receptors and the signal transduction pathways to mount an effective antiviral response against SARS and MERS coronavirus infection are discussed. On the other hand, the counter-measures evolved by SARS and MERS coronaviruses to circumvent host defense are also dissected. With a better understanding of the dynamic interaction between host and coronaviruses, it is hoped that insights on the pathogenesis of newly-identified highly pathogenic human coronaviruses and new strategies in antiviral development can be derived.

Development of human protein reference database as an initial platform for approaching systems biology in humans

DEFF Research Database (Denmark)

Peri, Suraj; Navarro, J Daniel; Amanchy, Ramars

2003-01-01

Human Protein Reference Database (HPRD) is an object database that integrates a wealth of information relevant to the function of human proteins in health and disease. Data pertaining to thousands of protein-protein interactions, posttranslational modifications, enzyme/substrate relationships...

The unstructured linker arms of Mlh1-Pms1 are important for interactions with DNA during mismatch repair

Science.gov (United States)

Plys, Aaron J.; Rogacheva, Maria V.; Greene, Eric C.; Alani, Eric

2012-01-01

DNA mismatch repair (MMR) models have proposed that MSH proteins identify DNA polymerase errors while interacting with the DNA replication fork. MLH proteins (primarily Mlh1-Pms1 in baker’s yeast) then survey the genome for lesion-bound MSH proteins. The resulting MSH-MLH complex formed at a DNA lesion initiates downstream steps in repair. MLH proteins act as dimers and contain long (20 – 30 nanometers) unstructured arms that connect two terminal globular domains. These arms can vary between 100 to 300 amino acids in length, are highly divergent between organisms, and are resistant to amino acid substitutions. To test the roles of the linker arms in MMR, we engineered a protease cleavage site into the Mlh1 linker arm domain of baker’s yeast Mlh1-Pms1. Cleavage of the Mlh1 linker arm in vitro resulted in a defect in Mlh1-Pms1 DNA binding activity, and in vivo proteolytic cleavage resulted in a complete defect in MMR. We then generated a series of truncation mutants bearing Mlh1 and Pms1 linker arms of varying lengths. This work revealed that MMR is greatly compromised when portions of the Mlh1 linker are removed, whereas repair is less sensitive to truncation of the Pms1 linker arm. Purified complexes containing truncations in Mlh1 and Pms1 linker arms were analyzed and found to have differential defects in DNA binding that also correlated with the ability to form a ternary complex with Msh2-Msh6 and mismatch DNA. These observations are consistent with the unstructured linker domains of MLH proteins providing distinct interactions with DNA during MMR. PMID:22659005

Signatures of pleiotropy, economy and convergent evolution in a domain-resolved map of human-virus protein-protein interaction networks.

Science.gov (United States)

Garamszegi, Sara; Franzosa, Eric A; Xia, Yu

2013-01-01

A central challenge in host-pathogen systems biology is the elucidation of general, systems-level principles that distinguish host-pathogen interactions from within-host interactions. Current analyses of host-pathogen and within-host protein-protein interaction networks are largely limited by their resolution, treating proteins as nodes and interactions as edges. Here, we construct a domain-resolved map of human-virus and within-human protein-protein interaction networks by annotating protein interactions with high-coverage, high-accuracy, domain-centric interaction mechanisms: (1) domain-domain interactions, in which a domain in one protein binds to a domain in a second protein, and (2) domain-motif interactions, in which a domain in one protein binds to a short, linear peptide motif in a second protein. Analysis of these domain-resolved networks reveals, for the first time, significant mechanistic differences between virus-human and within-human interactions at the resolution of single domains. While human proteins tend to compete with each other for domain binding sites by means of sequence similarity, viral proteins tend to compete with human proteins for domain binding sites in the absence of sequence similarity. Independent of their previously established preference for targeting human protein hubs, viral proteins also preferentially target human proteins containing linear motif-binding domains. Compared to human proteins, viral proteins participate in more domain-motif interactions, target more unique linear motif-binding domains per residue, and contain more unique linear motifs per residue. Together, these results suggest that viruses surmount genome size constraints by convergently evolving multiple short linear motifs in order to effectively mimic, hijack, and manipulate complex host processes for their survival. Our domain-resolved analyses reveal unique signatures of pleiotropy, economy, and convergent evolution in viral-host interactions that are

Human neuronal cell protein responses to Nipah virus infection

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Hassan Sharifah

2007-06-01

Full Text Available Abstract Background Nipah virus (NiV, a recently discovered zoonotic virus infects and replicates in several human cell types. Its replication in human neuronal cells, however, is less efficient in comparison to other fully susceptible cells. In the present study, the SK-N-MC human neuronal cell protein response to NiV infection is examined using proteomic approaches. Results Method for separation of the NiV-infected human neuronal cell proteins using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE was established. At least 800 protein spots were resolved of which seven were unique, six were significantly up-regulated and eight were significantly down-regulated. Six of these altered proteins were identified using mass spectrometry (MS and confirmed using MS/MS. The heterogenous nuclear ribonucleoprotein (hnRNP F, guanine nucleotide binding protein (G protein, voltage-dependent anion channel 2 (VDAC2 and cytochrome bc1 were present in abundance in the NiV-infected SK-N-MC cells in contrast to hnRNPs H and H2 that were significantly down-regulated. Conclusion Several human neuronal cell proteins that are differentially expressed following NiV infection are identified. The proteins are associated with various cellular functions and their abundance reflects their significance in the cytopathologic responses to the infection and the regulation of NiV replication. The potential importance of the ratio of hnRNP F, and hnRNPs H and H2 in regulation of NiV replication, the association of the mitochondrial protein with the cytopathologic responses to the infection and induction of apoptosis are highlighted.

Prolactin-inducible proteins in human breast cancer cells

International Nuclear Information System (INIS)

Shiu, R.P.; Iwasiow, B.M.

1985-01-01

The mechanism of action of prolactin in target cells and the role of prolactin in human breast cancer are poorly understood phenomena. The present study examines the effect of human prolactin (hPRL) on the synthesis of unique proteins by a human breast cancer cell line, T-47D, in serum-free medium containing bovine serum albumin. [ 35 S]Methionine-labeled proteins were analysed by sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis and fluorography. Treatment of cells with hPRL (1-1000 ng/ml) and hydrocortisone (1 microgram/ml) for 36 h or longer resulted in the synthesis and secretion of three proteins having molecular weights of 11,000, 14,000, and 16,000. Neither hPRL nor hydrocortisone alone induced these proteins. Of several other peptide hormones tested, only human growth hormone, a hormone structurally and functionally similar to hPRL, could replace hPRL in causing protein induction. These three proteins were, therefore, referred to as prolactin-inducible proteins (PIP). Each of the three PIPs was purified to homogeneity by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and specific antibodies were generated to them in rabbits. By immunoprecipitation and immunoblotting (Western blot) of proteins secreted by T-47D cells, it was demonstrated that the three PIPs were immunologically identical to one another. In addition, the 16-kDa and 14-kDa proteins (PIP-16 and PIP-14), and not the 11-kDa protein (PIP-11), incorporated [ 3 H]glycosamine. Furthermore, 2-deoxyglucose (2 mM) and tunicamycin (0.5 micrograms/ml), two compounds known to inhibit glycosylation, blocked the production of PIP-16 and PIP-14, with a concomitant increase in the accumulation of PIP-11

Identification of proteins specific for human herpesvirus 6-infected human T cells

International Nuclear Information System (INIS)

Balachandran, N.; Amelse, R.E.; Zhou, W.W.; Chang, C.K.

1989-01-01

Proteins specific for human herpesvirus 6 (HHV-6)-infected human T cells (HSB-2) were examined by using polyclonal rabbit antibodies and monoclonal antibodies against HHV-6-infected cells and human sera. More than 20 proteins and six glycoproteins specific for HHV-6-infected cells were identified from [ 35 S]methionine- and [ 3 H]glucosamine-labeled total-cell extracts. Polyclonal rabbit antibodies immunoprecipitated 33 [ 35 S]methionine-labeled HHV-6-specific polypeptides with approximate molecular weights ranging from 180,000 to 31,000. In immunoprecipitation and Western immunoblot reactions, a patient's serum also recognized more than 30 HHV-6-specific proteins and seven glycoproteins. In contrast, sera from individuals with high-titered antibodies against other human herpesviruses reacted with fewer HHV-6-infected cell proteins, and only a 135,000-M r polypeptide was prominent. Monoclonal antibodies to HHV-6-infected cells reacted with single and multiple polypeptides specific for virus-infected cells and immunoprecipitated three distinct sets of glycoproteins, which were designated gp105k and gp82k, gp116k, gp64k, and gp54k, and gp102k

Identification of proteins specific for human herpesvirus 6-infected human T cells

International Nuclear Information System (INIS)

Balachandran, N.; Amelse, R.E.; Zhou, W.W.; Chang, C.K.

1989-01-01

Proteins specific for human herpesvirus 6 (HHV-6)-infected human T cells (HSB-2) were examined by using polyclonal rabbit antibodies and monoclonal antibodies against HHV-6-infected cells and human sera. More than 20 proteins and six glycoproteins specific for HHV-6-infected cells were identified from [ 35 S]methionine- and [ 3 H]glucosamine-labeled total-cell extracts. Polyclonal rabbit antibodies immunoprecipitated 33 [ 35 S]methionine-labeled HHV-6-specific polypeptides with approximate molecular weights ranging from 180,000 to 31,000. In immunoprecipitation and Western immunoblot reactions, a patient's serum also recognized more than 30 HHV-6-specific proteins and seven glycoproteins. In contrast, sera from individuals with high-titered antibodies against other human herpes viruses reacted with few HHV-6-infected cell proteins, and only a 135,000-M/sub r/ polypeptide was prominent. Monoclonal antibodies to HHV-6-infected cells reacted with single and multiple polypeptides specific for virus-infected cells and immunoprecipitated three distinct sets of glycoproteins, which were designated gp105K and gp92k, gp116k, gp64k, and gp54k, and gp102k

A catalogue of human secreted proteins and its implications

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Shivakumar Keerthikumar

2016-11-01

Full Text Available Under both normal and pathological conditions, cells secrete variety of proteins through classical and non-classical secretory pathways into the extracellular space. Majority of these proteins represent pathophysiology of the cell from which it is secreted. Recently, though more than 92% of the protein coding genes has been mapped by human proteome map project, but number of those proteins that constitutes secretome of the cell still remains elusive. Secreted proteins or the secretome can be accessible in bodily fluids and hence are considered as potential biomarkers to discriminate between healthy and diseased individuals. In order to facilitate the biomarker discovery and to further aid clinicians and scientists working in these arenas, we have compiled and catalogued secreted proteins from the human proteome using integrated bioinformatics approach. In this study, nearly 14% of the human proteome is likely to be secreted through classical and non-classical secretory pathways. Out of which, ~38% of these secreted proteins were found in extracellular vesicles including exosomes and shedding microvesicles. Among these secreted proteins, 94% were detected in human bodily fluids including blood, plasma, serum, saliva, semen, tear and urine. We anticipate that this high confidence list of secreted proteins could serve as a compendium of candidate biomarkers. In addition, the catalogue may provide functional insights in understanding the molecular mechanisms involved in various physiological and pathophysiological conditions of the cell.

Kazakh therapy on differential protein expression of Achilles tendon healing in a 7-day postoperative rabbit model.

Science.gov (United States)

Nuerai, Shawutali; Ainuer, Jialili; Jiasharete, Jielile; Darebai, Redati; Kayrat, Aldyarhan; Tang, Bin; Jiangannur, Zheyiken; Bai, Jingping; Makabel, Bolat

2011-12-01

To compare the effect of cast immobilization with that of early Kiymil arkili emdew (Kazakh exercise therapy) on the post-operative healing of Achilles tendon rupture in rabbits, and to observe the influence of early Kiymil arkili emdew on the differentially expressed proteins in the healing tendon. Forty-five New Zealand white rabbits were randomly divided into three groups (Arm A: control group; Arm B: postoperative immobilization group; and Arm C: postoperative early Kiymil arkili emdew group). After tenotomy, the rabbits of the two experimental groups received microsurgery to repair the ruptured tendons, and then received either cast immobilization or early Kiymil arkili emdew treatment. Achilles tendon tissue samples were collected 7 days after the surgery, and two-dimensional gel electrophoresis and MALDI-TOF-MS technique were used to analyze differentially expressed proteins in the tendon tissue of the three Arms. A total of 462.67 +/- 11.59, 532.33 +/- 27.79, and 515.33 +/- 6.56 protein spots were detected by the two-dimensional polyacrylamide gels in the Achilles tendon samples of the rabbits in Arms A, B, and C, respectively. Nineteen differentially expressed protein spots were randomly selected from Arm C. Among them, 7 were unique, and 15 had five times higher abundance than those in Arm B. These included annexin A2, gelsolin isoforms and alpha-1 Type III collagen. It was confirmed by western blot that gelsolin isoform b, annexin A2, etc. had specific and incremental expression in Arm C. The self-protective instincts of humans were overlooked in the classical postoperative treatment for Achilles tendon rupture with cast immobilization. Kiymil arkili emdew induced the specific and incremental expression of proteins in the repaired Achilles tendon in the early healing stage in a rabbit model, compared with those treated with postoperative cast immobilization. These differentially expressed proteins may contribute to the healing of the Achilles tendon via

Signatures of pleiotropy, economy and convergent evolution in a domain-resolved map of human-virus protein-protein interaction networks.

Directory of Open Access Journals (Sweden)

Sara Garamszegi

Full Text Available A central challenge in host-pathogen systems biology is the elucidation of general, systems-level principles that distinguish host-pathogen interactions from within-host interactions. Current analyses of host-pathogen and within-host protein-protein interaction networks are largely limited by their resolution, treating proteins as nodes and interactions as edges. Here, we construct a domain-resolved map of human-virus and within-human protein-protein interaction networks by annotating protein interactions with high-coverage, high-accuracy, domain-centric interaction mechanisms: (1 domain-domain interactions, in which a domain in one protein binds to a domain in a second protein, and (2 domain-motif interactions, in which a domain in one protein binds to a short, linear peptide motif in a second protein. Analysis of these domain-resolved networks reveals, for the first time, significant mechanistic differences between virus-human and within-human interactions at the resolution of single domains. While human proteins tend to compete with each other for domain binding sites by means of sequence similarity, viral proteins tend to compete with human proteins for domain binding sites in the absence of sequence similarity. Independent of their previously established preference for targeting human protein hubs, viral proteins also preferentially target human proteins containing linear motif-binding domains. Compared to human proteins, viral proteins participate in more domain-motif interactions, target more unique linear motif-binding domains per residue, and contain more unique linear motifs per residue. Together, these results suggest that viruses surmount genome size constraints by convergently evolving multiple short linear motifs in order to effectively mimic, hijack, and manipulate complex host processes for their survival. Our domain-resolved analyses reveal unique signatures of pleiotropy, economy, and convergent evolution in viral

Review: Optimizing ruminant conversion of feed protein to human food protein.

Science.gov (United States)

Broderick, G A

2017-11-20

Ruminant livestock have the ability to produce high-quality human food from feedstuffs of little or no value for humans. Balanced essential amino acid composition of meat and milk from ruminants makes those protein sources valuable adjuncts to human diets. It is anticipated that there will be increasing demand for ruminant proteins in the future. Increasing productivity per animal dilutes out the nutritional and environmental costs of maintenance and rearing dairy animals up to production. A number of nutritional strategies improve production per animal such as ration balancing in smallholder operations and small grain supplements to ruminants fed high-forage diets. Greenhouse gas emission intensity is reduced by increased productivity per animal; recent research has developed at least one effective inhibitor of methane production in the rumen. There is widespread over-feeding of protein to dairy cattle; milk and component yields can be maintained, and sometimes even increased, at lower protein intake. Group feeding dairy cows according to production and feeding diets higher in rumen-undegraded protein can improve milk and protein yield. Supplementing rumen-protected essential amino acids will also improve N efficiency in some cases. Better N utilization reduces urinary N, which is the most environmentally unstable form of excretory N. Employing nutritional models to more accurately meet animal requirements improves nutrient efficiency. Although smallholder enterprises, which are concentrated in tropical and semi-tropical regions of developing countries, are subject to different economic pressures, nutritional biology is similar at all production levels. Rather than milk volume, nutritional strategies should maximize milk component yield, which is proportional to market value as well as food value when milk nutrients are consumed directly by farmers and their families. Moving away from Holsteins toward smaller breeds such as Jerseys, Holstein-Jersey crosses or

Protein dynamics in individual human cells: experiment and theory.

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Ariel Aharon Cohen

Full Text Available A current challenge in biology is to understand the dynamics of protein circuits in living human cells. Can one define and test equations for the dynamics and variability of a protein over time? Here, we address this experimentally and theoretically, by means of accurate time-resolved measurements of endogenously tagged proteins in individual human cells. As a model system, we choose three stable proteins displaying cell-cycle-dependant dynamics. We find that protein accumulation with time per cell is quadratic for proteins with long mRNA life times and approximately linear for a protein with short mRNA lifetime. Both behaviors correspond to a classical model of transcription and translation. A stochastic model, in which genes slowly switch between ON and OFF states, captures measured cell-cell variability. The data suggests, in accordance with the model, that switching to the gene ON state is exponentially distributed and that the cell-cell distribution of protein levels can be approximated by a Gamma distribution throughout the cell cycle. These results suggest that relatively simple models may describe protein dynamics in individual human cells.

Gains of ubiquitylation sites in highly conserved proteins in the human lineage

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Kim Dong Seon

2012-11-01

Full Text Available Abstract Background Post-translational modification of lysine residues of specific proteins by ubiquitin modulates the degradation, localization, and activity of these target proteins. Here, we identified gains of ubiquitylation sites in highly conserved regions of human proteins that occurred during human evolution. Results We analyzed human ubiquitylation site data and multiple alignments of orthologous mammalian proteins including those from humans, primates, other placental mammals, opossum, and platypus. In our analysis, we identified 281 ubiquitylation sites in 252 proteins that first appeared along the human lineage during primate evolution: one protein had four novel sites; four proteins had three sites each; 18 proteins had two sites each; and the remaining 229 proteins had one site each. PML, which is involved in neurodevelopment and neurodegeneration, acquired three sites, two of which have been reported to be involved in the degradation of PML. Thirteen human proteins, including ERCC2 (also known as XPD and NBR1, gained human-specific ubiquitylated lysines after the human-chimpanzee divergence. ERCC2 has a Lys/Gln polymorphism, the derived (major allele of which confers enhanced DNA repair capacity and reduced cancer risk compared with the ancestral (minor allele. NBR1 and eight other proteins that are involved in the human autophagy protein interaction network gained a novel ubiquitylation site. Conclusions The gain of novel ubiquitylation sites could be involved in the evolution of protein degradation and other regulatory networks. Although gains of ubiquitylation sites do not necessarily equate to adaptive evolution, they are useful candidates for molecular functional analyses to identify novel advantageous genetic modifications and innovative phenotypes acquired during human evolution.

Preliminary structural characterization of human SOUL, a haem-binding protein

International Nuclear Information System (INIS)

Freire, Filipe; Romão, Maria João; Macedo, Anjos L.; Aveiro, Susana S.; Goodfellow, Brian J.; Carvalho, Ana Luísa

2009-01-01

This manuscript describes the overexpression, purification and crystallization of human SOUL protein (hSOUL). hSOUL is a 23 kDa haem-binding protein that was first identified as the PP23 protein isolated from human full-term placenta. Human SOUL (hSOUL) is a 23 kDa haem-binding protein that was first identified as the PP 23 protein isolated from human full-term placentas. Here, the overexpression, purification and crystallization of hSOUL are reported. The crystals belonged to space group P6 4 22, with unit-cell parameters a = b = 145, c = 60 Å and one protein molecule in the asymmetric unit. X-ray diffraction data were collected to 3.5 Å resolution at the ESRF. A preliminary model of the three-dimensional structure of hSOUL was obtained by molecular replacement using the structures of murine p22HBP, obtained by solution NMR, as search models

Mining the human tissue proteome for protein citrullination.

Science.gov (United States)

Lee, Chien-Yun; Wang, Dongxue; Wilhelm, Mathias; Zolg, Daniel Paul; Schmidt, Tobias; Schnatbaum, Karsten; Reimer, Ulf; Pontén, Fredrik; Uhlén, Mathias; Hahne, Hannes; Kuster, Bernhard

2018-04-02

Citrullination is a post-translational modification of arginine catalyzed by five peptidylarginine deiminases (PADs) in humans. The loss of a positive charge may cause structural or functional alterations and while the modification has been linked to several diseases including rheumatoid arthritis and cancer, its physiological or pathophysiological roles remain largely unclear. In part this is owing to limitations in available methodology able to robustly enrich, detect and localize the modification. As a result, only few citrullination sites have been identified on human proteins with high confidence. In this study, we mined data from mass spectrometry-based deep proteomic profiling of 30 human tissues to identify citrullination sites on endogenous proteins. Database searching of ~70 million tandem mass spectra yielded ~13,000 candidate spectra which were further triaged by spectrum quality metrics and the detection of the specific neutral loss of isocyanic acid from citrullinated peptides to reduce false positives. Because citrullination is easily confused with deamidation, we synthetized ~2,200 citrullinated and 1,300 deamidated peptides to build a library of reference spectra. This led to the validation of 375 citrullination sites on 209 human proteins. Further analysis showed that >80% of the identified modifications sites were new and for 56% of the proteins, citrullination was detected for the first time. Sequence motif analysis revealed a strong preference for Asp and Gly, residues around the citrullination site. Interestingly, while the modification was detected in 26 human tissues with the highest levels found in brain and lung, citrullination levels did not correlate well with protein expression of the PAD enzymes. Even though the current work represents the largest survey of protein citrullination to date, the modification was mostly detected on high abundant proteins arguing that the development of specific enrichment methods would be required in order

Systematic high-yield production of human secreted proteins in Escherichia coli

International Nuclear Information System (INIS)

Dai Xueyu; Chen Qiang; Lian Min; Zhou Yanfeng; Zhou Mo; Lu Shanyun; Chen Yunjia; Luo Jingchu; Gu Xiaocheng; Jiang Ying; Luo Ming; Zheng Xiaofeng

2005-01-01

Human secreted proteins play a very important role in signal transduction. In order to study all potential secreted proteins identified from the human genome sequence, systematic production of large amounts of biologically active secreted proteins is a prerequisite. We selected 25 novel genes as a trial case for establishing a reliable expression system to produce active human secreted proteins in Escherichia coli. Expression of proteins with or without signal peptides was examined and compared in E. coli strains. The results indicated that deletion of signal peptides, to a certain extent, can improve the expression of these proteins and their solubilities. More importantly, under expression conditions such as induction temperature, N-terminus fusion peptides need to be optimized in order to express adequate amounts of soluble proteins. These recombinant proteins were characterized as well-folded proteins. This system enables us to rapidly obtain soluble and highly purified human secreted proteins for further functional studies

Hassan v United Kingdom: The Interaction of Human Rights Law and International Humanitarian Law with regard to the Deprivation of Liberty in Armed Conflicts

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Cedric De Koker

2015-08-01

Full Text Available In 'Hassan' v 'United Kingdom', the Grand Chamber of the European Court of Human Rights reviewed the deprivation of liberty of a young male by British armed forces during the phase of active hostilities in Iraq, which had raised issues relating to extraterritoriality, the right to liberty and security in times of armed conflict and the relationship between international humanitarian law (IHL and human rights law (HRL.1 In its judgment of 16 September 2014, the Court ruled that by reason of the co-existence of the safeguards provided by IHL and by the European Convention on Human Rights (ECHR in time of armed conflict, the grounds of permitted deprivation of liberty found in both bodies of law should, as far as possible, be accommodated and applied concomitantly. The greatest merit of the judgment is that for the first time it explicitly offered its view on the interaction between IHL and HRL and did not rely on the lex specialis principle, the traditional but flawed method for explaining the relationship between these spheres of law. However, the judgment is also a missed opportunity as the Court limited its analysis to the case at hand and provided limited guidance for the future, leaving a number of questions unaddressed.

Structural analysis of recombinant human protein QM

International Nuclear Information System (INIS)

Gualberto, D.C.H.; Fernandes, J.L.; Silva, F.S.; Saraiva, K.W.; Affonso, R.; Pereira, L.M.; Silva, I.D.C.G.

2012-01-01

Full text: The ribosomal protein QM belongs to a family of ribosomal proteins, which is highly conserved from yeast to humans. The presence of the QM protein is necessary for joining the 60S and 40S subunits in a late step of the initiation of mRNA translation. Although the exact extra-ribosomal functions of QM are not yet fully understood, it has been identified as a putative tumor suppressor. This protein was reported to interact with the transcription factor c-Jun and thereby prevent c-Jun actives genes of the cellular growth. In this study, the human QM protein was expressed in bacterial system, in the soluble form and this structure was analyzed by Circular Dichroism and Fluorescence. The results of Circular Dichroism showed that this protein has less alpha helix than beta sheet, as described in the literature. QM protein does not contain a leucine zipper region; however the ion zinc is necessary for binding of QM to c-Jun. Then we analyzed the relationship between the removal of zinc ions and folding of protein. Preliminary results obtained by the technique Fluorescence showed a gradual increase in fluorescence with the addition of increasing concentration of EDTA. This suggests that the zinc is important in the tertiary structure of the protein. More studies are being made for better understand these results. (author)

Protein Crystal Recombinant Human Insulin

Science.gov (United States)

1994-01-01

The comparison of protein crystal, Recombiant Human Insulin; space-grown (left) and earth-grown (right). On STS-60, Spacehab II indicated that space-grown crystals are larger and of greater optical clarity than their earth-grown counterparts. Recombiant Human Insulin facilitates the incorporation of glucose into cells. In diabetics, there is either a decrease in or complete lack of insulin, thereby leading to several harmful complications. Principal Investigator is Larry DeLucas.

Prediction of the Ebola Virus Infection Related Human Genes Using Protein-Protein Interaction Network.

Science.gov (United States)

Cao, HuanHuan; Zhang, YuHang; Zhao, Jia; Zhu, Liucun; Wang, Yi; Li, JiaRui; Feng, Yuan-Ming; Zhang, Ning

2017-01-01

Ebola hemorrhagic fever (EHF) is caused by Ebola virus (EBOV). It is reported that human could be infected by EBOV with a high fatality rate. However, association factors between EBOV and host still tend to be ambiguous. According to the "guilt by association" (GBA) principle, proteins interacting with each other are very likely to function similarly or the same. Based on this assumption, we tried to obtain EBOV infection-related human genes in a protein-protein interaction network using Dijkstra algorithm. We hope it could contribute to the discovery of novel effective treatments. Finally, 15 genes were selected as potential EBOV infection-related human genes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Proprioceptive Interaction between the Two Arms in a Single-Arm Pointing Task.

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Kazuyoshi Kigawa

Full Text Available Proprioceptive signals coming from both arms are used to determine the perceived position of one arm in a two-arm matching task. Here, we examined whether the perceived position of one arm is affected by proprioceptive signals from the other arm in a one-arm pointing task in which participants specified the perceived position of an unseen reference arm with an indicator paddle. Both arms were hidden from the participant's view throughout the study. In Experiment 1, with both arms placed in front of the body, the participants received 70-80 Hz vibration to the elbow flexors of the reference arm (= right arm to induce the illusion of elbow extension. This extension illusion was compared with that when the left arm elbow flexors were vibrated or not. The degree of the vibration-induced extension illusion of the right arm was reduced in the presence of left arm vibration. In Experiment 2, we found that this kinesthetic interaction between the two arms did not occur when the left arm was vibrated in an abducted position. In Experiment 3, the vibration-induced extension illusion of one arm was fully developed when this arm was placed at an abducted position, indicating that the brain receives increased proprioceptive input from a vibrated arm even if the arm was abducted. Our results suggest that proprioceptive interaction between the two arms occurs in a one-arm pointing task when the two arms are aligned with one another. The position sense of one arm measured using a pointer appears to include the influences of incoming information from the other arm when both arms were placed in front of the body and parallel to one another.

Molecular cloning of the gene for the human placental GTP-binding protein Gp (G25K): Identification of this GTP-binding protein as the human homolog of the yeast cell-division-cycle protein CDC42

International Nuclear Information System (INIS)

Shinjo, K.; Koland, J.G.; Hart, M.J.; Narasimhan, V.; Cerione, R.A.; Johnson, D.I.; Evans, T.

1990-01-01

The authors have isolated cDNA clones from a human placental library that code for a low molecular weight GTP-binding protein originally designated G p (also called G25K). This identification is based on comparisons with the available peptide sequences for the purified human G p protein and the use of two highly specific anti-peptide antibodies. The predicted amino acid sequence of the protein is very similar to those of various members of the ras superfamily of low molecular weight GTP-binding proteins, including the N-, Ki-, and Ha-ras proteins (30-35% identical), the rho proteins and the rac proteins. The highest degree of sequence identity (80%) is found with the Saccharomyces cerevisiae cell division-cycle protein CDC42. The human placental gene, which they designate CDC42Hs, complements the cdc42-1 mutation in S. cerevisiae, which suggests that this GTP-binding protein is the human homolog of the yeast protein

Development of an Arm Phantom for Testing Non-Invasive Blood Pressure Monitors

Science.gov (United States)

Anderson-Jackson, LaTecia D.

Approximately one in every three adults age 20 older are diagnosed with high blood pressure or hypertension. It is estimated that hypertension affects 78 million people in the United States, is equally prevalent in both men and woman (Crabtree, Stuart-Shor, & McAllister, 2013). In the United States, around 78% of people suffering from hypertension are aware of their condition, with only 68% using hypertensive medications to control their blood pressure (Writing Group et al., 2010). Clinically, blood pressure measurements may lack accuracy, which can be attributed to various factors, including device limitations, cuff mis-sizing and misplacement, white-coat effect, masked hypertension, and lifestyle factors. The development of an arm phantom to simulate physiologic properties of a human arm and arterial BP waveforms may allow us to better assess the accuracy of non-invasive blood pressure (NIBP) monitors. The objective of this study are to: (1) Develop an arm phantom to replicate physiological properties of the human arm, and (2) Incorporate the arm phantom into a mock circulatory flow loop to simulate different physiological blood pressure readings on the bench. A tissue mimicking material, styrene-ethylene-butylene-styrene (SEBS), a co-block polymer was used to develop the arm phantom for in-vitro testing. To determine the optimal mechanical properties for the arm phantom, individual arm components were isolated and tested. A protocol was developed to evaluate various components for optimal arm phantom development. Mechanical testing was conducted on 10%, 15%, and 20% SEBS gel samples for modulus of elasticity measurements in order to simulate physiological properties of the human arm. As a result of the SEBS polymer being a new material for this application, this investigation will contribute to resolving the limitations that occurred during experimentation. In this study, we demonstrated that although SEBS polymer may be an ideal material to use for simulating

Human plasminogen binding protein tetranectin

DEFF Research Database (Denmark)

Kastrup, J S; Rasmussen, H; Nielsen, B B

1997-01-01

The recombinant human plasminogen binding protein tetranectin (TN) and the C-type lectin CRD of this protein (TN3) have been crystallized. TN3 crystallizes in the tetragonal space group P4(2)2(1)2 with cell dimensions a = b = 64.0, c = 75.7 A and with one molecule per asymmetric unit. The crystals...... to at least 2.5 A. A full data set has been collected to 3.0 A. The asymmetric unit contains one monomer of TN. Molecular replacement solutions for TN3 and TN have been obtained using the structure of the C-type lectin CRD of rat mannose-binding protein as search model. The rhombohedral space group indicates...

A biologically inspired neural network controller for ballistic arm movements

Directory of Open Access Journals (Sweden)

Schmid Maurizio

2007-09-01

Full Text Available Abstract Background In humans, the implementation of multijoint tasks of the arm implies a highly complex integration of sensory information, sensorimotor transformations and motor planning. Computational models can be profitably used to better understand the mechanisms sub-serving motor control, thus providing useful perspectives and investigating different control hypotheses. To this purpose, the use of Artificial Neural Networks has been proposed to represent and interpret the movement of upper limb. In this paper, a neural network approach to the modelling of the motor control of a human arm during planar ballistic movements is presented. Methods The developed system is composed of three main computational blocks: 1 a parallel distributed learning scheme that aims at simulating the internal inverse model in the trajectory formation process; 2 a pulse generator, which is responsible for the creation of muscular synergies; and 3 a limb model based on two joints (two degrees of freedom and six muscle-like actuators, that can accommodate for the biomechanical parameters of the arm. The learning paradigm of the neural controller is based on a pure exploration of the working space with no feedback signal. Kinematics provided by the system have been compared with those obtained in literature from experimental data of humans. Results The model reproduces kinematics of arm movements, with bell-shaped wrist velocity profiles and approximately straight trajectories, and gives rise to the generation of synergies for the execution of movements. The model allows achieving amplitude and direction errors of respectively 0.52 cm and 0.2 radians. Curvature values are similar to those encountered in experimental measures with humans. The neural controller also manages environmental modifications such as the insertion of different force fields acting on the end-effector. Conclusion The proposed system has been shown to properly simulate the development of

Cow's milk proteins in human milk.

Science.gov (United States)

Coscia, A; Orrù, S; Di Nicola, P; Giuliani, F; Rovelli, I; Peila, C; Martano, C; Chiale, F; Bertino, E

2012-01-01

Cow's milk proteins (CMPs) are among the best characterized food allergens. Cow's milk contains more than twenty five different proteins, but only whey proteins alpha-lactalbumin, beta-lactoglobulin, bovine serum albumin (BSA), and lactoferrin, as well as the four caseins, have been identified as allergens. Aim of this study was to investigate by proteomics techniques cow's milk allergens in human colostrum of term and preterm newborns' mothers, not previously detected, in order to understand if such allergens could be cause of sensitization during lactation. Term colostrum samples from 62 healthy mothers and preterm colostrum samples from 11 healthy mothers were collected for this purpose. The most relevant finding was the detection of the intact bovine alpha-S1-casein in both term and preterm colostrum. Using this method, which allows direct proteins identification, beta-lactoglobulin was not detected in any of colostrum samples. According to our results bovine alpha 1 casein that is considered a major cow's milk allergen is readily secreted in human milk: further investigations are needed in order to clarify if alpha-1-casein has a major role in sensitization or tolerance to cow's milk of exclusively breastfed predisposed infants.

Localization Performance of Multiple Vibrotactile Cues on Both Arms.

Science.gov (United States)

Wang, Dangxiao; Peng, Cong; Afzal, Naqash; Li, Weiang; Wu, Dong; Zhang, Yuru

2018-01-01

To present information using vibrotactile stimuli in wearable devices, it is fundamental to understand human performance of localizing vibrotactile cues across the skin surface. In this paper, we studied human ability to identify locations of multiple vibrotactile cues activated simultaneously on both arms. Two haptic bands were mounted in proximity to the elbow and shoulder joints on each arm, and two vibrotactile motors were mounted on each band to provide vibration cues to the dorsal and palmar side of the arm. The localization performance under four conditions were compared, with the number of the simultaneously activated cues varying from one to four in each condition. Experimental results illustrate that the rate of correct localization decreases linearly with the increase in the number of activated cues. It was 27.8 percent for three activated cues, and became even lower for four activated cues. An analysis of the correct rate and error patterns show that the layout of vibrotactile cues can have significant effects on the localization performance of multiple vibrotactile cues. These findings might provide guidelines for using vibrotactile cues to guide the simultaneous motion of multiple joints on both arms.

Xylosylation of proteins by expression of human xylosyltransferase 2 in plants.

Science.gov (United States)

Matsuo, Kouki; Atsumi, Go

2018-04-12

Through the years, the post-translational modification of plant-made recombinant proteins has been a considerable problem. Protein glycosylation is arguably the most important post-translational modification; thus, for the humanization of protein glycosylation in plants, the introduction, repression, and knockout of many glycosylation-related genes has been carried out. In addition, plants lack mammalian-type protein O-glycosylation pathways; thus, for the synthesis of mammalian O-glycans in plants, the construction of these pathways is necessary. In this study, we successfully xylosylated the recombinant human proteoglycan core protein, serglycin, by transient expression of human xylosyltransferase 2 in Nicotiana benthamiana plants. When human serglycin was co-expressed with human xylosyltransferase 2 in plants, multiple serine residues of eight xylosylation candidates were xylosylated. From the results of carbohydrate assays for total soluble proteins, some endogenous plant proteins also appeared to be xylosylated, likely through the actions of xylosyltransferase 2. The xylosylation of core proteins is the initial step of the glycosaminoglycan part of the synthesis of proteoglycans. In the future, these novel findings may lead to whole mammalian proteoglycan synthesis in plants. Copyright © 2018 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Robotic arm

Science.gov (United States)

Kwech, Horst

1989-04-18

A robotic arm positionable within a nuclear vessel by access through a small diameter opening and having a mounting tube supported within the vessel and mounting a plurality of arm sections for movement lengthwise of the mounting tube as well as for movement out of a window provided in the wall of the mounting tube. An end effector, such as a grinding head or welding element, at an operating end of the robotic arm, can be located and operated within the nuclear vessel through movement derived from six different axes of motion provided by mounting and drive connections between arm sections of the robotic arm. The movements are achieved by operation of remotely-controllable servo motors, all of which are mounted at a control end of the robotic arm to be outside the nuclear vessel.

Protein buffering in model systems and in whole human saliva.

Directory of Open Access Journals (Sweden)

Andreas Lamanda

Full Text Available The aim of this study was to quantify the buffer attributes (value, power, range and optimum of two model systems for whole human resting saliva, the purified proteins from whole human resting saliva and single proteins. Two model systems, the first containing amyloglucosidase and lysozyme, and the second containing amyloglucosidase and alpha-amylase, were shown to provide, in combination with hydrogencarbonate and di-hydrogenphosphate, almost identical buffer attributes as whole human resting saliva. It was further demonstrated that changes in the protein concentration as small as 0.1% may change the buffer value of a buffer solution up to 15 times. Additionally, it was shown that there was a protein concentration change in the same range (0.16% between saliva samples collected at the time periods of 13:00 and others collected at 9:00 am and 17:00. The mode of the protein expression changed between these samples corresponded to the change in basic buffer power and the change of the buffer value at pH 6.7. Finally, SDS Page and Ruthenium II tris (bathophenantroline disulfonate staining unveiled a constant protein expression in all samples except for one 50 kDa protein band. As the change in the expression pattern of that 50 kDa protein band corresponded to the change in basic buffer power and the buffer value at pH 6.7, it was reasonable to conclude that this 50 kDa protein band may contain the protein(s belonging to the protein buffer system of human saliva.

Functional similarities between the dictyostelium protein AprA and the human protein dipeptidyl-peptidase IV.

Science.gov (United States)

Herlihy, Sarah E; Tang, Yu; Phillips, Jonathan E; Gomer, Richard H

2017-03-01

Autocrine proliferation repressor protein A (AprA) is a protein secreted by Dictyostelium discoideum cells. Although there is very little sequence similarity between AprA and any human protein, AprA has a predicted structural similarity to the human protein dipeptidyl peptidase IV (DPPIV). AprA is a chemorepellent for Dictyostelium cells, and DPPIV is a chemorepellent for neutrophils. This led us to investigate if AprA and DPPIV have additional functional similarities. We find that like AprA, DPPIV is a chemorepellent for, and inhibits the proliferation of, D. discoideum cells, and that AprA binds some DPPIV binding partners such as fibronectin. Conversely, rAprA has DPPIV-like protease activity. These results indicate a functional similarity between two eukaryotic chemorepellent proteins with very little sequence similarity, and emphasize the usefulness of using a predicted protein structure to search a protein structure database, in addition to searching for proteins with similar sequences. © 2016 The Protein Society.

Corticospinal contribution to arm muscle activity during human walking

DEFF Research Database (Denmark)

Barthélemy, Dorothy; Nielsen, Jens Bo

2010-01-01

inhibitory interneurones, the suppression is in all likelihood caused by removal of a corticospinal contribution to the ongoing EMG activity. The data thus suggest that the motor cortex makes an active contribution, through the corticospinal tract, to the ongoing EMG activity in arm muscles during walking....

