Miracle-dz/UniFAR-FTUs huggingface dataset:
Overexpression of human fibroblast caldesmon fragment containing actin- , Ca++/calmodulin-, and tropomyosin-binding domains stabilizes endogenous tropomyosin and microfilaments

Fibroblast caldesmon is a protein postulated to participate in the modulation of the actin cytoskeleton and the regulation of actin-based motility. The cDNAs encoding the NH2-terminal (aa.1-243, CaD40) and COOH-terminal (aa.244-538, CaD39) fragments of human caldesmon were subcloned into expression vectors and we previously reported that bacterially produced CaD39 protein retains its actin-binding properties as well as its ability to enhance low M(r) tropomyosin (TM) binding to actin and to inhibit TM-actin-activated HMM ATPase activity in vitro (Novy, R. E., J. R. Sellers, L.-F. Liu, and J. J.-C. Lin. 1993. Cell Motil. Cytoskeleton. 26:248-261). Bacterially produced CaD40 does not bind actin. To study the in vivo effects of CaD39 expression on the stability of actin filaments in CHO cells, we isolated and characterized stable CHO transfectants which express varying amounts of CaD39. We found that expression of CaD39 in CHO cells stabilized microfilament bundles as well as endogenous TM. CaD39-expressing clones displayed an increased resistance to cytochalasin B and Triton X-100 treatments and yielded increased amounts of TM-containing actin filaments in microfilament isolation procedures. In addition, analysis of these clones with immunoblotting and indirect immunofluorescence microscopy with anti-TM antibody revealed that stabilized endogenous TM and enhanced TM-containing microfilament bundles parallel increased amounts of CaD39 expression. The increased TM observed corresponded to a decrease in TM turnover rate and did not appear to be due to increased synthesis of endogenous TM. Additionally, the phenomenon of stabilized TM did not occur in stable CHO clones expressing CaD40. Therefore, it is likely that CaD39 can enhance TM's binding to F-actin in vivo, thus reducing TM's rate of turnover and stabilizing actin microfilament bundles.
Masking the Overhead of Protocol Layering

Protocol layering has been advocated as a way of dealing with the complexity of computer communication. It has also been criticized for its performance overhead. In this paper, we present some insights in the design of protocols, and how these insights can be used to mask the overhead of layering, in a way similar to client caching in a file system. With our techniques, we achieve an order of magnitude improvement in end-to-end message latency in the Horus communication framework. Over an ATM network, we are able to do a round-trip message exchange, of varying levels of semantics, in about 170 mseconds, using a protocol stack of four layers that were written in ML, a high-level functional language.
Impact of diabetes mellitus on incidence of hepatocellular carcinoma in chronic hepatitis C patients treated with interferon‐based antiviral therapy

There is strong evidence linking chronic hepatitis C virus (HCV) infection and Type 2 diabetes mellitus (DM). Recent studies have suggested that DM is associated with increased risk of developing hepatocellular carcinoma (HCC). The aim of our cohort study was to assess whether DM influence the incidence of HCC in chronic hepatitis C patients treated with interferon (IFN)‐based antiviral therapy. A total of 1,470 chronic hepatitis C patients treated with IFN or pegylated‐IFN plus ribavirin therapy were enrolled. Of them, 253 (17%) patients had DM at entry. Evaluation of HCC incidence was performed by Kaplan–Meier method and Cox proportional hazards analysis. Patients with baseline DM were significantly older and had higher body mass index, serum transaminase levels and fibrosis scores and lower platelet counts compared to non‐DM subjects. Sustained virological response (SVR) was achieved in 160 (63%) of DM and 867 (71%) of non‐DM patients (p = 0.008). During a median follow‐up period of 4.3 years, HCC developed in 21 (8.3%) of DM and 66 (5.4%) of non‐DM patients (p = 0.017). However, DM was not an independent covariate by Cox proportional hazards analysis. In a subgroup analysis, DM (hazard ratio, 4.32; 95% confidence interval, 1.23–15.25; p = 0.023) was an independent predictor of HCC in the SVR patients without baseline cirrhosis, despite a low HCC incidence. In conclusion, DM has a selective impact on HCC development among chronic hepatitis C patients after IFN‐based therapy. DM may increase the HCC risk in chronic hepatitis C without cirrhosis after eradication of HCV.
Usefulness of Self-Monitoring of Urinary Salt Excretion in Hypertensive Patients

