Interplay between the RNA binding‐protein Musashi and developmental signaling pathways

Musashi comprises an evolutionarily conserved family of RNA‐binding proteins (RBP) that regulate cell fate decisions during embryonic development and play key roles in the maintenance of self‐renewal and differentiation of stem cells and adult tissues. More recently, several studies have shown that any dysregulation of MSI1 and MSI2 can lead to cellular dysfunctions promoting tissue instability and tumorigenesis. Moreover, several reports have characterized many molecular interactions between members of the Musashi family with ligands and receptors of the signaling pathways responsible for controlling normal embryonic development: Notch, Transforming Growth Factor Beta (TGF‐β), Wingless (Wnt) and Hedgehog Signaling (Hh); all of which, when altered, are strongly associated with cancer onset and progression, especially in pediatric tumors. In this context, the present review aims to compile possible cross‐talks between Musashi proteins and members of the above cited molecular pathways for which dysregulation plays important roles during carcinogenesis and may be modulated by these RBP.     

A comprehensive biochemical characterization of settlement stage leptocephalus larvae of bonefish (Albula vulpes)

Little is known about early development of the near-threatened bonefish (Albula vulpes), a member of superorder Elopomorpha. Members of Elopomorpha are partially defined by their synapomorphic leptocephalus larval stage, for which the nutritional requirements are not well understood. Characterizing the nutritional profile, including major nutrients (such as lipids) used for energetic processes, can help to gain a better understanding of the nutritional requirements for leptocephalus larvae. A total of 24 settlement stage A. vulpes leptocephalus larvae were collected at Long Caye Island, Belize. Samples were used to determine various biochemical characteristics including lipid class, fatty acid and glycosaminoglycan compositions. Each of these biochemical components plays a role in early developmental processes such as cellular membrane formation and is crucial for healthy development. Biochemical characteristics of settlement stage A. vulpes leptocephalus are presented in this study for the first time. The dominant lipid classes and fatty acids detected in these samples were consistent with prior studies using closely related species like the Japanese eel, indicating possible similarities in diets at this stage. In the future, similar analyses can be applied to other species that share the leptocephalus life stage to determine if nutritional requirements at this stage of development are unique to this species. The findings in this study will also help to facilitate the establishment of adequate aquaculture systems for captive bonefish, ultimately leading to improved management strategies for wild bonefish habitats.     

Ophioderma peruana,a new species of brittlestar (Echinodermata,Ophiuroidea, Ophiodermatidae) from?the Peruvian coast

Ophioderma peruana sp. n. is a new species of Ophiodermatidae, extending the distribution of the genus Ophioderma to Lobos de Afuera Island, Peru, easily distinguishable from its congeners by its peculiarly fragmented dorsal arm plates. Dense granules, rounded or polygonal cover the disc, the radial shields may be naked or completely covered by granules. A good character for recognizing this species in the field is the dorsal side of the disc which is brown with disc granules lighter cream and brown, the arms are mottled with whitish spots and the ventral part of the disc on the interradial part is brown and the radial part bright yellow.     

Abscisic acid and the herbicide safener cyprosulfamide cooperatively enhance abiotic stress tolerance in rice

Plants adapt to abiotic stress by undergoing diverse biochemical and physiological changes that involve hormone-dependent signaling pathways. The effects of plant hormones can be mimicked by exogenous chemical regulators such as herbicide safeners, which not only enhance stress tolerance but also confer hormetic benefits such as increased vigor and yield. In this study, rice plants growing in normal and saline soils were exposed to abscisic acid (ABA), the safener cyprosulfamide or both compounds together. We found that cyprosulfamide, either alone or in combination with ABA, protected the plants from salinity stress and induced vigorous growth, including the formation of new tillers and early flowering. Proteomic analysis identified several proteins that were induced by stress and/or the chemical treatments, including the late embryogenesis abundant protein OsLEA3, a putative mitochondrial translocase and a putative fumarylacetoacetate hydrolase. The corresponding genes were induced by stress and/or the individual chemical treatments, but expression dropped back when the stress was removed. However, the combination of ABA and cyprosulfamide prolonged the expression of all three genes beyond the stress period, and allowed the plants to maintain their enhanced growth characteristics. These data support a model involving cooperation between the cyprosulfamide and ABA signaling pathways. Accordingly, it was found that cyprosulfamide induces ABA synthesis more robustly than salinity stress, allowing the two regulators to converge on certain downstream target genes. We discuss the impact of our results on current models for the hormonal regulation of stress response pathways in rice and other plants.     