Heat shock proteins on the human sperm surface.

Science.gov (United States)

Naaby-Hansen, Soren; Herr, John C

2010-01-01

The sperm plasma membrane is known to be critical to fertilization and to be highly regionalized into domains of head, mid- and principal pieces. However, the molecular composition of the sperm plasma membrane and its alterations during genital tract passage, capacitation and the acrosome reaction remains to be fully dissected. A two-dimensional gel-based proteomic study previously identified 98 human sperm proteins which were accessible for surface labelling with both biotin and radioiodine. In this report twelve dually labelled protein spots were excised from stained gels or PDVF membranes and analysed by mass spectrometry (MS) and Edman degradation. Seven members from four different heat shock protein (HSP) families were identified including HYOU1 (ORP150), HSPC1 (HSP86), HSPA5 (Bip), HSPD1 (HSP60), and several isoforms of the two testis-specific HSP70 chaperones HSPA2 and HSPA1L. An antiserum raised against the testis-specific HSPA2 chaperone reacted with three 65kDa HSPA2 isoforms and three high molecular weight surface proteins (78-79kDa, 84kDa and 90-93kDa). These proteins, together with seven 65kDa HSP70 forms, reacted with human anti-sperm IgG antibodies that blocked in vitro fertilization in humans. Three of these surface biotinylated human sperm antigens were immunoprecipitated with a rabbit antiserum raised against a linear peptide epitope in Chlamydia trachomatis HSP70. The results indicate diverse HSP chaperones are accessible for surface labelling on human sperm. Some of these share epitopes with C. trachomatis HSP70, suggesting an association between genital tract infection, immunity to HSP70 and reproductive failure. 2009 Elsevier Ireland Ltd. All rights reserved.

Robotic arm

International Nuclear Information System (INIS)

Kwech, H.

1989-01-01

A robotic arm positionable within a nuclear vessel by access through a small diameter opening and having a mounting tube supported within the vessel and mounting a plurality of arm sections for movement lengthwise of the mounting tube as well as for movement out of a window provided in the wall of the mounting tube is disclosed. An end effector, such as a grinding head or welding element, at an operating end of the robotic arm, can be located and operated within the nuclear vessel through movement derived from six different axes of motion provided by mounting and drive connections between arm sections of the robotic arm. The movements are achieved by operation of remotely-controllable servo motors, all of which are mounted at a control end of the robotic arm to be outside the nuclear vessel. 23 figs

Human Cells as Platform to Produce Gamma-Carboxylated Proteins.

Science.gov (United States)

de Sousa Bomfim, Aline; de Freitas, Marcela Cristina Corrêa; Covas, Dimas Tadeu; de Sousa Russo, Elisa Maria

2018-01-01

The gamma-carboxylated proteins belong to a family of proteins that depend on vitamin K for normal biosynthesis. The major representative gamma-carboxylated proteins are the coagulation system proteins, for example, factor VII, factor IX, factor X, prothrombin, and proteins C, S, and Z. These molecules have harbored posttranslational modifications, such as glycosylation and gamma-carboxylation, and for this reason they need to be produced in mammalian cell lines. Human cells lines have emerged as the most promising alternative to the production of gamma-carboxylated proteins. In this chapter, the methods to generate human cells as a platform to produce gamma-carboxylated proteins, for example the coagulation factors VII and IX, are presented. From the cell line modification up to the vitamin K adaptation of the produced cells is described in the protocols presented in this chapter.

Imparting albumin-binding affinity to a human protein by mimicking the contact surface of a bacterial binding protein.

Science.gov (United States)

Oshiro, Satoshi; Honda, Shinya

2014-04-18

Attachment of a bacterial albumin-binding protein module is an attractive strategy for extending the plasma residence time of protein therapeutics. However, a protein fused with such a bacterial module could induce unfavorable immune reactions. To address this, we designed an alternative binding protein by imparting albumin-binding affinity to a human protein using molecular surface grafting. The result was a series of human-derived 6 helix-bundle proteins, one of which specifically binds to human serum albumin (HSA) with adequate affinity (KD = 100 nM). The proteins were designed by transferring key binding residues of a bacterial albumin-binding module, Finegoldia magna protein G-related albumin-binding domain (GA) module, onto the human protein scaffold. Despite 13-15 mutations, the designed proteins maintain the original secondary structure by virtue of careful grafting based on structural informatics. Competitive binding assays and thermodynamic analyses of the best binders show that the binding mode resembles that of the GA module, suggesting that the contacting surface of the GA module is mimicked well on the designed protein. These results indicate that the designed protein may act as an alternative low-risk binding module to HSA. Furthermore, molecular surface grafting in combination with structural informatics is an effective approach for avoiding deleterious mutations on a target protein and for imparting the binding function of one protein onto another.

Insight into bacterial virulence mechanisms against host immune response via the Yersinia pestis-human protein-protein interaction network.

Science.gov (United States)

Yang, Huiying; Ke, Yuehua; Wang, Jian; Tan, Yafang; Myeni, Sebenzile K; Li, Dong; Shi, Qinghai; Yan, Yanfeng; Chen, Hui; Guo, Zhaobiao; Yuan, Yanzhi; Yang, Xiaoming; Yang, Ruifu; Du, Zongmin

2011-11-01

A Yersinia pestis-human protein interaction network is reported here to improve our understanding of its pathogenesis. Up to 204 interactions between 66 Y. pestis bait proteins and 109 human proteins were identified by yeast two-hybrid assay and then combined with 23 previously published interactions to construct a protein-protein interaction network. Topological analysis of the interaction network revealed that human proteins targeted by Y. pestis were significantly enriched in the proteins that are central in the human protein-protein interaction network. Analysis of this network showed that signaling pathways important for host immune responses were preferentially targeted by Y. pestis, including the pathways involved in focal adhesion, regulation of cytoskeleton, leukocyte transendoepithelial migration, and Toll-like receptor (TLR) and mitogen-activated protein kinase (MAPK) signaling. Cellular pathways targeted by Y. pestis are highly relevant to its pathogenesis. Interactions with host proteins involved in focal adhesion and cytoskeketon regulation pathways could account for resistance of Y. pestis to phagocytosis. Interference with TLR and MAPK signaling pathways by Y. pestis reflects common characteristics of pathogen-host interaction that bacterial pathogens have evolved to evade host innate immune response by interacting with proteins in those signaling pathways. Interestingly, a large portion of human proteins interacting with Y. pestis (16/109) also interacted with viral proteins (Epstein-Barr virus [EBV] and hepatitis C virus [HCV]), suggesting that viral and bacterial pathogens attack common cellular functions to facilitate infections. In addition, we identified vasodilator-stimulated phosphoprotein (VASP) as a novel interaction partner of YpkA and showed that YpkA could inhibit in vitro actin assembly mediated by VASP.

Casein and soy protein meals differentially affect whole-body and splanchnic protein metabolism in healthy humans.

Science.gov (United States)

Luiking, Yvette C; Deutz, Nicolaas E P; Jäkel, Martin; Soeters, Peter B

2005-05-01

Dietary protein quality is considered to be dependent on the degree and velocity with which protein is digested, absorbed as amino acids, and retained in the gut as newly synthesized protein. Metabolic animal studies suggest that the quality of soy protein is inferior to that of casein protein, but confirmatory studies in humans are lacking. The study objective was to assess the quality of casein and soy protein by comparing their metabolic effects in healthy human subjects. Whole-body protein kinetics, splanchnic leucine extraction, and urea production rates were measured in the postabsorptive state and during 8-h enteral intakes of isonitrogenous [0.42 g protein/(kg body weight . 8 h)] protein-based test meals, which contained either casein (CAPM; n = 12) or soy protein (SOPM; n = 10) in 2 separate groups. Stable isotope techniques were used to study metabolic effects. With enteral food intake, protein metabolism changed from net protein breakdown to net protein synthesis. Net protein synthesis was greater in the CAPM group than in the SOPM group [52 +/- 14 and 17 +/- 14 nmol/(kg fat-free mass (FFM) . min), respectively; P CAPM (P = 0.07). Absolute splanchnic extraction of leucine was higher in the subjects that consumed CAPM [306 +/- 31 nmol/(kg FFM . min)] vs. those that consumed SOPM [235 +/- 29 nmol/(kg FFM . min); P < 0.01]. In conclusion, a significantly larger portion of soy protein is degraded to urea, whereas casein protein likely contributes to splanchnic utilization (probably protein synthesis) to a greater extent. The biological value of soy protein must be considered inferior to that of casein protein in humans.

Functional similarities between the dictyostelium protein AprA and the human protein dipeptidyl‐peptidase IV

Science.gov (United States)

Herlihy, Sarah E.; Tang, Yu; Phillips, Jonathan E.

2017-01-01

Abstract Autocrine proliferation repressor protein A (AprA) is a protein secreted by Dictyostelium discoideum cells. Although there is very little sequence similarity between AprA and any human protein, AprA has a predicted structural similarity to the human protein dipeptidyl peptidase IV (DPPIV). AprA is a chemorepellent for Dictyostelium cells, and DPPIV is a chemorepellent for neutrophils. This led us to investigate if AprA and DPPIV have additional functional similarities. We find that like AprA, DPPIV is a chemorepellent for, and inhibits the proliferation of, D. discoideum cells, and that AprA binds some DPPIV binding partners such as fibronectin. Conversely, rAprA has DPPIV‐like protease activity. These results indicate a functional similarity between two eukaryotic chemorepellent proteins with very little sequence similarity, and emphasize the usefulness of using a predicted protein structure to search a protein structure database, in addition to searching for proteins with similar sequences. PMID:28028841

Characterization of a cocaine binding protein in human placenta

International Nuclear Information System (INIS)

Ahmed, M.S.; Zhou, D.H.; Maulik, D.; Eldefrawi, M.E.

1990-01-01

[ 3 H]-Cocaine binding sites are identified in human placental villus tissue plasma membranes. These binding sites are associated with a protein and show saturable and specific binding of [ 3 H]-cocaine with a high affinity site of 170 fmole/mg protein. The binding is lost with pretreatment with trypsin or heat. The membrane bound protein is solubilized with the detergent 3-(3-cholamidopropyl)dimethyl-ammonio-1-propane sulphonate (CHAPS) with retention of its saturable and specific binding of [ 3 H]-cocaine. The detergent-protein complex migrates on a sepharose CL-6B gel chromatography column as a protein with an apparent molecular weight of 75,900. The protein has an S 20,w value of 5.1. The binding of this protein to norcocaine, pseudococaine, nomifensine, imipramine, desipramine, amphetamine and dopamine indicates that it shares some, but not all, the properties of the brain cocaine receptor. The physiologic significance of this protein in human placenta is currently unclear

Evidence for radical-oxidation of plasma proteins in humans

International Nuclear Information System (INIS)

Wang, D.; Davies, M.; Dean, R.; Fu, S.; Taurins, A.; Sullivans, D.

1998-01-01

Oxidation of proteins by radicals has been implicated in many pathological processes. The hydroxyl radical is known to generate protein-bound hydroxylated derivatives of amino acids, for example hydroxyvaline (from Val), hydroxyleucine (from Leu), o-tyrosine (from Phe), and DOPA (from Tyr). In this study, we have investigated the occurrence of these oxidised amino acids in human plasma proteins from both normal subjects and dialysis patients. By employing previously established HPLC methods [Fu et al. Biochemical Journal, 330, 233-239, 1998], we have found that oxidised amino acids exist in normal human plasma proteins (n=32). The level of these oxidised amino acids is not correlated to age. Similar levels of oxidised amino acids are found in the plasma proteins of the dialysis patients (n=6), but a more detailed survey is underway. The relative abundance of the oxidised amino acids is similar to that resulting from oxidation of BSA by hydroxy radicals or Fenton systems [Fu et al. Biochemical Journal, 333, 519-525, 1998]. The results suggest that metal-ion catalysed oxyl-radical chemistry may be a key contributor to the oxidative damage in plasma proteins in vivo in humans

Proteins aggregation and human diseases

International Nuclear Information System (INIS)

Hu, Chin-Kun

2015-01-01

Many human diseases and the death of most supercentenarians are related to protein aggregation. Neurodegenerative diseases include Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), frontotemporallobar degeneration, etc. Such diseases are due to progressive loss of structure or function of neurons caused by protein aggregation. For example, AD is considered to be related to aggregation of Aβ40 (peptide with 40 amino acids) and Aβ42 (peptide with 42 amino acids) and HD is considered to be related to aggregation of polyQ (polyglutamine) peptides. In this paper, we briefly review our recent discovery of key factors for protein aggregation. We used a lattice model to study the aggregation rates of proteins and found that the probability for a protein sequence to appear in the conformation of the aggregated state can be used to determine the temperature at which proteins can aggregate most quickly. We used molecular dynamics and simple models of polymer chains to study relaxation and aggregation of proteins under various conditions and found that when the bending-angle dependent and torsion-angle dependent interactions are zero or very small, then protein chains tend to aggregate at lower temperatures. All atom models were used to identify a key peptide chain for the aggregation of insulin chains and to find that two polyQ chains prefer anti-parallel conformation. It is pointed out that in many cases, protein aggregation does not result from protein mis-folding. A potential drug from Chinese medicine was found for Alzheimer's disease. (paper)

Proteins aggregation and human diseases

Science.gov (United States)

Hu, Chin-Kun

2015-04-01

Many human diseases and the death of most supercentenarians are related to protein aggregation. Neurodegenerative diseases include Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), frontotemporallobar degeneration, etc. Such diseases are due to progressive loss of structure or function of neurons caused by protein aggregation. For example, AD is considered to be related to aggregation of Aβ40 (peptide with 40 amino acids) and Aβ42 (peptide with 42 amino acids) and HD is considered to be related to aggregation of polyQ (polyglutamine) peptides. In this paper, we briefly review our recent discovery of key factors for protein aggregation. We used a lattice model to study the aggregation rates of proteins and found that the probability for a protein sequence to appear in the conformation of the aggregated state can be used to determine the temperature at which proteins can aggregate most quickly. We used molecular dynamics and simple models of polymer chains to study relaxation and aggregation of proteins under various conditions and found that when the bending-angle dependent and torsion-angle dependent interactions are zero or very small, then protein chains tend to aggregate at lower temperatures. All atom models were used to identify a key peptide chain for the aggregation of insulin chains and to find that two polyQ chains prefer anti-parallel conformation. It is pointed out that in many cases, protein aggregation does not result from protein mis-folding. A potential drug from Chinese medicine was found for Alzheimer's disease.

Dengue-2 Structural Proteins Associate with Human Proteins to Produce a Coagulation and Innate Immune Response Biased Interactome

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Soares Luis RB

2011-01-01

Full Text Available Abstract Background Dengue virus infection is a public health threat to hundreds of millions of individuals in the tropical regions of the globe. Although Dengue infection usually manifests itself in its mildest, though often debilitating clinical form, dengue fever, life-threatening complications commonly arise in the form of hemorrhagic shock and encephalitis. The etiological basis for the virus-induced pathology in general, and the different clinical manifestations in particular, are not well understood. We reasoned that a detailed knowledge of the global biological processes affected by virus entry into a cell might help shed new light on this long-standing problem. Methods A bacterial two-hybrid screen using DENV2 structural proteins as bait was performed, and the results were used to feed a manually curated, global dengue-human protein interaction network. Gene ontology and pathway enrichment, along with network topology and microarray meta-analysis, were used to generate hypothesis regarding dengue disease biology. Results Combining bioinformatic tools with two-hybrid technology, we screened human cDNA libraries to catalogue proteins physically interacting with the DENV2 virus structural proteins, Env, cap and PrM. We identified 31 interacting human proteins representing distinct biological processes that are closely related to the major clinical diagnostic feature of dengue infection: haemostatic imbalance. In addition, we found dengue-binding human proteins involved with additional key aspects, previously described as fundamental for virus entry into cells and the innate immune response to infection. Construction of a DENV2-human global protein interaction network revealed interesting biological properties suggested by simple network topology analysis. Conclusions Our experimental strategy revealed that dengue structural proteins interact with human protein targets involved in the maintenance of blood coagulation and innate anti

Natural Resource Extraction, Armed Violence, and Environmental Degradation.

Science.gov (United States)

Downey, Liam; Bonds, Eric; Clark, Katherine

2010-12-01

The goal of this article is to demonstrate that environmental sociologists cannot fully explain the relationship between humans and the natural world without theorizing a link between natural resource extraction, armed violence, and environmental degradation. The authors begin by arguing that armed violence is one of several overlapping mechanisms that provide powerful actors with the means to (a) prevail over others in conflicts over natural resources and (b) ensure that natural resources critical to industrial production and state power continue to be extracted and sold in sufficient quantities to promote capital accumulation, state power, and ecological unequal exchange. The authors then identify 10 minerals that are critical to the functioning of the U.S. economy and/or military and demonstrate that the extraction of these minerals often involves the use of armed violence. They further demonstrate that armed violence is associated with the activities of the world's three largest mining companies, with African mines that receive World Bank funding, and with petroleum and rainforest timber extraction. The authors conclude that the natural resource base on which industrial societies stand is constructed in large part through the use and threatened use of armed violence. As a result, armed violence plays a critical role in fostering environmental degradation and ecological unequal exchange.

The spiral arms of the Milky Way: The relative location of each different arm tracer within a typical spiral arm width

Energy Technology Data Exchange (ETDEWEB)

Vallée, Jacques P., E-mail: jacques.vallee@nrc-cnrc.gc.ca [National Research Council Canada, National Science Infrastructure portfolio, Herzberg Astronomy and Astrophysics, 5071 West Saanich Road, Victoria, B.C., V9E 2E7 (Canada)

2014-07-01

From the Sun's location in the Galactic disk, different arm tracers (CO, H I, hot dust, etc.) have been employed to locate a tangent to each spiral arm. Using all various and different observed spiral arm tracers (as published elsewhere), we embark on a new goal, namely the statistical analysis of these published data (data mining) to statistically compute the mean location of each spiral arm tracer. We show for a typical arm cross-cut, a separation of 400 pc between the mid-arm and the dust lane (at the inner edge of the arm, toward the Galactic center). Are some arms major and others minor? Separating arms into two sets, as suggested by some, we find the same arm widths between the two sets. Our interpretation is that we live in a multiple (four-arm) spiral (logarithmic) pattern (around a pitch angle of 12°) for the stars and gas in the Milky Way, with a sizable interarm separation (around 3 kpc) at the Sun's location and the same arm width for each arm (near 400 pc from mid-arm to dust lane).

The spiral arms of the Milky Way: The relative location of each different arm tracer within a typical spiral arm width

International Nuclear Information System (INIS)

Vallée, Jacques P.

2014-01-01

From the Sun's location in the Galactic disk, different arm tracers (CO, H I, hot dust, etc.) have been employed to locate a tangent to each spiral arm. Using all various and different observed spiral arm tracers (as published elsewhere), we embark on a new goal, namely the statistical analysis of these published data (data mining) to statistically compute the mean location of each spiral arm tracer. We show for a typical arm cross-cut, a separation of 400 pc between the mid-arm and the dust lane (at the inner edge of the arm, toward the Galactic center). Are some arms major and others minor? Separating arms into two sets, as suggested by some, we find the same arm widths between the two sets. Our interpretation is that we live in a multiple (four-arm) spiral (logarithmic) pattern (around a pitch angle of 12°) for the stars and gas in the Milky Way, with a sizable interarm separation (around 3 kpc) at the Sun's location and the same arm width for each arm (near 400 pc from mid-arm to dust lane).

Protein S binding to human endothelial cells is required for expression of cofactor activity for activated protein C

NARCIS (Netherlands)

Hackeng, T. M.; Hessing, M.; van 't Veer, C.; Meijer-Huizinga, F.; Meijers, J. C.; de Groot, P. G.; van Mourik, J. A.; Bouma, B. N.

1993-01-01

An important feedback mechanism in blood coagulation is supplied by the protein C/protein S anticoagulant pathway. In this study we demonstrate that the binding of human protein S to cultured human umbilical vein endothelial cells (HUVECs) is required for the expression of cofactor activity of

Production of tissue microarrays, immunohistochemistry staining and digitalization within the human protein atlas.

Science.gov (United States)

Kampf, Caroline; Olsson, Ingmarie; Ryberg, Urban; Sjöstedt, Evelina; Pontén, Fredrik

2012-05-31

The tissue microarray (TMA) technology provides the means for high-throughput analysis of multiple tissues and cells. The technique is used within the Human Protein Atlas project for global analysis of protein expression patterns in normal human tissues, cancer and cell lines. Here we present the assembly of 1 mm cores, retrieved from microscopically selected representative tissues, into a single recipient TMA block. The number and size of cores in a TMA block can be varied from approximately forty 2 mm cores to hundreds of 0.6 mm cores. The advantage of using TMA technology is that large amount of data can rapidly be obtained using a single immunostaining protocol to avoid experimental variability. Importantly, only limited amount of scarce tissue is needed, which allows for the analysis of large patient cohorts (1 2). Approximately 250 consecutive sections (4 μm thick) can be cut from a TMA block and used for immunohistochemical staining to determine specific protein expression patterns for 250 different antibodies. In the Human Protein Atlas project, antibodies are generated towards all human proteins and used to acquire corresponding protein profiles in both normal human tissues from 144 individuals and cancer tissues from 216 different patients, representing the 20 most common forms of human cancer. Immunohistochemically stained TMA sections on glass slides are scanned to create high-resolution images from which pathologists can interpret and annotate the outcome of immunohistochemistry. Images together with corresponding pathology-based annotation data are made publically available for the research community through the Human Protein Atlas portal (www.proteinatlas.org) (Figure 1) (3 4). The Human Protein Atlas provides a map showing the distribution and relative abundance of proteins in the human body. The current version contains over 11 million images with protein expression data for 12.238 unique proteins, corresponding to more than 61% of all proteins

Noninvasive Electroencephalogram Based Control of a Robotic Arm for Reach and Grasp Tasks

Science.gov (United States)

Meng, Jianjun; Zhang, Shuying; Bekyo, Angeliki; Olsoe, Jaron; Baxter, Bryan; He, Bin

2016-01-01

Brain-computer interface (BCI) technologies aim to provide a bridge between the human brain and external devices. Prior research using non-invasive BCI to control virtual objects, such as computer cursors and virtual helicopters, and real-world objects, such as wheelchairs and quadcopters, has demonstrated the promise of BCI technologies. However, controlling a robotic arm to complete reach-and-grasp tasks efficiently using non-invasive BCI has yet to be shown. In this study, we found that a group of 13 human subjects could willingly modulate brain activity to control a robotic arm with high accuracy for performing tasks requiring multiple degrees of freedom by combination of two sequential low dimensional controls. Subjects were able to effectively control reaching of the robotic arm through modulation of their brain rhythms within the span of only a few training sessions and maintained the ability to control the robotic arm over multiple months. Our results demonstrate the viability of human operation of prosthetic limbs using non-invasive BCI technology. PMID:27966546

[Cow's milk protein allergy through human milk].

Science.gov (United States)

Denis, M; Loras-Duclaux, I; Lachaux, A

2012-03-01

Cow's milk protein allergy (CMPA) is the first allergy that affects infants. In this population, the incidence rate reaches 7.5%. The multiplicity and aspecificity of the symptoms makes its diagnosis sometimes complicated, especially in the delayed type (gastrointestinal, dermatological, and cutaneous). CMPA symptoms can develop in exclusively breastfed infants with an incidence rate of 0.5%. It, therefore, raises questions about sensitization to cow's milk proteins through breast milk. Transfer of native bovine proteins such as β-lactoglobulin into the breast milk is controversial: some authors have found bovine proteins in human milk but others point to cross-reactivity between human milk proteins and cow's milk proteins. However, it seems that a small percentage of dietary proteins can resist digestion and become potentially allergenic. Moreover, some authors suspect the transfer of some of these dietary proteins from the maternal bloodstream to breast milk, but the mechanisms governing sensitization are still being studied. Theoretically, CMPA diagnosis is based on clinical observations, prick-test or patch-test results, and cow's milk-specific IgE antibody concentration. A positive food challenge test usually confirms the diagnosis. No laboratory test is available to make a certain diagnosis, but the detection of eosinophil cationic protein (ECP) in the mother's milk, for example, seems to be advantageous since it is linked to CMA. Excluding cow's milk from the mother's diet is the only cure when she still wants to breastfeed. Usually, cow's milk proteins are reintroduced after 6 months of exclusion. Indeed, the prognosis for infants is very good: 80% acquire a tolerance before the age of 3 or 4 years. Mothers should not avoid dairy products during pregnancy and breastfeeding as preventive measures against allergy. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Human Immunodeficiency Virus Proteins Mimic Human T Cell Receptors Inducing Cross-Reactive Antibodies

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Robert Root-Bernstein

2017-10-01

Full Text Available Human immunodeficiency virus (HIV hides from the immune system in part by mimicking host antigens, including human leukocyte antigens. It is demonstrated here that HIV also mimics the V-β-D-J-β of approximately seventy percent of about 600 randomly selected human T cell receptors (TCR. This degree of mimicry is greater than any other human pathogen, commensal or symbiotic organism studied. These data suggest that HIV may be evolving into a commensal organism just as simian immunodeficiency virus has done in some types of monkeys. The gp120 envelope protein, Nef protein and Pol protein are particularly similar to host TCR, camouflaging HIV from the immune system and creating serious barriers to the development of safe HIV vaccines. One consequence of HIV mimicry of host TCR is that antibodies against HIV proteins have a significant probability of recognizing the corresponding TCR as antigenic targets, explaining the widespread observation of lymphocytotoxic autoantibodies in acquired immunodeficiency syndrome (AIDS. Quantitative enzyme-linked immunoadsorption assays (ELISA demonstrated that every HIV antibody tested recognized at least one of twelve TCR, and as many as seven, with a binding constant in the 10−8 to 10−9 m range. HIV immunity also affects microbiome tolerance in ways that correlate with susceptibility to specific opportunistic infections.

FINE SPECIFICITY OF CELLULAR IMMUNE-RESPONSES IN HUMANS TO HUMAN CYTOMEGALOVIRUS IMMEDIATE-EARLY 1-PROTEIN

NARCIS (Netherlands)

ALP, NJ; ALLPORT, TD; VANZANTEN, J; RODGERS, B; SISSONS, JGP; BORYSIEWICZ, LK

Cell-mediated immunity is important in maintaining the virus-host equilibrium in persistent human cytomegalovirus (HCMV) infection. The HCMV 72-kDa major immediate early 1 protein (IE1) is a target for CD8+ cytotoxic T cells in humans, as is the equivalent 89-kDa protein in mouse. Less is known

Abundance in proteins expressed after functional electrical stimulation cycling or arm cycling ergometry training in persons with chronic spinal cord injury.

Science.gov (United States)

Gorgey, Ashraf S; Graham, Zachary A; Bauman, William A; Cardozo, Christopher; Gater, David R

2017-07-01

Longitudinal design. The study determined the effects of two forms of exercise training on the abundance of two proteins, (glucose transporter-4 [GLUT-4], adenosine monophosphate kinase [AMPK]) involved in glucose utilization and the transcriptional coactivator that regulates the genes involved in energy metabolism and mitochondrial biogenesis (peroxisome proliferator-activated receptor (PPAR) coactivator 1 alpha [PGC-1α]), in muscles in men with chronic motor-complete spinal cord injury (SCI). Clinical trial at a Medical Center. Nine men with chronic motor-complete SCI participated in functional electrical stimulation lower extremity cycling (FES-LEC; n = 4) or arm cycling ergometer (arm-cycling ergometer [ACE]; n = 5) 5 days/week for 16 weeks. Whole body composition was measured by dual energy X-ray absorptiometry. An intravenous glucose tolerance test was performed to measure glucose effectiveness (Sg) and insulin sensitivity (Si). Muscle biopsies of the right vastus lateralis (VL) and triceps muscles were collected one week prior to and post the exercise training intervention. Neither training intervention altered body composition or carbohydrate metabolism. GLUT-4 increased by 3.8 fold in the VL after FES training and increased 0.6 fold in the triceps after ACE training. PGC-1α increased by 2.3 fold in the VL after FES training and 3.8 fold in the triceps after ACE training. AMPK increased by 3.4 fold in the VL after FES training and in the triceps after ACE training. FES-LEC and ACE training were associated with greater protein expressions in the trained muscles by effectively influencing the abundance of GLUT-4, AMPK and PGC-1α. Thus, FES-LEC training of paralyzed muscle can modulate protein expression similar to that of trained and innervated muscle.

Purification of human alpha uterine protein.

Science.gov (United States)

Sutcliffe, R G; Bolton, A E; Sharp, F; Nicholson, L V; MacKinnon, R

1980-03-01

Human alpha uterine protein (AUP) has been prepared from extracts of decudua by antibody affinity chromatography, DEAE Sepharose chromatography and by filtration through Sephadex G-150. This procedure yielded a protein fraction containing AUP, which was labelled with 125I by chloramine T. When analysed by SDS gel electrophoresis this radioiodinated protein fraction was found to contain predominantly a single species of protein which was precipitated by antibodies against AUP in antibody-antigen crossed electrophoresis. Rabbit anti-AUP precipitated 55-65% of the tracer in a double-antibody system. Sephadex G150 gel filtration of AUP obtained before and after affinity chromatography provided a molecular weight estimate of 50000. Since SDS gel electrophoresis revealed a polypeptide molecular weight of 23000-25000, it is suggested that AUP is a dimer.

Structural studies of human glioma pathogenesis-related protein 1

Energy Technology Data Exchange (ETDEWEB)

Asojo, Oluwatoyin A., E-mail: oasojo@unmc.edu [College of Medicine, Nebraska Medical Center, Omaha, NE 68198-6495 (United States); Koski, Raymond A.; Bonafé, Nathalie [L2 Diagnostics LLC, 300 George Street, New Haven, CT 06511 (United States); College of Medicine, Nebraska Medical Center, Omaha, NE 68198-6495 (United States)

2011-10-01

Structural analysis of a truncated soluble domain of human glioma pathogenesis-related protein 1, a membrane protein implicated in the proliferation of aggressive brain cancer, is presented. Human glioma pathogenesis-related protein 1 (GLIPR1) is a membrane protein that is highly upregulated in brain cancers but is barely detectable in normal brain tissue. GLIPR1 is composed of a signal peptide that directs its secretion, a conserved cysteine-rich CAP (cysteine-rich secretory proteins, antigen 5 and pathogenesis-related 1 proteins) domain and a transmembrane domain. GLIPR1 is currently being investigated as a candidate for prostate cancer gene therapy and for glioblastoma targeted therapy. Crystal structures of a truncated soluble domain of the human GLIPR1 protein (sGLIPR1) solved by molecular replacement using a truncated polyalanine search model of the CAP domain of stecrisp, a snake-venom cysteine-rich secretory protein (CRISP), are presented. The correct molecular-replacement solution could only be obtained by removing all loops from the search model. The native structure was refined to 1.85 Å resolution and that of a Zn{sup 2+} complex was refined to 2.2 Å resolution. The latter structure revealed that the putative binding cavity coordinates Zn{sup 2+} similarly to snake-venom CRISPs, which are involved in Zn{sup 2+}-dependent mechanisms of inflammatory modulation. Both sGLIPR1 structures have extensive flexible loop/turn regions and unique charge distributions that were not observed in any of the previously reported CAP protein structures. A model is also proposed for the structure of full-length membrane-bound GLIPR1.

Human Rights in Armed Conflicts and Constitutional Law

OpenAIRE

Antonios Maniatis

2017-01-01

The main purpose of this paper is to determine the impact of both International Humanitarian Law and anti-piracy International Law on Constitutional Law. International Law is endowed with a rich set of norms on the protection of private individuals in armed conflicts and copes with the diachronic crime of maritime piracy, which may be considered as a private war in the high seas. Constitutional Law has been traditionally geared at two generations of fundamental rights. The paper will aim at a...

UVA photolysis using the protein-bound sensitizers present in human lens

International Nuclear Information System (INIS)

Ortwerth, B.J.; Olesen, P.R.

1994-01-01

This research was undertaken to demonstrate that the protein-bound chromophores in aged human lens can act as sensitizers for protein damage by UVA light. The water-insoluble (WI) proteins from pooled human and bovine lenses were solubilized by sonication in water and illuminated with UV light similar in output to that transmitted by the cornea. Analysis of the irradiated proteins showed a linear decrease in sulfhydryl groups with a 30% loss after 2 h. No loss was seen when native α-crystallin was irradiated under the same conditions. A 25% loss of histidine residues was also observed with the human lens WI fraction, and sodium dodecyl sulfate polyacrylamide gels indicated considerable protein cross-linking. Similar photodamage was seen with a WI fraction from old bovine lenses. While the data show the presence of UVA sensitizers, some histidine destruction and protein cross-linking were also obtained with α-crystallin and with lysozyme which argue that part of the histidine loss in the human WISS was likely due to tryptophan acting as a sensitizer. (Author)

Small GTP-binding proteins in human endothelial cells

NARCIS (Netherlands)

de Leeuw, H. P.; Koster, P. M.; Calafat, J.; Janssen, H.; van Zonneveld, A. J.; van Mourik, J. A.; Voorberg, J.

1998-01-01

Small GTP-binding proteins of the Ras superfamily control an extensive number of intracellular events by alternating between GDP- and GTP-bound conformation. The presence of members of this protein family was examined in human umbilical vein endothelial cells employing RT-PCR. Sequence analysis of

A Drosophila gene encoding a protein resembling the human β-amyloid protein precursor

International Nuclear Information System (INIS)

Rosen, D.R.; Martin-Morris, L.; Luo, L.; White, K.

1989-01-01

The authors have isolated genomic and cDNA clones for a Drosophila gene resembling the human β-amyloid precursor protein (APP). This gene produces a nervous system-enriched 6.5-kilobase transcript. Sequencing of cDNAs derived from the 6.5-kilobase transcript predicts an 886-amino acid polypeptide. This polypeptide contains a putative transmembrane domain and exhibits strong sequence similarity to cytoplasmic and extracellular regions of the human β-amyloid precursor protein. There is a high probability that this Drosophila gene corresponds to the essential Drosophila locus vnd, a gene required for embryonic nervous system development

NRAGE induces β-catenin/Arm O-GlcNAcylation and negatively regulates Wnt signaling

International Nuclear Information System (INIS)

Chen, Yuxin; Jin, Lei; Xue, Bin; Jin, Dong; Sun, Fenyong; Wen, Chuanjun

2017-01-01

The Wnt pathway is crucial for animal development, as well as tumor formation. Understanding the regulation of Wnt signaling will help to elucidate the mechanism of the cell cycle, cell differentiation and tumorigenesis. It is generally accepted that in response to Wnt signals, β-catenin accumulates in the cytoplasm and is imported into the nucleus where it recruits LEF/TCF transcription factors to activate the expression of target genes. In this study, we report that human NRAGE, a neurotrophin receptor p75 (p75NTR) binding protein, markedly suppresses the expression of genes activated by the Wnt pathway. Consistent with this finding, loss of function of NRAGE by RNA interference (RNAi) activates the Wnt pathway. Moreover, NRAGE suppresses the induction of axis duplication by microinjected β-catenin in Xenopus embryos. To our surprise, NRAGE induces nuclear localization of β-catenin and increases its DNA binding ability. Further studies reveal that NRAGE leads to the modification of β-catenin/Arm with O-linked beta-N-acetylglucosamine (O-GlcNAc), and failure of the association between β-catenin/Arm and pygopus(pygo) protein, which is required for transcriptional activation of Wnt target genes. Therefore, our findings suggest a novel mechanism for regulating Wnt signaling. - Highlights: • NRAGE suppresses the expressions of Wnt pathway downstream genes. • NRAGE induces nuclear localization of β-catenin and increases its DNA binding ability. • NRAGE activity leads to the O-GlcNAcylation of β-catenin.

Comparative studies of human and chicken retinol-binding proteins and prealbumins.

Science.gov (United States)

Kopelman, M; Mokady, S; Cogan, U

1976-08-09

Microheterogeneity of retinol-binding proteins of human plasma and urine, and of chicken plasma was studied by polyacrylamide gel electrophoresis. All three protein systems were found microheterogenous. Incorporation of retinol into the protein preparations on the one hand, and depletion of these proteins from retinol on the other hand, enabled us to clarify the extent to which the presence or absence of the ligand affects the apparent heterogeneity. Upon electrophoresis, each of the native proteins displayed two pairs of protein zones. It appeared that within each pair the fast moving band corresponded to aporetinol-binding protein which upon binding of retinol was converted to a holoprotein with a slightly lower mobility. However, it did not seem that proteins of one pair were converted to proteins of the second pair upon binding of retinol, substantiating ghe microheterogenous character of this protein system. A rapid, two step procedure for isolation of prealbumins from plasma is described. The method which consists of DEAE-cellulose chromatography follwed by preparative electrophoresis was utilized to separate human and chicken prealbumins. Routine dodecyl sulphate electrophoresis resulted in partial dissociation of human prealbumin but in no dissociation of the chicken protein. More drastic treatments prior to electrophoresis were needed to effect complete disruption of both proteins into subunits.

Inhibition of casein kinase 2 modulates XBP1-GRP78 arm of unfolded protein responses in cultured glial cells.

Directory of Open Access Journals (Sweden)

Toru Hosoi

Full Text Available Stress signals cause abnormal proteins to accumulate in the endoplasmic reticulum (ER. Such stress is known as ER stress, which has been suggested to be involved in neurodegenerative diseases, diabetes, obesity and cancer. ER stress activates the unfolded protein response (UPR to reduce levels of abnormal proteins by inducing the production of chaperon proteins such as GRP78, and to attenuate translation through the phosphorylation of eIF2α. However, excessive stress leads to apoptosis by generating transcription factors such as CHOP. Casein kinase 2 (CK2 is a serine/threonine kinase involved in regulating neoplasia, cell survival and viral infections. In the present study, we investigated a possible linkage between CK2 and ER stress using mouse primary cultured glial cells. 4,5,6,7-tetrabromobenzotriazole (TBB, a CK2-specific inhibitor, attenuated ER stress-induced XBP-1 splicing and subsequent induction of GRP78 expression, but was ineffective against ER stress-induced eIF2α phosphorylation and CHOP expression. Similar results were obtained when endogenous CK2 expression was knocked-down by siRNA. Immunohistochemical analysis suggested that CK2 was present at the ER. These results indicate CK2 to be linked with UPR and to resist ER stress by activating the XBP-1-GRP78 arm of UPR.

ARMin III – Arm Therapy Exoskeleton with an Ergonomic Shoulder Actuation

Directory of Open Access Journals (Sweden)

Tobias Nef

2009-01-01

Full Text Available Rehabilitation robots have become important tools in stroke rehabilitation. Compared to manual arm training, robot-supported training can be more intensive, of longer duration and more repetitive. Therefore, robots have the potential to improve the rehabilitation process in stroke patients. Whereas a majority of previous work in upper limb rehabilitation robotics has focused on end-effector-based robots, a shift towards exoskeleton robots is taking place because they offer a better guidance of the human arm, especially for movements with a large range of motion. However, the implementation of an exoskeleton device introduces the challenge of reproducing the motion of the human shoulder, which is one of the most complex joints of the body. Thus, this paper starts with describing a simplified model of the human shoulder. On the basis of that model, a new ergonomic shoulder actuation principle that provides motion of the humerus head is proposed, and its implementation in the ARMin III arm therapy robot is described. The focus lies on the mechanics and actuation principle. The ARMin III robot provides three actuated degrees of freedom for the shoulder and one for the elbow joint. An additional module provides actuated lower arm pro/supination and wrist flexion/extension. Five ARMin III devices have been manufactured and they are currently undergoing clinical evaluation in hospitals in Switzerland and in the United States.

DNA-binding polarity of human replication protein A positions nucleases in nucleotide excision repair.

