bluuebunny/crossref_metadata_2025 huggingface dataset:
Dose effect on intramuscular metabolic stress during low-intensity resistance exercise with blood flow restriction
Authors: Suga Tadashi , Okita Koichi , Morita Noriteru , Yokota Takashi , Hirabayashi Kagami , Horiuchi Masahiro , Takada Shingo , Omokawa Masashi , Kinugawa Shintaro , Tsutsui Hiroyuki
Published: April 2010

Our previous study reported that metabolic stress in skeletal muscle achieved by combining moderate blood flow restriction (BFR) with low-intensity resistance exercise at 20% of one repetition maximum (1 RM) could not reach the level achieved by high-intensity resistance exercise. Since the previous protocol is typical of current regimens of this type, we sought in this study to optimize the exercise protocol for low-intensity resistance exercise with BFR by examining the dose effects of exercise intensity and pressure. Twelve healthy subjects participated in this study. They were asked to perform unilateral plantar flexion for 2 min (30 repetitions/min) under six different conditions: two resistance exercises (20% 1 RM and 65% 1 RM) without BFR, and four BFR protocols. The four BFR protocols included three different exercise intensities (20, 30, and 40% 1 RM) with moderate pressure (MP) using 130% of systolic blood pressure (147 ± 17 mmHg, mean ± SD) and 20% 1 RM with high pressure at 200 mmHg. Intramuscular metabolites and pH were obtained by 31P-magnetic resonance spectroscopy. Significant dose effects on intramuscular metabolites and pH were observed for exercise intensity ( P < 0.001) but not for BFR pressure. The BFR protocol combining 30% 1 RM with MP had similar results as the high-intensity load at 65% 1 RM. Intramuscular metabolic stress during BFR exercise might be susceptible to increasing exercise intensity. To replace high-intensity resistance exercise, the BFR protocol might require an intensity of ≥30% 1 RM.
The innervation and organization of motor units in a series-fibered human muscle: the brachioradialis
Authors: Lateva Zoia C. , McGill Kevin C. , Johanson M. Elise
Published: April 2010

We studied the innervation and organization of motor units in the brachioradialis muscle of 25 normal human subjects. We recorded intramuscular EMG signals at points separated by 15 mm along the proximodistal muscle axis during moderate isometric contractions, identified from 27 to 61 (mean 39) individual motor units per subject using EMG decomposition, and estimated the locations of the endplates and distal muscle/tendon junctions from the motor-unit action potential (MUAP) propagation patterns and terminal standing waves. In three subjects all the motor units were innervated in a single endplate zone. In the other 22 subjects, the motor units were innervated in 3–6 (mean 4) distinct endplate zones separated by 15–55 mm along the proximodistal axis. One-third of the motor units had fibers innervated in more than one zone. The more distally innervated motor units had distinct terminal waves indicating tendonous termination, while the more proximal motor units lacked terminal waves, indicating intrafascicular termination. Analysis of blocked MUAP components revealed that 19% of the motor units had at least one doubly innervated fiber, i.e., a fiber innervated in two different endplate zones by two different motoneurons, and thus belonging to two different motor units. These results are consistent with the brachioradialis muscle having a series-fibered architecture consisting of multiple, overlapping bands of muscle fibers in most individuals and a simple parallel-fibered architecture in some individuals.
Skeletal muscle dysfunction in muscle-specific LKB1 knockout mice
Authors: Thomson David M. , Hancock Chad R. , Evanson Bradley G. , Kenney Steven G. , Malan Brandon B. , Mongillo Anthony D. , Brown Jacob D. , Hepworth Squire , Fillmore Natasha , Parcell Allen C. , Kooyman David L. , Winder William W.
Published: April 2010

Liver kinase B1 (LKB1) is a tumor-suppressing protein that is involved in the regulation of muscle metabolism and growth by phosphorylating and activating AMP-activated protein kinase (AMPK) family members. Here we report the development of a myopathic phenotype in skeletal and cardiac muscle-specific LKB1 knockout (mLKB1-KO) mice. The myopathic phenotype becomes overtly apparent at 30–50 wk of age and is characterized by decreased body weight and a proportional reduction in fast-twitch skeletal muscle weight. The ability to ambulate is compromised with an often complete loss of hindlimb function. Skeletal muscle atrophy is associated with a 50–75% reduction in mammalian target of rapamycin pathway phosphorylation, as well as lower peroxisome proliferator-activated receptor-α coactivator-1 content and cAMP response element binding protein phosphorylation (43 and 40% lower in mLKB1-KO mice, respectively). Maximum in situ specific force production is not affected, but fatigue is exaggerated, and relaxation kinetics are slowed in the myopathic mice. The increased fatigue is associated with a 30–78% decrease in mitochondrial protein content, a shift away from type IIA/D toward type IIB muscle fibers, and a tendency ( P = 0.07) for decreased capillarity in mLKB1-KO muscles. Hearts from myopathic mLKB1-KO mice exhibit grossly dilated atria, suggesting cardiac insufficiency and heart failure, which likely contributes to the phenotype. These findings indicate that LKB1 plays a critical role in the maintenance of both skeletal and cardiac function.
Nociceptive Processing by Anterior Cingulate Pyramidal Neurons
Authors: Shyu Bai-Chuang , Sikes Robert W. , Vogt Leslie J. , Vogt Brent A.
Published: April 2010

