Bubble Measurements Downstream of Hydraulic Jumps

A phase Doppler anemometer (PDA) system was used to measure the velocity profiles and air bubble size distributions downstream of two-dimensional hydraulic jumps for different upstream flow conditions in a 1.92m long laboratory flume. The PDA detected bubbles from 1 to 500 [microns] in diameter, and more were found at the bottom of the downstream flow near the elevation of the upstream free surface. This distribution was more marked for smaller bubbles, those with diameters less that 100 [microns]. The migration of the bubbles is controlled by the effects of buoyancy and by turbulent mixing; the relative magnitude of their effects on bubble distribution depends strongly on bubble size, and also on the energy of the upstream flow

The DAXX co-repressor is directly recruited to active regulatory elements genome-wide to regulate autophagy programs in a model of human prostate cancer.

While carcinoma of the prostate is the second most common cause of cancer death in the US, current methods and markers used to predict prostate cancer (PCa) outcome are inadequate. This study was aimed at understanding the genome-wide binding and regulatory role of the DAXX transcriptional repressor, recently implicated in PCa. ChIP-Seq analysis of genome-wide distribution of DAXX in PC3 cells revealed over 59,000 DAXX binding sites, found at regulatory enhancers and promoters. ChIP-Seq analysis of DNA methyltransferase 1 (DNMT1), which is a key epigenetic partner for DAXX repression, revealed that DNMT1 binding was restricted to a small number of DAXX sites. DNMT1 and DAXX bound close to transcriptional activator motifs. DNMT1 sites were found to be dependent on DAXX for recruitment by analyzing DNMT1 ChIP-Seq following DAXX knockdown (K/D), corroborating previous findings that DAXX recruits DNMT1 to repress its target genes. Massively parallel RNA sequencing (RNA-Seq) was used to compare the transcriptomes of WT and DAXX K/D PC3 cells. Genes induced by DAXX K/D included those involved in autophagy, and DAXX ChIP-Seq peaks were found close to the transcription start sites (TSS) of autophagy genes, implying they are more likely to be regulated by DAXX. In conclusion, DAXX binds active regulatory elements and co-localizes with DNMT1 in the prostate cancer genome. Given DAXX's putative regulatory role in autophagy, future studies may consider DAXX as a candidate marker and therapeutic target for prostate cancer

Quantification of cooperativity in the self-assembly of H-bonded rosettes.

The self-assembly of triaminopyrimidines with barbiturates and with cyanates was investigated in chloroform solution. Equimolar mixtures of two complementary components form stable macrocyclic 3 : 3 complexes (rosettes). The thermodynamics of self-assembly were quantified by using 1H NMR titrations to measure the strength of pairwise H-bonding interactions between two rosette components (K), allosteric cooperativity associated with formation of a second H-bonding interaction with each component, and the effective molarity for cyclisation of the rosette motif (EM). Pyrimidine-cyanurate interactions are an order of magnitude more favourable than pyrimidine-barbiturate interactions, so the cyanurate rosettes are significantly more stable than barbiturate rosettes. There is no allosteric cooperativity associated with rosette formation, but the chelate cooperativity quantified by the product K EM is exceptionally high (102-104), indicating that there are no other species present that compete with rosette assembly. The values of EM for rosette formation are approximately 2 M for all four rosettes studied and are not affected by differences in peripheral substituents or intrinsic H-bond strength.Marie Sklodowska-Curie grant agreement No 642793

Solvent similarity index.

The Solvent Similarity Index (SSI) is a quantitative parameter we introduce for the comparison of the solvation properties of any solvent or solvent mixture. The Surface Site Interaction Model for Liquids at Equilibrium (SSIMPLE) was used to calculate the free energy of solvation of a single Surface Site Interaction Point (SSIP) on a solute. The SSIP representation of molecular surfaces was used to calculate the free energy of solvation for all possible solute polarities, generating a unique solvation profile for any solvent or solvent mixture. Quantitative comparison of the solvation profiles of two solvents was used as the basis for calculating the solvation similarity index. Values of SSI were calculated for all pairwise comparisons of 261 pure solvents at 298 K, and the results were used to classify solvents into groups according to their solvation properties. Applications to understanding the solvation properties of binary solvent mixtures and for identification of alternative solvents are illustrated.Engineering and Physical Sciences Research Council (EP/M506485/1

Biology of recently discovered cytokines: Discerning the pro- and anti-inflammatory properties of interleukin-27

IL-27 is a recently identified heterodimeric cytokine produced in response to microbial and host derived inflammatory cues. Initial studies indicated that IL-27 promotes the generation of Th1 responses required for resistance to intracellular infection and unveiled the molecular mechanisms mediating this effect. However, subsequent work uncovered a role for IL-27 in the suppression of Th1 and Th2 responses. Thus, by discussing its pleotropic functions in the context of infection-induced immunity and by drawing parallels to fellow IL-6/IL-12 family cytokines, this review will attempt to reconcile the pro- and anti-inflammatory effects of IL-27

Molecular replication using covalent base-pairs with traceless linkers.

A unique feature of kinetically inert covalent base-pairing is that the nature of the chemical information that is transferred can be modulated by changing the chemical connectivity between the two bases. Formation of esters between phenols and benzoic acids has been used as a base-pairing strategy for sequence information transfer in template-directed synthesis of linear oligomers, but the copy strand produced by this process has the complementary sequence to the template strand. It is possible to form a base-pair between two benzoic acids by using a hydroquinone linker, which is eliminated when the product duplex is hydrolysed. Using this approach, covalent template-directed synthesis was carried out using a benzoic acid 3-mer template to produce an identical copy. This direct replication process was used in iterative rounds of replication leading to an increase of the population of the copied oligomer.Engineering and Physical Sciences Research Council (EP/P027067/1

Influence of non-covalent preorganization on supramolecular effective molarities.