We investigated the usefulness of measuring urinary salt excretion by using a self-monitoring device. Subjects were 34 hypertensive patients who underwent successful 24-h home urine collection five times and 25 volunteers. Four volunteers were diagnosed as having hypertension based on home blood pressure (BP) readings. All subjects were asked to measure daily urinary salt excretion for 30 days by using a self-monitoring device which estimates 24-h salt excretion by overnight urine. The mean urinary salt excretion during the 30 days was 8.36 ± 1.52 g/day and the range (maximum-minimum value) was 5.47 ± 20.05 g/day in all subjects. Mean urinary salt excretion decreased from 8.52 ± 1.63 g/day for the first 10 days to 8.31 ± 1.54 g/day for the last 10 days (p < 0.05). The mean urinary salt excretion determined by a self-monitoring device using overnight urine was positively associated with that determined by 24-h home urine for five times in the hypertensive subjects (r = 0.63, p < 0.01). Results indicate that a self-monitoring device seems to be useful to monitor daily salt intake and to guide salt restriction.
Salicylate Downregulates 11β-HSD1 Expression in Adipose Tissue in Obese Mice and in Humans, Mediating Insulin Sensitization

Recent trials show salicylates improve glycemic control in type 2 diabetes, but the mechanism is poorly understood. Expression of the glucocorticoid-generating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in adipose tissue is increased in vitro by proinflammatory cytokines and upregulated in obesity. 11β-HSD1 inhibition enhances insulin sensitivity. We hypothesized that salicylates downregulate 11β-HSD1 expression, contributing to their metabolic efficacy. We treated diet-induced obese (DIO) 11β-HSD1–deficient mice and C57Bl/6 mice with sodium salicylate for 4 weeks. Glucose tolerance was assessed in vivo. Tissue transcript levels were assessed by quantitative PCR and enzyme activity by incubation with 3H-steroid. Two weeks’ administration of salsalate was also investigated in a randomized double-blind placebo-controlled crossover study in 16 men, with measurement of liver 11β-HSD1 activity in vivo and adipose tissue 11β-HSD1 transcript levels ex vivo. In C57Bl/6 DIO mice, salicylate improved glucose tolerance and downregulated 11β-HSD1 mRNA and activity selectively in visceral adipose. DIO 11β-HSD1–deficient mice were resistant to these metabolic effects of salicylate. In men, salsalate reduced 11β-HSD1 expression in subcutaneous adipose, and in vitro salicylate treatment reduced adipocyte 11β-HSD1 expression and induced adiponectin expression only in the presence of 11β-HSD1 substrate. Reduced intra-adipose glucocorticoid regeneration by 11β-HSD1 is a novel mechanism that contributes to the metabolic efficacy of salicylates.
Bayesian Divergence-Time Estimation with Genome-Wide Single-Nucleotide Polymorphism Data of Sea Catfishes (Ariidae) Supports Miocene Closure of the Panamanian Isthmus

Abstract The closure of the Isthmus of Panama has long been considered to be one of the best defined biogeographic calibration points for molecular divergence‐time estimation. However, geological and biological evidence has recently cast doubt on the presumed timing of the initial isthmus closure around 3 Ma but has instead suggested the existence of temporary land bridges as early as the Middle or Late Miocene. The biological evidence supporting these earlier land bridges was based either on only few molecular markers or on concatenation of genome‐wide sequence data, an approach that is known to result in potentially misleading branch lengths and divergence times, which could compromise the reliability of this evidence. To allow divergence‐time estimation with genomic data using the more appropriate multispecies coalescent (MSC) model, we here develop a new method combining the single‐nucleotide polymorphism‐based Bayesian species‐tree inference of the software SNAPP with a molecular clock model that can be calibrated with fossil or biogeographic constraints. We validate our approach with simulations and use our method to reanalyze genomic data of Neotropical army ants (Dorylinae) that previously supported divergence times of Central and South American populations before the isthmus closure around 3 Ma. Our reanalysis with the MSC model shifts all of these divergence times to ages younger than 3 Ma, suggesting that the older estimates supporting the earlier existence of temporary land bridges were artifacts resulting at least partially from the use of concatenation. We then apply our method to a new restriction‐site associated DNA‐sequencing data set of Neotropical sea catfishes (Ariidae) and calibrate their species tree with extensive information from the fossil record. We identify a series of divergences between groups of Caribbean and Pacific sea catfishes around 10 Ma, indicating that processes related to the emergence of the isthmus led to vicariant speciation already in the Late Miocene, millions of years before the final isthmus closure.
Preoperative (neoadjuvant) chemoradiotherapy in oesophageal cancer

