Penicacids A-C, three new mycophenolic acid derivatives and immunosuppressive activities from the marine-derived fungus Penicillium sp. SOF07

Three new mycophenolic acid derivatives, penicacids A-C (1-3), together with two known analogues, mycophenolic acid (MPA, 4) and 4'-hydroxy-MPA (5), were isolated from a fungus Penicillium sp. SOF07 derived from a South China Sea marine sediment. The structures of compounds 1-3 were elucidated on the basis of MS and NMR ((1)H, (13)C, HSQC and HMBC) data analyses and comparisons with the known compounds. Structure-activity relationship studies of compounds 1-5 focused on inosine-monophosphate dehydrogenase inhibition revealed that hydroxylation at C-4', methylation at C-7-OH, dual hydroxylation at C-2'/C-3' double bond of MPA diminished bioactivity whereas glucosyl hydroxylation at C-4' correlated to bioactivity comparable to that observed for MPA.     

Identification of a previously unknown antigen-specific regulatory T cell and its mechanism of suppression

Despite increasing evidence for the existence of antigen-specific regulatory T cells, the mechanisms underlying suppression remain unclear. In this study we have identified and cloned a novel subset of antigen-specific regulatory T cells and demonstrated that these T cells possess a unique combination of cell surface markers and array of cytokines. The regulatory T cells are able to inhibit the function of T cells carrying the same T-cell receptor specificity and prevent skin allograft rejection in an antigen-specific, dose-dependent manner. The regulatory T cells are able to acquire alloantigen from antigen-presenting cells, present the alloantigen to activated syngeneic CD8+ T cells and then send death signals to CD8+ T cells. These findings provide a novel mechanism of regulatory T-cell-mediated, antigen-specific suppression.     

Construction of a high density integrated genetic map for cucumber (Cucumis sativus L.)

The high-density consensus map was constructed based on the GY14 × PI 183967 map from an inter-subspecific cross and the extended S94 × S06 map from an intra-subspecific cross. The consensus map was composed of 1,369 loci, including 1,152 SSR loci, 192 SRAP loci, 21 SCAR loci and one STS locus as well as three gene loci of fruit external quality traits in seven chromosomes, and spanned 700.5 cM, of which 682.7 cM (97.5%) were covered by SSR markers. The average genetic distance and physical interval between loci were 0.51 cM and ~268 kbp, respectively. Additionally, the physical position of the sequence-associated markers aligned along the assembled cucumber genome sequence established a relationship between genetic maps and cucumber genome sequence and to a great extent validated the order of markers in individual maps and consensus map. This consensus map with a high marker density and well-ordered markers is a saturated and reliable linkage map for genetic analysis of cucumber or the Cucurbitaceae family of plants.     

Determinants of Medication Adherence to Antihypertensive Medications among a Chinese Population Using Morisky Medication Adherence Scale

Background and Objectives

Poor adherence to medications is one of the major public health challenges. Only one-third of the population reported successful control of blood pressure, mostly caused by poor drug adherence. However, there are relatively few reports studying the adherence levels and their associated factors among Chinese patients. This study aimed to study the adherence profiles and the factors associated with antihypertensive drug adherence among Chinese patients.

Methods

A cross-sectional study was conducted in an outpatient clinic located in the New Territories Region of Hong Kong. Adult patients who were currently taking at least one antihypertensive drug were invited to complete a self-administered questionnaire, consisting of basic socio-demographic profile, self-perceived health status, and self-reported medication adherence. The outcome measure was the Morisky Medication Adherence Scale (MMAS-8). Good adherence was defined as MMAS scores greater than 6 points (out of a total score of 8 points).

Results

From 1114 patients, 725 (65.1%) had good adherence to antihypertensive agents. Binary logistic regression analysis was conducted. Younger age, shorter duration of antihypertensive agents used, job status being employed, and poor or very poor self-perceived health status were negatively associated with drug adherence.

