Many structurally flexible regions play important roles in biological processes. It has been shown that extended loopy regions are very abundant in the protein universe and that they have been conserved through evolution. Here, we present NORSp, a publicly available predictor for disordered regions in protein. Specifically, NORSp predicts long regions with NO Regular Secondary structure. Upon user submission of a protein sequence, NORSp will analyse the protein for its secondary structure, presence of transmembrane helices and coiled-coil. It will then return email to the user about the presence and position of disordered regions. NORSp can be accessed from http://cubic.bioc.columbia.edu/services/NORSp/.
The different effects of regular and stochastic stimulation on the flexor reflex of patients with the spinal cord totally divided and of normal subjects and on the blink reflex of normal subjects were studied.
As database management systems expand their array of analytical functionality, they become powerful research engines for biomedical data analysis and drug discovery. Databases can hold most of the data types commonly required in life sciences and consequently can be used as flexible platforms for the implementation of knowledgebases. Performing data analysis in the database simplifies data management by minimizing the movement of data from disks to memory, allowing pre-filtering and post-processing of datasets, and enabling data to remain in a secure, highly available environment. This article describes the Oracle Database 10g implementation of BLAST and Regular Expression Searches and provides case studies of their usage in bioinformatics. http://www.oracle.com/technology/software/index.html
Behavioral contrast and response-ratio sensitivity to reinforcement were compared in multiple schedules in which components alternated strictly or according to a pseudorandom sequence. Average component durations in the two regimes were always 60 s, and order of presentation of component alternation regimes was counterbalanced across subjects. In Part 1, the reinforcer rate in one component was reduced from 60 per hour to zero, while that in the other component was unchanged. Positive behavioral contrast occurred in the constant component in that response rates increased, but neither the reliability nor the magnitude of contrast was affected by the manner in which components alternated. Part 2 was similar, except that a number of different reinforcer rates were used in the varied component. Neither contrast nor sensitivity of response ratios to changes in reinforcer ratios depended on the regime of component alternation. Thus, the predictability in time of future reinforcement conditions, which is a feature of regular multiple scheduling, does not appear to be a determinant of multiple-schedule performance.
Intratumoral hypoxia and paracrine insulin stimulate the expression of hypoxia inducible factor-1α (HIF-1α) in pancreatic cancer cells. In the present studies, we investigated whether insulin-induced HIF-1α expression is a prerequisite for insulin to induce other trophic effects in MiaPaCa2 human pancreatic cancer cells and whether inhibition of HIF-1α expression would decrease tumor glycolysis and improve host energy homeostasis. We found that hypoxia was a prerequisite for induction of HIF-1α mRNA expression by insulin in MiaPaCa2 cells. Under hypoxic conditions, insulin stimulated glycolysis, cell proliferation, and the secretion of vascular endothelial growth factor in regular MiaPaCa2 cells but not in a MiaPaCa2 variant (si-MiaPaCa2) that expressed specific short interfering RNA for HIF-1α and therefore lacked HIF-1α protein. This suggests that HIF-1α expression is required for insulin to induce other trophic effects. When si-MiaPaCa2 cells were transplanted into the pancreas of athymic mice, they were less tumorigenic and expressed less hexokinase than regular MiaPaCa2 cells. Body weight gain was attenuated in mice hosting tumors composed of regular MiaPaCa2 but not si-MiaPaCa2 cells. These results suggest that an interaction between insulin and HIF-1α helps sustain pancreatic cancer cells and disturbs host energy homeostasis.
Malignant mesotheliomas are tumors known for their extensive heterogeneity. Apart from the three classical patterns, predominantly epithelioid, sarcomatoid, and biphasic, some rare variants do exist. In some cases, one can find uncommon additional mesodermal tumor components. These tumors have previously been called “mesodermomas” and, like regular mesotheliomas, are usually associated with a previous asbestos exposure. We examined eight cases of mesodermomas by light microscopy, immunohistochemistry and comparative genomic hybridization (CGH). Besides biphasic and epithelioid areas, unusual epithelial, chondroid, osseous, or even angioblastic elements may be found to varying degrees. Immunohistochemical analysis shows similar staining results as with regular mesotheliomas. CGH reveals a high number of chromosomal imbalances (16.5 per case; range, 11–27). In 10 classical biphasic mesotheliomas that served as a control, defects of comparable number and severity could not be detected (8 per case; range, 2–16). The most frequent defects of mesodermomas (losses on 1p, 4pq, 9p, 13q, 14q, and gains on 1q and 15q), however, could also be found in mesotheliomas of the classical type. Thus, our results support the classification of the so-called mesodermomas as a separate tumor subgroup while maintaining the relationship to the classical mesotheliomas. Therefore...