Oesophageal cancer carries a poor prognosis. The 5‐year survival rate following resection ranges from 10 to 35 per cent. Recent evidence suggests that the addition of non‐surgical treatments to surgery may improve resection rates, reduce the risk of recurrence and improve survival. This review examines the role of preoperative chemoradiotherapy (CRT) in oesophageal cancer.
High incidence rates of invasive pneumococcal disease in the White Mountain Apache population.

OBJECTIVE In this article we determine the incidence and clinical spectrum of invasive pneumococcal disease in the White Mountain Apache population, a group known to have a high incidence of invasive disease due to Haemophilus influenzae type b. DESIGN Patients from whom cultures of normally sterile body sites yielded Streptococcus pneumoniae were identified retrospectively through review of hospital laboratory records from a 6.8-year period. Clinical data were reviewed and incidence rates were computed. SETTING The Whiteriver Indian Health Service Hospital is located on the 1.7-million-acre White Mountain Apache Reservation in eastern Arizona. PATIENTS Approximately 10,000 members of the White Mountain Apache Tribe reside on or near the reservation and receive health care through the Whiteriver Indian Health Service Hospital. OUTCOME MEASURES The average annual incidence rates of invasive pneumococcal disease were calculated and clinical characteristics were reviewed. RESULTS One hundred thirty-eight cases of invasive pneumococcal disease were identified. The average annual incidence rate was 207 per 100,000 population, and 156 per 100,000 population when adjusted for age by direct standardization to the 1988 US population. The incidence rate was highest in children between 1 and 2 years--2396 per 100,000. The overall case-fatality rate was 5%. Pneumococcal pneumonia was the diagnosis in 79% of the patients 5 years of age or older. Alcohol abuse, identified in 66% of the cases in adults, was the most common underlying medical condition. CONCLUSION The incidence rates in White Mountain Apaches are the highest reported for any population. A vaccine effective in children would greatly benefit this population.
Control of anthocyanin and non-flavonoid compounds by anthocyanin-regulating MYB and bHLH transcription factors in Nicotiana benthamiana leaves

Coloration of plant organs such as fruit, leaves and flowers through anthocyanin production is governed by a combination of MYB and bHLH type transcription factors (TFs). In this study we introduced Rosea1 (ROS1, a MYB type) and Delila (DEL, a bHLH type), into Nicotiana benthamiana leaves by agroinfiltration. ROS1 and DEL form a pair of well-characterized TFs from Snapdragon (Antirrhinum majus), which specifically induce anthocyanin accumulation when expressed in tomato fruit. In N. benthamiana, robust induction of a single anthocyanin, delphinidin-3-rutinoside (D3R) was observed after expression of both ROS1 and DEL. Surprisingly in addition to D3R, a range of additional metabolites were also strongly and specifically up-regulated upon expression of ROS1 and DEL. Except for the D3R, these induced compounds were not derived from the flavonoid pathway. Most notable among these are nornicotine conjugates with butanoyl, hexanoyl, and octanoyl hydrophobic moieties, and phenylpropanoid-polyamine conjugates such as caffeoyl putrescine. The defensive properties of the induced molecules were addressed in bioassays using the tobacco specialist lepidopteran insect Manduca sexta. Our study showed that the effect of ROS1 and DEL expression in N. benthamiana leaves extends beyond the flavonoid pathway. Apparently the same transcription factor may regulate different secondary metabolite pathways in different plant species.
AKAP3 Selectively Binds PDE4A Isoforms in Bovine Spermatozoa1

