Mechanical Disturbance Research Articles

Integration of proprioceptive and visual feedback during online control of reaching.

Visual and proprioceptive feedback both contribute to perceptual decisions, but it remains unknown how these feedback signals are integrated together or consider factors such as delays and variance during online control. We investigated this question by having participants reach to a target with randomly applied mechanical and/or visual disturbances. We observed that the presence of visual feedback during a mechanical disturbance did not increase the size of the muscle response significantly but did decrease variance, consistent with a dynamic Bayesian integration model. In a control experiment, we verified that vision had a potent influence when mechanical and visual disturbances were both present but opposite in sign. These results highlight a complex process for multisensory integration, where visual feedback has a relatively modest influence when the limb is mechanically disturbed, but a substantial influence when visual feedback becomes misaligned with the limb.NEW & NOTEWORTHY Visual feedback is more accurate, but proprioceptive feedback is faster. How should you integrate these sources of feedback to guide limb movement? As predicted by dynamic Bayesian models, the size of the muscle response to a mechanical disturbance was essentially the same whether visual feedback was present or not. Only under artificial conditions, such as when shifting the position of a cursor representing hand position, can one observe a muscle response from visual feedback.

Effects of mire disturbance by Sika deer on physico-chemical properties of peat soils and greenhouse gas flux in Ozegahara Mire, Japan

ABSTRACT Ozegahara Mire is the largest alpine mire in Japan. The mire has been preserved as the precious peatland ecosystem with high ecological diversity. After the late 20th century, the mire has been exposed to ecosystem disturbance by mire flooding due to heavy rain as well as invaded Sika deer. Especially, browsing and digging of the mire vegetation by invaded Sika deer have caused considerable impacts on not only vegetation but also physicochemical properties of the mire peat soil. Little information has been published on the effect of flooding and Sika deer disturbance on greenhouse gas emission from the mire. This study aims to provide investigation about the effects of Sika deer disturbance on the soil physicochemical properties and the emission of carbon dioxide (CO2) and methane (CH4) from Ozegahara Mire. Soil and gas samples were collected at 14 fixed plots on 5 sites with and without mire disturbance by Sika deer at eastern Naka-tashiro of Ozegahara Mire through 5 months of 2019 (June to October). Groundwater levels at the study sites were measured each month using hand measurements and continuously using water level loggers. Soil samples were collected with a trowel and gas samples were collected in cylindrical polyvinyl chloride chambers installed on the study sites. Subsequent physicochemical analysis of the soil samples and the gas chromatographic analysis of the gas samples were conducted at the laboratory. Groundwater level displayed similar seasonal change in two sites, being affected by precipitation. The concentrations of NH4 + nitrogen in the disturbed sites were higher than those in the undisturbed sites. Mechanical disturbance of the peat soils by deer resulted in mineralization of organic matter. CO2 and CH4 fluxes from the disturbed sites were lower than those from the undisturbed sites where highest fluxes were recorded in August. Negative correlation was found between CO2 and groundwater level (r = −0.327, p < 0.05), suggesting the importance of groundwater level in greenhouse gas flux. These results indicate the marked influences of the mire disturbance by Sika deer on physicochemical properties of the peat soils and greenhouse gas fluxes at Ozegahara Mire.

Host Factors in Dysregulation of the Gut Barrier Function during Alcohol-Associated Liver Disease.

Chronic alcohol consumption and alcohol-associated liver disease (ALD) represent a major public health problem worldwide. Only a minority of patients with an alcohol-use disorder (AUD) develop severe forms of liver disease (e.g., steatohepatitis and fibrosis) and finally progress to the more advanced stages of ALD, such as severe alcohol-associated hepatitis and decompensated cirrhosis. Emerging evidence suggests that gut barrier dysfunction is multifactorial, implicating microbiota changes, alterations in the intestinal epithelium, and immune dysfunction. This failing gut barrier ultimately allows microbial antigens, microbes, and metabolites to translocate to the liver and into systemic circulation. Subsequent activation of immune and inflammatory responses contributes to liver disease progression. Here we review the literature about the disturbance of the different host defense mechanisms linked to gut barrier dysfunction, increased microbial translocation, and impairment of liver and systemic inflammatory responses in the different stages of ALD.

