bluuebunny/crossref_metadata_2025 huggingface dataset:
Dependence of the Encapsidation Function of the Adenovirus L1 52/55-Kilodalton Protein on Its Ability To Bind the Packaging Sequence
Authors: Perez-Romero Pilar , Gustin Kurt E. , Imperiale Michael J.
Published: January 2006

The adenovirus IVa2 and L1 52/55-kDa proteins are involved in the assembly of new virus particles. Both proteins bind to the packaging sequence of the viral chromosome, and the lack of expression of either protein results in no virus progeny: the absence of the L1 52/55-kDa protein leads to formation of only empty capsids, and the absence of the IVa2 protein results in no capsid assembly. Furthermore, the IVa2 and L1 52/55-kDa proteins interact with each other during adenovirus infection. However, what is not yet clear is when and how this interaction occurs during the course of the viral infection. We defined the domains of the L1 52/55-kDa protein required for interaction with the IVa2 protein, DNA binding, and virus replication by constructing L1 52/55-kDa protein truncations. We found that the N-terminal 173 amino acids of the L1 52/55-kDa protein are essential for interaction with the IVa2 protein. However, for both DNA binding and complementation of the
pm
8001 mutant virus, which does not express the L1 52/55-kDa protein, the amino-terminal 331 amino acids of the L1 52/55-kDa protein are necessary. These results suggest that the production of infectious virus particles depends on the ability of the L1 52/55-kDa protein to bind to DNA.
Genetic Identification of Adenovirus Type 5 Genes That Influence Viral Spread
Authors: Subramanian T. , Vijayalingam S. , Chinnadurai G.
Published: January 2006

The mechanisms that control cell-to-cell spread of human adenoviruses (Ad) are not well understood. Two early viral proteins, E1B-19K and E3-ADP, appear to have opposing effects since viral mutants that are individually deficient in E1B-19K produce large plaques (G. Chinnadurai, Cell
33:
759-766, 1983), while mutants deficient in E3-ADP produce small plaques (A. E. Tollefson et al., J. Virol.
70:
2296-2306, 1996) on infected cell monolayers. We have used a genetic strategy to identify different viral genes that influence adenovirus type 5 (Ad5) spread in an epithelial cancer cell line. An Ad5 mutant (
dl
327; lacking most of the E3 region) with the restricted-spread (small-plaque) phenotype was randomly mutagenized with UV, and 27 large-plaque (
lp
) mutants were isolated. A combination of analyses of viral proteins and genomic DNA sequences have indicated that 23 mutants contained lesions in the E1B region affecting either 19K or both 19K and 55K proteins. Four other
lp
mutants contained lesions in early regions E1A and E4, in the early L1 region that codes for the i-leader protein, and in late regions that code for the viral structural proteins, penton base, and fiber. Our results suggest that the requirement of E3-ADP for Ad spread could be readily compensated for by abrogation of the functions of E1B-19K and provide genetic evidence that these two viral proteins influence viral spread in opposing manners. In addition to E1B and E3 proteins, other early and late proteins that regulate viral replication and infectivity also influence lateral viral spread. Our studies have identified novel mutations that could be exploited in designing efficient oncolytic Ad vectors.
Reovirus Induces and Benefits from an Integrated Cellular Stress Response
Authors: Smith Jennifer A. , Schmechel Stephen C. , Raghavan Arvind , Abelson Michelle , Reilly Cavan , Katze Michael G. , Kaufman Randal J. , Bohjanen Paul R. , Schiff Leslie A.
Published: January 2006

Following infection with most reovirus strains, viral protein synthesis is robust, even when cellular translation is inhibited. To gain further insight into pathways that regulate translation in reovirus-infected cells, we performed a comparative microarray analysis of cellular gene expression following infection with two strains of reovirus that inhibit host translation (clone 8 and clone 87) and one strain that does not (Dearing). Infection with clone 8 and clone 87 significantly increased the expression of cellular genes characteristic of stress responses, including the integrated stress response. Infection with these same strains decreased transcript and protein levels of P58
IPK
, the cellular inhibitor of the eukaryotic initiation factor 2α (eIF2α) kinases PKR and PERK. Since infection with host shutoff-inducing strains of reovirus impacted cellular pathways that control eIF2α phosphorylation and unphosphorylated eIF2α is required for translation initiation, we examined reovirus replication in a variety of cell lines with mutations that impact eIF2α phosphorylation. Our results revealed that reovirus replication is more efficient in the presence of eIF2α kinases and phosphorylatable eIF2α. When eIF2α is phosphorylated, it promotes the synthesis of ATF4, a transcription factor that controls cellular recovery from stress. We found that the presence of this transcription factor increased reovirus yields 10- to 100-fold. eIF2α phosphorylation also led to the formation of stress granules in reovirus-infected cells. Based on these results, we hypothesize that eIF2α phosphorylation facilitates reovirus replication in two ways—first, by inducing ATF4 synthesis, and second, by creating an environment that places abundant reovirus transcripts at a competitive advantage for limited translational components.
cdc2/Cyclin B1-Dependent Phosphorylation of EBNA2 at Ser243 Regulates Its Function in Mitosis
Authors: Yue Wei , Shackelford Julia , Pagano Joseph S.
Published: January 2006

Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2) transactivates EBV genes in latently infected B cells. We have shown that mitotic hyperphosphorylation of EBNA2 suppresses its ability to transactivate the latent membrane protein 1 (LMP1) promoter. In this follow-up study, we identify EBNA2 Ser243 as a phosphorylation site for mitotic cdc2/cyclin B1 kinase. Mutation at Ser243, which mimics constitutive phosphorylation of the protein, decreases endogenous levels of both LMP1 and EBNA2. Moreover, mutation at Ser243 reduces the ability of EBNA2 to transactivate Cp, the promoter for all six EBV EBNA genes. Our data implicate EBNA2 Ser243 as a cdc2/cyclin B1 site of phosphorylation important for EBNA2's cotranscriptional function in mitosis.
Identification of Spliced Gammaherpesvirus 68 LANA and v-Cyclin Transcripts and Analysis of Their Expression In Vivo during Latent Infection
Authors: Allen Robert D. , Dickerson Shelley , Speck Samuel H.
Published: January 2006

Regulation of orf73 (LANA) gene expression is critical to the establishment and maintenance of latency following infection by members of the gamma-2 herpesvirus (rhadinovirus) family. Previous studies of murine gammaherpesvirus 68 (γHV68) have demonstrated that loss of LANA function results in a complete failure to establish virus latency in the spleens of laboratory mice. Here we report the characterization of alternatively spliced LANA and v-cyclin (orf72) transcripts encoded by γHV68. Similar to other rhadinoviruses, alternative splicing, coupled with alternative 3′ processing, of a ca. 16-kb transcriptional unit can lead to expression of either LANA or v-cyclin during γHV68 infection. Spliced LANA and v-cyclin transcripts were initially identified from an analysis of the γHV68 latently infected B-cell lymphoma cell line S11E, but were also detected during lytic infection of NIH 3T12 fibroblasts. 5′ Random amplification of cDNA ends (RACE) analyses identified two distinct promoters, p1 and p2, that drive expression of spliced LANA transcripts. Analysis of p1 and p2, using transiently transfected reporter constructs, mapped the minimal sequences required for promoter activity and demonstrated that both promoters are active in the absence of any viral antigens. Analysis of spliced LANA and v-cyclin transcripts in spleens recovered from latently infected mice at days 16 and 42 postinfection revealed that spliced v-cyclin transcripts can only be detected sporadically, suggesting that these may be associated with cells reactivating from latency. In contrast, spliced LANA transcripts were detected in ca. 1 in 4,000 splenocytes harvested at day 16 postinfection. Notably, based on the frequency of viral genome-positive splenocytes at day 16 postinfection (ca. 1 in 200), only 5 to 10% of viral genome-positive splenocytes express LANA. The failure of the majority of infected splenocytes at day 16 postinfection to express LANA may contribute to the contraction in the frequency of latently infected splenocytes as chronic infection is established, due to failure to maintain the viral episome in proliferating B cells.
FRIEDMANN COSMOLOGY ON CODIMENSION 2 BRANE WITH TIME-DEPENDENT TENSION
Authors: ZHANG HONGSHENG , GUO QI , CAI RONG-GEN
Published: January 2006

A solution of codimension 2 brane is found for which four-dimensional Friedmann cosmology is recovered on the brane with time-dependent tension, in the Einstein frame. The effective parameter p/ρ of equation of state on the brane can be quintessence like, de Sitter like or phantom like, depending on the integration constants of the solution.
ELECTROMAGNETIC WAVES, GRAVITATIONAL COUPLING AND DUALITY ANALYSIS
Authors: ABREU E. M. C. , PINHEIRO C. , DINIZ S. A. , KHANNA F. C.
Published: January 2006

In this letter we introduce a particular solution for parallel electric and magnetic fields, in a gravitational background, which satisfy free-wave equations and the phenomenology suggested by astrophysical plasma physics. These free-wave equations are computed such that the electric field does not induce the magnetic field and vice versa. In a gravitational field, we analyze the Maxwell equations and the corresponding electromagnetic waves. A continuity equation is presented. A commutative and noncommutative analysis of the electromagnetic duality is described.
HODGE DUALITY AND COSMOLOGICAL CONSTANT
Authors: NISHINO HITOSHI , RAJPOOT SUBHASH
Published: January 2006

We present a simple mechanism to eliminate cosmological constants both in supersymmetric and non-supersymmetric theories. This mechanism is based on the Hodge (Poincaré) duality between a 0-form and D-form field strengths in D-dimensional spacetime. The new key ingredient is the introduction of an extra Chern–Simons term into the D-form field strength H dual to the 0-form field strength. Our formulation can also be made consistent with supersymmetry. Typical applications to four-dimensional N = 1 supergravity and to ten-dimensional type IIA supergravity are given. The success of our formulation for both supersymmetric and non-supersymmetric systems strongly indicates the validity of our mechanism even after supersymmetry breakings at the classical level. Our mechanism may well be applicable to quantized systems, at least for supersymmetric cases with fundamental D-brane actions available.
ROBOT ARM CONTROL USING AN ELECTRO-RHEOLOGICAL (ER) CLUTCH-BRAKE MECHANISM: MODEL VALIDATION
Authors: TAN K. P. , STANWAY R. , BULLOUGH W. A.
Published: January 2006

