Oxygen-Vacancy Engineering of Cerium-Oxide Nanoparticles for Antioxidant Activity

© 2019 American Chemical Society. To address an important challenge in the engineering of antioxidant nanoparticles, the present work devised a surface-to-bulk migration of oxygen vacancies in the oxygen radical-scavenging cerium-oxide nanoparticles. The study highlights the significance of surface oxygen vacancies in the intended cellular internalization and, subsequently, the radical scavenging activity of the nanoparticles inside the cells. The findings advise future development of therapeutic antioxidant nanomaterials to also include engineering of the particles for enhanced surface defects not only for the accessibility of their oxygen vacancies but also, equally important, rendering them bioavailable for cellular uptake

Reduction in Physical Match Performance at the Start of the Second Half in Elite Soccer

Purpose: Soccer referees' physical match performances at the start of the second half (46-60 min) were evaluated in relation to both the corresponding phase of the first half (0-15 min) and players' performances during the same match periods. Methods: Match analysis data were collected (Prozone, UK) from 12 soccer referees on 152 English Premier League matches during the 2008/09 soccer season. Physical match performance categories for referees and players were total distance, high-speed running distance (speed >5.5 m/s), and sprinting distance (>7.0 m/s). The referees' heart rate was recorded from the start of their warm-up to the end of the match. The referees' average distances (in meters) from the ball and fouls were also calculated. Results: No substantial differences were observed in duration (16:42 ± 2:35 vs 16:27 ± 1:00 min) or intensity (107 ± 11 vs 106 ± 14 beats/ min) of the referees' preparation periods immediately before each half. Physical match performance was reduced during the initial phase of the second half when compared with the first half in both referees (effect sizes-standardized mean differences-0.19 to 0.73) and players (effect sizes 0.20 to 1.01). The degree of the decreased performance was consistent between referees and players for total distance (4.7 m), high-speed running (1.5 m), and sprinting (1.1 m). The referees were closer to the ball (effect size 0.52) during the opening phase the second half. Conclusion: Given the similarity in the referees' preparation periods, it may be that the reduced physical match performances observed in soccer referees during the opening stages of the second half are a consequence of a slower tempo of play

Autofix for backward-fit sidechains: using MolProbity and real-space refinement to put misfits in their place

Misfit sidechains in protein crystal structures are a stumbling block in using those structures to direct further scientific inference. Problems due to surface disorder and poor electron density are very difficult to address, but a large class of systematic errors are quite common even in well-ordered regions, resulting in sidechains fit backwards into local density in predictable ways. The MolProbity web site is effective at diagnosing such errors, and can perform reliable automated correction of a few special cases such as 180° flips of Asn or Gln sidechain amides, using all-atom contacts and H-bond networks. However, most at-risk residues involve tetrahedral geometry, and their valid correction requires rigorous evaluation of sidechain movement and sometimes backbone shift. The current work extends the benefits of robust automated correction to more sidechain types. The Autofix method identifies candidate systematic, flipped-over errors in Leu, Thr, Val, and Arg using MolProbity quality statistics, proposes a corrected position using real-space refinement with rotamer selection in Coot, and accepts or rejects the correction based on improvement in MolProbity criteria and on χ angle change. Criteria are chosen conservatively, after examining many individual results, to ensure valid correction. To test this method, Autofix was run and analyzed for 945 representative PDB files and on the 50S ribosomal subunit of file 1YHQ. Over 40% of Leu, Val, and Thr outliers and 15% of Arg outliers were successfully corrected, resulting in a total of 3,679 corrected sidechains, or 4 per structure on average. Summary Sentences: A common class of misfit sidechains in protein crystal structures is due to systematic errors that place the sidechain backwards into the local electron density. A fully automated method called “Autofix” identifies such errors for Leu, Val, Thr, and Arg and corrects over one third of them, using MolProbity validation criteria and Coot real-space refinement of rotamers

Sex-Specific Expression of the X-Linked Histone Demethylase Gene Jarid1c in Brain

Jarid1c, an X-linked gene coding for a histone demethylase, plays an important role in brain development and function. Notably, JARID1C mutations cause mental retardation and increased aggression in humans. These phenotypes are consistent with the expression patterns we have identified in mouse brain where Jarid1c mRNA was detected in hippocampus, hypothalamus, and cerebellum. Jarid1c expression and associated active histone marks at its 5′end are high in P19 neurons, indicating that JARID1C demethylase plays an important role in differentiated neuronal cells. We found that XX mice expressed Jarid1c more highly than XY mice, independent of their gonadal types (testes versus ovaries). This increased expression in XX mice is consistent with Jarid1c escape from X inactivation and is not compensated by expression from the Y-linked paralogue Jarid1d, which is expressed at a very low level compared to the X paralogue in P19 cells. Our observations suggest that sex-specific expression of Jarid1c may contribute to sex differences in brain function

