Marketing Products With Wildlife: How to Make It Benefit Conservation

A key obstacle to wildlife conservation is a scarcity of funding. A recent paper [Courchamp, F., Jaric, I., Albert, C., Meinard, Y., Ripple, W. J., and Chapron, G. (2018). The paradoxical extinction of the most charismatic animals. PLoS Biol. 16:e2003997. doi: 10.1371/journal.pbio.2003997] illustrates how for-profit businesses' widespread use of threatened wildlife imagery could create complacency in the public about their conservation. A wildlife imagery royalty, whereby businesses that use threatened wildlife in their marketing pay a small percentage of their sales to the conservation of those species could be revolutionary for conservation funding. However, businesses are not currently compelled to support the protection of the species espoused in their products. We build upon the arguments presented by recent publications [Good, C., Burnham, D., and Macdonald, D. W. (2017). A cultural conscience for conservation. Animals 7:52. doi: 10.3390/ani7070052; Courchamp, F., Jaric, I., Albert, C., Meinard, Y., Ripple, W. J., and Chapron, G. (2018). The paradoxical extinction of the most charismatic animals. PLoS Biol. 16:e2003997. doi: 10.1371/journal.pbio.2003997] to explore limitations and a number of key pathways that may help bring a wildlife imagery royalty to fruition.

Modeling inter-trial variability of pointing movements during visuomotor adaptation

Trial-to-trial variability during visuomotor adaptation is usually explained as the result of two different sources, planning noise and execution noise. The estimation of the underlying variance parameters from observations involving varying feedback conditions cannot be achieved by standard techniques (Kalman filter) because they do not account for recursive noise propagation in a closed-loop system. We therefore developed a method to compute the exact likelihood of the output of a time-discrete and linear adaptation system as has been used to model visuomotor adaptation (Smith et al. in PLoS Biol 4(6):e179, 2006), observed under closed-loop and error-clamp conditions. We identified the variance parameters by maximizing this likelihood and compared the model prediction of the time course of variance and autocovariance with empiric data. The observed increase in variability during the early training phase could not be explained by planning noise and execution noise with constant variances. Extending the model by signal-dependent components of either execution noise or planning noise showed that the observed temporal changes of the trial-to-trial variability can be modeled by signal-dependent planning noise rather than signal-dependent execution noise. Comparing the variance time course between different training schedules showed that the signal-dependent increase of planning variance was specific for the fast adapting mechanism, whereas the assumption of constant planning variance was sufficient for the slow adapting mechanisms.

Role of the somatosensory cortex in motor memory consolidation

Motor memories become resistant to interference by the process of consolidation, which leads to long-term retention. Studies have shown involvement of the somatosensory cortex in motor learning-related plasticity, but not directly in motor memory consolidation. This Neuro Forum article reviews evidence from a continuous theta-burst transcranial magnetic stimulation (cTBS) study by Kumar and colleagues (Kumar N, Manning TF, Ostry DJ. PLoS Biol 17: e3000469, 2019) that demonstrates the role of somatosensory, rather than motor, cortex in human motor memory consolidation during implicit motor learning.

Unlocked capacity of proteins to attack membranes characteristic of aggregation: the evil for diseases and aging from Pandora’s box

Aggregation of specific proteins is characteristic of a large spectrum of human diseases including all neurodegenerative diseases, while aggregation of non-specific proteins has been now identified to be a biomarker for cellular aging down to Escherichia coli. Previously, as facilitated with our discovery in 2005 that “completely insoluble” proteins could be all solubilized in unsalted water [Song (2009) FEBS Lett. 583: 953], we found that the TDP-43 prion-like domain in fact contains an intrinsic membrane-interacting subdomain [Lim et al. [2016] PLoS Biol. 14, e1002338]. We decrypted that ALS-causing mutations/cofactor-depletion act to render the wellstructured folds of cytosolic VAPB-MSP domain and SOD1 into highly disordered states, thus becoming buffer-insoluble. Most surprisingly, this also unlocks the amphiphilic/hydrophobic regions universally exiting in proteins, which thus acquire a novel capacity in abnormally interacting with membranes [Qin et al. (2013) F1000Res 2-221.v2; Lim (2016) BBA-Biomembranes. 1858: 2223]. Here we aimed extend our discovery to address two fundamental questions: 1) why many E. coli proteins become aggregated in aging; and 2) whether aggregation-prone proteins can also acquire a novel capacity in interacting with membranes; by dissecting the 557-residue S1 ribosomal protein into 7 fragments to disrupt its 6 S1 folds, followed by extensive CD and NMR characterizations. The results reveal that we have successfully eliminated all 6 S1 folds and fragment 4 becomes highly disordered and thus buffer-insoluble. Most strikingly, F4 does acquire a capacity in transforming into a helical conformation in membrane environments. Here, for the first time, our study deciphers that like ALScausing mutants, the disruption of a well-folded E. coli cytosolic protein also unlocks its amphiphilic/hydrophobic regions which are capable of abnormally interacting with membranes. Therefore, proteins, the most important functional players for all forms of life, can transform into membrane-toxic forms triggering diseases and aging, if their hydrophobic/amphiphilic regions are unlocked by genetic, pathological or/and environmental factors, which is characteristic of severe aggregation.

