The β3‐integrin endothelial adhesome regulates microtubule‐dependent cell migration

Integrin β3 is seen as a key anti‐angiogenic target for cancer treatment due to its expression on neovasculature, but the role it plays in the process is complex; whether it is pro‐ or anti‐angiogenic depends on the context in which it is expressed. To understand precisely β3's role in regulating integrin adhesion complexes in endothelial cells, we characterised, by mass spectrometry, the β3‐dependent adhesome. We show that depletion of β3‐integrin in this cell type leads to changes in microtubule behaviour that control cell migration. β3‐integrin regulates microtubule stability in endothelial cells through Rcc2/Anxa2‐driven control of active Rac1 localisation. Our findings reveal that angiogenic processes, both in vitro and in vivo, are more sensitive to microtubule targeting agents when β3‐integrin levels are reduced.     

Comparative morphology of populations of Monstera Adans. (Araceae) from natural forest fragments in Northeast Brazil using elliptic Fourier Analysis of leaf outlines

Summary  A comparative study of the leaf outline morphometrics of Monstera adansonii var. klotzschiana, M. adansonii var. laniata and M. praetermissa was carried out. The study focused on populations in isolated montane humid (brejo) forests of Ceará state in Northeast Brazil and compared them with populations from Amazonia and the Brazilian Atlantic Forest. Digitised outlines were prepared from a total of 1,695 field-collected leaf images from 20 populations, and elliptic Fourier analysis was used to generate matrices of coefficients, from which six shape variables (principal components) were extracted using Principal Components Analysis. Intra-population variability and inter-population differences were analysed with multivariate distance methods. Separate analyses were carried out for each of three leaf size classes (juvenile, submature, mature) because of the strong heteroblasty typical of this genus. Juvenile leaves were the least variable size class within populations of M. adansonii var. klotzschiana. The shape variables expressed very similar types of variation in all three size classes. The Ceará brejo populations of M. adansonii var. klotzschiana showed significant differences between mature leaf outlines in all pairwise comparisons; the Pacatuba population was the most distinct. The Ceará populations did not cluster together exclusively. In all three size classes, populations clustered together into their taxonomic groups, most clearly so in mature leaves. No correlation between morphological and geographic distance matrices was found, nor between morphological and molecular distance. The study showed that leaf outline shape is a practicable and useful quantitative trait for studying morphological variability at species, varietal and population levels. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

The effects of mispair and nonpair correction in hybrid DNA on base ratios (G + C content) and total amounts of DNA

Base ratios and total DNA amounts can vary substantially between and within higher taxa and genera, and even within species. Gene conversion is one of several mechanisms that could cause such changes. For base substitutions, disparity in conversion direction is accompanied by an equivalent disparity in base ratio at the heterozygous site. Disparity in the direction of gene conversion at meiosis is common and can be extreme. For transitions (which give purine [R]/pyrimidine [Y] mispairs) and for transversions giving unlike R/R and Y/Y mispairs in hybrid DNA, this disparity could give slow but systematic changes in G + C percentage. For transversions giving like R/R and Y/Y mispairs, it could change AT/TA and CG/GC ratios. From the extent of correction direction disparity, one can deduce properties of repair enzymes, such as the ability (1) to excise preferentially the purine from one mispair and the pyrimidine from the other for two different R/Y mispairs from a single heterozygous site and (2) to excise one base preferentially from unlike R/R or Y/Y mispairs. Frame-shifts usually show strong disparity in conversion direction, with preferential cutting of the nonlooped or the looped-out strand of the nonpair in heterozygous h-DNA. The opposite directions of disparity for frame-shifts and their intragenic suppressors as Ascobolus suggest that repair enzymes have a strong, systematic bias as to which strand is cut. The conversion spectra of mutations induced with different mutagens suggest that the nonlooped strand is preferentially cut, so that base additions generally convert to mutant and deletions generally convert to wild-type forms. Especially in nonfunctional or noncoding DNA, this could cause a general increase in DNA amounts. Conversion disparity, selection, mutation, and other processes interact, affecting rates of change in base ratios and total DNA.      

Interdependency of stress relaxation and afferent nerve discharge in rat small intestine

Background and aimsTo be able to characterize intestinal mechano-electrical transduction, i.e. the mechanoreceptor behaviour, quantitative nerve studies with controlled and quantified stimulus are needed. This study aimed to determine the relationship between mechanical stress relaxation and afferent discharge adaptation evoked by fast isovolumetric bag distensions in the rat jejunum.MethodsMultiunit afferent activity was recorded in vivo from jejunum afferents from five male Wistar rats. The jejunum was distended via a bag at a distension speed of 0.5 ml/s to volumes of 0.2, 0.25, 0.3 and 0.4 ml, respectively. The distension was stopped and the volume was kept constant for 2 min to induce stress relaxation. The pressure in the bag, the afferent discharge (spike rate) and the diameter of the segment during the relaxation time were recorded simultaneously.ResultsThe afferent discharge responses to distension showed a pattern with a peak during the sudden loading followed by decreasing activity with time. At distension volumes of 0.2, 0.25, 0.3 and 0.4 ml, the afferent discharge declined faster and to a greater extent (94%, 91%,96% and 87%) than the stress decreased (55%, 45%, 59% and 56%) during stress relaxation (p<0.001). Both the stress and the afferent discharge during the constant volume distension were independent of the distension volumes (p>0.5). The stress and the afferent discharge during the distension can be described mathematically on the basis of the quasi-linear theory of viscoelasticity. The association between the stress and the afferent discharge during the constant volume distension is linear with the same slope under various distension volumes.ConclusionsIntestinal mechanoreceptors were sensitive to the stress stimulus and a linear association between the stress relaxation and afferent discharge adaptation was found. The quasi-linear theory of visco-elasticity can be transferred to analysis of mechanical stimulus evoked afferent discharge.     