Robot arm positioning is an important factor in the robotic process. However, the robot manipulator experiences positioning inaccuracies. This positioning error is due to the dynamic inefficiencies of its actuator: DC servomotor. In a bid to resolve this actuator problem, an electro-rheological (ER) clutch-brake mechanism is employed. This clutch-brake mechanism can actuate and halt the motion of the robot arm. This rotary mechanism consists of two similar clutches that are driven to rotate in the opposite directions and an individual ER brake that provides braking torques to halt the manipulator at the required positions. The main aim of this paper is to establish a control strategy for the ER actuated robot arm by means of model validation with the experimental results. This study is conducted to understand the ER robotic positioning control for future applications.
Cultured slow vs. fast skeletal muscle cells differ in physiology and responsiveness to stimulation
Authors: Huang Yen-Chih , Dennis Robert G. , Baar Keith
Published: January 2006

In vitro studies have used protein markers to distinguish between myogenic cells isolated from fast and slow skeletal muscles. The protein markers provide some support for the hypothesis that satellite cells from fast and slow muscles are different, but the data are equivocal. To test this hypothesis directly, three-dimensional skeletal muscle constructs were engineered from myogenic cells isolated from fast tibialis anterior (TA) and slow soleus (SOL) muscles of rats and functionality was tested. Time to peak twitch tension (TPT) and half relaxation time (RT1/2) were ∼30% slower in constructs from the SOL. The slower contraction and relaxation times for the SOL constructs resulted in left shift of the force-frequency curve compared with those from the TA. Western blot analysis showed a 60% greater quantity of fast myosin heavy chain in the TA constructs. 14 days of chronic low-frequency electrical stimulation resulted in a 15% slower TPT and a 14% slower RT1/2, but no change in absolute force production in the TA constructs. In SOL constructs, slow electrical stimulation resulted in an 80% increase in absolute force production with no change in TPT or RT1/2. The addition of cyclosporine A did not prevent the increase in force in SOL constructs after chronic low-frequency electrical stimulation, suggesting that calcineurin is not responsible for the increase in force. We conclude that myogenic cells associated with a slow muscle are imprinted to produce muscle that contracts and relaxes slowly and that calcineurin activity cannot explain the response to a slow pattern of electrical stimulation.
PKC-δ mediates activation of ERK1/2 and induction of iNOS by IL-1β in vascular smooth muscle cells
Authors: Ginnan Roman , Guikema Benjamin J. , Singer Harold A. , Jourd'heuil David
Published: January 2006

Although the inflammatory cytokine interleukin-1β (IL-β) is an important regulator of gene expression in vascular smooth muscle (VSM), the signal transduction pathways leading to transcriptional activation upon IL-1β stimulation are poorly understood. Recent studies have implicated IL-1β-mediated ERK1/2 activation in the upregulation of type II nitric oxide synthase (iNOS) in VSM. We report that these events are mediated in a phospholipase C (PLC)- and protein kinase C (PKC)-δ-dependent manner utilizing a signaling mechanism independent of p21ras (Ras) and Raf1 activation. Stimulation of rat aortic VSM cells with IL-1β activated PLC-γ and pharmacological inhibition of PLC attenuated IL-1β-induced ERK1/2 activation and subsequent iNOS expression. Stimulation with IL-1β activated PKC-α and -δ, which was blocked using the PLC inhibitor U-73122. Pharmacological studies using isoform-specific PKC inhibitors and adenoviral overexpression of constitutively active PKC-δ indicated that ERK1/2 activation was PKC-α independent and PKC-δ dependent. Similarly, adenoviral overexpression of constitutively activated PKC-δ enhanced iNOS expression. IL-1β stimulation did not induce either Ras or Raf1 activity. The absence of a functional role for Ras and Raf1 related to ERK1/2 activation and iNOS expression was further confirmed by adenoviral overexpression of dominant-negative Ras and treatment with the Raf1 inhibitor GW5074. Taken together, we have outlined a novel transduction pathway implicating PKC-δ as a critical component of the IL-1-dependent activation of ERK in VSM cells.
Expression of β-catenin is necessary for physiological growth of adult skeletal muscle
Authors: Armstrong Dustin D. , Wong Vicki L. , Esser Karyn A.
Published: January 2006

Expression of β-catenin is known to be important for developmental processes such as embryonic pattern formation and determination of cell fate. Inappropriate expression, however, has been linked to pathological states such as cancer. Here we report that expression of β-catenin is necessary for physiological growth of skeletal muscle in response to mechanical overload. Conditional inactivation of β-catenin was induced in control and overloaded muscle through intramuscular injection of adenovirus expressing Cre recombinase in β-catenin floxed mice. Individual muscle fiber analysis was performed to identify positively transfected/inactivated cells and determine fiber cross-sectional area. The results demonstrate that fiber growth is completely inhibited when the β-catenin expression is lost. This effect was cell autonomous, as fibers that did not exhibit recombination in the floxed mice grew to the same magnitude as infected/noninfected fibers from wild-type mice. These findings suggest that β-catenin may be a primary molecular site through which multiple signaling pathways converge in regulating physiological growth.
Quadriceps H-Reflex Modulation During Pedaling
Authors: Larsen Birgit , Voigt Michael
Published: January 2006