Cardiovagal baroreflex sensitivity (BRS), the arterial baroreflex-mediated change in the R-R interval per unit change in systolic blood pressure, decreases with advancing age in sedentary adult humans. We determined the effects of regular aerobic exercise on the age-related decline in cardiovagal BRS.In the cross-sectional study, 133 healthy men 18-79 years of age who were either sedentary, performing moderate aerobic exercise, or endurance exercise trained were studied. Among the sedentary men, cardiovagal BRS (phase IV of Valsalva’s manoeuvre) was progressively lower (P < 0·05) in the middle-aged (≈33 %) and older (≈60 %) groups compared with the young group. In contrast, cardiovagal BRS was similar in the young and middle-aged men in the moderate exercise and endurance-trained groups. Cardiovagal BRS was lower (P < 0·05) in the older exercising men, but the magnitude of decline across age (≈30 %) was only half as great as that in sedentary men. Cardiovagal BRS was 40-75 % greater (P < 0·05) in middle-aged and older men who exercised regularly compared with their sedentary peers.In the intervention study, a 3 month aerobic exercise intervention (primarily walking) increased cardiovagal BRS by an average of 25 % (P < 0·05) in 13 previously sedentary middle-aged and older (56 ± 1 years) healthy men.Our results demonstrate for the first time that regular aerobic exercise: (1) attenuates the age-associated decline in cardiovagal BRS; and (2) partially restores the loss of cardiovagal BRS in previously sedentary middle-aged and older healthy men.
In experimental animals chronic elevations in arterial blood flow increase the lumen diameter and reduce the intima-media thickness (IMT) of the arterial segment involved. We determined whether intermittent elevations in active muscle blood flow associated with regular aerobic leg exercise induced such expansive arterial remodelling in the common femoral artery of humans.In the cross-sectional study 53 sedentary (47 ± 2 years) and 55 endurance exercise-trained (47 ± 2 years) men were studied. Common femoral artery lumen diameter (B-mode ultrasound) was 7 % greater (9.62 ± 0.12 vs. 9.03 ± 0.13 mm), and femoral IMT (0.46 ± 0.02 vs. 0.55 ± 0.02 mm) and IMT/lumen ratio were 16–21 % smaller in the endurance-trained men (all P < 0.001). Basal femoral artery blood flow (duplex ultrasound) was not different, shear stress tended to be lower (P = 0.08), and mean femoral tangential wall stress was 30 % higher in the endurance-trained men (P < 0.001).In the intervention study 22 men (51 ± 2 years) were studied before and after 3 months of regular aerobic leg exercise (primarily walking). After training, the femoral diameter increased by 9 % (8.82 ± 0.18 vs. 9.60 ± 0.20 mm), and IMT (0.65 ± 0.05 vs. 0.56 ± 0.05 mm) and the IMT/lumen ratio were ≈15–20 % smaller (all P < 0.001). Basal femoral blood flow and shear stress were not different after training...
The capacity of the vascular endothelium locally to release tissue-type plasminogen activator (t-PA) is critical for effective endogenous fibrinolysis. We determined the influence of ageing and regular aerobic exercise on the net release of t-PA across the human forearm in vivo using both cross-sectional and intervention approaches. First, we studied 62 healthy men aged 22-35 or 50-75 years of age who were either sedentary or endurance exercise-trained. Net endothelial release rates of t-PA were calculated as the product of the arteriovenous concentration gradient and forearm plasma flow to intra-arterial bradykinin and sodium nitroprusside. Second, we studied 10 older (60 ± 2 years) healthy sedentary men before and after a 3 month aerobic exercise intervention. Net endothelial t-PA release was significantly blunted with age in the sedentary men. At the highest dose of bradykinin the increase in t-PA antigen release was ≈35 % less (P < 0.05) in the older (from −1.0 ± 0.4 to 37.8 ± 3.8 ng (100 ml tissue)−1 min−1) compared with young (from 0.1 ± 0.6 to 56.6 ± 9.2 ng (100 ml tissue)−1 min−1) men. In contrast, the endurance-trained men did not demonstrate an age-related decline in the net release of t-PA antigen. After the exercise intervention...
Weight loss is accompanied by several metabolic adaptations that work together to promote rapid, efficient regain. We employed a rodent model of regain to examine the effects of a regular bout of treadmill exercise on these adaptations. Obesity was induced in obesity-prone rats with 16 wk of high-fat feeding and limited physical activity. Obese rats were then weight reduced (∼14% of body wt) with a calorie-restricted, low-fat diet and maintained at that reduced weight for 8 wk by providing limited provisions of the diet with (EX) or without (SED) a daily bout of treadmill exercise (15 m/min, 30 min/day, 6 days/wk). Weight regain, energy balance, fuel utilization, adipocyte cellularity, and humoral signals of adiposity were monitored during eight subsequent weeks of ad libitum feeding while the rats maintained their respective regimens of physical activity. Regular exercise decreased the rate of regain early in relapse and lowered the defended body weight. During weight maintenance, regular exercise reduced the biological drive to eat so that it came closer to matching the suppressed level of energy expenditure. The diurnal extremes in fuel preference observed in weight-reduced rats were blunted, since exercise promoted the oxidation of fat during periods of feeding (dark cycle) and promoted the oxidation of carbohydrate (CHO) later in the day during periods of deprivation (light cycle) . At the end of relapse...
