Comparison of vildagliptin twice daily vs. sitagliptin once daily using continuous glucose monitoring (CGM): Crossover pilot study (J-VICTORIA study)

Background

The role of Lipoprotein (a) cholesterol {Lp(a)-C}as an additional and/or independent risk factor for cardiovascular disease (CVD) is not clear. We evaluated the associations between Lp(a)-C and other CVD risk factors including plasma lipoprotein concentrations and body fatness in overweight and obese African American children.

Methods

A cross-sectional analysis was carried out using data from a sample of 121 African American children aged 9-11 years with Body Mass Index (BMI)'s greater than the 85th percentile. Body height, weight and waist circumference (WC) were measured. Fasting plasma concentrations of Lp(a)-C, Total cholesterol (TC), High density lipoprotein cholesterol (HDL-C), Very low density lipoprotein cholesterol (VLDL-C), Intermediate density lipoprotein cholesterol (IDL-C), Low density lipoprotein cholesterol (LDL-C), and Triacylglycerides (TAG) were analyzed using the vertical auto profile (VAP) cholesterol method.

Results

After adjusting for child age, gender, and pubertal status, Lp(a)-C was positively associated with both HDL-C and TC, and negatively associated with VLDL-C and TAG. Including BMIz and WC as additional covariates did not alter the direction of the relationships between Lp(a)-C and the other lipoproteins. Finally, after adjusting for the other plasma lipoproteins, Lp(a)-C remained strongly associated with HDL-C, whereas the associations of Lp(a)-C with the other lipoproteins were not significant when HDL-C was simultaneously included in the regression models.

Conclusions

Lp(a)-C was positively associated with HDL-C and this association is not influenced by other lipoprotein subclasses or by the degree of obesity. We conclude that Lp(a) cholesterol is not an independent risk factor for CVD in African American children.     

Centriole and PCM cooperatively recruit CEP192 to spindle poles to promote bipolar spindle assembly

The pericentriolar material (PCM) that accumulates around the centriole expands during mitosis and nucleates microtubules. Here, we show the cooperative roles of the centriole and PCM scaffold proteins, pericentrin and CDK5RAP2, in the recruitment of CEP192 to spindle poles during mitosis. Systematic depletion of PCM proteins revealed that CEP192, but not pericentrin and/or CDK5RAP2, was crucial for bipolar spindle assembly in HeLa, RPE1, and A549 cells with centrioles. Upon double depletion of pericentrin and CDK5RAP2, CEP192 that remained at centriole walls was sufficient for bipolar spindle formation. In contrast, through centriole removal, we found that pericentrin and CDK5RAP2 recruited CEP192 at the acentriolar spindle pole and facilitated bipolar spindle formation in mitotic cells with one centrosome. Furthermore, the perturbation of PLK1, a critical kinase for PCM assembly, efficiently suppressed bipolar spindle formation in mitotic cells with one centrosome. Overall, these data suggest that the centriole and PCM scaffold proteins cooperatively recruit CEP192 to spindle poles and facilitate bipolar spindle formation.     

Fine mapping of a gene for low-tiller number, Ltn, in japonica rice (Oryza sativa L.) variety Aikawa 1

Tillering is one of the most important agronomic traits related to grain production in rice (Oryza sativa L.). A japonica-type variety, Aikawa 1, is known to have low-tiller number. The detailed location of a low-tillering gene, Ltn, which has been localized on chromosome 8 in Aikawa 1, was confirmed by molecular mapping. Using BC₅F₂ individuals derived from a cross between IR64 and Aikawa 1, the low-tillering gene was mapped to an interval defined by SSR markers ssr5816-3 and A4765. This was designated as Ltn because there was no reported gene for tillering in the region of chromosome 8. Through high-resolution linkage analysis, the candidate region of Ltn was located between DNA markers ssr6049-23 and ind6049-1 corresponding to 38.6 kbp on the Nipponbare genome sequence. These DNA markers, which were tightly linked to Ltn, are useful for marker-assisted selection in breeding studies.     

Effects of a bout of traditional and original sumo training on neutrophil immune function in amateur university sumo wrestlers

In order to examine in detail the influence on the neutrophil immune function in sumo wrestlers of performing traditional and original training we examined changes in the neutrophil immune function in 17 male amateur university sumo wrestlers (aged 20.2 ± 1.5 years), before (‘Pre’) and after the training (‘Post’) for 2.5 h under fasting conditions. Assays included blood leukocyte and neutrophil counts, serum concentration of immunoglobulins, complements, myogenic enzymes and neutrophil oxidative burst activity (OBA) and phagocytic activity (PA). Myogenic enzymes, neutrophil counts, the ratio of neutrophil counts:leukocyte counts significantly increased and immunoglobulins and complements decreased in Post compared with Pre. There was a positive correlation between the change of neutrophil counts before and after the training and the change of creatine kinase (r = 0.667, p < 0.01). The Post OBA significantly increased and PA significantly decreased compared with Pre. It was concluded that sumo training causes muscular damage and an increase in the neutrophil count as a response. In this time, although OBA increased, PA decreased after training. Compensation between PA and reactive oxygen species production may exist to maintain the overall integrity of the neutrophil immune function. Copyright © 2008 John Wiley & Sons, Ltd.     