Although the cingulate cortex is frequently activated in acute human pain studies, postsynaptic responses are not known nor are links between nociceptive afferents, neuronal responses, and outputs to other structures. Intracellular potentials were recorded from neurobiotin-injected, pyramidal neurons in anterior cingulate area 24b following noxious stimulation of the sciatic nerve in anesthetized rabbits. Layer IIIc pyramids had extensive and horizontally oriented basal dendrites in layer IIIc where nociceptive afferents terminate. They had the longest excitatory postsynaptic potentials (EPSPs; 545 ms) that were modulated with hyperpolarizing currents. Pyramids in layer V had an intermediate tuft of oblique apical dendrites in layer IIIc that were 150–350 μm from somata in layer Va and 351–550 μm in layer Vb. Although average EPSP durations were short in layers II–IIIab (222 ± 31), Va (267 ± 65), and Vb (159 ± 31), there were five neurons in layers IIIab–Va that had EPSP durations lasting >300 ms (548 ± 63 ms). Neurons in layers IIIc, Va, and Vb had the highest amplitude EPSPs (6.25, 6.84 ± 0.58, and 6.4 ± 0.47 mV, respectively), whereas those in layers II–IIIab were 5 ± 0.56 mV. Nociceptive responses in layer Vb were complex and some had initial inhibitory postsynaptic potentials with shorter-duration EPSPs. Layers II–IIIab had dye-coupled pyramids and EPSPs in these layers had short durations (167 ± 33 ms) compared with those in layers IIIc–Va (487 ± 28 ms). In conclusion there are two populations of anterior cingulate cortex pyramids with EPSPs of significantly different durations, although their dendritic morphologies do not predict EPSP duration. Short-duration EPSPs are thalamic-mediated, nociceptive responses lasting ≤200 ms. Longer, “integrative” EPSPs are >350 ms and are likely modulated by intracortical axon collateral discharges. These findings suggest that links between nociception and projections to cortical and motor systems are instantaneous because nociceptive responses are generated directly by pyramidal projection neurons in all layers.
Kinetics of Fast Short-Term Depression Are Matched to Spike Train Statistics to Reduce Noise
Authors: Khanbabaie Reza , Nesse William H. , Longtin Andre , Maler Leonard
Published: April 2010

Short-term depression (STD) is observed at many synapses of the CNS and is important for diverse computations. We have discovered a form of fast STD (FSTD) in the synaptic responses of pyramidal cells evoked by stimulation of their electrosensory afferent fibers (P-units). The dynamics of the FSTD are matched to the mean and variance of natural P-unit discharge. FSTD exhibits switch-like behavior in that it is immediately activated with stimulus intervals near the mean interspike interval (ISI) of P-units (∼5 ms) and recovers immediately after stimulation with the slightly longer intervals (>7.5 ms) that also occur during P-unit natural and evoked discharge patterns. Remarkably, the magnitude of evoked excitatory postsynaptic potentials appear to depend only on the duration of the previous ISI. Our theoretical analysis suggests that FSTD can serve as a mechanism for noise reduction. Because the kinetics of depression are as fast as the natural spike statistics, this role is distinct from previously ascribed functional roles of STD in gain modulation, synchrony detection or as a temporal filter.
Phase-Dependent Modulation of Percutaneously Elicited Multisegmental Muscle Responses After Spinal Cord Injury
Authors: Dy Christine J. , Gerasimenko Yury P. , Edgerton V. Reggie , Dyhre-Poulsen Poul , Courtine Grégoire , Harkema Susan J.
Published: April 2010

Phase-dependent modulation of monosynaptic reflexes has been reported for several muscles of the lower limb of uninjured rats and humans. To assess whether this step-phase-dependent modulation can be mediated at the level of the human spinal cord, we compared the modulation of responses evoked simultaneously in multiple motor pools in clinically complete spinal cord injury (SCI) compared with noninjured (NI) individuals. We induced multisegmental responses of the soleus, medial gastrocnemius, tibialis anterior, medial hamstring, and vastus lateralis muscles in response to percutaneous spinal cord stimulation over the Th11–Th12 vertebrae during standing and stepping on a treadmill. Individuals with SCI stepped on a treadmill with partial body-weight support and manual assistance of leg movements. The NI group demonstrated phase-dependent modulation of evoked potentials in all recorded muscles with the modulation of the response amplitude corresponding with changes in EMG amplitude in the same muscle. The SCI group demonstrated more variation in the pattern of modulation across the step cycle and same individuals in the SCI group could display responses with a magnitude as great as that of modulation observed in the NI group. The relationship between modulation and EMG activity during the step cycle varied from noncorrelated to highly correlated patterns. These findings demonstrate that the human lumbosacral spinal cord can phase-dependently modulate motor neuron excitability in the absence of functional supraspinal influence, although with much less consistency than that in NI individuals.
Abnormal Anterior Pretectal Nucleus Activity Contributes to Central Pain Syndrome
Authors: Murray Peter D. , Masri Radi , Keller Asaf
Published: April 2010

