The sense of taste: Development, regeneration, and dysfunction.
Gustation or the sense of taste is a primary sense, which functions as a gatekeeper for substances that enter the body. Animals, including humans, ingest foods that contain appetitive taste stimuli, including those that have sweet, moderately salty and umami (glutamate) components, and tend to avoid bitter-tasting items, as many bitter compounds are toxic. Taste is mediated by clusters of heterogeneous taste receptors cells (TRCs) organized as taste buds on the tongue, and these convey taste information from the oral cavity to higher order brain centers via the gustatory sensory neurons of the seventh and ninth cranial ganglia. One remarkable aspect of taste is that taste perception is mostly uninterrupted throughout life yet TRCs within buds are constantly renewed; every 1-2 months all taste cells have been steadily replaced. In the past decades we have learned a substantial amount about the cellular and molecular regulation of taste bud cell renewal, and how taste buds are initially established during embryogenesis. Here I review more recent findings pertaining to taste development and regeneration, as well as discuss potential mechanisms underlying taste dysfunction that often occurs with disease or its treatment. This article is categorized under: Infectious Diseases > Stem Cells and Development Cancer > Stem Cells and Development Neurological Diseases > Stem Cells and Development.


Correlation between the discharges of motor units recorded from the same and from different finger muscles in man.
1. Cross-correlation analysis of the discharges of individual motor units recorded from various different finger muscles has been performed during weak, isometric, voluntary contractions in man. 2. The dominant feature in 88% of the cross-correlograms studied was a narrow, central peak, the area of which significantly exceeded that expected for independent processes (P less than 0.001). The highest bin counts in these central peaks were mostly within 5 ms of time zero in the histograms, and the base of these peaks extended between 5 and 31 ms (modal value = 13 ms with 90% of the values lying between 8 and 18 ms). The width and displacement of the central cross-correlogram peaks were similar irrespective of whether the contributory spike trains were recorded from motor units active in the same finger muscle or recorded from motor units in different, co-activated finger muscles. 3. The time course of the central peaks in this study was found to be consistent with the hypothesis that it is generated by the joint occurrence of EPSPs evoked in motoneurones by branches of common stem presynaptic fibres using the theoretical model developed by Kirkwood (Kirkwood & Sears, 1978). The model parameters providing the best fit with our experimental data imply that synaptic contacts on motoneurones made by these common inputs lie on average peripherally in the dendritic tree and generate small (less than 300 microV) EPSPs superimposed on a high level of background synaptic noise. 4. Minima (troughs) were found either side of the central peak in 27% of the cross-correlograms studied, and their appearance was invariably associated with a large central peak. These secondary features could not be modelled with the same operator parameters that describe the central peaks. Their presence was particularly noticed in association with very regular discharges from the output motoneurones. 5. Smaller and broader secondary peaks symmetrically displaced 30-55 ms either side of the large, narrow central peak were observed in 7% of the cross-correlograms studied. We suggest that these secondary features which were found at lags shorter than the interspike interval of the contributory motor unit spike trains reflect the autocorrelation functions of the spike trains of common input fibres. On this basis the observed displacement of these secondary peaks from the primary feature in the cross-correlogram indicate firing rates for common input fibres in the range 18-33 impulses s-1. 6. In a small number of cases (1.4%) the cross-correlogram was flat and indistinguishable from the results of cross-correlating independent spike train data.


Sucrose incubation increases freezing tolerance of asparagus (Asparagus officinalis L.) embryogenic cell suspensions.
The freezing tolerance of asparagus (Asparagus officinalis L.) embryogenic cells, as determined by electrolyte leakage, was increased by the incubation of samples in medium containing 0.8 M sucrose. To elucidate the mechanism involved, we investigated the changes in soluble carbohydrates, cell ultrastructure and proteins accompanying the increase in freezing tolerance following incubation in sugar-rich medium. During sugar incubation, the intracellular sucrose content increased from 67 mol g-1FW to 429 mol g-1FW; it was also metabolized into fructose and glucose, as determined by high-performance liquid chromatography. Microscopy revealed that sugar incubation induced plasmolysis of embryogenic cells and drastic changes in cell ultrastructure with the appearance of rough endoplasmic reticulum (rER). Furthermore, immunoblotting analysis with anti-dehydrin antiserum revealed that a dehydrin-like protein appeared only when maximal freezing tolerance was induced by sugar incubation. These results suggest that freezing tolerance of asparagus embryogenic cells is increased by a complex mechanism involving notably changes in cell ultrastructure and accumulation of certain sugars and proteins during sugar incubation.


Role of the BACTEC radiometric method in the evaluation of patients with clinically probable tuberculous meningitis.
Confirmation of tuberculous meningitis (TBM) and initiation of treatment are often delayed due to limitations in isolating Mycobacterium tuberculosis from cerebrospinal fluid (CSF). To evaluate the role of the BACTEC radiometric method in a clinical setting for the early diagnosis of TBM. Patients meeting criteria for clinically probable TBM over a 3 year period were included. Clinical features, results of CSF investigations (protein, glucose, cell count, Ziehl-Neelsen staining, culture in Löwenstein-Jensen (LJ) medium and BACTEC) and brain CT imaging were reviewed. Drug sensitivity was tested using BACTEC. Patients were started on standard treatment and functional outcome, and response at discharge and follow-up were assessed. Patients were divided according to whether or not M. tuberculosis was isolated by BACTEC and the clinical, radiological, and laboratory features compared. Sixty patients were evaluated. The mean age was 30 years +/- 11.7 years. Headache and fever were the most common symptoms and the mean duration was 26 days. CT findings were hydrocephalus (n=21), basal exudates (n=16), and tuberculoma (n=14). In 40 patients, M. tuberculosis was isolated by BACTEC and average 15 days was required for detection, whereas it was 30 days in LJ medium. Results of drug-sensitivity testing (n=32) were obtained average 7 days after isolation. Patients from whom M. tuberculosis had been isolated by BACTEC more often had tuberculomas in CT imaging (P=0.018). Use of the BACTEC method allows early confirmation in patients with clinically probable TBM. It can guide clinicians in the rational use of anti-tuberculosis treatment by confirming diagnosis and identifying drug- sensitivity.


[Digestive function of the residual pancreas after partial duodenopancreatectomy for chronic pancreatitis (author's transl)].
Forty-eight patients with chronic recurrent pancreatitis treated by resection of the head of the pancreas were restudied more than a year post-operatively. In addition to general features such as symptoms, alcohol consumption and work ability, faecal weight, its fat content, fat and fatty acid balance and faecal chymotrypsin were measured. According to the patients' own estimate, late results were good or very good in 70-90%. Faecal fat content and balance indicated high-grade exocrine pancreatic insufficiency in 80 and 90%, respectively. But it was easily controlled by drugs. In a third of the cases there was the need to supplement the diet with medium-chain triglycerides. Its components are satisfactorily absorbed even when the fat utilisation is severely abnormal.


Can CO2 sequestration in basalt efficiently reduce greenhouse gas emission?
The research on the Columbia River Basalt is a unique combination of projects that minimise CO2 emissions to the atmosphere. Both are underground waste disposal projects: CO2 waste versus nuclear waste. The recent Wallula CO2 project and the previous nuclear-waste project in the Columbia River Basalt (CRB), USA, provide the database for a high-capacity CO2 sequestration model. Due to geomechanical constraints, the injection rate of CO2 sequestration must be limited in order not to jeopardise the integrity of the reservoir and cap rock. The interbed in the continental flood basalt tested in the Wallula project only allows injection at a rate in the range of 9-19 kg CO2/s, depending on permeability (4 × 10-14-10-13 m2) and porosity (0.1-0.15). At the end of a 50-year injection period, the fraction of CO2 converted to carbonate minerals is 37.1-67.1%. Underground space for waste disposal is a rare asset. The Columbia River Basalt occupies an area of 200,000 km2. Fifty years of CO2 sequestration from a single well would require about the same fraction of the area as that of a nuclear waste repository (0.025%). The repository design is for a capacity of 70,000 MTHM (metric tons heavy metal). If all the waste is spent nuclear fuel, it originates from 1.2 × 104-8.4 × 104 TWh electric power production, depending on reactor type. The CO2 injection well operating at maximum capacity (19 kg CO2/s) represents 50 TWh generated in a gas power station minus the energy consumed for CO2 separation, i.e. less than 0.4% of the nuclear option.


Quantitation of genomic methylation using ligation-mediated PCR.
We have developed a new technique for the quantitation of CpG methylation of genomic DNA. This method measures the conversion of a larger amplified DNA fragment to a shorter DNA product correlating with demethylation. The procedure uses pairs of non-isoschizomeric enzymes, one of which is methylation-sensitive, to cleave genomic DNA at closely spaced sites. The extent of cleavage by the methylation-sensitive restriction enzyme is quantitated by amplification of these digestion products with ligation-mediated PCR and radioactive labeling of the product. The ratio of the two amplified fragments correlates with the degree of methylation at the restriction site. The analysis is rapid, quantitative, internally controlled and requires small quantities of genomic DNA.


Representation of attended versus remembered locations in prefrontal cortex.
A great deal of research on the prefrontal cortex (PF), especially in nonhuman primates, has focused on the theory that it functions predominantly in the maintenance of short-term memories, and neurophysiologists have often interpreted PF's delay-period activity in the context of this theory. Neuroimaging results, however, suggest that PF's function extends beyond the maintenance of memories to include aspects of attention, such as the monitoring and selection of information. To explore alternative interpretations of PF's delay-period activity, we investigated the discharge rates of single PF neurons as monkeys attended to a stimulus marking one location while remembering a different, unmarked location. Both locations served as potential targets of a saccadic eye movement. Although the task made intensive demands on short-term memory, the largest proportion of PF neurons represented attended locations, not remembered ones. The present findings show that short-term memory functions cannot account for all, or even most, delay-period activity in the part of PF explored. Instead, PF's delay-period activity probably contributes more to the process of attentional selection.


A framework to improve the quality of treatment for depression in primary care.
New forms of medication and brief psychotherapy have dramatically changed how depressive disorders have been treated over the past two decades. In spite of these changes, the quality of treatment for depression remains poor at the population level. In this article, the authors review current concepts and theory regarding the quality of treatment for depression. They present a conceptual model of four points in the course of a treatment episode when clinicians could deviate from guidelines. Using the model, the authors review research that supports guideline recommendations and that can inform clinicians' decisions. They suggest several areas for future study and action, including extending awareness and recognition outside the medical care setting to schools and workplaces, addressing growing concerns about possible overtreatment, using qualitative research approaches to gain an understanding of patient perspectives on treatment, and improving the measurement for quality of treatment.