Science.gov (United States)

de Laat, W L; Appeldoorn, E; Sugasawa, K; Weterings, E; Jaspers, N G; Hoeijmakers, J H

1998-08-15

The human single-stranded DNA-binding replication A protein (RPA) is involved in various DNA-processing events. By comparing the affinity of hRPA for artificial DNA hairpin structures with 3'- or 5'-protruding single-stranded arms, we found that hRPA binds ssDNA with a defined polarity; a strong ssDNA interaction domain of hRPA is positioned at the 5' side of its binding region, a weak ssDNA-binding domain resides at the 3' side. Polarity appears crucial for positioning of the excision repair nucleases XPG and ERCC1-XPF on the DNA. With the 3'-oriented side of hRPA facing a duplex ssDNA junction, hRPA interacts with and stimulates ERCC1-XPF, whereas the 5'-oriented side of hRPA at a DNA junction allows stable binding of XPG to hRPA. Our data pinpoint hRPA to the undamaged strand during nucleotide excision repair. Polarity of hRPA on ssDNA is likely to contribute to the directionality of other hRPA-dependent processes as well.

Greasy tactics in the plant-pathogen molecular arms race.

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Boyle, Patrick C; Martin, Gregory B

2015-03-01

The modification of proteins by the attachment of fatty acids is a targeting tactic involved in mechanisms of both plant immunity and bacterial pathogenesis. The plant plasma membrane (PM) is a key battleground in the war against disease-causing microbes. This membrane is armed with an array of sensor proteins that function as a surveillance system to detect invading pathogens. Several of these sensor proteins are directed to the plasma membrane through the covalent addition of fatty acids, a process termed fatty acylation. Phytopathogens secrete effector proteins into the plant cell to subvert these surveillance mechanisms, rendering the host susceptible to infection. The targeting of effectors to specific locales within plant cells, particularly the internal face of the host PM, is critical for their virulence function. Several bacterial effectors hijack the host fatty acylation machinery to be modified and directed to this contested locale. To find and fight these fatty acylated effectors the plant leverages lipid-modified intracellular sensors. This review provides examples featuring how fatty acylation is a battle tactic used by both combatants in the molecular arms race between plants and pathogens. Also highlighted is the exploitation of a specific form of host-mediated fatty acid modification, which appears to be exclusively employed by phytopathogenic effector proteins. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Resveratrol-induced cytotoxicity in human Burkitt's lymphoma cells is coupled to the unfolded protein response

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Yan Ying

2010-08-01

Full Text Available Abstract Background Resveratrol (RES, a natural phytoalexin found at high levels in grapes and red wine, has been shown to induce anti-proliferation and apoptosis of human cancer cell lines. However, the underlying molecular mechanisms are at present only partially understood. Method The effects of RES on activation of unfolded protein responses (UPR were evaluated using Western blotting, semi-quantitative and real-time RT-PCR. Cell death was evaluated using Annexin V/PI staining and subsequent FACS. Results Similar as tunicamycin, treatment with RES lead to the activation of all 3 branches of the UPR, with early splicing of XBP-1 indicative of IRE1 activation, phosphorylation of eIF2α consistent with ER resident kinase (PERK activation, activating transcription factor 6 (ATF6 splicing, and increase in expression levels of the downstream molecules GRP78/BiP, GRP94 and CHOP/GADD153 in human Burkitt's lymphoma Raji and Daudi cell lines. RES was shown to induce cell death, which could be attenuated by thwarting upregulation of CHOP. Conclusions Our data suggest that activation of the apoptotic arm of the UPR and its downstream effector CHOP/GADD153 is involved, at least in part, in RES-induced apoptosis in Burkitt's lymphoma cells.

PPI finder: a mining tool for human protein-protein interactions.

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Min He

Full Text Available BACKGROUND: The exponential increase of published biomedical literature prompts the use of text mining tools to manage the information overload automatically. One of the most common applications is to mine protein-protein interactions (PPIs from PubMed abstracts. Currently, most tools in mining PPIs from literature are using co-occurrence-based approaches or rule-based approaches. Hybrid methods (frame-based approaches by combining these two methods may have better performance in predicting PPIs. However, the predicted PPIs from these methods are rarely evaluated by known PPI databases and co-occurred terms in Gene Ontology (GO database. METHODOLOGY/PRINCIPAL FINDINGS: We here developed a web-based tool, PPI Finder, to mine human PPIs from PubMed abstracts based on their co-occurrences and interaction words, followed by evidences in human PPI databases and shared terms in GO database. Only 28% of the co-occurred pairs in PubMed abstracts appeared in any of the commonly used human PPI databases (HPRD, BioGRID and BIND. On the other hand, of the known PPIs in HPRD, 69% showed co-occurrences in the literature, and 65% shared GO terms. CONCLUSIONS: PPI Finder provides a useful tool for biologists to uncover potential novel PPIs. It is freely accessible at http://liweilab.genetics.ac.cn/tm/.

Enhanced vulnerability of human proteins towards disease-associated inactivation through divergent evolution.

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Medina-Carmona, Encarnación; Fuchs, Julian E; Gavira, Jose A; Mesa-Torres, Noel; Neira, Jose L; Salido, Eduardo; Palomino-Morales, Rogelio; Burgos, Miguel; Timson, David J; Pey, Angel L

2017-09-15

Human proteins are vulnerable towards disease-associated single amino acid replacements affecting protein stability and function. Interestingly, a few studies have shown that consensus amino acids from mammals or vertebrates can enhance protein stability when incorporated into human proteins. Here, we investigate yet unexplored relationships between the high vulnerability of human proteins towards disease-associated inactivation and recent evolutionary site-specific divergence of stabilizing amino acids. Using phylogenetic, structural and experimental analyses, we show that divergence from the consensus amino acids at several sites during mammalian evolution has caused local protein destabilization in two human proteins linked to disease: cancer-associated NQO1 and alanine:glyoxylate aminotransferase, mutated in primary hyperoxaluria type I. We demonstrate that a single consensus mutation (H80R) acts as a disease suppressor on the most common cancer-associated polymorphism in NQO1 (P187S). The H80R mutation reactivates P187S by enhancing FAD binding affinity through local and dynamic stabilization of its binding site. Furthermore, we show how a second suppressor mutation (E247Q) cooperates with H80R in protecting the P187S polymorphism towards inactivation through long-range allosteric communication within the structural ensemble of the protein. Our results support that recent divergence of consensus amino acids may have occurred with neutral effects on many functional and regulatory traits of wild-type human proteins. However, divergence at certain sites may have increased the propensity of some human proteins towards inactivation due to disease-associated mutations and polymorphisms. Consensus mutations also emerge as a potential strategy to identify structural hot-spots in proteins as targets for pharmacological rescue in loss-of-function genetic diseases. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please

[Effect of freezing and cooking on the texture and electrophoretic pattern of the proteins of octopus arms (Octopus vulgaris)].

Science.gov (United States)

Reyes, Genara; Nirchio, Mauro; Bello, Rafael; Borderías, Javier

2014-09-01

Texture is the most valuable feature in cephalopods. Factors that mainly affect the texture of octopus are: freezing, scalding and cooking. The aim of this study was to assess the effect of freezing, scalding and length of cooking time on the texture and electrophoretic pattern of proteins of octopus arms. Octopuses were trapped near Margarita Island and carried with ice to the laboratory where they were packed and subjected to: a) freezing at -27 degrees C or at -20 degrees C b) scalding c) cooking for 25 min, 35 min or 45 min. Shear force was determined by Kramer cell on strips of octopus arms. SDS-PAGE was done according to the Laemmli method with 12% polyacrilamide gels. A sensory evaluation of the preference of texture was carried out using a hedonic scale of 7-points and a non-trained panel. Octopus texture was not affected by freezing temperature or scalding. Frozen octopus was softer after cooking than fresh. The longer the cooking time was, the softer the octopus was. Myosin heavy chain (MHC) was not significantly affected by scalding or cooking; however large aggregates heavier than MHC, new bands and loss of resolution of the bands appeared. Myosin and paramyosin bands were more affected by freezing prior to cooking.

Taq I RFLP in the human cellular retinol-binding protein (CRBP) gene

Energy Technology Data Exchange (ETDEWEB)

Pellegrino, A [Istituto di Ricovero e Cura a Carattere Scientifico SANATRIX, Vena (Italy); Garofalo, S; Cocozza, S; Monticelli, A; Varrone, S [CNR Universita degli Studi di Napoli (Italy); Faraonio, R; Colantuoni, V [Universita degli Studi di Napoli (Italy)

1988-08-11

The probe was a Pst I - Bam HI fragment of cDNA, about 600 bp long, encoding for the human CRBP gene. The clone was isolated by screening a human liver cDNA library in the expression vector pEX with antibodies against rat CRBP. Taq I digestion of genomic DNA and hybridization with the CRBP probe detects a two allele polymorphism with allelic fragments of 3.0 kb and 2.7 kb. There are two invariant bands at 2.4 and 2.2 kb. Human CRBP gene has been mapped on the long arm of chromosome 3 using somatic cell hybrids. Co-dominant segregation was observed in two caucasian families (10 individuals).

Are animal models predictive for human postmortem muscle protein degradation?

Science.gov (United States)

Ehrenfellner, Bianca; Zissler, Angela; Steinbacher, Peter; Monticelli, Fabio C; Pittner, Stefan

2017-11-01

A most precise determination of the postmortem interval (PMI) is a crucial aspect in forensic casework. Although there are diverse approaches available to date, the high heterogeneity of cases together with the respective postmortal changes often limit the validity and sufficiency of many methods. Recently, a novel approach for time since death estimation by the analysis of postmortal changes of muscle proteins was proposed. It is however necessary to improve the reliability and accuracy, especially by analysis of possible influencing factors on protein degradation. This is ideally investigated on standardized animal models that, however, require legitimization by a comparison of human and animal tissue, and in this specific case of protein degradation profiles. Only if protein degradation events occur in comparable fashion within different species, respective findings can sufficiently be transferred from the animal model to application in humans. Therefor samples from two frequently used animal models (mouse and pig), as well as forensic cases with representative protein profiles of highly differing PMIs were analyzed. Despite physical and physiological differences between species, western blot analysis revealed similar patterns in most of the investigated proteins. Even most degradation events occurred in comparable fashion. In some other aspects, however, human and animal profiles depicted distinct differences. The results of this experimental series clearly indicate the huge importance of comparative studies, whenever animal models are considered. Although animal models could be shown to reflect the basic principles of protein degradation processes in humans, we also gained insight in the difficulties and limitations of the applicability of the developed methodology in different mammalian species regarding protein specificity and methodic functionality.

Delta-like protein (DLK) is a novel immunohistochemical marker for human hepatoblastomas

DEFF Research Database (Denmark)

Dezso, Katalin; Halász, Judit; Bisgaard, Hanne Cathrine

2008-01-01

Delta-like protein (DLK) is a membrane protein with mostly unknown function. It is expressed by several embryonic tissues among others by the hepatoblasts of rodent and human fetal livers. We have investigated in the present study if this protein is expressed in human hepatoblastomas. The presenc...

Libyan armed conflict 2011: Mortality, injury and population displacement

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Mohamed A. Daw

2015-09-01

Conclusion: The Libyan armed conflict resulted in great human loss and social damage mirrored by high rates of mortality, injury and human displacement. Such parameters peaked as the conflict escalated and differed according to the Libyan regions and provinces involved. National and international efforts should be combined to overcome the consequences of these conflicts.

Isolated effects of peripheral arm and central body cooling on arm performance.

Science.gov (United States)

Giesbrecht, G G; Wu, M P; White, M D; Johnston, C E; Bristow, G K

1995-10-01

Whole body cooling impairs manual arm performance. The independent contributions of local (peripheral) and/or whole body (central) cooling are not known. Therefore, a protocol was developed in which the arm and the rest of the body could be independently cooled. Biceps temperature (Tmus), at a depth of 20 mm, and esophageal temperature (Tes) were measured. Six subjects were immersed to the clavicles in a tank (body tank) of water under 3 conditions: 1) cold body-cold arm (CB-CA); 2) warm body-cold arm (WB-CA); and 3) cold body-warm arm (CB-WA). In the latter two conditions, subjects placed their dominant arm in a separate (arm) tank. Water temperature (Tw) in each tank was independently controlled. In conditions requiring cold body and/or cold arm, Tw in the appropriate tanks was 8 degrees C. In conditions requiring warm body and/or warm arm, Tw in the appropriate tanks was adjusted between 29 and 38 degrees C to maintain body/arm temperature at baseline values. A battery of 6 tests, requiring fine or gross motor movements, were performed immediately before immersion and after 15, 45, and 70 minutes of immersion. In CB-CA, Tes decreased from an average of 37.2 to 35.6 degrees C and Tmus decreased from 34.6 to 22.0 degrees C. In WB-CA, Tmus decreased to 18.1 degrees C (Tes = 37.1 degrees C), and in CB-WA, Tes decreased to 35.8 degrees C (Tmus = 34.5 degrees C). By the end of immersion, there were significant decrements (43-85%) in the performance of all tests in CB-CA and WB-CA (p body and/or the arm elicits large decrements in finger, hand and arm performance. The decrements are due almost entirely to the local effects of arm tissue cooling.

Protein biosynthesis in isolated human scalp hair follicles.

Science.gov (United States)

Vermorken, A J; Weterings, P J; Bloemendal, H

1979-02-15

The present study demonstrates that protein biosynthesis can be studied in single isolated human scalp hair follicles. The matrix and the sheath are the main regions where amino acids are built in. Incorporation is linear for at least five hours. The newly synthesized proteins can be separated into a water-soluble, a urea-soluble and a urea-insoluble fraction. Product analysis has been performed on the first two fractions, revealing different protein patterns.

Diffusion of protein through the human cornea.

Science.gov (United States)

Charalel, Resmi A; Engberg, Kristin; Noolandi, Jaan; Cochran, Jennifer R; Frank, Curtis; Ta, Christopher N

2012-01-01

To determine the rate of diffusion of myoglobin and bovine serum albumin (BSA) through the human cornea. These small proteins have hydrodynamic diameters of approximately 4.4 and 7.2 nm, and molecular weights of 16.7 and 66 kDa, for myoglobin and BSA, respectively. Diffusion coefficients were measured using a diffusion chamber where the protein of interest and balanced salt solution were in different chambers separated by an ex vivo human cornea. Protein concentrations in the balanced salt solution chamber were measured over time. Diffusion coefficients were calculated using equations derived from Fick's law and conservation of mass in a closed system. Our experiments demonstrate that the diffusion coefficient of myoglobin is 5.5 ± 0.9 × 10(-8) cm(2)/s (n = 8; SD = 1.3 × 10(-8) cm(2)/s; 95% CI: 4.6 × 10(-8) to 6.4 × 10(-8) cm(2)/s) and the diffusion coefficient of BSA is 3.1 ± 1.0 × 10(-8) cm(2)/s (n = 8; SD = 1.4 × 10(-8) cm(2)/s; 95% CI: 2.1 × 10(-8) to 4.1 × 10(-8) cm(2)/s). Our study suggests that molecules as large as 7.2 nm may be able to passively diffuse through the human cornea. With applications in pharmacotherapy and the development of an artificial cornea, further experiments are warranted to fully understand the limits of human corneal diffusion and its clinical relevance. Copyright © 2012 S. Karger AG, Basel.

Prediction and characterization of human ageing-related proteins by using machine learning.

Science.gov (United States)

Kerepesi, Csaba; Daróczy, Bálint; Sturm, Ádám; Vellai, Tibor; Benczúr, András

2018-03-06

Ageing has a huge impact on human health and economy, but its molecular basis - regulation and mechanism - is still poorly understood. By today, more than three hundred genes (almost all of them function as protein-coding genes) have been related to human ageing. Although individual ageing-related genes or some small subsets of these genes have been intensively studied, their analysis as a whole has been highly limited. To fill this gap, for each human protein we extracted 21000 protein features from various databases, and using these data as an input to state-of-the-art machine learning methods, we classified human proteins as ageing-related or non-ageing-related. We found a simple classification model based on only 36 protein features, such as the "number of ageing-related interaction partners", "response to oxidative stress", "damaged DNA binding", "rhythmic process" and "extracellular region". Predicted values of the model quantify the relevance of a given protein in the regulation or mechanisms of the human ageing process. Furthermore, we identified new candidate proteins having strong computational evidence of their important role in ageing. Some of them, like Cytochrome b-245 light chain (CY24A) and Endoribonuclease ZC3H12A (ZC12A) have no previous ageing-associated annotations.

Protein tyrosine adduct in humans self-poisoned by chlorpyrifos

International Nuclear Information System (INIS)

Li, Bin; Eyer, Peter; Eddleston, Michael; Jiang, Wei; Schopfer, Lawrence M.; Lockridge, Oksana

2013-01-01

Studies of human cases of self-inflicted poisoning suggest that chlorpyrifos oxon reacts not only with acetylcholinesterase and butyrylcholinesterase but also with other blood proteins. A favored candidate is albumin because in vitro and animal studies have identified tyrosine 411 of albumin as a site covalently modified by organophosphorus poisons. Our goal was to test this proposal in humans by determining whether plasma from humans poisoned by chlorpyrifos has adducts on tyrosine. Plasma samples from 5 self-poisoned humans were drawn at various time intervals after ingestion of chlorpyrifos for a total of 34 samples. All 34 samples were analyzed for plasma levels of chlorpyrifos and chlorpyrifos oxon (CPO) as a function of time post-ingestion. Eleven samples were analyzed for the presence of diethoxyphosphorylated tyrosine by mass spectrometry. Six samples yielded diethoxyphosphorylated tyrosine in pronase digests. Blood collected as late as 5 days after chlorpyrifos ingestion was positive for CPO-tyrosine, consistent with the 20-day half-life of albumin. High plasma CPO levels did not predict detectable levels of CPO-tyrosine. CPO-tyrosine was identified in pralidoxime treated patients as well as in patients not treated with pralidoxime, indicating that pralidoxime does not reverse CPO binding to tyrosine in humans. Plasma butyrylcholinesterase was a more sensitive biomarker of exposure than adducts on tyrosine. In conclusion, chlorpyrifos oxon makes a stable covalent adduct on the tyrosine residue of blood proteins in humans who ingested chlorpyrifos. - Highlights: • Chlorpyrifos-poisoned patients have adducts on protein tyrosine. • Diethoxyphosphate-tyrosine does not lose an alkyl group. • Proteins in addition to AChE and BChE are modified by organophosphates

Protein tyrosine adduct in humans self-poisoned by chlorpyrifos

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Li, Bin, E-mail: binli@unmc.edu [Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-5950 (United States); Eyer, Peter, E-mail: peter.eyer@lrz.uni-muenchen.de [Walther-Straub-Institut Für Pharmakologie und Toxikologie, Ludwig-Maximilians-Universität München, 80336 München (Germany); Eddleston, Michael, E-mail: M.Eddleston@ed.ac.uk [Clinical Pharmacology Unit, University of Edinburgh, Edinburgh (United Kingdom); Jiang, Wei, E-mail: wjiang@unmc.edu [Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-5950 (United States); Schopfer, Lawrence M., E-mail: lmschopf@unmc.edu [Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-5950 (United States); Lockridge, Oksana, E-mail: olockrid@unmc.edu [Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-5950 (United States)

2013-06-15

Studies of human cases of self-inflicted poisoning suggest that chlorpyrifos oxon reacts not only with acetylcholinesterase and butyrylcholinesterase but also with other blood proteins. A favored candidate is albumin because in vitro and animal studies have identified tyrosine 411 of albumin as a site covalently modified by organophosphorus poisons. Our goal was to test this proposal in humans by determining whether plasma from humans poisoned by chlorpyrifos has adducts on tyrosine. Plasma samples from 5 self-poisoned humans were drawn at various time intervals after ingestion of chlorpyrifos for a total of 34 samples. All 34 samples were analyzed for plasma levels of chlorpyrifos and chlorpyrifos oxon (CPO) as a function of time post-ingestion. Eleven samples were analyzed for the presence of diethoxyphosphorylated tyrosine by mass spectrometry. Six samples yielded diethoxyphosphorylated tyrosine in pronase digests. Blood collected as late as 5 days after chlorpyrifos ingestion was positive for CPO-tyrosine, consistent with the 20-day half-life of albumin. High plasma CPO levels did not predict detectable levels of CPO-tyrosine. CPO-tyrosine was identified in pralidoxime treated patients as well as in patients not treated with pralidoxime, indicating that pralidoxime does not reverse CPO binding to tyrosine in humans. Plasma butyrylcholinesterase was a more sensitive biomarker of exposure than adducts on tyrosine. In conclusion, chlorpyrifos oxon makes a stable covalent adduct on the tyrosine residue of blood proteins in humans who ingested chlorpyrifos. - Highlights: • Chlorpyrifos-poisoned patients have adducts on protein tyrosine. • Diethoxyphosphate-tyrosine does not lose an alkyl group. • Proteins in addition to AChE and BChE are modified by organophosphates.

Determination of human muscle protein fractional synthesis rate

DEFF Research Database (Denmark)

Bornø, Andreas; Hulston, Carl J; van Hall, Gerrit

2014-01-01

In the present study, different MS methods for the determination of human muscle protein fractional synthesis rate (FSR) using [ring-(13)C6 ]phenylalanine as a tracer were evaluated. Because the turnover rate of human skeletal muscle is slow, only minute quantities of the stable isotopically...

The Neanderthal lower arm.

Science.gov (United States)

De Groote, Isabelle

2011-10-01

Neanderthal forearms have been described as being very powerful. Different individual features in the lower arm bones have been described to distinguish Neanderthals from modern humans. In this study, the overall morphology of the radius and ulna is considered, and morphological differences among Neanderthals, Upper Paleolithic Homo sapiens and recent H. sapiens are described. Comparisons among populations were made using a combination of 3D geometric morphometrics and standard multivariate methods. Comparative material included all available complete radii and ulnae from Neanderthals, early H. sapiens and archaeological and recent human populations, representing a wide geographical and lifestyle range. There are few differences among the populations when features are considered individually. Neanderthals and early H. sapiens fell within the range of modern human variation. When the suite of measurements and shapes were analyzed, differences and similarities became apparent. The Neanderthal radius is more laterally curved, has a more medially placed radial tuberosity, a longer radial neck, a more antero-posteriorly ovoid head and a well-developed proximal interosseous crest. The Neanderthal ulna has a more anterior facing trochlear notch, a lower M. brachialis insertion, larger relative mid-shaft size and a more medio-lateral and antero-posterior sinusoidal shaft. The Neanderthal lower arm morphology reflects a strong cold-adapted short forearm. The forearms of H. sapiens are less powerful in pronation and supination. Many differences between Neanderthals and H. sapiens can be explained as a secondary consequence of the hyper-polar body proportions of the Neanderthals, but also as retentions of the primitive condition of other hominoids. Copyright © 2011 Elsevier Ltd. All rights reserved.

SMC Progressively Aligns Chromosomal Arms in Caulobacter crescentus but Is Antagonized by Convergent Transcription

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Ngat T. Tran

2017-08-01

Full Text Available The structural maintenance of chromosomes (SMC complex plays an important role in chromosome organization and segregation in most living organisms. In Caulobacter crescentus, SMC is required to align the left and the right arms of the chromosome that run in parallel down the long axis of the cell. However, the mechanism of SMC-mediated alignment of chromosomal arms remains elusive. Here, using genome-wide methods and microscopy of single cells, we show that Caulobacter SMC is recruited to the centromeric parS site and that SMC-mediated arm alignment depends on the chromosome-partitioning protein ParB. We provide evidence that SMC likely tethers the parS-proximal regions of the chromosomal arms together, promoting arm alignment. Furthermore, we show that highly transcribed genes near parS that are oriented against SMC translocation disrupt arm alignment, suggesting that head-on transcription interferes with SMC translocation. Our results demonstrate a tight interdependence of bacterial chromosome organization and global patterns of transcription.

Evolutionary distance from human homologs reflects allergenicity of animal food proteins.

Science.gov (United States)

Jenkins, John A; Breiteneder, Heimo; Mills, E N Clare

2007-12-01

In silico analysis of allergens can identify putative relationships among protein sequence, structure, and allergenic properties. Such systematic analysis reveals that most plant food allergens belong to a restricted number of protein superfamilies, with pollen allergens behaving similarly. We have investigated the structural relationships of animal food allergens and their evolutionary relatedness to human homologs to define how closely a protein must resemble a human counterpart to lose its allergenic potential. Profile-based sequence homology methods were used to classify animal food allergens into Pfam families, and in silico analyses of their evolutionary and structural relationships were performed. Animal food allergens could be classified into 3 main families--tropomyosins, EF-hand proteins, and caseins--along with 14 minor families each composed of 1 to 3 allergens. The evolutionary relationships of each of these allergen superfamilies showed that in general, proteins with a sequence identity to a human homolog above approximately 62% were rarely allergenic. Single substitutions in otherwise highly conserved regions containing IgE epitopes in EF-hand parvalbumins may modulate allergenicity. These data support the premise that certain protein structures are more allergenic than others. Contrasting with plant food allergens, animal allergens, such as the highly conserved tropomyosins, challenge the capability of the human immune system to discriminate between foreign and self-proteins. Such immune responses run close to becoming autoimmune responses. Exploiting the closeness between animal allergens and their human homologs in the development of recombinant allergens for immunotherapy will need to consider the potential for developing unanticipated autoimmune responses.

Have Third-World Arms Industries Reduced Arms Imports?

OpenAIRE

Looney, R.E.

1989-01-01

Current Research on Peace and Violence, no. 1, 1989. Refereed Journal Article In 1945 only Argentina, Brazil, India and South Africa in the Third World possessed domestic arms industries which produced weapons systems other than small arms and ammunition (SIPRI, 1987, 76).

Human HOXA5 homeodomain enhances protein transduction and its application to vascular inflammation

International Nuclear Information System (INIS)

Lee, Ji Young; Park, Kyoung sook; Cho, Eun Jung; Joo, Hee Kyoung; Lee, Sang Ki; Lee, Sang Do; Park, Jin Bong; Chang, Seok Jong; Jeon, Byeong Hwa

2011-01-01

Highlights: → We have developed an E. coli protein expression vector including human specific gene sequences for protein cellular delivery. → The plasmid was generated by ligation the nucleotides 770-817 of the homeobox A5 mRNA sequence. → HOXA5-APE1/Ref-1 inhibited TNF-alpha-induced monocyte adhesion to endothelial cells. → Human HOXA5-PTD vector provides a powerful research tools for uncovering cellular functions of proteins or for the generation of human PTD-containing proteins. -- Abstract: Cellular protein delivery is an emerging technique by which exogenous recombinant proteins are delivered into mammalian cells across the membrane. We have developed an Escherichia coli expression vector including human specific gene sequences for protein cellular delivery. The plasmid was generated by ligation the nucleotides 770-817 of the homeobox A5 mRNA sequence which was matched with protein transduction domain (PTD) of homeodomain protein A5 (HOXA5) into pET expression vector. The cellular uptake of HOXA5-PTD-EGFP was detected in 1 min and its transduction reached a maximum at 1 h within cell lysates. The cellular uptake of HOXA5-EGFP at 37 o C was greater than in 4 o C. For study for the functional role of human HOXA5-PTD, we purified HOXA5-APE1/Ref-1 and applied it on monocyte adhesion. Pretreatment with HOXA5-APE1/Ref-1 (100 nM) inhibited TNF-α-induced monocyte adhesion to endothelial cells, compared with HOXA5-EGFP. Taken together, our data suggested that human HOXA5-PTD vector provides a powerful research tools for uncovering cellular functions of proteins or for the generation of human PTD-containing proteins.

A Bioinspired 10 DOF Wearable Powered Arm Exoskeleton for Rehabilitation

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Soumya Kanti Manna

2013-01-01

Full Text Available The developed exoskeleton device (Exorn has ten degrees of freedom to control joints starting from shoulder griddle to wrist to provide better redundancy, portability, and flexibility to the human arm motion. A 3D conceptual model is being designed to make the system wearable by human arm. All the joints are simple revolute joints with desired motion limit. A Simulink model of the human arm is being developed with proper mass and length to determine proper torque required for actuating those joints. Forward kinematics of the whole system has been formulated for getting desired dexterous workspace. A proper and simple Graphical User Interface (GUI and the required embedded system have been designed for providing physiotherapy lessons to the patients. In the literature review it has been found that researchers have generally ignored the motion of shoulder griddle. Here we have implemented those motions in our design. It has also been found that people have taken elbow pronation and supination motion as a part of shoulder internal and external rotation though both motions are quite different. A predefined resolved motion rate control structure with independent joint control is used so that all movements can be controlled in a predefined way.

Detection of the human endogenous retrovirus ERV3-encoded Env-protein in human tissues using antibody-based proteomics.

Science.gov (United States)

Fei, Chen; Atterby, Christina; Edqvist, Per-Henrik; Pontén, Fredrik; Zhang, Wei Wei; Larsson, Erik; Ryan, Frank P

2014-01-01

There is growing evidence to suggest that human endogenous retroviruses (HERVs) have contributed to human evolution, being expressed in development, normal physiology and disease. A key difficulty in the scientific evaluation of this potential viral contribution is the accurate demonstration of virally expressed protein in specific human cells and tissues. In this study, we have adopted the endogenous retrovirus, ERV3, as our test model in developing a reliable high-capacity methodology for the expression of such endogenous retrovirus-coded protein. Two affinity-purified polyclonal antibodies to ERV3 Env-encoded protein were generated to detect the corresponding protein expression pattern in specific human cells, tissues and organs. Sampling included normal tissues from 144 individuals ranging from childhood to old age. This included more than forty different tissues and organs and some 216 different cancer tissues representing the twenty commonest forms of human cancer. The Rudbeck Laboratory, Uppsala University and Uppsala University Hospital, Uppsala, Sweden. The potential expression at likely physiological level of the ERV3Env encoded protein in a wide range of human cells, tissues and organs. We found that ERV3 encoded Env protein is expressed at substantive levels in placenta, testis, adrenal gland, corpus luteum, Fallopian tubes, sebaceous glands, astrocytes, bronchial epithelium and the ducts of the salivary glands. Substantive expression was also seen in a variety of epithelial cells as well as cells known to undergo fusion in inflammation and in normal physiology, including fused macrophages, myocardium and striated muscle. This contrasted strongly with the low levels expressed in other tissues types. These findings suggest that this virus plays a significant role in human physiology and may also play a possible role in disease. This technique can now be extended to the study of other HERV genomes within the human chromosomes that may have contributed to

N-terminally truncated GADD34 proteins are convenient translation enhancers in a human cell-derived in vitro protein synthesis system.

Science.gov (United States)

Mikami, Satoshi; Kobayashi, Tominari; Machida, Kodai; Masutani, Mamiko; Yokoyama, Shigeyuki; Imataka, Hiroaki

2010-07-01

Human cell-derived in vitro protein synthesis systems are useful for the production of recombinant proteins. Productivity can be increased by supplementation with GADD34, a protein that is difficult to express in and purify from E. coli. Deletion of the N-terminal 120 or 240 amino acids of GADD34 improves recovery of this protein from E. coli without compromising its ability to boost protein synthesis in an in vitro protein synthesis system. The use of N-terminally truncated GADD34 proteins in place of full-length GADD34 should improve the utility of human cell-based cell-free protein synthesis systems.

Arm Pain

Science.gov (United States)

... be a sign of a heart attack. Seek emergency treatment if you have: Arm, shoulder or back ... http://www.mayoclinic.org/symptoms/arm-pain/basics/definition/SYM-20050870 . Mayo Clinic Footer Legal Conditions and ...

UV-induced DNA-binding proteins in human cells

International Nuclear Information System (INIS)

Glazer, P.M.; Greggio, N.A.; Metherall, J.E.; Summers, W.C.

1989-01-01

To investigate the response of human cells to DNA-damaging agents such as UV irradiation, the authors examined nuclear protein extracts of UV-irradiated HeLa cells for the presence of DNA-binding proteins. Electrophoretically separated proteins were transferred to a nitrocellulose filter that was subsequently immersed in a binding solution containing radioactively labeled DNA probes. Several DNA-binding proteins were induced in HeLa cells after UV irradiation. These included proteins that bind predominantly double-stranded DNA and proteins that bind both double-stranded and single-stranded DNA. The binding proteins were induced in a dose-dependent manner by UV light. Following a dose of 12 J/m 2 , the binding proteins in the nuclear extracts increased over time to a peak in the range of 18 hr after irradiation. Experiments with metabolic inhibitors (cycloheximide and actinomycin D) revealed that de novo synthesis of these proteins is not required for induction of the binding activities, suggesting that the induction is mediated by protein modification

Chlamydomonas Outer Arm Dynein Alters Conformation in Response to Ca2+

OpenAIRE

Sakato, Miho; Sakakibara, Hitoshi; King, Stephen M.

2007-01-01

We have previously shown that Ca2+ directly activates ATP-sensitive microtubule binding by a Chlamydomonas outer arm dynein subparticle containing the β and γ heavy chains (HCs). The γ HC–associated LC4 light chain is a member of the calmodulin family and binds 1-2 Ca2+ with KCa = 3 × 10−5 M in vitro, suggesting it may act as a Ca2+ sensor for outer arm dynein. Here we investigate interactions between the LC4 light chain and γ HC. Two IQ consensus motifs for binding calmodulin-like proteins a...

Identifying protein phosphorylation sites with kinase substrate specificity on human viruses.

Directory of Open Access Journals (Sweden)

Neil Arvin Bretaña

Full Text Available Viruses infect humans and progress inside the body leading to various diseases and complications. The phosphorylation of viral proteins catalyzed by host kinases plays crucial regulatory roles in enhancing replication and inhibition of normal host-cell functions. Due to its biological importance, there is a desire to identify the protein phosphorylation sites on human viruses. However, the use of mass spectrometry-based experiments is proven to be expensive and labor-intensive. Furthermore, previous studies which have identified phosphorylation sites in human viruses do not include the investigation of the responsible kinases. Thus, we are motivated to propose a new method to identify protein phosphorylation sites with its kinase substrate specificity on human viruses. The experimentally verified phosphorylation data were extracted from virPTM--a database containing 301 experimentally verified phosphorylation data on 104 human kinase-phosphorylated virus proteins. In an attempt to investigate kinase substrate specificities in viral protein phosphorylation sites, maximal dependence decomposition (MDD is employed to cluster a large set of phosphorylation data into subgroups containing significantly conserved motifs. The experimental human phosphorylation sites are collected from Phospho.ELM, grouped according to its kinase annotation, and compared with the virus MDD clusters. This investigation identifies human kinases such as CK2, PKB, CDK, and MAPK as potential kinases for catalyzing virus protein substrates as confirmed by published literature. Profile hidden Markov model is then applied to learn a predictive model for each subgroup. A five-fold cross validation evaluation on the MDD-clustered HMMs yields an average accuracy of 84.93% for Serine, and 78.05% for Threonine. Furthermore, an independent testing data collected from UniProtKB and Phospho.ELM is used to make a comparison of predictive performance on three popular kinase

Identifying protein phosphorylation sites with kinase substrate specificity on human viruses.

Science.gov (United States)

Bretaña, Neil Arvin; Lu, Cheng-Tsung; Chiang, Chiu-Yun; Su, Min-Gang; Huang, Kai-Yao; Lee, Tzong-Yi; Weng, Shun-Long

2012-01-01

Viruses infect humans and progress inside the body leading to various diseases and complications. The phosphorylation of viral proteins catalyzed by host kinases plays crucial regulatory roles in enhancing replication and inhibition of normal host-cell functions. Due to its biological importance, there is a desire to identify the protein phosphorylation sites on human viruses. However, the use of mass spectrometry-based experiments is proven to be expensive and labor-intensive. Furthermore, previous studies which have identified phosphorylation sites in human viruses do not include the investigation of the responsible kinases. Thus, we are motivated to propose a new method to identify protein phosphorylation sites with its kinase substrate specificity on human viruses. The experimentally verified phosphorylation data were extracted from virPTM--a database containing 301 experimentally verified phosphorylation data on 104 human kinase-phosphorylated virus proteins. In an attempt to investigate kinase substrate specificities in viral protein phosphorylation sites, maximal dependence decomposition (MDD) is employed to cluster a large set of phosphorylation data into subgroups containing significantly conserved motifs. The experimental human phosphorylation sites are collected from Phospho.ELM, grouped according to its kinase annotation, and compared with the virus MDD clusters. This investigation identifies human kinases such as CK2, PKB, CDK, and MAPK as potential kinases for catalyzing virus protein substrates as confirmed by published literature. Profile hidden Markov model is then applied to learn a predictive model for each subgroup. A five-fold cross validation evaluation on the MDD-clustered HMMs yields an average accuracy of 84.93% for Serine, and 78.05% for Threonine. Furthermore, an independent testing data collected from UniProtKB and Phospho.ELM is used to make a comparison of predictive performance on three popular kinase-specific phosphorylation site

Arms trade and its impact on global health.

Science.gov (United States)

Mahmudi-Azer, Salahaddin

2006-01-01

The most obvious adverse impact of the arms trade on health is loss of life and maiming from the use of weapons in conflicts. Wealthy countries suffer damage to their health and human services when considerable resources are diverted to military expenditure. However, the relative impact of military expenditures and conflict on third world countries is much greater, and often devastating, by depriving a significant portion of the population of essential food, medicine, shelter, education, and economic opportunities. Further, the physical and psychological damage inflicted specifically on children is debilitating - through loss of (or separation from) families, loss of education, destruction of homes, exposure to murder and other violence, sexual abuse, abduction, torture, slavery, and forcible conscription as soldiers. This article outlines the socio-economic impact of the global arms trade in general and the damage done to human health and the environment, specifically.

The human-bacterial pathogen protein interaction networks of Bacillus anthracis, Francisella tularensis, and Yersinia pestis.

Directory of Open Access Journals (Sweden)

Matthew D Dyer

2010-08-01

Full Text Available Bacillus anthracis, Francisella tularensis, and Yersinia pestis are bacterial pathogens that can cause anthrax, lethal acute pneumonic disease, and bubonic plague, respectively, and are listed as NIAID Category A priority pathogens for possible use as biological weapons. However, the interactions between human proteins and proteins in these bacteria remain poorly characterized leading to an incomplete understanding of their pathogenesis and mechanisms of immune evasion.In this study, we used a high-throughput yeast two-hybrid assay to identify physical interactions between human proteins and proteins from each of these three pathogens. From more than 250,000 screens performed, we identified 3,073 human-B. anthracis, 1,383 human-F. tularensis, and 4,059 human-Y. pestis protein-protein interactions including interactions involving 304 B. anthracis, 52 F. tularensis, and 330 Y. pestis proteins that are uncharacterized. Computational analysis revealed that pathogen proteins preferentially interact with human proteins that are hubs and bottlenecks in the human PPI network. In addition, we computed modules of human-pathogen PPIs that are conserved amongst the three networks. Functionally, such conserved modules reveal commonalities between how the different pathogens interact with crucial host pathways involved in inflammation and immunity.These data constitute the first extensive protein interaction networks constructed for bacterial pathogens and their human hosts. This study provides novel insights into host-pathogen interactions.

Recombinant human bone morphogenetic protein induces bone formation

International Nuclear Information System (INIS)

Wang, E.A.; Rosen, V.; D'Alessandro, J.S.; Bauduy, M.; Cordes, P.; Harada, T.; Israel, D.I.; Hewick, R.M.; Kerns, K.M.; LaPan, P.; Luxenberg, D.P.; McQuaid, D.; Moutsatsos, I.K.; Nove, J.; Wozney, J.M.