Central pain syndrome (CPS) is a debilitating condition that affects a large number of patients with a primary lesion or dysfunction in the CNS, most commonly due to spinal cord injury, stroke, and multiple sclerosis lesions. The pathophysiological processes underlying the development and maintenance of CPS are poorly understood. We have recently shown, in an animal model of CPS, that neurons in the posterior thalamic nucleus (PO) have increased spontaneous and evoked activity. We also demonstrated that these changes are due to suppressed inhibitory inputs from the zona incerta (ZI). The anterior pretectal nucleus (APT) is a diencephalic nucleus that projects on both the PO and ZI, suggesting that it might be involved in the pathophysiology of CPS. Here we test the hypothesis that CPS is associated with abnormal APT activity by recording single units from APT in anesthetized rats with CPS resulting from spinal cord lesions. The firing rate of APT neurons was increased in spinal-lesioned animals, compared with sham-operated controls. This increase was due to a selective increase in firing of tonic neurons that project to and inhibit ZI and an increase in bursts in fast bursting and slow rhythmic neurons. We also show that, in normal animals, suppressing APT results in increased PO spontaneous activity and evoked responses in a subpopulation of PO neurons. Taken together, these findings suggest that APT regulates ZI inputs to PO and that enhanced APT activity during CPS contributes to the abnormally high activity of PO neurons in CPS.
Effects of Category-Specific Costs on Neural Systems for Perceptual Decision-Making
Authors: Fleming Stephen M. , Whiteley Louise , Hulme Oliver J. , Sahani Maneesh , Dolan Raymond J.
Published: April 2010

Perceptual judgments are often biased by prospective losses, leading to changes in decision criteria. Little is known about how and where sensory evidence and cost information interact in the brain to influence perceptual categorization. Here we show that prospective losses systematically bias the perception of noisy face-house images. Asymmetries in category-specific cost were associated with enhanced blood-oxygen-level-dependent signal in a frontoparietal network. We observed selective activation of parahippocampal gyrus for changes in category-specific cost in keeping with the hypothesis that loss functions enact a particular task set that is communicated to visual regions. Across subjects, greater shifts in decision criteria were associated with greater activation of the anterior cingulate cortex (ACC). Our results support a hypothesis that costs bias an intermediate representation between perception and action, expressed via general effects on frontal cortex, and selective effects on extrastriate cortex. These findings indicate that asymmetric costs may affect a neural implementation of perceptual decision making in a similar manner to changes in category expectation, constituting a step toward accounting for how prospective losses are flexibly integrated with sensory evidence in the brain.
Learning Not to Generalize: Modular Adaptation of Visuomotor Gain
Authors: Pearson Toni S. , Krakauer John W. , Mazzoni Pietro
Published: April 2010

When a new sensorimotor mapping is learned through practice, learning commonly transfers to unpracticed regions of task space, that is, generalization ensues. Does generalization reflect fixed properties of movement representations in the nervous system and thereby limit what visuomotor mappings can and cannot be learned? Or does what needs to be learned determine the shape of generalization? We used the broad generalization properties of visuomotor gain adaptation to address these questions. Adaptation to a single gain for reaching movements is known to generalize broadly across movement directions. By training subjects on two different gains in two directions, we set up a potential conflict between generalization patterns: if generalization of gain adaptation indicates fixed properties of movement amplitude encoding, then learning two different gains in different directions should not be possible. Conversely, if generalization is flexible, then it should be possible to learn two gains. We found that subjects were able to learn two gains simultaneously, although more slowly than when they adapted to a single gain. Analysis of the resulting double-gain generalization patterns, however, unexpectedly revealed that generalization around each training direction did not arise de novo, but could be explained by a weighted combination of single-gain generalization patterns, in which the weighting takes into account the relative angular separation between training directions. Our findings therefore demonstrate that the mappings to each training target can be fully learned through reweighting of single-gain generalization patterns and not through a categorical alteration of these functions. These results are consistent with a modular decomposition approach to visuomotor adaptation, in which a complex mapping results from a combination of simpler mappings in a “mixture-of-experts” architecture.
A Version of Hilbert's 13th Problem for Infinitely Differentiable Functions
Authors: Akashi Shigeo , Kodama Satoshi
Published: April 2010

In 1957, Kolmogorov and Arnold gave a solution to the 13th problem which had been formulated by Hilbert in 1900. Actually, it is known that there exist many open problems which can be derived from the original problem. From the function-theoretic point of view, Hilbert's 13th problem can be exactly characterized as the superposition representability problem for continuous functions of several variables. In this paper, the solution to the superposition representability problem for infinitely differentiable functions of several variables is given.
Four Years of Real‐Time GRB Followup by BOOTES‐1B (2005–2008)
Authors: Jelínek Martin , Castro-Tirado Alberto J. , de Ugarte Postigo Antonio , Kubánek Petr , Guziy Sergey , Gorosabel Javier , Cunniffe Ronan , Vítek Stanislav , Hudec René , Reglero Victor , Sabau-Graziati Lola
Published: April 2010

Four years of BOOTES‐1B GRB follow‐up history are summarised for the first time in the form of a table. The successfully followed events are described case by case. Further, the data are used to show the GRB trigger rate in Spain on a per‐year basis, resulting in an estimate of 18 triggers and about 51 hours of telescope time per year for real‐time triggers. These numbers grow to about 22 triggers and 77 hours per year if we include also the GRBs observable within 2 hours after the trigger.
RTSP-based Mobile Peer-to-Peer Streaming System
Authors: Peltotalo Jani , Harju Jarmo , Väätämöinen Lassi , Bouazizi Imed , Curcio Igor D. D.
Published: April 2010

Peer-to-peer is emerging as a potentially disruptive technology for content distribution in the mobile Internet. In addition to the already well-known peer-to-peer file sharing, real-time peer-to-peer streaming is gaining popularity. This paper presents an effective real-time peer-to-peer streaming system for the mobile environment. The basis for the system is a scalable overlay network which groups peer into clusters according to their proximity using RTT values between peers as a criteria for the cluster selection. The actual media delivery in the system is implemented using the partial RTP stream concept: the original RTP sessions related to a media delivery are split into a number of so-called partial streams according to a predefined set of parameters in such a way that it allows low-complexity reassembly of the original media session in real-time at the receiving end. Partial streams also help in utilizing the upload capacity with finer granularity than just per one original stream. This is beneficial in mobile environments where bandwidth can be scarce.
Oscillation Criteria for Second‐Order Delay, Difference, and Functional Equations
Authors: Kikina L. K. , Stavroulakis I. P.
Published: April 2010

