High-resolution habitat and bathymetry maps for 65,000 sq. km of Earth’s remotest coral reefs

Coral Reefs - With compelling evidence that half the world’s coral reefs have been lost over the last four decades, there is urgent motivation to understand where reefs are located and their...     

Myocardial remodeling after discrete radiofrequency injury: effects of tissue inhibitor of matrix metalloproteinase-1 gene deletion

Discrete myocardial lesions created through the delivery of radiofrequency (RF) energy can expand; however, the mechanisms have not been established. Matrix metalloproteinases (MMPs) play an important role in myocardial remodeling, and MMP activity can be regulated by the tissue inhibitors of the metalloproteinases (TIMPs). This study examined the role of TIMP-1 in postinjury myocardial remodeling. Lesions were created on the left ventricular (LV) epicardium of wild-type (WT, 8-12 wk, 129SVE) and age-matched TIMP-1 gene-deficient (timp-1(-/-)) mice through the delivery of RF current (80 degrees C, 30 s). Heart mass, LV scar volumes, and collagen content were measured at 1 h and 3, 7, and 28 days postinjury (n = 10 each). Age-matched, nonablated mice were used as reference controls (n = 5). Heart mass indexed to tibial length increased in WT and timp-1(-/-) mice but was greater in the timp-1(-/-) mice by 7 days. Scar volumes increased in a time-dependent manner in both groups but were higher in the timp-1(-/-) mice than the WT mice at 7 days (1.48 +/- 0.09 vs. 1.20 +/- 0.11 mm(3).mg(-1).mm, P < 0.05) and remained higher at 28 days. In the remote myocardium, wall thickness was greater and relative collagen content was lower in the timp-1(-/-) mice at 28 days postinjury. Discrete myocardial RF lesions expand in a time-dependent manner associated with myocyte hypertrophy remote to the scar. Moreover, postinjury myocardial remodeling was more extensive with TIMP-1 gene deletion. Thus TIMP-1 either directly or through modulation of MMP activity may regulate myocardial remodeling following infliction of a discrete injury.     

Synthesis and activity of 1-aryl-1'-imidazolyl methyl ethers as non-thiol farnesyltransferase inhibitors

A series of imidazole-containing methyl ethers (4-5) have been designed and synthesized as potent and selective farnesyltransferase inhibitors (FTIs) by transposition of the D-ring to the methyl group on the imidazole of the previously reported FTIs 3. Several compounds such as 4h and 5b demonstrate superior enzymatic activity to the current benchmark compound tipifarnib (1) with IC(50) values in the lower subnanomolar range, while maintaining excellent cellular activity comparable to tipifarnib. The compounds are characterized as being simple, easier to make, and possess no chiral center involved.     

Design, synthesis, and activity of 4-quinolone and pyridone compounds as nonthiol-containing farnesyltransferase inhibitors

As a part of our efforts to identify potent inhibitors of farnesyltransferase (FTase), modification of the structure of tipifarnib through structure-based design was undertaken by replacing the 2-quinolones with 4-quinolones and pyridones, and subsequent relocation of the D-ring to the N-methyl group on the imidazole ring. This study has yielded a novel series of potent and selective FTase inhibitors. The X-ray structure of tipifarnib (1) in complex with FTase was described.     

Bradykinin receptor gene variant and human physical performance.

Accumulating evidence suggests that athletic performance is strongly influenced by genetic variation. One such locus of influence is the gene for angiotensin-I converting enzyme (ACE), which exhibits a common variant [ACE insertion (I)/deletion (D)]. ACE can drive formation of vasoconstrictor ANG II but preferentially degrades vasodilator bradykinin. The ACE I allele is associated with higher kinin activity. A common gene variant in the kinin beta(2) receptor (B(2)R) exists: the -9 as opposed to +9 allele is associated with higher receptor mRNA expression. We tested whether this variant was associated with the efficiency of muscular contraction [delta efficiency (DE)] in 115 healthy men and women, or with running distance among 81 Olympic standard track athletes. We further sought evidence of biological interaction with ACE I/D genotype. DE was highly significantly associated with B(2)R genotype (23.84 +/- 2.41 vs. 24.25 +/- 2.81 vs. 26.05 +/- 2.26% for those of +9/+9 vs. +9/-9 vs. -9/-9 genotype; n = 25, 61, and 29, respectively; P = 0.0008 for ANOVA adjusted for sex). There was evidence for interaction with ACE I/D genotype, with individuals who were ACE II, with B(2)R -9/-9 having the highest DE at baseline. The ACE I/B(2)R -9 "high kinin receptor activity" haplotype was significantly associated with endurance (predominantly aerobic) event among elite athletes (P = 0.003). These data suggest that common genetic variation in the B(2)R is associated with efficiency of skeletal muscle contraction and with distance event of elite track athletes and that at least part of the associations of ACE and fitness phenotypes is through elevation of kinin activity.     

Ciprofibrate therapy in patients with hypertriglyceridemia and low high density lipoprotein (HDL)-cholesterol: greater reduction of non-HDL cholesterol in subjects with excess body weight (The CIPROAMLAT study)

Background

Microalbuminuria and subsequent progression to proteinuria and nephropathy is associated with increased oxidative stress, increased inflammatory cytokines and increased cardiovascular (CVD) risk. The common functional IL-6 -174G>C gene variant is also associated with elevated levels of inflammatory cytokines and CVD risk.

Methods

The aim of this study was to examine the association between the IL-6 -174G>C gene variant with plasma total antioxidant status (TAOS) in 552 subjects with type 2 diabetes in relation to urinary protein excretion.

Results

In subjects free from CVD, there was a significant interaction between urinary protein excretion (normoalbuminuria/ microalbuminuria/proteinuria) and the -174C allele (compared to -174GG) in determining plasma TAOS (p value for interaction = 0.03). In the -174C allele carriers there was a significant association between plasma TAOS and urinary protein excretion: normalbuminuria v microalbuminuria v proteinuria: 44.30% ± 11.32 vs. 39.74% ± 14.83 vs. 37.93% ± 16.42, ANOVA p = 0.025. In those with CVD, no interaction or association was observed with the -174C allele (p = 0.246).

Conclusion

The IL-6 -174G>C gene variant is associated with differences in plasma oxidative stress in response to altered protein excretion in subjects with type 2 diabetes.     

Site-specific genomic (SSG) and random domain-localized (RDL) mutagenesis in yeast

Background  

A valuable weapon in the arsenal available to yeast geneticists is the ability to introduce specific mutations into yeast genome. In particular, methods have been developed to introduce deletions into the yeast genome using PCR fragments. These methods are highly efficient because they do not require cloning in plasmids.     

Acridine orange induces translocation of phosphatidylserine to red blood cell surface

Clustering of band-3 on red blood cell (RBC) surface has been assumed to catalyze RBC phagocytosis. In studying this subject, acridine orange (AO) has commonly been employed on the assumption that it specifically induces band-3 clustering. In the present study, we show that AO strongly induces translocation of phosphatidylserine (PS) to RBC surface. Because surface PS is well known to induce RBC intercellular interaction, these findings suggest that the use of AO as a specific inducer of band-3 clustering is questionable. It is possible that band-3 clustering and PS translocation are interdependent, and this interrelationship has yet to be explored. erythrocytes; adherence; acridine orange; band-3; phosphatidylserine