1990-01-01

The authors have purified and characterized active recombinant human bone morphogenetic protein (BMP) 2A. Implantation of the recombinant protein in rats showed that a single BMP can induce bone formation in vivo. A dose-response and time-course study using the rat ectopic bone formation assay revealed that implantation of 0.5-115 μg of partially purified recombinant human BMP-2A resulted in cartilage by day 7 and bone formation by day 14. The time at which bone formation occurred was dependent on the amount of BMP-2A implanted; at high doses bone formation could be observed at 5 days. The cartilage- and bone-inductive activity of the recombinant BMP-2A is histologically indistinguishable from that of bone extracts. Thus, recombinant BMP-2A has therapeutic potential to promote de novo bone formation in humans

The nucleotide sequence of human transition protein 1 cDNA

Energy Technology Data Exchange (ETDEWEB)

Luerssen, H; Hoyer-Fender, S; Engel, W [Universitaet Goettingen (West Germany)

1988-08-11

The authors have screened a human testis cDNA library with an oligonucleotide of 81 mer prepared according to a part of the published nucleotide sequence of the rat transition protein TP 1. They have isolated a cDNA clone with the length of 441 bp containing the coding region of 162 bp for human transition protein 1. There is about 84% homology in the coding region of the sequence compared to rat. The human cDNA-clone encodes a polypeptide of 54 amino acids of which 7 are different to that of rat.

Dual arm master controller development

Science.gov (United States)

Kuban, D. P.; Perkins, G. S.

1985-01-01

The advanced servomanipulator (ASM) slave was designed with an anthropomorphic stance gear/torque tube power drives, and modular construction. These features resulted in increased inertia, friction, and backlash relative to tape driven manipulators. Studies were performed which addressed to human factor design and performance tradeoffs associated with the corresponding master controller best suited for the ASM. The results of these studies, as well as the conceptual design of the dual arm master controller, are presented.

Neanderthal and Denisova tooth protein variants in present-day humans.

Directory of Open Access Journals (Sweden)

Clément Zanolli

Full Text Available Environment parameters, diet and genetic factors interact to shape tooth morphostructure. In the human lineage, archaic and modern hominins show differences in dental traits, including enamel thickness, but variability also exists among living populations. Several polymorphisms, in particular in the non-collagenous extracellular matrix proteins of the tooth hard tissues, like enamelin, are involved in dental structure variation and defects and may be associated with dental disorders or susceptibility to caries. To gain insights into the relationships between tooth protein polymorphisms and dental structural morphology and defects, we searched for non-synonymous polymorphisms in tooth proteins from Neanderthal and Denisova hominins. The objective was to identify archaic-specific missense variants that may explain the dental morphostructural variability between extinct and modern humans, and to explore their putative impact on present-day dental phenotypes. Thirteen non-collagenous extracellular matrix proteins specific to hard dental tissues have been selected, searched in the publicly available sequence databases of Neanderthal and Denisova individuals and compared with modern human genome data. A total of 16 non-synonymous polymorphisms were identified in 6 proteins (ameloblastin, amelotin, cementum protein 1, dentin matrix acidic phosphoprotein 1, enamelin and matrix Gla protein. Most of them are encoded by dentin and enamel genes located on chromosome 4, previously reported to show signs of archaic introgression within Africa. Among the variants shared with modern humans, two are ancestral (common with apes and one is the derived enamelin major variant, T648I (rs7671281, associated with a thinner enamel and specific to the Homo lineage. All the others are specific to Neanderthals and Denisova, and are found at a very low frequency in modern Africans or East and South Asians, suggesting that they may be related to particular dental traits or

Protein biosynthesis in cultured human hair follicle cells.

Science.gov (United States)

Weterings, P J; Vermorken, A J; Bloemendal, H

1980-10-31

A new technique has been used for culturing human keratinocytes. The cells grow on the basement membrane-like capsules of bovine lenses. Lens cells were removed from the capsules by rigid trypsinization. In order to exclude any contamination with remaining living cells the isolated capsules were irradiated with X-rays at a dose of 10,000 rad. In this way human epithelial cells can be brought in culture from individual hair follicles. Since feeder cells are not used in this culture technique, the biosynthesis of keratinocyte proteins can be studied in these cultures. The newly synthesized proteins can be separated into a water-soluble, a urea-soluble, and a urea-insoluble fraction. Product analysis has been performed on the first two fractions revealing protein patterns identical to those of intact hair follicles. Product analysis of the urea-soluble fractions of microdissected hair follicles shows that the protein pattern of the cultured keratinocytes resembles the protein pattern of the hair follicle sheath. Studies on the metabolism of benzo(a)pyrene revealed that the enzyme aryl hydrocarbon hydroxylase (AHH) is present in cultured hair follicle cells. A possible use of our culture system for eventual detection of inherited predisposition for smoking-dependent lung cancer is discussed.

Human-like behavior of robot arms: general considerations and the handwriting task-part II: The robot arm in handwriting

NARCIS (Netherlands)

Potkonjak, V.; Kostic, D.; Tzafestas, S.; Popovic, M.; Lazarevic, M.; Djordjevic, G.

2001-01-01

This paper (Part II) investigates the motion of a redundant anthropomorphic arm during the writing task. Two approaches are applied. The first is based on the concept of distributed positioning which is suitable to model the "writing" task before the occurrence of fatigue symptoms. The second

HIP2: An online database of human plasma proteins from healthy individuals

Directory of Open Access Journals (Sweden)

Shen Changyu

2008-04-01

Full Text Available Abstract Background With the introduction of increasingly powerful mass spectrometry (MS techniques for clinical research, several recent large-scale MS proteomics studies have sought to characterize the entire human plasma proteome with a general objective for identifying thousands of proteins leaked from tissues in the circulating blood. Understanding the basic constituents, diversity, and variability of the human plasma proteome is essential to the development of sensitive molecular diagnosis and treatment monitoring solutions for future biomedical applications. Biomedical researchers today, however, do not have an integrated online resource in which they can search for plasma proteins collected from different mass spectrometry platforms, experimental protocols, and search software for healthy individuals. The lack of such a resource for comparisons has made it difficult to interpret proteomics profile changes in patients' plasma and to design protein biomarker discovery experiments. Description To aid future protein biomarker studies of disease and health from human plasma, we developed an online database, HIP2 (Healthy Human Individual's Integrated Plasma Proteome. The current version contains 12,787 protein entries linked to 86,831 peptide entries identified using different MS platforms. Conclusion This web-based database will be useful to biomedical researchers involved in biomarker discovery research. This database has been developed to be the comprehensive collection of healthy human plasma proteins, and has protein data captured in a relational database schema built to contain mappings of supporting peptide evidence from several high-quality and high-throughput mass-spectrometry (MS experimental data sets. Users can search for plasma protein/peptide annotations, peptide/protein alignments, and experimental/sample conditions with options for filter-based retrieval to achieve greater analytical power for discovery and validation.

neXtProt: organizing protein knowledge in the context of human proteome projects.

Science.gov (United States)

Gaudet, Pascale; Argoud-Puy, Ghislaine; Cusin, Isabelle; Duek, Paula; Evalet, Olivier; Gateau, Alain; Gleizes, Anne; Pereira, Mario; Zahn-Zabal, Monique; Zwahlen, Catherine; Bairoch, Amos; Lane, Lydie

2013-01-04

About 5000 (25%) of the ~20400 human protein-coding genes currently lack any experimental evidence at the protein level. For many others, there is only little information relative to their abundance, distribution, subcellular localization, interactions, or cellular functions. The aim of the HUPO Human Proteome Project (HPP, www.thehpp.org ) is to collect this information for every human protein. HPP is based on three major pillars: mass spectrometry (MS), antibody/affinity capture reagents (Ab), and bioinformatics-driven knowledge base (KB). To meet this objective, the Chromosome-Centric Human Proteome Project (C-HPP) proposes to build this catalog chromosome-by-chromosome ( www.c-hpp.org ) by focusing primarily on proteins that currently lack MS evidence or Ab detection. These are termed "missing proteins" by the HPP consortium. The lack of observation of a protein can be due to various factors including incorrect and incomplete gene annotation, low or restricted expression, or instability. neXtProt ( www.nextprot.org ) is a new web-based knowledge platform specific for human proteins that aims to complement UniProtKB/Swiss-Prot ( www.uniprot.org ) with detailed information obtained from carefully selected high-throughput experiments on genomic variation, post-translational modifications, as well as protein expression in tissues and cells. This article describes how neXtProt contributes to prioritize C-HPP efforts and integrates C-HPP results with other research efforts to create a complete human proteome catalog.

Cigarette smoke induces endoplasmic reticulum stress and the unfolded protein response in normal and malignant human lung cells

Directory of Open Access Journals (Sweden)

Yang Jin

2008-08-01

Full Text Available Abstract Background Although lung cancer is among the few malignancies for which we know the primary etiological agent (i.e., cigarette smoke, a precise understanding of the temporal sequence of events that drive tumor progression remains elusive. In addition to finding that cigarette smoke (CS impacts the functioning of key pathways with significant roles in redox homeostasis, xenobiotic detoxification, cell cycle control, and endoplasmic reticulum (ER functioning, our data highlighted a defensive role for the unfolded protein response (UPR program. The UPR promotes cell survival by reducing the accumulation of aberrantly folded proteins through translation arrest, production of chaperone proteins, and increased degradation. Importance of the UPR in maintaining tissue health is evidenced by the fact that a chronic increase in defective protein structures plays a pathogenic role in diabetes, cardiovascular disease, Alzheimer's and Parkinson's syndromes, and cancer. Methods Gene and protein expression changes in CS exposed human cell cultures were monitored by high-density microarrays and Western blot analysis. Tissue arrays containing samples from 110 lung cancers were probed with antibodies to proteins of interest using immunohistochemistry. Results We show that: 1 CS induces ER stress and activates components of the UPR; 2 reactive species in CS that promote oxidative stress are primarily responsible for UPR activation; 3 CS exposure results in increased expression of several genes with significant roles in attenuating oxidative stress; and 4 several major UPR regulators are increased either in expression (i.e., BiP and eIF2α or phosphorylation (i.e., phospho-eIF2α in a majority of human lung cancers. Conclusion These data indicate that chronic ER stress and recruitment of one or more UPR effector arms upon exposure to CS may play a pivotal role in the etiology or progression of lung cancers, and that phospho-eIF2α and BiP may have

Translational analysis of mouse and human placental protein and mRNA reveals distinct molecular pathologies in human preeclampsia.

Science.gov (United States)

Cox, Brian; Sharma, Parveen; Evangelou, Andreas I; Whiteley, Kathie; Ignatchenko, Vladimir; Ignatchenko, Alex; Baczyk, Dora; Czikk, Marie; Kingdom, John; Rossant, Janet; Gramolini, Anthony O; Adamson, S Lee; Kislinger, Thomas

2011-12-01

Preeclampsia (PE) adversely impacts ~5% of pregnancies. Despite extensive research, no consistent biomarkers or cures have emerged, suggesting that different molecular mechanisms may cause clinically similar disease. To address this, we undertook a proteomics study with three main goals: (1) to identify a panel of cell surface markers that distinguish the trophoblast and endothelial cells of the placenta in the mouse; (2) to translate this marker set to human via the Human Protein Atlas database; and (3) to utilize the validated human trophoblast markers to identify subgroups of human preeclampsia. To achieve these goals, plasma membrane proteins at the blood tissue interfaces were extracted from placentas using intravascular silica-bead perfusion, and then identified using shotgun proteomics. We identified 1181 plasma membrane proteins, of which 171 were enriched at the maternal blood-trophoblast interface and 192 at the fetal endothelial interface with a 70% conservation of expression in humans. Three distinct molecular subgroups of human preeclampsia were identified in existing human microarray data by using expression patterns of trophoblast-enriched proteins. Analysis of all misexpressed genes revealed divergent dysfunctions including angiogenesis (subgroup 1), MAPK signaling (subgroup 2), and hormone biosynthesis and metabolism (subgroup 3). Subgroup 2 lacked expected changes in known preeclampsia markers (sFLT1, sENG) and uniquely overexpressed GNA12. In an independent set of 40 banked placental specimens, GNA12 was overexpressed during preeclampsia when co-incident with chronic hypertension. In the current study we used a novel translational analysis to integrate mouse and human trophoblast protein expression with human microarray data. This strategy identified distinct molecular pathologies in human preeclampsia. We conclude that clinically similar preeclampsia patients exhibit divergent placental gene expression profiles thus implicating divergent

The bone morphogenetic protein antagonist gremlin 1 is overexpressed in human cancers and interacts with YWHAH protein

International Nuclear Information System (INIS)

Namkoong, Hong; Shin, Seung Min; Kim, Hyun Kee; Ha, Seon-Ah; Cho, Goang Won; Hur, Soo Young; Kim, Tae Eung; Kim, Jin Woo

2006-01-01

Basic studies of oncogenesis have demonstrated that either the elevated production of particular oncogene proteins or the occurrence of qualitative abnormalities in oncogenes can contribute to neoplastic cellular transformation. The purpose of our study was to identify an unique gene that shows cancer-associated expression, and characterizes its function related to human carcinogenesis. We used the differential display (DD) RT-PCR method using normal cervical, cervical cancer, metastatic cervical tissues, and cervical cancer cell lines to identify genes overexpressed in cervical cancers and identified gremlin 1 which was overexpressed in cervical cancers. We determined expression levels of gremlin 1 using Northern blot analysis and immunohistochemical study in various types of human normal and cancer tissues. To understand the tumorigenesis pathway of identified gremlin 1 protein, we performed a yeast two-hybrid screen, GST pull down assay, and immunoprecipitation to identify gremlin 1 interacting proteins. DDRT-PCR analysis revealed that gremlin 1 was overexpressed in uterine cervical cancer. We also identified a human gremlin 1 that was overexpressed in various human tumors including carcinomas of the lung, ovary, kidney, breast, colon, pancreas, and sarcoma. PIG-2-transfected HEK 293 cells exhibited growth stimulation and increased telomerase activity. Gremlin 1 interacted with homo sapiens tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta polypeptide (14-3-3 eta; YWHAH). YWHAH protein binding site for gremlin 1 was located between residues 61–80 and gremlin 1 binding site for YWHAH was found to be located between residues 1 to 67. Gremlin 1 may play an oncogenic role especially in carcinomas of the uterine cervix, lung, ovary, kidney, breast, colon, pancreas, and sarcoma. Over-expressed gremlin 1 functions by interaction with YWHAH. Therefore, Gremlin 1 and its binding protein YWHAH could be good targets for developing diagnostic and

Electromechanical and robot-assisted arm training for improving activities of daily living, arm function, and arm muscle strength after stroke.

Science.gov (United States)

Mehrholz, Jan; Pohl, Marcus; Platz, Thomas; Kugler, Joachim; Elsner, Bernhard

2015-11-07

Electromechanical and robot-assisted arm training devices are used in rehabilitation, and may help to improve arm function after stroke. To assess the effectiveness of electromechanical and robot-assisted arm training for improving activities of daily living, arm function, and arm muscle strength in people after stroke. We also assessed the acceptability and safety of the therapy. We searched the Cochrane Stroke Group's Trials Register (last searched February 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2015, Issue 3), MEDLINE (1950 to March 2015), EMBASE (1980 to March 2015), CINAHL (1982 to March 2015), AMED (1985 to March 2015), SPORTDiscus (1949 to March 2015), PEDro (searched April 2015), Compendex (1972 to March 2015), and Inspec (1969 to March 2015). We also handsearched relevant conference proceedings, searched trials and research registers, checked reference lists, and contacted trialists, experts, and researchers in our field, as well as manufacturers of commercial devices. Randomised controlled trials comparing electromechanical and robot-assisted arm training for recovery of arm function with other rehabilitation or placebo interventions, or no treatment, for people after stroke. Two review authors independently selected trials for inclusion, assessed trial quality and risk of bias, and extracted data. We contacted trialists for additional information. We analysed the results as standardised mean differences (SMDs) for continuous variables and risk differences (RDs) for dichotomous variables. We included 34 trials (involving 1160 participants) in this update of our review. Electromechanical and robot-assisted arm training improved activities of daily living scores (SMD 0.37, 95% confidence interval (CI) 0.11 to 0.64, P = 0.005, I² = 62%), arm function (SMD 0.35, 95% CI 0.18 to 0.51, P arm muscle strength (SMD 0.36, 95% CI 0.01 to 0.70, P = 0.04, I² = 72%), but the quality of the evidence was low to very low

Human protein status modulates brain reward responses to food cues1–3

NARCIS (Netherlands)

Griffioen-Roose, S.; Smeets, P.A.M.; Heuvel, van den E.M.; Boesveldt, S.; Finlayson, G.; Graaf, de C.

2014-01-01

Background: Protein is indispensable in the human diet, and its intake appears tightly regulated. The role of sensory attributes of foods in protein intake regulation is far from clear. Objective: We investigated the effect of human protein status on neural responses to different food cues with the

Crystal structure of human protein kinase CK2

DEFF Research Database (Denmark)

Niefind, K; Guerra, B; Ermakowa, I

2001-01-01

The crystal structure of a fully active form of human protein kinase CK2 (casein kinase 2) consisting of two C-terminally truncated catalytic and two regulatory subunits has been determined at 3.1 A resolution. In the CK2 complex the regulatory subunits form a stable dimer linking the two catalyt...... as a docking partner for various protein kinases. Furthermore it shows an inter-domain mobility in the catalytic subunit known to be functionally important in protein kinases and detected here for the first time directly within one crystal structure.......The crystal structure of a fully active form of human protein kinase CK2 (casein kinase 2) consisting of two C-terminally truncated catalytic and two regulatory subunits has been determined at 3.1 A resolution. In the CK2 complex the regulatory subunits form a stable dimer linking the two catalytic...... subunits, which make no direct contact with one another. Each catalytic subunit interacts with both regulatory chains, predominantly via an extended C-terminal tail of the regulatory subunit. The CK2 structure is consistent with its constitutive activity and with a flexible role of the regulatory subunit...

Reprogramming the articulated robotic arm for glass handling by using Arduino microcontroller

Science.gov (United States)

Razali, Zol Bahri; Kader, Mohamed Mydin M. Abdul; Kadir, Mohd Asmadi Akmal; Daud, Mohd Hisam

2017-09-01

The application of articulated robotic arm in industries is raised due to the expansion of using robot to replace human task, especially for the harmful tasks. However a few problems happen with the program use to schedule the arm, Thus the purpose of this project is to design, fabricate and integrate an articulated robotic arm by using Arduino microcontroller for handling glass sorting system. This project was designed to segregate glass and non-glass waste which would be pioneer step for recycling. This robotic arm has four servo motors to operate as a whole; three for the body and one for holding mechanism. This intelligent system is controlled by Arduino microcontroller and build with optical sensor to provide the distinguish objects that will be handled. Solidworks model was used to produce the detail design of the robotic arm and make the mechanical properties analysis by using a CAD software.

Human thyroid peroxidase: complete cDNA and protein sequence, chromosome mapping, and identification of two alternately spliced mRNAs

International Nuclear Information System (INIS)

Kimura, S.; Kotani, T.; McBride, O.W.; Umeki, K.; Hirai, K.; Nakayama, T.; Ohtaki, S.

1987-01-01

Two forms of human thyroid peroxidase cDNAs were isolated from a λgt11 cDNA library, prepared from Graves disease thyroid tissue mRNA, by use of oligonucleotides. The longest complete cDNA, designated phTPO-1, has 3048 nucleotides and an open reading frame consisting of 933 amino acids, which would encode a protein with a molecular weight of 103,026. Five potential asparagine-linked glycosylation sites are found in the deduced amino acid sequence. The second peroxidase cDNA, designated phTPO-2, is almost identical to phTPO-1 beginning 605 base pairs downstream except that it contains 1-base-pair difference and lacks 171 base pairs in the middle of the sequence. This results in a loss of 57 amino acids corresponding to a molecular weight of 6282. Interestingly, this 171-nucleotide sequence has GT and AG at its 5' and 3' boundaries, respectively, that are in good agreement with donor and acceptor splice site consensus sequences. Using specific oligonucleotide probes for the mRNAs derived from the cDNA sequences hTOP-1 and hTOP-2, the authors show that both are expressed in all thyroid tissues examined and the relative level of two mRNAs is different in each sample. The results suggest that two thyroid peroxidase proteins might be generated through alternate splicing of the same gene. By using somatic cell hybrid lines, the thyroid peroxidase gene was mapped to the short arm of human chromosome 2

Inter-Arm Difference in Brachial Blood Pressure in the General Population of Koreans.

Science.gov (United States)

Song, Bo Mi; Kim, Hyeon Chang; Shim, Jee-Seon; Lee, Myung Ha; Choi, Dong Phil

2016-05-01

We investigated the inter-arm difference in blood pressure of the general Korean population to identify associated factors. A total of 806 participants aged 30 to 64 years without history of major cardiovascular disease were analyzed in this cross-sectional study. They participated in the Cardiovascular and Metabolic Disease Etiology Research Center cohort study that began in 2013. Brachial blood pressure was measured simultaneously for both arms using an automated oscillometric device equipped with two cuffs in seated position. After five minutes of rest, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured three times. The average of the three measurements was used for analysis. Multivariate logistic regression models were used to identify factors associated with inter-arm differences in blood pressure. The mean inter-arm difference was 3.3 mmHg for SBP and 2.0 mmHg for DBP. Large inter-arm differences (≥10 mmHg) in SBP and in DBP were found in 3.7% and 0.9% of subjects, respectively. A large inter-arm difference in SBP was associated with mean SBP (p=0.002) and C-reactive protein (p=0.014) while a large inter-arm different in DBP was only associated with body mass index (p=0.015). Sex, age, and anti-hypertensive medication use were not associated with differences in inter-arm blood pressure. Large inter-arm difference in blood pressure is only present in a small portion of healthy Korean adults. Our findings suggest that high SBP, chronic inflammation, and obesity may be associated with larger difference in inter-arm blood pressure.

HOMOLOGY BETWEEN SEGMENTS OF HUMAN HEMOSTATIC PROTEINS AND PROTEINS OF VIRUSES WHICH CAUSE ACUTE RESPIRATORY INFECTIONS OR DISEASES WITH SIMILAR SYMPTOMS

Directory of Open Access Journals (Sweden)

I. N. Zhilinskaya

2017-01-01

Full Text Available Objectives: To identify homologous segments of human hemostatic and viral proteins and to assess the role of human hemostatic proteins in viral replication. Materials and Methods: The following viruses were chosen for comparison: influenza B (B/Astrakhan/2/2017, coronaviruses (Hcov229E and SARS-Co, type 1 adenovirus (adenoid 71, measles (ICHINOSE-BA and rubella (Therien. The primary structures of viral proteins and 41 human hemostatic proteins were obtained from open–access www.ncbi.nlm.nih. gov and www.nextprot.org databases, respectively. Sequence homology was determined by comparing 12-amino-acid segments. Those sequences identical in ≥ 8 positions were considered homologous. Results: The analysis shows that viral proteins contain segments which mimic a number of human hemostatic proteins. Most of these segments, except those of adenovirus proteins, are homologous with coagulation factors. The increase in viral virulence, as in case of SARS-Co, correlates with an increased number of segments homologous with hemostatic proteins. Conclusion: Hemostasis plays an important role in viral replication and pathogenesis. The conclusion is consistent with the literature data about the relationship of hemostasis and inflammatory response to viral infections.

In vivo extracellular matrix protein expression by human periodontal ...

African Journals Online (AJOL)

It is well known that the orthodontic force applied to teeth generates a series of events that remodel the periodontal ligament (PDL). Extracellular matrix proteins (ECM) are described as molecular regulators of these events. However, the exact contribution of these proteins in human PDL modeling by orthodontic force ...

ARM Airborne Carbon Measurements (ARM-ACME) and ARM-ACME 2.5 Final Campaign Reports

Energy Technology Data Exchange (ETDEWEB)

Biraud, S. C. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Tom, M. S. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sweeney, C. [NOAA Earth Systems Research Lab., Boulder, CO (United States)

2016-01-01

We report on a 5-year multi-institution and multi-agency airborne study of atmospheric composition and carbon cycling at the Atmospheric Radiation Measurement (ARM) Climate Research Facility’s Southern Great Plains (SGP) site, with scientific objectives that are central to the carbon-cycle and radiative-forcing goals of the U.S. Global Change Research Program and the North American Carbon Program (NACP). The goal of these measurements is to improve understanding of 1) the carbon exchange of the Atmospheric Radiation Measurement (ARM) SGP region; 2) how CO₂ and associated water and energy fluxes influence radiative-forcing, convective processes, and CO₂ concentrations over the ARM SGP region, and 3) how greenhouse gases are transported on continental scales.

Copper, Zinc Superoxide Dismutase is Primarily a Cytosolic Protein in Human Cells

Science.gov (United States)

Crapo, James D.; Oury, Tim; Rabouille, Catherine; Slot, Jan W.; Chang, Ling-Yi

1992-11-01

The intracellular localization of human copper, zinc superoxide dismutase (Cu,Zn-SOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) was evaluated by using EM immunocytochemistry and both isolated human cell lines and human tissues. Eight monoclonal antibodies raised against either native or recombinant human Cu,Zn-SOD and two polyclonal antibodies raised against either native or recombinant human Cu,Zn-SOD were used. Fixation with 2% paraformaldehyde/0.2% glutaraldehyde was found necessary to preserve normal distribution of the protein. Monoclonal antibodies were less effective than polyclonal antibodies in recognizing the antigen after adequate fixation of tissue. Cu,Zn-SOD was found widely distributed in the cell cytosol and in the cell nucleus, consistent with it being a soluble cytosolic protein. Mitochondria and secretory compartments did not label for this protein. In human cells, peroxisomes showed a labeling density slightly less than that of cytoplasm.

Mechanism of immunoglobulin G4 Fab-arm exchange

NARCIS (Netherlands)

Rispens, Theo; Ooijevaar-de Heer, Pleuni; Bende, Onno; Aalberse, Rob C.

2011-01-01

Immunoglobulin G (IgG) antibodies are symmetrical molecules that may be regarded as covalent dimers of 2 half-molecules, each consisting of a light chain and a heavy chain. Human IgG4 is an unusually dynamic antibody, with half-molecule exchange ("Fab-arm exchange") resulting in asymmetrical,

Human Antimicrobial Peptides and Proteins

Directory of Open Access Journals (Sweden)

Guangshun Wang

2014-05-01

Full Text Available As the key components of innate immunity, human host defense antimicrobial peptides and proteins (AMPs play a critical role in warding off invading microbial pathogens. In addition, AMPs can possess other biological functions such as apoptosis, wound healing, and immune modulation. This article provides an overview on the identification, activity, 3D structure, and mechanism of action of human AMPs selected from the antimicrobial peptide database. Over 100 such peptides have been identified from a variety of tissues and epithelial surfaces, including skin, eyes, ears, mouths, gut, immune, nervous and urinary systems. These peptides vary from 10 to 150 amino acids with a net charge between −3 and +20 and a hydrophobic content below 60%. The sequence diversity enables human AMPs to adopt various 3D structures and to attack pathogens by different mechanisms. While α-defensin HD-6 can self-assemble on the bacterial surface into nanonets to entangle bacteria, both HNP-1 and β-defensin hBD-3 are able to block cell wall biosynthesis by binding to lipid II. Lysozyme is well-characterized to cleave bacterial cell wall polysaccharides but can also kill bacteria by a non-catalytic mechanism. The two hydrophobic domains in the long amphipathic α-helix of human cathelicidin LL-37 lays the basis for binding and disrupting the curved anionic bacterial membrane surfaces by forming pores or via the carpet model. Furthermore, dermcidin may serve as ion channel by forming a long helix-bundle structure. In addition, the C-type lectin RegIIIα can initially recognize bacterial peptidoglycans followed by pore formation in the membrane. Finally, histatin 5 and GAPDH(2-32 can enter microbial cells to exert their effects. It appears that granulysin enters cells and kills intracellular pathogens with the aid of pore-forming perforin. This arsenal of human defense proteins not only keeps us healthy but also inspires the development of a new generation of personalized

Localization of age-related macular degeneration-associated ARMS2 in cytosol, not mitochondria

Science.gov (United States)

Wang, Gaofeng; Spencer, Kylee L.; Court, Brenda L.; Olson, Lana M.; Scott, William K.; Haines, Jonathan L.; Pericak-Vance, Margaret A.

2010-01-01

PURPOSE To analyze the relationship between ARMS2 and HTRA1 in the association with age-related macular degeneration (AMD) in an independent case-control dataset, and to investigate the subcellular localization of the ARMS2 protein in an in vitro system. METHOD Two SNPs in ARMS2 and HTRA1 were genotyped in 685 cases and 269 controls by Taqman Assay. Allelic association was tested by a χ2 test. A likelihood ratio test (LRT) of full vs. reduced models was utilized to analyze the interaction between ARMS2 and smoking and HTRA1 and smoking, after adjusting for CFH and age. Immunofluorescence and immunoblot were applied to localize ARMS2 in retinal epithelial ARPE-19 cells and COS7 cell transfected by ARMS2 constructs. RESULT Both significantly associated SNP rs10490924 and rs11200638 (P<0.0001) are in strong linkage disequilibrium (LD) (D′=0.97, r2=0.93) that generates virtually identical association test and odds ratios. In separate logistic regression models the interaction effect for both smoking with ARMS2 and with HTRA1 was not statistically significant. Immunofluorescence and immunoblot show that both endogenous and exogenous ARMS2 are mainly distributed in the cytosol, not the mitochondria. Comparing to wild type, ARMS2 A69S is more likely to be associated with cytoskeleton in COS7 cells. CONCLUSIONS The significant associations in ARMS2 and HTRA1 are with polymorphisms in strong LD that confer virtually identical risks, preventing differentiation at the statistical level. We found that ARMS2 was mainly distributed in the cytosol, not in mitochondrial outer membrane as previously reported, suggesting that ARMS2 may not confer risk to AMD through the mitochondrial pathway. PMID:19255159

Purification, crystallization and X-ray diffraction analysis of human dynamin-related protein 1 GTPase-GED fusion protein

International Nuclear Information System (INIS)

Klinglmayr, Eva; Wenger, Julia; Mayr, Sandra; Bossy-Wetzel, Ella; Puehringer, Sandra

2012-01-01

The crystallization and initial diffraction analysis of human Drp1 GTPase-GED fusion protein are reported. The mechano-enzyme dynamin-related protein 1 plays an important role in mitochondrial fission and is implicated in cell physiology. Dysregulation of Drp1 is associated with abnormal mitochondrial dynamics and neuronal damage. Drp1 shares structural and functional similarities with dynamin 1 with respect to domain organization, ability to self-assemble into spiral-like oligomers and GTP-cycle-dependent membrane scission. Structural studies of human dynamin-1 have greatly improved the understanding of this prototypical member of the dynamin superfamily. However, high-resolution structural information for full-length human Drp1 covering the GTPase domain, the middle domain and the GTPase effector domain (GED) is still lacking. In order to obtain mechanistic insights into the catalytic activity, a nucleotide-free GTPase-GED fusion protein of human Drp1 was expressed, purified and crystallized. Initial X-ray diffraction experiments yielded data to 2.67 Å resolution. The hexagonal-shaped crystals belonged to space group P2 1 2 1 2, with unit-cell parameters a = 53.59, b = 151.65, c = 43.53 Å, one molecule per asymmetric unit and a solvent content of 42%. Expression of selenomethionine-labelled protein is currently in progress. Here, the expression, purification, crystallization and X-ray diffraction analysis of the Drp1 GTPase-GED fusion protein are presented, which form a basis for more detailed structural and biophysical analysis

Powered manipulator control arm

International Nuclear Information System (INIS)

Le Mouee, Theodore; Vertut, Jean; Marchal, Paul; Germon, J.C.; Petit, Michel

1975-01-01

A remote operated control arm for powered manipulators is described. It includes an assembly allowing several movements with position sensors for each movement. The number of possible arm movements equals the number of possible manipulator movements. The control systems may be interrupted as required. One part of the arm is fitted with a system to lock it with respect to another part of the arm without affecting the other movements, so long as the positions of the manipulator and the arm have not been brought into complete coincidence. With this system the locking can be ended when complete concordance is achieved [fr

Human sperm degradation of zona pellucida proteins contributes to fertilization.

Science.gov (United States)

Saldívar-Hernández, Analilia; González-González, María E; Sánchez-Tusié, Ana; Maldonado-Rosas, Israel; López, Pablo; Treviño, Claudia L; Larrea, Fernando; Chirinos, Mayel

2015-09-02

The mammalian oocyte extracellular matrix known as the zona pellucida (ZP) acts as a barrier to accomplish sperm fusion with the female gamete. Although penetration of the ZP is a limiting event to achieve fertilization, this is one of the least comprehended stages of gamete interaction. Even though previous studies suggest that proteases of sperm origin contribute to facilitate the passage of sperm through the ZP, in human this process is not yet fully understood. The aim of this study was to determine the ability of human sperm to degrade recombinant human ZP (rhZPs) proteins and to characterize the proteases involved in this process. Purified rhZP2, rhZP3 and rhZP4 proteins were incubated with capacitated sperm and the proteolytic activity was determined by Western blot analysis. To further characterize the proteases involved, parallel incubations were performed in the presence of the protease inhibitors o-phenanthroline, benzamidine and MG-132 meant to block the activity of metalloproteases, serine proteases and the proteasome, respectively. Additionally, protease inhibitors effect on sperm-ZP binding was evaluated by hemizona assay. The results showed that rhZPs were hydrolyzed in the presence of capacitated sperm. O-phenanthroline inhibited the degradation of rhZP3, MG-132 inhibited the degradation of rhZP4 and benzamidine inhibited the degradation of the three proteins under investigation. Moreover, hemizona assays demonstrated that sperm proteasome inhibition impairs sperm interaction with human native ZP. This study suggests that sperm proteasomes could participate in the degradation of ZP, particularly of the ZP4 protein. Besides, metalloproteases may be involved in specific degradation of ZP3 while serine proteases may contribute to unspecific degradation of the ZP. These findings suggest that localized degradation of ZP proteins by sperm is probably involved in ZP penetration and may be of help in understanding the mechanisms of fertilization in humans.

The etiology of human age-related cataract. Proteins don't last forever.

Science.gov (United States)

Truscott, Roger J W; Friedrich, Michael G

2016-01-01

It is probable that the great majority of human cataract results from the spontaneous decomposition of long-lived macromolecules in the human lens. Breakdown/reaction of long-lived proteins is of primary importance and recent proteomic analysis has enabled the identification of the particular crystallins, and their exact sites of amino acid modification. Analysis of proteins from cataractous lenses revealed that there are sites on some structural proteins that show a consistently greater degree of deterioration than age-matched normal lenses. The most abundant posttranslational modification of aged lens proteins is racemization. Deamidation, truncation and crosslinking, each arising from the spontaneous breakdown of susceptible amino acids within proteins, are also present. Fundamental to an understanding of nuclear cataract etiology, it is proposed that once a certain degree of modification at key sites occurs, that protein-protein interactions are disrupted and lens opacification ensues. Since long-lived proteins are now recognized to be present in many other sites of the body, such as the brain, the information gleaned from detailed analyses of degraded proteins from aged lenses will apply more widely to other age-related human diseases. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Deorphanizing the human transmembrane genome: A landscape of uncharacterized membrane proteins.

Science.gov (United States)

Babcock, Joseph J; Li, Min

2014-01-01

The sequencing of the human genome has fueled the last decade of work to functionally characterize genome content. An important subset of genes encodes membrane proteins, which are the targets of many drugs. They reside in lipid bilayers, restricting their endogenous activity to a relatively specialized biochemical environment. Without a reference phenotype, the application of systematic screens to profile candidate membrane proteins is not immediately possible. Bioinformatics has begun to show its effectiveness in focusing the functional characterization of orphan proteins of a particular functional class, such as channels or receptors. Here we discuss integration of experimental and bioinformatics approaches for characterizing the orphan membrane proteome. By analyzing the human genome, a landscape reference for the human transmembrane genome is provided.

Resveratrol-induced cytotoxicity in human Burkitt's lymphoma cells is coupled to the unfolded protein response

International Nuclear Information System (INIS)

Yan, Ying; Gao, Yan-Yan; Liu, Bao-Qin; Niu, Xiao-Fang; Zhuang, Ying; Wang, Hua-Qin

2010-01-01

Resveratrol (RES), a natural phytoalexin found at high levels in grapes and red wine, has been shown to induce anti-proliferation and apoptosis of human cancer cell lines. However, the underlying molecular mechanisms are at present only partially understood. The effects of RES on activation of unfolded protein responses (UPR) were evaluated using Western blotting, semi-quantitative and real-time RT-PCR. Cell death was evaluated using Annexin V/PI staining and subsequent FACS. Similar as tunicamycin, treatment with RES lead to the activation of all 3 branches of the UPR, with early splicing of XBP-1 indicative of IRE1 activation, phosphorylation of eIF2α consistent with ER resident kinase (PERK) activation, activating transcription factor 6 (ATF6) splicing, and increase in expression levels of the downstream molecules GRP78/BiP, GRP94 and CHOP/GADD153 in human Burkitt's lymphoma Raji and Daudi cell lines. RES was shown to induce cell death, which could be attenuated by thwarting upregulation of CHOP. Our data suggest that activation of the apoptotic arm of the UPR and its downstream effector CHOP/GADD153 is involved, at least in part, in RES-induced apoptosis in Burkitt's lymphoma cells

Extended wavelength anisotropy resolved multidimensional emission spectroscopy (ARMES) measurements: better filters, validation standards, and Rayleigh scatter removal methods

Science.gov (United States)

Casamayou-Boucau, Yannick; Ryder, Alan G.

2017-09-01

Anisotropy resolved multidimensional emission spectroscopy (ARMES) provides valuable insights into multi-fluorophore proteins (Groza et al 2015 Anal. Chim. Acta 886 133-42). Fluorescence anisotropy adds to the multidimensional fluorescence dataset information about the physical size of the fluorophores and/or the rigidity of the surrounding micro-environment. The first ARMES studies used standard thin film polarizers (TFP) that had negligible transmission between 250 and 290 nm, preventing accurate measurement of intrinsic protein fluorescence from tyrosine and tryptophan. Replacing TFP with pairs of broadband wire grid polarizers enabled standard fluorescence spectrometers to accurately measure anisotropies between 250 and 300 nm, which was validated with solutions of perylene in the UV and Erythrosin B and Phloxine B in the visible. In all cases, anisotropies were accurate to better than ±1% when compared to literature measurements made with Glan Thompson or TFP polarizers. Better dual wire grid polarizer UV transmittance and the use of excitation-emission matrix measurements for ARMES required complete Rayleigh scatter elimination. This was achieved by chemometric modelling rather than classical interpolation, which enabled the acquisition of pure anisotropy patterns over wider spectral ranges. In combination, these three improvements permit the accurate implementation of ARMES for studying intrinsic protein fluorescence.

Dual arm master controller concept

International Nuclear Information System (INIS)

Kuban, D.P.; Perkins, G.S.

1984-01-01

The Advanced Servomanipulator (ASM) slave was designed with an anthropomorphic stance, gear/torque tube power drives, and modular construction. These features resulted in increased inertia, friction, and backlash relative to tape-driven manipulators. Studies were performed which addressed the human factors design and performance trade-offs associated with the corresponding master controller best suited for the ASM. The results of these studies, as well as the conceptual design of the dual arm master controller, are presented. 6 references, 3 figures

ARM Airborne Carbon Measurements VI (ARM-ACME VI) Field Campaign Report

Energy Technology Data Exchange (ETDEWEB)

Biraud, Sebastien [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

2017-05-01

From October 1, 2015 through September 30, 2016, AAF deployed a Cessna 206 aircraft over the Southern Great Plains, collecting observations of trace gas mixing ratios over the ARM/SGP Central Facility. The aircraft payload included two Atmospheric Observing Systems (AOS Inc.) analyzers for continuous measurements of CO2, and a 12-flask sampler for analysis of carbon cycle gases (CO2, CO, CH4, N2O, 13CO2). The aircraft payload also includes solar/infrared radiation measurements. This research (supported by DOE ARM and TES programs) builds upon previous ARM-ACME missions. The goal of these measurements is to improve understanding of: (a) the carbon exchange of the ARM region; (b) how CO2 and associated water and energy fluxes influence radiative forcing, convective processes, and CO2 concentrations over the ARM region, and (c) how greenhouse gases are transported on continental scales.

An Inverse Optimal Control Approach to Explain Human Arm Reaching Control Based on Multiple Internal Models.

