Mapping multiple RNA modifications simultaneously by proximity barcode sequencing.

RNA is subject to a multitude of different chemical modifications that collectively represent the epitranscriptome. Individual RNA modifications including N6-methyladenosine (mA) on mRNA play essential roles in the posttranscriptional control of gene expression. Recent technological advances have enabled the transcriptome-wide mapping of certain RNA modifications, to reveal their broad relevance and characteristic distribution patterns.

HYSCORE and QM/MM Studies of Second Sphere Variants of the Type 1 Copper Site in Azurin: Influence of Mutations on the Hyperfine Couplings of Remote Nitrogens.

Secondary coordination sphere (SCS) interactions have been shown to play important roles in tuning reduction potentials and electron transfer (ET) properties of the Type 1 copper proteins, but the precise roles of these interactions are not fully understood. In this work, we examined the influence of F114P, F114N, and N47S mutations in the SCS on the electronic structure of the T1 copper center in azurin (Az) by studying the hyperfine couplings of (i) histidine remote N nitrogens and (ii) the amide N using the two-dimensional (2D) pulsed electron paramagnetic resonance (EPR) technique HYSCORE (hyperfine sublevel correlation) combined with quantum mechanics/molecular mechanics (QM/MM) and DLPNO-CCSD calculations. Our data show that some components of hyperfine tensor and isotropic coupling in N47SAz and F114PAz (but not F114NAz) deviate by up to ∼±20% from WTAz, indicating that these mutations significantly influence the spin density distribution between the Cu site and coordinating ligands.

Moral Distress, Mental Health, and Risk and Resilience Factors Among Military Personnel Deployed to Long-Term Care Facilities During the COVID-19 Pandemic: Research Protocol and Participation Metrics.

Background: The earliest days of the COVID-19 pandemic in Canada were marked by a significant surge in COVID-19 cases and COVID-19-related deaths among residents of long-term care facilities (LTCFs). As part of Canada's response to the COVID-19 pandemic, Canadian Armed Forces (CAF) personnel were mobilized for an initial emergency domestic deployment to the hardest-hit LTCFs (Operation LASER LTCF) to support the remaining civilian staff in ensuring the continued delivery of care to residents. Akin to what was observed following past CAF international humanitarian missions, there was an expected increased risk of exposure to multiple stressors that may be psychologically traumatic and potentially morally injurious in nature (ie, related to core values, eg, witnessing human suffering).

Molecular understanding of heteronuclear active sites in heme-copper oxidases, nitric oxide reductases, and sulfite reductases through biomimetic modelling.

Heme-copper oxidases (HCO), nitric oxide reductases (NOR), and sulfite reductases (SiR) catalyze the multi-electron and multi-proton reductions of O2, NO, and SO32-, respectively. Each of these reactions is important to drive cellular energy production through respiratory metabolism and HCO, NOR, and SiR evolved to contain heteronuclear active sites containing heme/copper, heme/nonheme iron, and heme-[4Fe-4S] centers, respectively. The complexity of the structures and reactions of these native enzymes, along with their large sizes and/or membrane associations, make it challenging to fully understand the crucial structural features responsible for the catalytic properties of these active sites.

Blast in Context: The Neuropsychological and Neurocognitive Effects of Long-Term Occupational Exposure to Repeated Low-Level Explosives on Canadian Armed Forces' Breaching Instructors and Range Staff.

Currently, there is strong interest within the military to better understand the effects of long-term occupational exposure to repeated low-level blast on health and performance. To gain traction on the chronic sequelae of blast, we focused on -a tactical technique for gaining entry into closed/blocked spaces by placing explosives and maintaining a calculated safe distance from the detonation. Using a cross-sectional design, we compared the neuropsychological and neurocognitive profiles of breaching instructors and range staff to sex- and age-matched Canadian Armed Forces (CAF) controls.

The relationship between methods of scoring the alternate uses task and the neural correlates of divergent thinking: Evidence from voxel-based morphometry.

Divergent thinking tests have been used extensively in neuroscientific studies of creativity. However, output from tests of divergent thinking can be scored in different ways, and those scores can influence assessments of divergent thinking performance and its relationship with brain activation. Here we sought to investigate the relationship between various methods of scoring the Alternate Uses Task (AUT)-a well-known test of divergent thinking-and regional grey matter volume (GMV) using voxel-based morphometry (VBM).

Effect of letrozole for ovulation induction combined with intrauterine insemination on women with polycystic ovary syndrome.

To evaluate the efficacy and safety of letrozole on ovulation induction and pregnancy in infertility patients with polycystic ovary syndrome (PCOS). In addition, the insulin resistance was analyzed in these patients. Progressive description study with comparison.

The Reflective Mind: Examining Individual Differences in Susceptibility to Base Rate Neglect with fMRI.

Performance on heuristics and bias tasks has been shown to be susceptible to bias. In turn, susceptibility to bias varies as a function of individual differences in cognitive abilities (e.g.

Topographical memory for newly-learned maps is differentially affected by route-based versus landmark-based learning: a functional MRI study.

Humans rely on topographical memory to encode information about spatial aspects of environments. However, even though people adopt different strategies when learning new maps, little is known about the impact of those strategies on topographical memory, and their neural correlates. To examine that issue, we presented participants with 40 unfamiliar maps, each of which displayed one major route and three landmarks.

One-way traffic: The inferior frontal gyrus controls brain activation in the middle temporal gyrus and inferior parietal lobule during divergent thinking.

