Evidence that the pre-mRNA splicing factor Clf1p plays a role in DNA replication in Saccharomyces cerevisiae

Clf1p is an essential, highly conserved protein in S. cerevisiae that has been implicated in pre-mRNA splicing. Clf1p's ortholog in Drosophila, Crn, is required for normal cell proliferation. Cells depleted of Clf1p arrest primarily with large buds, a single nucleus, a 2C DNA content, and a short, intact mitotic spindle. We isolated temperature-sensitive clf1 mutants that exhibit similar mitotic defects when released to the restrictive temperature from an early S-phase block. While these mutants also accumulate unspliced pre-mRNA at the restrictive temperature, the mitotic arrest does not appear to result from a failure to splice tubulin pre-mRNA. Moreover, the same mutants exhibit a delayed entry into S phase when released to the restrictive temperature from a G1 phase block. This delay could not be suppressed by disruption of the S-phase CDK inhibitor SIC1, suggesting that Clf1p is involved in DNA replication. Consistent with this possibility, we find that Clf1p (but not the mutant clf1p) interacts with the DNA replication initiation protein Orc2p in two-hybrid and co-immunoprecipitation assays, that Clf1p preferentially associates with origins of DNA replication, and that this association is Orc2p dependent. These observations suggest that Clf1p plays a direct role in the initiation of DNA replication.     

Brain mechanisms of pain affect and pain modulation

Recent animal studies reveal ascending nociceptive and descending modulatory pathways that may contribute to the affective-motivational aspects of pain and play a critical role in the modulation of pain. In humans, a reliable pattern of cerebral activity occurs during the subjective experience of pain. Activity within the anterior cingulate cortex and possibly in other classical limbic structures, appears to be closely related to the subjective experience of pain unpleasantness and may reflect the regulation of endogenous mechanisms of pain modulation.     

Some observations on the effect of Daflon (micronized purified flavonoid fraction of Rutaceae aurantiae) in bancroftian filarial lymphoedema

BACKGROUND: Morbidity management is a core component of the global programme for the elimination of lymphatic filariasis. In a double-blind clinical trial, the tolerability and efficacy of Daflon (500 mg) + DEC (25 mg) or DEC (25 mg) alone, twice daily for 90 days, was studied in 26 patients with bancroftian filarial lymphoedema. RESULTS: None of the patients in either drug group reported any adverse reaction throughout the treatment period (90 days). Haematological and biochemical parameters were within normal limits and there was no significant difference between the pre-treatment (day 0) and post-treatment (day 90) values. The group receiving Daflon showed significant reduction in oedema volume from day 90 (140.6 PlusMinus; 18.8 ml) to day 360 (71.8 PlusMinus; 20.7 ml) compared to the pre-treatment (day 0, 198.4 PlusMinus; 16.5 ml) value. This accounted for a 63.8% reduction in oedema volume by day 360 (considering the pre-treatment (day 0) as 100%). In the DEC group, the changes in oedema volume (between day 1 and day 360) were not significant when compared to the pre-treatment (day 0) value. The percentage reduction at day 360 was only 9%, which was not significant (P > 0.05). CONCLUSION: This study has shown that Daflon (500 mg, twice a day for 90 days) is both safe and efficacious in reducing oedema volume in bancroftian filarial lymphoedema. Further clinical trials are essential for strengthening the evidence base on the role of this drug in the morbidity management of lymphatic filariasis.     

Direct intracardiac injection of umbilical cord-derived stromal cells and umbilical cord blood-derived endothelial cells for the treatment of ischemic cardiomyopathy

The development of new therapeutic strategies is necessary to reduce the worldwide social and economic impact of cardiovascular disease, which produces high rates of morbidity and mortality. A therapeutic option that has emerged in the last decade is cell therapy. The aim of this study was to compare the effect of transplanting human umbilical cord-derived stromal cells (UCSCs), human umbilical cord blood-derived endothelial cells (UCBECs) or a combination of these two cell types for the treatment of ischemic cardiomyopathy (IC) in a Wistar rat model. IC was induced by left coronary artery ligation, and baseline echocardiography was performed seven days later. Animals with a left ventricular ejection fraction (LVEF) of ≤40% were selected for the study. On the ninth day after IC was induced, the animals were randomized into the following experimental groups: UCSCs, UCBECs, UCSCs plus UCBECs, or vehicle (control). Thirty days after treatment, an echocardiographic analysis was performed, followed by euthanasia. The animals in all of the cell therapy groups, regardless of the cell type transplanted, had less collagen deposition in their heart tissue and demonstrated a significant improvement in myocardial function after IC. Furthermore, there was a trend of increasing numbers of blood vessels in the infarcted area. The median value of LVEF increased by 7.19% to 11.77%, whereas the control group decreased by 0.24%. These results suggest that UCSCs and UCBECs are promising cells for cellular cardiomyoplasty and can be an effective therapy for improving cardiac function following IC.     

