Antidiabetic effect and mode of action of cytopiloyne

Cytopiloyne was identified as a novel polyacetylenic compound. However, its antidiabetic properties are poorly understood. The aim of the present study was to investigate the anti-diabetic effect and mode of action of cytopiloyne on type 2 diabetes (T2D). We first evaluated the therapeutic effect of cytopiloyne on T2D in db/db mice. We found that one dose of cytopiloyne reduced postprandial glucose levels while increasing blood insulin levels. Accordingly, long-term treatment with cytopiloyne reduced postprandial blood glucose levels, increased blood insulin, improved glucose tolerance, suppressed the level of glycosylated hemoglobin A1c (HbA1c), and protected pancreatic islets in db/db mice. Next, we studied the anti-diabetic mechanism of action of cytopiloyne. We showed that cytopiloyne failed to decrease blood glucose in streptozocin- (STZ-)treated mice whose β cells were already destroyed. Additionally, cytopiloyne dose dependently increased insulin secretion and expression in β cells. The increase of insulin secretion/expression of cytopiloyne was regulated by protein kinase C α (PKC α ) and its activators, calcium, and diacylglycerol (DAG). Overall, our data suggest that cytopiloyne treats T2D via regulation of insulin production involving the calcium/DAG/PKC α cascade in β cells. These data thus identify the molecular mechanism of action of cytopiloyne and prove its therapeutic potential in T2D

Training Effects of Virtual Reality on Reaching Behaviors in Children with Cerebral Palsy: Case Report

Virtual reality (VR) is a computer technology that artificially generates sensory information in a form that people perceive as real-world objects and events. It has been proposed that VR can improve upper-extremity function in children with cerebral palsy (CP) by decreasing physical disabilities, precisely adjusting the difficulty of task and feedback, enhancing motivation and manipulating perceptual information. The purpose of this study was to investigate the training effects of VR on reaching behavior in a child with CP. This case was a 6-year-old boy with spastic quadriplegic CP who had good cooperation and normal cognition. A single-subject A-B-A design was used. The case received 3 baseline, 4 intervention, and 2 follow-up measures. He received a 4-week (3 times a week) individualized VR training using VR-hand function training system and Eyetoy-play system with therapist\u27s manual guidance. The outcome measures included (1) four reaching kinematic parameters (movement time (MT), path, peak velocity (PV), and number of movement units (MU)) in 2 activities (pegboard and mail-delivery) at 3 directions (abduction, adduction, and forward); (2) touching a swing ball; and (3) the fine motor domain of Peabody Development Motor Scale-2nd edition (PDMS2). Visual inspection and 2-standard deviation band method were used to compare the outcome measures between the two adjacent phases. Improvements were found in the kinematic parameters in all directions from baseline to intervention, and the effects were maintained in some directions from intervention to follow-up. Improvement was also shown in the ability to touch a swing ball, but the effect was not maintained from intervention to follow-up. Furthermore, there was an increase (11 points) in the PDMS2 scores from baseline to intervention and an increase (1 point) from intervention to follow-up. This case study demonstrated the potential effect of VR training program to improve the upper-extremity function in children with CP. The training effects might retain for 1 month post intervention

Clinical parameters associated with absence of endocervical/transformation zone component in conventional cervical Papanicolaou smears

AbstractObjectiveTo study clinical factors predicting the absence of endocervical/transformation zone (EC/TZ) components of conventional cervical Papanicolaou (Pap) smears.Materials and methodsThe medical charts of patients who received Pap smears between March 2006 and August 2006 in the hospital were reviewed. The results of their Pap smears were retrieved while their demographic and clinical information were obtained from the medical charts. After excluding 378 cases with incomplete demographic data and 1397 cases with a history of pelvic irradiation, pelvic malignancy, and hysterectomy, 5662 cases were enrolled for data analysis. The relationship between clinical parameters and the absence of EC/TZ component was analyzed by Pearson Chi-square tests with Yates continuity correction and binary logistic regression tests.ResultsThe incidence of satisfactory but absence of EC/TZ component was 8.7% (491/5662). Pregnancy increased the absence of EC/TZ component [odds ratio (OR}: 2.84, 95% confidence interval (CI): 2.14–3.77, p<0.0001]. Postpartum status and endocervical polyps decreased incidence (OR: 0.61, 95% CI: 0.38–0.98, p = 0.043 and OR: 0.33, 95% CI: 0.25–0.44, p<0.0001, respectively).ConclusionsPregnancy is the only clinical factor associated with increased incidence of absence of EC/TZ cells. For these pregnant women undergoing a Pap smear, a more effective strategy may be needed to get a satisfactory smear with adequate EC/TZ components