Contrary to earlier approaches that focused on the contributions of isolated brain regions to the emergence of creativity, there is now growing consensus that creative thought emerges from the interaction of multiple brain regions, often embedded within larger brain networks. Specifically, recent evidence from studies of divergent thinking suggests that kernel ideas emerge in posterior brain regions residing within the semantic system and/or the default mode network (DMN), and that the prefrontal cortex (PFC) regions within the executive control network (ECN) constrain those ideas for generating outputs that meet task demands. However, despite knowing that regions within these networks exhibit interaction, to date the direction of the relationship has not been tested directly.

Task switching following 24 h of total sleep deprivation: a functional MRI study.

Task switching is a ubiquitous feature of many human activities that involve multitasking. In addition, owing to occupational demands, many individuals are required to engage in task switching under various levels of sleep deprivation, such as those who work in military and medical contexts. Nevertheless, little is known about the effects that sleep loss has on the neural bases of task switching.

Sbp1 modulates the translation of Pab1 mRNA in a poly(A)- and RGG-dependent manner.

RNA-binding protein Sbp1 facilitates the decapping pathway in mRNA metabolism and inhibits global mRNA translation by an unclear mechanism. Here we report molecular interactions responsible for Sbp1-mediated translation inhibition of mRNA encoding the polyadenosine-binding protein (Pab1), an essential translation factor that stimulates mRNA translation and inhibits mRNA decapping in eukaryotic cells. We demonstrate that the two distal RRMs of Sbp1 bind to the poly(A) sequence in the 5'UTR of the Pab1 mRNA specifically and cooperatively while the central RGG domain of the protein interacts directly with Pab1.

The effectiveness of transdermal testosterone gel 1% (androgel) for poor responders undergoing in vitro fertilization.

The study was conducted on 110 poor responders undergoing in vitro fertilization (IVF) from October 2015 to July 2016 at the IVF Center of Millitary Medical University, Vietnam. Its aim is to investigate the effectiveness of transdermal androgel before using controlled ovarian stimulation on patients undergoing IVF. A prospective, descriptive study was conducted to compare between the group of patients who used testosterone gel and the group of those who did not in terms of the following indicators: the number of oocytes retrieved, MII oocytes, fertilization rate, number of embryos, pregnancy rate, and embryo implantation rate.

Insights into an efficient light-driven hybrid P450 BM3 enzyme from crystallographic, spectroscopic and biochemical studies.

Background: In order to perform selective CH functionalization upon visible light irradiation, Ru(II)-diimine functionalized P450 heme enzymes have been developed. The sL407C-1 enzyme containing the Ru(bpy)PhenA (bpy=2,2'-bipyridine and PhenA=5-acetamido-1,10-phenanthroline) photosensitizer (1) covalently attached to the non-native single cysteine L407C of the P450BM3 heme domain mutant, displays high photocatalytic activity in the selective CH bond hydroxylation of several substrates.

Methods: A combination of X-ray crystallography, site-directed mutagenesis, transient absorption measurements and enzymatic assays was used to gain insights into its photocatalytic activity and electron transfer pathway.

Chromogenic nitrophenolate-based substrates for light-driven hybrid P450 BM3 enzyme assay.

The incorporation of a p-nitrophenoxy moiety in substrates has enabled the development of colorimetric assays to rapidly screen for O-demethylation activity of P450 enzymes. For the light-driven hybrid P450 BM3 enzymes, where a Ru(II) photosensitizer powers the enzyme upon visible light irradiation, we have investigated a family of p-nitrophenoxy derivatives as useful chromogenic substrates compatible with the light-driven approach. The validation of this assay and its adaptability to a 96-well plate format will enable the screening of the next generation of hybrid P450 BM3 enzymes towards C-H bond functionalization of non-natural substrates.

Ru(II)-diimine functionalized metalloproteins: From electron transfer studies to light-driven biocatalysis.

The unique photochemical properties of Ru(II)-diimine complexes have helped initiate a series of seminal electron transfer studies in metalloenzymes. It has thus been possible to experimentally determine rate constants for long-range electron transfers. These studies have laid the foundation for the investigation of reactive intermediates in heme proteins and for the design of light-activated biocatalysts.

Transfer of training from one working memory task to another: behavioural and neural evidence.

N-back working memory (WM) tasks necessitate the maintenance and updating of dynamic rehearsal sets during performance. The delayed matching-to-sample (dMTS) task is another WM task, which in turn involves the encoding, maintenance, and retrieval of stimulus representations in sequential order. Because both n-back and dMTS engage WM function, we hypothesized that compared to a control task not taxing WM, training on the n-back task would be associated with better performance on dMTS by virtue of training a shared mental capacity.

The effects of a single night of sleep deprivation on fluency and prefrontal cortex function during divergent thinking.

The dorsal and ventral aspects of the prefrontal cortex (PFC) are the two regions most consistently recruited in divergent thinking tasks. Given that frontal tasks have been shown to be vulnerable to sleep loss, we explored the impact of a single night of sleep deprivation on fluency (i.e.

Right inferior frontal gyrus activation as a neural marker of successful lying.

There is evidence to suggest that successful lying necessitates cognitive effort. We tested this hypothesis by instructing participants to lie or tell the truth under conditions of high and low working memory (WM) load. The task required participants to register a response on 80 trials of identical structure within a 2 (WM Load: high, low) × 2 (Instruction: truth or lie) repeated-measures design.

Sound attenuation of the indoor/outdoor range E-A-R plug.

The sound attenuation provided by the AOSafety Indoor/Outdoor Range E-A-R Plug was examined. This device, currently used in military operations in several countries, is comprised of two plugs that provide conventional ("indoor" plug) and level-dependent sound reduction (the "outdoor" plug), respectively. The effects of the user's gender and repeated fittings were explored.