PLOS Biology: New Articles

  • Scaling up area-based conservation to implement the Global Biodiversity Framework’s 30x30 target: The role of Nature’s Strongholds

    by John G. Robinson, Danielle LaBruna, Tim O’Brien, Peter J. Clyne, Nigel Dudley, Sandy J. Andelman, Elizabeth L. Bennett, Avecita Chicchon, Carlos Durigan, Hedley Grantham, Margaret Kinnaird, Sue Lieberman, Fiona Maisels, Adriana Moreira, Madhu Rao, Emma Stokes, Joe Walston, James EM Watson

    The Global Biodiversity Framework (GBF), signed in 2022 by Parties to the Convention on Biological Diversity, recognized the importance of area-based conservation, and its goals and targets specify the characteristics of protected and conserved areas (PCAs) that disproportionately contribute to biodiversity conservation. To achieve the GBF’s target of conserving a global area of 30% by 2030, this Essay argues for recognizing these characteristics and scaling them up through the conservation of areas that are: extensive (typically larger than 5,000 km2); have interconnected PCAs (either physically or as part of a jurisdictional network, and frequently embedded in larger conservation landscapes); have high ecological integrity; and are effectively managed and equitably governed. These areas are presented as “Nature’s Strongholds,” illustrated by examples from the Congo and Amazon basins. Conserving Nature’s Strongholds offers an approach to scale up initiatives to address global threats to biodiversity.

  • <i>Yersinia pestis</i> can infect the Pawlowsky glands of human body lice and be transmitted by louse bite

    by David M. Bland, Dan Long, Rebecca Rosenke, B. Joseph Hinnebusch

    Yersinia pestis, the causative agent of plague, is a highly lethal vector-borne pathogen responsible for killing large portions of Europe’s population during the Black Death of the Middle Ages. In the wild, Y. pestis cycles between fleas and rodents; occasionally spilling over into humans bitten by infectious fleas. For this reason, fleas and the rats harboring them have been considered the main epidemiological drivers of previous plague pandemics. Human ectoparasites, such as the body louse (Pediculus humanus humanus), have largely been discounted due to their reputation as inefficient vectors of plague bacilli. Using a membrane-feeder adapted strain of body lice, we show that the digestive tract of some body lice become chronically infected with Y. pestis at bacteremia as low as 1 × 105 CFU/ml, and these lice routinely defecate Y. pestis. At higher bacteremia (≥1 × 107 CFU/ml), a subset of the lice develop an infection within the Pawlowsky glands (PGs), a pair of putative accessory salivary glands in the louse head. Lice that developed PG infection transmitted Y. pestis more consistently than those with bacteria only in the digestive tract. These glands are thought to secrete lubricant onto the mouthparts, and we hypothesize that when infected, their secretions contaminate the mouthparts prior to feeding, resulting in bite-based transmission of Y. pestis. The body louse’s high level of susceptibility to infection by gram-negative bacteria and their potential to transmit plague bacilli by multiple mechanisms supports the hypothesis that they may have played a role in previous human plague pandemics and local outbreaks.

  • Alkenyl oxindole is a novel PROTAC moiety that recruits the CRL4<sup>DCAF11</sup> E3 ubiquitin ligase complex for targeted protein degradation

    by Ying Wang, Tianzi Wei, Man Zhao, Aima Huang, Fan Sun, Lu Chen, Risheng Lin, Yubao Xie, Ming Zhang, Shiyu Xu, Zhihui Sun, Liang Hong, Rui Wang, Ruilin Tian, Guofeng Li

    Alkenyl oxindoles have been characterized as autophagosome-tethering compounds (ATTECs), which can target mutant huntingtin protein (mHTT) for lysosomal degradation. In order to expand the application of alkenyl oxindoles for targeted protein degradation, we designed and synthesized a series of heterobifunctional compounds by conjugating different alkenyl oxindoles with bromodomain-containing protein 4 (BRD4) inhibitor JQ1. Through structure-activity relationship study, we successfully developed JQ1-alkenyl oxindole conjugates that potently degrade BRD4. Unexpectedly, we found that these molecules degrade BRD4 through the ubiquitin-proteasome system, rather than the autophagy-lysosomal pathway. Using pooled CRISPR interference (CRISPRi) screening, we revealed that JQ1-alkenyl oxindole conjugates recruit the E3 ubiquitin ligase complex CRL4DCAF11 for substrate degradation. Furthermore, we validated the most potent heterobifunctional molecule HL435 as a promising drug-like lead compound to exert antitumor activity both in vitro and in a mouse xenograft tumor model. Our research provides new employable proteolysis targeting chimera (PROTAC) moieties for targeted protein degradation, providing new possibilities for drug discovery.

  • The promise and pitfalls of synteny in phylogenomics

    by Jacob L. Steenwyk, Nicole King

    Reconstructing the tree of life remains a central goal in biology. Early methods, which relied on small numbers of morphological or genetic characters, often yielded conflicting evolutionary histories, undermining confidence in the results. Investigations based on phylogenomics, which use hundreds to thousands of loci for phylogenetic inquiry, have provided a clearer picture of life’s history, but certain branches remain problematic. To resolve difficult nodes on the tree of life, 2 recent studies tested the utility of synteny, the conserved collinearity of orthologous genetic loci in 2 or more organisms, for phylogenetics. Synteny exhibits compelling phylogenomic potential while also raising new challenges. This Essay identifies and discusses specific opportunities and challenges that bear on the value of synteny data and other rare genomic changes for phylogenomic studies. Synteny-based analyses of highly contiguous genome assemblies mark a new chapter in the phylogenomic era and the quest to reconstruct the tree of life.

  • Simple visual stimuli are sufficient to drive responses in action observation and execution neurons in macaque ventral premotor cortex

    by Sofie De Schrijver, Thomas Decramer, Peter Janssen

    Neurons responding during action execution and action observation were discovered in the ventral premotor cortex 3 decades ago. However, the visual features that drive the responses of action observation/execution neurons (AOENs) have not been revealed at present. We investigated the neural responses of AOENs in ventral premotor area F5c of 4 macaques during the observation of action videos and crucial control stimuli. The large majority of AOENs showed highly phasic responses during the action videos, with a preference for the moment that the hand made contact with the object. They also responded to an abstract shape moving towards but not interacting with an object, even when the shape moved on a scrambled background, implying that most AOENs in F5c do not require the perception of causality or a meaningful action. Additionally, the majority of AOENs responded to static frames of the videos. Our findings show that very elementary stimuli, even without a grasping context, are sufficient to drive responses in F5c AOENs.