Miracle-dz/UniFAR-FTUs huggingface dataset:
Impaired phasic insulin and amylin secretion in diabetic rats

Leahy, Jack L. , and Mark S. Fineman. Impaired phasic insulin and amylin secretion in diabetic rats. Am. J. Physiol. 275 (Endocrinol. Metab. 38): E457–E462, 1998. —We have proposed that a hyperstimulated insulin secretion causing b-cell degranulation is the basis for the impaired glucosepotentiated insulin secretion in type 2 diabetes (‘‘overworked b-cell’’). To confirm this idea, we previously investigated tolbutamide-infused euglycemic rats. Two novel kinds of b-cell dysfunction were observed: altered phasic glucosepotentiated insulin secretion with preferential sparing of the first phase and a raised secreted ratio of amylin to insulin. The current study tested these parameters in 90% (intact b-cell insulin stores) and 95% (markedly lowered insulin stores) pancreatectomized (Px) diabetic rats. Rats underwent pancreas perfusion 5–6 wk postsurgery. Controls showed nonchanging insulin secretion during a 20-min perfusion of 16.7 mM glucose 1 10 mM arginine. In contrast, both Px groups showed an altered phasic pattern, with the first phase being supernormal (for the b-cell mass) but the second phase reduced in tandem with the insulin content. Amylin secretion from control and 90% Px rats paralleled the insulin output, so that the amylin-to-insulin ratio averaged 0.12 6 0.03% in the controls and 0.16 6 0.01% in the 90% Px rats over the two secretory phases. In contrast, the amylin-to-insulin ratio in 95% Px rats equaled that of controls during the first phase (0.12 6 0.1%) but was twice normal during the second phase (0.32 6 0.4%). These results confirm the validity of the overworked b-cell schema by showing identical b-cell functional defects in Px rats and tolbutamide-infused normoglycemic rats.
MED28 Regulates Epithelial–Mesenchymal Transition Through NFκB in Human Breast Cancer Cells

MED28, a mammalian Mediator subunit, was found highly expressed in several types of malignancy, including breast cancer. Recently, we have identified a role of MED28 in regulating both cell growth and migration in human breast cancer cells. In epithelium‐derived solid tumor, migration and invasion are preceded by the progression of epithelial–mesenchymal transition (EMT) which calls for downregulation of epithelial markers as well as upregulation of mesenchymal markers, among other features. The objective of this study was to investigate a putative role of MED28 in the progression of EMT in human breast cancer cells. In fibroblast‐like MDA‐MB‐231 cells, suppression of MED28 attenuated the mesenchymal morphology, concomitantly with a reduction of several mesenchymal biomarkers and Snail, a transcriptional repressor of E‐cadherin. The suppression effect was also accompanied by downregulation of p‐NFκB/p65. However, overexpression of MED28 exhibited in an opposite manner. In epithelial MCF7 cells, administration of Adriamycin®, an experimental EMT induction system, led to a mesenchyme‐like appearance correlated with increased expression of MED28, p‐p65, and Snail, and a reciprocal change of epithelial and mesenchymal markers. Furthermore, suppression of MED28 attenuated the experimental EMT effect and restored the original expression status of E‐cadherin and MMP9 in MCF7 cells. Our data indicate that MED28 modulates the development of EMT through NFκB in human breast cancer cells, further reinforcing the significance of MED28 in the progression of breast cancer on top of its role in cell growth and migration. J. Cell. Physiol. 232: 1337–1345, 2017. © 2016 Wiley Periodicals, Inc.
Stacked biofuel cells separated by artificial lipid bilayers

This paper reports stacked biofuel cells (SBFC) separated by artificial lipid bilayers which are bimolecular membranes and several nm membranes. First, we designed and fabricated SBFCs with a screen printer and a 3D printer. Then, we evaluated electrochemical reaction of electrodes of the SBFC and measured the output voltages of single, double, triple and quad SBFCs. Finally, we demonstrated to drive a digital clock powered by the quad SBFC. These results indicate the potentially for developing the high voltage BFC implanted in living organisms.
Functional Characterization of a Novel R2R3-MYB Transcription Factor Modulating the Flavonoid Biosynthetic Pathway from Epimedium sagittatum

