Deciphering Network Crosstalk: The Current Status and Potential of miRNA Regulatory Networks on the HSP40 Molecular Chaperone Network

Molecular chaperone networks fulfill complex roles in protein homeostasis and are essential for maintaining cell health. Hsp40s (commonly referred to as J-proteins) have critical roles in development and are associated with a variety of human diseases, yet little is known regarding the J-proteins with respect to the post-transcriptional mechanisms that regulate their expression. With relatively small alterations in their abundance and stoichiometry altering their activity, post-transcriptional regulation potentially has significant impact on the functions of J-proteins. MicroRNAs (miRNAs) are a large group of non-coding RNAs that form a complex regulatory network impacting gene expression. Here we review and investigate the current knowledge and potential intersection of miRNA regulatory networks with the J-Protein chaperone network. Analysis of datasets from the current version of TargetScan revealed a great number of predicted microRNAs targeting J-proteins compared to the limited reports of interactions to date. There are likely unstudied regulatory interactions that influence chaperone biology contained within our analysis. We go on to present some criteria for prioritizing candidate interactions including potential cooperative targeting of J-Proteins by multiple miRNAs. In summary, we offer a view on the scope of regulation of J-Proteins through miRNAs with the aim of guiding future investigations by identifying key regulatory nodes within these two complex cellular networks

Specificity of the ribosomal A site for aminoacyl-tRNAs

Although some experiments suggest that the ribosome displays specificity for the identity of the esterified amino acid of its aminoacyl-tRNA substrate, a study measuring dissociation rates of several misacylated tRNAs containing the GAC anticodon from the A site showed little indication for such specificity. In this article, an expanded set of misacylated tRNAs and two 2′-deoxynucleotide-substituted mRNAs are used to demonstrate the presence of a lower threshold in koff values for aa-tRNA binding to the A site. When a tRNA binds sufficiently well to reach this threshold, additional stabilizing effects due to the esterified amino acid or changes in tRNA sequence are not observed. However, specificity for different amino acid side chains and the tRNA body is observed when tRNA binding is sufficiently weaker than this threshold. We propose that uniform aa-tRNA binding to the A site may be a consequence of a conformational change in the ribosome, induced by the presence of the appropriate combination of contributions from the anticodon, amino acid and tRNA body

Activity of loggerhead turtles during the U-shaped dive: insights using angular velocity metrics

Understanding the behavioural ecology of endangered taxa can inform conservation strategies. The activity budgets of the loggerhead turtle Caretta caretta are still poorly understood because many tracking methods show only horizontal displacement and ignore dives and associated behaviours. However, time-depth recorders have enabled researchers to identify flat, U-shaped dives (or type 1a dives) and these are conventionally labelled as resting dives on the seabed because they involve no vertical displacement of the animal. Video- and acceleration-based studies have demonstrated this is not always true. Focusing on sea turtles nesting on the Cabo Verde archipelago, we describe a new metric derived from magnetometer data, absolute angular velocity, that integrates indices of angular rotation in the horizontal plane to infer activity. Using this metric, we evaluated the variation in putative resting behaviours during the bottom phase of type 1a dives for 5 individuals over 13 to 17 d at sea during a single inter-nesting interval (over 75 turtle d in total). We defined absolute resting within the bottom phase of type 1a dives as periods with no discernible acceleration or angular movement. Whilst absolute resting constituted a significant proportion of each turtle’s time budget for this 1a dive type, turtles allocated 16−38% of their bottom time to activity, with many dives being episodic, comprised of intermittent bouts of rest and rotational activity. This implies that previously considered resting behaviours are complex and need to be accounted for in energy budgets, particularly since energy budgets may impact conservation strategies. © The authors 2021. Open Access under Creative Commons by Attribution Licence. Use, distribution and reproduction are unrestricted. Authors and original publication must be credite

Behavioral Biomarkers for Animal Health: A Case Study Using Animal-Attached Technology on Loggerhead Turtles