Abstract Cyclic AMP plays an important role in regulating sperm motility and acrosome reaction through activation of cAMP-dependent protein kinase A (PKA). Phosphodiesterases (PDEs) modulate the levels of cyclic nucleotides by catalyzing their degradation. Although PDE inhibitors specific to PDE1 and PDE4 are known to alter sperm motility and capacitation in humans, little is known about the role or subcellular distribution of PDEs in spermatozoa. The localization of PKA is regulated by A-kinase anchoring proteins (AKAPs), which may also control the intracellular distribution of PDE. The present study was undertaken to investigate the role and localization of PDE4 during sperm capacitation. Addition of Rolipram or RS25344, PDE4-specific inhibitors significantly increased the progressive motility of bovine spermatozoa. Immunolocalization techniques detected both PDE4A and AKAP3 (formerly known as AKAP110) in the principal piece of bovine spermatozoa. The PDE4A5 isoform was detected primarily in the Triton X-100-soluble fraction of caudal epididymal spermatozoa. However, in ejaculated spermatozoa it was seen primarily in the SDS-soluble fraction, indicating a shift in PDE4A5 localization into insoluble organelles during sperm capacitation. AKAP3 was detected only in the SDS-soluble fraction of both caudal and ejaculated sperm. Immunoprecipitation experiments using COS cells cotransfected with AKAP3 and either Pde4a5 or Pde4d provide evidence that PDE4A5 but not PDE4D interacts with AKAP3. Pulldown assays using sperm cell lysates confirm this interaction in vitro. These data suggest that AKAP3 binds both PKA and PDE4A and functions as a scaffolding protein in spermatozoa to regulate local cAMP concentrations and modulate sperm functions.
MORPHOLOGICAL CORRELATES OF INCREASED COUPLING RESISTANCE AT AN ELECTROTONIC SYNAPSE

Close appositions between axonal membranes are present in the septum between adjacent axonal segments of the septate or lateral giant axons of the crayfish Procambarus. In sections the closely apposed membranes appear separated by a space or gap. The use of lanthanum indicates that there may be structures connecting the apposed membranes. The apparent gap is actually a network of channels continuous with the extracellular space. Adjacent axonal segments are electrotonically coupled at the septa. The coupling resistance is increased by mechanical injury of an axon, immersion in low Cl- solutions, and immersion in low Ca++ solutions, followed by a return to normal physiological solution. Septa at which coupling resistance had been measured were examined in the electron microscope. The induced increases in coupling resistance are associated with separation of the junctional membranes (with the exception of the moderate increases during immersion in low Ca++ solutions). Schwann cell processes are present between the separated axonal membranes. When nerve cords in low Cl- solutions are returned to normal physiological solution, coupling, i.e., electrotonic synapses. A model of an electrotonic synapse is proposed in which tween axonal membranes are again found. The association between the morphological and physiological findings provides further evidence that the junctions are the sites of electrotonic coupling, i.e., electrotonic, synapses. A model of an electrotonic synapse is proposed in which intercytoplasmic channels not open to the extracellular space are interlaced with a hexagonal network of extracellular channels between the apposed junctional membranes.
Evaluation of the Safety and Efficacy of a Non-contact Radiofrequency Device for the Improvement in Contour and Circumferential Reduction of the Inner and Outer Thigh.

BACKGROUND AND OBJECTIVE When evaluating self-image, research confirms that the main focus of dissatisfaction for the majority of women is the size and shape of their bodies, particularly their hips, waist and thighs. The appearance of a woman's thighs is often distanced from what she views as her ideal shape and size and is largely out of her control due to gender specific fat deposition. The issue of excessive subcutaneous fat deposits in the lateral thigh area is enhanced by the resistivity of local adipocytes to lipolysis. Subjects in this study underwent treatment of the bilateral inner and outer thighs using a non-contact field radiofrequency device (BTL Vanquish Flex Applicator, BTL Industries Inc., Boston, MA). The main objective of this study is to evaluate the safety and efficacy of the device for reducing the circumference of the inner and outer thighs as well as improving the overall contour of the treatment area. MATERIALS AND METHODS A total of 30 female subjects age 32 to 59 (average 42.4) were enrolled in the study. After meeting the inclusion/ exclusion criteria each subject received 4 weekly 30-minute bilateral thigh treatments (1 hour total treatment time). As the primary outcomes, circumferential reduction was measured and clinical before and after photographs were taken for assessment. Safety of the device was assessed by means of reported adverse events. RESULTS All 30 subjects completed the entire treatment series and 1 month follow-up visit. The average reduction measured on both thighs was 3.86 cm with statistical significance P< 0.05. There was no significant change in weight for any of the subjects. During the course of the study two adverse events occurred, but were deemed unrelated to the treatment. CONCLUSIONS Based on the measurements obtained the device under investigation was considered safe and effective in terms of improved contour and circumferential reduction of inner and outer thighs.
Inhalation of carbon monoxide prevents liver injury and inflammation following hind limb ischemia/reperfusion