Cisplatin fastens chromatin irreversibly even at a high chloride concentration.

Cisplatin is one of the most potent anti-cancer drugs developed so far. Recent studies highlighted several intriguing roles of histones in cisplatin's anti-cancer effect. Thus, the effect of nucleosome formation should be considered to give a better account of the anti-cancer effect of cisplatin. Here we investigated this important issue via single-molecule measurements. Surprisingly, the reduced activity of cisplatin under [NaCl] = 180 mM, corresponding to the total concentration of cellular ionic species, is still sufficient to impair the integrity of a nucleosome by retaining its condensed structure firmly, even against severe mechanical and chemical disturbances. Our finding suggests that such cisplatin-induced fastening of chromatin can inhibit nucleosome remodelling required for normal biological functions. The in vitro chromatin transcription assay indeed revealed that the transcription activity was effectively suppressed in the presence of cisplatin. Our direct physical measurements on cisplatin-nucleosome adducts suggest that the formation of such adducts be the key to the anti-cancer effect by cisplatin.

INFLUENCE OF MELATONIN ON AGE-RELATED CHANGES IN CARBOHYDRATE METABOLISM AND ANTIOXIDANT CAPACITY IN THE BLOOD OF ALLOXAN DIABETIC RATS

Melatonin and its metabolites have potent antioxidant/anti-inflammatory properties, and they have proven to be highly effective in a variety of disorders linked to inflammation and oxidative stress. The object of this experimental research was to ascertain the influence of aging on the level of basal glycemia and activities of glucose-6-phosphate dehydrogenase [EC1.1.1.49], pyruvate kinase [EC 2.7.1.40] and glutathione reductase [EC1.6.4.2] in erythrocytes of alloxan diabetic rats on the background of melatonin injections. Methods: We used 100 male Wistar rats, two age groups: the - 2-month (adult), and II - 4-month (old). Alloxan diabetes was evoked via injecting the rats with a 5% solution of alloxan monohydrate intraperitoneally in a dose of 170 mg/kg. Four days after diabetes induction, rats were divided into diabetic (untreated) and melatonin-diabetic group (10 mg/kg, daily and intraperitoneally for six weeks). Blood was taken from the tail vein evaluate the basal glycemia on 5-th and 47-th day after the injection of alloxan. Rats were sacrificed at the 47-th day of the experiment accordance with the ethical treatment of animals. Determinations of the enzymes activities were by standard methods. Statistical analysis was performed using Statistica 10 StatSoft Inc. Results. The level of basal glycemia on the fifth day of the experiment in animals of both groups increased on average by 115% from baseline values. We founded that on 47-th day this index was higher in group of old rats on 20% more than in adult rats. Pyruvate kinase activity in erythrocytes of adult and old animals with diabetes decreased by 34% and 51% respectively compared with the control. glucose-6-phosphate dehydrogenase activity in erythrocytes of adult and old animals with diabetes decreased by 25% and 44% respectively compared with the control on 47-th day. The changes may be the result of age-related disorders of glucose metabolism due to disturbances in free radical mechanisms. Glutathione reductase activity in erythrocytes of adult and old animals with diabetes decreased by 30% and 36% respectively compared with the control on 47-th day. A 42-days injection of melatonin to the alloxan diabetic rats of both groups contributed to a normalization of the level of basal glycemia, the activities of pyruvate kinase and glutathione reductase in the rat blood, as well as to a considerable increase of the activity of glucose-6-phosphate dehydrogenase, whose level exceeded by average 9% this particular index in the control group of animals. Under the influence of melatonin increase activity of glucose-6-phosphate dehydrogenase in the blood of rats may be due to the increasing number of substrate for glucose-6-phosphate dehydrogenase (stimulating the flow of glucose into cells and its phosphorylation) and direct action. Conclusion. In this case melatonin probably increases use of glucose for regeneration of NADPH2 and aerobic oxidation of glucose that indicate an acceleration of antioxidative protection and energy production in blood of adult and old diabetic rats.