The main aims of this study were 1) to investigate possible phase-, speed-, and task-dependent changes in the quadriceps H-reflex during pedaling, and to achieve this, 2) to develop an optimized H-reflex recording and processing procedure for recording of quadriceps H-reflexes during movement. It was hypothesized that the behavior of the quadriceps H-reflex concerning phase, speed, and task dependency corresponds to the behavior of the soleus H-reflex during rhythmical leg movements. The applied H-reflex procedure appeared to be reliable for obtaining the quadriceps H-reflex modulation during leg movement. The vastus lateralis (VL) and rectus femoris (RF) H-reflexes showed a phase-dependent modulation during pedaling at a frequency of 80 rpm with almost parallel changes in the reflex amplitude and motor recruitment level. However, when the speed of movement was reduced from 80 to 40 revolutions per minute (rpm) and crank load simultaneously increased (i.e., a halving of the movement speed with a constant motor recruitment level), the quadriceps H-reflex modulation pattern changed significantly in relation to the pattern of motor recruitment, i.e., at 40 rpm, the reflex excitability remained high during a gradual derecruitment during power generation in downstroke. Comparison of the “operationally defined H-reflex gain function” obtained during 1) pedaling at 80 rpm and 2) isometric quadriceps contractions in sitting position showed no significant task-dependent changes in the quadriceps H-reflex. Consequently, the hypothesis was only partly corroborated, and the findings indicate differences in the neural control of the soleus and the quadriceps muscle during rhythmical movements.
Distinct Transmitter Release Properties Determine Differences in Short-Term Plasticity at Functional and Silent Synapses
Authors: Cabezas Carolina , Buño Washington
Published: January 2006

Recent evidence suggests that functional and silent synapses are not only postsynaptically different but also presynaptically distinct. The presynaptic differences may be of functional importance in memory formation because a proposed mechanism for long-term potentiation is the conversion of silent synapses into functional ones. However, there is little direct experimentally evidence of these differences. We have investigated the transmitter release properties of functional and silent Schaffer collateral synapses and show that on the average functional synapses displayed a lower percentage of failures and higher excitatory postsynaptic current (EPSC) amplitudes than silent synapses at +60 mV. Moreover, functional but not silent synapses show paired-pulse facilitation (PPF) at +60 mV and thus presynaptic short-term plasticity will be distinct in the two types of synapse. We examined whether intraterminal endoplasmic reticulum Ca2+stores influenced the release properties of these synapses. Ryanodine (100 μM) and thapsigargin (1 μM) increased the percentage of failures and decreased both the EPSC amplitude and PPF in functional synapses. Caffeine (10 mM) had the opposite effects. In contrast, silent synapses were insensitive to both ryanodine and caffeine. Hence we have identified differences in the release properties of functional and silent synapses, suggesting that synaptic terminals of functional synapses express regulatory molecular mechanisms that are absent in silent synapses.
Contralateral White Noise Selectively Changes Left Human Auditory Cortex Activity in a Lexical Decision Task
Authors: Behne Nicole , Wendt Beate , Scheich Henning , Brechmann André
Published: January 2006

In a previous study, we hypothesized that the approach of presenting information-bearing stimuli to one ear and noise to the other ear may be a general strategy to determine hemispheric specialization in auditory cortex (AC). In that study, we confirmed the dominant role of the right AC in directional categorization of frequency modulations by showing that fMRI activation of right but not left AC was sharply emphasized when masking noise was presented to the contralateral ear. Here, we tested this hypothesis using a lexical decision task supposed to be mainly processed in the left hemisphere. Subjects had to distinguish between pseudowords and natural words presented monaurally to the left or right ear either with or without white noise to the other ear. According to our hypothesis, we expected a strong effect of contralateral noise on fMRI activity in left AC. For the control conditions without noise, we found that activation in both auditory cortices was stronger on contralateral than on ipsilateral word stimulation consistent with a more influential contralateral than ipsilateral auditory pathway. Additional presentation of contralateral noise did not significantly change activation in right AC, whereas it led to a significant increase of activation in left AC compared with the condition without noise. This is consistent with a left hemispheric specialization for lexical decisions. Thus our results support the hypothesis that activation by ipsilateral information-bearing stimuli is upregulated mainly in the hemisphere specialized for a given task when noise is presented to the more influential contralateral ear.
Comorbidity and Physical Function: Results from the Aging and Longevity Study in the Sirente Geographic Area (ilSIRENTE Study)
Authors: Cesari Matteo , Onder Graziano , Russo Andrea , Zamboni Valentina , Barillaro Christian , Ferrucci Luigi , Pahor Marco , Bernabei Roberto , Landi Francesco
Published: January 2006