Epimedium species have been widely used both as traditional Chinese medicinal plants and ornamental perennials. Both flavonols, acting as the major bioactive components (BCs) and anthocyanins, predominantly contributing to the color diversity of Epimedium flowers belong to different classes of flavonoids. It is well-acknowledged that flavonoid biosynthetic pathway is predominantly regulated by R2R3-MYB transcription factor (TF) as well as bHLH TF and WD40 protein at the transcriptional level. MYB TFs specifically regulating anthocyanin or flavonol biosynthetic pathway have been already isolated and functionally characterized from Epimedium sagittatum, but a R2R3-MYB TF involved in regulating both these two pathways has not been functionally characterized to date in Epimedium plants. In this study, we report the functional characterization of EsMYB9, a R2R3-MYB TF previously isolated from E. sagittatum. The previous study indicated that EsMYB9 belongs to a small subfamily of R2R3-MYB TFs containing grape VvMYB5a and VvMYB5b TFs, which regulate flavonoid biosynthetic pathway. The present studies show that overexpression of EsMYB9 in tobacco leads to increased transcript levels of flavonoid pathway genes and increased contents of anthocyanins and flavonols. Yeast two-hybrid assay indicates that the C-terminal region of EsMYB9 contributes to the autoactivation activity, and EsMYB9 interacts with EsTT8 or AtTT8 bHLH regulator. Transient reporter assay shows that EsMYB9 slightly activates the expression of EsCHS (chalcone synthase) promoter in transiently transformed leaves of Nicotiana benthamiana, but the addition of AtTT8 or EsTT8 bHLH regulator strongly enhances the transcriptional activation of EsMYB9 against five promoters of the flavonoid pathway genes except EsFLS (flavonol synthase). In addition, co-transformation of EsMYB9 and EsTT8 in transiently transfected tobacco leaves strongly induces the expressions of flavonoid biosynthetic genes. The potential role of EsMYB9 in modulating the biosynthesis and accumulation of sucrose-induced anthocyanin and flavonol-derived BCs is also discussed. These findings suggest that EsMYB9 is a novel R2R3-MYB TF, which regulates the flavonoid biosynthetic pathway in Epimedium, but distinctly different with the anthocyanin or flavonol-specific MYB regulators identified previously in Epimedium plants.
The Excite Trial: relationship of intensity of constraint induced movement therapy to improvement in the wolf motor function test.

PURPOSE To examine the relationship between change scores on the log mean Wolf Motor Function Test (lmWMFT) and the intensity of supervised Constraint Induced Movement Therapy (CIMT) in participants with subacute and chronic stroke. METHODS A retrospective analysis of data from 169 EXCITE participants who received CIMT either immediately after randomization or one year later was undertaken. During waking hours, participants wore a restraining mitt on the less affected extremity. The lmWMFT was administered before and after the two week treatment block. RESULTS Significant relationships were seen between the intensity of training and functional score in the immediate, lower functional group for whom more training in adaptive task practice resulted in poorer outcomes (p=0.01) and in the immediate, higher functioning group for whom more training in repetitive task practice resulted in poorer outcomes (p=0.02). Female participants in the immediate group showed less progress in lmWMFT scores with greater amounts of total training (p=0.01). Functional level, gender, and concordance did not modify any other relationship. Both higher functioning participants who trained within the normal ratio (N=50) and who were exposed to more than the prescribed adaptive task practice (N=11) experienced a significant improvement in the lmWMFT score (p=0.03 and p=0.02, respectively) compared to those higher functioning participants who experienced excessive repetitive task practice. CONCLUSION Applying CIMT to a large sample of participants with stroke resulted in directionally inappropriate but significant relationships between intensity and lmWMFT scores in the immediate but not the delayed group. Our data also suggest that functional improvements observed in the EXCITE Trial might be attributable to training components other than the designated ratio of training approaches (adaptive and repetitive task practice).
Quality of life as an outcome indicator in patients with seasonal affective disorder: results from the Can-SAD study