A family of closely related zinc porphyrin-pyridine complexes were used to examine the influence of linker preorganization on supramolecular effective molarities for formation of intramolecular H-bonds. Each pyridine ligand was equipped with a side-chain containing two H-bond acceptors, one on the end of the chain (terminal) and one in the middle of the chain (linker). These H-bond acceptors make intramolecular interactions with phenol H-bond donors on the porphyrin periphery. Two different H-bonding acceptors were used as linker groups in order to construct frameworks with significantly different degrees of preorganization: ester linkers populate the H-bonded state 60-70% of the time, whereas amide linkers populate the H-bonded state 90-100% of the time. Thus the amide linkers provide a significantly more preorganised ligand framework than the ester linkers. Effective molarities (EM) for intramolecular H-bonds between the terminal H-bond acceptor groups on the ligands (esters and amides) and the porphyrin phenol groups were quantified using 32 chemical double mutant cycles. The values of EM for interactions with the terminal H-bond acceptors are independent of the nature of the linker H-bond acceptor (weakly bonded ester or strongly bonded amide), which indicates that preorganization of the linker has no effect on chelate cooperativity in these systems.We thank the EPSRC, the China Scholarship Council, and the University of Sheffield for funding.This is the final version of the article. It first appeared from the Royal Society of Chemistry via http://dx.doi.org/10.1039/C5OB00231

Effects of Elevated H\u3csup\u3e+\u3c/sup\u3e And P\u3csub\u3ei\u3c/sub\u3e on The Contractile Mechanics of Skeletal Muscle Fibres From Young and Old Men: Implications for Muscle Fatigue in Humans

The present study aimed to identify the mechanisms responsible for the loss in muscle power and increased fatigability with ageing by integrating measures of whole‐muscle function with single fibre contractile mechanics. After adjusting for the 22% smaller muscle mass in old (73–89 years, n = 6) compared to young men (20–29 years, n = 6), isometric torque and power output of the knee extensors were, respectively, 38% and 53% lower with age. Fatigability was ∼2.7‐fold greater with age and strongly associated with reductions in the electrically‐evoked contractile properties. To test whether cross‐bridge mechanisms could explain age‐related decrements in knee extensor function, we exposed myofibres (n = 254) from the vastus lateralis to conditions mimicking quiescent muscle and fatiguing levels of acidosis (H+) (pH 6.2) and inorganic phosphate (Pi) (30 mm). The fatigue‐mimicking condition caused marked reductions in force, shortening velocity and power and inhibited the low‐ to high‐force state of the cross‐bridge cycle, confirming findings from non‐human studies that these ions act synergistically to impair cross‐bridge function. Other than severe age‐related atrophy of fast fibres (−55%), contractile function and the depressive effects of the fatigue‐mimicking condition did not differ in fibres from young and old men. The selective loss of fast myosin heavy chain II muscle was strongly associated with the age‐related decrease in isometric torque (r = 0.785) and power (r = 0.861). These data suggest that the age‐related loss in muscle strength and power are primarily determined by the atrophy of fast fibres, but the age‐related increased fatigability cannot be explained by an increased sensitivity of the cross‐bridge to H+ and Pi

Liposome Enhanced Detection of Amyloid Protein Aggregates.

Thioflavin-T is used to image amyloid aggregates because of the excellent turn-on fluorescence properties, but binding affinities are low. By mounting multiple dye units on the surface of a vesicle, the binding affinity for α-synuclein fibrils is increased by three orders of magnitude, and the optical response is increased. Cooperative interactions of the dye headgroup and lipid with the protein provide a general strategy for the construction of multivalent amyloid probes based on vesicles.Engineering and Physical Sciences Research Council (EP/R005397/1 and EP/P008224/1)

Mix and match recognition modules for the formation of H-bonded duplexes.

Oligomeric molecules equipped with complementary H-bond recognition sites form stable duplexes in non-polar solvents. The use of a single H-bond between a good H-bond donor and a good H-bond acceptor as the recognition motif appended to a non-polar backbone leads to an architecture with interchangeable recognition alphabets. The interactions of three different families of H-bond acceptor oligomers (pyridine, pyridine N-oxide or phosphine oxide recognition module) with a family of H-bond donor oligomers (phenol recognition module) are compared. All three donor-acceptor combinations form stable duplexes, where the stability of the 1 : 1 complex increases with increasing numbers of recognition modules. The effective molarity for formation of intramolecular H-bonds that lead to zipping up of the duplex (EM) increases with decreasing flexibility of the recognition modules: 14 mM for the phosphine oxides which are connected to the backbone via a flexible linker; 40 mM for the pyridine N-oxides which have three fewer degrees of torsional freedom, and 80 mM for the pyridines where the geometry of the H-bond is more directional. However, the pyridine-phenol H-bond is an order of magnitude weaker than the other two types of H-bond, so overall the pyridine N-oxides form the most stable duplexes with the highest degree of cooperativity. The results show that it is possible to use different recognition motifs with the same duplex architecture, and this makes it possible to tune overall stabilities of the complexes by varying the components.We thank the EPSRC and ERC for fundin