Significance of mesial temporal atrophy in relation to intracranial ictal and interictal stereo EEG abnormalities.
We studied 31 consecutive patients with temporal and extratemporal epilepsy who underwent presurgical evaluation with stereotaxic depth EEG (SEEG) to assess the relationships between amygdalo-hippocampal (AM-HF) atrophy and the location of SEEG seizure onset and SEEG interictal abnormalities. Scalp EEG recordings with sphenoidal electrodes had shown bitemporal ictal or interictal epileptic abnormalities in all. Patients underwent high quality MRI scans, including MRI volumetric measurements of mesial temporal structures. None had foreign tissue lesions. The final conclusions of the SEEG investigation coincided with the lateralization obtained by MRI volumetric measurements in the eight patients who had significant unilateral atrophy of the amygdala, hippocampus or both (> 2 SD below the mean of controls). In these patients with unilateral atrophy, all or > 75% of clinical seizures originated from the atrophic side. The seven patients with bilateral, but significantly asymmetrical, mesial atrophy had bilateral seizure onsets with > 70% originating from the more atrophic side in four, from the less atrophic side in two, and without predominance in one. The one patient with severe bilateral symmetrical atrophy had seizures originating equally from both sides. Five patients had no atrophy on MRI, but depth electrodes revealed predominant unilateral ictal temporal onsets in four of them. There was no significant correlation between the frequency of SEEG interictal spikes and the amount of AM-HF atrophy. However, we found a significant correlation between the severity of SEEG background disturbance in AM and HF and the degree of atrophy of these structures. Patients with unilateral atrophy were more frequently free of seizures after surgery than those with bilateral or no atrophy (P < 0.05). We conclude that unilateral mesial atrophy predicts ipsilateral mesial SEEG seizure onset despite bitemporal extracranial EEG foci. However, in patients with significant bilateral mesial atrophy, SEEG seizures may originate from either side, even in the presence of significant asymmetry. Finally, the identification of unilateral mesial atrophy has prognostic importance.


Overall symptom measurement: which approach?
The syndrome of preschool wheeze includes a wide range of symptomology, measurement of which necessitates assessment of severity as well as prevalence. Most wheezing in this age group is episodic and associated with viral infections, and it is often difficult to distinguish wheeze from other lower respiratory symptoms. An overall measure of symptom severity should include the frequency, duration and magnitude both of episodes and interval symptoms. However, little attention has been paid to either the distinction of acute virus-related episodes from day-to-day symptoms, or their quantification. The type of medication used is sometimes considered as a measure of symptom severity. Since there is no consensus about either the criteria for the use of anti-inflammatory agents or their modulating effect, this practice is unreliable. Without an agreed method to define symptom severity, it is difficult to assess the validity of either population questionnaires or symptom diaries for use in clinical trials. Validation using objective measures is urgently required.


Discriminating Metabolic Health Status in a Cohort of Nursing Students: Protocol for a Cross-Sectional Study.
Obesity is currently a worldwide health crisis. Nurses are integral members of the primary health care team and have an important role in managing obesity and administering physical activity (PA) for patients. However, research shows that nurses tend to be overweight or obese, have poor metabolic health, and do not meet PA recommendations. This is problematic because PA is linked to both physiological and psychological well-being and may also influence how nurses counsel their patients. Nursing students are the next generation of nurses; however, there is limited research examining PA (among other lifestyle factors) and metabolic health in nursing students. The goal of this research is to examine multiple lifestyle factors (including PA, nutrition, sleep, and stress) and determine whether these factors are associated with metabolic health in full-time undergraduate nursing students. An estimated 320 nursing students (18 years of age and older) will be assessed for their metabolic health. Metabolic status will be determined by measuring body mass index (BMI), waist-to-hip ratio (WHR), body fat percentage [skinfold measures (FitSystems Inc)], resting blood pressure [automated oscillatory (Omron Healthcare Inc)], and fasting blood glucose (glucometer). Lifestyle factors will also be measured, including PA and sleep [the International Physical Activity Questionnaire (IPAQ) and 7-day accelerometry (wGT3X-BT, Actigraph LLC)], nutrition [3-day diet log (Nutritionist Pro, Axxya Systems)], and stress [the Depression Anxiety Stress Scale, heart rate variability assessments, and salivary cortisol (ELISA, Eagle Biosciences)]. The association between metabolic status and PA, sleep quantity and quality, nutrition, and stress will be examined by linear regression analyses. Differences by year of study in metabolic health status, PA, sleep, nutrition, and stress will be examined by 1-way analyses of variance (ANOVAs). To determine the ability of PA, sleep, nutrition, and stress to discriminate prevalent overweight and obesity or poor metabolic status, logistic regression and receiver operating characteristic (ROC) curves will be constructed. Statistical analyses will be performed in Stata (version 16.1, StataCorp LLC). Based on pilot data, we believe senior nursing students will have worse metabolic health (ie, higher BMI and WHR, increased body fat percentage, higher blood pressure, and increased fasting blood glucose) compared to first-year students. We hypothesize that poor PA participation, poor sleep quantity and quality, increased food intake, poor nutrition, and increased stress will be associated with worse metabolic health in full-time nursing students. The study received funding in February 2020. Due to the coronavirus disease 2019 (COVID-19) pandemic, work on this study has been delayed. We are currently completing our application for institutional research ethics approval. Data collection is projected to begin in January 2021, with data collection and analyses expected to be completed by May 2022. This study will be the first published research to examine the relationship between lifestyle choices and metabolic status in nursing students attending a Canadian institution. More importantly, the results of this study will support the development of an informed intervention that will target the identified lifestyle factors, improving the physiological and mental health and well-being of nursing students. PRR1-10.2196/21342.


The effect of timing of administration of oestradiol benzoate on characteristics of oestrus, timing of ovulation and fertility in Bos indicus heifers synchronised with a progesterone releasing intravaginal insert.
To compare the timing of onset of oestrus and ovulation, characteristics of oestrus, and fertility in Bos indicus heifers synchronised with a progesterone releasing intravaginal insert (IVP4) and administration of oestradiol benzoate (ODB) either at the time of removal of the insert or 24 h later. Cohort study. Bos indicus and Bos indicus cross heifers were treated on two farms (Farm A, n = 273; Farm B, n = 47) with an IVP4 for 8 days with 1.0 mg of ODB administered at the time of device insertion and 250 mg of cloprostenol at the time of device removal. Heifers in the ODB-0 group were administered 0.75 mg of ODB at the time of device removal while heifers in the ODB-24 group were administered the same dose of ODB 24 h after device removal. Heifers were inseminated once daily after detection of oestrus. Heifers not detected in oestrus by 72 h after removal of inserts were inseminated at that time. Oestrus was detected in heifers on Farm A using heatmount detectors while on Farm B oestrus in heifers was monitored using radiotelemetry of mounting pressure. Ovarian follicular development was monitored daily in 30 heifers on Farm B from the time of administration of inserts until ovulation to a maximum of 96 h after removal of inserts, and again 11 days after removal of inserts (Day 19). A blood sample was collected from all heifers on Farm B on Day 19 and analysed for plasma concentration of progesterone. Pregnancy was diagnosed 6 to 8 weeks after insemination. Administration of ODB at the time of removal of inserts shortened the time interval to oestrus and ovulation (P < 0.001), increased the number of mounts recorded during oestrus (P = 0.04) and reduced the odds of pregnancy (P = 0.03). The proportion of heifers ovulating on Farm B was 67% and was not affected by treatment group (P = 0.61). The mean diameter of the largest follicle measured in ovaries was greater at the time of removal of inserts (9.1 +/- 0.6 vs 10.7 +/- 0.4; P = 0.03) and at the expected time of the LH surge (8.1 +/- 0.4 vs 11.5 +/- 0.3 mm; P < 0.001) in heifers that ovulated compared to heifers that failed to ovulate, respectively. Emergence of a new follicular wave was not detected during the synchronisation treatment in heifers that failed to ovulate. Concentrations of progesterone in plasma on Day 19 were less in non-pregnant heifers (P = 0.05) compared to heifers subsequently diagnosed as pregnant to insemination and were affected by the diameter of the ovulatory follicle (P = 0.01). Administration of ODB at the time of removal of inserts can shorten the time interval to oestrus and ovulation and can reduce fertility when insemination is carried out once daily. Further work is needed to determine if prolonged suppression of follicular development, anovulatory oestrus and premature ovulation occuring in some heifers is associated with administration of ODB.


Reduced pollinator service in small populations of Arabidopsis lyrata at its southern range limit.
Even though a high fraction of angiosperm plants depends on animal pollinators for sexual reproduction, little is known how pollinator service changes across the ranges of plant species and whether it may contribute to range limits. Here, we tested for variation in pollinator service in the North American Arabidopsis lyrata from its southern to northern range edge and evaluated the driving mechanisms. We monitored insect pollinators using time-lapse cameras in 13 populations over two years and spotted 67 pollinating insect taxa, indicating the generalist nature of this plant-pollinator system. Pollinator service was highest at intermediate local flower densities and higher in large compared to small plant populations. Southern populations had generally smaller population sizes, and visitation rate and pollination ratio decreased with latitude. We also found that pollinator visitation was positively correlated with the richness of other flowering plants. This study indicates that plant populations at southern range edges receive only marginal pollinator service if they are small, and the effect of lower pollination is also detectable within populations across the range when the local flower density is low. Results, therefore, suggest the potential for an Allee effect in pollination that manifests itself across spatial scales.


Dynamics of Three-Body Correlations in Quenched Unitary Bose Gases.
We investigate dynamical three-body correlations in the Bose gas during the earliest stages of evolution after a quench to the unitary regime. The development of few-body correlations is theoretically observed by determining the two- and three-body contacts. We find that the growth of three-body correlations is gradual compared to two-body correlations. The three-body contact oscillates coherently, and we identify this as a signature of Efimov trimers. We show that the growth of three-body correlations depends nontrivially on parameters derived from both the density and Efimov physics. These results demonstrate the violation of scaling invariance of unitary bosonic systems via the appearance of log-periodic modulation of three-body correlations.