Consider the second‐order linear delay differential equation x′′(t) + p(t)x(τ(t)) = 0, t ≥ t0, where p ∈ C([t0, ∞), ℝ+), τ ∈ C([t0, ∞), ℝ), τ(t) is nondecreasing, τ(t) ≤ t for t ≥ t0 and limt→∞τ(t) = ∞, the (discrete analogue) second‐order difference equation Δ2x(n) + p(n)x(τ(n)) = 0, where Δx(n) = x(n + 1) − x(n), Δ2 = Δ∘Δ, p : ℕ → ℝ+, τ : ℕ → ℕ, τ(n) ≤ n − 1, and limn→∞τ(n) = +∞, and the second‐order functional equation x(g(t)) = P(t)x(t) + Q(t)x(g2(t)), t ≥ t0, where the functions P, Q ∈ C([t0, ∞), ℝ+), g ∈ C([t0, ∞), ℝ), g(t)≢t for t ≥ t0, limt→∞g(t) = ∞, and g2 denotes the 2th iterate of the function g, that is, g0(t) = t, g2(t) = g(g(t)), t ≥ t0. The most interesting oscillation criteria for the second‐order linear delay differential equation, the second‐order difference equation and the second‐order functional equation, especially in the case where and for the second‐order linear delay differential equation, and 0 < liminft→∞{Q(t)P(g(t))} ≤ 1/4 and limsupt→∞{Q(t)P(g(t))} < 1, for the second‐order functional equation, are presented.
Tooth Decay in Alcohol Abusers Compared to Alcohol and Drug Abusers
Authors: Dasanayake Ananda P. , Warnakulasuriya Saman , Harris Colin K. , Cooper Derek J. , Peters Timothy J. , Gelbier Stanley
Published: April 2010

Alcohol and drug abuse are detrimental to general and oral health. Though we know the effects of these harmful habits on oral mucosa, their independent and combined effect on the dental caries experience is unknown and worthy of investigation. We compared 363 “alcohol only” abusers to 300 “alcohol and drug” abusers to test the hypothesis that various components of their dental caries experience are significantly different due to plausible sociobiological explanations. After controlling for the potential confounders, we observe that the “alcohol and drug” group had a 38% higher risk of having decayed teeth compared to the “alcohol only” group (). As expected, those who belonged to a higher social class (; 95%  –2.75) and drank wine (; 95%  –2.96) had a higher risk of having more filled teeth. We conclude that the risk of tooth decay among “alcohol only” abusers is significantly lower compared to “alcohol and drug” abusers.
A New Demodulation and Modulation Method Designed for FMCW Radar
Authors: Shen Wei , Wen Biyang
Published: April 2010

An efficient demodulation method
designed for FMCW (Frequency‐Modulated Continuous Wave)
radar is presented. It is a kind of modified DFT (IDFT) algorithm;
the spectrum segment of interest can be easily extracted from
the original signal without calculating the whole DFT/FFT. It
provides fast demodulation and extraction of desired frequency bands in our HFSWR (High‐Frequency Surface Wave Radar)
system. The proposed approach enhances the performances of
radar system and reduces the computing complexity. The new
structure could also be inversely used for signal modulation. And
also arbitrary sampling rate conversion could be achieved with
the combination of forward and backward structure.
Who Benefits Most from College?
Authors: Brand Jennie E. , Xie Yu
Published: April 2010

In this article, we consider how the economic return to a college education varies across members of the U.S. population. Based on principles of comparative advantage, scholars commonly presume that positive selection is at work, that is, individuals who are most likely to select into college also benefit most from college. Net of observed economic and noneconomic factors influencing college attendance, we conjecture that individuals who are least likely to obtain a college education benefit the most from college. We call this theory the negative selection hypothesis. To adjudicate between the two hypotheses, we study the effects of completing college on earnings by propensity score strata using an innovative hierarchical linear model with data from the National Longitudinal Survey of Youth 1979 and the Wisconsin Longitudinal Study. For both cohorts, for both men and women, and for every observed stage of the life course, we find evidence suggesting negative selection. Results from auxiliary analyses lend further support to the negative selection hypothesis.
“Dyading” in the Pediatric Clinic Improves Access to Care
Authors: O'Connor Mary E. , Spinks Cherie , Mestas Tricia A. , Sabel Allison L. , Melinkovich Paul
Published: April 2010

Objective: This project evaluates the effect of “dyading” on pediatric outpatient care. Methods: In “dyading,” the medical assistant (MA) works with the provider in the exam room during the chart review, history taking, and patient education. In sequential care, the patient interacts with the MA, then the provider, then the MA again, with waiting in between. The authors measured visit time (from the MA starting with patient to the end of visit), the mean number of patients seen in a clinic session per provider, and patient satisfaction. Results: After implementation of “dyading,” mean visit time decreased from 37 ± 14 to 25 ± 11 minutes, the mean number of visits/session increased from 8.24 to 9.25, and waiting in the exam room reported by families decreased from 77% to 46%. Conclusions: “Dyading” decreased visit time, which increased the number of patients seen, thereby improving access to care. Patient time in the exam room decreased, which freed up exam rooms.
Racial Variation in Vocational Rehabilitation Outcomes: A Structural Equation Modeling Approach
Authors: Martin Frank H.
Published: April 2010