Background: Physical function measures have gained increased importance in the evaluation of older persons. The presence of comorbidity is a major and growing issue in geriatrics. Objective: To evaluate the relationship between comorbidity and physical function in community-dwelling older persons. Methods: Data are from baseline evaluation of the ilSIRENTE study (n = 364). Physical performance was assessed using the Short Physical Performance Battery (SPPB) and the 4-meter walking test. Muscle strength was measured by hand-grip strength. Functional performance was assessed using Basic and Instrumental Activities of Daily Living (ADLs and IADLs, respectively). Comorbidity was defined as ≧3 clinical conditions. Analyses of covariance and linear regressions were performed to evaluate the relationship between comorbidity and physical function. Results: The mean age of participants was 85.9 (SD = 4.9) years. About one third (37.4%) of participants reported ≧3 clinical conditions. Participants with comorbidity had significantly worse results in all the physical function tests. Participants with comorbidity had significantly lower adjusted results for the 4-meter walking test (0.444 m/s) and the SPPB score (6.131) compared to those without comorbidity (0.531 m/s and 7.221; all p = 0.001, respectively). Participants with comorbidity were more IADL-impaired (3.152) than participants without comorbidity (2.767; p = 0.04). No significant association of ADLs and hand-grip strength with comorbidity was reported. Similar strengths of association for the 4-meter walking test (per SD increase, β = –0.280; p = 0.001) and the SPPB (per SD increase, β = –0.285; p = 0.001) with comorbidity were reported. Conclusions: Physical function measures, especially walking speed and SPPB, are associated with comorbidity. Physical performance measures may improve the clinical evaluation of older persons.
Factors Related to Institutionalization among the Frail Elderly with Home-Visiting Nursing Service in Japan
Authors: Oura Asae , Washio Masakazu , Wada Jyun-ichi , Arai Yumiko , Mori Mitsuru
Published: January 2006

A dramatic increase in the number of elderly people in Japan has led to a concurrent increase in the number of frail elderly in need of care. It is estimated that the number of frail elderly will reach 3.9 million by the year 2010. Family members are often both physically and mentally burdened with caring for the frail elderly. The present study was conducted to identify the risk factors for institutionalization among the frail elderly receiving in-home care in Japan.
Stochastic Modeling of Blood Coagulation Initiation
Authors: Lo Ken , Denney William S. , Diamond Scott L.
Published: January 2006

A kinetic Monte Carlo simulation was developed using the deterministic reaction network developed by the Mann laboratory for tissue-factor (TF)-initiated blood coagulation. The model predicted thrombin dynamics in recalcified whole blood (3-fold diluted) pretreated with convulxin (platelet GPVI activator) and picomolar levels of TF (0–14 pM). The model did not accurately predict coagulation times at low TF (0–0.7 pM). The simulation revealed that ∼0.2 pM TF was the critical concentration to cause 50% of reactions containing 3-fold diluted whole blood to reach a clotting threshold of 0.05 U/ml thrombin by 1 h. Simulations of 1 nl of blood (5 pM TF) revealed small stochastic variations in thrombin initiation time, while 16.6 pl simulations were highly stochastic at this level of TF (50 molecules/16.6 pl). Further experiment and simulation will require evaluation of mechanisms of coagulation kinetics at subpicomolar levels of TF.
Coagulation under Flow: The Influence of Flow-Mediated Transport on the Initiation and Inhibition of Coagulation
Authors: Fogelson Aaron L. , Tania Nessy
Published: January 2006

A mathematical model of intravascular coagulation is presented; it encompasses the biochemistry of the tissue factor pathway, platelet activation and deposition on the subendothelium, and flow- and diffusion-mediated transport of coagulation proteins and platelets. Simulation experiments carried out with the model indicate the predominant role played by the physical processes of platelet deposition and flow-mediated removal of enzymes in inhibiting coagulation in the vicinity of vascular injury. Sufficiently rapid production of factors IXa and Xa by the TF:VIIa complex can overcome this inhibition and lead to formation of significant amounts of the tenase complex on the surface of activated platelets and, as a consequence, to substantial thrombin production. Chemical inhibitors are seen to play almost no (TFPI) or little (AT-III and APC) role in determining whether substantial thrombin production will occur. The role of APC is limited by the necessity for diffusion of thrombin from the site of injury to nearby endothelial cells to form the thrombomodulin-thrombin complex and for diffusion in the reverse direction of the APC made by this complex. TFPI plays an insignificant part in inhibiting the TF:VIIa complex under the conditions studied whether its action involves sequential binding of TFPI to Xa and then TFPI:Xa to TF:VIIa, or direct binding of TFPI to Xa already bound to the TF:VIIa complex.
Blood Coagulation and Propagation of Autowaves in Flow
Authors: Ermakova Elena A. , Panteleev Mikhail A. , Shnol Emmanuil E.
Published: January 2006

This study analyses the effect of flow and boundary reactions on spatial propagation of waves of blood coagulation. A simple model of coagulation in plasma consisting of three differential reaction-diffusion equations was used for numerical simulations. The vessel was simulated as a two-dimensional channel of constant width, and the anticoagulant influence of thrombomodulin present on the undamaged vessel wall was taken into account. The results of the simulations showed that this inhibition could stop the coagulation process in the absence of flow in narrow channels. For the used mathematical model of coagulation this was the case if the width was below 0.2 mm. In wider vessels, the process could be stopped by the rapid blood flow. The required flow rate increased with the increase of the damage region size. For example, in a 0.5-mm wide channel with 1-mm long damage region, the propagation of coagulation may be terminated at the flow rate of more than 20 mm/min.
Understanding Muscle Architectural Adaptation: Macro- and Micro-Level Research
Authors: Blazevich Anthony J. , Sharp N.C. Craig
Published: January 2006