Mechanisms of self-assembly and fibrillization of the prion-like domains

The mechanism of the self-assembly and fibrillization of the prion-like domains lies at the heart of their physiology and pathology. Here with the same methods previously established, we aimed to further decipher the mechanism by characterizing two prion-like sequences with the electrostatic properties very different from that of the full-length TDP-43 prion-like domain with a very basic pI value: namely the C-half of the TDP-43 prion-like domain only abundant in Gly, Ser, Asn and Gln with a pI of ~6.3, and the FUS prion-like domain enriched with Gly, Ser, Gln and Tyr with a pI of ~3.5. Interestingly, the C-half with the TDP-43 unique hydrophobic region removed is no longer able to form insoluble aggregates/fibrils but still capable of self-assembling into the reversible hydrogel with cross-β structures, despite being much slower than the full-length. On the other hand, the FUS prion-like domain rapidly self-assembles into the reversible hydrogel with cross-β fibrillar structures in 1 mM phosphate buffer at pH 6.8 but its self-assembly becomes very slow in 50 mM MES buffer at pH 5.5. Our study reveals that despite having completely different electrostatic properties, the full-length and C-half of the TDP-43 prion-like domain, as well as FUS prion-like domain all have the similar pH-dependence in self-assembly as we previously reported (Lim et al., [2016] PLOS Biol 14:e1002338). This unambiguously indicates that the self-assembly of the prion-like domains is not generally governed by the electrostatic interaction. Rather, their self-assembly and fibrillization are specified by the sequences despite being highly polar and degenerative. Furthermore, our study provides the first evidence that the formation of reversible hydrogel with cross-β structures is separable from fibrillization of the prion-like domain. Finally, our results also successfully reconcile the previous discrepancy about the conformation and mechanism of the self-assembly of the FUS prion-like domain.

Three timescales in prism adaptation

It has been proposed that motor adaptation depends on at least two learning systems, one that learns fast but with poor retention and another that learns slowly but with better retention (Smith MA, Ghazizadeh A, Shadmehr R. PLoS Biol 4: e179, 2006). This two-state model has been shown to account for a range of behavior in the force field adaptation task. In the present study, we examined whether such a two-state model could also account for behavior arising from adaptation to a prismatic displacement of the visual field. We first confirmed that an “adaptation rebound,” a critical prediction of the two-state model, occurred when visual feedback was deprived after an adaptation-extinction episode. We then examined the speed of decay of the prism aftereffect (without any visual feedback) after repetitions of 30, 150, and 500 trials of prism exposure. The speed of decay decreased with the number of exposure trials, a phenomenon that was best explained by assuming an “ultraslow” system, in addition to the fast and slow systems. Finally, we compared retention of aftereffects 24 h after 150 or 500 trials of exposure: retention was significantly greater after 500 than 150 trials. This difference in retention could not be explained by the two-state model but was well explained by the three-state model as arising from the difference in the amount of adaptation of the “ultraslow process.” These results suggest that there are not only fast and slow systems but also an ultraslow learning system in prism adaptation that is activated by prolonged prism exposure of 150–500 trials.

How the Double Spherules of Infectious Bronchitis Virus Impact Our Understanding of RNA Virus Replicative Organelles

ABSTRACT Powered by advances in electron tomography, recent studies have extended our understanding of how viruses construct “replication factories” inside infected cells. Their function, however, remains an area of speculation with important implications for human health. It is clear from these studies that whatever their purpose, organelle structure is dynamic (M. Ulasli, M. H. Verheije, C. A. de Haan, and F. Reggiori, Cell. Microbiol. 12:844-861, 2010) and intricate (K. Knoops, M. Kikkert, S. H. Worm, J. C. Zevenhoven-Dobbe, Y. van der Meer, et al., PLOS Biol. 6:e226, 2008). But by concentrating on medically important viruses, these studies have failed to take advantage of the genetic variation inherent in a family of viruses that is as diverse as the archaea, bacteria, and eukaryotes combined (C. Lauber, J. J. Goeman, M. del Carmen Parquet, P. T. Nga, E. J. Snijder, et al., PLOS Pathog. 9:e1003500, 2013). In this climate, Maier et al. (H. J. Maier, P. C. Hawes, E. M. Cottam, J. Mantell, P. Verkade, et al., mBio 4:e00801-13, 2013) explored the replicative structures formed by an avian coronavirus that appears to have diverged at an early point in coronavirus evolution and shed light on controversial aspects of viral biology.

Mathematical modelling of Wnt/β-catenin signalling

The Wnt/β-catenin pathway plays an important role in development and disease. Theoretical approaches have been used to describe this pathway and have provided intriguing insights into its signalling characteristics. In the present paper, we review mathematical models of the pathway. We focus on a quantitative kinetic model for canonical Wnt/β-catenin signalling describing the reactions of the pathway's core compounds [Lee, Salic, Krüger, Heinrich and Kirschner (2003) PLoS Biol. 1, 116–132]. Numerous modifications and further analyses with respect to signalling characteristics, transcriptional feedback and cross-talk were performed. In addition, the role of β-catenin in gene expression and cell–cell adhesion as well as spatial aspects of signalling are investigated in various theoretical models.

Genomic Content of Neisseria Species

ABSTRACT The physical properties of most bacterial genomes are largely unexplored. We have previously demonstrated that the strict human pathogen Neisseria gonorrhoeae is polyploid, carrying an average of three chromosome copies per cell and only maintaining one pair of replication forks per chromosome (D. M. Tobiason and H. S. Seifert, PLos Biol. 4:1069-1078, 2006). We are following up this initial report to test several predictions of the polyploidy model of gonococcal chromosome organization. We demonstrate that the N. gonorrhoeae chromosomes exist solely as monomers and not covalently linked dimers, and in agreement with the monomer status, we show that distinct nucleoid regions can be detected by electron microscopy. Two different approaches to isolate heterozygous N. gonorrhoeae resulted in the formation of merodiploids, showing that even with more than one chromosome copy, these bacteria are genetically haploid. We show that the closely related bacterium Neisseria meningitidis is also polyploid, while the commensal organism Neisseria lactamica maintains chromosomes in single copy. We conclude that the pathogenic Neisseria strains are homozygous diploids.