No differential effects of divergent isocaloric supplements on signaling for muscle protein turnover during recovery from muscle-damaging eccentric exercise

Unaccustomed high-intensity eccentric exercise (ECC) can provoke muscle damage including several days of muscle force loss. Post-exercise dietary supplementation may provide a strategy to accelerate rate of force regain by affecting mechanisms related to muscle protein turnover. The aim of the current study was to investigate if protein signaling mechanisms involved in muscle protein turnover would be differentially affected by supplementation with either whey protein hydrolysate and carbohydrate (WPH+CHO) versus isocaloric carbohydrate (CHO) after muscle-damaging ECC. Twenty-four young healthy participants received either WPH+CHO (n = 12) or CHO supplements (n = 12) during post-exercise recovery from 150 maximal unilateral eccentric contractions. Prior to, at 3 h and at 24, 48, 96 and/or 168 h post-exercise, muscle strength, muscle soreness, and Akt-mTOR and FOXO signaling proteins, were measured in an ECC exercising leg and in the contralateral non-exercise control leg (CON). After ECC, muscle force decreased by 23–27 % at 24 h post-exercise, which was followed by gradual, although not full recovery at 168 h post-exercise, with no differences between supplement groups. Phosphorylation of mTOR, p70S6K and rpS6 increased and phosphorylation of FOXO1 and FOXO3 decreased in the ECC leg, with no differences between supplement groups. Phosphorylation changes were also observed for rpS6, FOXO1 and FOXO3a in the CON leg, suggesting occurrence of remote tissue effects. In conclusion, divergent dietary supplementation types did not produce differences in signaling for muscle turnover during recovery from muscle-damaging exercise.     

Geographical variation in mutualistic networks: similarity,turnover and partner fidelity

Although species and their interactions in unison represent biodiversity and all the ecological and evolutionary processes associated with life, biotic interactions have, contrary to species, rarely been integrated into the concepts of spatial β-diversity. Here, we examine β-diversity of ecological networks by using pollination networks sampled across the Canary Islands. We show that adjacent and distant communities are more and less similar, respectively, in their composition of plants, pollinators and interactions than expected from random distributions. We further show that replacement of species is the major driver of interaction turnover and that this contribution increases with distance. Finally, we quantify that species-specific partner compositions (here called partner fidelity) deviate from random partner use, but vary as a result of ecological and geographical variables. In particular, breakdown of partner fidelity was facilitated by increasing geographical distance, changing abundances and changing linkage levels, but was not related to the geographical distribution of the species. This highlights the importance of space when comparing communities of interacting species and may stimulate a rethinking of the spatial interpretation of interaction networks. Moreover, geographical interaction dynamics and its causes are important in our efforts to anticipate effects of large-scale changes, such as anthropogenic disturbances.     

CNS Cell Distribution and Axon Orientation Determine Local Spinal Cord Mechanical Properties

Mechanical signaling plays an important role in cell physiology and pathology. Many cell types, including neurons and glial cells, respond to the mechanical properties of their environment. Yet, for spinal cord tissue, data on tissue stiffness are sparse. To investigate the regional and direction-dependent mechanical properties of spinal cord tissue at a spatial resolution relevant to individual cells, we conducted atomic force microscopy (AFM) indentation and tensile measurements on acutely isolated mouse spinal cord tissue sectioned along the three major anatomical planes, and correlated local mechanical properties with the underlying cellular structures. Stiffness maps revealed that gray matter is significantly stiffer than white matter irrespective of directionality (transverse, coronal, and sagittal planes) and force direction (compression or tension) (K_g= ∼130 Pa vs. K_w= ∼70 Pa); both matters stiffened with increasing strain. When all data were pooled for each plane, gray matter behaved like an isotropic material under compression; however, subregions of the gray matter were rather heterogeneous and anisotropic. For example, in sagittal sections the dorsal horn was significantly stiffer than the ventral horn. In contrast, white matter behaved transversely isotropic, with the elastic stiffness along the craniocaudal (i.e., longitudinal) axis being lower than perpendicular to it. The stiffness distributions we found under compression strongly correlated with the orientation of axons, the areas of cell nuclei, and cellular in plane proximity. Based on these morphological parameters, we developed a phenomenological model to estimate local mechanical properties of central nervous system (CNS) tissue. Our study may thus ultimately help predicting local tissue stiffness, and hence cell behavior in response to mechanical signaling under physiological and pathological conditions, purely based on histological data.     