Background. Although a host of studies have now examined the relationship between quality of life (QoL) and non-seasonal depression, few have measured QoL in seasonal affective disorder (SAD). We report here on results from the Can-SAD trial, which assessed the impact of treatment with either antidepressant medication or light therapy upon QoL in patients diagnosed with SAD. Method. This Canadian double-blind, multicentre, randomized controlled trial included 96 patients who met strict diagnostic criteria for SAD. Eligible patients were randomized to 8 weeks of treatment with either: (1) 10000 lux light treatment and a placebo capsule or (2) 100 lux light treatment (placebo light) and 20 mg fluoxetine. QoL was measured with the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and the Medical Outcomes Study (MOS) Short-Form General Health Survey (SF-20) at baseline and 8 weeks. Results. Both intervention groups showed significant improvement in QoL over time with no significant differences being detected by treatment condition. Q-LES-Q scores increased significantly in seven of eight domains, with the average scores rising from 48·0 (S.D.=10·7) at baseline to 69·1 (S.D.=15·6) at week 8. Treatment-related improvement in QoL was strongly associated with improvement in depression symptoms. Discussion. Patients with SAD report markedly impaired QoL during the winter months. Treatment with light therapy or antidepressant medication is associated with equivalent marked improvement in perceived QoL. Studies of treatment interventions for SAD should routinely include broader indices of patient outcome, such as the assessment of psychosocial functioning or life quality.
Mutations outside the rifampicin resistance-determining region associated with rifampicin resistance in Mycobacterium tuberculosis.

OBJECTIVES Ninety-six percent of rifampicin resistance in Mycobacterium tuberculosis was shown to be associated with mutations inside the 81 bp rifampicin resistance-determining region (RRDR) located in the centre of the rpoB gene. The detection of rifampicin resistance by targeting the RRDR failed to match with a resistant phenotype in 4% of all cases. Our study aims to identify the mutations outside the RRDR that are associated with rifampicin resistance in M. tuberculosis. METHODS AND RESULTS Among 50 rifampicin-resistant and 20 rifampicin-susceptible clinical isolates of M. tuberculosis, 2 of the rifampicin-resistant isolates did not harbour any known mutations in the RRDR. Sequencing analysis of the whole rpoB gene identified two rare mutations, V146F and I572F. A molecular structure model based on Thermus thermophilus RpoB revealed that both these substituted amino acids are located in close proximity to the rifampicin-binding pocket of the β-subunit. Substitutions of simple amino acids for bulky ones are likely to affect the protein-drug interaction. Cloning and transformation of the mutated rpoB gene into wild-type Mycobacterium smegmatis and M. tuberculosis successfully elevated the MIC of rifampicin and conferred the rifampicin resistance phenotype. CONCLUSIONS Our study showed that amino acid positions 146 and 572 are associated with rifampicin resistance in M. tuberculosis in addition to the RRDR. Molecular assays for identifying rifampicin-resistant M. tuberculosis might be improved in terms of accuracy by including these two positions.
Metabolic Derangements in Excessive Insulin and Sulfonylurea Therapy

Mild streptozotocin diabetic rats, characterized by normal or slightly elevated fasting blood glucose levels and glucose intolerance, treated with excessive doses of monocomponent pork insulin (0.5 U/day) (I) or glybenclamide (0.6 mg/day) (S) were compared to controls (C) and streptozotocin-diabetic rats without treatment (D). Intravenous glucose tolerance tests (0.75 g/kg) were performed in all animals and repeated after overtreatment. Insulin binding and insulin-induced D-(U-14C)-glucose transport and oxidation were also determined in isolated epididymal adipocytes. Diabetic rats showed a failure in the initial phase of insulin release and glucose intolerance as compared with (C). In overtreated rats glucose tolerance worsened (p < 0.05) after therapy. Maximal insulin binding by isolated adipocytes at tracer insulin concentration was unchanged after excessive insulin or sulfonylurea therapy. Besides, glucose transport and oxidation in the cells of overtreated rats were greater than in D and even greater than in C. These apparently divergent results, i.e. deterioration of glucose tolerance with increased insulin action in adipocytes suggest that overtreatment induces a state of resistance to hormone action in other target tissue(s) than the adipose one, possibly muscle.
The Mycobacterium tuberculosis Protein Kinase K Modulates Activation of Transcription from the Promoter of Mycobacterial Monooxygenase Operon through Phosphorylation of the Transcriptional Regulator VirS*