Recent research using muscle-imaging techniques has revealed a remarkable plasticity of human muscle architecture where significant changes in fascicle lengths and angles have resulted from the chronic performance, or cessation, of strong muscle contractions. However, there is a paucity of data describing architectural adaptations to chronic stretching, disuse and immobilization, illness, and aging, and those data that are available are equivocal. Understanding their impact is important in order that effective interventions for illness/injury management and rehabilitation, and programs to improve the physical capacity of workers, the aged and athletes can be determined. Nonetheless, recent advances in myocellular research could provide a framework allowing the prediction of architectural changes in these understudied areas. Examination of the site-specific response to mechanical stress of calpain-dependent ubiquitin-proteasome proteolysis, or of the cellular response to stress after the knockout (or incapacitation) of sarcomeric and cytoskeletal proteins involved in cellular signal transduction, provides an exciting paradigm by which myocellular adaptation can be described. Such research might contribute to the understanding of macro-level changes in muscle architecture.
Long-Term Culture of Human Urothelial Cells – A Qualitative Analysis
Authors: Fossum Magdalena , Lundberg Fredrik , Holmberg Kerstin , Schoumans Jacqueline , Kratz Gunnar , Nordenskjöld Agneta
Published: January 2006

Today, in vitro culturing of autologous cells is an established method in the field of tissue reconstruction. It can be applied to urothelial cells and could have many clinical implications in urological reconstructive surgery. This development calls for quality controls concerning cells used for clinical treatment when cells are autotransplanted back to the patient. We have studied cultured cells in order to detect whether genetic or morphologic changes occur. Urothelial cells isolated from bladder lavage were cultured according to different protocols based on the presence or absence of feeder cells. Genetic studies were performed by means of karyotyping with standard G-banding and interphase fluorescent in situ hybridization (FISH) analyses. The morphology of these epithelial cells was judged as well as immunostaining for epithelial cell markers. In addition, to minimize the risk of feeder cell contamination, proliferation studies were performed on cultures including feeder cells that had been pretreated with different doses of mitomycin or radiation. In initial studies, when using feeder cells in each passage according to standard protocols, urothelial cells proliferated unfavourably after the fourth passage with increasing numbers of mouse cells as well as urothelial tetraploid cells. We could also show that urothelial cells from bladder lavage need feeder cells in order to establish primary cultures. Further propagation up to 14 passages was performed without feeder cells and the urothelial cells retained normal karyotypes. We also found that mitomycin treatment had its main effect on feeder cells during the first 2 h. When feeder cells were irradiated, 20 Gy was effective and no feeder cell contamination was seen. In conclusion, we found that a high standard of quality in urothelial cell culturing can be achieved with a careful culturing technique.
Osteocyte Lacuna Population Densities in Sheep, Elk and Horse Calcanei
Authors: Skedros John G.
Published: January 2006

Osteocytes, the most prevalent cell type in bone, appear to communicate via gap junctions. In limb-bone diaphyses, it has been hypothesized that these cellular networks have the capacity to monitor habitual strains, which can differ significantly between cortical locations of the same bone. Regional differences in microdamage associated with prevalent/predominant strain mode (tension, compression, or shear) and/or magnitude may represent an important ‘variable’ detected by this network. This hypothesis was indirectly addressed by examining bones subjected to habitual bending for correlations of osteocyte lacuna population densities (n/mm2 bone area, Ot.Lc.N/B.Ar) with locations experiencing high and low strain, and/or prevalent/predominant tension, compression, and shear. We examined dorsal (‘compression’), plantar (‘tension’), and medial/lateral (‘shear’ or neutral axis) cortices of mid-diaphyseal sections of calcanei of adult sheep, elk, and horses. Ot.Lc.N/B.Ar data, quantified in backscattered electron images, were also evaluated in a context of various additional structural and material variables (e.g. % ash, cortical thickness, porosity, and secondary osteon population). Results showed significant differences in dorsal versus plantar comparisons with the highest Ot.Lc.N/B.Ar in dorsal cortices of sheep and elk (p < 0.0001); but this was a statistical trend in the equine calcanei (p = 0.14). There were no consistent transcortical (pericortical to endocortical) differences, and Ot.Lc.N/B.Ar in neutral axes was not consistently different from dorsal/plantar cortices. Correlations of Ot.Lc.N/B.Ar with structural and material parameters were also poor and/or inconsistent within or between species. These results provide little or no evidence that the number of osteocyte lacunae has a functional role in mechanotransduction pathways that are typically considered in bone adaptation. Although dorsal/plantar differences may be adaptations for prevalent/predominant strain modes and/or associated microdamage, it is also plausible that they are strongly influenced by differences in the bone formation rates that produced the tissue in these locations.
Neuromuscular Organization of the Superior Longitudinalis Muscle in the Human Tongue
Authors: Slaughter Katrina , Li Haiyan , Sokoloff Alan J.
Published: January 2006