Vertebrates are recognized as sentient beings. Consequently, urgent priority is now being given to understanding the needs and maximizing the welfare of animals under human care. The general health of animals is most commonly determined by physiological indices e.g., blood sampling, but may also be assessed by documenting behavior. Physiological health assessments, although powerful, may be stressful for animals, time-consuming and costly, while assessments of behavior can also be time-consuming, subject to bias and suffer from a poorly defined link between behavior and health. However, behavior is recognized as having the potential to code for stress and well-being and could, therefore, be used as an indicator of health, particularly if the process of quantifying behavior could be objective, formalized and streamlined to be time efficient. This study used Daily Diaries (DDs) (motion-sensitive tags containing tri-axial accelerometers and magnetometers), to examine aspects of the behavior of bycaught loggerhead turtles, Caretta caretta in various states of health. Although sample size limited statistical analysis, significant behavioral differences (in terms of activity level and turn rate) were found between “healthy” turtles and those with external injuries to the flippers and carapace. Furthermore, data visualization (spherical plots) clearly showed atypical orientation behavior in individuals suffering gas emboli and intestinal gas, without complex data analysis. Consequently, we propose that the use of motion-sensitive tags could aid diagnosis and inform follow-up treatment, thus facilitating the rehabilitation process. This is particularly relevant given the numerous rehabilitation programs for bycatch sea turtles in operation. In time, tag-derived behavioral biomarkers, TDBBs for health could be established for other species with more complex behavioral repertoires such as cetaceans and pinnipeds which also require rehabilitation and release. Furthermore, motion-sensitive data from animals under human care and wild conspecifics could be compared in order to define a set of objective behavioral states (including activity levels) for numerous species housed in zoos and aquaria and/or wild species to help maximize their welfare

XMM-Newton observations of the Galactic Supernova Remnant CTB 109 (G109.1-1.0)

We present the analysis of the X-ray Multi-Mirror Mission (XMM-Newton) European Photon Imaging Camera (EPIC) data of the Galactic supernova remnant (SNR) CTB 109 (G109.1-1.0). CTB 109 is associated with the anomalous X-ray pulsar (AXP) 1E 2259+586 and has an unusual semi-circular morphology in both the X-ray and the radio, and an extended X-ray bright interior region known as the `Lobe'. The deep EPIC mosaic image of the remnant shows no emission towards the west where a giant molecular cloud complex is located. No morphological connection between the Lobe and the AXP is found. We find remarkably little spectral variation across the remnant given the large intensity variations. All spectra of the shell and the Lobe are well fitted by a single-temperature non-equilibrium ionization model for a collisional plasma with solar abundances (kT = 0.5 - 0.7 keV, tau = n_e t = 1 - 4 x 10^11 s cm^-3, N_H = 5 - 7 x 10^21 cm^-2). There is no indication of nonthermal emission in the Lobe or the shell. We conclude that the Lobe originated from an interaction of the SNR shock wave with an interstellar cloud. Applying the Sedov solution for the undisturbed eastern part of the SNR, and assuming full equilibration between the electrons and ions behind the shock front, the SNR shock velocity is derived as v_s = 720 +/- 60 km s^-1, the remnant age as t = (8.8 +/- 0.9) x 10^3 d_3 yr, the initial energy as E_0 = (7.4 +/- 2.9) x 10^50 d_3^2.5 ergs, and the pre-shock density of the nuclei in the ambient medium as n_0 = (0.16 +/- 0.02) d_3^-0.5 cm^-3, at an assumed distance of D = 3.0 d_3 kpc. Assuming CTB 109 and 1E 2259+586 are associated, these values constrain the age and the environment of the progenitor of the SNR and the pulsar.Comment: Accepted for publication in ApJ. 9 figures. Figs. 1 + 2 are in color (fig1.jpg, fig2.jpg

Cluster Lenses

Clusters of galaxies are the most recently assembled, massive, bound structures in the Universe. As predicted by General Relativity, given their masses, clusters strongly deform space-time in their vicinity. Clusters act as some of the most powerful gravitational lenses in the Universe. Light rays traversing through clusters from distant sources are hence deflected, and the resulting images of these distant objects therefore appear distorted and magnified. Lensing by clusters occurs in two regimes, each with unique observational signatures. The strong lensing regime is characterized by effects readily seen by eye, namely, the production of giant arcs, multiple-images, and arclets. The weak lensing regime is characterized by small deformations in the shapes of background galaxies only detectable statistically. Cluster lenses have been exploited successfully to address several important current questions in cosmology: (i) the study of the lens(es) - understanding cluster mass distributions and issues pertaining to cluster formation and evolution, as well as constraining the nature of dark matter; (ii) the study of the lensed objects - probing the properties of the background lensed galaxy population - which is statistically at higher redshifts and of lower intrinsic luminosity thus enabling the probing of galaxy formation at the earliest times right up to the Dark Ages; and (iii) the study of the geometry of the Universe - as the strength of lensing depends on the ratios of angular diameter distances between the lens, source and observer, lens deflections are sensitive to the value of cosmological parameters and offer a powerful geometric tool to probe Dark Energy. In this review, we present the basics of cluster lensing and provide a current status report of the field.Comment: About 120 pages - Published in Open Access at: http://www.springerlink.com/content/j183018170485723/ . arXiv admin note: text overlap with arXiv:astro-ph/0504478 and arXiv:1003.3674 by other author