Influence of mechanical action on the development of electrodynamic phenomena in ionized gas

A special feature of this work is the study of the effect of mechanical mode disturbances on the discharge and plasma flow. It is found that the mechanical impact of a shock wave in a dense gas in an electric field of high intensity almost to the ignition voltage causes an electrical “breakdown” as current peaks. The ultrasonic effect on the flow of the reacting plasma of the air as shown by the analytical study of the thin layer of the plasma flow changes the type of flow.

Transverse Stress Applying Technology for High-Current Superconducting Conductors Testing

High-current superconducting conductors are widely used in fusion magnets, high energy accelerators and high magnetic field facilities. It's urgent to carry out experimental research on DC performance of new conductors to meet the development needs of these magnets. A new test facility with maximum background magnetic field of 6 T and maximum sample current of 30 kA is developed. For the purpose of preventing the sample conductors from premature quenches due to mechanical disturbance under the magnetic field, it is necessary to apply a certain transverse stress to the sample through sample support. In this paper, two different kinds of transverse stress applying technologies, active method and passive method, are developed. The general design of these two kinds of sample supports, the influence of cooling and powering process on sample transverse stress with active sample support, the assembly gap analysis of passive sample support are described in detail. The used sample supports respectively for Nb-Ti Rutherford cable, MgB <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> Cable-in-conduit Conductors (CICC) and Bi-2212 sub-cable testing are presented. Comprehensively considering the stability margin of conductor sample and the influence of transverse stress on performance of the sample, the selection basis of transverse stress applying at room temperature is also summarized.

The Effectiveness of Acupuncture Therapy in Patient with Hemorrhoid: A Case Report

Background: Hemorrhoid is an anorectal disease due to mechanical disturbances in the anal cushion and hemorrhoid venous plexus blood flow obstruction. Symptoms that often accur are bleeding, pain, prolapse, itching, and mucus discharge. Acupuncture is non-pharmacological therapeutic modalities that has been shown to improve hemorrhoid symptoms.&#x0D; Case: A 37-year-old woman complained of hemorroid lump with pain since last 1 year. Physical examination showed a reddish hemorrhoid prolapse, about 1.5 cm in the posterior anal without bleeding. The pain score with NRS is 4. Acupuncture therapy was performed 3 times a week at acupoints GV20, TE6, LU6, ST25, BL34, ST36, EX-UE2 and BL57. Then given continuous wave electrical stimulation, 4 Hz, 30 minutes retention. After 11 treatments, pain disappeared with NRS 0 and lump was reduced to about 0.5 cm.&#x0D; Conclusion: Acupuncture can improve the symptoms of hemorrhoids, which are seen by the relief of pain and the reduction of lumps.&#x0D; &#x0D; Keywords: Acupuncture, hemorrhoid, hemorrhoid pain, hemorrhoid prolapse

Immediate Effects of Kinesio Taping on Rectus Abdominis Diastasis in Postpartum Women-Preliminary Report.

Background: Rectus abdominis diastasis (RAD) is an excessive divarication of the rectus abdominis muscle with concurrent stretching and thinning of the linea alba, which occurs due to mechanical and functional disturbances in the anterior abdominal wall and the whole body. The primary objective of this study is a palpation assessment of RAD in postpartum women before and after the application of KT tapes and a subsequent comparison of the results with those from a sham intervention group. Methods: A randomized clinical trial was conducted in the Physical Therapy Department at Wroclaw Medical University. The participants were randomly assigned to one of two groups: the KT group (intervention), in which KT tapes were applied (48 h intervention) and the sham KT group (control, sham intervention), in which non-stretch tapes were used (cloth surgical tape, 48 h intervention). In all participants, a palpation assessment of RAD was conducted and the inter-recti distance was measured using a digital caliper at three sites: at the umbilicus and 4.5 cm above and below it. Measurements were taken before and after the intervention. Results: The gathered results show a statistically significant reduction in rectus abdominis diastasis at each of the observed sites after the application of KT tapes in the intervention group (p < 0.05). In the intergroup comparison, a statistically significantly lower RAD (at umbilicus) was found after the intervention (p = 0.005) in KT group. Conclusions: the application of KT tapes using the corrective technique can contribute to reducing RAD in women up to 12 months after delivery.