Science.gov (United States)

Oguz, Ozgur S; Zhou, Zhehua; Glasauer, Stefan; Wollherr, Dirk

2018-04-03

Human motor control is highly efficient in generating accurate and appropriate motor behavior for a multitude of tasks. This paper examines how kinematic and dynamic properties of the musculoskeletal system are controlled to achieve such efficiency. Even though recent studies have shown that the human motor control relies on multiple models, how the central nervous system (CNS) controls this combination is not fully addressed. In this study, we utilize an Inverse Optimal Control (IOC) framework in order to find the combination of those internal models and how this combination changes for different reaching tasks. We conducted an experiment where participants executed a comprehensive set of free-space reaching motions. The results show that there is a trade-off between kinematics and dynamics based controllers depending on the reaching task. In addition, this trade-off depends on the initial and final arm configurations, which in turn affect the musculoskeletal load to be controlled. Given this insight, we further provide a discomfort metric to demonstrate its influence on the contribution of different inverse internal models. This formulation together with our analysis not only support the multiple internal models (MIMs) hypothesis but also suggest a hierarchical framework for the control of human reaching motions by the CNS.

Characterization of the human GARP (Golgi associated retrograde protein) complex

International Nuclear Information System (INIS)

Liewen, Heike; Meinhold-Heerlein, Ivo; Oliveira, Vasco; Schwarzenbacher, Robert; Luo Guorong; Wadle, Andreas; Jung, Martin; Pfreundschuh, Michael; Stenner-Liewen, Frank

2005-01-01

The Golgi associated retrograde protein complex (GARP) or Vps fifty-three (VFT) complex is part of cellular inter-compartmental transport systems. Here we report the identification of the VFT tethering factor complex and its interactions in mammalian cells. Subcellular fractionation shows that human Vps proteins are found in the smooth membrane/Golgi fraction but not in the cytosol. Immunostaining of human Vps proteins displays a vesicular distribution most concentrated at the perinuclear envelope. Co-staining experiments with endosomal markers imply an endosomal origin of these vesicles. Significant accumulation of VFT complex positive endosomes is found in the vicinity of the Trans Golgi Network area. This is in accordance with a putative role in Golgi associated transport processes. In Saccharomyces cerevisiae, GARP is the main effector of the small GTPase Ypt6p and interacts with the SNARE Tlg1p to facilitate membrane fusion. Accordingly, the human homologue of Ypt6p, Rab6, specifically binds hVps52. In human cells, the 'orphan' SNARE Syntaxin 10 is the genuine binding partner of GARP mediated by hVps52. This reveals a previously unknown function of human Syntaxin 10 in membrane docking and fusion events at the Golgi. Taken together, GARP shows significant conservation between various species but diversification and specialization result in important differences in human cells

Unique expression of cytoskeletal proteins in human soft palate muscles.

Science.gov (United States)

Shah, Farhan; Berggren, Diana; Holmlund, Thorbjörn; Levring Jäghagen, Eva; Stål, Per

2016-03-01

The human oropharyngeal muscles have a unique anatomy with diverse and intricate functions. To investigate if this specialization is also reflected in the cytoarchitecture of muscle fibers, intermediate filament proteins and the dystrophin-associated protein complex have been analyzed in two human palate muscles, musculus uvula (UV) and musculus palatopharyngeus (PP), with immunohistochenmical and morphological techniques. Human limb muscles were used as reference. The findings show that the soft palate muscle fibers have a cytoskeletal architecture that differs from the limb muscles. While all limb muscles showed immunoreaction for a panel of antibodies directed against different domains of cytoskeletal proteins desmin and dystrophin, a subpopulation of palate muscle fibers lacked or had a faint immunoreaction for desmin (UV 11.7% and PP 9.8%) and the C-terminal of the dystrophin molecule (UV 4.2% and PP 6.4%). The vast majority of these fibers expressed slow contractile protein myosin heavy chain I. Furthermore, an unusual staining pattern was also observed in these fibers for β-dystroglycan, caveolin-3 and neuronal nitric oxide synthase nNOS, which are all membrane-linking proteins associated with the dystrophin C-terminus. While the immunoreaction for nNOS was generally weak or absent, β-dystroglycan and caveolin-3 showed a stronger immunostaining. The absence or a low expression of cytoskeletal proteins otherwise considered ubiquitous and important for integration and contraction of muscle cells indicate a unique cytoarchitecture designed to meet the intricate demands of the upper airway muscles. It can be concluded that a subgroup of muscle fibers in the human soft palate appears to have special biomechanical properties, and their unique cytoarchitecture must be taken into account while assessing function and pathology in oropharyngeal muscles. © 2015 Anatomical Society.

Deep Arm/Ear-ECG Image Learning for Highly Wearable Biometric Human Identification.

Science.gov (United States)

Zhang, Qingxue; Zhou, Dian

2018-01-01

In this study, to advance smart health applications which have increasing security/privacy requirements, we propose a novel highly wearable ECG-based user identification system, empowered by both non-standard convenient ECG lead configurations and deep learning techniques. Specifically, to achieve a super wearability, we suggest situating all the ECG electrodes on the left upper-arm, or behind the ears, and successfully obtain weak but distinguishable ECG waveforms. Afterwards, to identify individuals from weak ECG, we further present a two-stage framework, including ECG imaging and deep feature learning/identification. In the former stage, the ECG heartbeats are projected to a 2D state space, to reveal heartbeats' trajectory behaviors and produce 2D images by a split-then-hit method. In the second stage, a convolutional neural network is introduced to automatically learn the intricate patterns directly from the ECG image representations without heavy feature engineering, and then perform user identification. Experimental results on two acquired datasets using our wearable prototype, show a promising identification rate of 98.4% (single-arm-ECG) and 91.1% (ear-ECG), respectively. To the best of our knowledge, it is the first study on the feasibility of using single-arm-ECG/ear-ECG for user identification purpose, which is expected to contribute to pervasive ECG-based user identification in smart health applications.

Plastid and mitochondrion genomic sequences from Arctic Chlorella sp. ArM0029B

Science.gov (United States)

2014-01-01

Background Chorella is the representative taxon of Chlorellales in Trebouxiophyceae, and its chloroplast (cp) genomic information has been thought to depend only on studies concerning Chlorella vulgaris and GenBank information of C. variablis. Mitochondrial (mt) genomic information regarding Chlorella is currently unavailable. To elucidate the evolution of organelle genomes and genetic information of Chlorella, we have sequenced and characterized the cp and mt genomes of Arctic Chlorella sp. ArM0029B. Results The 119,989-bp cp genome lacking inverted repeats and 65,049-bp mt genome were sequenced. The ArM0029B cp genome contains 114 conserved genes, including 32 tRNA genes, 3 rRNA genes, and 79 genes encoding proteins. Chlorella cp genomes are highly rearranged except for a Chlorella-specific six-gene cluster, and the ArM0029B plastid resembles that of Chlorella variabilis except for a 15-kb gene cluster inversion. In the mt genome, 62 conserved genes, including 27 tRNA genes, 3 rRNA genes, and 32 genes encoding proteins were determined. The mt genome of ArM0029B is similar to that of the non-photosynthetic species Prototheca and Heicosporidium. The ArM0029B mt genome contains a group I intron, with an ORF containing two LAGLIDADG motifs, in cox1. The intronic ORF is shared by C. vulgaris and Prototheca. The phylogeny of the plastid genome reveals that ArM0029B showed a close relationship of Chlorella to Parachlorella and Oocystis within Chlorellales. The distribution of the cox1 intron at 721 support membership in the order Chlorellales. Mitochondrial phylogenomic analyses, however, indicated that ArM0029B shows a greater affinity to MX-AZ01 and Coccomyxa than to the Helicosporidium-Prototheca clade, although the detailed phylogenetic relationships among the three taxa remain to be resolved. Conclusions The plastid genome of ArM0029B is similar to that of C. variabilis. The mt sequence of ArM0029B is the first genome to be reported for Chlorella. Chloroplast

NovelFam3000 – Uncharacterized human protein domains conserved across model organisms

Science.gov (United States)

Kemmer, Danielle; Podowski, Raf M; Arenillas, David; Lim, Jonathan; Hodges, Emily; Roth, Peggy; Sonnhammer, Erik LL; Höög, Christer; Wasserman, Wyeth W

2006-01-01

Background Despite significant efforts from the research community, an extensive portion of the proteins encoded by human genes lack an assigned cellular function. Most metazoan proteins are composed of structural and/or functional domains, of which many appear in multiple proteins. Once a domain is characterized in one protein, the presence of a similar sequence in an uncharacterized protein serves as a basis for inference of function. Thus knowledge of a domain's function, or the protein within which it arises, can facilitate the analysis of an entire set of proteins. Description From the Pfam domain database, we extracted uncharacterized protein domains represented in proteins from humans, worms, and flies. A data centre was created to facilitate the analysis of the uncharacterized domain-containing proteins. The centre both provides researchers with links to dispersed internet resources containing gene-specific experimental data and enables them to post relevant experimental results or comments. For each human gene in the system, a characterization score is posted, allowing users to track the progress of characterization over time or to identify for study uncharacterized domains in well-characterized genes. As a test of the system, a subset of 39 domains was selected for analysis and the experimental results posted to the NovelFam3000 system. For 25 human protein members of these 39 domain families, detailed sub-cellular localizations were determined. Specific observations are presented based on the analysis of the integrated information provided through the online NovelFam3000 system. Conclusion Consistent experimental results between multiple members of a domain family allow for inferences of the domain's functional role. We unite bioinformatics resources and experimental data in order to accelerate the functional characterization of scarcely annotated domain families. PMID:16533400

NovelFam3000 – Uncharacterized human protein domains conserved across model organisms

Directory of Open Access Journals (Sweden)

Sonnhammer Erik LL

2006-03-01

Full Text Available Abstract Background Despite significant efforts from the research community, an extensive portion of the proteins encoded by human genes lack an assigned cellular function. Most metazoan proteins are composed of structural and/or functional domains, of which many appear in multiple proteins. Once a domain is characterized in one protein, the presence of a similar sequence in an uncharacterized protein serves as a basis for inference of function. Thus knowledge of a domain's function, or the protein within which it arises, can facilitate the analysis of an entire set of proteins. Description From the Pfam domain database, we extracted uncharacterized protein domains represented in proteins from humans, worms, and flies. A data centre was created to facilitate the analysis of the uncharacterized domain-containing proteins. The centre both provides researchers with links to dispersed internet resources containing gene-specific experimental data and enables them to post relevant experimental results or comments. For each human gene in the system, a characterization score is posted, allowing users to track the progress of characterization over time or to identify for study uncharacterized domains in well-characterized genes. As a test of the system, a subset of 39 domains was selected for analysis and the experimental results posted to the NovelFam3000 system. For 25 human protein members of these 39 domain families, detailed sub-cellular localizations were determined. Specific observations are presented based on the analysis of the integrated information provided through the online NovelFam3000 system. Conclusion Consistent experimental results between multiple members of a domain family allow for inferences of the domain's functional role. We unite bioinformatics resources and experimental data in order to accelerate the functional characterization of scarcely annotated domain families.

Protein profile of human hepatocarcinoma cell line SMMC-7721: Identification and functional analysis

Institute of Scientific and Technical Information of China (English)

Yi Feng; Zhong-Min Tian; Ming-Xi Wan; Zhao-Bin Zheng

2007-01-01

AIM: To investigate the protein profile of human hepatocarcinoma cell line SMMC-7721, to analyze the specific functions of abundant expressed proteins in the processes of hepatocarcinoma genesis, growth and metastasis, to identify the hepatocarcinoma-specific biomarkers for the early prediction in diagnosis, and to explore the new drug targets for liver cancer therapy.METHODS: Total proteins from human hepatocarcinomacell line SMMC-7721 were separated by two-dimensional electrophoresis (2DE). The silver-stained gel was analyzed by 2DE software Image Master 2D Elite.Interesting protein spots were identified by peptide mass fingerprinting based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS)and database searching.RESULTS: We obtained protein profile of human hepatocarcinoma cell line SMMC-7721. Among the twenty-one successfully identified proteins, mitofilin,endoplasmic reticulum protein ERp29, ubiquinol-cytochrome C reductase complex core protein Ⅰ,peroxisomal enoyl CoA hydratase, peroxiredoxin-4 and probable 3-oxoacid CoA transferase 1 precursor were the six novel proteins identified in human hepatocarcinoma cells or tissues. Specific functions of the identified heat-shock proteins were analyzed in detail, and the results suggested that these proteins might promote tumorigenesis via inhibiting cell death induced by several cancer-related stresses or via inhibiting apoptosis at multiple points in the apoptotic signal pathway. Other identified chaperones and cancer-related proteins were also analyzed.CONCLUSION: Based on the protein profile of SMMC-7721 cells, functional analysis suggests that the identified chaperones and cancer-related proteins have their own pathways to contribute to the tumorigenesis, tumor growth and metastasis of liver cancer. Furthermore, proteomic analysis is indicated to be feasible in the cancer study.

ARM Mentor Selection Process

Energy Technology Data Exchange (ETDEWEB)

Sisterson, D. L. [Argonne National Lab. (ANL), Argonne, IL (United States)

2015-10-01

The Atmospheric Radiation Measurement (ARM) Program was created in 1989 with funding from the U.S. Department of Energy (DOE) to develop several highly instrumented ground stations to study cloud formation processes and their influence on radiative transfer. In 2003, the ARM Program became a national scientific user facility, known as the ARM Climate Research Facility. This scientific infrastructure provides for fixed sites, mobile facilities, an aerial facility, and a data archive available for use by scientists worldwide through the ARM Climate Research Facility—a scientific user facility. The ARM Climate Research Facility currently operates more than 300 instrument systems that provide ground-based observations of the atmospheric column. To keep ARM at the forefront of climate observations, the ARM infrastructure depends heavily on instrument scientists and engineers, also known as lead mentors. Lead mentors must have an excellent understanding of in situ and remote-sensing instrumentation theory and operation and have comprehensive knowledge of critical scale-dependent atmospheric processes. They must also possess the technical and analytical skills to develop new data retrievals that provide innovative approaches for creating research-quality data sets. The ARM Climate Research Facility is seeking the best overall qualified candidate who can fulfill lead mentor requirements in a timely manner.

Competitive Protein Adsorption of Albumin and Immunoglobulin G from Human Serum onto Polymer Surfaces

DEFF Research Database (Denmark)

Holmberg, Maria; Hou, Xiaolin

2010-01-01

protein adsorption from diluted human serum solutions with relatively low protein concentrations, but the nonfouling character was weakened when less diluted human serum solutions with higher protein concentrations were used. The observed adsorption trend is independent of adsorption time, indicating...

Degradation of Human PDZ-Proteins by Human Alphapapillomaviruses Represents an Evolutionary Adaptation to a Novel Cellular Niche

Science.gov (United States)

Van Doorslaer, Koenraad; DeSalle, Rob; Einstein, Mark H.; Burk, Robert D.

2015-01-01

In order to complete their life cycle, papillomaviruses have evolved to manipulate a plethora of cellular pathways. The products of the human Alphapapillomavirus E6 proteins specifically interact with and target PDZ containing proteins for degradation. This viral phenotype has been suggested to play a role in viral oncogenesis. To analyze the association of HPV E6 mediated PDZ-protein degradation with cervical oncogenesis, a high-throughput cell culture assay was developed. Degradation of an epitope tagged human MAGI1 isoform was visualized by immunoblot. The correlation between HPV E6-induced degradation of hMAGI1 and epidemiologically determined HPV oncogenicity was evaluated using a Bayesian approach within a phylogenetic context. All tested oncogenic types degraded the PDZ-containing protein hMAGI1d; however, E6 proteins isolated from several related albeit non-oncogenic viral types were equally efficient at degrading hMAGI1. The relationship between both traits (oncogenicity and PDZ degradation potential) is best explained by a model in which the potential to degrade PDZ proteins was acquired prior to the oncogenic phenotype. This analysis provides evidence that the ancestor of both oncogenic and non-oncogenic HPVs acquired the potential to degrade human PDZ-containing proteins. This suggests that HPV E6 directed degradation of PDZ-proteins represents an ancient ecological niche adaptation. Phylogenetic modeling indicates that this phenotype is not specifically correlated with oncogenic risk, but may act as an enabling phenotype. The role of PDZ protein degradation in HPV fitness and oncogenesis needs to be interpreted in the context of Alphapapillomavirus evolution. PMID:26086730

Degradation of Human PDZ-Proteins by Human Alphapapillomaviruses Represents an Evolutionary Adaptation to a Novel Cellular Niche.

Directory of Open Access Journals (Sweden)

Koenraad Van Doorslaer

2015-06-01

Full Text Available In order to complete their life cycle, papillomaviruses have evolved to manipulate a plethora of cellular pathways. The products of the human Alphapapillomavirus E6 proteins specifically interact with and target PDZ containing proteins for degradation. This viral phenotype has been suggested to play a role in viral oncogenesis. To analyze the association of HPV E6 mediated PDZ-protein degradation with cervical oncogenesis, a high-throughput cell culture assay was developed. Degradation of an epitope tagged human MAGI1 isoform was visualized by immunoblot. The correlation between HPV E6-induced degradation of hMAGI1 and epidemiologically determined HPV oncogenicity was evaluated using a Bayesian approach within a phylogenetic context. All tested oncogenic types degraded the PDZ-containing protein hMAGI1d; however, E6 proteins isolated from several related albeit non-oncogenic viral types were equally efficient at degrading hMAGI1. The relationship between both traits (oncogenicity and PDZ degradation potential is best explained by a model in which the potential to degrade PDZ proteins was acquired prior to the oncogenic phenotype. This analysis provides evidence that the ancestor of both oncogenic and non-oncogenic HPVs acquired the potential to degrade human PDZ-containing proteins. This suggests that HPV E6 directed degradation of PDZ-proteins represents an ancient ecological niche adaptation. Phylogenetic modeling indicates that this phenotype is not specifically correlated with oncogenic risk, but may act as an enabling phenotype. The role of PDZ protein degradation in HPV fitness and oncogenesis needs to be interpreted in the context of Alphapapillomavirus evolution.

Degradation of Human PDZ-Proteins by Human Alphapapillomaviruses Represents an Evolutionary Adaptation to a Novel Cellular Niche.

Science.gov (United States)

Van Doorslaer, Koenraad; DeSalle, Rob; Einstein, Mark H; Burk, Robert D

2015-06-01

In order to complete their life cycle, papillomaviruses have evolved to manipulate a plethora of cellular pathways. The products of the human Alphapapillomavirus E6 proteins specifically interact with and target PDZ containing proteins for degradation. This viral phenotype has been suggested to play a role in viral oncogenesis. To analyze the association of HPV E6 mediated PDZ-protein degradation with cervical oncogenesis, a high-throughput cell culture assay was developed. Degradation of an epitope tagged human MAGI1 isoform was visualized by immunoblot. The correlation between HPV E6-induced degradation of hMAGI1 and epidemiologically determined HPV oncogenicity was evaluated using a Bayesian approach within a phylogenetic context. All tested oncogenic types degraded the PDZ-containing protein hMAGI1d; however, E6 proteins isolated from several related albeit non-oncogenic viral types were equally efficient at degrading hMAGI1. The relationship between both traits (oncogenicity and PDZ degradation potential) is best explained by a model in which the potential to degrade PDZ proteins was acquired prior to the oncogenic phenotype. This analysis provides evidence that the ancestor of both oncogenic and non-oncogenic HPVs acquired the potential to degrade human PDZ-containing proteins. This suggests that HPV E6 directed degradation of PDZ-proteins represents an ancient ecological niche adaptation. Phylogenetic modeling indicates that this phenotype is not specifically correlated with oncogenic risk, but may act as an enabling phenotype. The role of PDZ protein degradation in HPV fitness and oncogenesis needs to be interpreted in the context of Alphapapillomavirus evolution.

The arms race control

International Nuclear Information System (INIS)

Nemo, J.

2010-01-01

Written in 1961, this paper presents the content of a book entitled 'The arms race control' where the author outlined the difference between disarmament and arms control, described the economic and moral role of arms race, the importance of force balance for international security. He wandered whether arms control could ensure this balance and whether nuclear balance meant force balance. Force balance then appears to be a precarious and unsteady component of international security. He commented the challenges of disarmament, recalled some arguments for a nuclear disarmament. Then he discussed what would be an arms control with or without disarmament (either nuclear or conventional)

Progesterone-associated proteins PP12 and PP14 in the human endometrium.

Science.gov (United States)

Rutanen, E M; Koistinen, R; Seppälä, M; Julkunen, M; Suikkari, A M; Huhtala, M L

1987-01-01

Two proteins, designated as PP12 and PP14 were originally isolated from soluble extracts of the human placenta and its adjacent membranes. We have shown that they are synthesized by decidualized/secretory endometrium and not by placenta. Both proteins occur at high concentrations in human amniotic fluid, which is therefore an excellent source for purification. PP12 is a 34-kDa glycoprotein, which has an N-terminal amino acid sequence of Ala-Pro-Trp-Gln-Cys-Ala-Pro-Cys-Ser-Ala. This is identical with that of somatomedin-binding protein purified from the amniotic fluid. PP12 too binds somatomedin-C, or IGF-I (insulin-like growth factor-I). Human secretory endometrium synthesizes and secretes PP12, and progesterone stimulates its secretion. PP14 is a 28-kDa glycoprotein. Its N-terminal sequence shows homology to that of beta-lactoglobulins from various species. We have found PP14 in the human endometrium, serum and milk. Immunologically, PP14 is related to progestagen-associated endometrial protein (PEP), alpha-2 pregnancy-associated endometrial protein (alpha-2, PEG), endometrial protein 15 (EP15), alpha-uterine protein (AUP) and chorionic alpha-2 microglobulin (CAG-2). In ovulatory menstrual cycles, the concentration of PP14 increases in endometrial tissue as the secretory changes advance. In serum, the PP14 concentration begins to rise later than the progesterone levels, and high serum PP14 levels are maintained for the first days of the next cycle. By contrast, no elevation of serum PP14 level is seen in anovulatory cycles. Our results show that progesterone-associated proteins are synthesized by the human endometrium and appear in the peripheral circulation, where they can be quantitatively measured using immunochemical techniques.

Usability testing of the human-machine interface for the Light Duty Utility Arm System

International Nuclear Information System (INIS)

Kiebel, G.R.; Ellis, J.E.; Masliah, M.R.

1994-01-01

This report describes the usability testing that has been done for the control and data acquisition system for the Light Duty Utility Arm (LDUA) System. A program of usability testing has been established as a part of a process for making the LDUA as easy to use as possible. The LDUA System is being designed to deploy a family of tools, called End Effectors, into underground storage tanks by means of a robotic arm on the end of a telescoping mast, and to collect and manage the data that they generate. The LDUA System uses a vertical positioning mast, to lower the arm into a tank through an existing 30.5 cm access riser. A Mobile Deployment Subsystem is used to position the mast and arm over a tank riser for deployment, and to transport them from tank to tank. The LDUA System has many ancillary subsystems including the Operations Control Trailer, the Tank Riser Interface and Confinement Subsystem, the Decontamination Subsystem, and the End Effector Exchange Subsystem. This work resulted in the identification of several important improvements to the LDUA control and data acquisition system before the design was frozen. The most important of these were color coding of joints in motion, simultaneous operator control of multiple joints, and changes to the field-of-views of the camera lenses for the robot and other camera systems

How do octopuses use their arms?

Science.gov (United States)

Mather, J A

1998-09-01

A taxonomy of the movement patterns of the 8 flexible arms of octopuses is constructed. Components consist of movements of the arm itself, the ventral suckers and their stalks, as well as the relative position of arms and the skin web between them. Within 1 arm, combinations of components result in a variety of behaviors. At the level of all arms, 1 group of behaviors is described as postures, on the basis of the spread of all arms and the web to make a 2-dimensional surface whose position differs in the 3rd dimension. Another group of arm behaviors is actions, more or less coordinated and involving several to all arms. Arm control appears to be based on radial symmetry, relative equipotentiality of all arms, relative independence of each arm, and separability of components within the arm. The types and coordination of arm behaviors are discussed with relationship to biomechanical limits, muscle structures, and neuronal programming.

New Exoskeleton Arm Concept Design And Actuation For Haptic Interaction With Virtual Objects

Science.gov (United States)

Chakarov, D.; Veneva, I.; Tsveov, M.; Tiankov, T.

2014-12-01

In the work presented in this paper the conceptual design and actuation of one new exoskeleton of the upper limb is presented. The device is designed for application where both motion tracking and force feedback are required, such as human interaction with virtual environment or rehabilitation tasks. The choice is presented of mechanical structure kinematical equivalent to the structure of the human arm. An actuation system is selected based on braided pneumatic muscle actuators. Antagonistic drive system for each joint is shown, using pulley and cable transmissions. Force/displacement diagrams are presented of two antagonistic acting muscles. Kinematics and dynamic estimations are performed of the system exoskeleton and upper limb. Selected parameters ensure in the antagonistic scheme joint torque regulation and human arm range of motion.

Human trabecular meshwork cells express BMP antagonist mRNAs and proteins.

Science.gov (United States)

Tovar-Vidales, Tara; Fitzgerald, Ashley M; Clark, Abbot F

2016-06-01

Glaucoma patients have elevated aqueous humor and trabecular meshwork (TM) levels of transforming growth factor-beta2 (TGF-β2). TGF-β2 has been associated with increased extracellular matrix (ECM) deposition (i.e. fibronectin), which is attributed to the increased resistance of aqueous humor outflow through the TM. We have previously demonstrated that bone morphogenetic protein (BMP) 4 selectively counteracts the profibrotic effect of TGF-β2 with respect to ECM synthesis in the TM, and this action is reversed by the BMP antagonist gremlin. Thus, the BMP and TGF-β signaling pathways antagonize each other's antifibrotic and profibrotic roles. The purpose of this study was to determine whether cultured human TM cells: (a) express other BMP antagonists including noggin, chordin, BMPER, BAMBI, Smurf1 and 2, and (b) whether expression of these proteins is regulated by exogenous TGF-β2 treatment. Primary human trabecular meshwork (TM) cells were grown to confluency and treated with TGF-β2 (5 ng/ml) for 24 or 48 h in serum-free medium. Untreated cell served as controls. qPCR and Western immunoblots (WB) determined that human TM cells expressed mRNAs and proteins for the BMP antagonist proteins: noggin, chordin, BMPER, BAMBI, and Smurf1/2. Exogenous TGF-β2 decreased chordin, BMPER, BAMBI, and Smurf1 mRNA and protein expression. In contrast, TGF-β2 increased secreted noggin and Smurf2 mRNA and protein levels. BMP antagonist members are expressed in the human TM. These molecules may be involved in the normal function of the TM as well as TM pathogenesis. Altered expression of BMP antagonist members may lead to functional changes in the human TM. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genome-scale metabolic model of Pichia pastoris with native and humanized glycosylation of recombinant proteins.

Science.gov (United States)

Irani, Zahra Azimzadeh; Kerkhoven, Eduard J; Shojaosadati, Seyed Abbas; Nielsen, Jens

2016-05-01

Pichia pastoris is used for commercial production of human therapeutic proteins, and genome-scale models of P. pastoris metabolism have been generated in the past to study the metabolism and associated protein production by this yeast. A major challenge with clinical usage of recombinant proteins produced by P. pastoris is the difference in N-glycosylation of proteins produced by humans and this yeast. However, through metabolic engineering, a P. pastoris strain capable of producing humanized N-glycosylated proteins was constructed. The current genome-scale models of P. pastoris do not address native nor humanized N-glycosylation, and we therefore developed ihGlycopastoris, an extension to the iLC915 model with both native and humanized N-glycosylation for recombinant protein production, but also an estimation of N-glycosylation of P. pastoris native proteins. This new model gives a better prediction of protein yield, demonstrates the effect of the different types of N-glycosylation of protein yield, and can be used to predict potential targets for strain improvement. The model represents a step towards a more complete description of protein production in P. pastoris, which is required for using these models to understand and optimize protein production processes. © 2015 Wiley Periodicals, Inc.

Activation of human natural killer cells by the soluble form of cellular prion protein

International Nuclear Information System (INIS)

Seong, Yeon-Jae; Sung, Pil Soo; Jang, Young-Soon; Choi, Young Joon; Park, Bum-Chan; Park, Su-Hyung; Park, Young Woo; Shin, Eui-Cheol

2015-01-01

Cellular prion protein (PrP C ) is widely expressed in various cell types, including cells of the immune system. However, the specific roles of PrP C in the immune system have not been clearly elucidated. In the present study, we investigated the effects of a soluble form of recombinant PrP C protein on human natural killer (NK) cells. Recombinant soluble PrP C protein was generated by fusion of human PrP C with the Fc portion of human IgG 1 (PrP C -Fc). PrP C -Fc binds to the surface of human NK cells, particularly to CD56 dim NK cells. PrP C -Fc induced the production of cytokines and chemokines and the degranulation of granzyme B from NK cells. In addition, PrP C -Fc facilitated the IL-15-induced proliferation of NK cells. PrP C -Fc induced phosphorylation of ERK-1/2 and JNK in NK cells, and inhibitors of the ERK or the JNK pathways abrogated PrP C -Fc-induced cytokine production in NK cells. In conclusion, the soluble form of recombinant PrP C -Fc protein activates human NK cells via the ERK and JNK signaling pathways. - Highlights: • Recombinant soluble PrP C (PrP C -Fc) was generated by fusion of human PrP C with IgG1 Fc portion. • PrP C -Fc protein induces the production of cytokines and degranulation from human NK cells. • PrP C -Fc protein enhances the IL-15-induced proliferation of human NK cells. • PrP C -Fc protein activates human NK cells via the ERK and JNK signaling pathways

[Production of human proteins in the blood of transgenic animals

NARCIS (Netherlands)

Massoud, M.; Bischoff, Rainer; Dalemans, W.; Pointu, H.; Attal, J.; Schultz, H.; Clesse, D.; Stinnakre, M.G.; Pavirani, A.; Houdebine, L.M.

1990-01-01

The human alpha 1-antitrypsin gene has been microinjected into rabbit embryos. A line of transgenic rabbits has thus been established. Human alpha 1-antitrypsin was found in the blood of transgenic animals at the concentration of 1 mg/ml plasma. The human protein was active and separable from its

Recombinant Protein Truncation Strategy for Inducing Bactericidal Antibodies to the Macrophage Infectivity Potentiator Protein of Neisseria meningitidis and Circumventing Potential Cross-Reactivity with Human FK506-Binding Proteins

OpenAIRE

Bielecka, Magdalena K.; Devos, Nathalie; Gilbert, Mélanie; Hung, Miao-Chiu; Weynants, Vincent; Heckels, John E.; Christodoulides, Myron

2014-01-01

A recombinant macrophage infectivity potentiator (rMIP) protein of Neisseria meningitidis induces significant serum bactericidal antibody production in mice and is a candidate meningococcal vaccine antigen. However, bioinformatics analysis of MIP showed some amino acid sequence similarity to human FK506-binding proteins (FKBPs) in residues 166 to 252 located in the globular domain of the protein. To circumvent the potential concern over generating antibodies that could recognize human protein...

CyARM: Haptic Sensing Device for Spatial Localization on Basis of Exploration by Arms

Directory of Open Access Journals (Sweden)

Junichi Akita

2009-01-01

Full Text Available We introduce a new type of perception aid device based on user's exploration action, which is named as CyARM (acronym of “Cyber Arm”. The user holds this device in her/his arm, the extension of the arm is controlled by tension in wires, which are attached to her/his body according to the distance to the object. This user interface has unique characteristics that give users the illusion of an imaginary arm that extends to existing objects. The implementations of CyARM and our two experiments to investigate the efficiency and effectiveness of CyARM are described. The results show that we could confirm that CyARM can be used to recognize the presence of an object in front of the user and to measure the relative distance to the object.

Complete cDNA sequence coding for human docking protein

Energy Technology Data Exchange (ETDEWEB)

Hortsch, M; Labeit, S; Meyer, D I

1988-01-11

Docking protein (DP, or SRP receptor) is a rough endoplasmic reticulum (ER)-associated protein essential for the targeting and translocation of nascent polypeptides across this membrane. It specifically interacts with a cytoplasmic ribonucleoprotein complex, the signal recognition particle (SRP). The nucleotide sequence of cDNA encoding the entire human DP and its deduced amino acid sequence are given.

Optimizing the measurement of mitochondrial protein synthesis in human skeletal muscle.

Science.gov (United States)

Burd, Nicholas A; Tardif, Nicolas; Rooyackers, Olav; van Loon, Luc J C

2015-01-01

The measurement of mitochondrial protein synthesis after food ingestion, contractile activity, and/or disease is often used to provide insight into skeletal muscle adaptations that occur in the longer term. Studies have shown that protein ingestion stimulates mitochondrial protein synthesis in human skeletal muscle. Minor differences in the stimulation of mitochondrial protein synthesis occur after a single bout of resistance or endurance exercise. There appear to be no measurable differences in mitochondrial protein synthesis between critically ill patients and aged-matched controls. However, the mitochondrial protein synthetic response is reduced at a more advanced age. In this paper, we discuss the challenges involved in the measurement of human skeletal muscle mitochondrial protein synthesis rates based on stable isotope amino acid tracer methods. Practical guidelines are discussed to improve the reliability of the measurement of mitochondrial protein synthesis rates. The value of the measurement of mitochondrial protein synthesis after a single meal or exercise bout on the prediction of the longer term skeletal muscle mass and performance outcomes in both the healthy and disease populations requires more work, but we emphasize that the measurements need to be reliable to be of any value to the field.

Identification of actin binding protein, ABP-280, as a binding partner of human Lnk adaptor protein.

Science.gov (United States)

He, X; Li, Y; Schembri-King, J; Jakes, S; Hayashi, J

2000-08-01

Human Lnk (hLnk) is an adaptor protein with multiple functional domains that regulates T cell activation signaling. In order to identify cellular Lnk binding partners, a yeast two-hybrid screening of human spleen cDNA library was carried out using human hLnk as bait. A polypeptide sequence identical to the C-terminal segment of the actin binding protein (ABP-280) was identified as a hLnk binding protein. The expressed hLnk and the FLAG tagged C-terminal 673 amino acid residues of ABP-280 or the endogenous ABP-280 in COS-7 cells could be co-immunoprecipitated using antibodies either to hLnk, FLAG or ABP-280, respectively. Furthermore, immunofluorescence confocal microscope showed that hLnk and ABP-280 co-localized at the plasma membrane and at juxtanuclear region of COS-7 cells. In Jurkat cells, the endogenous hLnk also associates with the endogenous ABP-280 indicating that the association of these two proteins is physiological. The interacting domains of both proteins were mapped using yeast two-hybrid assays. Our results indicate that hLnk binds to the residues 2006-2454 (repeats 19-23C) of ABP-280. The domain in hLnk that associates with ABP-280 was mapped to an interdomain region of 56 amino acids between pleckstrin homology and Src homology 2 domains. These results suggest that hLnk may exert its regulatory role through its association with ABP-280.

De novo origin of human protein-coding genes.

Directory of Open Access Journals (Sweden)

Dong-Dong Wu

2011-11-01

Full Text Available The de novo origin of a new protein-coding gene from non-coding DNA is considered to be a very rare occurrence in genomes. Here we identify 60 new protein-coding genes that originated de novo on the human lineage since divergence from the chimpanzee. The functionality of these genes is supported by both transcriptional and proteomic evidence. RNA-seq data indicate that these genes have their highest expression levels in the cerebral cortex and testes, which might suggest that these genes contribute to phenotypic traits that are unique to humans, such as improved cognitive ability. Our results are inconsistent with the traditional view that the de novo origin of new genes is very rare, thus there should be greater appreciation of the importance of the de novo origination of genes.

De Novo Origin of Human Protein-Coding Genes

Science.gov (United States)

Wu, Dong-Dong; Irwin, David M.; Zhang, Ya-Ping

2011-01-01

The de novo origin of a new protein-coding gene from non-coding DNA is considered to be a very rare occurrence in genomes. Here we identify 60 new protein-coding genes that originated de novo on the human lineage since divergence from the chimpanzee. The functionality of these genes is supported by both transcriptional and proteomic evidence. RNA–seq data indicate that these genes have their highest expression levels in the cerebral cortex and testes, which might suggest that these genes contribute to phenotypic traits that are unique to humans, such as improved cognitive ability. Our results are inconsistent with the traditional view that the de novo origin of new genes is very rare, thus there should be greater appreciation of the importance of the de novo origination of genes. PMID:22102831

Research on the Optimization Method of Arm Movement in the Assembly Workshop Based on Ergonomics

Science.gov (United States)

Hu, X. M.; Qu, H. W.; Xu, H. J.; Yang, L.; Yu, C. C.

2017-12-01

In order to improve the work efficiency and comfortability, Ergonomics is used to research the work of the operator in the assembly workshop. An optimization algorithm of arm movement in the assembly workshop is proposed. In the algorithm, a mathematical model of arm movement is established based on multi rigid body movement model and D-H method. The solution of inverse kinematics equation on arm movement is solved through kinematics theory. The evaluation functions of each joint movement and the whole arm movement are given based on the comfortability of human body joint. The solution method of the optimal arm movement posture based on the evaluation functions is described. The software CATIA is used to verify that the optimal arm movement posture is valid in an example and the experimental result show the effectiveness of the algorithm.

EXPRESSION AND SIGNIFICANCE OF ERK PROTEIN IN HUMAN BREAST CARCINOMA

Institute of Scientific and Technical Information of China (English)

张秀梅; 李柏林; 宋敏; 宋继谒

2004-01-01

Objective: To investigate the expression of ERK and p-ERK protein in human breast cancer and their corresponding tissue, to assess the significance of ERK signal pathway in tumorigenesis and progression of breast carcinoma. Methods: 40 breast cancer cases were used in S-P immunohistochemistry technique and Western Blot study. Results: The expression of ERK1, ERK2, and p- ERK protein levels increased remarkably in breast cancer tissues in comparison to normal tissues (P<0.01). The expression was upregulated by 1.32-, 1.53-and 4.27-fold, respectively. The overexpressions of ERK1, ERK2, and p- ERK proteins were obviously correlated with clinical stage of breast cancer. Protein levels of ERK and p-ERK were higher in stage III patients than in stage I and stage II patients (P<0.05). These proteins were strongly related with axillary lymph node metastasis of breast cancer, but not correlated with histopathological type and status of ER and PR of breast cancer. Expression of ERK1, and ERK2, protein showed a positive linear correlation. Conclusion: ERK signal transduction pathway is a key factor during human breast tumorigenesis and breast cancer progression.

CCAAT/enhancer-binding proteins regulate expression of the human steroidogenic acute regulatory protein (StAR) gene.

Science.gov (United States)

Christenson, L K; Johnson, P F; McAllister, J M; Strauss, J F

1999-09-10

Two putative CCAAT/enhancer-binding protein (C/EBP) response elements were identified in the proximal promoter of the human steroidogenic acute regulatory protein (StAR) gene, which encodes a key protein-regulating steroid hormone synthesis. Expression of C/EBPalpha and -beta increased StAR promoter activity in COS-1 and HepG2 cells. Cotransfection of C/EBPalpha or -beta and steroidogenic factor 1, a transcription factor required for cAMP regulation of StAR expression, into COS-1 augmented 8-bromoadenosine 3':5'-cyclic monophosphate (8-Br-cAMP)-stimulated promoter activity. When the putative C/EBP response elements were mutated, individually or together, a pronounced decline in basal StAR promoter activity in human granulosa-lutein cells resulted, but the fold stimulation of promoter activity by 8-Br-cAMP was unaffected. Recombinant C/EBPalpha and -beta bound to the two identified sequences but not the mutated elements. Human granulosa-lutein cell nuclear extracts also bound these elements but not the mutated sequences. An antibody to C/EBPbeta, but not C/EBPalpha, supershifted the nuclear protein complex associated with the more distal element. The complex formed by nuclear extracts with the proximal element was not supershifted by either antibody. Western blot analysis revealed the presence of C/EBPalpha and C/EBPbeta in human granulosa-lutein cell nuclear extracts. C/EBPbeta levels were up-regulated 3-fold by 8-Br-cAMP treatment. Our studies demonstrate a role for C/EBPbeta as well as yet to be identified proteins, which can bind to C/EBP response elements, in the regulation of StAR gene expression and suggest a mechanism by which C/EBPbeta participates in the cAMP regulation of StAR gene transcription.