Cocoa Consumption Alters the Global DNA Methylation of Peripheral Leukocytes in Humans with Cardiovascular Disease Risk Factors: A Randomized Controlled Trial

DNA methylation regulates gene expression and can be modified by different bioactive compounds in foods, such as polyphenols. Cocoa is a rich source of polyphenols, but its role in DNA methylation is still unknown. The objective was to assess the effect of cocoa consumption on DNA methylation and to determine whether the enzymes involved in the DNA methylation process participate in the mechanisms by which cocoa exerts these effects in humans. The global DNA methylation levels in the peripheral blood were evaluated in 214 volunteers who were pre-hypertensive, stage-1 hypertensive or hypercholesterolemic. The volunteers were divided into two groups: 110 subjects who consumed cocoa (6 g/d) for two weeks and 104 control subjects. In addition, the peripheral blood mononuclear cells (PBMCs) from six subjects were treated with a cocoa extract to analyze the mRNA levels of the DNA methyltransferases (DNMTs), methylenetetrahydrofolate reductase (MTHFR), and methionine synthase reductase (MTRR) genes. Cocoa consumption significantly reduced the DNA methylation levels (2.991±0.366 vs. 3.909±0.380, p<0.001). Additionally, we found an association between the cocoa effects on DNA methylation and three polymorphisms located in the MTHFR, MTRR, and DNMT3B genes. Furthermore, in PBMCs, the cocoa extract significantly lowered the mRNA levels of the DNMTs, MTHFR, and MTRR. Our study demonstrates for the first time that the consumption of cocoa decreases the global DNA methylation of peripheral leukocytes in humans with cardiovascular risk factors. In vitro experiments with PBMCs suggest that cocoa may exert this effect partially via the down-regulation of DNMTs, MTHFR and MTRR, which are key genes involved in this epigenetic process.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00511420","term_id":"NCT00511420"}}NCT00511420 and {"type":"clinical-trial","attrs":{"text":"NCT00502047","term_id":"NCT00502047"}}NCT00502047     

Loss of the Cytoskeletal Protein Pdlim7 Predisposes Mice to Heart Defects and Hemostatic Dysfunction

The actin-associated protein Pdlim7 is essential for heart and fin development in zebrafish; however, the expression and function of this PDZ-LIM family member in the mammal has remained unclear. Here, we show that Pdlim7 predominantly localizes to actin-rich structures in mice including the heart, vascular smooth muscle, and platelets. To test the requirement for Pdlim7 in mammalian development and function, we analyzed a mouse strain with global genetic inactivation of Pdlim7. We demonstrate that Pdlim7 loss-of-function leads to significant postnatal mortality. Inactivation of Pdlim7 does not disrupt cardiac development, but causes mild cardiac dysfunction in adult mice. Adult Pdlim7 ^-/- mice displayed increased mitral and tricuspid valve annulus to body weight ratios. These structural aberrations in Pdlim7 ^-/- mice were supported by three-dimensional reconstructions of adult cardiac valves, which revealed increased surface area to volume ratios for the mitral and tricuspid valve leaflets. Unexpectedly, we found that loss of Pdlim7 triggers systemic venous and arterial thrombosis, leading to significant mortality shortly after birth in Pdlim7 ^+/- (11/60) and Pdlim7 ^-/- (19/35) mice. In line with a prothrombotic phenotype, adult Pdlim7 ^-/- mice exhibit dramatically decreased tail bleed times compared to controls. These findings reveal a novel and unexpected function for Pdlim7 in maintaining proper hemostasis in neonatal and adult mice.     