Numerous studies have indicated racial and ethnic disparities in the vocational rehabilitation (VR) system, including differences in acceptance, services provided, closure types, and employment outcomes. Few of these studies, however, have used advanced multivariate techniques or latent constructs to measure quality of employment outcomes (QEO) or tested hypothesized models for the relationship between race, personal history characteristics, and VR employment outcomes. This study tested an implied conceptual model for the relationship between race, personal history characteristics, and QEO for White, Black, and Hispanic participants in the VR system. The study used structural equation modeling (SEM) and 2006 RSA 911 data. The implied conceptual model was tested for goodness of fit and multiple-group invariance. The final structural model indicated moderate model fit. It also indicated interaction effects for race by gender and for race by public support. Study limitations and suggestions for further research are described.
Education and entrepreneurial activity: A comparison of White and South Asian Men
Authors: Thompson Piers , Jones-Evans Dylan , Kwong Caleb C.Y.
Published: April 2010

Although a large body of literature exists on ethnic entrepreneurship and the relationship between education and entrepreneurial activity, comparatively little work has been undertaken to study the impact that university-level education has upon entrepreneurship within different ethnic minority groups. This article examines the entrepreneurial activity rates for graduates and non-graduates of three differing ethnic groups in the UK and shows that university education has differing influences across ethnic groups. While Pakistani graduate respondents were more likely to be involved in entrepreneurial activities as compared to non-graduates, education appeared to have less impact on increasing the interest in entrepreneurship of Indian adults. This is likely to be a reflection of the differing forces that have traditionally driven individuals from these communities into entrepreneurship, as indicated by a large Pakistani move from necessity-driven entrepreneurship to opportunity-driven entrepreneurship. Therefore, the relationship between entrepreneurship and education varies by ethnic minority group, and policy initiatives to increase entrepreneurship within these groups needs to be adjusted accordingly to be effective.
Is achievement of short-term goals a valid measure of patient progress in inpatient neurological rehabilitation?
Authors: Black Susan Jane , Brock Kim Alison , Kennedy Genevieve , Mackenzie Meaghan
Published: April 2010

Objective: To determine whether the use of short-term goal setting is effective in monitoring patient progress, with regard to achievement of rehabilitation goals for discharge and predicted length of hospital stay.

Design: A prospective observational cohort study.

Setting: An inpatient rehabilitation unit co-located with a large tertiary teaching hospital.

Subjects: Consecutive cases admitted to rehabilitation with a neurological condition and a planned length of stay of three weeks or longer.

Procedure: Discharge and short-term goals and predicted length were set in the initial team meeting. Goals were set, and achievement scored, in the domains of health, social functioning, communication and cognition, mobility and activities of daily living (ADLs) and a composite goal of global function. Actual length of stay and discharge destination were recorded.

Results: Data from 53 consecutive cases were examined, with 45 cases returning home. The median length of stay was 49 days (interquartile (IQ) 30—74). Significant correlations (P<0.05) were demonstrated between short-term goal achievement and discharge goals for continence (ρ = 0.62), transfers (ρ = 0.53), personal activities of daily living (ρ = 0.47) and global function (ρ = 0.62). For those that returned home, there were significant correlations (P<0.05) between adherence to predicted length of stay and achieving their initial goals in transfers (ρ = 0.44), walking (ρ = 0.51) and global function (ρ = 0.55).

Conclusion: Short-term goal setting is a valid measure of patient progress in inpatient neurological rehabilitation and can be used to identify patients who are not progressing as anticipated, facilitating review of the rehabilitation plan.
Polychlorinated biphenyls have inhibitory effect on testicular steroidogenesis by downregulation of P45017α and P450scc
Authors: Han Dae-Yong , Kang Sang-Rim , Park Oh-Sung , Cho Jae-Hyeon , Won Chung-Kil , Park Hyeon-Soo , Park Kwang-Il , Kim Eun-Hee , Kim Gon-Sup
Published: April 2010

Polychlorinated biphenyls (PCBs) are environmental pollutants that are quite toxic to biological systems. This study examined the inhibitory effect of PCB126 and PCB114 on testicular steroidogenesis in male rats. Male Sprague Dawley rats received weekly intraperitoneal injections of PCB126 (0.2 mg/kg) or PCB114 (20 mg/kg) or vehicle (corn oil). Animals from each group were sacrificed at 2, 5 and 8 weeks after the injections. Blood and testis tissue samples were collected for the hormone assay, Western blotting and reverse transcriptase polymerase chain reaction (RT-PCR). The testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were assayed, and the expression levels of the mRNA and proteins associated with the testosterone biosynthesis pathway were measured to determine the effect of PCB126 and PCB114 on testicular steroidogenesis. The results showed that the testis weight was significantly higher in the PCB126-treated rats given eight shots. Moreover, the serum testosterone levels were significantly lower in the PCB126 and PCB114-treated groups than the control. The transcription and translation levels of P45017α and P450scc were significantly lower in the PCB126-treated groups than the control. These results suggest that PCB126 may affect testicular steroidogenesis by downregulating P45017α, P450 scc and have inhibitory effect on the testicular functions.
Effect of alpha-ketoglutarate andN-acetyl cysteine on cyanide-induced oxidative stress mediated cell death in PC12 cells
Authors: Satpute RM , Hariharakrishnan J. , Bhattacharya R.
Published: April 2010