Designing, Fabrication and Controlling Of Multipurpose3-DOF Robotic Arm

Science.gov (United States)

Nabeel, Hafiz Muhammad; Azher, Anum; Usman Ali, Syed M.; Wahab Mughal, Abdul

2013-12-01

In the present work, we have successfully designed and developed a 3-DOF articulated Robotic Arm capable of performing typical industrial tasks such as painting or spraying, assembling and handling automobiles parts and etc., in resemblance to a human arm. The mechanical assembly is designed on SOLIDWORKS and aluminum grade 6061 -T6 is used for its fabrication in order to reduce the structure weight. We have applied inverse kinematics to determine the joint angles, equations are fed into an efficient microcontroller ATMEGA16 which performs all the calculations to determine the joint angles on the basis of given coordinates to actuate the joints through motorized control. Good accuracy was obtained with quadrature optical encoders installed in each joint to achieve the desired position and a LabVIEW based GUI is designed to provide human machine interface.

Designing, Fabrication and Controlling Of Multipurpose3-DOF Robotic Arm

International Nuclear Information System (INIS)

Nabeel, Hafiz Muhammad; Azher, Anum; Ali, Syed M Usman; Mughal, Abdul Wahab

2013-01-01

In the present work, we have successfully designed and developed a 3-DOF articulated Robotic Arm capable of performing typical industrial tasks such as painting or spraying, assembling and handling automobiles parts and etc., in resemblance to a human arm. The mechanical assembly is designed on SOLIDWORKS and aluminum grade 6061 -T6 is used for its fabrication in order to reduce the structure weight. We have applied inverse kinematics to determine the joint angles, equations are fed into an efficient microcontroller ATMEGA16 which performs all the calculations to determine the joint angles on the basis of given coordinates to actuate the joints through motorized control. Good accuracy was obtained with quadrature optical encoders installed in each joint to achieve the desired position and a LabVIEW based GUI is designed to provide human machine interface

Rev and Rex proteins of human complex retroviruses function with the MMTV Rem-responsive element

Directory of Open Access Journals (Sweden)

Dudley Jaquelin P

2009-02-01

Full Text Available Abstract Background Mouse mammary tumor virus (MMTV encodes the Rem protein, an HIV Rev-like protein that enhances nuclear export of unspliced viral RNA in rodent cells. We have shown that Rem is expressed from a doubly spliced RNA, typical of complex retroviruses. Several recent reports indicate that MMTV can infect human cells, suggesting that MMTV might interact with human retroviruses, such as human immunodeficiency virus (HIV, human T-cell leukemia virus (HTLV, and human endogenous retrovirus type K (HERV-K. In this report, we test whether the export/regulatory proteins of human complex retroviruses will increase expression from vectors containing the Rem-responsive element (RmRE. Results MMTV Rem, HIV Rev, and HTLV Rex proteins, but not HERV-K Rec, enhanced expression from an MMTV-based reporter plasmid in human T cells, and this activity was dependent on the RmRE. No RmRE-dependent reporter gene expression was detectable using Rev, Rex, or Rec in HC11 mouse mammary cells. Cell fractionation and RNA quantitation experiments suggested that the regulatory proteins did not affect RNA stability or nuclear export in the MMTV reporter system. Rem had no demonstrable activity on export elements from HIV, HTLV, or HERV-K. Similar to the Rem-specific activity in rodent cells, the RmRE-dependent functions of Rem, Rev, or Rex in human cells were inhibited by a dominant-negative truncated nucleoporin that acts in the Crm1 pathway of RNA and protein export. Conclusion These data argue that many retroviral regulatory proteins recognize similar complex RNA structures, which may depend on the presence of cell-type specific proteins. Retroviral protein activity on the RmRE appears to affect a post-export function of the reporter RNA. Our results provide additional evidence that MMTV is a complex retrovirus with the potential for viral interactions in human cells.

Structure and Function of Human Tyrosinase and Tyrosinase-Related Proteins

NARCIS (Netherlands)

Lai, Xuelei; Wichers, Harry J.; Soler-Lopez, Montserrat; Dijkstra, Bauke W.

2018-01-01

Melanin is the main pigment responsible for the color of human skin, hair and eye. Its biosynthesis requires three melanogenic enzymes, tyrosinase (TYR), and the tyrosinase-related proteins TYRP1 and TYRP2. The difficulty of isolating pure and homogeneous proteins from endogenous sources has

The quest of the human proteome and the missing proteins: digging deeper.

Science.gov (United States)

Reddy, Panga Jaipal; Ray, Sandipan; Srivastava, Sanjeeva

2015-05-01

Given the diverse range of transcriptional and post-transcriptional mechanisms of gene regulation, the estimates of the human proteome is likely subject to scientific surprises as the field of proteomics has gained momentum worldwide. In this regard, the establishment of the "Human Proteome Draft" using high-resolution mass spectrometry (MS), tissue microarrays, and immunohistochemistry by three independent research groups (laboratories of Pandey, Kuster, and Uhlen) accelerated the pace of proteomics research. The Chromosome Centric Human Proteome Project (C-HPP) has taken initiative towards the completion of the Human Proteome Project (HPP) so as to understand the proteomics correlates of common complex human diseases and biological diversity, not to mention person-to-person and population differences in response to drugs, nutrition, vaccines, and other health interventions and host-environment interactions. Although high-resolution MS-based and antibody microarray approaches have shown enormous promises, we are still unable to map the whole human proteome due to the presence of numerous "missing proteins." In December 2014, at the Indian Institute of Technology Bombay, Mumbai the 6(th) Annual Meeting of the Proteomics Society, India (PSI) and the International Proteomics Conference was held. As part of this interdisciplinary summit, a panel discussion session on "The Quest of the Human Proteome and Missing Proteins" was organized. Eminent scientists in the field of proteomics and systems biology, including Akhilesh Pandey, Gilbert S. Omenn, Mark S. Baker, and Robert L. Mortiz, shed light on different aspects of the human proteome drafts and missing proteins. Importantly, the possible reasons for the "missing proteins" in shotgun MS workflow were identified and debated by experts as low tissue expression, lack of enzymatic digestion site, or protein lost during extraction, among other contributing factors. To capture the missing proteins, the experts' collective

Activation of human natural killer cells by the soluble form of cellular prion protein

Energy Technology Data Exchange (ETDEWEB)

Seong, Yeon-Jae [Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon (Korea, Republic of); Hafis Clinic, Seoul (Korea, Republic of); Sung, Pil Soo; Jang, Young-Soon; Choi, Young Joon [Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon (Korea, Republic of); Park, Bum-Chan [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Park, Su-Hyung [Laboratory of Translational Immunology and Vaccinology, Graduate School of Medical Science and Engineering, KAIST, Daejeon (Korea, Republic of); Park, Young Woo [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Shin, Eui-Cheol, E-mail: ecshin@kaist.ac.kr [Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon (Korea, Republic of)

2015-08-21

Cellular prion protein (PrP{sup C}) is widely expressed in various cell types, including cells of the immune system. However, the specific roles of PrP{sup C} in the immune system have not been clearly elucidated. In the present study, we investigated the effects of a soluble form of recombinant PrP{sup C} protein on human natural killer (NK) cells. Recombinant soluble PrP{sup C} protein was generated by fusion of human PrP{sup C} with the Fc portion of human IgG{sub 1} (PrP{sup C}-Fc). PrP{sup C}-Fc binds to the surface of human NK cells, particularly to CD56{sup dim} NK cells. PrP{sup C}-Fc induced the production of cytokines and chemokines and the degranulation of granzyme B from NK cells. In addition, PrP{sup C}-Fc facilitated the IL-15-induced proliferation of NK cells. PrP{sup C}-Fc induced phosphorylation of ERK-1/2 and JNK in NK cells, and inhibitors of the ERK or the JNK pathways abrogated PrP{sup C}-Fc-induced cytokine production in NK cells. In conclusion, the soluble form of recombinant PrP{sup C}-Fc protein activates human NK cells via the ERK and JNK signaling pathways. - Highlights: • Recombinant soluble PrP{sup C} (PrP{sup C}-Fc) was generated by fusion of human PrP{sup C} with IgG1 Fc portion. • PrP{sup C}-Fc protein induces the production of cytokines and degranulation from human NK cells. • PrP{sup C}-Fc protein enhances the IL-15-induced proliferation of human NK cells. • PrP{sup C}-Fc protein activates human NK cells via the ERK and JNK signaling pathways.

Human muscle proteins: analysis by two-dimensional electrophoresis

Energy Technology Data Exchange (ETDEWEB)

Giometti, C.S.; Danon, M.J.; Anderson, N.G.

1983-09-01

Proteins from single frozen sections of human muscle were separated by two-dimensional gel electrophoresis and detected by fluorography or Coomassie Blue staining. The major proteins were identical in different normal muscles obtained from either sex at different ages, and in Duchenne and myotonic dystrophy samples. Congenital myopathy denervation atrophy, polymyositis, and Becker's muscular dystrophy samples, however, showed abnormal myosin light chain compositions, some with a decrease of fast-fiber myosin light chains and others with a decrease of slow-fiber light chains. These protein alterations did not correlate with any specific disease, and may be cause by generalized muscle-fiber damage.

Human intestinal mucus proteins isolated by transanal irrigation and proctosigmoidoscopy

Directory of Open Access Journals (Sweden)

Paola Andrea Gómez Buitrago

2014-10-01

Full Text Available Human intestinal mucus essentially consists of a network of Mucin2 glycoproteins embedded in many lower molecular weight proteins. This paper contributes to the proteomic study of human intestinal mucus by comparing two sample collection methods (transanal irrigation and brush cytology during proctosigmoidoscopy and analysis techniques (electrophoresis and digestion in solution. The entire sample collection and treatment process is explained, including protein extraction, digestion and desalination and peptide characterisation using a nanoAcquity UPLC chromatograph coupled to an HDMS spectrometer equipped with a nanoESI source. Collecting mucus via transanal irrigation provided a larger sample volume and protein concentration from a single patient. The proctosigmoidoscopy sample could be analysed via digestion in solution after depleting albumin. The analysis indicates that a simple mucus lysis method can evaluate the electrophoresis and digestion in solution techniques. Studying human intestinal mucus complexes is important because they perform two essential survival functions for humans as the first biochemical and physical defences for the gastrointestinal tract and a habitat for intestinal microbiota, which are primarily hosted in the colon and exceeds the human genetic information and cell number 100- and 10-fold (1.

Gene-specific correlation of RNA and protein levels in human cells and tissues

DEFF Research Database (Denmark)

Edfors, Fredrik; Danielsson, Frida; Hallström, Björn M.

2016-01-01

An important issue for molecular biology is to establish whether transcript levels of a given gene can be used as proxies for the corresponding protein levels. Here, we have developed a targeted proteomics approach for a set of human non-secreted proteins based on parallel reaction monitoring...... to measure, at steady-state conditions, absolute protein copy numbers across human tissues and cell lines and compared these levels with the corresponding mRNA levels using transcriptomics. The study shows that the transcript and protein levels do not correlate well unless a gene-specific RNA-to-protein (RTP...

Protein Turnover Measurements in Human Serum by Serial Immunoaffinity LC-MS/MS.

Science.gov (United States)

Farrokhi, Vahid; Chen, Xiaoying; Neubert, Hendrik

2018-02-01

The half-life of target proteins is frequently an important parameter in mechanistic pharmacokinetic and pharmacodynamic (PK/PD) modeling of biotherapeutics. Clinical studies for accurate measurement of physiologically relevant protein turnover can reduce the uncertainty in PK/PD model-based predictions, for example, of the therapeutic dose and dosing regimen in first-in-human clinical trials. We used a targeted mass spectrometry work flow based on serial immunoaffinity enrichment ofmultiple human serum proteins from a [5,5,5- 2 H 3 ]-L-leucine tracer pulse-chase study in healthy volunteers. To confirm the reproducibility of turnover measurements from serial immunoaffinity enrichment, multiple aliquots from the same sample set were subjected to protein turnover analysis in varying order. Tracer incorporation was measured by multiple-reaction-monitoring mass spectrometry and target turnover was calculated using a four-compartment pharmacokinetic model. Five proteins of clinical or therapeutic relevance including soluble tumor necrosis factor receptor superfamily member 12A, tissue factor pathway inhibitor, soluble interleukin 1 receptor like 1, soluble mucosal addressin cell adhesion molecule 1, and muscle-specific creatine kinase were sequentially subjected to turnover analysis from the same human serum sample. Calculated half-lives ranged from 5-15 h; however, no tracer incorporation was observed for mucosal addressin cell adhesion molecule 1. The utility of clinical pulse-chase studies to investigate protein turnover can be extended by serial immunoaffinity enrichment of target proteins. Turnover analysis from serum and subsequently from remaining supernatants provided analytical sensitivity and reproducibility for multiple human target proteins in the same sample set, irrespective of the order of analysis. © 2017 American Association for Clinical Chemistry.

Long interspersed element-1 protein expression is a hallmark of many human cancers.

Science.gov (United States)

Rodić, Nemanja; Sharma, Reema; Sharma, Rajni; Zampella, John; Dai, Lixin; Taylor, Martin S; Hruban, Ralph H; Iacobuzio-Donahue, Christine A; Maitra, Anirban; Torbenson, Michael S; Goggins, Michael; Shih, Ie-Ming; Duffield, Amy S; Montgomery, Elizabeth A; Gabrielson, Edward; Netto, George J; Lotan, Tamara L; De Marzo, Angelo M; Westra, William; Binder, Zev A; Orr, Brent A; Gallia, Gary L; Eberhart, Charles G; Boeke, Jef D; Harris, Chris R; Burns, Kathleen H

2014-05-01

Cancers comprise a heterogeneous group of human diseases. Unifying characteristics include unchecked abilities of tumor cells to proliferate and spread anatomically, and the presence of clonal advantageous genetic changes. However, universal and highly specific tumor markers are unknown. Herein, we report widespread long interspersed element-1 (LINE-1) repeat expression in human cancers. We show that nearly half of all human cancers are immunoreactive for a LINE-1-encoded protein. LINE-1 protein expression is a common feature of many types of high-grade malignant cancers, is rarely detected in early stages of tumorigenesis, and is absent from normal somatic tissues. Studies have shown that LINE-1 contributes to genetic changes in cancers, with somatic LINE-1 insertions seen in selected types of human cancers, particularly colon cancer. We sought to correlate this observation with expression of the LINE-1-encoded protein, open reading frame 1 protein, and found that LINE-1 open reading frame 1 protein is a surprisingly broad, yet highly tumor-specific, antigen. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

The MCM-associated protein MCM-BP is important for human nuclear morphology.

Science.gov (United States)

Jagannathan, Madhav; Sakwe, Amos M; Nguyen, Tin; Frappier, Lori

2012-01-01

Mini-chromosome maintenance complex-binding protein (MCM-BP) was discovered as a protein that is strongly associated with human MCM proteins, known to be crucial for DNA replication in providing DNA helicase activity. The Xenopus MCM-BP homologue appears to play a role in unloading MCM complexes from chromatin after DNA synthesis; however, the importance of MCM-BP and its functional contribution to human cells has been unclear. Here we show that depletion of MCM-BP by sustained expression of short hairpin RNA (shRNA) results in highly abnormal nuclear morphology and centrosome amplification. The abnormal nuclear morphology was not seen with depletion of other MCM proteins and was rescued with shRNA-resistant MCM-BP. MCM-BP depletion was also found to result in transient activation of the G2 checkpoint, slowed progression through G2 and increased replication protein A foci, indicative of replication stress. In addition, MCM-BP depletion led to increased cellular levels of MCM proteins throughout the cell cycle including soluble MCM pools. The results suggest that MCM-BP makes multiple contributions to human cells that are not limited to unloading of the MCM complex.

Whole-body CT in polytrauma patients: the effect of arm position on abdominal image quality when using a human phantom

Energy Technology Data Exchange (ETDEWEB)

Jeon, Pil-Hyun [Yonsei University, Wonju (Korea, Republic of); Wonju Christian Hospital, Wonju (Korea, Republic of); Kim, Hee-Joung; Lee, Chang-Lae; Kim, Dae-Hong [Yonsei University, Wonju (Korea, Republic of); Lee, Won-Hyung; Jeon, Sung-Su [Wonju Christian Hospital, Wonju (Korea, Republic of)

2012-06-15

For a considerable number of emergency computed tomography (CT) scans, patients are unable to position their arms above their head due to traumatic injuries. The arms-down position has been shown to reduce image quality with beam-hardening artifacts in the dorsal regions of the liver, spleen, and kidneys, rendering these images non-diagnostic. The purpose of this study was to evaluate the effect of arm position on the image quality in patients undergoing whole-body CT. We acquired CT scans with various acquisition parameters at voltages of 80, 120, and 140 kVp and an increasing tube current from 200 to 400 mAs in 50 mAs increments. The image noise and the contrast assessment were considered for quantitative analyses of the CT images. The image noise (IN), the contrast-to-noise ratio (CNR), the signal-to-noise ratio (SNR), and the coefficient of variation (COV) were evaluated. Quantitative analyses of the experiments were performed with CT scans representative of five different arm positions. Results of the CT scans acquired at 120 kVp and 250 mAs showed high image quality in patients with both arms raised above the head (SNR: 12.4, CNR: 10.9, and COV: 8.1) and both arms flexed at the elbows on the chest (SNR: 11.5, CNR: 10.2, and COV: 8.8) while the image quality significantly decreased with both arms in the down position (SNR: 9.1, CNR: 7.6, and COV: 11). Both arms raised, one arm raised, and both arms flexed improved the image quality compared to arms in the down position by reducing beam-hardening and streak artifacts caused by the arms being at the side of body. This study provides optimal methods for achieving higher image quality and lower noise in abdominal CT for trauma patients.

Whole-body CT in polytrauma patients: The effect of arm position on abdominal image quality when using a human phantom

Science.gov (United States)

Jeon, Pil-Hyun; Kim, Hee-Joung; Lee, Chang-Lae; Kim, Dae-Hong; Lee, Won-Hyung; Jeon, Sung-Su

2012-06-01

For a considerable number of emergency computed tomography (CT) scans, patients are unable to position their arms above their head due to traumatic injuries. The arms-down position has been shown to reduce image quality with beam-hardening artifacts in the dorsal regions of the liver, spleen, and kidneys, rendering these images non-diagnostic. The purpose of this study was to evaluate the effect of arm position on the image quality in patients undergoing whole-body CT. We acquired CT scans with various acquisition parameters at voltages of 80, 120, and 140 kVp and an increasing tube current from 200 to 400 mAs in 50 mAs increments. The image noise and the contrast assessment were considered for quantitative analyses of the CT images. The image noise (IN), the contrast-to-noise ratio (CNR), the signal-to-noise ratio (SNR), and the coefficient of variation (COV) were evaluated. Quantitative analyses of the experiments were performed with CT scans representative of five different arm positions. Results of the CT scans acquired at 120 kVp and 250 mAs showed high image quality in patients with both arms raised above the head (SNR: 12.4, CNR: 10.9, and COV: 8.1) and both arms flexed at the elbows on the chest (SNR: 11.5, CNR: 10.2, and COV: 8.8) while the image quality significantly decreased with both arms in the down position (SNR: 9.1, CNR: 7.6, and COV: 11). Both arms raised, one arm raised, and both arms flexed improved the image quality compared to arms in the down position by reducing beam-hardening and streak artifacts caused by the arms being at the side of body. This study provides optimal methods for achieving higher image quality and lower noise in abdominal CT for trauma patients.

Whole-body CT in polytrauma patients: the effect of arm position on abdominal image quality when using a human phantom

International Nuclear Information System (INIS)

Jeon, Pil-Hyun; Kim, Hee-Joung; Lee, Chang-Lae; Kim, Dae-Hong; Lee, Won-Hyung; Jeon, Sung-Su

2012-01-01

For a considerable number of emergency computed tomography (CT) scans, patients are unable to position their arms above their head due to traumatic injuries. The arms-down position has been shown to reduce image quality with beam-hardening artifacts in the dorsal regions of the liver, spleen, and kidneys, rendering these images non-diagnostic. The purpose of this study was to evaluate the effect of arm position on the image quality in patients undergoing whole-body CT. We acquired CT scans with various acquisition parameters at voltages of 80, 120, and 140 kVp and an increasing tube current from 200 to 400 mAs in 50 mAs increments. The image noise and the contrast assessment were considered for quantitative analyses of the CT images. The image noise (IN), the contrast-to-noise ratio (CNR), the signal-to-noise ratio (SNR), and the coefficient of variation (COV) were evaluated. Quantitative analyses of the experiments were performed with CT scans representative of five different arm positions. Results of the CT scans acquired at 120 kVp and 250 mAs showed high image quality in patients with both arms raised above the head (SNR: 12.4, CNR: 10.9, and COV: 8.1) and both arms flexed at the elbows on the chest (SNR: 11.5, CNR: 10.2, and COV: 8.8) while the image quality significantly decreased with both arms in the down position (SNR: 9.1, CNR: 7.6, and COV: 11). Both arms raised, one arm raised, and both arms flexed improved the image quality compared to arms in the down position by reducing beam-hardening and streak artifacts caused by the arms being at the side of body. This study provides optimal methods for achieving higher image quality and lower noise in abdominal CT for trauma patients.

SGLT2 Protein Expression Is Increased in Human Diabetic Nephropathy

Science.gov (United States)

Wang, Xiaoxin X.; Levi, Jonathan; Luo, Yuhuan; Myakala, Komuraiah; Herman-Edelstein, Michal; Qiu, Liru; Wang, Dong; Peng, Yingqiong; Grenz, Almut; Lucia, Scott; Dobrinskikh, Evgenia; D'Agati, Vivette D.; Koepsell, Hermann; Kopp, Jeffrey B.; Rosenberg, Avi Z.; Levi, Moshe

2017-01-01

There is very limited human renal sodium gradient-dependent glucose transporter protein (SGLT2) mRNA and protein expression data reported in the literature. The first aim of this study was to determine SGLT2 mRNA and protein levels in human and animal models of diabetic nephropathy. We have found that the expression of SGLT2 mRNA and protein is increased in renal biopsies from human subjects with diabetic nephropathy. This is in contrast to db-db mice that had no changes in renal SGLT2 protein expression. Furthermore, the effect of SGLT2 inhibition on renal lipid content and inflammation is not known. The second aim of this study was to determine the potential mechanisms of beneficial effects of SGLT2 inhibition in the progression of diabetic renal disease. We treated db/db mice with a selective SGLT2 inhibitor JNJ 39933673. We found that SGLT2 inhibition caused marked decreases in systolic blood pressure, kidney weight/body weight ratio, urinary albumin, and urinary thiobarbituric acid-reacting substances. SGLT2 inhibition prevented renal lipid accumulation via inhibition of carbohydrate-responsive element-binding protein-β, pyruvate kinase L, SCD-1, and DGAT1, key transcriptional factors and enzymes that mediate fatty acid and triglyceride synthesis. SGLT2 inhibition also prevented inflammation via inhibition of CD68 macrophage accumulation and expression of p65, TLR4, MCP-1, and osteopontin. These effects were associated with reduced mesangial expansion, accumulation of the extracellular matrix proteins fibronectin and type IV collagen, and loss of podocyte markers WT1 and synaptopodin, as determined by immunofluorescence microscopy. In summary, our study showed that SGLT2 inhibition modulates renal lipid metabolism and inflammation and prevents the development of nephropathy in db/db mice. PMID:28196866

Elemental analysis of human serum and serum protein fractions by thermal neutron activation

International Nuclear Information System (INIS)

Woittiez, J.R.W.

1984-01-01

Some applications of thermal neutron activation for the determination of elemental contents in human serum and human serum protein fractions are presented. Firstly total serum is dealt with, secondly serum protein fractions obtained by gel filtration are described. A brief review on the role of (trace) elements in human health and disease and a compilation of literature data for elemental contents in human serum, as obtained by neutron activation techniques, are given. The most important sources of statistical and systematic errors are evaluated. Results for the contents of sodium, potassium, magnesium, bromine, iron, copper, zinc, selenium, rubidium, cesium and antimony in serum are given, with emphasis on control of accuracy and precision. The possible relation between selenium in blood and cancer occurrence in humans is discussed. The results of elemental analyses from cancer patients and from a patient receiving a cytostatic treatment are presented. A survey of literature results for the determination of protein-bound elemental contents in serum is presented. Subsequently, results from a study on the behaviour of elements during gel filtration are discussed. Gel-element and protein-element interactions are studied. Finally the protein-bound occurrence of trace elements in human serum is determined by gel filtration and neutron activation analysis. Results for both desalting and fractionation are given, for the elements bromine, copper, manganese, vanadium, selenium, zinc, rubidium, iron and iodine. (Auth.)

Armed conflict and child health.

Science.gov (United States)

Rieder, Michael; Choonara, Imti

2012-01-01

Armed conflict has a major impact on child health throughout the world. One in six children worldwide lives in an area of armed conflict and civilians are more likely to die than soldiers as a result of the conflict. In stark contrast to the effect on children, the international arms trade results in huge profits for the large corporations involved in producing arms, weapons and munitions. Armed conflict is not inevitable but is an important health issue that should be prevented.

Knock-in of Enhanced Green Fluorescent Protein or/and Human Fibroblast Growth Factor 2 Gene into β-Casein Gene Locus in the Porcine Fibroblasts to Produce Therapeutic Protein.

Science.gov (United States)

Lee, Sang Mi; Kim, Ji Woo; Jeong, Young-Hee; Kim, Se Eun; Kim, Yeong Ji; Moon, Seung Ju; Lee, Ji-Hye; Kim, Keun-Jung; Kim, Min-Kyu; Kang, Man-Jong

2014-11-01

Transgenic animals have become important tools for the production of therapeutic proteins in the domestic animal. Production efficiencies of transgenic animals by conventional methods as microinjection and retrovirus vector methods are low, and the foreign gene expression levels are also low because of their random integration in the host genome. In this study, we investigated the homologous recombination on the porcine β-casein gene locus using a knock-in vector for the β-casein gene locus. We developed the knock-in vector on the porcine β-casein gene locus and isolated knock-in fibroblast for nuclear transfer. The knock-in vector consisted of the neomycin resistance gene (neo) as a positive selectable marker gene, diphtheria toxin-A gene as negative selection marker, and 5' arm and 3' arm from the porcine β-casein gene. The secretion of enhanced green fluorescent protein (EGFP) was more easily detected in the cell culture media than it was by western blot analysis of cell extract of the HC11 mouse mammary epithelial cells transfected with EGFP knock-in vector. These results indicated that a knock-in system using β-casein gene induced high expression of transgene by the gene regulatory sequence of endogenous β-casein gene. These fibroblasts may be used to produce transgenic pigs for the production of therapeutic proteins via the mammary glands.

Hello to Arms

Science.gov (United States)

2005-01-01

This image highlights the hidden spiral arms (blue) that were discovered around the nearby galaxy NGC 4625 by the ultraviolet eyes of NASA's Galaxy Evolution Explorer. The image is composed of ultraviolet and visible-light data, from the Galaxy Evolution Explorer and the California Institute of Technology's Digitized Sky Survey, respectively. Near-ultraviolet light is colored green; far-ultraviolet light is colored blue; and optical light is colored red. As the image demonstrates, the lengthy spiral arms are nearly invisible when viewed in optical light while bright in ultraviolet. This is because they are bustling with hot, newborn stars that radiate primarily ultraviolet light. The youthful arms are also very long, stretching out to a distance four times the size of the galaxy's core. They are part of the largest ultraviolet galactic disk discovered so far. Located 31 million light-years away in the constellation Canes Venatici, NGC 4625 is the closest galaxy ever seen with such a young halo of arms. It is slightly smaller than our Milky Way, both in size and mass. However, the fact that this galaxy's disk is forming stars very actively suggests that it might evolve into a more massive and mature galaxy resembling our own. The armless companion galaxy seen below NGC 4625 is called NGC 4618. Astronomers do not know why it lacks arms but speculate that it may have triggered the development of arms in NGC 4625.

An artificial flexible robot arm based on pneumatic muscle actuators

Directory of Open Access Journals (Sweden)

Renn Jyh-Chyang

2017-01-01

Full Text Available The purpose of this paper is to develop a novel human-friendly artificial flexible robot arm using four parallel-connected pneumatic muscle actuators (PMAs. The PMA is a flexible silicone rubber actuator which has some behaviors nearest to the real biological muscle including translational and rotational motions. An inverse kinematic model for the motion control is also developed. Finally, from experiment results, it is proved that not only the axial contraction control of a single PMA but also the attitude control of the whole pneumatic flexible robot arm using PID controller are satisfactory.

Bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles as novel tumor targeting carriers

International Nuclear Information System (INIS)

Ding Hong; Yong, Ken-Tye; Roy, Indrajit; Hu Rui; Zhao Lingling; Law, Wing-Cheung; Ji Wei; Liu Liwei; Bergey, Earl J; Prasad, Paras N; Wu Fang; Zhao Weiwei

2011-01-01

In this study, we have developed a novel carrier, micelle-type bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles (NPs), for the detection and treatment of pancreatic cancer. These NPs contained 4-arm-PEG as corona, and PLGA as core, the particle surface was conjugated with cyclo(arginine-glycine-aspartate) (cRGD) as ligand for in vivo tumor targeting. The hydrodynamic size of the NPs was determined to be 150-180 nm and the critical micellar concentration (CMC) was estimated to be 10.5 mg l -1 . Our in vitro study shows that these NPs by themselves had negligible cytotoxicity to human pancreatic cancer (Panc-1) and human glioblastoma (U87) cell lines. Near infrared (NIR) microscopy and flow cytometry demonstrated that the cRGD conjugated PLGA-4-arm-PEG polymeric NPs were taken up more efficiently by U87MG glioma cells, over-expressing the α v β 3 integrin, when compared with the non-targeted NPs. Whole body imaging showed that the cRGD conjugated PLGA-4-arm-PEG branched polymeric NPs had the highest accumulation in the pancreatic tumor site of mice at 48 h post-injection. Physical, hematological, and pathological assays indicated low in vivo toxicity of this NP formulation. These studies on the ability of these bioconjugated PLGA-4-arm-PEG polymeric NPs suggest that the prepared polymeric NPs may serve as a promising platform for detection and targeted drug delivery for pancreatic cancer.

Bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles as novel tumor targeting carriers

Energy Technology Data Exchange (ETDEWEB)

Ding Hong; Yong, Ken-Tye; Roy, Indrajit; Hu Rui; Zhao Lingling; Law, Wing-Cheung; Ji Wei; Liu Liwei; Bergey, Earl J; Prasad, Paras N [Department of Chemistry, Institute for Lasers, Photonics and Biophotonics, University at Buffalo, State University of New York, Buffalo, NY 14260 (United States); Wu Fang [Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14260 (United States); Zhao Weiwei, E-mail: bergeye@buffalo.edu, E-mail: pnprasad@buffalo.edu [Department of Microbiology and Immunology, University at Buffalo, State University of New York, Buffalo, NY 14215 (United States)

2011-04-22

In this study, we have developed a novel carrier, micelle-type bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles (NPs), for the detection and treatment of pancreatic cancer. These NPs contained 4-arm-PEG as corona, and PLGA as core, the particle surface was conjugated with cyclo(arginine-glycine-aspartate) (cRGD) as ligand for in vivo tumor targeting. The hydrodynamic size of the NPs was determined to be 150-180 nm and the critical micellar concentration (CMC) was estimated to be 10.5 mg l{sup -1}. Our in vitro study shows that these NPs by themselves had negligible cytotoxicity to human pancreatic cancer (Panc-1) and human glioblastoma (U87) cell lines. Near infrared (NIR) microscopy and flow cytometry demonstrated that the cRGD conjugated PLGA-4-arm-PEG polymeric NPs were taken up more efficiently by U87MG glioma cells, over-expressing the {alpha}{sub v{beta}3} integrin, when compared with the non-targeted NPs. Whole body imaging showed that the cRGD conjugated PLGA-4-arm-PEG branched polymeric NPs had the highest accumulation in the pancreatic tumor site of mice at 48 h post-injection. Physical, hematological, and pathological assays indicated low in vivo toxicity of this NP formulation. These studies on the ability of these bioconjugated PLGA-4-arm-PEG polymeric NPs suggest that the prepared polymeric NPs may serve as a promising platform for detection and targeted drug delivery for pancreatic cancer.

Mitochondrial Fusion Proteins and Human Diseases

Directory of Open Access Journals (Sweden)

Michela Ranieri

2013-01-01

Full Text Available Mitochondria are highly dynamic, complex organelles that continuously alter their shape, ranging between two opposite processes, fission and fusion, in response to several stimuli and the metabolic demands of the cell. Alterations in mitochondrial dynamics due to mutations in proteins involved in the fusion-fission machinery represent an important pathogenic mechanism of human diseases. The most relevant proteins involved in the mitochondrial fusion process are three GTPase dynamin-like proteins: mitofusin 1 (MFN1 and 2 (MFN2, located in the outer mitochondrial membrane, and optic atrophy protein 1 (OPA1, in the inner membrane. An expanding number of degenerative disorders are associated with mutations in the genes encoding MFN2 and OPA1, including Charcot-Marie-Tooth disease type 2A and autosomal dominant optic atrophy. While these disorders can still be considered rare, defective mitochondrial dynamics seem to play a significant role in the molecular and cellular pathogenesis of more common neurodegenerative diseases, for example, Alzheimer’s and Parkinson’s diseases. This review provides an overview of the basic molecular mechanisms involved in mitochondrial fusion and focuses on the alteration in mitochondrial DNA amount resulting from impairment of mitochondrial dynamics. We also review the literature describing the main disorders associated with the disruption of mitochondrial fusion.

Unequal-Arms Michelson Interferometers

Science.gov (United States)

Tinto, Massimo; Armstrong, J. W.

2000-01-01

Michelson interferometers allow phase measurements many orders of magnitude below the phase stability of the laser light injected into their two almost equal-length arms. If, however, the two arms are unequal, the laser fluctuations can not be removed by simply recombining the two beams. This is because the laser jitters experience different time delays in the two arms, and therefore can not cancel at the photo detector. We present here a method for achieving exact laser noise cancellation, even in an unequal-arm interferometer. The method presented in this paper requires a separate readout of the relative phase in each arm, made by interfering the returning beam in each arm with a fraction of the outgoing beam. By linearly combining the two data sets with themselves, after they have been properly time shifted, we show that it is possible to construct a new data set that is free of laser fluctuations. An application of this technique to future planned space-based laser interferometer detector3 of gravitational radiation is discussed.

P16INK4a Positive Cells in Human Skin Are Indicative of Local Elastic Fiber Morphology, Facial Wrinkling, and Perceived Age

DEFF Research Database (Denmark)

Waaijer, Mariëtte E C; Gunn, David A; Adams, Peter D

2016-01-01

Senescent cells are more prevalent in aged human skin compared to young, but evidence that senescent cells are linked to other biomarkers of aging is scarce. We counted cells positive for the tumor suppressor and senescence associated protein p16INK4a in sun-protected upper-inner arm skin biopsies...... wrinkles and a higher perceived age. Participants in the lowest tertile of epidermal p16INK4a counts looked 3 years younger than those in the highest tertile, independently of chronological age and elastic fiber morphology. In conclusion, p16INK4a positive cell numbers in sun-protected human arm skin...

SU-F-207-03: Dosimetric Effect of the Position of Arms in Torso CT Scan with Tube Current Modulation

International Nuclear Information System (INIS)

Liu, H; Gao, Y; Xu, X; Zhuo, W; Wu, J

2015-01-01

Purpose: To evaluate the patient organ dose differences between the arms-raised and arms-lowered postures in Torso multidetector computed tomography (MDCT) scan protocols with tube current modulation (TCM). Methods: Patient CT organ doses were simulated using the Monte Carlo method with human phantoms and a validated CT scanner model. A set of adult human phantoms with arms raised and arms lowered postures were developed using advanced BREP-based mesh surface geometries. Organ doses from routine Torso scan protocols such as chest, abdomen-pelvis, and CAP scans were simulated. The organ doses differences caused by two different posutres were investigated when tube current modulation (TCM) were applied during the CT scan. Results: With TCM applied, organ doses of all the listed organs of arms-lowered posture phantom are larger than those of arms raised phantom. The dose difference for most of the organs or tissues are larger than 50%, and the skin doses difference for abdomen-pelvis scan even reaches 112.03%. This is due to the fact that the tube current for patient with arms-lowered is much higher than for the arms raised posture. Conclusion: Considering CT scan with TCM, which is commonly applied clinically, patients who could not raise their arms will receive higher radiation dose than the arms raised patient, with dose differences for some tissues such as the skin being larger than 100%. This is due to the additional tube current necessary to penetrate the arms while maintaining consistent image quality. National Nature Science Foundation of China(No.11475047)

Proteomic data from human cell cultures refine mechanisms of chaperone-mediated protein homeostasis.

Science.gov (United States)

Finka, Andrija; Goloubinoff, Pierre

2013-09-01

In the crowded environment of human cells, folding of nascent polypeptides and refolding of stress-unfolded proteins is error prone. Accumulation of cytotoxic misfolded and aggregated species may cause cell death, tissue loss, degenerative conformational diseases, and aging. Nevertheless, young cells effectively express a network of molecular chaperones and folding enzymes, termed here "the chaperome," which can prevent formation of potentially harmful misfolded protein conformers and use the energy of adenosine triphosphate (ATP) to rehabilitate already formed toxic aggregates into native functional proteins. In an attempt to extend knowledge of chaperome mechanisms in cellular proteostasis, we performed a meta-analysis of human chaperome using high-throughput proteomic data from 11 immortalized human cell lines. Chaperome polypeptides were about 10% of total protein mass of human cells, half of which were Hsp90s and Hsp70s. Knowledge of cellular concentrations and ratios among chaperome polypeptides provided a novel basis to understand mechanisms by which the Hsp60, Hsp70, Hsp90, and small heat shock proteins (HSPs), in collaboration with cochaperones and folding enzymes, assist de novo protein folding, import polypeptides into organelles, unfold stress-destabilized toxic conformers, and control the conformal activity of native proteins in the crowded environment of the cell. Proteomic data also provided means to distinguish between stable components of chaperone core machineries and dynamic regulatory cochaperones.

Effects of UVB-induced oxidative stress on protein expression and specific protein oxidation in normal human epithelial keratinocytes: a proteomic approach

Directory of Open Access Journals (Sweden)

De Marco Federico

2010-03-01

Full Text Available Abstract Background The UVB component of solar ultraviolet irradiation is one of the major risk factors for the development of skin cancer in humans. UVB exposure elicits an increased generation of reactive oxygen species (ROS, which are responsible for oxidative damage to proteins, DNA, RNA and lipids. In order to examine the biological impact of UVB irradiation on skin cells, we used a parallel proteomics approach to analyze the protein expression profile and to identify oxidatively modified proteins in normal human epithelial keratinocytes. Results The expression levels of fifteen proteins - involved in maintaining the cytoskeleton integrity, removal of damaged proteins and heat shock response - were differentially regulated in UVB-exposed cells, indicating that an appropriate response is developed in order to counteract/neutralize the toxic effects of UVB-raised ROS. On the other side, the redox proteomics approach revealed that seven proteins - involved in cellular adhesion, cell-cell interaction and protein folding - were selectively oxidized. Conclusions Despite a wide and well orchestrated cellular response, a relevant oxidation of specific proteins concomitantly occurs in UVB-irradiated human epithelial Keratinocytes. These modified (i.e. likely dysfunctional proteins might result in cell homeostasis impairment and therefore eventually promote cellular degeneration, senescence or carcinogenesis.

Standardization for cortisol determination in human blood by competitive protein-binding

International Nuclear Information System (INIS)

Okada, H.