Proper tongue function is essential for respiration and mastication, yet we lack basic information on the anatomical organization underlying human tongue movement. Here we use microdissection, acetylcholinesterase histochemistry, silver staining of nerves, alpha bungarotoxin binding and immunohistochemistry to describe muscle fiber architecture and motor endplate (MEP) distribution of the human superior longitudinalis muscle (SL). The human SL extends from tongue base to tongue tip and is composed of fiber bundles that range from 2.8 to 15.7 mm in length. Individual muscle fibers of the SL range from 1.2 to 17.3 mm in length (1.3–18.2% of muscle length). Seventy-one percent of SL fibers have blunt-blunt terminations; the remainder have blunt-taper terminations. Multiple MEPs are present along SL length and dual MEPs are present on some muscle fibers. These data demonstrate that the human SL is a muscle of ‘in-series’ design. We suggest that SL motor units are organized to innervate specific regions of the tongue body and that activation of SL motor units according to anteroposterior location is one strategy employed by the nervous system to control tongue shape and tongue movement.
An Electronic Prosthesis Mimicking the Dynamic Vestibular Function
Authors: Shkel Andrei M. , Zeng Fan-Gang
Published: January 2006

This paper presents a functional architecture, system level design, and electronic evaluation of a unilateral vestibular prosthesis. The sensing unit of the prosthesis is a custom-designed one-axis microelectromechanical system (MEMS) gyroscope. Similar to the natural semicircular canal, the MEMS gyroscope senses angular motion of the head and generates voltages proportional to the corresponding angular acceleration. The voltage is then converted into electric current pulses according to the physiological data relating angular acceleration to the spike count in the vestibular nerve. The current pulses can be delivered to stimulate the corresponding vestibular nerve branch. Electronic properties of the vestibular prosthesis prototype have been systematically evaluated and found to meet the design specifications. A unique feature of the present vestibular implant prototype is the scalability: the sensing unit, pulse generator, and the current source can be potentially implemented on a single chip using integrated MEMS technology.
Evolution of the Amygdala: New Insights from Studies in Amphibians
Authors: Laberge Frédéric , Mühlenbrock-Lenter Sabine , Grunwald Wolfgang , Roth Gerhard
Published: January 2006

The histology of amphibian brains gives an impression of relative simplicity when compared with that of reptiles or mammals. The amphibian telencephalon is small and contains comparatively few and large neurons, which in most parts constitute a dense periventricular cellular layer. However, the view emerging from the last decade is that the brains of all tetrapods, including amphibians, share a general bauplan resulting from common ancestry and the need to perform similar vital functions. To what extent this common organization also applies to higher brain functions is unknown due to a limited knowledge of the neurobiology of early vertebrates. The amygdala is widely recognized as a brain center critical for basic forms of emotional learning (e.g., fear conditioning) and its structure in amphibians could suggest how this capacity evolved. A functional systems approach is used here to synthesize the results of our anatomical investigations of the amphibian amygdala. It is proposed that the connectivity of the amphibian telencephalon portends a capacity for multi-modal association in a limbic system largely similar to that of amniote vertebrates. One remarkable exception is the presence of new sensory-associative regions of the amygdala in amniotes: the posterior dorsal ventricular ridge plus lateral nuclei in reptiles and the basolateral complex in mammals. These presumably homologous regions apparently are capable of modulating the phylogenetically older central amygdala and allow more complex forms of emotional learning.
Neurological Deficits in the Life and Works of Frida Kahlo
Authors: Budrys Valmantas
Published: January 2006

World-famous Mexican painter Frida Kahlo is an impressive example of an artist whose entire life and creativity were extremely influenced by chronic, severe illness. Many of her best-known works depict her physical and mental suffering. She was one of those very uncommon artists who dared to show their nude, sick body. This article describes biographical events and works of Frida Kahlo that are closely related to neurology: congenital anomaly (spina bifida), poliomyelitis, spine injury, neuropathic pain.
The Stoic Argument Ex Gradibus Entium
Authors: Gelinas Luke
Published: January 2006

In this paper I offer an interpretation of the Stoic argumentum ex gradibus entium as it appears in Book II of Cicero's De Natura Deorum. In addition to displaying certain similarities to later formulations of the so-called "ontological argument," particularly Anselm's, I argue that the argument ex gradibus entium was a versatile feature of Stoic philosophical theology, capable of employment in relation to two distinct topics: the existence of god and the identification of god's essential nature with the world. I claim that the instance of the argument ex gradibus entium at ND II 18-21 is a token of this latter type, and show that there are no textual reasons precluding this interpretation. In light of the fact that the argument can be analyzed more effectively in this role, I suggest that this particular instance of the argument is best thought of as an attempt on the part of the Stoics to identify the world with god rather than as a strict proof for god's bare existence. I end with some reflections on the general type of the Stoic argument qua precursor to two of Anselm's ontological proofs. Although I think it is a mistake to call the Stoic argument "ontological" in a strict sense, it may, I suggest, have shared a similar conceptual underpinning with at least one of Anselm's famous formulations.
Ethical Justice and Political Justice
Authors: Lockwood Thornton
Published: January 2006