Bone conduction pathways confer directional cues to salamanders.

Sound and vibration are generated by mechanical disturbances within the environment, and the ability to detect and localize these acoustic cues is generally important for survival, as suggested by the early emergence of inherently directional otolithic ears in vertebrate evolutionary history. However, fossil evidence indicates that the water-adapted ear of early terrestrial tetrapods lacked specialized peripheral structures to transduce sound pressure (e.g. tympana). Therefore, early terrestrial hearing should have required nontympanic (or extratympanic) mechanisms for sound detection and localization. Here, we used atympanate salamanders to investigate the efficacy of extratympanic pathways to support directional hearing in air. We assessed peripheral encoding of directional acoustic information using directionally masked auditory brainstem response recordings. We used laser Doppler vibrometry to measure the velocity of sound pressure-induced head vibrations as a key extratympanic mechanism for aerial sound reception in atympanate species. We found that sound generates head vibrations that vary with the angle of the incident sound. This extratympanic pathway for hearing supports a figure-eight pattern of directional auditory sensitivity to airborne sound in the absence of a pressure-transducing tympanic ear.

Short-term dynamic responses of soil properties and soil fauna under contrasting tillage systems

Achieving sustainability is a worldwide current concern in agriculture that brings important challenges but also opportunities for rethinking agroecosystems. While many studies focused on tillage effects upon soil organisms, few of them have considered this into a temporal framework. In a study conducted in actual field conditions, we evaluated at short-term (7 months) the dynamic of several abiotic and biotic soil parameters under contrasting tillage systems. We hypothesised that (1) the reduction and especially the stopping of the soil mechanical perturbation lead overall to an improvement of the soil physical structure and the food resources available for soil fauna. (2) According to their specific ecological requirements, Collembola and Earthworms will show different dynamics of responses following alleviation of soil mechanical perturbation. (3) For a single group (either Collembola or earthworms), differences between tillage systems are dependent on the sampling period. We used a field set-up held on the INRA experimental station of Estrées-Mons (North of France). Three tillage systems were investigated: conventional tillage (with the soil inverted up to 25 cm depth) reduced tillage (limited to the first 7–8 cm depth) and no-tillage. Each treatment was replicated 4 times randomly (3 × 4 = 12 plots in total). Collembola and earthworms were sampled at each plot using standard methods. During the course of the experiment, two tillage operations were performed one in mid-March and one in mid-May. Samplings of soil fauna were performed on a regular basis according to tillage operation: 1 day before, and respectively 1; 7; 30; 49; 56; 104; 210 days after. Abiotic parameters (bulk density, SOC stock, Mean Weight Diameter (MWD) and aggregates size) and microflora (microbial and fungal biomass and their activity) were also monitored and used as explaining factors. Our findings showed that slightly reducing the intensity of soil mechanical perturbation, did not favour soil fauna. But, when stopping tillage, population sizes of earthworm and Collembola increased. This is related to the improvement of the distribution of, and accessibility to, organic matter as a basic food source (SOC stock, microbial and fungal biomass and their potential C mineralisation activity), the physical structure of the soil and the distribution of pore sizes as a space life (bulk density, MWD and aggregates size). Our kinetic study has shown that the different groups of soil fauna respond differently to mechanical soil disturbance. Overall, conservation tillage can foster one of the numerous services provided by the soil compartment, namely the soil biodiversity and therefore improve soil quality and health.