1978-01-01

Standardization for determination of cortisol from human plasma (17-hydroxycorticosteroids) using competitive protein-binding method is presented. Activated carbon coated with dextrans is used for separation of the hormone-protein complexe and hormone labelled free [pt

The importance of domestic law to international arms control

International Nuclear Information System (INIS)

Lehman, R.F. II.

1993-11-01

Studies of arms control and disarmament tend to focus on political, military, and diplomatic processes. Recently, in the context of the conversion of defense activities to civilian use, the economic aspects of arms control have also received renewed interest. The legal dimension, however, is in need of fresh examination. Both international and domestic law are sailing increasingly in uncharted waters. Recent arms control agreements and related developments in international peacekeeping have expanded the scope of international law and altered how one perceives certain fundamentals, including the principle of national sovereignty. Still, the nation state is largely unchallenged as the primary actor in international affairs. National governments retain near absolute sovereign rights and responsibilities even in an age of trans-national economic integration and codified international norms for human rights, freedom of the press, and the peaceful resolution of disputes. Indeed, the role of domestic law in arms control and disarmament may be more significant now than ever before. A brief review of relationships between arms control and domestic law should illustrate ways in which ones thinking has been underestimating the importance of domestic law. Hopefully, this survey will set the stage properly for the excellent, more detailed case studies by Elinor Hammarskjold and Alan Crawford. Toward that end, this paper will highlight a number of more general, and sometimes provocative, themes. These themes should be kept in mind when those two complementary presentations are considered

The importance of domestic law to international arms control

Energy Technology Data Exchange (ETDEWEB)

Lehman, R.F. II

1993-11-01

Studies of arms control and disarmament tend to focus on political, military, and diplomatic processes. Recently, in the context of the conversion of defense activities to civilian use, the economic aspects of arms control have also received renewed interest. The legal dimension, however, is in need of fresh examination. Both international and domestic law are sailing increasingly in uncharted waters. Recent arms control agreements and related developments in international peacekeeping have expanded the scope of international law and altered how one perceives certain fundamentals, including the principle of national sovereignty. Still, the nation state is largely unchallenged as the primary actor in international affairs. National governments retain near absolute sovereign rights and responsibilities even in an age of trans-national economic integration and codified international norms for human rights, freedom of the press, and the peaceful resolution of disputes. Indeed, the role of domestic law in arms control and disarmament may be more significant now than ever before. A brief review of relationships between arms control and domestic law should illustrate ways in which ones thinking has been underestimating the importance of domestic law. Hopefully, this survey will set the stage properly for the excellent, more detailed case studies by Elinor Hammarskjold and Alan Crawford. Toward that end, this paper will highlight a number of more general, and sometimes provocative, themes. These themes should be kept in mind when those two complementary presentations are considered.

Coupling of lever arm swing and biased Brownian motion in actomyosin.

Directory of Open Access Journals (Sweden)

Qing-Miao Nie

2014-04-01

Full Text Available An important unresolved problem associated with actomyosin motors is the role of Brownian motion in the process of force generation. On the basis of structural observations of myosins and actins, the widely held lever-arm hypothesis has been proposed, in which proteins are assumed to show sequential structural changes among observed and hypothesized structures to exert mechanical force. An alternative hypothesis, the Brownian motion hypothesis, has been supported by single-molecule experiments and emphasizes more on the roles of fluctuating protein movement. In this study, we address the long-standing controversy between the lever-arm hypothesis and the Brownian motion hypothesis through in silico observations of an actomyosin system. We study a system composed of myosin II and actin filament by calculating free-energy landscapes of actin-myosin interactions using the molecular dynamics method and by simulating transitions among dynamically changing free-energy landscapes using the Monte Carlo method. The results obtained by this combined multi-scale calculation show that myosin with inorganic phosphate (Pi and ADP weakly binds to actin and that after releasing Pi and ADP, myosin moves along the actin filament toward the strong-binding site by exhibiting the biased Brownian motion, a behavior consistent with the observed single-molecular behavior of myosin. Conformational flexibility of loops at the actin-interface of myosin and the N-terminus of actin subunit is necessary for the distinct bias in the Brownian motion. Both the 5.5-11 nm displacement due to the biased Brownian motion and the 3-5 nm displacement due to lever-arm swing contribute to the net displacement of myosin. The calculated results further suggest that the recovery stroke of the lever arm plays an important role in enhancing the displacement of myosin through multiple cycles of ATP hydrolysis, suggesting a unified movement mechanism for various members of the myosin family.

Coupling of lever arm swing and biased Brownian motion in actomyosin.

Science.gov (United States)

Nie, Qing-Miao; Togashi, Akio; Sasaki, Takeshi N; Takano, Mitsunori; Sasai, Masaki; Terada, Tomoki P

2014-04-01

An important unresolved problem associated with actomyosin motors is the role of Brownian motion in the process of force generation. On the basis of structural observations of myosins and actins, the widely held lever-arm hypothesis has been proposed, in which proteins are assumed to show sequential structural changes among observed and hypothesized structures to exert mechanical force. An alternative hypothesis, the Brownian motion hypothesis, has been supported by single-molecule experiments and emphasizes more on the roles of fluctuating protein movement. In this study, we address the long-standing controversy between the lever-arm hypothesis and the Brownian motion hypothesis through in silico observations of an actomyosin system. We study a system composed of myosin II and actin filament by calculating free-energy landscapes of actin-myosin interactions using the molecular dynamics method and by simulating transitions among dynamically changing free-energy landscapes using the Monte Carlo method. The results obtained by this combined multi-scale calculation show that myosin with inorganic phosphate (Pi) and ADP weakly binds to actin and that after releasing Pi and ADP, myosin moves along the actin filament toward the strong-binding site by exhibiting the biased Brownian motion, a behavior consistent with the observed single-molecular behavior of myosin. Conformational flexibility of loops at the actin-interface of myosin and the N-terminus of actin subunit is necessary for the distinct bias in the Brownian motion. Both the 5.5-11 nm displacement due to the biased Brownian motion and the 3-5 nm displacement due to lever-arm swing contribute to the net displacement of myosin. The calculated results further suggest that the recovery stroke of the lever arm plays an important role in enhancing the displacement of myosin through multiple cycles of ATP hydrolysis, suggesting a unified movement mechanism for various members of the myosin family.

Detection of cow's milk proteins and minor components in human milk using proteomics techniques.

Science.gov (United States)

Coscia, A; Orrù, S; Di Nicola, P; Giuliani, F; Varalda, A; Peila, C; Fabris, C; Conti, A; Bertino, E

2012-10-01

Cow's milk proteins (CMPs) are the best characterized food allergens. The aim of this study was to investigate cow's milk allergens in human colostrum of term and preterm newborns' mothers, and other minor protein components by proteomics techniques, more sensitive than other techniques used in the past. Sixty-two term and 11 preterm colostrum samples were collected, subjected to a treatment able to increase the concentration of the most diluted proteins and simultaneously to reduce the concentration of the proteins present at high concentration (Proteominer Treatment), and subsequently subjected to the steps of proteomic techniques. The most relevant finding in this study was the detection of the intact bovine alpha-S1-casein in human colostrum, then bovine alpha-1-casein could be considered the cow's milk allergen that is readily secreted in human milk and could be a cause of sensitization to cow's milk in exclusively breastfed predisposed infants. Another interesting result was the detection, at very low concentrations, of proteins previously not described in human milk (galectin-7, the different isoforms of the 14-3-3 protein and the serum amyloid P-component), probably involved in the regulation of the normal cell growth, in the pro-apoptotic function and in the regulation of tissue homeostasis. Further investigations are needed to understand if these families of proteins have specific biological activity in human milk.

Shared and Unique Proteins in Human, Mouse and Rat Saliva Proteomes: Footprints of Functional Adaptation

Directory of Open Access Journals (Sweden)

Robert C. Karn

2013-12-01

Full Text Available The overall goal of our study was to compare the proteins found in the saliva proteomes of three mammals: human, mouse and rat. Our first objective was to compare two human proteomes with very different analysis depths. The 89 shared proteins in this comparison apparently represent a core of highly-expressed human salivary proteins. Of the proteins unique to each proteome, one-half to 2/3 lack signal peptides and probably are contaminants instead of less highly-represented salivary proteins. We recently published the first rodent saliva proteomes with saliva collected from the genome mouse (C57BL/6 and the genome rat (BN/SsNHsd/Mcwi. Our second objective was to compare the proteins in the human proteome with those we identified in the genome mouse and rat to determine those common to all three mammals, as well as the specialized rodent subset. We also identified proteins unique to each of the three mammals, because differences in the secreted protein constitutions can provide clues to differences in the evolutionary adaptation of the secretions in the three different mammals.

Armed conflict and child health

OpenAIRE

Rieder, Michael; Choonara, Imti

2012-01-01

Armed conflict has a major impact on child health\\ud throughout the world. One in six children worldwide lives\\ud in an area of armed conflict and civilians are more likely\\ud to die than soldiers as a result of the conflict. In stark\\ud contrast to the effect on children, the international arms\\ud trade results in huge profits for the large corporations\\ud involved in producing arms, weapons and munitions.\\ud Armed conflict is not inevitable but is an important\\ud health issue that should be...

[Study for lung sound acquisition module based on ARM and Linux].

Science.gov (United States)

Lu, Qiang; Li, Wenfeng; Zhang, Xixue; Li, Junmin; Liu, Longqing

2011-07-01

A acquisition module with ARM and Linux as a core was developed. This paper presents the hardware configuration and the software design. It is shown that the module can extract human lung sound reliably and effectively.

Sexual violence in armed conflicts and modern international law

NARCIS (Netherlands)

Eboe-Osuji, C.G.

2011-01-01

Sexual violence in various forms is a particular brand of evil that women have endured during armed conflicts, from time immemorial. It is a problem that has continued to task the conscience of humanity, especially in our times. There has been no shortage of basic laws at the international level

Analysis of transcript and protein overlap in a human osteosarcoma cell line

Directory of Open Access Journals (Sweden)

Emanuelsson Olof

2010-12-01

Full Text Available Abstract Background An interesting field of research in genomics and proteomics is to compare the overlap between the transcriptome and the proteome. Recently, the tools to analyse gene and protein expression on a whole-genome scale have been improved, including the availability of the new generation sequencing instruments and high-throughput antibody-based methods to analyze the presence and localization of proteins. In this study, we used massive transcriptome sequencing (RNA-seq to investigate the transcriptome of a human osteosarcoma cell line and compared the expression levels with in situ protein data obtained in-situ from antibody-based immunohistochemistry (IHC and immunofluorescence microscopy (IF. Results A large-scale analysis based on 2749 genes was performed, corresponding to approximately 13% of the protein coding genes in the human genome. We found the presence of both RNA and proteins to a large fraction of the analyzed genes with 60% of the analyzed human genes detected by all three methods. Only 34 genes (1.2% were not detected on the transcriptional or protein level with any method. Our data suggest that the majority of the human genes are expressed at detectable transcript or protein levels in this cell line. Since the reliability of antibodies depends on possible cross-reactivity, we compared the RNA and protein data using antibodies with different reliability scores based on various criteria, including Western blot analysis. Gene products detected in all three platforms generally have good antibody validation scores, while those detected only by antibodies, but not by RNA sequencing, generally consist of more low-scoring antibodies. Conclusion This suggests that some antibodies are staining the cells in an unspecific manner, and that assessment of transcript presence by RNA-seq can provide guidance for validation of the corresponding antibodies.

Novel anti-c-Mpl monoclonal antibodies identified multiple differentially glycosylated human c-Mpl proteins in megakaryocytic cells but not in human solid tumors.

Science.gov (United States)

Zhan, Jinghui; Felder, Barbara; Ellison, Aaron R; Winters, Aaron; Salimi-Moosavi, Hossein; Scully, Sheila; Turk, James R; Wei, Ping

2013-06-01

Thrombopoietin and its cognate receptor, c-Mpl, are the primary molecular regulators of megakaryocytopoiesis and platelet production. To date the pattern of c-Mpl expression in human solid tumors and the distribution and biochemical properties of c-Mpl proteins in hematopoietic tissues are largely unknown. We have recently developed highly specific mouse monoclonal antibodies (MAb) against human c-Mpl. In this study we used these antibodies to demonstrate the presence of full-length and truncated human c-Mpl proteins in various megakaryocytic cell types, and their absence in over 100 solid tumor cell lines and in the 12 most common primary human tumor types. Quantitative assays showed a cell context-dependent distribution of full-length and truncated c-Mpl proteins. All forms of human c-Mpl protein were found to be modified with extensive N-linked glycosylation but different degrees of sialylation and O-linked glycosylation. Of note, different variants of full-length c-Mpl protein exhibiting differential glycosylation were expressed in erythromegakaryocytic leukemic cell lines and in platelets from healthy human donors. This work provides a comprehensive analysis of human c-Mpl mRNA and protein expression on normal and malignant hematopoietic and non-hematopoietic cells and demonstrates the multiple applications of several novel anti-c-Mpl antibodies.

The human TRPV6 channel protein is associated with cyclophilin B in human placenta.

Science.gov (United States)

Stumpf, Tobias; Zhang, Qi; Hirnet, Daniela; Lewandrowski, Urs; Sickmann, Albert; Wissenbach, Ulrich; Dörr, Janka; Lohr, Christian; Deitmer, Joachim W; Fecher-Trost, Claudia

2008-06-27

Transcellular calcium transport in the kidney, pancreas, small intestine, and placenta is partly mediated by transient receptor potential (TRP) channels. The highly selective TRPV6 calcium channel protein is most likely important for the calcium transfer in different specialized epithelial cells. In the human placenta the protein is expressed in trophoblast tissue, where it is implicated in the transepithelial calcium transfer from mother to the fetus. We enriched the TRPV6 channel protein endogenously expressed in placenta together with annexin A2 and cyclophilin B (CypB), which is a member of the huge immunophilin family. In the human placenta TRPV6 and CypB are mainly located intracellularly in the syncytiotrophoblast layer, but a small amount of the mature glycosylated TRPV6 channel protein and CypB is also expressed in microvilli apical membranes, the fetomaternal barrier. To understand the role of CypB on the TRPV6 channel function, we evaluated the effect of CypB co-expression on TRPV6-mediated calcium uptake into Xenopus laevis oocytes expressing TRPV6. A significant increase of TRPV6-mediated calcium uptake was observed after CypB/TRPV6 co-expression. This stimulatory effect of CypB was reversed by the immunosuppressive drug cyclosporin A, which inhibits the enzymatic activity of CypB. Cyclosporin A had no significant effect on TRPV6 and CypB protein expression levels in the oocytes. In summary, our results establish CypB as a new TRPV6 accessory protein with potential involvement in TRPV6 channel activation through its peptidyl-prolyl cis/trans isomerase activity.

Effects of age, sex and arm on the precision of arm position sense—left-arm superiority in healthy right-handers

OpenAIRE

Schmidt, Lena; Depper, Lena; Kerkhoff, Georg

2013-01-01

Position sense is an important proprioceptive ability. Disorders of arm position sense (APS) often occur after unilateral stroke, and are associated with a negative functional outcome. In the present study we assessed horizontal APS by measuring angular deviations from a visually defined target separately for each arm in a large group of healthy subjects. We analyzed the accuracy and instability of horizontal APS as a function of age, sex and arm. Subjects were required to specify verbally th...

Performance of arm locking in LISA

International Nuclear Information System (INIS)

McKenzie, Kirk; Spero, Robert E.; Shaddock, Daniel A.

2009-01-01

For the Laser Interferometer Space Antenna (LISA) to reach its design sensitivity, the coupling of the free-running laser frequency noise to the signal readout must be reduced by more than 14 orders of magnitude. One technique employed to reduce the laser frequency noise will be arm locking, where the laser frequency is locked to the LISA arm length. In this paper we detail an implementation of arm locking. We investigate orbital effects (changing arm lengths and Doppler frequencies), the impact of errors in the Doppler knowledge that can cause pulling of the laser frequency, and the noise limit of arm locking. Laser frequency pulling is examined in two regimes: at lock acquisition and in steady state. The noise performance of arm locking is calculated with the inclusion of the dominant expected noise sources: ultrastable oscillator (clock) noise, spacecraft motion, and shot noise. We find that clock noise and spacecraft motion limit the performance of dual arm locking in the LISA science band. Studying these issues reveals that although dual arm locking [A. Sutton and D. A. Shaddock, Phys. Rev. D 78, 082001 (2008)] has advantages over single (or common) arm locking in terms of allowing high gain, it has disadvantages in both laser frequency pulling and noise performance. We address this by proposing a modification to the dual arm-locking sensor, a hybrid of common and dual arm-locking sensors. This modified dual arm-locking sensor has the laser frequency pulling characteristics and low-frequency noise coupling of common arm locking, but retains the control system advantages of dual arm locking. We present a detailed design of an arm-locking controller and perform an analysis of the expected performance when used with and without laser prestabilization. We observe that the sensor phase changes beneficially near unity-gain frequencies of the arm-locking controller, allowing a factor of 10 more gain than previously believed, without degrading stability. With a time

Integrated Design Optimization of a 5-DOF Assistive Light-weight Anthropomorphic Arm

DEFF Research Database (Denmark)

Zhou, Lelai; Bai, Shaoping; Hansen, Michael Rygaard

2011-01-01

An integrated dimensional and drive train optimization method was developed for light-weight robotic arm design. The method deals with the determination of optimal link lengths and the optimal selection of motors and gearboxes from commercially available components. Constraints are formulated...... on the basis of kinematic performance and dynamic requirements, whereas the main objective is to minimize the weight. The design of a human-like arm, which is 10 kg in weight with a load capacity of 5 kg, is described....

Design of a multi-arm randomized clinical trial with no control arm.

Science.gov (United States)

Magaret, Amalia; Angus, Derek C; Adhikari, Neill K J; Banura, Patrick; Kissoon, Niranjan; Lawler, James V; Jacob, Shevin T

2016-01-01

Clinical trial designs that include multiple treatments are currently limited to those that perform pairwise comparisons of each investigational treatment to a single control. However, there are settings, such as the recent Ebola outbreak, in which no treatment has been demonstrated to be effective; and therefore, no standard of care exists which would serve as an appropriate control. For illustrative purposes, we focused on the care of patients presenting in austere settings with critically ill 'sepsis-like' syndromes. Our approach involves a novel algorithm for comparing mortality among arms without requiring a single fixed control. The algorithm allows poorly-performing arms to be dropped during interim analyses. Consequently, the study may be completed earlier than planned. We used simulation to determine operating characteristics for the trial and to estimate the required sample size. We present a potential study design targeting a minimal effect size of a 23% relative reduction in mortality between any pair of arms. Using estimated power and spurious significance rates from the simulated scenarios, we show that such a trial would require 2550 participants. Over a range of scenarios, our study has 80 to 99% power to select the optimal treatment. Using a fixed control design, if the control arm is least efficacious, 640 subjects would be enrolled into the least efficacious arm, while our algorithm would enroll between 170 and 430. This simulation method can be easily extended to other settings or other binary outcomes. Early dropping of arms is efficient and ethical when conducting clinical trials with multiple arms. Copyright © 2015 Elsevier Inc. All rights reserved.

Arm Motion Recognition and Exercise Coaching System for Remote Interaction

Directory of Open Access Journals (Sweden)

Hong Zeng

2016-01-01

Full Text Available Arm motion recognition and its related applications have become a promising human computer interaction modal due to the rapid integration of numerical sensors in modern mobile-phones. We implement a mobile-phone-based arm motion recognition and exercise coaching system that can help people carrying mobile-phones to do body exercising anywhere at any time, especially for the persons that have very limited spare time and are constantly traveling across cities. We first design improved k-means algorithm to cluster the collecting 3-axis acceleration and gyroscope data of person actions into basic motions. A learning method based on Hidden Markov Model is then designed to classify and recognize continuous arm motions of both learners and coaches, which also measures the action similarities between the persons. We implement the system on MIUI 2S mobile-phone and evaluate the system performance and its accuracy of recognition.

Microvascular responses to (hyper-)gravitational stress by short-arm human centrifuge: arteriolar vasoconstriction and venous pooling.

Science.gov (United States)

Habazettl, H; Stahn, Alexander; Nitsche, Andrea; Nordine, Michael; Pries, A R; Gunga, H-C; Opatz, O

2016-01-01

We hypothesized that lower body microvessels are particularly challenged during exposure to gravity and hypergravity leading to failure of resistance vessels to withstand excessive transmural pressure during hypergravitation and gravitation-dependent microvascular blood pooling. Using a short-arm human centrifuge (SAHC), 12 subjects were exposed to +1Gz, +2Gz and +1Gz, all at foot level, for 4 min each. Laser Doppler imaging and near-infrared spectroscopy were used to measure skin perfusion and tissue haemoglobin concentrations, respectively. Pretibial skin perfusion decreased by 19% during +1Gz and remained at this level during +2Gz. In the dilated area, skin perfusion increased by 24 and 35% during +1Gz and +2Gz, respectively. In the upper arm, oxygenated haemoglobin (Hb) decreased, while deoxy Hb increased with little change in total Hb. In the calf muscle, O2Hb and deoxy Hb increased, resulting in total Hb increase by 7.5 ± 1.4 and 26.6 ± 2.6 µmol/L at +1Gz and +2Gz, respectively. The dynamics of Hb increase suggests a fast and a slow component. Despite transmural pressures well beyond the upper myogenic control limit, intact lower body resistance vessels withstand these pressures up to +2Gz, suggesting that myogenic control may contribute only little to increased vascular resistance. The fast component of increasing total Hb indicates microvascular blood pooling contributing to soft tissue capacitance. Future research will have to address possible alterations of these acute adaptations to gravity after deconditioning by exposure to micro-g.

Sex differences in a human analogue of the Radial Arm Maze: the "17-Box Maze Test".

Science.gov (United States)

Rahman, Qazi; Abrahams, Sharon; Jussab, Fardin

2005-08-01

This study investigated sex differences in spatial memory using a human analogue of the Radial Arm Maze: a revision on the Nine Box Maze originally developed by called the 17-Box Maze Test herein. The task encourages allocentric spatial processing, dissociates object from spatial memory, and incorporates a within-participants design to provide measures of location and object, working and reference memory. Healthy adult males and females (26 per group) were administered the 17-Box Maze Test, as well as mental rotation and a verbal IQ test. Females made significantly fewer errors on this task than males. However, post hoc analysis revealed that the significant sex difference was specific to object, rather than location, memory measures. These were medium to large effect sizes. The findings raise the issue of task- and component-specific sexual dimorphism in cognitive mapping.

Effect of arm swing strategy on local dynamic stability of human gait

NARCIS (Netherlands)

Punt, M.; Bruijn, S.M.; Wittink, H.; van Dieen, J.H.

2015-01-01

Introduction: Falling causes long term disability and can even lead to death. Most falls occur during gait. Therefore improving gait stability might be beneficial for people at risk of falling. Recently arm swing has been shown to influence gait stability. However at present it remains unknown which

Nonspecific Arm Pain

Directory of Open Access Journals (Sweden)

Ali Moradi

2013-12-01

Full Text Available Nonspecific activity-related arm pain is characterized by an absence of objective physical findings and symptoms that do not correspond with objective pathophysiology. Arm pain without strict diagnosis is often related to activity, work-related activity in particular, and is often seen in patients with physically demanding work. Psychological factors such as catastrophic thinking, symptoms of depression, and heightened illness concern determine a substantial percentage of the disability associated with puzzling hand and arm pains. Ergonomic modifications can help to control symptoms, but optimal health may require collaborative management incorporating psychosocial and psychological elements of illness.

Nonspecific Arm Pain

Directory of Open Access Journals (Sweden)

Ali Moradi

2013-12-01

Full Text Available   Nonspecific activity-related arm pain is characterized by an absence of objective physical findings and symptoms that do not correspond with objective pathophysiology. Arm pain without strict diagnosis is often related to activity, work-related activity in particular, and is often seen in patients with physically demanding work. Psychological factors such as catastrophic thinking, symptoms of depression, and heightened illness concern determine a substantial percentage of the disability associated with puzzling hand and arm pains. Ergonomic modifications can help to control symptoms, but optimal health may require collaborative management incorporating psychosocial and psychological elements of illness.

Effects of age, sex and arm on the precision of arm position sense-left-arm superiority in healthy right-handers.

Science.gov (United States)

Schmidt, Lena; Depper, Lena; Kerkhoff, Georg

2013-01-01

Position sense is an important proprioceptive ability. Disorders of arm position sense (APS) often occur after unilateral stroke, and are associated with a negative functional outcome. In the present study we assessed horizontal APS by measuring angular deviations from a visually defined target separately for each arm in a large group of healthy subjects. We analyzed the accuracy and instability of horizontal APS as a function of age, sex and arm. Subjects were required to specify verbally the position of their unseen arm on a 0-90° circuit by comparing the current position with the target position indicated by a LED lamp, while the arm was passively moved by the examiner. Eighty-seven healthy subjects participated in the study, ranging from 20 to 77 years, subdivided into three age groups. The results revealed that APS was not a function of age or sex, but was significantly better in the non-dominant (left) arm in absolute errors (AE) but not in constant errors (CE) across all age groups of right-handed healthy subjects. This indicates a right-hemisphere superiority for left APS in right-handers and neatly fits to the more frequent and more severe left-sided body-related deficits in patients with unilateral stroke (i.e. impaired APS in left spatial neglect, somatoparaphrenia) or in individuals with abnormalities of the right cerebral hemisphere. These clinical issues will be discussed.

EML proteins in microtubule regulation and human disease.

Science.gov (United States)

Fry, Andrew M; O'Regan, Laura; Montgomery, Jessica; Adib, Rozita; Bayliss, Richard

2016-10-15

The EMLs are a conserved family of microtubule-associated proteins (MAPs). The founding member was discovered in sea urchins as a 77-kDa polypeptide that co-purified with microtubules. This protein, termed EMAP for echinoderm MAP, was the major non-tubulin component present in purified microtubule preparations made from unfertilized sea urchin eggs [J. Cell Sci. (1993) 104: , 445-450; J. Cell Sci. (1987) 87: (Pt 1), 71-84]. Orthologues of EMAP were subsequently identified in other echinoderms, such as starfish and sand dollar, and then in more distant eukaryotes, including flies, worms and vertebrates, where the name of ELP or EML (both for EMAP-like protein) has been adopted [BMC Dev. Biol. (2008) 8: , 110; Dev. Genes Evol. (2000) 210: , 2-10]. The common property of these proteins is their ability to decorate microtubules. However, whether they are associated with particular microtubule populations or exercise specific functions in different microtubule-dependent processes remains unknown. Furthermore, although there is limited evidence that they regulate microtubule dynamics, the biochemical mechanisms of their molecular activity have yet to be explored. Nevertheless, interest in these proteins has grown substantially because of the identification of EML mutations in neuronal disorders and oncogenic fusions in human cancers. Here, we summarize our current knowledge of the expression, localization and structure of what is proving to be an interesting and important class of MAPs. We also speculate about their function in microtubule regulation and highlight how the studies of EMLs in human diseases may open up novel avenues for patient therapy. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Arms control and disarmament

International Nuclear Information System (INIS)

Acton, P.

1992-01-01

Article VI of the Non-Proliferation Treaty commits each party to work towards nuclear disarmament and to negotiations to stop the nuclear arms race. All parties to the Treaty are included and a wide range of arms control and disarmament issues are covered. However the main focus at Treaty review conferences has been on nuclear disarmament by the nuclear weapon states which are party to the Treaty. This has led to bilateral United States - Soviet Union negotiations resulting in the Intermediate-range Nuclear Forces Treaty in December 1987 and the Strategic Arms Reduction Treaty (START) in July followed by unilateral arms control measures in September and October 1991. (UK)

Yeast prions and human prion-like proteins: sequence features and prediction methods.

Science.gov (United States)

Cascarina, Sean M; Ross, Eric D

2014-06-01

Prions are self-propagating infectious protein isoforms. A growing number of prions have been identified in yeast, each resulting from the conversion of soluble proteins into an insoluble amyloid form. These yeast prions have served as a powerful model system for studying the causes and consequences of prion aggregation. Remarkably, a number of human proteins containing prion-like domains, defined as domains with compositional similarity to yeast prion domains, have recently been linked to various human degenerative diseases, including amyotrophic lateral sclerosis. This suggests that the lessons learned from yeast prions may help in understanding these human diseases. In this review, we examine what has been learned about the amino acid sequence basis for prion aggregation in yeast, and how this information has been used to develop methods to predict aggregation propensity. We then discuss how this information is being applied to understand human disease, and the challenges involved in applying yeast prediction methods to higher organisms.

Training-induced changes in membrane transport proteins of human skeletal muscle

DEFF Research Database (Denmark)

Juel, C.

2006-01-01

Training improves human physical performance by inducing structural and cardiovascular changes, metabolic changes, and changes in the density of membrane transport proteins. This review focuses on the training-induced changes in proteins involved in sarcolemmal membrane transport. It is concluded...

Identification of proteins sensitive to thermal stress in human neuroblastoma and glioma cell lines.

Directory of Open Access Journals (Sweden)

Guilian Xu

Full Text Available Heat-shock is an acute insult to the mammalian proteome. The sudden elevation in temperature has far-reaching effects on protein metabolism, leads to a rapid inhibition of most protein synthesis, and the induction of protein chaperones. Using heat-shock in cells of neuronal (SH-SY5Y and glial (CCF-STTG1 lineage, in conjunction with detergent extraction and sedimentation followed by LC-MS/MS proteomic approaches, we sought to identify human proteins that lose solubility upon heat-shock. The two cell lines showed largely overlapping profiles of proteins detected by LC-MS/MS. We identified 58 proteins in detergent insoluble fractions as losing solubility in after heat shock; 10 were common between the 2 cell lines. A subset of the proteins identified by LC-MS/MS was validated by immunoblotting of similarly prepared fractions. Ultimately, we were able to definitively identify 3 proteins as putatively metastable neural proteins; FEN1, CDK1, and TDP-43. We also determined that after heat-shock these cells accumulate insoluble polyubiquitin chains largely linked via lysine 48 (K-48 residues. Collectively, this study identifies human neural proteins that lose solubility upon heat-shock. These proteins may represent components of the human proteome that are vulnerable to misfolding in settings of proteostasis stress.

Human-Chromatin-Related Protein Interactions Identify a Demethylase Complex Required for Chromosome Segregation

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Edyta Marcon

2014-07-01

Full Text Available Chromatin regulation is driven by multicomponent protein complexes, which form functional modules. Deciphering the components of these modules and their interactions is central to understanding the molecular pathways these proteins are regulating, their functions, and their relation to both normal development and disease. We describe the use of affinity purifications of tagged human proteins coupled with mass spectrometry to generate a protein-protein interaction map encompassing known and predicted chromatin-related proteins. On the basis of 1,394 successful purifications of 293 proteins, we report a high-confidence (85% precision network involving 11,464 protein-protein interactions among 1,738 different human proteins, grouped into 164 often overlapping protein complexes with a particular focus on the family of JmjC-containing lysine demethylases, their partners, and their roles in chromatin remodeling. We show that RCCD1 is a partner of histone H3K36 demethylase KDM8 and demonstrate that both are important for cell-cycle-regulated transcriptional repression in centromeric regions and accurate mitotic division.

Identification of Top-ranked Proteins within a Directional Protein Interaction Network using the PageRank Algorithm: Applications in Humans and Plants.

Science.gov (United States)

Li, Xiu-Qing; Xing, Tim; Du, Donglei

2016-01-01

Somatic mutation of signal transduction genes or key nodes of the cellular protein network can cause severe diseases in humans but can sometimes genetically improve plants, likely because growth is determinate in animals but indeterminate in plants. This article reviews protein networks; human protein ranking; the mitogen-activated protein kinase (MAPK) and insulin (phospho- inositide 3kinase [PI3K]/phosphatase and tensin homolog [PTEN]/protein kinase B [AKT]) signaling pathways; human diseases caused by somatic mutations to the PI3K/PTEN/ AKT pathway; use of the MAPK pathway in plant molecular breeding; and protein domain evolution. Casitas B-lineage lymphoma (CBL), PTEN, MAPK1 and PIK3CA are among PIK3CA the top-ranked proteins in directional rankings. Eight proteins (ACVR1, CDC42, RAC1, RAF1, RHOA, TGFBR1, TRAF2, and TRAF6) are ranked in the top 50 key players in both signal emission and signal reception and in interaction with many other proteins. Top-ranked proteins likely have major impacts on the network function. Such proteins are targets for drug discovery, because their mutations are implicated in various cancers and overgrowth syndromes. Appropriately managing food intake may help reduce the growth of tumors or malformation of tissues. The role of the protein kinase C/ fatty acid synthase pathway in fat deposition in PTEN/PI3K patients should be investigated. Both the MAPK and insulin signaling pathways exist in plants, and MAPK pathway engineering can improve plant tolerance to biotic and abiotic stresses such as salinity.

Development of a Multi-Arm Mobile Robot for Nuclear Decommissioning Tasks

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Mohamed J. Bakari

2008-11-01

Full Text Available This paper concerns the design of a two-arm mobile delivery platform for application within nuclear decommissioning tasks. The adoption of the human arm as a model of manoeuvrability, scale and dexterity is the starting point for operation of two seven-function arms within the context of nuclear decommissioning tasks, the selection of hardware and its integration, and the development of suitable control methods. The forward and inverse kinematics for the manipulators are derived and the proposed software architecture identified to control the movements of the arm joints and the performance of selected decommissioning tasks. We discuss the adoption of a BROKK demolition machine as a mobile platform and the integration with its hydraulic system to operate the two seven-function manipulators separately. The paper examines the modelling and development of a real-time control method using Proportional-Integral-Derivative (PID and Proportional-Integral-Plus (PIP control algorithms in the host computer with National Instruments functions and tools to control the manipulators and obtain feedback through wireless communication. Finally we consider the application of a third party device, such as a personal mobile phone, and its interface with LabVIEW software in order to operate the robot arms remotely.

Right-Arm Robotic-Aided-Therapy with the Light-Exoskeleton: A General Overview

Science.gov (United States)

Lugo-Villeda, Luis I.; Frisoli, Antonio; Sotgiu, Edoardo; Greco, Giovanni; Bergamasco, Massimo

Rehabilitation robotics applications and their developments have been spreading out as consequences of the actual needs in the human activities of daily living (ADL). Exoskeletons for rehabilitation are one of them, whose intrinsic characteristics are quite useful for applications where repetitive, robustness and accurate performance are a must. As a part of robotic-mediated-rehabilitation programme into the worldwide, the exoskeletons are trying to improve the ADL of disable people through the fusion of several disciplines that lets to expand the capabilities of wearing a powered robotic exoskeletal device for rehabilitation tasks. This fact deserves to present this contribution from a general scope point of view, i.e., the technologies integration and its associated knowledge. So far, the Light-Exoskeleton which is intended for human arm rehabilitation in post-stroke patients is introduced. Preliminary experimental results as well as the involved stages about the system show the capabilities of using a robotic-constrained-rehabilitation for human arm.

An Augmented Discrete-Time Approach for Human-Robot Collaboration

Directory of Open Access Journals (Sweden)

Peidong Liang

2016-01-01

Full Text Available Human-robot collaboration (HRC is a key feature to distinguish the new generation of robots from conventional robots. Relevant HRC topics have been extensively investigated recently in academic institutes and companies to improve human and robot interactive performance. Generally, human motor control regulates human motion adaptively to the external environment with safety, compliance, stability, and efficiency. Inspired by this, we propose an augmented approach to make a robot understand human motion behaviors based on human kinematics and human postural impedance adaptation. Human kinematics is identified by geometry kinematics approach to map human arm configuration as well as stiffness index controlled by hand gesture to anthropomorphic arm. While human arm postural stiffness is estimated and calibrated within robot empirical stability region, human motion is captured by employing a geometry vector approach based on Kinect. A biomimetic controller in discrete-time is employed to make Baxter robot arm imitate human arm behaviors based on Baxter robot dynamics. An object moving task is implemented to validate the performance of proposed methods based on Baxter robot simulator. Results show that the proposed approach to HRC is intuitive, stable, efficient, and compliant, which may have various applications in human-robot collaboration scenarios.

Analysis of the indel at the ARMS2 3′UTR in age-related macular degeneration

Science.gov (United States)

Wang, Gaofeng; Spencer, Kylee L.; Scott, William K.; Whitehead, Patrice; Court, Brenda L.; Ayala-Haedo, Juan; Mayo, Ping; Schwartz, Stephen G.; Kovach, Jaclyn L.; Gallins, Paul; Polk, Monica; Agarwal, Anita; Postel, Eric A.; Haines, Jonathan L.; Pericak-Vance, Margaret A.

2010-01-01

Controversy remains as to which gene at the chromosome 10q26 locus confers risk for age-related macular degeneration (AMD) and statistical genetic analysis is confounded by the strong linkage disequilibrium (LD) across the region. Functional analysis of related genetic variations could solve this puzzle. Recently Fritsche et al. reported that AMD is associated with unstable ARMS2 transcripts possibly caused by a complex insertion/deletion (indel; consisting of a 443 bp deletion and an adjacent 54 bp insertion) in its 3′UTR (untranslated region). To validate this indel, we sequenced our samples. We found that this indel is even more complex and is composed of two side-by-side indels separated by 17 bp: (1) 9 bp deletion with 10bp insertion; (2) 417 bp deletion with 27 bp insertion. The indel is significantly associated with the risk of AMD, but is also in strong LD with the non-synonymous single nucleotide polymorphism (SNP) rs10490924 (A69S). We also found that ARMS2 is expressed not only in placenta and retina but also in multiple human tissues. Using quantitative PCR, we found no correlation between the indel and ARMS2 mRNA level in human retina and blood samples. The lack of functional effects of the 3′UTR indel, the amino acid substitution of rs10490924 (A69S) and strong LD between them suggest that A69S, not the indel is the variant that confers risk of AMD. To our knowledge, it is the first time it's been shown that ARMS2 is widely expressed in human tissues. Conclusively, the indel at 3′UTR of ARMS2 actually contains two side-by-side indels. The indels are associated with risk of AMD, but not correlated with ARMS2 mRNA level. PMID:20182747

Neutron scattering studies on protein dynamics using the human myelin peripheral membrane protein P2

Directory of Open Access Journals (Sweden)

Laulumaa Saara

2015-01-01

Full Text Available Myelin is a multilayered proteolipid membrane structure surrounding selected axons in the vertebrate nervous system, which allows the rapid saltatory conduction of nerve impulses. Deficits in myelin formation and maintenance may lead to chronic neurological disease. P2 is an abundant myelin protein from peripheral nerves, binding between two apposing lipid bilayers. We studied the dynamics of the human myelin protein P2 and its mutated P38G variant in hydrated powders using elastic incoherent neutron scattering. The local harmonic vibrations at low temperatures were very similar for both samples, but the mutant protein had increased flexibility and softness close to physiological temperatures. The results indicate that a drastic mutation of proline to glycine at a functional site can affect protein dynamics, and in the case of P2, they may explain functional differences between the two proteins.

Neutron scattering studies on protein dynamics using the human myelin peripheral membrane protein P2

Science.gov (United States)

Laulumaa, Saara; Kursula, Petri; Natali, Francesca

2015-01-01

Myelin is a multilayered proteolipid membrane structure surrounding selected axons in the vertebrate nervous system, which allows the rapid saltatory conduction of nerve impulses. Deficits in myelin formation and maintenance may lead to chronic neurological disease. P2 is an abundant myelin protein from peripheral nerves, binding between two apposing lipid bilayers. We studied the dynamics of the human myelin protein P2 and its mutated P38G variant in hydrated powders using elastic incoherent neutron scattering. The local harmonic vibrations at low temperatures were very similar for both samples, but the mutant protein had increased flexibility and softness close to physiological temperatures. The results indicate that a drastic mutation of proline to glycine at a functional site can affect protein dynamics, and in the case of P2, they may explain functional differences between the two proteins.

Guidelines for the nomenclature of the human heat shock proteins

NARCIS (Netherlands)

Kampinga, Harm H.; Hageman, Jurre; Vos, Michel J.; Kubota, Hiroshi; Tanguay, Robert M.; Bruford, Elspeth A.; Cheetham, Michael E.; Chen, B.; Hightower, Lawrence E.