Mycobacterium tuberculosis encodes for 11 eukaryotic-like serine/threonine protein kinases. Genetic and biochemical studies show that these kinases regulate various cellular processes including cell shape and morphology, glucose and glutamine transport, phagosome-lysosome fusion and the expression, and/or activity of transcription factors. PknK is the largest predicted serine/threonine protein kinase in M. tuberculosis. Here, we have cloned, overexpressed, and purified protein kinase K (PknK) to near homogeneity and show that its ability to phosphorylate proteins is dependent on the invariant lysine (Lys55), and on two conserved threonine residues present in its activation loop. Despite being devoid of any apparent transmembrane domain, PknK is localized to the cell wall fraction, suggesting probable anchoring of the kinase to the cell membrane region. The pknK gene is located in the vicinity of the virS gene, which is known to regulate the expression of the mycobacterial monooxygenase (mymA) operon. We report here for the first time that VirS is in fact a substrate of PknK. In addition, four of the proteins encoded by mymA operon are also found to be substrates of PknK. Results show that VirS is a bona fide substrate of PknK in vivo, and PknK-mediated phosphorylation of VirS increases its affinity for mym promoter DNA. Reporter assays reveal that PknK modulates VirS-mediated stimulation of transcription from the mym promoter. These findings suggest that the expression of mymA operon genes is regulated through PknK-mediated phosphorylation of VirS.
Variation of wavelet entropy in electroencephalogram signal during neurofeedback training

Neurofeedback training NFT has an important role in improvement of cognitive functions in both clinical and healthy individuals. In this study, variation of wavelet entropy during low beta NFT was investigated. To investigate the effect of low beta NFT on wavelet entropy, correlation between the change in low beta activity and the change in wavelet entropy was computed. The results revealed that there is a highly significant negative correlation between the change in low beta activity and wavelet entropy. The given outcome suggests that enhancing low beta activity through NFT associated with decrements in wavelet entropy. Furthermore, we discuss a new implementation of NFT, based on wavelet entropy for future research. © 2012 Wiley Periodicals, Inc. Complexity, 2012
Effect of antioxidants on X-ray-induced γ-H2AX foci in human blood lymphocytes: preliminary observations.

PURPOSE To investigate the effect of a radioprotective oral agent containing a formulation of antioxidants and glutathione-elevating compounds on the extent of x-ray-induced γ-H2AX foci formation. MATERIALS AND METHODS The study was approved by local ethics committee and informed consent was obtained from each subject. In vitro experiments with blood lymphocytes of 25 healthy volunteers were performed without antioxidants and with antioxidants added either before or immediately after irradiation (10 mGy). For in vivo/in vitro tests, blood samples were obtained before, 15, 30, and 60 minutes (n=17) after, and 2, 3, and 5 hours (n=11) after oral ingestion of antioxidant pills and were irradiated (10 mGy). DNA double-strand breaks (DSBs) were quantified in isolated lymphocytes 5 minutes (in vitro and in vivo/in vitro) and 15 minutes (in vitro) after irradiation by enumerating γ-H2AX foci. To validate the data, additional in vitro experiments with use of 53BP1 as another independent marker for DSBs were performed. Nonirradiated samples served as controls. Statistical analyses were performed by using Wilcoxon rank-sum tests (in vitro), repeated-measures test, and Dunnett test (in vivo/in vitro). RESULTS In the in vitro experiments, 15-minute preincubation with antioxidants significantly reduced mean γ-H2AX foci levels by 23% (P<.0001), whereas addition of antioxidants immediately after irradiation did not lead to a reduction of x-ray-induced foci (P=.6905). Mean 53BP1 foci were also reduced by preincubation with the radioprotectant. In the in vivo/in vitro tests, oral pretreatment with antioxidants also led to a significant reduction of γ-H2AX foci formation; administration 60 minutes before irradiation resulted in a mean foci reduction of 58% (P<.0001). CONCLUSION The tested formulation of antioxidants significantly reduced formation of γ-H2AX and 53BP1 foci after irradiation at a radiologic radiation dose typical for computed tomographic imaging; administration 60 minutes prior to irradiation seems to be appropriate and leads to a significant reduction in foci.
NPML based range measure for localization in interference limited wireless sensor networks