Objective: Both first- (FGAs) and second-generation antipsychotics (SGAs) are routinely used in treating severe and persistent psychiatric disorders. However, until now no articles have analyzed systematically the safety of both classes of psychotropics during pregnancy. Data sources and search strategy: Medical literature information published in any language since 1950 was identified using MEDLINE/PubMed, TOXNET, EMBASE, and The Cochrane Library. Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from companies developing drugs. Search terms were pregnancy, psychotropic drugs, (a)typical-first-second-generation antipsychotics, and neuroleptics. A separate search was also conducted to complete the safety profile of each reviewed medication. Searches were last updated on July 2008. Data selection: All articles reporting primary data on the outcome of pregnancies exposed to antipsychotics were acquired, without methodological limitations. Conclusions: Reviewed information was too limited to draw definite conclusions on structural teratogenicity of FGAs and SGAs. Both classes of drugs seem to be associated with an increased risk of neonatal complications. However...
Background: Neurological soft signs (NSS) are hypothesized as candidate endophenotypes for schizophrenia, but their prevalence and relations with clinical and demographic data are unknown. The authors undertook a quantification (meta-analysis) of the published literature on NSS in patients with schizophrenia and healthy controls. A systematic search was conducted for published articles reporting NSS and related data using standard measures in schizophrenia and healthy comparison groups. Method: A systematic search was conducted for published articles reporting data on the prevalence of NSS in schizophrenia using standard clinical rating scales and healthy comparison groups. Meta-analyses were performed using the Comprehensive Meta-analysis software package. Effect sizes (Cohen d) indexing the difference between schizophrenic patients and the healthy controls were calculated on the basis of reported statistics. Potential moderator variables evaluated included age of patient samples, level of education, sample sex proportions, medication doses, and negative and positive symptoms. Results: A total of 33 articles met inclusion criteria for the meta-analysis. A large and reliable group difference (Cohen d) indicated that, on average, a majority of patients (73%) perform outside the range of healthy subjects on aggregate NSS measures. Cognitive performance and positive and negative symptoms share 2%–10% of their variance with NSS. Conclusions: NSS occur in a majority of the schizophrenia patient population and are largely distinct from symptomatic and cognitive features of the illness.
Objective To examine the influence of childhood economic strains on substance use in young adulthood and to assess the mediating roles of self-control as well as positive parenting during adolescence in a nationally representative longitudinal cohort. Methods The study included data from participants (n = 1,285) in the Panel Study of Income Dynamics, Child Development Supplement, and Transition to Adult. Structural equation modeling was used to evaluate the associations among risk factors during childhood and adolescence that predicted substance use in early adulthood. Results Conditions of economic strains, especially poverty, during childhood were associated with an increased likelihood of regular smoking in adulthood, which was partially mediated by poorer self-control during adolescence. Conclusions Self-control is negatively affected by economic strains and serves as a mediator between poverty and risk of regular smoking. Additional research is needed to better understand how economic strains effect the development of self-control.
We studied the time course of serum insulin level in a patient who injected large amounts of regular insulin in an attempted suicide. A 58‐year‐old woman attempted suicide by subcutaneously injecting herself with 2400 U regular insulin. On arrival, the serum glucose level was 2.4 mmol/L (44 mg/dL) and the serum insulin level was 40,000 pmol/L (5700 μIU/mL). The serum insulin level was high, with a maximum of 110,000 pmol/L (16,000 μIU/mL) at 13 h after injection, followed by an initial rapid decrease and a subsequent slow decrease, with hyperinsulinemia lasting as long as 5 days after injection. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2012.00211.x, 2012)
The aim of the present study was to compare the usefulness of premeal rapid‐acting and regular insulin in type 2 diabetes patients. A total of 56 type 2 diabetic patients were investigated during hospitalization. Premeal rapid‐acting insulin was applied instead of other medications. Premeal insulin was titrated to adjust premeal and bedtime blood glucose levels to 81–120 mg/dL. Premeal rapid‐acting insulin was changed to regular insulin just before a meal at the same dosage if the postmeal blood glucose level was lower than the premeal blood glucose level. A total of 15 patients changed to regular insulin, and 41 patients continued rapid‐acting insulin. The blood glucose level was comparable between these two groups. Body mass index was significantly lower in the patients using regular insulin. According to the multivariate logistic regression analysis, low body mass index was an independent variable accounting for the usefulness of regular insulin. Regular insulin, rather than rapid‐acting insulin, is a suitable choice for premeal insulin in lean type 2 diabetic patients.