Control constraint‐based optimal PID‐PSS design for a widespread operating power system using SAR algorithm

Nowaday's tuning of a power system stabilizer (PSS) over widespread operating conditions to safeguard the power system stability is a challenging task to power engineers. Therefore, there is a need to develop a robust and reliable PSS to produce clean and sustainable energy for power generation. In this research work, a control constraint-based optimal proportional, integral, and derivative (PID)-PSS using nature-inspired search optimization technique called search-and-rescue algorithm (SAR) is developed to suppress the low-frequency oscillations (LFOs) in a power system operating in a wide range of operational states. The wide variations in the system operating conditions are captured by the coefficients of interval polynomial and then simple inequality conditions are attained to assure the power system stability. Furthermore, a multi-objective function (MOF) is formulated to enhance the operation of the proposed PID-PSS for a widespread operating state and also to encounter practical working conditions. A human search-based optimization algorithm, that is, SAR, is implemented to acquire the PID-PSS gains. The design resilience of the proposed PID-PSS is investigated using two test cases of a one-machine infinite-bus (OMIB) power system operating at a widespread and also verified for static and dynamic mechanical disturbances. The simulation results show that the proposed optimal PID-PSS controller outperforms the most prominent controllers in the recent literature.

Effects of mire disturbance by Sika deer on nitrogen fixation and denitrification in Ozegahara Mire, Japan

ABSTRACT Ozegahara Mire is the largest alpine mire in Japan, and it has been preserved as the precious peatland ecosystem under oligotrophic condition. However, after the late 20 century, the mire has been exposed to ecosystem disturbance by invaded Sika deer. Browsing and digging of the mire vegetation by Sika deer have given considerable impacts on not only vegetation but also biochemical property of the peat soil, resulting in the changes in microbiological activities and nutrient dynamics. However, little information has been provided about the effect of deer disturbance on nitrogen (N) dynamics in the mire. This study aims to provide information about the effects of deer disturbance on nitrogen dynamic including N2 fixation and denitrification in Ozegahara Mire. Soil samples were collected at 6 plots on 2 sites with and without mire disturbance by Sika deer at eastern Naka-Tashiro of Ozegahara mire in July 2018. Mineral N contents and other physicochemical properties of the soil samples were measured. N2 fixation and denitrification activities of the soil samples were also measured at different incubation temperatures (15, 20 or 25°C) under either aerobic or anaerobic conditions by acetylene reduction activity (ARA) and inhibition methods, respectively. As results, the ARA in the disturbed sites were lower than those in the undisturbed sites and also lower under aerobic condition than anaerobic condition. Negative correlation was found between ARA and ammonium N in the soil (R 2 = 0.353, p< 0.05), suggesting that mechanical disturbance of the peat soils by deer enhanced mineralization of organic N to suppress N2 fixation. ARA was increased by elevated incubation temperature in the undisturbed sites, while no change in the disturbed sites. Denitrification activities was not affected by the disturbance by Sika deer, while higher under aerobic condition than in anaerobic condition, and in higher temperature than lower temperature. Multi-regression analysis of ARA affecting factors revealed that ARA was significantly influenced by temperature, ammonium N and disturbance. These results indicate the marked influences of the mire disturbance by Sika deer on N2 fixation and denitrification activities of the peat soils and N dynamics in Ozegahara Mire.