Effects of acid exposure on the conformation, stability, and aggregation of monoclonal antibodies

Exposure of antibodies to low pH is often unavoidable for purification and viral clearance. The conformation and stability of two humanized monoclonal antibodies (hIgG4-A and -B) directed against different antigens and a mouse monoclonal antibody (mIgG1) in 0.1M citrate at acidic pH were studied using circular dichroism (CD), differential scanning calorimetry (DSC), and sedimentation velocity. Near- and far-UV CD spectra showed that exposure of these antibodies to pH 2.7-3.9 induced only limited conformational changes, although the changes were greater at the lower pH. However, the acid conformation is far from unfolded or so-called molten globule structure. Incubation of hIgG4-A at pH 2.7 and 3.5 at 4 degrees C over the course of 24 h caused little change in the near-UV CD spectra, indicating that the acid conformation is stable. Sedimentation velocity showed that the hIgG4-A is largely monomeric at pH 2.7 and 3.5 as well as at pH 6.0. No time-dependent changes in sedimentation profile occurred upon incubation at these low pHs, consistent with the conformational stability observed by CD. The sedimentation coefficient of the monomer at pH 2.7 or 3.5 again suggested that no gross conformational changes occur at these pHs. DSC analysis of the antibodies showed thermal unfolding at pH 2.7-3.9 as well as at pH 6.0, but with decreased melting temperatures at the lower pH. These results are consistent with the view that the antibodies undergo limited conformational change, and that incubation at 4 degrees C at low pH results in no time-dependent conformational changes. Titration of hIgG4-A from pH 3.5 to 6.0 resulted in recovery of native monomeric proteins whose CD and DSC profiles resembled those of the original sample. However, titration from pH 2.7 resulted in lower recovery of monomeric antibody, indicating that the greater conformational changes observed at this pH cannot be fully reversed to the native structure by a simple pH titration.     

EMD: an ensemble algorithm for discovering regulatory motifs in DNA sequences

Background  

Understanding gene regulatory networks has become one of the central research problems in bioinformatics. More than thirty algorithms have been proposed to identify DNA regulatory sites during the past thirty years. However, the prediction accuracy of these algorithms is still quite low. Ensemble algorithms have emerged as an effective strategy in bioinformatics for improving the prediction accuracy by exploiting the synergetic prediction capability of multiple algorithms.     

Expression and localization of aquaporins in rat gastrointestinal tract

A family of water-selective channels, aquaporins (AQP), has beendemonstrated in various organs and tissues. However, the localizationand expression of the AQP family members in the gastrointestinal tracthave not been entirely elucidated. This study aimed to demonstrate theexpression and distribution of several types of the AQP family and tospeculate on their role in water transport in the rat gastrointestinal tract. By RNase protection assay, expression of AQP1-5 and AQP8 was examined in various portions through the gastrointestinal tract.AQP1 and AQP3 mRNAs were diffusely expressed from esophagus to colon,and their expression was relatively intense in the small intestine andcolon. In contrast, AQP4 mRNA was selectively expressed in the stomachand small intestine and AQP8 mRNA in the jejunum and colon.Immunohistochemistry and in situ hybridization demonstrated cellularlocalization of these AQP in these portions. AQP1 was localized onendothelial cells of lymphatic vessels in the submucosa and laminapropria throughout the gastrointestinal tract. AQP3 was detected on thecircumferential plasma membranes of stratified squamous epithelialcells in the esophagus and basolateral membranes of cardiac glandepithelia in the lower stomach and of surface columnar epithelia in thecolon. However, AQP3 was not apparently detected in the smallintestine. AQP4 was present on the basolateral membrane of the parietalcells in the lower stomach and selectively in the basolateral membranesof deep intestinal gland cells in the small intestine. AQP8 mRNAexpression was demonstrated in the absorptive columnar epithelial cellsof the jejunum and colon by in situ hybridization. These findings mayindicate that water crosses the epithelial layer through these waterchannels, suggesting a possible role of the transcellular route forwater intake or outlet in the gastrointestinal tract.     

Genome‐wide distribution and functions of the AAE complex in epigenetic regulation in Arabidopsis

Heterochromatin is widespread in eukaryotic genomes and has diverse impacts depending on its genomic context. Previous studies have shown that a protein complex, the ASI1‐AIPP1‐EDM2 (AAE) complex, participates in polyadenylation regulation of several intronic heterochromatin‐containing genes. However, the genome‐wide functions of AAE are still unknown. Here, we show that the ASI1 and EDM2 mostly target the common genomic regions on a genome‐wide level and preferentially interacts with genetic heterochromatin. Polyadenylation (poly(A) sequencing reveals that AAE complex has a substantial influence on poly(A) site usage of heterochromatin‐containing genes, including not only intronic heterochromatin‐containing genes but also the genes showing overlap with heterochromatin. Intriguingly, AAE is also involved in the alternative splicing regulation of a number of heterochromatin‐overlapping genes, such as the disease resistance gene RPP4. We provided evidence that genic heterochromatin is indispensable for the recruitment of AAE in polyadenylation and splicing regulation. In addition to conferring RNA processing regulation at genic heterochromatin‐containing genes, AAE also targets some transposable elements (TEs) outside of genes (including TEs sandwiched by genes and island TEs) for epigenetic silencing. Our results reveal new functions of AAE in RNA processing and epigenetic silencing, and thus represent important advances in epigenetic regulation.     

Cell shape controls rheotaxis in small parasitic bacteria

Mycoplasmas, a group of small parasitic bacteria, adhere to and move across host cell surfaces. The role of motility across host cell surfaces in pathogenesis remains unclear. Here, we used optical microscopy to visualize rheotactic behavior in three phylogenetically distant species of Mycoplasma using a microfluidic chamber that enabled the application of precisely controlled fluid flow. We show that directional movements against fluid flow occur synchronously with the polarized cell orienting itself to be parallel against the direction of flow. Analysis of depolarized cells revealed that morphology itself functions as a sensor to recognize rheological properties that mimic those found on host-cell surfaces. These results demonstrate the vital role of cell morphology and motility in responding to mechanical forces encountered in the native environment.