Exploiting the spatial locality of electron correlation within the parametric two-electron reduced-density-matrix method.
The parametric variational two-electron reduced-density-matrix (2-RDM) method is applied to computing electronic correlation energies of medium-to-large molecular systems by exploiting the spatial locality of electron correlation within the framework of the cluster-in-molecule (CIM) approximation [S. Li et al., J. Comput. Chem. 23, 238 (2002); J. Chem. Phys. 125, 074109 (2006)]. The 2-RDMs of individual molecular fragments within a molecule are determined, and selected portions of these 2-RDMs are recombined to yield an accurate approximation to the correlation energy of the entire molecule. In addition to extending CIM to the parametric 2-RDM method, we (i) suggest a more systematic selection of atomic-orbital domains than that presented in previous CIM studies and (ii) generalize the CIM method for open-shell quantum systems. The resulting method is tested with a series of polyacetylene molecules, water clusters, and diazobenzene derivatives in minimal and nonminimal basis sets. Calculations show that the computational cost of the method scales linearly with system size. We also compute hydrogen-abstraction energies for a series of hydroxyurea derivatives. Abstraction of hydrogen from hydroxyurea is thought to be a key step in its treatment of sickle cell anemia; the design of hydroxyurea derivatives that oxidize more rapidly is one approach to devising more effective treatments.


How do Nigerian newspapers report COVID-19 pandemic? The implication for awareness and prevention.
This study examined media coverage of COVID-19 in Nigeria with attention to the frequency and depth of coverage, story format, news sources, media tone and themes. Four widely read newspapers were content analysed between February 2020 and April 2020. Focus was on Daily Sun, Vanguard, Daily Trust and Leadership. Results indicated that the Nigerian media performed well in terms of covering the pandemic, which in turn created awareness. However, the coverage was not in-depth as most of the reported stories were short and were predominantly straight news. It was also observed that the media cited more of the Nigeria Centre for Disease Control (NCDC) and government officials. Further findings disclosed that most of the stories were alarming and induced panic. Most common topics were coverage of cases in Nigeria, death rates and concerns about Nigeria's preparedness. Public sensitization and education were sparingly covered. Ethics healthcare workers could adhere to received minimal attention. The media should focus more on sensitizing and educating the public on the necessary steps to take in curbing the virus. They should refrain from over usage of alarming and panic tone in presenting the stories of COVID-19 pandemic in Nigeria.


Eicosapentaenoic acid reduces hepatic synthesis and secretion of triacylglycerol by decreasing the activity of acyl-coenzyme A:1,2-diacylglycerol acyltransferase.
The mechanism for the reduced hepatic production of triacylglycerol in the presence of eicosapentaenoic acid was explored in short-term experiments using cultured parenchymal cells and microsomes from rat liver. Oleic, palmitic, stearic, and linoleic acids were the most potent stimulators of triacyl[3H]glycerol synthesis and secretion by hepatocytes, whereas erucic, alpha-linolenic, gamma-linolenic, arachidonic, docosahexaenoic, and eicosapentaenoic acids (in decreasing order) were less stimulatory. There was a linear correlation (r = 0.85, P less than 0.01) between synthesis and secretion of triacyl[3H]glycerol for the fatty acids examined. The extreme and opposite effects of eicosapentaenoic and oleic acids on triacylglycerol metabolism were studied in more detail. With increasing number of free fatty acid molecules bound per molecule of albumin, the rate of synthesis and secretion of triacyl[3H]glycerol increased, most markedly for oleic acid. Cellular uptake of the two fatty acids was similar, but more free eicosapentaenoic acid accumulated intracellularly. Eicosapentaenoic acid caused higher incorporation of [3H]water into phospholipid and lower incorporation into triacylglycerol and cholesteryl ester as compared to oleic acid. No difference was observed between the fatty acids on incorporation into cellular free fatty acids, monoacylglycerol and diacylglycerol. The amount of some 16- and 18-carbon fatty acids in triacylglycerol was significantly higher in the presence of oleic acid compared with eicosapentaenoic acid. Rat liver microsomes in the presence of added 1,2-dioleoyl-glycerol incorporated eicosapentaenoic acid and eicosapentaenoyl-CoA into triacylglycerol to a lesser extent than oleic acid and its CoA derivative. Decreased formation of triacylglycerol was also observed when eicosapentaenoyl-CoA was given together with oleoyl-CoA, whereas palmitoyl-CoA, stearoyl-CoA, linoleoyl-CoA, linolenoyl-CoA, and arachi-donoyl-CoA had no inhibitory effect. In conclusion, inhibition of acyl-CoA:1,2-diacylglycerol O-acyltransferase (EC 126.96.36.199) by eicosapentaenoic acid may be important for reduced synthesis and secretion of triacylglycerol from the liver.


Physiologic and metabolic alterations associated with seizures in normoxic and asphyxiated neonatal dogs.
The effect of asphyxia on seizures was determined in neonatal dogs. In normoxic (paralyzed and ventilated) neonatal dogs, bicuculline-induced seizures produced significant elevations of arterial blood pressure, PO2, glucose, lactate, and epinephrine. Cerebral blood flow increased severalfold; brain glucose, adenosine triphosphate (ATP), and phosphocreatine (PCr) did not decrease significantly. In contrast, seizures during asphyxia were associated with hypoxia, hypotension, hypercarbia, and acidosis. Significant cerebral ischemia developed. Brain glucose, ATP, and PCr were significantly depleted. Complete oxygen deprivation during neonatal seizures exhausts brain energy stores, which leads to cessation of seizure activity.


Stimulation of ammonia and 2-oxoglutarate-dependent o(2) evolution in isolated chloroplasts by dicarboxylates and the role of the chloroplast in photorespiratory nitrogen recycling.
Intact chloroplasts isolated from spinach (Spinacia oleracea L.) leaves showed a light-dependent O(2) evolution (5.5 +/- 0.75 micromoles per milligram chlorophyll per hour) when supplied with ammonia and 2-oxoglutarate. This (ammonia, 2-oxoglutarate)-dependent O(2) evolution was stimulated 2- to 4-fold by the dicarboxylates, malate, succinate, fumarate, glutarate, and l-tartarate. Evolution of O(2) in the presence of malate was dependent on the presence of both 2-oxoglutarate and NH(4)Cl; malate with only either 2-oxoglutarate and NH(4)Cl alone did not support O(2) evolution. Furthermore, in the presence of malate, the amount of O(2) evolved was solely dependent on the amount of NH(4)Cl or 2-oxoglutarate added and malate did not affect the ratio of O(2) evolved to NH(4)Cl or 2-oxoglutarate consumed. Studies with inhibitors (2-(3,4-dichlorophenyl)-1,1-dimethyl urea, methionine sulfoximine, and azaserine) indicated that the above activity was directly linked to glutamine synthetase and glutamate synthase activity in the chloroplast and was not caused by the metabolism of malate. The V(max)/2 of (ammonia, 2-oxoglutarate)-dependent O(2) evolution was reached at 32 micromolar NH(4)Cl and 6 millimolar (approximately) 2-oxoglutarate in the absence of malate, and at 22 micromolar NH(4)Cl and 73 micromolar 2-oxoglutarate when malate (3 millimolar) was present.Intact chloroplasts isolated from pea (Pisum sativum) leaves also showed a stimulation of (ammonia, 2-oxoglutarate)-dependent O(2) evolution by malate. However glutamine was required for this activity even though glutamine with only either NH(4)Cl or 2-oxoglutarate did not respond to malate stimulation.The measured rates of (ammonia, 2-oxoglutarate)-dependent O(2) evolution in isolated spinach chloroplasts in the presence of malate were about 19.5 +/- 4.5 micromoles O(2) evolved per milligram chlorophyll per hour. This is adequate to sustain photorespiratory NH(3) recycling and the refixation of NH(3) arising from NO(3) under ambient conditions in the light. The role of the chloroplast in photorespiratory NH(3) recycling and the nature of the associated transport of 2-oxoglutarate into the chloroplast is discussed.


Effect of pseudomonas elastase on human mononuclear phagocyte alpha 1-antitrypsin expression.
The net balance of neutrophil elastase and its inhibitor, alpha 1-antitrypsin (alpha 1-AT), is a critical determinant of connective tissue turnover during homeostasis and in disease states. In addition to liver-derived alpha 1-AT, which translocates from blood to tissues, this elastase-alpha 1-AT balance is maintained by expression of alpha 1-AT at the local tissue level in resident mononuclear phagocytes. Our previous studies have shown that this elastase-alpha 1-AT balance is also tightly controlled at a cellular level in that addition of exogenous neutrophil elastase (serpine-type elastase) to cultured mononuclear phagocytes is associated with an increase in expression of the alpha 1-AT gene. Subsequent studies have demonstrated that this novel regulatory loop involves interaction between exogenous neutrophil elastase and endogenous alpha 1-AT inducing a structural rearrangement in the alpha 1-AT molecule and exposing highly conserved conformation-specific domain of alpha 1-AT, which can then be recognized by a specific cell surface receptor, the serpine-enzyme complex receptor. In the following study, we examined the effect of a bacterial metalloelastase, Pseudomonas aeruginosa elastase, on expression of alpha 1-AT in human mononuclear phagocytes. We show that pseudomonas elastase inactivates monocyte-derived alpha 1-AT by limited proteolysis but, in so doing, alpha 1-AT becomes recognized by the serpine-enzyme complex receptor and mediates an increase in de novo synthesis of alpha 1-AT in these cells. However, the concentrations of pseudomonas elastase needed to proteolytically inactivate alpha 1-AT in monocyte culture fluid are higher than those required for inactivation of purified plasma alpha 1-AT.(ABSTRACT TRUNCATED AT 250 WORDS)


Arm span as measurement of response to growth hormone (GH) treatment in a group of children with meningomyelocele and GH deficiency.
Children with meningomyelocele (MMC) frequently have impaired linear growth. A number have associated structural brain defects with resultant GH deficiency (GHD). Reproducible measurements of height or length in MMC patients are often hampered by lower limb contractures, spasticity, and scoliosis. Arm span has been proposed as a more reproducible measure of linear growth. Five MMC children documented to have GHD were treated with recombinant human GH (hGH) for 1-3 yr. Their height, arm span, and growth velocity were compared with 32 children with idiopathic GHD treated similarly with hGH. These measures are compared with normal children by being expressed as standard deviation scores. The results of this study indicate that arm span measurements in GHD MMC patients are almost identical to height measurements in idiopathic GHD patients both before and during hGH therapy. The physical condition of children with MMC makes reproducible longitudinal height measurements difficult. Routine determinations of arm span measurements for children with MMC will assist in recognizing growth failure as well as monitoring treatment results.