Type 2 diabetes mellitus and risk of Alzheimer's disease

The evidences like biological and epidemiological support a link between type 2 diabetes mellitus (DM2) and Alzheimer's disease (AD). Persons with diabetes have a higher rate of cognitive decline and an increased risk of developing dementia of all types. Cognitive deficits in diabetic people get mainly affect the psychomotor efficiency areas like attention, learning and memory, mental ability, flexibility and speed, and executive function. The concrete epidemiological association has suggested the existence of a pathophysiological link. The factors of increased cognitive decline in DM2, however, are less clear. Increased atrophy of cortical and subcortical areas had clearly shows after controlling for diabetic vascular disease and inadequate circulation in cerebral areas.Most recent studies have focused on the role of insulin and insulin resistance as possible links between diabetes and AD. Disturbances in brain insulin signaling mechanisms may contribute to the molecular, biochemical, and histopathological lesions in AD. Hyperglycemia itself is a risk factor for cognitive dysfunction and dementia. Hypoglycemia may also have deleterious effects on cognitive function. Recurrent symptomatic and asymptomatic hypoglycemic episodes have been suggested to cause sub-clinical brain damage, and permanent cognitive impairment. Future trials are required to clarify the mechanistic link, to address the question whether cognitive decline may be prevented by an adequate metabolic control, and to elucidate the role of drugs that may cause hypoglycemic episodes.

Random response of a viscoelastic dielectric elastomer spherical balloon

The viscoelastic behavior of the dielectric elastomers (DEs) plays an important role in the time-dependent mechanical deformation. The increasingly demands to precise utilities and controls of the DEs are motivating the researchers to insight into the influence of the viscoelasticity on the dynamical response. In this paper, the random response of a DE spherical balloon subjected to electrical and/or mechanical disturbances is analytically studied. Based on a rheological model of two parallel units, the governing equations of the stretch ratio of the deformed and undeformed radius of the spherical balloon are derived from the Lagrange equation. Firstly, the influences of the pressure in balloon and the voltage on the membrane on the equilibrium positions are discussed. The big pressure and high voltage will both induce static instability. Then, by expanding the motion equations around the static equilibrium position, the relation of the resonant frequency with the viscoelasticity are revealed. Finally, an approximation procedure is adopted, which pave the way to adopt the stochastic averaging. The probabilistic density function (PDF) of the stretch ratio around the equilibrium position is obtained. The influences of system parameters, i.e., viscoelasticity, voltage, pressure, on the probability distribution are investigated in detail. The accuracy of the proposed procedure are also been evaluated by the Monte-Carlo simulation (MCS).

Analysis of Aero-Optical Jitter in Convective Turbulent Flows Using Stitching Method

In the typical analysis of aero-optical wave-front data, the three lowest-order spatial modes (namely, unsteady piston as well as and tilts) are removed from the experimentally measured wave fronts. These modes are commonly corrupted by mechanical disturbances. In this work, an algorithm called the stitching method was developed that takes advantage of the advective nature of the optical aberrations caused by turbulent structures to recover the unsteady global X-tilt and piston modes from experimental time-resolved wave fronts. One-dimensional modeling and related uncertainty analysis showed that for the wave fronts collected with sufficient sampling frequency, the algorithm is able to correctly recover the aero-optical component of the unsteady X tilt. In this manner, the time series of true wave fronts can be recovered. To further validate the stitching method, spatiotemporal wave-front measurements were conducted on a Mach 0.6/0.1 forced shear layer. The predicted results for the rms of the aero-optical X tilt from the stitching method agree well with the modeled results. Since the stitching method recovers the time series of the aero-optical global X tilt, the global tilt spectra were also computed and presented. This information can be used by system designers to specify the requirements for adaptive-optics system components, such as fast steering mirrors in airborne directed energy systems.

Signal denoising of viral particle in wide-field photon scattering parametric images using deep learning

Polarization parametric indirect microscopic imaging (PIMI) can obtain anisotropic nanoscale structural information of the sample by utilizing a polarization modulated illumination scheme and fitting the far-field variation of polarization states of the scattered photons. The rich scattering information of PIMI images can be exploited for identification of viral particles, aiming for early infection screening of viruses. Accurate processing and analysis of PIMI results is an important step for obtaining structural feature information of virus. However, the systematic noise, mainly caused by the mechanical or electrical disturbance from the modulation of the illumination when taking raw images, fairly degrades the image resolution and contrast, making the analysis of results more time-consuming with higher error rate. To achieve efficient noise suppressing in the obtained PIMI images, we developed a neural network-based framework of algorithms. A fairly effective denoising method particularly for PIMI imaging was proposed based on a U-Net. From both the numerical and experimental results, the developed method significantly improves the quality of PIMI images with the best capability of noise removal compared with the traditional denoising algorithms and other neural network architecture. This method can be employed as a fixed preprocessing procedure of raw PIMI images, which is greatly helpful to realize rapid, accurate and programmed analysis of results in PIMI applications.