Susceptibility of quagga mussels (Dreissena rostriformis bugensis) to hot-water sprays as a means of watercraft decontamination

The recent spread of dreissenid mussels to various bodies of water in the western US has sparked interest by many state and federal agencies to develop protocols to stop further expansion. Quagga mussels (Dreissena rostriformis bugensis) are of particular importance as they are currently the most widespread dreissenid species in the region. This project examined the susceptibility of quagga mussels to hot-water sprays at different temperatures and durations of spray contact at Lake Mead (Nevada-Arizona, USA). Emersed adult quagga mussels were exposed to hot-water sprays at 20, 40, 50, 54, 60, 70, and 80°C for 1, 2, 5, 10, 20, 40, 80, and 160?s. Sprays at ≥60°C for 5?s were shown to be 100% lethal. Sprays of 54°C for 10?s, 50°C for 20?s, and 40°C for 40?s also resulted in 100% mortality. A spray temperature of 60°C for 5?s is recommended for mitigating fouling by quagga mussels.     

SSR-enriched genetic linkage maps of bermudagrass (<Emphasis Type="Italic">Cynodon dactylon</Emphasis> × <Emphasis Type="Italic">transvaalensis</Emphasis>), and their comparison with allied plant genomes

Key message

We report SSR-enriched genetic maps of bermudagrass that: (1) reveal partial residual polysomic inheritance in the tetraploid species, and (2) provide insights into the evolution of chloridoid genomes.

Abstract

This study describes genetic linkage maps of two bermudagrass species, Cynodon dactylon (T89) and Cynodon transvaalensis (T574), that integrate heterologous microsatellite markers from sugarcane into frameworks built with single-dose restriction fragments (SDRFs). A maximum likelihood approach was used to construct two separate parental maps from a population of 110 F₁ progeny of a cross between the two parents. The T89 map is based on 291 loci on 34 cosegregating groups (CGs), with an average marker spacing of 12.5 cM. The T574 map is based on 125 loci on 14 CGs, with an average marker spacing of 10.7 cM. Six T89 and one T574 CG(s) deviated from disomic inheritance. Furthermore, marker segregation data and linkage phase analysis revealed partial residual polysomic inheritance in T89, suggesting that common bermudagrass is undergoing diploidization following whole genome duplication (WGD). Twenty-six T89 CGs were coalesced into 9 homo(eo)logous linkage groups (LGs), while 12 T574 CGs were assembled into 9 LGs, both putatively representing the basic chromosome complement (x?=?9) of the species. Eight T89 and two T574 CGs remain unassigned. The marker composition of bermudagrass ancestral chromosomes was inferred by aligning T89 and T574 homologs, and used in comparisons to sorghum and rice genome sequences based on 108 and 91 significant blast hits, respectively. Two nested chromosome fusions (NCFs) shared by two other chloridoids (i.e., zoysiagrass and finger millet) and at least three independent translocation events were evident during chromosome number reduction from 14 in the polyploid common ancestor of Poaceae to 9 in Cynodon.

     

Performance of Humans vs. Exploration Algorithms on the Tower of London Test

The Tower of London Test (TOL) used to assess executive functions was inspired in Artificial Intelligence tasks used to test problem-solving algorithms. In this study, we compare the performance of humans and of exploration algorithms. Instead of absolute execution times, we focus on how the execution time varies with the tasks and/or the number of moves. This approach used in Algorithmic Complexity provides a fair comparison between humans and computers, although humans are several orders of magnitude slower. On easy tasks (1 to 5 moves), healthy elderly persons performed like exploration algorithms using bounded memory resources, i.e., the execution time grew exponentially with the number of moves. This result was replicated with a group of healthy young participants. However, for difficult tasks (5 to 8 moves) the execution time of young participants did not increase significantly, whereas for exploration algorithms, the execution time keeps on increasing exponentially. A pre-and post-test control task showed a 25% improvement of visuo-motor skills but this was insufficient to explain this result. The findings suggest that naive participants used systematic exploration to solve the problem but under the effect of practice, they developed markedly more efficient strategies using the information acquired during the test.     

Comparative analysis of peanut NBS-LRR gene clusters suggests evolutionary innovation among duplicated domains and erosion of gene microsynteny

? Plant genomes contain numerous disease resistance genes (R genes) that play roles in defense against pathogens. Scarcity of genetic polymorphism makes peanut (Arachis hypogaea) especially vulnerable to a wide variety of pathogens. ? Here, we isolated and characterized peanut bacterial artificial chromosomes (BACs) containing a high density of R genes. Analysis of two genomic regions identified several TIR-NBS-LRR (Toll-interleukin-1 receptor, nucleotide-binding site, leucine-rich repeat) resistance gene analogs or gene fragments. We reconstructed their evolutionary history characterized by tandem duplications, possibly facilitated by transposon activities. We found evidence of both intergenic and intragenic gene conversions and unequal crossing-over, which may be driving forces underlying the functional evolution of resistance. ? Analysis of the sequence mutations, protein secondary structure and three-dimensional structures, all suggest that LRR domains are the primary contributor to the evolution of resistance genes. The central part of LRR regions, assumed to serve as the active core, may play a key role in the resistance function by having higher rates of duplication and DNA conversion than neighboring regions. The assumed active core is characterized by significantly enriched leucine residue composition, accumulation of positively selected sites, and shorter beta sheets. ? Homologous resistance gene analog (RGA)-containing regions in peanut, soybean, Medicago, Arabidopsis and grape have only limited gene synteny and microcollinearity.