MMP-9 (gelatinase B) expression is associated with disease-free survival and disease-specific survival in colorectal cancer patients.
Extracellular matrix degradation is required for invasion and metastasis formation in colorectal carcinoma (CRC), therefore, we have examined matrix metalloproteinases MMP-9 expression in tumors from patients with CRC. The study comprises of 360 patients who underwent bowel resection for stage II, III, IV tumors. Paraffin-embedded CRC tissue samples were used for immunohistochemical staining. Negative MMP-9 expression levels correlated with longer survival time as evaluated by disease-free survival and disease-specific survival (p =.023, p =.006). In multivariate survival (Cox) analysis, MMP9 was a significant independent predictor of DFS (p =.014), but not of DSS, which was independently predicted by disease recurrence, stage and localization. The detection of MMP-9 expression may be valuable in finding patients who are at high risk of developing disease recurrence.


Effect of quantum tunneling on single strand breaks in a modeled gas phase cytidine nucleotide induced by low energy electron: a theoretical approach.
Effect of quantum mechanical tunneling on single strand breaks induced by low energy electron (LEE) has been investigated in a modeled gas phase system, 2'-deoxycytidine-3'-monophosphate (3'-dCMPH). The potential energy curves for the sugar-phosphate C-O (3' C-O) bond cleavage have been generated using second order Møller-Plesset perturbation theory at the 6-31+G(d) accuracy level. Results from the electronic structure theory calculations in conjunction with our time dependent calculations for the 3' C-O bond rupture in 3'-dCMPH using local complex potential based time dependent wave packet approach show significant quantum tunneling of the 3' C-O bond from the bound vibrational states above 1 eV of the anionic potential energy curve. A comparison of the fragmentation profile with that of our earlier gas phase investigations based on Hartree-Fock and density functional theory--Becke, 3-parameter, Lee-Yang-Parr methods with 6-31+G(d) basis set is also provided. Further, inspection of the singly occupied molecular orbitals generated at different 3' C-O bond lengths clearly indicates the electron transfer from the low lying base-π(∗) shape resonance state to the phosphate P = O π(∗) orbital of the DNA backbone during the strand breaks. The decisive step during LEE induced strand breaks follows via "charge induced dissociation" (CID) for the metastable anion formed below 1 eV, whereas quantum mechanical tunnel-ing is out-weighted the CID mechanism for the LEE above 1 eV.


Weakening Circular Dichroism of Plasmonic Nanospirals Induced by Surface Grafting with Alkyl Ligands.
Silver nanospirals with strong chiroptical activity (characterized by circular dichroism) are grafted with achiral alkyl ligands, resulting in a weakening of the chiroptical activity. The chiroptical weakening is exacerbated with increasing bond energy of the Ag-ligand contacts, which is ascribed to the effective medium screening effect and electron withdrawal toward the alkyl ligands.


microRNA-22 acts as a metastasis suppressor by targeting metadherin in gastric cancer.
microRNA (miR)-22 has been reported to be downregulated in hepatocellular, lung, colorectal, ovarian and breast cancer, acting as a tumor suppressor. The present study investigated the potential effects of miR-22 on gastric cancer invasion and metastasis and the molecular mechanism. miR-22 expression was examined in tumor tissues of in 89 gastric cancer patients by in situ hybridization (ISH) analysis. Additionally, the association between miR-22 levels and clinicopathological parameters was analyzed. A luciferase assay was conducted for target identification. The ability of invasion and metastasis of gastric cancer cells in vitro and in vivo was evaluated by cell migration and invasion assays and in a xenograft model. The results showed that miR-22 was downregulated in the gastric cancer specimens and significantly correlated with the advanced clinical stage and lymph node metastasis. In addition, metadherin (MTDH) was shown to be a direct target of miR-22 and the expression of MTDH was inversely correlated with miR-22 expression in gastric cancer. Ectopic expression of miR-22 suppressed cell invasion and metastasis in vitro and in vivo. The present study suggested that miR-22 may be a valuable prognostic factor in gastric cancer. miR-22 inhibited gastric cancer cell invasion and metastasis by directly targeting MTDH. The novel miR-22/MTDH link confirmed in the present study provided a novel, potential therapeutic target for the treatment of gastric cancer.


Flexibility of sensory representations in prefrontal cortex depends on cell type.
Discrimination tasks require processing, interpreting, and linking sensory information to the appropriate motor response. We report that neurons in prefrontal cortex (PFC) represent visual motion with precision comparable to cortical neurons at early stages of motion processing, and readily adapt this representation to behavioral context. We found that direction selectivity, recorded while the monkeys discriminated directions, decreased when they judged motion speed and ignored its direction. This decrease was more pronounced in neurons classified as narrow-spiking (NS) putative interneurons than in broad-spiking (BS) putative pyramidal neurons. However, during passive fixation, when the link between motion and its behavioral relevance was removed, both cell types showed a severe selectivity loss. Our results show that flexible sensory representation during active discrimination tasks is achieved in the PFC by a specialized neuronal network of both NS neurons readily adjusting their selectivity to behavioral context, and BS neurons capable of maintaining relatively stable sensory representation.


Genomics of the HOX gene cluster.
The Hox family of homeobox genes encode transcription factors that control different aspects of metazoan development. They appear clustered in the genomes of those animals in which their relative positions have been mapped. Although clustering is assumed to be a general property of Hox genes in all bilaterians, just a few species have been studied in sufficient detail to support this claim. Linear duplication of genes inside the cluster, as well as full-cluster duplications account for the actual complexity of HOX clusters in the different animal groups that have been studied (mainly vertebrates). Understanding how the Hox genes are regulated during development will depend, ultimately, on the generation of more powerful tools for cloning intact HOX clusters and for elucidating their cis-regulatory components. To clarify the roles of the Hox genes themselves, we will need to characterize in detail their downstream targets, and some progress in this direction is coming mainly from the recent use of arrayed libraries. Moreover, a comprehensive study of Hox target genes in tissues and organisms promises, in the long term, to give us a clear idea of the role that Hox genes play during development and how they have evolved over time.


Red Light-Independent Instability of Oat Phytochrome mRNA in Vivo.
Phytochrome A (phyA) mRNA abundance decreased rapidly in total RNA samples isolated from 4-day-old etiolated oat seedlings following a red light pulse. Putative in vivo phyA mRNA degradation products were detectable both before and after red light treatment. Cordycepin-treated coleoptiles were unable to accumulate the chlorophyll a/b-binding protein mRNA in response to red light, indicating that cordycepin effectively inhibited mRNA synthesis. In cordycepin-treated coleoptiles, phyA mRNA rapidly decreased in abundance, consistent with the hypothesis that phyA mRNA is inherently unstable, rather than being destabilized after red light treatment of etiolated oat seedlings.


Zeaxanthin dipalmitate from Lycium chinense fruit reduces experimentally induced hepatic fibrosis in rats.
We previously reported that zeaxanthin dipalmitate (ZD), a carotenoid from Lycium chinense fruit, reduces myofibroblast-like cell proliferation and collagen synthesis in vitro. To determine whether ZD might reduce the severity of hepatic fibrosis in an animal model, hepatic fibrosis was induced in rats by bile duct ligation/scission (BDL) for a period of 6 weeks. Treatment of BDL rats with ZD at a dose of 25 mg/kg body weight significantly reduced the activities of aspartate transaminase (p<0.05) and alkaline phosphatase (p<0.001) in serum. Furthermore, collagen deposition was significantly reduced as assessed by the Sirius Red binding assay in BDL rats administered ZD at the dose of 25 mg/kg body weight (p<0.01). In addition, the levels of thiobarbituric acid-reactive substances and 4-hydroxyproline were reduced when BDL rats received ZD at the dose of 25 mg/kg body weight. These results showed that ZD effectively inhibited hepatic fibrosis in BDL rats, at least in part via its antioxidative activity.


Selective effects of tea extract and its phenolic compounds on human peripheral blood mononuclear cell cytokine secretions.
The effects of black tea extract (BTE) and some of its pure phenolics on human peripheral blood mononuclear cell (PBMC) cytokine secretion were examined in vitro. The main steps of the study included chromatographic analysis of BTE and commercial green tea extract, Polyphenon 60, determination of the total antioxidant capacity of both the extracts and their phenolics, and finally evaluation of their effects on PBMCs. Four major peaks in the chromatogram of BTE belonged to caffeine, gallic acid, epigallocatechin and epigallocatechin gallate, and the latter showed the highest antioxidant capacity. While pure phenolics at the concentration of 20 mM did not significantly affect PBMC cytokine secretion, BTE and Polyphenon 60 suppressed interleukin-1 beta, tumor necrosis factor-alpha and interleukin-6. Interestingly, the secretion of interferon-gamma after 24 h was slightly, but significantly, boosted by the extracts. BTE has selective pro-inflammatory cytokine-suppressing effects on human PBMCs.


Thirteen anti-Sm monoclonal antibodies immunoprecipitate the three cytoplasmic snRNP core protein precursors in six distinct subsets.
The small nuclear ribonucleoprotein particle (snRNP) common core proteins are the lupus-associated Sm autoantigens. In mouse fibroblasts the seven snRNP core proteins form a particle with a suggested stoichiometry of B2[D1,D2(E,F,G)2] D3. Core particle assembly occurs in the cytoplasm where newly synthesized snRNAs assemble with core proteins stored in three RNA-free complexes of (1) a 6S complex of [D1,D2(E,F,G)2] (2) a 20S complex of (B,D3 and an unidentified 70 kDa protein) and (3) a 2S-6S complex that minimally contains the B protein. In this report a panel of 13 anti-Sm monoclonal antibodies is shown to immunoprecipitate six different subsets of the cytoplasmic snRNP proteins. Four epitopes are shared by the three aforementioned complexes and five other epitopes are shared by two of the complexes. In addition, the 6S or 20S complexes are apparently disrupted by five of the antibodies. Kinetic studies show that the three cytoplasmic snRNP protein complexes have independent half-lives. These studies provide another approach for characterizing the Sm epitopes. They also complement previous in vitro snRNP assembly studies and suggest that snRNP core assembly occurs by the initial binding of snRNA to the 6S particle followed by addition of the B and D3 proteins.