The expanding number of members in the various human heat shock protein (HSP) families and the inconsistencies in their nomenclature have often led to confusion. Here, we propose new guidelines for the nomenclature of the human HSP families, HSPH (HSP110), HSPC (HSP90), HSPA (HSP70), DNAJ (HSP40),

Consideration of insects as a source of dietary protein for human consumption.

Science.gov (United States)

Churchward-Venne, Tyler A; Pinckaers, Philippe J M; van Loon, Joop J A; van Loon, Luc J C

2017-12-01

Consumption of sufficient dietary protein is fundamental to muscle mass maintenance and overall health. Conventional animal-based protein sources such as meat (ie, beef, pork, lamb), poultry, fish, eggs, and dairy are generally considered high-quality sources of dietary protein because they meet all of the indispensable amino-acid requirements for humans and are highly digestible. However, the production of sufficient amounts of conventional animal-based protein to meet future global food demands represents a challenge. Edible insects have recently been proposed as an alternative source of dietary protein that may be produced on a more viable and sustainable commercial scale and, as such, may contribute to ensuring global food security. This review evaluates the protein content, amino-acid composition, and digestibility of edible insects and considers their proposed quality and potential as an alternative protein source for human consumption. © The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Chaperone activity of human small heat shock protein-GST fusion proteins.

Science.gov (United States)

Arbach, Hannah; Butler, Caley; McMenimen, Kathryn A

2017-07-01

Small heat shock proteins (sHsps) are a ubiquitous part of the machinery that maintains cellular protein homeostasis by acting as molecular chaperones. sHsps bind to and prevent the aggregation of partially folded substrate proteins in an ATP-independent manner. sHsps are dynamic, forming an ensemble of structures from dimers to large oligomers through concentration-dependent equilibrium dissociation. Based on structural studies and mutagenesis experiments, it is proposed that the dimer is the smallest active chaperone unit, while larger oligomers may act as storage depots for sHsps or play additional roles in chaperone function. The complexity and dynamic nature of their structural organization has made elucidation of their chaperone function challenging. HspB1 and HspB5 are two canonical human sHsps that vary in sequence and are expressed in a wide variety of tissues. In order to determine the role of the dimer in chaperone activity, glutathione-S-transferase (GST) was genetically linked as a fusion protein to the N-terminus regions of both HspB1 and HspB5 (also known as Hsp27 and αB-crystallin, respectively) proteins in order to constrain oligomer formation of HspB1 and HspB5, by using GST, since it readily forms a dimeric structure. We monitored the chaperone activity of these fusion proteins, which suggest they primarily form dimers and monomers and function as active molecular chaperones. Furthermore, the two different fusion proteins exhibit different chaperone activity for two model substrate proteins, citrate synthase (CS) and malate dehydrogenase (MDH). GST-HspB1 prevents more aggregation of MDH compared to GST-HspB5 and wild type HspB1. However, when CS is the substrate, both GST-HspB1 and GST-HspB5 are equally effective chaperones. Furthermore, wild type proteins do not display equal activity toward the substrates, suggesting that each sHsp exhibits different substrate specificity. Thus, substrate specificity, as described here for full-length GST

Solution structure of the human signaling protein RACK1

Directory of Open Access Journals (Sweden)

Papa Priscila F

2010-06-01

Full Text Available Abstract Background The adaptor protein RACK1 (receptor of activated kinase 1 was originally identified as an anchoring protein for protein kinase C. RACK1 is a 36 kDa protein, and is composed of seven WD repeats which mediate its protein-protein interactions. RACK1 is ubiquitously expressed and has been implicated in diverse cellular processes involving: protein translation regulation, neuropathological processes, cellular stress, and tissue development. Results In this study we performed a biophysical analysis of human RACK1 with the aim of obtaining low resolution structural information. Small angle X-ray scattering (SAXS experiments demonstrated that human RACK1 is globular and monomeric in solution and its low resolution structure is strikingly similar to that of an homology model previously calculated by us and to the crystallographic structure of RACK1 isoform A from Arabidopsis thaliana. Both sedimentation velocity and sedimentation equilibrium analytical ultracentrifugation techniques showed that RACK1 is predominantly a monomer of around 37 kDa in solution, but also presents small amounts of oligomeric species. Moreover, hydrodynamic data suggested that RACK1 has a slightly asymmetric shape. The interaction of RACK1 and Ki-1/57 was tested by sedimentation equilibrium. The results suggested that the association between RACK1 and Ki-1/57(122-413 follows a stoichiometry of 1:1. The binding constant (KB observed for RACK1-Ki-1/57(122-413 interaction was of around (1.5 ± 0.2 × 106 M-1 and resulted in a dissociation constant (KD of (0.7 ± 0.1 × 10-6 M. Moreover, the fluorescence data also suggests that the interaction may occur in a cooperative fashion. Conclusion Our SAXS and analytical ultracentrifugation experiments indicated that RACK1 is predominantly a monomer in solution. RACK1 and Ki-1/57(122-413 interact strongly under the tested conditions.

Heterozygous KIDINS220/ARMS nonsense variants cause spastic paraplegia, intellectual disability, nystagmus, and obesity

NARCIS (Netherlands)

Josifova, Dragana J.; Monroe, Glen R.; Tessadori, Federico; de Graaff, Esther; van der Zwaag, Bert; Mehta, Sarju G.; Harakalova, Magdalena; Duran, Karen J.; Savelberg, Sanne M. C.; Nijman, Isaäc J.; Jungbluth, Heinz; Hoogenraad, Casper C.; Bakkers, Jeroen; Knoers, Nine V.; Firth, Helen V.; Beales, Philip L.; van Haaften, Gijs; van Haelst, Mieke M.

2016-01-01

We identified de novo nonsense variants in KIDINS220/ARMS in three unrelated patients with spastic paraplegia, intellectual disability, nystagmus, and obesity (SINO). KIDINS220 is an essential scaffold protein coordinating neurotrophin signal pathways in neurites and is spatially and temporally

C- Reactive Protein in Tuberculosis and Human Immunodeficiency ...

African Journals Online (AJOL)

This study was conducted to evaluate C-reactive protein (CRP) levels in Mycobacterium tuberculosis and human immunodeficiency virus (HIV) infections and the follow-up therapeutic response to tuberculosis (TB) among patients aged 19-68 years attending out-patient clinics of two hospitals in Abeokuta, Southwestern ...

Sulfur in human nutrition - effects beyond protein synthesis

NARCIS (Netherlands)

Gertjan Schaafsma

2008-01-01

That sulfur is essential to humans is based on the requirement of S-animo acids for normal growth and maintenance of nitrogen balance and not on the optimization of metabolic proccesses involving the synthesis of non-protein sulphur containing compounds. This paper reviews the significance of sulfur

Dual arm master controller development

International Nuclear Information System (INIS)

Kuban, D.P.; Perkins, G.S.

1985-01-01

The advanced servomanipulator (ASM) slave was designed with an anthropomorphic stance, gear/torque tube power drives, and modular construction. These features resulted in increased inertia, friction, and backlash relative to tape-driven manipulators. Studies were performed which addressed the human factors design and performance trade-offs associated with the corresponding master controller best suited for the ASM. The results of these studies, as well as the conceptual design of the dual arm master controller, are presented. This work was performed as part of the Consolidated Fuel Reprocessing Program at the Oak Ridge National Laboratory. 5 refs., 7 figs., 1 tab

Generation of human scFvs antibodies recognizing a prion protein epitope expressed on the surface of human lymphoblastoid cells

Directory of Open Access Journals (Sweden)

Imperiale Valentina

2007-07-01

Full Text Available Abstract Background A hallmark of prion disease is the transformation of normal cellular prion protein (PrPc into an infectious disease-associated isoform, (PrPsc. Anti-prion protein monoclonal antibodies are invaluable for structure-function studies of PrP molecules. Furthermore recent in vitro and in vivo studies indicate that anti-PrP monoclonal antibodies can prevent the incorporation of PrPc into propagating prions. In the present article, we show two new human phage antibodies, isolated on recombinant hamster prion protein (rHaPrP. Results We adopted an antibody phage display strategy to isolate specific human antibodies directed towards rHaPrP which has been used as a bait for panning the synthetic ETH-2 antibody phage library. Two phage antibodies clones named MA3.B4 and MA3.G3 were isolated and characterized under genetic biochemical and immunocytochemical aspects. The clones were found to recognize the prion protein in ELISA studies. In flow-cytometry studies, these human single chain Fragment variable (scFv phage-antibodies show a well defined pattern of reactivity on human lymphoblastoid and myeloid cells. Conclusion Sequence analysis of the gene encoding for the antibody fragments and antigen recognition patterns determined by flow-cytometry analysis indicate that the isolated scFvs recognize novel epitopes in the PrPc molecule. These new anti PrPc human antibodies are unique reagents for prion protein detection and may represent a biologic platform to develop new reagents to treat PrPsc associated disease.

Protein tyrosine adduct in humans self-poisoned by chlorpyrifos

Science.gov (United States)

Li, Bin; Eyer, Peter; Eddleston, Michael; Jiang, Wei; Schopfer, Lawrence M.; Lockridge, Oksana

2013-01-01

Studies of human cases of self-inflicted poisoning suggest that chlorpyrifos oxon reacts not only with acetylcholinesterase and butyrylcholinesterase but also with other blood proteins. A favored candidate is albumin because in vitro and animal studies have identified tyrosine 411 of albumin as a site covalently modified by organophosphorus poisons. Our goal was to test this proposal in humans by determining whether plasma from humans poisoned by chlorpyrifos has adducts on tyrosine. Plasma samples from 5 self-poisoned humans were drawn at various time intervals after ingestion of chlorpyrifos for a total of 34 samples. All 34 samples were analyzed for plasma levels of chlorpyrifos and chlorpyrifos oxon (CPO) as a function of time post-ingestion. Eleven samples were analyzed for the presence of diethoxyphosphorylated tyrosine by mass spectrometry. Six samples yielded diethoxyphosphorylated tyrosine in pronase digests. Blood collected as late as 5 days after chlorpyrifos ingestion was positive for CPO-tyrosine, consistent with the 20-day half-life of albumin. High plasma CPO levels did not predict detectable levels of CPO-tyrosine. CPO-tyrosine was identified in pralidoxime treated patients as well as in patients not treated with pralidoxime, indicating that pralidoxime does not reverse CPO binding to tyrosine in humans. Plasma butyrylcholinesterase was a more sensitive biomarker of exposure than adducts on tyrosine. In conclusion, chlorpyrifos oxon makes a stable covalent adduct on the tyrosine residue of blood proteins in humans who ingested chlorpyrifos. PMID:23566956

Highly specific salt bridges govern bacteriophage P22 icosahedral capsid assembly: identification of the site in coat protein responsible for interaction with scaffolding protein.

Science.gov (United States)

Cortines, Juliana R; Motwani, Tina; Vyas, Aashay A; Teschke, Carolyn M

2014-05-01

Icosahedral virus assembly requires a series of concerted and highly specific protein-protein interactions to produce a proper capsid. In bacteriophage P22, only coat protein (gp5) and scaffolding protein (gp8) are needed to assemble a procapsid-like particle, both in vivo and in vitro. In scaffolding protein's coat binding domain, residue R293 is required for procapsid assembly, while residue K296 is important but not essential. Here, we investigate the interaction of scaffolding protein with acidic residues in the N-arm of coat protein, since this interaction has been shown to be electrostatic. Through site-directed mutagenesis of genes 5 and 8, we show that changing coat protein N-arm residue 14 from aspartic acid to alanine causes a lethal phenotype. Coat protein residue D14 is shown by cross-linking to interact with scaffolding protein residue R293 and, thus, is intimately involved in proper procapsid assembly. To a lesser extent, coat protein N-arm residue E18 is also implicated in the interaction with scaffolding protein and is involved in capsid size determination, since a cysteine mutation at this site generated petite capsids. The final acidic residue in the N-arm that was tested, E15, is shown to only weakly interact with scaffolding protein's coat binding domain. This work supports growing evidence that surface charge density may be the driving force of virus capsid protein interactions. Bacteriophage P22 infects Salmonella enterica serovar Typhimurium and is a model for icosahedral viral capsid assembly. In this system, coat protein interacts with an internal scaffolding protein, triggering the assembly of an intermediate called a procapsid. Previously, we determined that there is a single amino acid in scaffolding protein required for P22 procapsid assembly, although others modulate affinity. Here, we identify partners in coat protein. We show experimentally that relatively weak interactions between coat and scaffolding proteins are capable of driving

Characterization of human chromosome 22 : Cloning of breakpoints of the constitutional translocation t(11;22)(q23;q11) and detection of small constitutional delections by microarray CGH

OpenAIRE

Tapia Paez, Isabel

2003-01-01

Chromosome 22 is the second smallest human chromosome, composing approximately 1.5% of the genome. The short arm of this acrocentric chromosome harbors ribosomal genes and the long arm contains the protein coding genes. This chromosome is gene-rich in comparison to the majority of other chromosomes, containing approximately 600 so far characterized genes. Many of these are involved in the etiology of a wide spectrum of diseases such as congenital and psychiatric disorders as...

Composition and Variation of Macronutrients, Immune Proteins, and Human Milk Oligosaccharides in Human Milk From Nonprofit and Commercial Milk Banks.

Science.gov (United States)

Meredith-Dennis, Laura; Xu, Gege; Goonatilleke, Elisha; Lebrilla, Carlito B; Underwood, Mark A; Smilowitz, Jennifer T

2018-02-01

When human milk is unavailable, banked milk is recommended for feeding premature infants. Milk banks use processes to eliminate pathogens; however, variability among methods exists. Research aim: The aim of this study was to compare the macronutrient (protein, carbohydrate, fat, energy), immune-protective protein, and human milk oligosaccharide (HMO) content of human milk from three independent milk banks that use pasteurization (Holder vs. vat techniques) or retort sterilization. Randomly acquired human milk samples from three different milk banks ( n = 3 from each bank) were analyzed for macronutrient concentrations using a Fourier transform mid-infrared spectroscopy human milk analyzer. The concentrations of IgA, IgM, IgG, lactoferrin, lysozyme, α-lactalbumin, α antitrypsin, casein, and HMO were analyzed by mass spectrometry. The concentrations of protein and fat were significantly ( p < .05) less in the retort sterilized compared with the Holder and vat pasteurized samples, respectively. The concentrations of all immune-modulating proteins were significantly ( p < .05) less in the retort sterilized samples compared with vat and/or Holder pasteurized samples. The total HMO concentration and HMOs containing fucose, sialic acid, and nonfucosylated neutral sugars were significantly ( p < .05) less in retort sterilized compared with Holder pasteurized samples. Random milk samples that had undergone retort sterilization had significantly less immune-protective proteins and total and specific HMOs compared with samples that had undergone Holder and vat pasteurization. These data suggest that further analysis of the effect of retort sterilization on human milk components is needed prior to widespread adoption of this process.

Towards a digital body: the virtual arm illusion

Directory of Open Access Journals (Sweden)

2008-08-01

Full Text Available The integration of the human brain with computers is an interesting new area of applied neuroscience, where one application is replacement of a person’s real body by a virtual representation. Here we demonstrate that a virtual limb can be made to feel part of your body if appropriate multisensory correlations are provided. We report an illusion that is invoked through tactile stimulation on a person’s hidden real right hand with synchronous virtual visual stimulation on an aligned 3D stereo virtual arm projecting horizontally out of their shoulder. An experiment with 21 male participants showed displacement of ownership towards the virtual hand, as illustrated by questionnaire responses and proprioceptive drift. A control experiment with asynchronous tapping was carried out with a different set of 20 male participants who did not experience the illusion. After 5 minutes of stimulation the virtual arm rotated. Evidence suggests that the extent of the illusion was also correlated with the degree of muscle activity onset in the right arm as measured by EMG during this period that the arm was rotating, for the synchronous but not the asynchronous condition. A completely virtual object can therefore be experienced as part of one’s self, which opens up the possibility that an entire virtual body could be felt as one’s own in future virtual reality applications or online games, and be an invaluable tool for the understanding of the brain mechanisms underlying body ownership.

Development of Glutamatergic Proteins in Human Visual Cortex across the Lifespan.

Science.gov (United States)

Siu, Caitlin R; Beshara, Simon P; Jones, David G; Murphy, Kathryn M

2017-06-21

Traditionally, human primary visual cortex (V1) has been thought to mature within the first few years of life, based on anatomical studies of synapse formation, and establishment of intracortical and intercortical connections. Human vision, however, develops well beyond the first few years. Previously, we found prolonged development of some GABAergic proteins in human V1 (Pinto et al., 2010). Yet as >80% of synapses in V1 are excitatory, it remains unanswered whether the majority of synapses regulating experience-dependent plasticity and receptive field properties develop late, like their inhibitory counterparts. To address this question, we used Western blotting of postmortem tissue from human V1 (12 female, 18 male) covering a range of ages. Then we quantified a set of postsynaptic glutamatergic proteins (PSD-95, GluA2, GluN1, GluN2A, GluN2B), calculated indices for functional pairs that are developmentally regulated (GluA2:GluN1; GluN2A:GluN2B), and determined interindividual variability. We found early loss of GluN1, prolonged development of PSD-95 and GluA2 into late childhood, protracted development of GluN2A until ∼40 years, and dramatic loss of GluN2A in aging. The GluA2:GluN1 index switched at ∼1 year, but the GluN2A:GluN2B index continued to shift until ∼40 year before changing back to GluN2B in aging. We also identified young childhood as a stage of heightened interindividual variability. The changes show that human V1 develops gradually through a series of five orchestrated stages, making it likely that V1 participates in visual development and plasticity across the lifespan. SIGNIFICANCE STATEMENT Anatomical structure of human V1 appears to mature early, but vision changes across the lifespan. This discrepancy has fostered two hypotheses: either other aspects of V1 continue changing, or later changes in visual perception depend on extrastriate areas. Previously, we showed that some GABAergic synaptic proteins change across the lifespan, but most

Immunological mechanism underlying the immune response to tecombinant human protein therapeutics

NARCIS (Netherlands)

Sauerborn, M.S.; Brinks, V.; Jiskoot, W.; Schellekens, H.

2010-01-01

Recombinant human (rhu) protein therapeutics are powerful tools to treat several severe diseases such as multiple sclerosis and diabetes mellitus, among others. A major drawback of these proteins is the production of anti-drug antibodies (ADAs). In some cases, these ADAs have neutralizing capacity

Understanding the conventional arms trade

Science.gov (United States)

Stohl, Rachel

2017-11-01

The global conventional arms trade is worth tens of billions of dollars every year and is engaged in by every country in the world. Yet, it is often difficult to control the legal trade in conventional arms and there is a thriving illicit market, willing to arm unscrupulous regimes and nefarious non-state actors. This chapter examines the international conventional arms trade, the range of tools that have been used to control it, and challenges to these international regimes.

Small heat shock proteins potentiate amyloid dissolution by protein disaggregases from yeast and humans.

Directory of Open Access Journals (Sweden)

Martin L Duennwald

Full Text Available How small heat shock proteins (sHsps might empower proteostasis networks to control beneficial prions or disassemble pathological amyloid is unknown. Here, we establish that yeast sHsps, Hsp26 and Hsp42, inhibit prionogenesis by the [PSI+] prion protein, Sup35, via distinct and synergistic mechanisms. Hsp42 prevents conformational rearrangements within molten oligomers that enable de novo prionogenesis and collaborates with Hsp70 to attenuate self-templating. By contrast, Hsp26 inhibits self-templating upon binding assembled prions. sHsp binding destabilizes Sup35 prions and promotes their disaggregation by Hsp104, Hsp70, and Hsp40. In yeast, Hsp26 or Hsp42 overexpression prevents [PSI+] induction, cures [PSI+], and potentiates [PSI+]-curing by Hsp104 overexpression. In vitro, sHsps enhance Hsp104-catalyzed disaggregation of pathological amyloid forms of α-synuclein and polyglutamine. Unexpectedly, in the absence of Hsp104, sHsps promote an unprecedented, gradual depolymerization of Sup35 prions by Hsp110, Hsp70, and Hsp40. This unanticipated amyloid-depolymerase activity is conserved from yeast to humans, which lack Hsp104 orthologues. A human sHsp, HspB5, stimulates depolymerization of α-synuclein amyloid by human Hsp110, Hsp70, and Hsp40. Thus, we elucidate a heretofore-unrecognized human amyloid-depolymerase system that could have applications in various neurodegenerative disorders.

The fungus Ustilago maydis and humans share disease-related proteins that are not found in Saccharomyces cerevisiae

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Steinberg Gero

2007-12-01

Full Text Available Abstract Background The corn smut fungus Ustilago maydis is a well-established model system for molecular phytopathology. In addition, it recently became evident that U. maydis and humans share proteins and cellular processes that are not found in the standard fungal model Saccharomyces cerevisiae. This prompted us to do a comparative analysis of the predicted proteome of U. maydis, S. cerevisiae and humans. Results At a cut off at 20% identity over protein length, all three organisms share 1738 proteins, whereas both fungi share only 541 conserved proteins. Despite the evolutionary distance between U. maydis and humans, 777 proteins were shared. When applying a more stringent criterion (≥ 20% identity with a homologue in one organism over at least 50 amino acids and ≥ 10% less in the other organism, we found 681 proteins for the comparison of U. maydis and humans, whereas the both fungi share only 622 fungal specific proteins. Finally, we found that S. cerevisiae and humans shared 312 proteins. In the U. maydis to H. sapiens homology set 454 proteins are functionally classified and 42 proteins are related to serious human diseases. However, a large portion of 222 proteins are of unknown function. Conclusion The fungus U. maydis has a long history of being a model system for understanding DNA recombination and repair, as well as molecular plant pathology. The identification of functionally un-characterized genes that are conserved in humans and U. maydis opens the door for experimental work, which promises new insight in the cell biology of the mammalian cell.

Production of functional human insulin-like growth factor binding proteins (IGFBPs) using recombinant expression in HEK293 cells.

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Wanscher, Anne Sofie Molsted; Williamson, Michael; Ebersole, Tasja Wainani; Streicher, Werner; Wikström, Mats; Cazzamali, Giuseppe

2015-04-01

Insulin-like growth factor binding proteins (IGFBPs) display many functions in humans including regulation of the insulin-like growth factor (IGF) signaling pathway. The various roles of human IGFBPs make them attractive protein candidates in drug discovery. Structural and functional knowledge on human proteins with therapeutic relevance is needed to design and process the next generation of protein therapeutics. In order to conduct structural and functional investigations large quantities of recombinant proteins are needed. However, finding a suitable recombinant production system for proteins such as full-length human IGFBPs, still remains a challenge. Here we present a mammalian HEK293 expression method suitable for over-expression of secretory full-length human IGFBP-1 to -7. Protein purification of full-length human IGFBP-1, -2, -3 and -5 was conducted using a two-step chromatography procedure and the final protein yields were between 1 and 12mg protein per liter culture media. The recombinant IGFBPs contained PTMs and exhibited high-affinity interactions with their natural ligands IGF-1 and IGF-2. Copyright © 2014 Elsevier Inc. All rights reserved.

NDUFAF5 Hydroxylates NDUFS7 at an Early Stage in the Assembly of Human Complex I*

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Rhein, Virginie F.; Carroll, Joe; Ding, Shujing; Fearnley, Ian M.; Walker, John E.

2016-01-01

Complex I (NADH ubiquinone oxidoreductase) in mammalian mitochondria is an L-shaped assembly of 45 proteins. One arm lies in the inner membrane, and the other extends about 100 Å into the matrix of the organelle. The extrinsic arm contains binding sites for NADH, the primary electron acceptor FMN, and seven iron-sulfur clusters that form a pathway for electrons linking FMN to the terminal electron acceptor, ubiquinone, which is bound in a tunnel in the region of the junction between the arms. The membrane arm contains four antiporter-like domains, energetically coupled to the quinone site and involved in pumping protons from the matrix into the intermembrane space contributing to the proton motive force. Seven of the subunits, forming the core of the membrane arm, are translated from mitochondrial genes, and the remaining subunits, the products of nuclear genes, are imported from the cytosol. Their assembly is coordinated by at least thirteen extrinsic assembly factor proteins that are not part of the fully assembled complex. They assist in insertion of co-factors and in building up the complex from smaller sub-assemblies. One such factor, NDUFAF5, belongs to the family of seven-β-strand S-adenosylmethionine-dependent methyltransferases. However, similar to another family member, RdmB, it catalyzes the introduction of a hydroxyl group, in the case of NDUFAF5, into Arg-73 in the NDUFS7 subunit of human complex I. This modification occurs early in the pathway of assembly of complex I, before the formation of the juncture between peripheral and membrane arms. PMID:27226634

Proteomic characterization of the human centrosome by protein correlation profiling

DEFF Research Database (Denmark)

Andersen, Jens S; Wilkinson, Christopher J; Mayor, Thibault

2003-01-01

chromosomes between dividing cells. Despite the importance of this organelle to cell biology and more than 100 years of study, many aspects of its function remain enigmatic and its structure and composition are still largely unknown. We performed a mass-spectrometry-based proteomic analysis of human...... centrosomes in the interphase of the cell cycle by quantitatively profiling hundreds of proteins across several centrifugation fractions. True centrosomal proteins were revealed by both correlation with already known centrosomal proteins and in vivo localization. We identified and validated 23 novel...... components and identified 41 likely candidates as well as the vast majority of the known centrosomal proteins in a large background of nonspecific proteins. Protein correlation profiling permits the analysis of any multiprotein complex that can be enriched by fractionation but not purified to homogeneity....

[Identification and characterization of proteins from human bronchial secretion (author's transl)].

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Laine, A; Hayem, A

1976-03-01

An analysis of bronchial mucus proteins was carried out by crossed immunoelectrophoresis. Before electrophoretic migration, sputum was treated with Ecteola-cellulose, which retains acid mucins. The proteins were then extracted by a phosphate/saline buffer pH 7.5. Crossed immunoelectrophoresis of the "bronchial extracts" was carried out with an anti-human serum: fifteen proteins were detected. Among them, IgA and protease inhibitiors play an important role in bronchial pathology. Bronchial extracts were also studied with immune serums against milk proteins, whole saliva and proteins of bronchial mucus. Bronchotransferrin, amylase and two esterases were characterized. Four other proteins were also detected with immune serums against bronchial mucus-proteins: their biological role is still unknown.

Student measurement of blood pressure using a simulator arm compared with a live subject's arm.

Science.gov (United States)

Lee, Jennifer J; Sobieraj, Diana M; Kuti, Effie L

2010-06-15

To compare accuracy of blood pressure measurements using a live subject and a simulator arm, and to determine students' preferences regarding measurement. This was a crossover study comparing blood pressure measurements from a live subject and a simulator arm. Students completed an anonymous survey instrument defining opinions on ease of measurement. Fifty-seven students completed blood pressure measurements on live subjects while 72 students completed blood pressure measurements using the simulator arm. There were no significant systematic differences between the 2 measurement techniques. Systolic blood pressure measurements from a live subject arm were less likely to be within 4 mm Hg compared with measurements of a simulator arm. Diastolic blood pressure measurements were not significantly different between the 2 techniques. Accuracy of student measurement of blood pressure using a simulator arm was similar to the accuracy with a live subject. There was no difference in students' preferences regarding measurement techniques.

Borehole tool outrigger arm displacement control mechanism

International Nuclear Information System (INIS)

Lee, A.G.

1985-01-01

As the outrigger arms of a borehole logging tool are flexed inwardly and outwardly according to the diameter of the borehole opening through which they pass, the corresponding axial displacements of the ends of the arms are controlled to determine the axial positions of the arms relative to the tool. Specifically, as the arm ends move, they are caused to rotate by a cam mechanism. The stiffness of the arms causes the arm ends to rotate in unison, and the exact positions of the arms on the tool are then controlled by the differential movements of the arm ends in the cams

Novel Design of a Soft Lightweight Pneumatic Continuum Robot Arm with Decoupled Variable Stiffness and Positioning.

Science.gov (United States)

Giannaccini, Maria Elena; Xiang, Chaoqun; Atyabi, Adham; Theodoridis, Theo; Nefti-Meziani, Samia; Davis, Steve

2018-02-01

Soft robot arms possess unique capabilities when it comes to adaptability, flexibility, and dexterity. In addition, soft systems that are pneumatically actuated can claim high power-to-weight ratio. One of the main drawbacks of pneumatically actuated soft arms is that their stiffness cannot be varied independently from their end-effector position in space. The novel robot arm physical design presented in this article successfully decouples its end-effector positioning from its stiffness. An experimental characterization of this ability is coupled with a mathematical analysis. The arm combines the light weight, high payload to weight ratio and robustness of pneumatic actuation with the adaptability and versatility of variable stiffness. Light weight is a vital component of the inherent safety approach to physical human-robot interaction. To characterize the arm, a neural network analysis of the curvature of the arm for different input pressures is performed. The curvature-pressure relationship is also characterized experimentally.

Nonparetic arm force does not overinhibit the paretic arm in chronic poststroke hemiparesis.

Science.gov (United States)

Dimyan, Michael A; Perez, Monica A; Auh, Sungyoung; Tarula, Erick; Wilson, Matthew; Cohen, Leonardo G

2014-05-01

To determine whether nonparetic arm force overinhibits the paretic arm in patients with chronic unilateral poststroke hemiparesis. Case-control neurophysiological and behavioral study of patients with chronic stroke. Research institution. Eighty-six referred patients were screened to enroll 9 participants (N=9) with a >6 month history of 1 unilateral ischemic infarct that resulted in arm hemiparesis with residual ability to produce 1Nm of wrist flexion torque and without contraindication to transcranial magnetic stimulation. Eight age- and handedness-matched healthy volunteers without neurologic diagnosis were studied for comparison. Not applicable. Change in interhemispheric inhibition targeting the ipsilesional primary motor cortex (M1) during nonparetic arm force. We hypothesized that interhemispheric inhibition would increase more in healthy controls than in patients with hemiparesis. Healthy age-matched controls had significantly greater increases in inhibition from their active to resting M1 than patients with stroke from their active contralesional to resting ipsilesional M1 in the same scenario (20%±7% vs -1%±4%, F1,12=6.61, P=.025). Patients with greater increases in contralesional to ipsilesional inhibition were better performers on the 9-hole peg test of paretic arm function. Our findings reveal that producing force with the nonparetic arm does not necessarily overinhibit the paretic arm. Though our study is limited in generalizability by the small sample size, we found that greater active contralesional to resting ipsilesional M1 inhibition was related with better recovery in this subset of patients with chronic poststroke. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Expression of androgen-binding protein (ABP) in human cardiac myocytes.

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Schock, H W; Herbert, Z; Sigusch, H; Figulla, H R; Jirikowski, G F; Lotze, U

2006-04-01

Cardiomyocytes are known to be androgen targets. Changing systemic steroid levels are thought to be linked to various cardiac ailments, including dilated cardiomyopathy (DCM). The mode of action of gonadal steroid hormones on the human heart is unknown to date. In the present study, we used high-resolution immunocytochemistry on semithin sections (1 microm thick), IN SITU hybridization, and mass spectrometry to investigate the expression of androgen-binding protein (ABP) in human myocardial biopsies taken from male patients with DCM. We observed distinct cytoplasmic ABP immunoreactivity in a fraction of the myocytes. IN SITU hybridization with synthetic oligonucleotide probes revealed specific hybridization signals in these cells. A portion of the ABP-positive cells contained immunostaining for androgen receptor. With SELDI TOF mass spectrometry of affinity purified tissue extracts of human myocardium, we confirmed the presence of a 50 kDa protein similar to ABP. Our observations provide evidence of an intrinsic expression of ABP in human heart. ABP may be secreted from myocytes in a paracrine manner perhaps to influence the bioavailabity of gonadal steroids in myocardium.

Purification and functional characterization of a protein: Bombyx mori human growth hormone like protein in silkworm pupa.

Directory of Open Access Journals (Sweden)

Jianqing Chen

Full Text Available Human growth hormone (hGH is a peptide hormone secreted by eosinophils of the human anterior pituitary, and a regulatory factor for a variety of metabolic pathways. A 30-kD protein from the pupa stage of silkworm was detected by Western blotting and confirmed by immunoprecipitation based on its ability to bind to anti-hGH antibody. This protein, named BmhGH-like protein, was purified from fresh silkworm pupas through low-temperature homogenization, filtration, and centrifugation to remove large impurity particles. The supernatants were precipitated, resuspended, and passed through a molecular sieve. Further purification by affinity chromatography and two-dimensional electrophoresis resulted in pure protein for analysis by MS MALDI-TOF-MS analysis. An alignment with predicted proteins indicated that BmhGH-like protein consisted of two lipoproteins, which we named hGH-L1 and hGH-L2. These proteins belong to the β-trefoil superfamily, with β domains similar to the spatial structure of hGH. Assays with K562 cells demonstrated that these proteins could promote cell division in vitro. To further validate the growth-promoting effects, hGH-L2 was cloned from pupa cDNA to create recombinant silkworm baculovirus vBmNPV-hGH-L2, which was used to infect silkworm BmN cells at low titer. Flow cytometric analysis demonstrated that the protein shortened the G0/G1 phase of the cells, and enabled the cells to rapidly traverse the G1/S phase transition point to enter S phase and promote cell division. Discovery of hGH-like protein in silkworm will once again arouse people's interest in the potential medicinal value of silkworm and establish the basis for the development of new hormone drugs.

Hepatitis C Virus E2 Protein Induces Upregulation of IL-8 Pathways and Production of Heat Shock Proteins in Human Thyroid Cells.

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Hammerstad, Sara Salehi; Stefan, Mihaela; Blackard, Jason; Owen, Randall P; Lee, Hanna J; Concepcion, Erlinda; Yi, Zhengzi; Zhang, Weijia; Tomer, Yaron

2017-02-01

Thyroiditis is one of the most common extrahepatic manifestations of hepatitis C virus (HCV) infection. By binding to surface cell receptor CD81, HCV envelope glycoprotein E2 mediates entry of HCV into cells. Studies have shown that different viral proteins may individually induce host responses to infection. We hypothesized that HCV E2 protein binding to CD81 expressed on thyroid cells activates a cascade of inflammatory responses that can trigger autoimmune thyroiditis in susceptible individuals. Human thyroid cell lines ML-1 and human thyrocytes in primary cell culture were treated with HCV recombinant E2 protein. The expression of major proinflammatory cytokines was measured at the messenger RNA and protein levels. Next-generation transcriptome analysis was used to identify early changes in gene expression in thyroid cells induced by E2. HCV envelope protein E2 induced strong inflammatory responses in human thyrocytes, resulting in production of interleukin (IL)-8, IL-6, and tumor necrosis factor-α. Furthermore, the E2 protein induced production of several heat shock proteins including HSP60, HSP70p12A, and HSP10, in human primary thyrocytes. In thyroid cell line ML-1, RNA sequencing identified upregulation of molecules involved in innate immune pathways with high levels of proinflammatory cytokines and chemokines and increased expression of costimulatory molecules, specifically CD40, known to be a major thyroid autoimmunity gene. Our data support a key role for HCV envelope protein E2 in triggering thyroid autoimmunity through activation of cytokine pathways by bystander mechanisms. Copyright © 2017 by the Endocrine Society

Improved protein extraction and protein identification from archival formalin-fixed paraffin-embedded human aortas.

Science.gov (United States)

Fu, Zongming; Yan, Kun; Rosenberg, Avraham; Jin, Zhicheng; Crain, Barbara; Athas, Grace; Heide, Richard S Vander; Howard, Timothy; Everett, Allen D; Herrington, David; Van Eyk, Jennifer E

2013-04-01

Evaluate combination of heat and elevated pressure to enhance protein extraction and quality of formalin-fixed (FF), and FF paraffin-embedded (FFPE) aorta for proteomics. Proteins were extracted from fresh frozen aorta at room temperature (RT). FF and FFPE aortas (3 months and 15 years) were extracted at RT, heat alone, or a combination of heat and high pressure. Protein yields were compared, and digested peptides from the extracts were analyzed with MS. Combined heat and elevated pressure increased protein yield from human FF or FFPE aorta compared to matched tissues with heat alone (1.5-fold) or at RT (8.3-fold), resulting in more proteins identified and with more sequence coverage. The length of storage did adversely affect the quality of proteins from FF tissue. For long-term storage, aorta was preserved better with FFPE than FF alone. Periostin and MGF-E8 were demonstrated suitable for MRM assays from FFPE aorta. Combination of heat and high pressure is an effective method to extract proteins from FFPE aorta for downstream proteomics. This method opens the possibility for use of archival and often rare FFPE aortas and possibly other tissues available to proteomics for biomarker discovery and quantification. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

MECHANISMS IN ENDOCRINOLOGY: Exogenous insulin does not increase muscle protein synthesis rate when administered systemically: a systematic review.

Science.gov (United States)

Trommelen, Jorn; Groen, Bart B L; Hamer, Henrike M; de Groot, Lisette C P G M; van Loon, Luc J C

2015-07-01

Though it is well appreciated that insulin plays an important role in the regulation of muscle protein metabolism, there is much discrepancy in the literature on the capacity of exogenous insulin administration to increase muscle protein synthesis rates in vivo in humans. To assess whether exogenous insulin administration increases muscle protein synthesis rates in young and older adults. A systematic review of clinical trials was performed and the presence or absence of an increase in muscle protein synthesis rate was reported for each individual study arm. In a stepwise manner, multiple models were constructed that excluded study arms based on the following conditions: model 1, concurrent hyperaminoacidemia; model 2, insulin-induced hypoaminoacidemia; model 3, supraphysiological insulin concentrations; and model 4, older, more insulin resistant, subjects. From the presented data in the current systematic review, we conclude that: i) exogenous insulin and amino acid administration effectively increase muscle protein synthesis, but this effect is attributed to the hyperaminoacidemia; ii) exogenous insulin administered systemically induces hypoaminoacidemia which obviates any insulin-stimulatory effect on muscle protein synthesis; iii) exogenous insulin resulting in supraphysiological insulin levels exceeding 50, 000  pmol/l may effectively augment muscle protein synthesis; iv) exogenous insulin may have a diminished effect on muscle protein synthesis in older adults due to age-related anabolic resistance; and v) exogenous insulin administered systemically does not increase muscle protein synthesis in healthy, young adults. © 2015 European Society of Endocrinology.

Preparation of scaffolds from human hair proteins for tissue-engineering applications

International Nuclear Information System (INIS)

Verma, Vipin; Verma, Poonam; Ray, Alok R; Ray, Pratima

2008-01-01

Human hair proteins were isolated and purified for the fabrication of tissue-engineering scaffolds. Their cellular compatibility was studied using NIH3T3 mice fibroblast cells. The proteins were characterized using FTIR spectroscopy, sodium dodecyl sulfate-polyacrylamide gel electrophoresis for molecular weights and two-dimensional polyacrylamide gel electrophoresis for their isoelectric points (pIs). The molecular weights of keratins were in the range of 40-60 kilo-Daltons (kDa) and of matrix proteins were in the range of 15-30 kDa. The pIs of keratins were found to be in the range of 4.5-5.3. Sponges of the proteins were formed by lyophilization. Scanning electron microscopy was performed to examine the surface. Swelling studies were carried out in phosphate buffer saline at physiological pH 7.4. The hydrophilic character of the protein surface was studied by determining an average contact angle, which came to be 37 0 . The wells of tissue culture plates were coated with these proteins for studying the attachment and morphology of the cells. The protein detachment study was done to ensure the adsorption of proteins on the wells until the completion of the experiments. The cellular growth on a protein-coated surface showed three-dimensional 'bulged' morphology due to cell-cell and cell-matrix contacts. The sponges of human hair proteins supported more cells for a longer period than control. The morphology and cell proliferation studies exhibited by NIH3T3 cells on these proteins have shown their potential to be used as tissue-engineering scaffolds with better cell-cell contacts and leucine-aspartic acid-valine (LDV)-mediated cell-matrix interactions