Cyanide is a mitochondrial poison, which is ubiquitously present in the environment. Cyanide-induced oxidative stress is known to play a key role in mediating the neurotoxicity and cell death in rat pheochromocytoma (PC12) cells. PC12 cells are widely used as a model for neurotoxicity assays in vitro. In the present study, we investigated the protective effects of alpha-ketoglutarate (A-KG), a potential cyanide antidote, and N-acetyl cysteine (NAC), an antioxidant against toxicity of cyanide in PC12 cells. Cells were treated with various concentrations (0.625—1.25 mM) of potassium cyanide (KCN) for 4 hours, in the presence or absence of simultaneous treatment of A-KG (0.5 mM) and NAC (0.25 mM). Cyanide caused marked decrease in the levels of cellular antioxidants like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR). Lipid peroxidation indicated by elevated levels of malondialdehyde (MDA) was found to be accompanied by decreased levels of reduced glutathione (GSH) and total antioxidant status (TAS) of the cells. Cyanide-treated cells showed notable increase in caspase-3 activity and induction of apoptotic type of cell death after 24 hours. A-KG and NAC alone were very effective in restoring the levels of GSH and TAS, but together they significantly resolved the effects of cyanide on antioxidant enzymes, MDA levels, and caspase-3 activity. The present study reveals that combination of A-KG and NAC has critical role in abbrogating the oxidative stress-mediated toxicity of cyanide in PC12 cells. The results suggest potential role of A-KG and NAC in cyanide antagonism.
Aripiprazole for the Treatment of Adolescent Tourette’s Syndrome
Authors: Lewis Kendra , Rappa Leonard , Sherwood-Jachimowicz Devon A. , Larose-Pierre Margareth
Published: April 2010

Gilles de la Tourette syndrome (GTS) is a neuropsychiatric, lifelong disorder with onset in childhood. The essential features of this disorder are multiple motor tics and one or more vocalizations. The neurochemical pathophysiology of GTS involves an unknown abnormality in the central dopaminergic system. Atypical antipsychotics, such as aripiprazole, serve as a new therapeutic option for GTS. The authors describe a unique case of Tourette’s syndrome (TS) in an adolescent in which aripiprazole resolved the patient’s symptoms. A 17-year-old, 5′11′′ tall, African American male weighing 220 lbs was diagnosed with TS at 9 years old. By age 16, the patient developed prominent symptoms of intermitted eye blinking, forehead raising, finger snapping, heavy breathing, and head bobbing. Clonidine, in addition to homeopathic remedies ( N-acetylcholine and alpha lipoic acid), was administered to the patient without significant diminution of symptoms. Later, aripiprazole was initiated at 5 mg/d. As a result, noticeable symptomatic improvement occurred within 48 hours. Aripiprazole was titrated over the next 4 weeks to 6.5 mg/d, with significant results. Over the next 6 months, aripiprazole was titrated again to 10 mg/d with additional symptom reduction. This case illustrates a patient who responded to aripiprazole with no reported adverse effects, when standard therapy failed to improve symptoms.
Giving older workers a voice: constraints on the employment of older people in the North West of England
Authors: Porcellato Lorna , Carmichael Fiona , Hulme Claire , Ingham Barbara , Prashar Arvin
Published: April 2010

This article contributes to the literature on older workers and employment, providing a regional perspective on the relationship between age and work. The study is based on interviews in conjunction with occupational-event calendars with 56 individuals in North West England. The primary aim was to gain in-depth understanding of perceived constraints that older people feel hinder their employment prospects within the context of their daily lives. Significant constraints on employment and re-employment were identified and attributed to health, negative perceptions of self, lack of formal human capital and undervaluation of experience, financial disincentives for employers to employ older workers and prevailing ageist attitudes.
Class and employment
Authors: Crompton Rosemary
Published: April 2010

Influential critics still argue that ‘class analysis’ is no longer relevant to the understandings required in ‘reflexive modernity’, while others argue for ‘new’, improved, approaches to the linked topics of class and employment. This article identifies and examines three related critical themes: continuing criticisms of employment-based class measures, the persistence of pseudo-debates (that is, ‘debates’ between authors using different definitions of ‘class’), and the adverse outcomes of the turning away from structural explanations associated with the rejection of employment-derived class. In the concluding sections, the negative consequences of the ‘individualist turn’, and the need for a continuing emphasis on structural measures such as employment class, are emphasised.
Characterisation of grain boundary cluster compactness in austenitic stainless steel
Authors: Rahimi S. , Engelberg D. L. , Marrow T. J.
Published: April 2010

The distribution of grain boundaries of particular crystallographic character can provide descriptive information on the properties of engineering materials. For example, the fraction and connectivity of corrosion susceptible grain boundaries typically correlates with the extent of intergranular corrosion and stress corrosion cracking resistance in sensitised austenitic stainless steels. A parameter defining the cluster compactness is proposed to describe the breakup of the network of corrosion susceptible grain boundaries. It may therefore provide a measure of intergranular stress corrosion cracking resistance. The cluster compactness of the network of random grain boundaries (>Σ29) in electron backscatter diffraction assessments of microstructure is shown to decrease with increasing fraction of Σ3 boundaries. However, the cluster compactness of the network of corroded grain boundaries identified after electrochemical testing is less sensitive to changes in microstructure obtained by thermomechanical processing.
The IgG-specific endoglycosidase EndoS inhibits both cellular and complement-mediated autoimmune hemolysis
Authors: Allhorn Maria , Briceño Juana G. , Baudino Lucie , Lood Christian , Olsson Martin L. , Izui Shozo , Collin Mattias
Published: April 2010