Molecular orientation arrangements in the smectic-C* variant liquid-crystal phases.
Recent experiments have identified three-layer and four-layer distorted helical structures in the smectic liquid-crystal phases Sm C*(FI1) and Sm C*(FI2), respectively. However, no theories have explained the existence of all these phases. A discrete phenomenological model of the free-energy is analyzed and found to predict the stability of distorted three-layer and four-layer structures, as well as simple helical solutions in smectic liquid crystals. A simple physical picture is provided to explain the stability of the phases exhibiting distorted helical structures.


A Novel Multi-Angle SAR Imaging System and Method Based on an Ultrahigh Speed Platform.
Considering the difficulty of pulse repetition frequency (PRF) design in multi-angle SAR when using ultra-high speed platforms, a multi-angle SAR imaging system in a unified coordinate system is proposed. The digital multi-beamforming is used in the system and multi-angle SAR data can be obtained in one flight. Therefore, the system improves the efficiency of data recording. An improved range migration algorithm (RMA) is used for data processing, and imaging is made in a unified imaging coordinate system. The resolution of different view images is the same, and there is a fixed delay between the images. On this basis, the SAR image fusion is performed after image matching. The results of simulation and measured data confirm the effectiveness of the system and the method.


Inhibition of volume-regulated anion channels by dominant-negative caveolin-1.
Caveolae are flask-shaped invaginations of the plasma membrane formed by the association of caveolin proteins with lipid rafts. In endothelial cells, caveolae function as signal transduction centers controlling NO synthesis and mechanotransduction. We now provide evidence that the endothelial volume-regulated anion channel (VRAC) is also under the control of the caveolar system. When calf pulmonary artery endothelial (CPAE) cells were transfected with caveolin-1 Delta1-81 (deletion of amino acids 1 to 81), activation of VRAC by hypotonic cell swelling was strongly impaired. Concomitantly, caveolin-1 Delta1-81 disturbed the formation of caveolin-1 containing lipid rafts as evidenced by sucrose density gradient centrifugation. In nontransfected cells, endogenous caveolin-1 typically associated with low-density, detergent-resistant lipid rafts. However, transient expression of caveolin-1 Delta1-81 caused a redistribution of endogenous caveolin-1 to high-density, detergent-soluble membrane fractions. We therefore conclude that the interaction between caveolin-1 and detergent-resistant lipid rafts is an important prerequisite for endothelial VRAC activity.


Mechanical evaluation of nHAp scaffold coated with poly-3-hydroxybutyrate for bone tissue engineering.
Regeneration of bone, cartilage and osteochondral tissues by tissue engineering has attracted intense attention due to its potential advantages over the traditional replacement of tissues with synthetic implants. Nevertheless, there is still a dearth of ideal or suitable scaffolds based on porous biomaterials, and the present study was undertaken to develop and evaluate a useful porous composite scaffold system. In this study, nano hydroxyapatite (nHAp) powder made (about 35-45 nm) by heating at temperature of 900 degrees C and porous hydroxyapatite (40, 50 and 60 wt% solution) for making scaffold, by using Polyurethane sponge replication method. In order to increase the scaffolds mechanical properties, they coated with 2, 4 and 6 wt% Poly-3-hydroxybutyrate (P3HB) for 30 sec and 60 sec, respectively; after the scaffold coated by Polymer and survey results, this scaffold is nHAp/P3HB composite. Based on these results, this scaffold is an optimized one among three tested above mentioned composition and can be utilized in bone tissue engineering. In the result, the best of scaffold is with 50 wt% HAp and 6 wt% P3HB and porosity of present is between 80-90% with compressive strength and modulus 1.51 MPa and 22.73 MPa, respectively, that it can be application in bone tissue engineering.


Toward a Better Understanding of Electrocochleography: Analysis of Real-Time Recordings.
Real-time electrocochleography (ECochG) has been used as a monitoring tool during cochlear implantation (CI), whereby, amplitude drops have been correlated with postoperative acoustic hearing results. However, no consensus has been reached as to how a single event of an amplitude drop should be characterized. The aim of this study was to identify ECochG events that predict loss of hearing 1 month after surgery. Fifty-five patients were included in this prospective cohort study. Real-time ECochG measurements were performed during CI electrode insertion. Single ECochG events were characterized according to their amplitude loss and slope steepness. Using receiver operating characteristic analyses, the most efficient cut-off criterion for a relative hearing loss of 25% was an amplitude loss of 61% at a fixed slope steepness of 0.2 µV/sec. Three-quarters of our population had at least one such event during implantation. Most events occurred shortly before full insertion. With increasing number of events, median residual hearing thresholds deteriorated for all frequencies. Larger amplitude drops trended toward worse hearing preservation. Signal recovery after an ECochG event could not be correlated to acoustic hearing outcomes. Our data suggest that amplitude drops exceeding 61% of the ongoing signal at a slope steepness of 0.2 µV/sec are correlated with worse acoustic hearing preservation. Clearly defined ECochG events have the potential to guide surgeons during CI in the future. This is essential if a fully automated data analysis is to be employed or benchmarking undertaken.


Gcn5p contributes to the bidirectional character of the UGA3-GLT1 yeast promoter.
Analysis of the UGA3-GLT1 bidirectional promoter has indicated that its transcriptional activation is determined by the combined action of Gcn4p and Gln3p, and that its bidirectional character is influenced by chromatin organization, through the action of an Abf1p binding site and a polydAdTtract. Results presented in this paper show that lack of Gcn5p impairs histone acetylation and nucleosomal organization of the UGA3-GLT1 promoter, resulting in an asymmetrical transcriptional activation response of UGA3 and GLT1. The phenotype displayed by a double mutant impaired in GCN5 and in the Abf1p binding site indicates that the combined action of these two elements determines the bidirectional capacity of the UGA3-GLT1 intergenic region.


Synergetic effects of granulocyte-colony stimulating factor and cognitive training on spatial learning and survival of newborn hippocampal neurons.
Granulocyte-Colony Stimulating Factor (G-CSF) is an endogenous hematopoietic growth factor known for its role in the proliferation and differentiation of cells of the myeloic lineage. Only recently its significance in the CNS has been uncovered. G-CSF attenuates apoptosis and controls proliferation and differentiation of neural stem cells. G-CSF activates upstream kinases of the cAMP response element binding protein (CREB), which is thought to facilitate the survival of neuronal precursors and to recruit new neurons into the dentate gyrus. CREB is also essential for spatial long-term memory formation. To assess the role and the potential of this factor on learning and memory-formation we systemically administered G-CSF in rats engaged in spatial learning in an eight-arm radial maze. G-CSF significantly improved spatial learning and increased in combination with cognitive training the survival of newborn neurons in the hippocampus as measured by bromodeoxyuridine and doublecortin immunohistochemistry. Additionally, G-CSF improved re-acquisition of spatial information after 26 days. These findings support the hypothesis that G-CSF can enhance learning and memory formation. Due to its easy applicability and its history as a well-tolerated hematological drug, the use of G-CSF opens up new neurological treatment opportunities in conditions where learning and memory-formation deficits occur.


Ondansetron treatment reduces rotavirus symptoms-A randomized double-blinded placebo-controlled trial.
Rotavirus and norovirus cause acute gastroenteritis with severe diarrhoea and vomiting, symptoms that may lead to severe dehydration and death. The objective of this randomized double-blinded placebo-controlled study was to investigate whether ondansetron, a serotonin receptor antagonist could attenuate rotavirus- and norovirus-induced vomiting and diarrhoea, which would facilitate oral rehydration and possibly accelerate recovery and reduce need for hospitalization. Children with acute gastroenteritis, aged 6 months to 16 years where enrolled (n = 104) and randomized to one single oral dose (0.15mg/kg) of ondansetron (n = 52) or placebo (n = 52). The number of diarrhoea and vomiting episodes during the 24 hours following treatment was reported as well as the number of days with symptoms. Pathogens in faeces were diagnosed by real-time PCR. Outcome parameters were analyzed for rotavirus- and norovirus-positive children. One dose of oral ondansetron reduced duration of rotavirus clinical symptoms (p = 0.014), with a median of two days. Furthermore, ondansetron reduced diarrhea episodes, most pronounced in children that had been sick for more than 3 days before treatment (p = 0.028). Ondansetron may be a beneficial treatment for children with rotavirus gastroenteritis. European Clinical Trial Database EudraCT 2011-005700-15.


The circadian system in cystic fibrosis mice is regulated by histone deacetylase 6.
Disordered sleep experienced by people with cystic fibrosis (CF) suggest a possible disruption in circadian regulation being associated with the loss of cystic fibrosis transmembrane conductance regulator (Cftr) function. To test this hypothesis, circadian regulation was assessed in an F508del/F508del CF mouse model. CF mice exhibited significant alterations in both timing of locomotor activity and in mean activity per hour in both light-dark (LD) and dark-dark (DD) photoperiods compared with wild-type (WT) controls. It was also noted that in DD periodicity increased in CF mice, whereas shortening in WT mice as is expected. CF mice also exhibited altered timing of circadian gene expression and a reduction of melatonin production at all time points. Mechanistically, the role of microtubules in regulating these outcomes was explored. Mice lacking expression of tubulin polymerization promoting protein (Tppp) effectively mimicked CF mouse phenotypes with each measured outcome. Depleting expression of the microtubule regulatory protein histone deacetylase 6 (Hdac6) from CF mice (CF/Hdac6) resulted in the reversal of each phenotype to WT profiles. These data demonstrate an innate disruption of circadian regulation in CF mice and identify a novel microtubule-related mechanism leading to this disruption that can be targeted for therapeutic intervention.


Staphylococcus lugdunensis: the coagulase-negative staphylococcus you don't want to ignore.
Staphylococcus lugdunensis is a virulent coagulase-negative staphylococcus (CoNS) that behaves like Staphylococcus aureus. Toxic shock syndrome, osteomyelitis, septic arthritis and postoperative endopthalmitis have been observed. Endocarditis complicated by heart failure, periannular abscess formation and embolic phenomenon have brought particular attention to this CoNS. Mortality rates for endocarditis appear higher when compared with other CoNS. Owing to the laboratory methods used, identification may be misleading. β-lactam antimicrobials are recommended pending sensitivities. Evaluation for endocarditis should be pursued in bacteremic patients due to its pathogenic potential.