The purpose of Aristotle's discussion of political justice (τò πoλιτικòν δικαιoν) in EN V.6-7 has been a matter of dispute. Although the notion of political justice which Aristotle seeks to elucidate is relatively clear, namely the notion of justice which obtains between free and equal citizens living within a community aiming at self-sufficiency under the rule of law, confusion arises when one asks how political justice relates to the other kinds of justice examined in EN V. Is political justice a highly determinate subdivision of justice which Aristotle examines alongside the other varieties of particular justice analyzed in EN V.2-5? Or is political justice related to the analysis of ethical agency which follows in EN V.8-11? The question is complicated by the fact that the passage in question – EN V 1134a17-1135a15 – has occasioned much speculation about textual dislocations and has been incorporated into chapter divisions differently according to the two prevalent modern editorial divisions of the Ethics.To resolve these problems, I argue that Aristotle's account of political justice is situated within an extended aporetic analysis which begins in EN V.6 and extends through EN V.8. Aristotle introduces the notion of political justice within the extended analysis concerning the ascription of character states because calling someone just or unjust presupposes that the person is a fully mature ethical agent, but anyone capable of political justice possesses such agency. Once the extended argument in the second half of EN V is properly understood, it appears that the received text is not in need of emendation. To further support my claim that Aristotle's account of political justice introduces a new inquiry which is not analogous to the analyses of particular justice in the first half of EN V, I compare political justice to the other species of justice.
There Is No Escape from Philosophy
Authors: Saaristo Antti
Published: January 2006

This article examines two empirical research traditions—experimental economics and the social identity approach in social psychology—that may be seen as attempts to falsify and verify the theory of collective intentionality, respectively. The article argues that both approaches fail to settle the issue. However, this is not necessarily due to the alleged immaturity of the social sciences but, possibly, to the philosophical nature of intentionality and intentional action. The article shows how broadly Davidsonian action theory, including Hacking’s notion of the looping effect of the human sciences, can be developed into an argument for the view that there is no theory-independent true nature of intentional action. If the Davidsonian line of thought is correct, the theory of collective intentionality is, in a sense, true if we accept the theory.
On Participation and Membership in Discursive Practices
Authors: Shockley Kenneth
Published: January 2006

For a view which grounds norms in the practices of a particular group, determining who is in that group will determine the scope of those norms. Such a view requires an account of what it is to be a member of the group subject to that practice. In this article, the author presents the beginnings of such an account, limiting his inquiry to discursive practices; we might characterize such practices as those which require, as a condition of participation, participants both to exchange reasons with one another and to recognize that practice as a common source of reasons. The author argues that membership in such groups is constituted by the conjunction of shared discursive practices, common recognition of the authority of that practice, and commitments between members. In the case of discursive practices, these features of membership are inseparable.
Self-monitoring of Physical Activity
Authors: Gleeson-Kreig JoAnn M.
Published: January 2006

Purpose: The purpose of this study was to test the effect of keeping daily activity records on physical activity levels and self-efficacy for physical activity in adults with type 2 diabetes, and to examine the feasibility and acceptability of this intervention from the perspective of the participants.

Methods: This intervention study included 58 individuals with type 2 diabetes aged 40 to 65 years. Participants were randomly assigned: individuals in the intervention group kept daily activity records for 6 weeks, mailed to the researcher every 2 weeks. Data collection was completed at the beginning of the study and 6 weeks later, using the habitual physical activity index and the self-efficacy for exercise scale. Participants in the intervention group also completed the perceived feasibility checklist.

Results: The intervention resulted in enhanced self-efficacy. Physical activity improved in both the intervention and control groups. Activity recording was judged to be acceptable and feasible.

Conclusions: Daily activity recording can be used as part of a program to increase physical activity self-efficacy levels. Focused interactions between health care providers and patients may be enough to motivate people to higher levels of physical activity. The relationship between self-efficacy and behavior is complex and should be the subject of further research.
Using Focus Groups to Develop a Culturally Competent Diabetes Self-management Program for Mexican Americans
Authors: Vincent Deborah , Clark Lauren , Zimmer Lorena Marquez , Sanchez Jessica
Published: January 2006

Purpose: The purpose of this study was to describe factors that facilitate or hinder diabetes self-management and elicit participants’ preferences and recommendations about the essential components of a culturally competent diabetes self-management program.

Methods: Latino patients with type 2 diabetes and their family caregivers were interviewed in focus groups. Four focus groups consisted of patients, and 2 groups consisted of family caregivers for a total of 40 participants. Participants were assigned to groups based on break characteristics of gender and preferred language.

Results: “Being in the dark” emerged as an important concern, and patient respondents wanted timely access to information that they deemed understandable about how to manage their diabetes. Family members’ support and understanding were crucial in maintaining lifestyle changes. Patient and family caregiver participants wanted a self-management program to incorporate information on how to modify traditional foods, home remedies, and stress management. Preferences for information delivery included group didactic and interactive sessions, written information, and videotapes. Higher technology strategies using computers were not seen as useful.

Conclusions: Culturally competent diabetes self-management for Latinos should incorporate the family and include techniques for stress management as well as diet modification. Information delivery should include a variety of techniques.