A novel method of estimating the range for localization in a interference limited wireless sensor network (WSN) is proposed in this paper. The received sensor signal indication (RSSI) algorithm is the most common algorithm for sensor range measurement, however in interference limited environments it is prone to erroneous estimation. Thus a non-parametric maximum likelihood (NPML) adaptive estimator for channel localization in interference limited channels is proposed for localization in OFDM based WSN. A complete receiver architecture based on NPML is also introduced. Performance of the proposed algorithm is shown using simulation.
On the roles of colour and scent in a specialized floral mimicry system.

BACKGROUND AND AIMS Sexually deceptive orchids achieve cross-pollination by mimicking the mating signals of female insects, generally hymenopterans. This pollination mechanism is often highly specific as it is based primarily on the mimicry of mating signals, especially the female sex pheromones of the targeted pollinator. Like many deceptive orchids, the Mediterranean species Ophrys arachnitiformis shows high levels of floral trait variation, especially in the colour of the perianth, which is either green or white/pinkinsh within populations. The adaptive significance of perianth colour polymorphism and its influence on pollinator visitation rates in sexually deceptive orchids remain obscure. METHODS The relative importance of floral scent versus perianth colour in pollinator attraction in this orchid pollinator mimicry system was evaluated by performing floral scent analyses by gas chromatography-mass spectrometry (GC-MS) and behavioural bioassays with the pollinators under natural conditions were performed. KEY RESULTS The relative and absolute amounts of behaviourally active compounds are identical in the two colour morphs of O. arachnitiformis. Neither presence/absence nor the colour of the perianth (green versus white) influence attractiveness of the flowers to Colletes cunicularius males, the main pollinator of O. arachnitiformis. CONCLUSION Chemical signals alone can mediate the interactions in highly specialized mimicry systems. Floral colour polymorphism in O. arachnitiformis is not subjected to selection imposed by C. cunicularius males, and an interplay between different non-adaptive processes may be responsible for the maintenance of floral colour polymorphism both within and among populations.
Assessment of pain and anxiety following surgical placement of dental implants.

PURPOSE To investigate the change in 89 patients' pain and anxiety following implant surgery and to evaluate the correlation among anxiety, pain, and influencing factors. MATERIALS AND METHODS Eighty-nine patients were included in this study. Subjective factors influencing pain perception included anxiety from the overall dental treatment (scored on the Dental Anxiety Scale [DAS]) and anxiety relative to the time from implant surgery. Objective factors were sex, age, and implant location and number. Patients completed questionnaires just before surgery (T0), immediately after surgery (T1), 1 day after surgery (T2), and 1 week after surgery (T3). RESULTS The average pain perception was highest at T2, followed by T1 and T3. Pain perception at T1 was significantly higher in women and for a larger number of implant placements. Pain perception at T2 was significantly higher in women and when DAS and anxiety scores were high. The pain score at T3 was significantly higher in women and when anxiety scores were high. The results from multiple linear regression analysis showed that pain perception was significantly higher at T1 in women and for a larger number of implant placements, and at T3 when the dental anxiety score was high. CONCLUSION Within the limitations of this study, a patient's anxiety represented by dental anxiety score and state of anxiety scores affected pain intensity 1 day after implant surgery. Sex and the number of implants affected pain intensity immediately after implant surgery. Patients who have high pain intensity 1 week after implant surgery showed high pain intensity at each time point.