Relationship between serum and hepatic 7S fragments of type IV collagen in chronic liver disease.
We evaluated the mechanism of increased serum concentrations of the 7S fragment of the N-terminal domain of type IV collagen (7S collagen) in chronic liver disease. We measured the concentrations of hepatic-free and deposited 7S collagens after extraction with Tris-HCl buffer and bacterial collagenase, then compared them with the serum levels in 8 normal controls and 48 patients with chronic liver disease. The hepatic 7S collagen levels extracted with Tris-HCl buffer and collagenase accounted for 7% and 93%, respectively, of the total 7S collagen levels in normal controls. Both hepatic 7S collagen levels as well as serum levels increased in accordance with the progress of liver disease. Serum levels of 7S collagen showed a closer correlation with the hepatic 7S collagen levels extracted with Tris-HCl buffer (r = .822), compared with those extracted with collagenase (r = .382). On the other hand, the histological degrees of liver fibrosis were highly correlated with the hepatic collagenase-extracted 7S collagen levels (r = .822), compared with serum and the hepatic Tris-HCl buffer-extracted levels (r = .478 and r = .537, respectively). Although there was no difference in serum and hepatic 7S collagen levels between B and C viral patients, the serum and hepatic Tris-HCl buffer-extracted 7S collagen levels were higher in patients with alcoholic cirrhosis than patients with viral cirrhosis. However, the hepatic collagenase-extracted levels were similar in both groups. Gel filtration demonstrated that the serum and hepatic Tris-HCl buffer-extracted 7S collagens were mainly eluted in the macromolecular 7S collagen-reactive fraction in cirrhosis, whereas the hepatic collagenase-extracted 7S collagen was eluted in the authentic 7S collagen-reactive fraction. The results suggest that serum 7S collagen levels are not a particularly reliable measure of hepatic fibrosis but reflect the enhanced metabolism, especially synthesis of type IV collagen in the liver.


The cingulate island sign within early Alzheimer's disease-specific hypoperfusion volumes of interest is useful for differentiating Alzheimer's disease from dementia with Lewy bodies.
In addition to occipital hypoperfusion, preserved metabolism of the posterior cingulate gyri (PCG) relative to the precunei is known as the cingulate island sign (CIS) in the patients with dementia with Lewy bodies (DLB). CIS has been detected using [(18)F]fluorodeoxyglucose positron emission tomography but not using brain perfusion single-photon emission computed tomography (SPECT). The purpose of this study was to optimize brain perfusion SPECT to enable differentiation of DLB from Alzheimer's disease (AD) using CIS and occipital hypoperfusion. Eighteen patients with probable DLB and 17 age-matched Pittsburgh compound B-positive patients with AD underwent technetium-99m ethyl cysteinate dimer SPECT. SPECT Z-score maps were generated using the easy Z-score imaging system (eZIS) analysis software (Matsuda H, Mizumura S, Nagao T, Ota T, Iizuka T, Nemoto K, Takemura N, Arai H, Homma A, AJNR Am J Neuroradiol 28(4):731-6, 2007), which included volumes of interest (VOIs) in which a group comparison between patients with AD and cognitively normal subjects revealed significant relative hypoperfusion. We used the Montreal Neurological Institute (MNI) space anatomical border to divide the bilateral PCG to precunei VOIs into two parts, the PCG and precunei. Z-scores in the PCG, precunei, and occipital areas and ratios were analysed and compared with receiver operating characteristic (ROC) curve analyses. The largest area under the curve (AUC) value for use in differentiating DLB from AD with the ratio of PCG to medial occipital was 0.87; the accuracy, sensitivity, and specificity were 85.7, 88.9, and 82.4 %, respectively. The AUC with the ratio of PCG to the precuneus was smaller, and it was 0.85, though no significant difference was observed between these two AUCs. The Z-score ratio of the PCG within the early-AD-specific VOI to medial-occipital area is clinically useful in discriminating demented patients with DLB from those with AD.


Chaperonin GroEL: a novel phylogenetically conserved protein with strong immunoreactivity of Avian Pathogenic Escherichia coli isolates from duck identified by immunoproteomics.
Avian Pathogenic Escherichia coli (APEC) is one of the most important bacterial pathogens of poultry. The lack of suitable vaccines and the emergence of multi-resistant strains have hampered the control of avian colibacillosis. To identify immunogenic proteins of APEC as vaccine candidates, immunoproteomics and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) were applied. Proteins from total cell lysates of APEC DE205B isolated from the brain of a duck with septicemia and neurological symptom in China were separated by two-dimensional electrophoresis (2-DE) and reacted with hyperimmune duck serum against DE205B. Fourteen immunoreactive spots were found, representing 11 distinct proteins. These included two predominant immunogenic components, outer membrane protein A (OmpA) and flagellin (FliC). GroEL, which is a member of the molecular chaperone family and identical structurally to eukaryotic heat shock protein 60 (Hsp60), and the other eight antigens are reported here as immunoreactive proteins of APEC for the first time. Subsequently, nine genes encoding the identified proteins were successfully cloned and expressed in E. coli BL21 (DE3). Seven of the recombinant proteins were able to react with hyperimmune duck serum and three of them, GroEL, OmpA and FliC, showed stronger immunoreactivity. Challenge studies revealed that, just like OmpA and FliC, recombinant GroEL stimulated a strong antibody response and supported protective efficacy against APEC infection in ducks. With high phylogenetic conservation, it is considered that GroEL would be an ideal immunogen of APEC for vaccine development.


Electromyographic activity of knee stabilizer muscles during six different balance board stimuli after anterior cruciate ligament surgery.
The purpose of this study was to compare the electrical activity of the knee stabilizers, in patients with ACL (anterior cruciate ligament) reconstructed and uninjured individuals during different balance board stimuli. Eleven post-surgery individuals and eleven uninjured controls participated in the study. The muscular activity of the vastus medialis obliquus, vastus lateralis, semitendinosus, biceps femoris and gastrocnemius medial were analyzed by surface electromyography during the execution of six different balance board activities. All electromyographic data were reported as percentage of RMS mean values obtained in maximal voluntary isometric contractions (MVIC) for each muscle. When comparing the individuals with ACL reconstructed and uninjured controls, minor electromyographic activity was observed (MVIC %) for all the muscles in the surgery group (P < 0.05), however, when comparing each exercise between the groups, a statistically significant difference for vastus lateralis was demonstrated in the floor exercise (P = 0.02) and for gastrocnemius on the round board (P = 0.04). Individuals ACL reconstructed presented a decrease in muscular activity during different balance board stimuli, which suggests that compensatory alterations after ACL may still exist even after a surgery to repair an ACL rupture.


Large scale recovery and purification of periplasmic recombinant protein from E. coli using expanded bed adsorption chromatography followed by new ion exchange media.
Expanded bed chromatography was used for the recovery and purification of modified Pseudomonas aeruginosa exotoxin A. The exotoxin accumulates in the periplasmic space of E. coli BL21 (lambda DE3), was released from the cells by osmotic shock and captured by applying the open cell suspension directly to an anion exchanger (STREAMLINE DEAE) using an expanded bed (STREAMLINE) column. Processing of 4.5 kg of E. coli using the expanded bed process was 3 times faster and did not require clarification of the bacterial extract, in comparison with the conventional purification method. Also, the recovered protein solution was 3 times more concentrated and the yield slightly higher.


Prehospital fibrinolysis versus primary percutaneous coronary intervention in ST-elevation myocardial infarction: a systematic review and meta-analysis of randomized controlled trials.
Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion strategy in patients with ST-elevation myocardial infarction (STEMI), but its benefit over prehospital fibrinolysis (FL) is not clear. We performed a systematic review and meta-analysis of randomized controlled trials in which outcomes of patients with STEMI managed with FL early in the prehospital setting versus PPCI were compared. Compared with PPCI, FL was consistently associated with similar rates of short-term (30-90 days) death (relative risk [RR] 0.94, 95 % CI 0.67-1.31) and cardiovascular death (RR 0.95, 95 % CI 0.64-1.4), a decreased risk of cardiogenic shock (RR 0.67, 95 % CI 0.48-0.95), and an increased risk of any stroke (RR 3.57, 95 % CI 1.39-9.17) and hemorrhagic stroke (RR 4.37, 95 % CI 1.25-15.26). FL was also associated with similar rates of 1-year mortality (RR 1.01, 95 % CI 0.75-1.34) and major bleeding (RR 1.31, 95 % CI 0.96-1.78) in comparison with PPCI, but with a notable level (I 2 index 30.5 % and 59.8 %) of heterogeneity among studies. Our study suggests that, compared with PPCI, FL performed in the early prehospital setting is associated with similar mortality rates, lower rates of cardiogenic shock, and higher rates of stroke in patients with STEMI. Although the number of studies comparing the two strategies is relatively low, our results support prehospital FL and transfer to hub percutaneous coronary intervention (PCI) centers as a valid alternative to PPCI, allowing potential limitation of resources allocated to developing proximity 24/7 PCI facilities.


Treatment of chronic prostatitis lowers serum prostate specific antigen.
We evaluated men with documented chronic prostatitis and elevated serum prostate specific antigen (PSA) to determine whether treatment with antibiotics and anti-inflammatory drugs lowers serum PSA. We retrospectively reviewed the records of 95 men who presented with serum PSA greater than 4 ng./ml. and were subsequently diagnosed with chronic prostatitis with greater than 10 white blood cells per high power field in expressed prostatic excretions. Patients meeting these criteria were treated with a 4-week course of antibiotics and a nonsteroidal anti-inflammatory agent. In all patients followup PSA was determined within 2 months of treatment. Mean PSA decreased 36.4% from 8.48 ng./ml. before to 5.39 after treatment (p <0.001). In 44 patients (46.3%) serum PSA decreased to below 4 ng./ml. (mean 2.48) and these patients no longer had an indication for biopsy. In the remaining 51 patients serum PSA remained elevated at greater than 4 ng./ml. and they underwent double sextant transrectal ultrasound guided biopsy. Pathological study showed prostate cancer in 13 cases (25.5%), chronic inflammation in 37 (72.5%) and only benign prostatic hypertrophy in 1 (1.05%). PSA in the 13 patients with prostate cancer decreased with treatment only 4.8% from 8.32 to 7.92 ng./ml. (p >0.05). Followup PSA at a mean of 11.4 months was determined in 19 of the 44 men who responded to treatment. Mean PSA increased only 4.5% from 2.35 to 2.46 ng./ml. (p >0.05) during this followup interval. In almost half of the patients diagnosed with elevated PSA and chronic prostatitis serum PSA normalized with treatment and there was no longer an indication for transrectal ultrasound guided biopsy. Our study suggests that chronic prostatitis is an important cause of elevated PSA and when it is identified, treatment can decrease the percent of negative biopsies.