Nestin-Cre Mice Are Affected by Hypopituitarism, Which Is Not Due to Significant Activity of the Transgene in the Pituitary Gland

Nestin-Cre mice express Cre recombinase under control of the rat nestin promoter and central nervous system (CNS) enhancer. While endogenous Nestin is expressed in some other tissues including the pituitary gland, Nestin-Cre mice induce recombination predominantly in the CNS. For this reason, they have been widely used to explore gene function or cell fate in the latter. Pituitary hormonal deficiencies, or hypopituitarism, are associated with a wide range of symptoms and with a significant morbidity. These can have a neural and/or a pituitary origin as the gland's secretions are controlled by the hypothalamus. We report here that Nestin-Cre mice themselves are affected by mild hypopituitarism. Hence, physiological consequences are expected, especially in combination with defects resulting from Cre mediated deletion of any gene under investigation. To further investigate the origin of this phenotype, we re-examined the activity of the transgene. We compared it with expression of Nestin itself in the context of the hypothalamo-pituitary axis, especially in the light of a recent report showing pituitary Nestin-Cre activity, which contrasts with previous data. Our results disagree with those of this recent study and do not support the claim that Nestin positive cells are present in the pituitary anlagen, the Rathke's pouch (RP). Moreover we did not observe any significant activity in the post-natal pituitary, in agreement with the initial report

A perspective on the measurement of time in plant disease epidemiology

The growth and development of plant pathogens and their hosts generally respond strongly to the temperature of their environment. However, most studies of plant pathology record pathogen/host measurements against physical time (e.g. hours or days) rather than thermal time (e.g. degree-days or degree-hours). This confounds the comparison of epidemiological measurements across experiments and limits the value of the scientific literature

Half-Time Strategies to Enhance Second-Half Performance in Team-Sports Players: A Review and Recommendations

The competitive demands of numerous intermittent team sports require that two consecutive periods of play are separated by a half-time break. Typically, half-time allows players to: return to the changing rooms, temporarily relax from the cognitive demands of the first half of match-play, rehydrate, re-fuel, attend to injury or equipment concerns, and to receive tactical instruction and coach feedback in preparation for the second half. These passive practices have been associated with physiological changes which impair physical and cognitive performance in the initial stages of the second half. An increased risk of injury has also been observed following half-time. On the day of competition, modification of half-time practices may therefore provide Sports Scientists and Strength and Conditioning Coaches with an opportunity to optimise second half performance. An overview of strategies that may benefit team sports athletes is presented; specifically, the efficacy of: heat maintenance strategies (including passive and active methods), hormonal priming (through video feedback), post-activation potentiation, and modified hydro-nutritional practices are discussed. A theoretical model of applying these strategies in a manner that compliments current practice is also presented

Gating at the Mouth of the Acetylcholine Receptor Channel: Energetic Consequences of Mutations in the αM2-Cap

Gating of nicotinic acetylcholine receptors from a C(losed) to an O(pen) conformation is the initial event in the postsynaptic signaling cascade at the vertebrate nerve-muscle junction. Studies of receptor structure and function show that many residues in this large, five-subunit membrane protein contribute to the energy difference between C and O. Of special interest are amino acids located at the two transmitter binding sites and in the narrow region of the channel, where C↔O gating motions generate a low↔high change in the affinity for agonists and in the ionic conductance, respectively. We have measured the energy changes and relative timing of gating movements for residues that lie between these two locations, in the C-terminus of the pore-lining M2 helix of the α subunit (‘αM2-cap’). This region contains a binding site for non-competitive inhibitors and a charged ring that influences the conductance of the open pore. αM2-cap mutations have large effects on gating but much smaller effects on agonist binding, channel conductance, channel block and desensitization. Three αM2-cap residues (αI260, αP265 and αS268) appear to move at the outset of channel-opening, about at the same time as those at the transmitter binding site. The results suggest that the αM2-cap changes its secondary structure to link gating motions in the extracellular domain with those in the channel that regulate ionic conductance