Conclusion

This study reported a high proportion of poor medication adherence among hypertensive subjects. Patients with factors associated with poor adherence should be more closely monitored to optimize their drug taking behavior.     

SNP-based pool genotyping and haplotype analysis accelerate fine-mapping of the wheat genomic region containing stripe rust resistance gene <Emphasis Type="Italic">Yr26</Emphasis>

Key message

NGS-assisted super pooling emerging as powerful tool to accelerate gene mapping and haplotype association analysis within target region uncovering specific linkage SNPs or alleles for marker-assisted gene pyramiding.

Abstract

Conventional gene mapping methods to identify genes associated with important agronomic traits require significant amounts of financial support and time. Here, a single nucleotide polymorphism (SNP)-based mapping approach, RNA-Seq and SNP array assisted super pooling analysis, was used for rapid mining of a candidate genomic region for stripe rust resistance gene Yr26 that has been widely used in wheat breeding programs in China. Large DNA and RNA super-pools were genotyped by Wheat SNP Array and sequenced by Illumina HiSeq, respectively. Hundreds of thousands of SNPs were identified and then filtered by multiple filtering criteria. Among selected SNPs, over 900 were found within an overlapping interval of less than 30 Mb as the Yr26 candidate genomic region in the centromeric region of chromosome arm 1BL. The 235 chromosome-specific SNPs were converted into KASP assays to validate the Yr26 interval in different genetic populations. Using a high-resolution mapping population (>?30,000 gametes), we confined Yr26 to a 0.003-cM interval. The Yr26 target region was anchored to the common wheat IWGSC RefSeq v1.0 and wild emmer WEWSeq v.1.0 sequences, from which 488 and 454 kb fragments were obtained. Several candidate genes were identified in the target genomic region, but there was no typical resistance gene in either genome region. Haplotype analysis identified specific SNPs linked to Yr26 and developed robust and breeder-friendly KASP markers. This integration strategy can be applied to accelerate generating many markers closely linked to target genes/QTL for a trait of interest in wheat and other polyploid species.

     

pH, healing rate, and symptom relief in patients with GERD

Gastroesophageal reflux symptoms are common and occur in all of us from time to time. In others, reflux may be associated with ulcerative esophagitis. The symptoms may be aggravated by large meals, coffee, smoking and position. Physiological and pathological reflux can be separated by the frequency and duration of the exposure of the lower esophagus to acid. Pathological reflux results in symptoms and also esophagitis and ulceration in some patients. Although gastroesophageal reflux disease (GERD) is considered to result from a disorder of motility in the esophagus, gastric acid and peptic activity are deemed pivotal to the initiation and continuation of the esophageal damage and the development of symptoms. Acid exposure in the esophagus is normally less than 4 percent of the 24 hours with a pH below 4. An increase over 4 percent of the time with a pH less than 4 is considered pathological. Hence, antisecretory drugs have become the principle approach to the treatment of reflux symptoms and esophagitis since they reduce the acidity, of gastric juice and the activity of pepsin. Importantly, they also reduce the volume of gastric juice available for reflux into the esophagus. There is a clear relationship between the degree and duration of acid suppression and the relief of heartburn and healing of esophagitis. Pharmacodynamic studies with different dose regimens of the H2-receptor antagonists and the proton pump inhibitors show a difference in the degree and duration of the antisecretory effect, and this correlates closely with the results of clinical trials with respect to the healing of esophagitis and the relief of symptoms. Proton pump inhibitors achieve healing rates by week four, which are not achieved by H2-receptor antagonists even after 12 weeks of treatment. The advantage of proton pump inhibitors over H2-receptor antagonists is due to the greater degree, longer duration of effect and more complete inhibition of acid secretion that maintains intragastric pH above 4 for a maximal duration. Although there is no significant difference between proton pump inhibitors with respect to healing of esophagitis, symptom relief occurs earlier with lansoprazole than omeprazole, and this is probably due to the greater oral bioavailability and faster onset of action of lansoprazole when compared to omeprazole.