An overview of the Phalaenopsis orchid genome through BAC end sequence analysis

<p>Abstract</p> <p>Background</p> <p><it>Phalaenopsis </it>orchids are popular floral crops, and development of new cultivars is economically important to floricultural industries worldwide. Analysis of orchid genes could facilitate orchid improvement. Bacterial artificial chromosome (BAC) end sequences (BESs) can provide the first glimpses into the sequence composition of a novel genome and can yield molecular markers for use in genetic mapping and breeding.</p> <p>Results</p> <p>We used two BAC libraries (constructed using the <it>Bam</it>HI and <it>Hin</it>dIII restriction enzymes) of <it>Phalaenopsis equestris </it>to generate pair-end sequences from 2,920 BAC clones (71.4% and 28.6% from the <it>Bam</it>HI and <it>Hin</it>dIII libraries, respectively), at a success rate of 95.7%. A total of 5,535 BESs were generated, representing 4.5 Mb, or about 0.3% of the <it>Phalaenopsis </it>genome. The trimmed sequences ranged from 123 to 1,397 base pairs (bp) in size, with an average edited read length of 821 bp. When these BESs were subjected to sequence homology searches, it was found that 641 (11.6%) were predicted to represent protein-encoding regions, whereas 1,272 (23.0%) contained repetitive DNA. Most of the repetitive DNA sequences were gypsy- and copia-like retrotransposons (41.9% and 12.8%, respectively), whereas only 10.8% were DNA transposons. Further, 950 potential simple sequence repeats (SSRs) were discovered. Dinucleotides were the most abundant repeat motifs; AT/TA dimer repeats were the most frequent SSRs, representing 253 (26.6%) of all identified SSRs. Microsynteny analysis revealed that more BESs mapped to the whole-genome sequences of poplar than to those of grape or <it>Arabidopsis</it>, and even fewer mapped to the rice genome. This work will facilitate analysis of the <it>Phalaenopsis </it>genome, and will help clarify similarities and differences in genome composition between orchids and other plant species.</p> <p>Conclusion</p> <p>Using BES analysis, we obtained an overview of the <it>Phalaenopsis </it>genome in terms of gene abundance, the presence of repetitive DNA and SSR markers, and the extent of microsynteny with other plant species. This work provides a basis for future physical mapping of the <it>Phalaenopsis </it>genome and advances our knowledge thereof.</p

Increased Risk for Entamoeba histolytica Infection and Invasive Amebiasis in HIV Seropositive Men Who Have Sex with Men in Taiwan

Entamoeba histolytica, morphologically identical to but genetically different from E. dispar and E. moshkovskii, is the causative agent of amebiasis. Recently there have been reports of increased risk for amebiasis among men who have sex with men (MSM) due to oral-anal sexual contact in several developed countries. In this longitudinal follow-up study, the incidence of amebiasis was determined among HIV-infected patients using serological and specific amebic antigen assays. DNA extracted from stool samples containing E. histolytica were analyzed by PCR, sequenced, and compared. Clinical manifestations and treatment response of invasive amebiasis in HIV-infected patients were reviewed. The results demonstrated that HIV-infected MSM were at significantly higher risk of amebiasis than patients from other risk groups. Clustering of E. histolytica isolates by sequencing analyses from geographically unrelated patients suggested person-to-person transmission. Despite immunosuppression, amebic liver abscesses and colitis responded favorably to metronidazole therapy. It is important to investigate in areas of high incidence of both amebiasis and HIV (sub-Saharan Africa) how generalizable these findings are

Patients Infected with CRF07_BC Have Significantly Lower Viral Loads than Patients with HIV-1 Subtype B: Mechanism and Impact on Disease Progression

The circulating recombinant form (CRF) 07_BC is the most prevalent HIV-1 strain among injection drug users (IDUs) in Taiwan. It contains a 7 amino-acid deletion in its p6gag. We conducted a cohort study to compare viral loads and CD4 cell count changes between patients infected with subtype B and CRF07_BC and to elucidate its mechanism. Twenty-one patients infected with CRF07_BC and 59 patients with subtype B were selected from a cohort of 667 HIV-1/AIDS patients whom have been followed up for 3 years. Generalized estimated equation was used to analyze their clinical data and the results showed that patients infected with CRF07_BC had significantly lower viral loads (about 58,000 copies per ml less) than patients with subtype B infection (p = 0.002). The replicative capacity of nine CRF07_BC and four subtype B isolates were compared and the results showed that the former had significantly lower replicative capacity than the latter although all of them were CCR5- tropic and non-syncytium inducing viruses. An HIV-1-NL4-3 mutant virus which contains a 7 amino-acid deletion in p6gag (designated as 7d virus) was generated and its live cycle was investigated. The results showed that 7d virus had significantly lower replication capacity, poorer protease-mediated processing and viral proteins production. Electron microscopic examination of cells infected with wild-type or 7d virus demonstrated that the 7d virus had poorer and slower viral maturation processes: more viruses attached to the cell membrane and higher proportion of immature virions outside the cells. The interaction between p6gag and Alix protein was less efficient in cells infected with 7d virus. In conclusion, patients infected with CRF07_BC had significantly lower viral loads than patients infected with subtype B and it may due to the deletion of 7 amino acids which overlaps with Alix protein-binding domain of the p6gag

Twisting of the DNA-binding surface by a β-strand-bearing proline modulates DNA gyrase activity

DNA gyrase is the only topoisomerase capable of introducing (−) supercoils into relaxed DNA. The C-terminal domain of the gyrase A subunit (GyrA-CTD) and the presence of a gyrase-specific ‘GyrA-box’ motif within this domain are essential for this unique (−) supercoiling activity by allowing gyrase to wrap DNA around itself. Here we report the crystal structure of Xanthomonas campestris GyrA-CTD and provide the first view of a canonical GyrA-box motif. This structure resembles the GyrA-box-disordered Escherichia coli GyrA-CTD, both adopting a non-planar β-pinwheel fold composed of six seemingly spirally arranged β-sheet blades. Interestingly, structural analysis revealed that the non-planar architecture mainly stems from the tilted packing seen between blades 1 and 2, with the packing geometry likely being defined by a conserved and unusual β-strand-bearing proline. Consequently, the GyrA-box-containing blade 1 is placed at an angled spatial position relative to the other DNA-binding blades, and an abrupt bend is introduced into the otherwise flat DNA-binding surface. Mutagenesis studies support that the proline-induced structural twist contributes directly to gyrase’s (−) supercoiling activity. To our knowledge, this is the first demonstration that a β-strand-bearing proline may impact protein function. Potential relevance of β-strand-bearing proline to disease phenylketonuria is also noted