A Distinct Triplex DNA Unwinding Activity of ChlR1 Helicase

Mutations in the human ChlR1 (DDX11) gene are associated with a unique genetic disorder known as Warsaw breakage syndrome characterized by cellular defects in genome maintenance. The DNA triplex helix structures that form by Hoogsteen or reverse Hoogsteen hydrogen bonding are examples of alternate DNA structures that can be a source of genomic instability. In this study, we have examined the ability of human ChlR1 helicase to destabilize DNA triplexes. Biochemical studies demonstrated that ChlR1 efficiently melted both intermolecular and intramolecular DNA triplex substrates in an ATP-dependent manner. Compared with other substrates such as replication fork and G-quadruplex DNA, triplex DNA was a preferred substrate for ChlR1. Also, compared with FANCJ, a helicase of the same family, the triplex resolving activity of ChlR1 is unique. On the other hand, the mutant protein from a Warsaw breakage syndrome patient failed to unwind these triplexes. A previously characterized triplex DNA-specific antibody (Jel 466) bound triplex DNA structures and inhibited ChlR1 unwinding activity. Moreover, cellular assays demonstrated that there were increased triplex DNA content and double-stranded breaks in ChlR1-depleted cells, but not in FANCJ^−/− cells, when cells were treated with a triplex stabilizing compound benzoquinoquinoxaline, suggesting that ChlR1 melting of triple-helix structures is distinctive and physiologically important to defend genome integrity. On the basis of our results, we conclude that the abundance of ChlR1 known to exist in vivo is likely to be a strong deterrent to the stability of triplexes that can potentially form in the human genome.     

Inducing autoflocculation in the diatom <Emphasis Type="Italic">Phaeodactylum tricornutum</Emphasis> through CO<Subscript>2</Subscript> regulation

The effect of pH on flocculation was studied using the diatom Phaeodactylum tricornutum and the green algae Scenedesmus cf. obliquus as surrogate species. There was a distinct, species-specific threshold of pH where flocculation started. P. tricornutum started to flocculate at pH 10.5 and S. cf. obliquus at pH 11.3. Above this threshold, settling rates up to 360 cm h⁻¹ were observed for P. tricornutum and the concentrating factor was up to 60-fold. The combined effect of pH, turbulence, and cell density on flocculation of P. tricornutum was additionally studied in a factorial 5³-design experiment. pH was the most important factor affecting flocculation, but at the pH threshold (pH 10.5), the concentrating factor was increased by increasing cell density and turbulence. Algae increases the pH during photosynthesis, and the P. tricornutum and S. cf. obliquus cultures increased the pH to a maximum of 10.8 and 9.5, respectively, after discontinuing the CO₂ supply. For P. tricornutum, this was above the flocculation threshold, and rapid settling of this species due to increased pH was observed in a matter of hours after the CO₂ supply was turned off. This could be used as a simple, low-cost, initial dewatering step for this species.     

Inhibitors of histone demethylases

Methylated lysines are important epigenetic marks. The enzymes involved in demethylation have recently been discovered and found to be involved in cancer development and progression. Despite the relative recent discovery of these enzymes a number of inhibitors have already appeared. Most of the inhibitors are either previously reported inhibitors of related enzymes or compounds derived from these. Development in terms of selectivity and potency is still pertinent. Several reports on the development of functional assays have been published.