In academia, journals serve as a proxy for quality, where prestigious journals are presumed to publish articles of higher quality than their less prestigious counterparts. Concerns over editorial bias in selecting articles, however, challenge this claim. This article develops a framework for evaluating this bias in legal academia, examining over 25,000 articles from nearly 200 general interest law reviews. Examining published articles in law reviews—the dominant venue for scholarship—and subsequent citations to these articles, we find that, with few exceptions, law reviews publish more articles from faculty at their own institution than from faculty at other law schools. Law review publications of their own faculty are cited less frequently than publications of outside faculty. This disparity is more pronounced among higher-ranked law reviews, but occurs across the entire distribution of journals. We correspondingly find that law faculty publish their lesser-cited articles in their own law review relative to their articles published in other law reviews. These findings suggest that legal scholarship, in contrast to other academic disciplines, exhibits bias in article selection at the expense of lower quality (JEL codes: I2, J7 and J24)
to which asthma morbidity in the community occurs in patients who are
having relatively little treatment or in those on step 3 or above of
the British asthma management guidelines is uncertain. We have looked
at this in a community population in southern Nottinghamshire. METHODS—A cross
sectional review of treatment in all patients over the age of four with
diagnosed asthma was carried out in five large general practices
(population 38 865) in 1995/6 using computerised general practice
records. The patients' usual treatment was obtained from prescription
data and categorised by the appropriate step on the British guidelines
on asthma management. Two measures of morbidity, the request for 10 or
more short acting β agonist inhalers a year or the need for a course
of oral corticosteroids in the last year, were related to the regular
treatment of the patients. RESULTS—Of the 3373 patients (8.7%) given a diagnosis of asthma, the percentage on steps
1, 2, 3, 4, and 5 of treatment were 54%, 22%, 11%, 3.6%, and 1%,
respectively, with a further 8% having had no treatment. During the
past year 13.6% had been prescribed 10 or more β agonist inhalers
and 12.5% had received at least one course of oral corticosteroids.
Both measures occurred more frequently in patients taking more
prophylactic treatment (step 3 or above). Nevertheless...
Anthropogenic noise impacts behaviour and physiology in many species, but responses could change with repeat exposures. As repeat exposures can vary in regularity, identifying regimes with less impact is important for regulation. We use a 16-day split-brood experiment to compare effects of regular and random acoustic noise (playbacks of recordings of ships), relative to ambient-noise controls, on behaviour, growth and development of larval Atlantic cod (Gadus morhua). Short-term noise caused startle responses in newly hatched fish, irrespective of rearing noise. Two days of both regular and random noise regimes reduced growth, while regular noise led to faster yolk sac use. After 16 days, growth in all three sound treatments converged, although fish exposed to regular noise had lower body width–length ratios. Larvae with lower body width–length ratios were easier to catch in a predator-avoidance experiment. Our results demonstrate that the timing of acoustic disturbances can impact survival-related measures during development. Much current work focuses on sound levels, but future studies should consider the role of noise regularity and its importance for noise management and mitigation measures.
Chronic musculoskeletal pain is a significant health problem and is associated with increases in pain during acute physical activity. Regular physical activity is protective against many chronic diseases; however, it is unknown if it plays a role in development of chronic pain. The current study induced physical activity by placing running wheels in home cages of mice for 5 days or 8 wk and compared these to sedentary mice without running wheels in their home cages. Chronic muscle pain was induced by repeated intramuscular injection of pH 4.0 saline, exercise-enhanced pain was induced by combining a 2-h fatiguing exercise task with a low-dose muscle inflammation (0.03% carrageenan), and acute muscle inflammation was induced by 3% carrageenan. We tested the responses of the paw (response frequency) and muscle (withdrawal threshold) to nociceptive stimuli. Because the rostral ventromedial medulla (RVM) is involved in exercise-induced analgesia and chronic muscle pain, we tested for changes in phosphorylation of the NR1 subunit of the N-methyl-d-aspartate (NMDA) receptor in the RVM. We demonstrate that regular physical activity prevents the development of chronic muscle pain and exercise-induced muscle pain by reducing phosphorylation of the NR1 subunit of the NMDA receptor in the central nervous system. However...
The growth of 50 children receiving regular inhaled
corticosteroids was segregated into divisions of six weeks from the
start of treatment and compared with their growth when not receiving regular corticosteroids using a random effects regression model. Growth
suppression was most marked during the initial six weeks after starting
treatment, with most suppression occurring during the initial 18 weeks.
Thereafter the children's growth was similar to their growth when not
receiving treatment. These findings have important consequences for
patterns of treatment of asthma in children.