Halogen bond tunability II: the varying roles of electrostatic and dispersion contributions to attraction in halogen bonds

In a previous study we investigated the effects of aromatic fluorine substitution on the strengths of the halogen bonds in halobenzene…acetone complexes (halo?=?chloro, bromo, and iodo). In this work, we have examined the origins of these halogen bonds (excluding the iodo systems), more specifically, the relative contributions of electrostatic and dispersion forces in these interactions and how these contributions change when halogen σ-holes are modified. These studies have been carried out using density functional symmetry adapted perturbation theory (DFT-SAPT) and through analyses of intermolecular correlation energies and molecular electrostatic potentials. It is found that electrostatic and dispersion contributions to attraction in halogen bonds vary from complex to complex, but are generally quite similar in magnitude. Not surprisingly, increasing the size and positive nature of a halogen’s σ-hole dramatically enhances the strength of the electrostatic component of the halogen bonding interaction. Not so obviously, halogens with larger, more positive σ-holes tend to exhibit weaker dispersion interactions, which is attributable to the lower local polarizabilities of the larger σ-holes.

Consortium diversity of a sulfate‐reducing biofilm developed at acidic pH influent conditions in a down‐flow fluidized bed reactor

Sulfate reduction is an appropriate approach for the treatment of effluents with sulfate and dissolved metals. In sulfate‐reducing reactors, acetate may largely contribute to the residual organic matter, because not all sulfate reducers are able to couple the oxidation of acetate to the reduction of sulfate, limiting the treatment efficiency. In this study, we investigated the diversity of a bacterial community in the biofilm of a laboratory scale down‐flow fluidized bed reactor, which was developed under sulfidogenic conditions at an influent pH between 4 and 6. The sequence analysis of the microbial community showed that the 16S rRNA gene sequence of almost 50% of the clones had a high similarity with Anaerolineaceae. At second place, 33% of the 16S rRNA phylotypes were affiliated with the sulfate‐reducing bacteria Desulfobacca acetoxidans and Desulfatirhabdium butyrativorans, suggesting that acetotrophic sulfate reduction was occurring in the system. The remaining bacterial phylotypes were related to fermenting bacteria found at the advanced stage of reactor operation. The results indicate that the acetotrophic sulfate‐reducing bacteria were able to remain within the biofilm, which is a significant result because few natural consortia harbor complete oxidizing sulfate‐reducers, improving the acetate removal via sulfate reduction in the reactor.     

The Effect of a Physical Activity Program on the Total Number of Primary Care Visits in Inactive Patients: A 15-Month Randomized Controlled Trial

Background

Effective promotion of exercise could result in substantial savings in healthcare cost expenses in terms of direct medical costs, such as the number of medical appointments. However, this is hampered by our limited knowledge of how to achieve sustained increases in physical activity.

Objectives

To assess the effectiveness of a Primary Health Care (PHC) based physical activity program in reducing the total number of visits to the healthcare center among inactive patients, over a 15-month period.

Research Design

Randomized controlled trial.

Subjects

Three hundred and sixty-two (n = 362) inactive patients suffering from at least one chronic condition were included. One hundred and eighty-three patients (n = 183; mean (SD); 68.3 (8.8) years; 118 women) were randomly allocated to the physical activity program (IG). One hundred and seventy-nine patients (n = 179; 67.2 (9.1) years; 106 women) were allocated to the control group (CG). The IG went through a three-month standardized physical activity program led by physical activity specialists and linked to community resources.

Measures

The total number of medical appointments to the PHC, during twelve months before and after the program, was registered. Self-reported health status (SF-12 version 2) was assessed at baseline (month 0), at the end of the intervention (month 3), and at 12 months follow-up after the end of the intervention (month 15).

Results

The IG had a significantly reduced number of visits during the 12 months after the intervention: 14.8 (8.5). The CG remained about the same: 18.2 (11.1) (P = .002).

Conclusions

Our findings indicate that a 3-month physical activity program linked to community resources is a short-duration, effective and sustainable intervention in inactive patients to decrease rates of PHC visits.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00714831","term_id":"NCT00714831"}}NCT00714831