Optimization of a series of quinazolinone-derived antagonists of CXCR3

The evaluation of the CXCR3 antagonist AMG 487 in clinic trials was complicated due to the formation of an active metabolite. In this Letter, we will discuss the further optimization of the quinazolinone series that led to the discovery of compounds devoid of the formation of the active metabolite that was seen with AMG 487. In addition, these compounds also feature increased potency and good pharmacokinetic properties. We will also discuss the efficacy of the lead compound 34 in a mouse model of cellular recruitment induced by bleomycin.     

Co‐benefits,trade‐offs,barriers and policies for greenhouse gas mitigation in the agriculture,forestry and other land use (AFOLU) sector

The agriculture, forestry and other land use (AFOLU) sector is responsible for approximately 25% of anthropogenic GHG emissions mainly from deforestation and agricultural emissions from livestock, soil and nutrient management. Mitigation from the sector is thus extremely important in meeting emission reduction targets. The sector offers a variety of cost‐competitive mitigation options with most analyses indicating a decline in emissions largely due to decreasing deforestation rates. Sustainability criteria are needed to guide development and implementation of AFOLU mitigation measures with particular focus on multifunctional systems that allow the delivery of multiple services from land. It is striking that almost all of the positive and negative impacts, opportunities and barriers are context specific, precluding generic statements about which AFOLU mitigation measures have the greatest promise at a global scale. This finding underlines the importance of considering each mitigation strategy on a case‐by‐case basis, systemic effects when implementing mitigation options on the national scale, and suggests that policies need to be flexible enough to allow such assessments. National and international agricultural and forest (climate) policies have the potential to alter the opportunity costs of specific land uses in ways that increase opportunities or barriers for attaining climate change mitigation goals. Policies governing practices in agriculture and in forest conservation and management need to account for both effective mitigation and adaptation and can help to orient practices in agriculture and in forestry towards global sharing of innovative technologies for the efficient use of land resources. Different policy instruments, especially economic incentives and regulatory approaches, are currently being applied however, for its successful implementation it is critical to understand how land‐use decisions are made and how new social, political and economic forces in the future will influence this process.     

Cryptic phenology in plants: Case studies,implications, and recommendations

Plant phenology—the timing of cyclic or recurrent biological events in plants—offers insight into the ecology, evolution, and seasonality of plant‐mediated ecosystem processes. Traditionally studied phenologies are readily apparent, such as flowering events, germination timing, and season‐initiating budbreak. However, a broad range of phenologies that are fundamental to the ecology and evolution of plants, and to global biogeochemical cycles and climate change predictions, have been neglected because they are “cryptic”—that is, hidden from view (e.g., root production) or difficult to distinguish and interpret based on common measurements at typical scales of examination (e.g., leaf turnover in evergreen forests). We illustrate how capturing cryptic phenology can advance scientific understanding with two case studies: wood phenology in a deciduous forest of the northeastern USA and leaf phenology in tropical evergreen forests of Amazonia. Drawing on these case studies and other literature, we argue that conceptualizing and characterizing cryptic plant phenology is needed for understanding and accurate prediction at many scales from organisms to ecosystems. We recommend avenues of empirical and modeling research to accelerate discovery of cryptic phenological patterns, to understand their causes and consequences, and to represent these processes in terrestrial biosphere models.     

Common and rare species respond to similar niche processes in macroinvertebrate metacommunities

Ecologists have long investigated why communities are composed of a few common species and many rare species. Most studies relate rarity to either niche differentiation among species or spatial processes. There is a parallel between these processes and the processes proposed to explain the structure of metacommunities. Based on a metacommunity perspective and on data on stream macroinvertebrates from different regions of Brazil, we answer two questions. 1) Are sets of common and rare species affected by similar niche and spatial processes? 2) How does the community composition of common and of rare species differ? The main hypothesis we test is that common species are mainly affected by environmental factors, whereas rare species are mostly influenced by dispersal limitation. We used variation partitioning to determine the proportion of variation explained by the environment and space in common and rare species matrices. Contrary to our expectations, evidence supported the idea that both common and rare species are affected mainly by environmental factors, even after controlling for the differing information content between common and rare species matrices. Moreover, the abundance of some common species is also a good predictor of variation in rare species matrices. Niche differences are unlikely to be the sole cause of patterns of rarity in these metacommunities. We suggest that sets of common and rare species react to similar major environmental gradients and that rare species also respond to processes that operate at a more fine‐grained spatial scale, particularly biotic interactions. We extend the view that species sorting is the dominant process structuring metacommunities and argue that future studies focusing on rarity would benefit from a metacommunity perspective.     