The elementary mass action rate constants of P-gp transport for a confluent monolayer of MDCKII-hMDR1 cells.
The human multi-drug resistance membrane transporter, P-glycoprotein, or P-gp, has been extensively studied due to its importance to human health and disease. Thus far, the kinetic analysis of P-gp transport has been limited to steady-state Michaelis-Menten approaches or to compartmental models, neither of which can prove molecular mechanisms. Determination of the elementary kinetic rate constants of transport will be essential to understanding how P-gp works. The experimental system we use is a confluent monolayer of MDCKII-hMDR1 cells that overexpress P-gp. It is a physiologically relevant model system, and transport is measured without biochemical manipulations of P-gp. The Michaelis-Menten mass action reaction is used to model P-gp transport. Without imposing the steady-state assumptions, this reaction depends upon several parameters that must be simultaneously fitted. An exhaustive fitting of transport data to find all possible parameter vectors that best fit the data was accomplished with a reasonable computation time using a hierarchical algorithm. For three P-gp substrates (amprenavir, loperamide, and quinidine), we have successfully fitted the elementary rate constants, i.e., drug association to P-gp from the apical membrane inner monolayer, drug dissociation back into the apical membrane inner monolayer, and drug efflux from P-gp into the apical chamber, as well as the density of efflux active P-gp. All three drugs had overlapping ranges for the efflux active P-gp, which was a benchmark for the validity of the fitting process. One novel finding was that the association to P-gp appears to be rate-limited solely by drug lateral diffusion within the inner monolayer of the plasma membrane for all three drugs. This would be expected if P-gp structure were open to the lipids of the apical membrane inner monolayer, as has been suggested by recent structural studies. The fitted kinetic parameters show how P-gp efflux of a wide range of xenobiotics has been maximized.


Unconscious priming by illusory figures: the role of the salient region.
In this study we provide evidence that unconscious priming can be obtained as a result of the processing of the salient region (SR) of illusory figures and without that of illusory contours (ICs). We used a metacontrast masking paradigm where illusory figures were masked by real figures. In Experiment 1 we found a clear priming effect when participants were asked to discriminate between square and diamond masks preceded by congruent or incongruent illusory square or diamond primes. It is likely that metacontrast impairs the processing of ICs but not of the SR; therefore the above result strongly suggests that the priming effect was specifically related to the processing of the SR. In Experiment 2 participants were tested in the same task as in Experiment 1 with additional primes in which the inducers were presented in the same locations but their shapes were changed so as to modify the global configuration. We termed these primes High, Low, and No Salient Region (HSR, LSR, and NSR, respectively). The HSR condition replicated Experiment 1, whereas in the LSR and NSR conditions the priming effect got progressively smaller. The results of Experiment 1 were replicated with the priming effect significantly larger in the HSR than in all other conditions. It was also larger in the HSR than in LSR condition and smallest but still present in the NSR condition. Taken together, these results indicate that the unconscious processing of only the SR yields a priming effect and that a reduction of the saliency of the SR leads to a reduction of the priming effect, while its elimination does not abolish it.


Cardiac magnetic resonance imaging in patients with Fabry's disease.
Fabry's disease (FD) is a rare hereditary disorder caused by the loss of alpha galactosidase A activity leading to accumulation of glycosphingolipids in various organs including hypertrophy of the heart. Most reports on cardiac involvement in FD focus on the left ventricular hypertrophy (LVH) and its relation to diastolic function. However, recent studies demonstrated large subset of patients with FD and right ventricle (RV) hypertophy. The accurate depiction of RV volumes, function and mass is possible with cardiovascular magnetic resonance (CMR). The CMR study can be also used to identify typically localised regions of intramyocardial fibrosis (infero-lateral segments of the LV), which have been shown to be a marker of inefficacious response to enzyme replacement therapy. We present series of 8 patients with genetically confirmed FD who underwent CMR study. We demonstrated a typical concentric and diffuse pattern of LVH with RV involvement in patients with the most severe LVH without significant impact on RV function and volumes. We showed that myocardial fibrosis can be observed not only in LV but also in RV. In 2 patients FD coexisted with symptomatic coronary artery disease with evidence of subendocardial myocardial fibrosis typical for ischaemic origin in one patient. The CMR confirmation of the presence of FD in one patient at an early stage of the disease, before the onset of advanced hypertrophy or failure of other organs, supports the value of this imaging technique in differential diagnosis of concentric and diffuse LVH.


Progesterone treatment of boar spermatozoa improves male pronuclear formation after intracytoplasmic sperm injection into porcine oocytes.
Boar spermatozoa were prepared for intracytoplasmic sperm injection (ICSI) by two different treatments to facilitate sperm chromatin decondensation and improve fertilisation rates after ICSI in pigs: spermatozoa were either frozen and thawed without cryoprotectants, or treated with progesterone. Morphological changes of the sperm heads after the treatments were examined and then the activation of oocytes and the transformation of the sperm nucleus following ICSI were assessed. After freezing and thawing, the plasma membrane and acrosomal contents over the apical region of sperm head were lost in all the spermatozoa. Following treatment with 1 mg/ml progesterone, the acrosome reaction was induced in 61% of spermatozoa. After injection of three types of spermatozoa, non-treated spermatozoa and progesterone-treated (i.e. acrosome-reacted) spermatozoa induced oocyte activation, but frozen-thawed spermatozoa induced oocyte activation at a significantly lower rate. Sixty-two per cent of sperm heads remained orcein-negative for 6 h, however, resulting in delayed sperm chromatin decondensation and low male pronuclear formation in the oocytes injected with a non-treated spermatazoon. Since the treatments of freezing and thawing and progesterone for spermatozoa accelerated the initial change in sperm chromatin and the latter treatment induced oocyte activation earlier, it is considered that the delay in oocyte activation and decondensation of sperm chromatin after injection of non-treated spermatozoa is caused by the existence of the sperm plasma membrane. These results show that progesterone treatment efficiently induces the acrosome reaction in boar spermatozoa without destroying their potency for oocyte activation, and the induction of the acrosome reaction results in the promotion of male pronuclear formation after ICSI.


Sex determination by three-dimensional geometric morphometrics of the vault and midsagittal curve of the neurocranium in a modern Greek population sample.
The aim of this study is to assess sexual dimorphism of adult crania in the vault and midsagittal curve of the vault using three-dimensional geometric morphometric methods. The study sample consisted of 176 crania of known sex (94 males, 82 females) belonging to individuals who lived during the 20th century in Greece. The three-dimensional co-ordinates of 31 ecto-cranial landmarks and 30 semi-landmarks were digitized using a MicroScribe 3DX contact digitizer. Generalized Procrustes analysis (GPA) was used to obtain size and shape variables for statistical analysis. Shape, size and form analyses were carried out by logistic regression and three discriminant function analyses. Results indicate that there are shape differences between sexes. Females in the region of the parietal bones are narrower and the axis forming the frontal and occipital bones is more elongated; the frontal bone is more vertical. Sex-specific shape differences give better classification results in the vault (79%) compared with the midsagittal curve of the neurocranium (68.8%). Size alone yielded better results for cranial vault (82%), while for the midsagittal curve of the vault the result is poorer (68.1%). As anticipated, the classification accuracy improves when both size and shape are combined (89.2% for vault, and 79.4% for midsagittal curve of the vault). These latter findings imply that, in contrast to the midsagittal curve of the neurocranium, the shape of the cranial vault can be used as an indicator of sex in the modern Greek population.


Method for assessing the dynamics and efficiency of diving fins.
This article presents a method for an evaluation of the dynamic ability and efficiency of diving fins. There is paucity in the literature on the process of selecting optimal fins. As a result, there are efforts made to develop a methodology for selecting fins that meet the proposed criteria. In the present study, an analysis on the two types of fins most popular within the commercial market was conducted. The experiment took place in a test water tunnel fully equipped with a measuring system and strain gauges for recording forced interaction between the moving fin and flowing water. The tested fins rested on an artificial leg, which moved respectively, thereby developing movement algorithms. This forced fluid flow was implemented by a pump that was able to control the fluids velocity, and a non-invasive method involving an ultrasonic flow meter was used to measure the fluids velocity. Finally, the fin efficiency was calculated as the ratio of multiplication of generated thrust to electrical energy consumption whilst also considering the mechanical efficiency of the leg manipulator. The results of these experiments are discussed in depth and a method is created for the subsequent stage in which a new type of fins called biomimetic is to be analyzed and compared.


Numerical analysis of the biomechanical effects on micro-vessels by ultrasound-driven cavitation.
The goal of this study was to evaluate the biomechanical effects such as sonoporation or permeability, produced by ultrasound- driven microbubbles (UDM) within microvessels with various parameters. In this study, a bubble-fluid-solid coupling system was established through combination of finite element method. The stress, strain and permeability of the vessel wall were theoretically simulated for different ultrasound frequencies, vessel radius and vessel thickness. the bubble oscillation induces the vessel wall dilation and invagination under a pressure of 0.1 MPa. The stress distribution over the microvessel wall was heterogeneous and the maximum value of the midpoint on the inner vessel wall could reach 0.7 MPa as a frequency ranges from 1 to 3 MHz, and a vessel radius and an initial microbubble radius fall within the range of 3.5-13 μm and 1-4 μm, respectively. With the same conditions, the maximum shear stress was equal to 1.2 kPa and occurred at a distance of ±5 μm from the midpoint of 10 μm and the maximum value of permeability was 3.033 × 10^-13. Results of the study revealed a strong dependence of biomechanical effects on the excitation frequency, initial bubble radius, and vessel radius. Numerical simulations could provide insight into understanding the mechanism behind bubble-vessel interactions by UDM, which may explore the potential for further improvements to medical applications.