EVALUATION OF OXIDATIV STATE PROTEINASE-INHIBITORY SYSTEM AND ENDOTOXICOSIS IN PATIENTS WITH COPD

The aim of the work was to study the relationship between indicators of proteinase-inhibitory system, oxidative stress and endotoxicosis in patients with COPD. 67 patients with COPD, men with an average age of 53.12.2 years, with the duration of the disease on average 12.51.7 years, in the stable phase of the pathological process with II-IV degrees of ventilation disorders according to the GOLD were examined. The activation of trypsin as an indicator of the state of the proteinase-inhibitory system involved in bronchopulmonary diseases pathogenesis, a probable decrease in the activity of its obligate α1-antitrypsin inhibitor, lipid peroxidation secondary metabolites accumulation, total antioxidant activity, molecules of average weight level increase in serum of COPD patients were found. At the examined patients endotoxicosis with initiation of disturbances of mechanisms of recovery in bronchopulmonary system is noted. Together, these events lead to a vicious circle of persistent inflammation, accompanied by chronic oxidative stress and the process persistence. In our opinion, further studies should focus on identifying the molecular mechanisms determining the heterogeneity of COPD progression, since it is known that in some patients the disease can progress rapidly, while other patients may remain relatively stable for many years.

Dissecting the neurobiology of linguistic disorganisation and impoverishment in schizophrenia

Schizophrenia provides a quintessential disease model of how disturbances in the molecular mechanisms of neurodevelopment lead to disruptions in the emergence of cognition. The central and often persistent feature of this illness is the disorganisation and impoverishment of language and related expressive behaviours. Though clinically more prominent, the periodic perceptual distortions characterised as psychosis are non-specific and often episodic. While several insights into psychosis have been gained based on study of the dopaminergic system, the mechanistic basis of linguistic disorganisation and impoverishment is still elusive. Key findings from cellular to systems-level studies highlight the role of ubiquitous, inhibitory processes in language production. Dysregulation of these processes at critical time periods, in key brain areas, provides a surprisingly parsimonious account of linguistic disorganisation and impoverishment in schizophrenia. This review links the notion of excitatory/inhibitory (E/I) imbalance at cortical microcircuits to the expression of language behaviour characteristic of schizophrenia, through the building blocks of neurochemistry, neurophysiology, and neurocognition.

Association of Caspase 3 Activation and H2AX γ Phosphorylation in the Aging Brain: Studies on Untreated and Irradiated Mice.

Phosphorylation of H2AX is a response to DNA damage, but γH2AX also associates with mitosis and/or apoptosis. We examined the effects of X-rays on DNA integrity to shed more light on the significance of H2AX phosphorylation and its relationship with activation of caspase 3 (CASP3), the main apoptotic effector. After administration of the S phase marker BrdU, brains were collected from untreated and irradiated (10 Gray) 24-month-old mice surviving 15 or 30 min after irradiation. After paraffin embedding, brain sections were single- or double-stained with antibodies against γH2AX, p53-binding protein 1 (53BP1) (which is recruited during the DNA damage response (DDR)), active CASP3 (cCASP3), 5-Bromo-2-deoxyuridine (BrdU), and phosphorylated histone H3 (pHH3) (which labels proliferating cells). After statistical analysis, we demonstrated that irradiation not only induced a robust DDR with the appearance of γH2AX and upregulation of 53BP1 but also that cells with damaged DNA attempted to synthesize new genetic material from the rise in BrdU immunostaining, with increased expression of cCASP3. Association of γH2AX, 53BP1, and cCASP3 was also evident in normal nonirradiated mice, where DNA synthesis appeared to be linked to disturbances in DNA repair mechanisms rather than true mitotic activity.