Locomotion and palaeoclimate explain the re-evolution of quadrupedal body form in Brachymeles lizards

Evolutionary reversals, including re-evolution of lost structures, are commonly found in phylogenetic studies. However, we lack an understanding of how these reversals happen mechanistically. A snake-like body form has evolved many times in vertebrates, and occasionally a quadrupedal form has re-evolved, including in Brachymeles lizards. We use body form and locomotion data for species ranging from snake-like to quadrupedal to address how a quadrupedal form could re-evolve. We show that large, quadrupedal species are faster at burying and surface locomotion than snake-like species, indicating a lack of expected performance trade-off between these modes of locomotion. Species with limbs use them while burying, suggesting that limbs are useful for burying in wet, packed substrates. Palaeoclimatological data suggest that Brachymeles originally evolved a snake-like form under a drier climate probably with looser soil in which it was easier to dig. The quadrupedal clade evolved as the climate became humid, where limbs and large size facilitated fossorial locomotion in packed soils.     

2-Phenyl-9H-purine-6-carbonitrile derivatives as selective cathepsin S inhibitors

Starting from previously disclosed equally potent cathepsin K and S inhibitor 4-propyl-6-(3-trifluoromethylphenyl)pyrimidine-2-carbonitrile 1, a novel 2-phenyl-9H-purine-6-carbonitrile scaffold was identified to provide potent and selective cathepsin S inhibitors.     

Fungal bioremediation of polyethylene: Challenges and perspectives

Plastics have become ubiquitous in both their adoption as materials and as environmental contaminants. Widespread pollution of these versatile, man-made and largely petroleum-derived polymers has resulted from their long-term mass production, inappropriate disposal and inadequate end of life management. Polyethylene (PE) is at the forefront of this problem, accounting for one-third of plastic demand in Europe in part due to its extensive use in packaging. Current recycling and incineration processes do not represent sustainable solutions to tackle plastic waste, especially once it becomes littered, and the development of new waste-management and remediation technologies are needed. Mycoremediation (fungal-based biodegradation) of PE has been the topic of several studies over the last two decades. The utility of these studies is limited by an inconclusive definition of biodegradation and a lack of knowledge regarding the biological systems responsible. This review highlights relevant features of fungi as potential bioremediation agents, before discussing the evidence for fungal biodegradation of both high- and low-density PE. An up-to-date perspective on mycoremediation as a future solution to PE waste is provided.     

NmeCas9 is an intrinsically high-fidelity genome-editing platform

Background

The development of CRISPR genome editing has transformed biomedical research. Most applications reported thus far rely upon the Cas9 protein from Streptococcus pyogenes SF370 (SpyCas9). With many RNA guides, wildtype SpyCas9 can induce significant levels of unintended mutations at near-cognate sites, necessitating substantial efforts toward the development of strategies to minimize off-target activity. Although the genome-editing potential of thousands of other Cas9 orthologs remains largely untapped, it is not known how many will require similarly extensive engineering to achieve single-site accuracy within large genomes. In addition to its off-targeting propensity, SpyCas9 is encoded by a relatively large open reading frame, limiting its utility in applications that require size-restricted delivery strategies such as adeno-associated virus vectors. In contrast, some genome-editing-validated Cas9 orthologs are considerably smaller and therefore better suited for viral delivery.

Results

Here we show that wildtype NmeCas9, when programmed with guide sequences of the natural length of 24 nucleotides, exhibits a nearly complete absence of unintended editing in human cells, even when targeting sites that are prone to off-target activity with wildtype SpyCas9. We also validate at least six variant protospacer adjacent motifs (PAMs), in addition to the preferred consensus PAM (5′-N₄GATT-3′), for NmeCas9 genome editing in human cells.

Conclusions

Our results show that NmeCas9 is a naturally high-fidelity genome-editing enzyme and suggest that additional Cas9 orthologs may prove to exhibit similarly high accuracy, even without extensive engineering.

     

Movement and sound generation by the toadfish swimbladder

Although sound-producing (sonic) muscles attached to fish swimbladders are the fastest known vertebrate muscles, the functional requirement for such extreme speed has never been addressed. We measured movement of the swimbladder caused by sonic muscle stimulation in the oyster toadfish Opsanus tau and related it to major features of the sound waveform. The movement pattern is complex and produces sound inefficiently because the sides and bottom of the bladder move in opposite in and out directions, and both movement and sound decay rapidly. Sound amplitude is related to speed of swimbladder movement, and slow movements do not produce perceptible sound. Peak sound amplitude overlaps fundamental frequencies of the male's mating call because of muscle mechanics and not the natural frequency of the bladder. These findings suggest that rapid muscle speed evolved to generate sound from an inefficient highly damped system.     

Enzymology of Phanerochaete chrysosporium with respect to the degradation of recalcitrant compounds and xenobiotics

The archetypal white-rot fungus Phanerochaete chrysosporium has been shown to degrade a variety of persistent environmental pollutants. Many of the enzymes responsible for pollutant degradation, which are normally involved in the degradation of wood, are extracellular. Thus, P. chrysosporium is able to degrade toxic or insoluble chemicals more efficiently than other microorganisms. P. chrysosporium has a range of oxidative and reductive mechanisms and uses highly reactive, nonspecific redox mediators which increase the number of chemicals that can be effectively degraded. This review gives an overview of the enzymes that are believed to be important for bioremediation and briefly discusses the degradation of some individual chemicals. Received: 25 April 2000 / Received revision: 05 June 2000 / Accepted: 04 July 2000