EndoS from Streptococcus pyogenes is an immunomodulating enzyme that specifically hydrolyzes glycans from human immunoglobulin G and thereby affects antibody effector functions. Autoimmune hemolytic anemia is caused by antibody-mediated red blood cell (RBC) destruction and often resists treatment with corticosteroids that also cause frequent adverse effects. We show here that anti-RhD (anti-D) and rabbit anti–human-RBC antibodies (anti-RBC) mediated destruction of RBC, ie, phagocytosis, complement activation, and hemolysis in vitro and in vivo was inhibited by EndoS. Phagocytosis by monocytes in vitro was inhibited by pretreatment of anti-D with EndoS before sensitization of RBCs and abrogated by direct addition of EndoS to blood containing sensitized RBCs. The toxic effects of monocytes stimulated with anti-D–sensitized RBCs, as measured by interleukin-8 secretion and oxygen metabolite production, was restrained by EndoS. Agglutination of RBCs and complement-mediated hemolysis in vitro in whole human blood caused by rabbit anti-RBCs was inhibited by EndoS. Development of anemia in mice caused by a murine anti-RBC immunoglobulin G2a monoclonal autoantibody and complement activation and erythrophagocytosis by Kupffer cells in the liver were reduced by EndoS. Our data indicate that EndoS is a potential therapeutic agent that might be evaluated as an alternative to current treatment regimens against antibody-mediated destruction of RBCs.
Bax Inhibitor-1 down-regulation in the progression of chronic liver diseases
Authors: Kotsafti Andromachi , Farinati Fabio , Cardin Romilda , Burra Patrizia , Bortolami Marina
Published: April 2010

Background

Bax inhibitor-1 (BI-1) is an evolutionary conserved endoplasmic reticulum protein that, when overexpressed in mammalian cells, suppresses the apoptosis induced by Bax, a pro-apoptotic member of the Bcl-2 family. The aims of this study were: (1) to clarify the role of intrinsic anti- and pro-apoptotic mediators, evaluating Bax and BI-1 mRNA and protein expressions in liver tissues from patients with different degrees of liver damage; (2) to determine whether HCV and HBV infections modulate said expression.

Methods

We examined 62 patients: 39 with chronic hepatitis (CH) (31 HCV-related and 8 HBV-related); 7 with cirrhosis (6 HCV-related and 1 HBV-related); 13 with hepatocellular carcinoma (HCC) [7 in viral cirrhosis (6 HCV- and 1 HBV-related), 6 in non-viral cirrhosis]; and 3 controls. Bax and BI-1 mRNAs were quantified by real-time PCR, and BI-1 protein expression by Western blot.

Results

CH tissues expressed significantly higher BI-1 mRNA levels than cirrhotic tissues surrounding HCC (P < 0.0001) or HCC (P < 0.0001). Significantly higher Bax transcripts were observed in HCV-genotype-1-related than in HCV-genotype-3-related CH (P = 0.033). A positive correlation emerged between BI-1 and Bax transcripts in CH tissues, even when HCV-related CH and HCV-genotype-1-related CH were considered alone (P = 0.0007, P = 0.0005 and P = 0.0017, respectively).

Conclusions

BI-1 expression is down-regulated as liver damage progresses. The high BI-1 mRNAs levels observed in early liver disease may protect virus-infected cells against apoptosis, while their progressive downregulation may facilitate hepatocellular carcinogenesis. HCV genotype seems to have a relevant role in Bax transcript expression.
Changes of tau profiles in brains of the hamsters infected with scrapie strains 263 K or 139 A possibly associated with the alteration of phosphate kinases
Authors: Wang Gui-Rong , Shi Song , Gao Chen , Zhang Bao-Yun , Tian Chan , Dong Chen-Fang , Zhou Rui-Min , Li Xiao-Li , Chen Cao , Han Jun , Dong Xiao-Ping
Published: April 2010

Background

Phospho-tau deposition has been described in a rare genetic human prion disease, Gerstmann-Sträussler-Scheinker syndrome, but is not common neuropathological picture for other human and animal transmissible spongiform encephalopathies (TSEs). This study investigated the possible changes of tau and phosphorylated tau (p-tau, at Ser396, Ser404, and Ser202/Thr205) in scrapie experimental animals.

Methods

The profiles of tau and p-tau (p-tau, at Ser396, Ser404, and Ser202/Thr205) in the brain tissues of agents 263K- or 139A-infected hamsters were evaluated by Western blots and real-time PCR. Meanwhile, the transcriptional and expressive levels of GSK3β and CDK5 in the brains were tested.

Results

The contents of total tau and p-tau at Ser202/Thr205 increased, but p-tau at Ser396 and Ser404 decreased at the terminal stages, regardless of scrapie strains. Transcriptional levels of two tau isoforms were also increased. Additionally, it showed higher CDK5, but lower GSK3β transcriptional and expressive levels in the brains of scrapie-infected animals. Analysis of brain samples collected from different times after inoculated with agent 263 K revealed that the changes of tau profiles and phosphate kinases were time-relative events.