Folate-Modified Liposomes Loaded with Telmisartan Enhance Anti-Atherosclerotic Potency for Advanced Atherosclerosis in ApoE-/- Mice.
For the effective inhibition of atherosclerotic plaque rupture, there is an urgent need to develop a carrier which can specifically deliver the therapeutic agents to atherosclerotic lesions. Since the representative hallmark of plaques in advanced atherosclerosis is the large number of macrophages which highly upregulate folate receptor beta (FR-β), we herein investigated the potential of folate-modified liposomes (FA-P-LP) as the carrier for active targeting of atherosclerotic plaques. In vitro cellular uptake tests, FA-P-LP exhibited an enhanced uptake in activated RAW264.7 macrophages with high expression of FR-β, whereas this enhanced effect was dramatically diminished when the cells were pretreated with excess amount of free folate, indicating that FA-P-LP were mainly taken up by the receptor-mediated endocytosis. From the in vivo distribution assay, it was confirmly demonstrated that FA-P-LP significantly accumulated in atherosclerotic lesions and were co-localized with macrophages within plaques. Thereafter, we utilized the FA-P-LP to deliver an angiotensin receptor blocker (ARB), telmisartan (Tel), to macrophages in atherosclerotic plaques and evaluated their therapeutic effects on plaque destabilization. After 12 weeks treatment in ApoE-/- mice with established atherosclerosis, FA-P-LP/Tel exerted a marked improvement in key advanced plaque properties without affecting the plasma lipid level and blood pressure. These beneficial effects include the regression of atherosclerotic plaques possibly attributing to the enhanced cellular cholesterol efflux and reduced macrophage infiltration, an increase in the protective collagen layer overlying lesions resulting from suppression of collagenase activity and decrease in matrix 2/9 (MMP 2/9) expression, suppression of oxidative stress, and a reduction in plaque necrosis and calcification. Thus, administration of Tel in a targeted liposome could stabilize the advanced atherosclerotic lesions independent of lipid lowering and blood pressure decrease. In conclusion, FA-P-LP could effectively home to the atherosclerotic lesion through the active targeting mechanism after systemic administration, indicating their high potential as the carrier for atherosclerosis therapy. Together, the FA-P-LP/Tel would be considered as a promising nanotherapeutic approach to prevent plaque rupture, providing an alternative regimen for clinical treatment of advanced atherosclerosis.


Periodic magnetic field as a polarized and focusing thermal neutron spectrometer and monochromator.
A novel periodic magnetic field (PMF) optic is shown to act as a prism, lens, and polarizer for neutrons and particles with a magnetic dipole moment. The PMF has a two-dimensional field in the axial direction of neutron propagation. The PMF alternating magnetic field polarity provides strong gradients that cause separation of neutrons by wavelength axially and by spin state transversely. The spin-up neutrons exit the PMF with their magnetic spins aligned parallel to the PMF magnetic field, and are deflected upward and line focus at a fixed vertical height, proportional to the PMF period, at a downstream focal distance that increases with neutron energy. The PMF has no attenuation by absorption or scatter, as with material prisms or crystal monochromators. Embodiments of the PMF include neutron spectrometer or monochromator, and applications include neutron small angle scattering, crystallography, residual stress analysis, cross section measurements, and reflectometry. Presented are theory, experimental results, computer simulation, applications of the PMF, and comparison of its performance to Stern-Gerlach gradient devices and compound material and magnetic refractive prisms.


Affective Mobilizations: Pinkwashing and Racialized Homophobia in Out There.
This paper focuses on the affective economies which materialize around race, sexuality and queerness in the British context to enable the production and mobilization of an exceptionalist discourse of gay-friendly and post-homophobic Britain (i.e., pinkwashing). The author investigates the discursive workings of pinkwashing coupled with the racialization of homophobia, through a critical reading of the BBC Two documentary Out There (2013a), written and narrated by British gay-identified writer, activist and artist, Stephen Fry. The documentary captures and is in fact captured within a global moment of human rights speculation in which some European nation-states have invested in affective discourses of queer futurities as a marker of their capacity for tolerance, in contrast to predominantly racialized subjects/communities within and outside of Europe, increasingly naturalized as always already homophobic (i.e., racializing homophobia). My reading of the documentary demonstrates the interconnection between pinkwashing and racialized homophobia as discursive inventions which depend on the mobilization of affects such as love, pride, terror, hate and (un)happiness, as currencies of governance. Far from being universal or abstract, I contend that British LGBTQ human rights speculative discourse draws on a highly racialized affective economy-which constructs racialized communities within Britain and racialized populations and states outside the West, as excessively homophobic, rendering pre-dominantly gay male British subjects (and homopatriarchy) as exceptional patriots.


Alleged dowry death: a study of homicidal burns.
Homicidal burning of married women in India is a major concern for the Government, law-enforcing authorities, the judiciary, the police and medico-legal experts all over the country who are associated with dowry disputes. Dowry death, a heinous crime, is gradually engulfing and polluting the entire society. Sections 304(B) and 498(A) of the Indian Penal Code (IPC) have been introduced and Sections 174 Criminal Procedure Code (Cr PC) and 176 Cr PC have been modified but, instead of deterring dowry deaths, the occurrences are increasing day by day and the number of cases coming for post-mortem examination is rising. Both parties, that is, the parents and in-laws of the deceased, are becoming adept at manufacturing circumstantial evidence to serve their own interests. Therefore, to establish the truth and for the smooth administration of justice, reliable unbiased medical evidence has to be corroborated. This study presents retrospective research carried out in the tertiary care teaching hospital of MKCG Medical College, Berhampur, Eastern India, for a five-year period between January 1998 to December 2002. From a total of 58 burned wives, 32 (55.1%) were homicidal burns. These cases were analyzed in view of epidemiological and medico-legal aspects. The majority of the affected women (90.63%) were in the 18 to 26 years of age group. Death occurred within the first few years of marriage and most of them had no children. All the victims belonged to the Hindu religion and 62.5% of incidents occurred during the daytime. In 71.87% cases the incident occurred in rural areas. Eighty-three per cent of cases occurred in a joint family within the house. In most cases, kerosene was the accelerant and flame was the causative agent. In more than 68.75% of cases the total body surface area involved was more than 80%. Most victims died at the time of the incident, or within the subsequent 24 hours, due to hypovolumeic shock. The education status in 70.21% cases was either illiterate or under matriculation. More stringent laws and female independence both mentally and economically will reduce the homicidal burns in young brides.


Confidence and gradation in causal judgment.
When comparing the roles of the lightning strike and the dry climate in causing the forest fire, one might think that the lightning strike is more of a cause than the dry climate, or one might think that the lightning strike completely caused the fire while the dry conditions did not cause it at all. Psychologists and philosophers have long debated whether such causal judgments are graded; that is, whether people treat some causes as stronger than others. To address this debate, we first reanalyzed data from four recent studies. We found that causal judgments were actually multimodal: although most causal judgments made on a continuous scale were categorical, there was also some gradation. We then tested two competing explanations for this gradation: the confidence explanation, which states that people make graded causal judgments because they have varying degrees of belief in causal relations, and the strength explanation, which states that people make graded causal judgments because they believe that causation itself is graded. Experiment 1 tested the confidence explanation and showed that gradation in causal judgments was indeed moderated by confidence: people tended to make graded causal judgments when they were unconfident, but they tended to make more categorical causal judgments when they were confident. Experiment 2 tested the causal strength explanation and showed that although confidence still explained variation in causal judgments, it did not explain away the effects of normality, causal structure, or the number of candidate causes. Overall, we found that causal judgments were multimodal and that people make graded judgments both when they think a cause is weak and when they are uncertain about its causal role.


Inhibition of the calcium channel by intracellular protons in single ventricular myocytes of the guinea-pig.
1. The inhibitory effects of intracellular protons (Hi+) on the L-type Ca2+ channel activity were investigated in single ventricular myocytes of guinea-pigs by using the patch-clamp method in the open-cell-attached patch configuration, where 'run down' of the channel was partially prevented. 2. Hi+ reduced the unitary Ba2+ current of the Ca2+ channel by 10-20% without changing the maximum slope conductance. 3. Hi+ did not alter the number of channels in patches containing one or two channels. 4. Hi+ markedly reduced the mean current normalized by the unitary current, which gave the open-state probability multiplied by the number of channels in the patch. The dose-response curve between Hi+ and the open-state probability indicated half-maximum inhibition at pHi 6.6 and an apparent Hill coefficient of 1. 5. Hi+ shifted both the steady-state activation and inactivation curves in a negative direction by 10-15 mV, and the effects were reversible. 6. Hi+ did not affect the fast open-closed kinetics represented by the C-C-O scheme, apart from increasing the slow time constant of the closed time. 7. Hi+ increased the percentage of blank sweeps and reduced that of non-blank sweeps resulting in a decreased probability of channel opening. 8. Photo-oxidation with Rose Bengal abolished the reducing effect of Hi+ on the open-state probability (Po) in two out of ten experiments, suggesting the possible involvement of histidine residues in the Hi+ effect. 9. The above results indicate that Hi+ inhibits the Ba2+ current mainly by affecting the slow gating mechanism of the channel.


Cerebral Blood Flow after Acute Bypass with Parent Artery Trapping in Patients with Ruptured Supraclinoid Internal Carotid Artery Aneurysms.
Bypass with parent artery trapping is an alternative treatment method for ruptured internal carotid artery (ICA) aneurysms when clipping or coiling is contraindicated. However, the efficacy and safety of this strategy during the acute stage of subarachnoid hemorrhage (SAH) is undetermined. A retrospective review of 955 consecutive patients presenting SAH between 2006 and 2014 identified 17 patients with ruptured ICA aneurysms treated by bypass with parent artery trapping within 72 hours after the bleeding (bypass group). The 26 cases with ruptured posterior communicating artery aneurysms treated with clipping during the same period were defined as a control group (clipping group). Postoperative cerebral blood flow (CBF) was evaluated by single photon emission computed tomography (SPECT). We analyzed the postoperative hemodynamic status, surgical complications, and the clinical outcomes. Postoperative rebleeding did not occur in any of the cases. CBF in the first postoperative week in the bypass group was lower than that in the clipping group (P = .0165). This CBF decrease improved in the second postoperative week and did not differ from that of the clipping group. The incidence of acute ischemic complications was significantly higher in the bypass group (P = .0284), but the incidence of delayed cerebral ischemia did not differ between the 2 groups. The incidence of favorable outcomes at 6 months was 82.4% in the bypass group and 81% in the clipping group. Although the transient CBF decrease with acute ischemic complications should be noted, acute bypass with parent artery trapping is safe and effective for unclippable/uncoilable ruptured ICA aneurysms.