Stress‐associated H3K4 methylation accumulates during postnatal development and aging of rhesus macaque brain

Epigenetic modifications are critical determinants of cellular and developmental states. Epigenetic changes, such as decreased H3K27me3 histone methylation on insulin/IGF1 genes, have been previously shown to modulate lifespan through gene expression regulation. However, global epigenetic changes during aging and their biological functions, if any, remain elusive. Here, we examined the histone modification H3K4 dimethylation (H3K4me2) in the prefrontal cortex of individual rhesus macaques at different ages by chromatin immunoprecipitation, followed by deep sequencing (ChIP‐seq) at the whole genome level. Through integrative analysis of the ChIP‐seq profiles with gene expression data, we found that H3K4me2 increased at promoters and enhancers globally during postnatal development and aging, and those that correspond to gene expression changes in cis are enriched for stress responses, such as the DNA damage response. This suggests that metabolic and environmental stresses experienced by an organism are associated with the progressive opening of chromatin. In support of this, we also observed increased expression of two H3K4 methyltransferases, SETD7 and DPY30, in aged macaque brain.     

Homogeneity of the 16S rDNA sequence among geographically disparate isolates of Taylorella equigenitalis

Background

At present, six accessible sequences of 16S rDNA from Taylorella equigenitalis (T. equigenitalis) are available, whose sequence differences occur at a few nucleotide positions. Thus it is important to determine these sequences from additional strains in other countries, if possible, in order to clarify any anomalies regarding 16S rDNA sequence heterogeneity. Here, we clone and sequence the approximate full-length 16S rDNA from additional strains of T. equigenitalis isolated in Japan, Australia and France and compare these sequences to the existing published sequences.

Results

Clarification of any anomalies regarding 16S rDNA sequence heterogeneity of T. equigenitalis was carried out. When cloning, sequencing and comparison of the approximate full-length 16S rDNA from 17 strains of T. equigenitalis isolated in Japan, Australia and France, nucleotide sequence differences were demonstrated at the six loci in the 1,469 nucleotide sequence. Moreover, 12 polymorphic sites occurred among 23 sequences of the 16S rDNA, including the six reference sequences.

Conclusion

High sequence similarity (99.5% or more) was observed throughout, except from nucleotide positions 138 to 501 where substitutions and deletions were noted.     

Desflurane consumption during automated closed-circuit delivery is higher than when a conventional anesthesia machine is used with a simple vaporizer-O2-N2O fresh gas flow sequence

Background

Current analgesics have drawbacks such as delays in acquisition, lag-times for effect, and side effects. We recently presented a preliminary report of a new analgesic method involving a two-minute sciatic nerve press, which resulted in immediate short-term relief of pain associated with dental and renal diseases. The present study investigated whether this technique was effective for pain associated with other disease types, and whether the relief was effective for up to one hour.

Methods

This randomized, placebo-controlled, parallel-group trial was conducted in four hospitals in Anhui Province, China. Patients with pain were sequentially recruited by participating physicians during clinic visits, and 135 patients aged 15 – 80 years were enrolled. Dental disease patients included those with acute pulpitis and periapical abscesses. Renal disease patients included those with kidney infections and/or stones. Tumor patients included those with nose, breast, stomach and liver cancers, while Emergency Room patients had various pathologies. Patients were randomly assigned to receive a "sciatic nerve press" in which pressure was applied simultaneously to the sciatic nerves at the back of both thighs, or a "placebo press" in which pressure was applied to a parallel region on the front of the thighs. Each fist applied a pressure of 11 – 20 kg for 2 minutes. Patients rated their level of pain before and after the procedure.

Results

The "sciatic nerve press" produced immediate relief of pain in all patient groups. Emergency patients reported a 43.5% reduction in pain (p < 0.001). Significant pain relief for dental, renal and tumor patients lasted for 60 minutes (p < 0.001). The peak pain relief occurred at the 10 – 20^th minutes, and the relief decreased 47% by the 60^th minutes.

Conclusion

Two minutes of pressure on both sciatic nerves produced immediate significant short-term conduction analgesia. This technique is a convenient, safe and powerful method for the short-term treatment of clinical pain associated with a diverse range of pathologies.

Trial registration

Current Controlled Trials ACTRN012606000439549     

Plant collecting spread and densities: their potential impact on biogeographical studies in Thailand

Aims To produce representative aggregate maps of plant collection locations in Thailand and discuss their impact on biogeographical studies in Thailand and the surrounding region. Location Thailand. Methods A representative data set comprising 6593 plant specimen records for Thailand has been assembled. The data set contains ± all known collections for fifteen representative plant families and further records for another 104. All records are localized to Changwat (province), 6441 to at least quarter degree square. Results Analysis shows that the spread of collecting activity in Thailand is markedly uneven; 20% of collections come from a single Changwat (Chiang Mai) and 53% of Changwat have fifty or fewer collections. The distribution of collections by Changwat and by quarter degree square is erratic with most squares and Changwat having few collections, both in proportionate and absolute terms. Some of the most densely forested Changwats and squares appear undercollected. Distribution maps for common, easily recognized tree species in the genus Syzygium show distributional gaps. Conclusions Thailand is defined as an undercollected country. Even within the few well‐collected quarter degree squares the spread of collecting is still poor; almost all collections being localized to one of three mountain ranges or their foothills. There are many gaps in collecting activity which make impossible a straightforward interpretation of biogeographical pattern. It is argued that targeted collecting activity is needed, that assembly of this type of data set is therefore essential and that our data set and its interpretation is a model for all countries in the region.