An “orientation sphere” visualization for examining animal head movements

Animal behavior is elicited, in part, in response to external conditions, but understanding how animals perceive the environment and make the decisions that bring about these behavioral responses is challenging. Animal heads often move during specific behaviors and, additionally, typically have sensory systems (notably vision, smell, and hearing) sampling in defined arcs (normally to the front of their heads). As such, head‐mounted electronic sensors consisting of accelerometers and magnetometers, which can be used to determine the movement and directionality of animal heads (where head “movement” is defined here as changes in heading [azimuth] and/or pitch [elevation angle]), can potentially provide information both on behaviors in general and also clarify which parts of the environment the animals might be prioritizing (“environmental framing”). We propose a new approach to visualize the data of such head‐mounted tags that combines the instantaneous outputs of head heading and pitch in a single intuitive spherical plot. This sphere has magnetic heading denoted by “longitude” position and head pitch by “latitude” on this “orientation sphere” (O‐sphere). We construct the O‐sphere for the head rotations of a number of vertebrates with contrasting body shape and ecology (oryx, sheep, tortoises, and turtles), illustrating various behaviors, including foraging, walking, and environmental scanning. We also propose correcting head orientations for body orientations to highlight specific heading‐independent head rotation, and propose the derivation of O‐sphere‐metrics, such as angular speed across the sphere. This should help identify the functions of various head behaviors. Visualizations of the O‐sphere provide an intuitive representation of animal behavior manifest via head orientation and rotation. This has ramifications for quantifying and understanding behaviors ranging from navigation through vigilance to feeding and, when used in tandem with body movement, should provide an important link between perception of the environment and response to it in free‐ranging animals.Deanship of Scientific Research at the King Saud University through Vice Deanship of Research Chairs; The National Geographic Global Exploration Fund. Grant Number: #GEFNE89‐13; European Research Council under the European Union's Horizon 2020 research and innovation program Grant. Grant Number: 715874; Royal Society/Wolfson Lab refurbishment scheme; Royal Society. Grant Number: 2009/R3 JP090604; Natural Environment Research Council. Grant Numbers: NE/I002030/1, NE/R001669/1; King Abdullah University of Science and Technology. Grant Number: CAASE.http://www.ecolevol.orghj2020Mammal Research InstituteZoology and Entomolog

Meta-analysis of small RNA-sequencing errors reveals ubiquitous post-transcriptional RNA modifications

Recent advances in DNA-sequencing technology have made it possible to obtain large datasets of small RNA sequences. Here we demonstrate that not all non-perfectly matched small RNA sequences are simple technological sequencing errors, but many hold valuable biological information. Analysis of three small RNA datasets originating from Oryza sativa and Arabidopsis thaliana small RNA-sequencing projects demonstrates that many single nucleotide substitution errors overlap when aligning homologous non-identical small RNA sequences. Investigating the sites and identities of substitution errors reveal that many potentially originate as a result of post-transcriptional modifications or RNA editing. Modifications include N1-methyl modified purine nucleotides in tRNA, potential deamination or base substitutions in micro RNAs, 3′ micro RNA uridine extensions and 5′ micro RNA deletions. Additionally, further analysis of large sequencing datasets reveal that the combined effects of 5′ deletions and 3′ uridine extensions can alter the specificity by which micro RNAs associate with different Argonaute proteins. Hence, we demonstrate that not all sequencing errors in small RNA datasets are technical artifacts, but that these actually often reveal valuable biological insights to the sites of post-transcriptional RNA modifications