Conclusion

These data suggest that changes of profiles of p-tau at Ser396, Ser404 and Ser202/Thr205 are illness-correlative phenomena in TSEs, which may arise of the alteration of phosphate kinases. Alteration of tau, p-tau (Ser396, Ser404, and Ser202/Thr205), GSK3β and CDK5 were either intermediate or consequent events in TSE pathogenesis and proposed the potential linkage of these bioactive proteins with the pathogenesis of prion diseases.
Tropomyosin3 overexpression and a potential link to epithelial-mesenchymal transition in human hepatocellular carcinoma
Authors: Choi Hye-Sun , Yim Seon-Hee , Xu Hai-Dong , Jung Seung-Hyun , Shin Seung-Hun , Hu Hae-Jin , Jung Chan-Kwon , Choi Jong Young , Chung Yeun-Jun
Published: April 2010

Background

Since hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide, it is still important to understand hepatocarcinogenesis mechanisms and identify effective markers for tumor progression to improve prognosis. Amplification and overexpression of Tropomyosin3 (TPM3) are frequently observed in HCC, but its biological meanings have not been properly defined. In this study, we aimed to elucidate the roles of TPM3 and related molecular mechanisms.

Methods

TPM3-siRNA was transfected into 2 HCC cell lines, HepG2 and SNU-475, which had shown overexpression of TPM3. Knockdown of TPM3 was verified by real-time qRT-PCR and western blotting targeting TPM3. Migration and invasion potentials were examined using transwell membrane assays. Cell growth capacity was examined by colony formation and soft agar assays.

Results

Silencing TPM3 resulted in significant suppression of migration and invasion capacities in both HCC cell lines. To elucidate the mechanisms behind suppressed migration and invasiveness, we examined expression levels of Snail and E-cadherin known to be related to epithelial-mesenchymal transition (EMT) after TPM3 knockdown. In the TPM3 knockdown cells, E-cadherin expression was significantly upregulated and Snail downregulated compared with negative control. TPM3 knockdown also inhibited colony formation and anchorage independent growth of HCC cells.

Conclusions

Based on our findings, we formulate a hypothesis that overexpression of TPM3 activates Snail mediated EMT, which will repress E-cadherin expression and that it confers migration or invasion potentials to HCC cells during hepatocarcinogenesis. To our knowledge, this is the first evidence that TPM3 gets involved in migration and invasion of HCCs by modifying EMT pathway.
Establishment and identification of a rabbit model of peritoneal carcinomatosis from gastric cancer
Authors: Mei Lie-Jun , Yang Xiao-Jun , Tang Li , Hassan Alaa Hammed al-shammaa , Yonemura Yutaka , Li Yan
Published: April 2010

Background

Gastric cancer peritoneal carcinomatosis is a common clinical problem, but there are no suitable large animal models to study this problem. This study was to establish a stable rabbit peritoneal carcinomatosis model of gastric cancer using VX2 tumor, and analyze the clinico-pathological features.

Methods

VX2 tumor was implanted into 36 New Zealand rabbits by 3 methods: laparotomic orthotopic injection of cancer cells into the submucosal layer of the stomach (Group A), laparotomic implantation of tumor tissue into the greater omentum immediately beneath the gastric antrum (Group B), and percutaneous injection of tumor cells directly into the peritoneal cavity (Group C), 12 rabbits in each group. The animals were closely observed and detailed clinico-pathological studies were conducted.

Results

The success rates of peritoneal carcinomatosis formation were 100% (12/12), 91.7% (11/12) and 58.3% (7/12), respectively, for Groups A, B and C (P = 0.019, A versus C; P = 0.077, B versus C; P = 0.500, A versus B, Fisher's exact test). Two weeks after submucosal cancer cells injection in Group A, ulcerative gastric cancer with peritoneal carcinomatosis showed typical VX2 tumor pathology, with widespread intraperitoneal metastatic nodules, bloody ascites and perspicuous pulmonary metastases. The clinico-pathological progression pattern was very similar to patients of advanced gastric cancer with peritoneal carcinomatosis. Groups B and C showed similar pattern of cancer progression, but less aggressive.

Conclusions

First large animal model of peritoneal carcinomatosis from gastric cancer has been established by laparotomic orthotopic injection of VX2 cancer cells into the submucosal layer of the stomach, providing a more suitable model for surgical interventional studies. The clinico-pathological features of this model resemble human peritoneal carcinomatosis.
Steroidogenic factor-1 (SF-1) gene mutation as a frequent cause of primary amenorrhea in 46,XY female adolescents with low testosterone concentration
Authors: Philibert Pascal , Leprieur Elodie , Zenaty Delphine , Thibaud Elisabeth , Polak Michel , Frances Anne-Marie , Lespinasse James , Raingeard Isabelle , Servant Nadège , Audran Françoise , Paris Françoise , Sultan Charles
Published: April 2010

Background

Primary amenorrhea due to 46,XY disorders of sex differentiation (DSD) is a frequent reason for consultation in endocrine and gynecology clinics. Among the genetic causes of low-testosterone primary amenorrhea due to 46,XY DSD, SRY gene is reported to be frequently involved, but other genes, such as SF1 and WT1, have never been studied for their prevalence.

Methods

We directly sequenced SRY, SF1 and WT1 genes in 15 adolescent girls with primary amenorrhea, low testosterone concentration, and XY karyotype, to determine the prevalence of mutations. We also analyzed the LH receptor gene in patients with high LH and normal FSH concentrations.

Results

Among the 15 adolescents with primary amenorrhea and low testosterone concentration, we identified two new SRY mutations, five new SF1 mutations and one new LH receptor gene mutation. Our study confirms the 10-15% prevalence of SRY mutations and shows the high prevalence (33%) of SF1 abnormalities in primary amenorrhea due to 46,XY DSD with low plasma testosterone concentration.

Conclusions

The genetic analysis of low-testosterone primary amenorrhea is complex as several factors may be involved. This work underlines the need to systematically analyze the SF1 sequence in girls with primary amenorrhea due to 46,XY DSD and low testosterone, as well as in newborns with 46,XY DSD.