The induction of heme oxygenase (HO), the rate limiting enzyme in the conversion of heme into carbon monoxide (CO) and biliverdin, limits liver injury following remote trauma such as hind limb ischemia/reperfusion (I/R). Using intravital video microscopy, we tested the hypothesis that inhaled CO (250 ppm) would mimic HO‐derived liver protection. Hind limb I/R significantly decreased sinusoidal diameter and volumetric flow, increased leukocyte accumulation within sinusoids, increased leukocyte rolling and adhesion within postsinusoidal venules, and significantly increased hepatocyte injury compared with naïve animals. Inhalation of CO alone did not alter any microcirculatory or inflammatory parameters. Inhalation of CO following I/R restored volumetric flow, decreased stationary leukocytes within sinusoids, decreased leukocyte rolling and adhesion within postsinusoidal venules, and significantly reduced hepatocellular injury following hind limb I/R. HO inhibition did not alter microcirculatory parameters in naïve mice, but did increase inflammation, as well as increase hepatocyte injury following hind limb I/R. Inhalation of CO during HO inhibition significantly reduced such microcirculatory deficits, hepatic inflammation, and injury in response to hind limb I/R. In conclusion, these results suggest that HO‐derived hepatic protection is mediated by CO, and inhalation of low concentrations of CO may represent a novel therapeutic approach to prevent remote organ injury during systemic inflammatory response syndrome, or SIRS.
Relation between neurocognitive impairment, embolic load, and cerebrovascular reactivity following on- and off-pump coronary artery bypass grafting.

OBJECTIVES To evaluate the effect of on-pump and off-pump coronary artery bypass grafting (CABG) on postoperative cognitive impairment and cerebrovascular reactivity, with attention for the perioperative high-intensity transient signals (HITS). DESIGN A prospective comparative study. SETTING Urban university hospital. PATIENTS Candidates for cardiac surgery. METHODS Measurement of HITS as a reflection of embolic load was performed in 50 patients (on-pump CABG, n = 32; off-pump CABG, n = 18). To measure cognitively induced cerebrovascular reactivity, cerebral blood flow velocity (BFV) was measured preoperatively in 66 patients, early postoperatively (after 6 days) in 63 patients, and late postoperatively (after 6 months) in 44 patients during five cognitive tasks. In the same session, seven standardized neuropsychological tests were administered. RESULTS A higher embolic load was found in the on-pump group (p < 0.01). In the on-pump group, aortic cannulation was the most important HITS-prone surgical maneuver. Repeated-measures multivariate analysis of variance (using surgical technique as between-subjects factor and significant differences between both groups as covariates) on the group data revealed no significant differences in neuropsychological performance and BFV immediately after surgery or at 6 months after surgery, compared with preoperative performance. No main effect of surgery was found for neuropsychological performance and BFV. No significant correlations were found between the number of HITS and the degree of postoperative neuropsychological impairment. Individual comparisons revealed that 60% (59.4% in the on-pump group; 61.1% in the off-pump group) of the patients undergoing CABG showed evidence of cognitive impairment soon after surgery. In 24.2%, the cognitive sequelae persisted at 6 months follow-up (31.8% in the on-pump group; 9.1% in the off-pump group). The cognitive impairment index (sum of impaired neuropsychological tests) showed a significant difference after 6 months between both surgery groups with fewer neurocognitive tests that remained impaired in the off-pump group. CONCLUSIONS In off-pump surgery, significantly fewer HITS were observed. On an individual level, more favorable results in neuropsychological test performance were demonstrated in the off-pump group after 6 months. The number of HITS showed no correlation with degrees of early and late postoperative neuropsychological impairment.