Ichnology and sedimentology of a tide‐influenced delta in the Ordovician from the northeastern Alborz range of Iran (Kopet Dagh region)

The Middle–Late Ordovician Ghelli Formation in the Kopet Dagh region northeastern Alborz range of Iran is composed of siliciclastic rocks deposited in a variety of turbidite to marginal marine environments (deep marine clastic fan and related environments and prodelta, distal delta front, proximal delta front and distributary channels). The ichnology of the middle member of the Ghelli Formation is here reported. Combined sedimentological and ichnological analysis allows recognition of a tide‐influenced deltaic succession in the middle member of the Ghelli Formation consisting of three main facies associations: lower distributary channels, delta front and prodelta facies. Twenty‐two ichnogenera have been identified in this marginal marine succession: Arenicolites, Arthrophycus, Bergaueria, Chondrites, Conichnus, Cruziana, Cylindrichnus, Didymaulichnus, Diplichnites, Diplocraterion, Helminthopsis, Gyrochorte, Lockeia, Macaronichnus, Monomorphichnus, Palaeophycus, Planolites, Rosselia, Rusophcus, Skolithos, Teichichnus and ?Scolicia. Their distribution is clearly linked with lithofacies and depositional palaeoenvironments. The ichnological analysis reveals that the trace fossil suites developed in these environments indicate low diversity and low to moderate abundance of burrows, poor development of tiering and sporadic distribution. Low ichnodiversity and low bioturbation intensities with higher bioturbation clusters consist of facies‐crossing ichnogenera, and the impoverishment of suspension‐feeding trophic types indicates ‘stressed’, non‐archetypal expression of the Cruziana ichnofacies. The periodic higher intensities of bioturbation due to variations in hydrodynamic regimes of tidal currents reflect the archetypal of the Cruziana ichnofacies (and rare Skolithos ichnofacies).     

Ubiquitin‐specific protease‐like 1 (USPL1) is a SUMO isopeptidase with essential,non‐catalytic functions

Isopeptidases are essential regulators of protein ubiquitination and sumoylation. However, only two families of SUMO isopeptidases are at present known. Here, we report an activity‐based search with the suicide inhibitor haemagglutinin (HA)‐SUMO‐vinylmethylester that led to the identification of a surprising new SUMO protease, ubiquitin‐specific protease‐like 1 (USPL1). Indeed, USPL1 neither binds nor cleaves ubiquitin, but is a potent SUMO isopeptidase both in vitro and in cells. C13orf22l—an essential but distant zebrafish homologue of USPL1—also acts on SUMO, indicating functional conservation. We have identified invariant USPL1 residues required for SUMO binding and cleavage. USPL1 is a low‐abundance protein that colocalizes with coilin in Cajal bodies. Its depletion does not affect global sumoylation, but causes striking coilin mislocalization and impairs cell proliferation, functions that are not dependent on USPL1 catalytic activity. Thus, USPL1 represents a third type of SUMO protease, with essential functions in Cajal body biology.     

Biological soil crusts in ecological restoration: emerging research and perspectives

Drylands encompass over 40% of terrestrial ecosystems and face significant anthropogenic degradation causing a loss of ecosystem integrity, services, and deterioration of social‐ecological systems. To combat this degradation, some dryland restoration efforts have focused on the use of biological soil crusts (biocrusts): complex communities of cyanobacteria, algae, lichens, bryophytes, and other organisms living in association with the top millimeters of soil. Biocrusts are common in many ecosystems and especially drylands. They perform a suite of ecosystem functions: stabilizing soil surfaces to prevent erosion, contributing carbon through photosynthesis, fixing nitrogen, and mediating the hydrological cycle in drylands. Biocrusts have emerged as a potential tool in restoration; developing methods to implement effective biocrust restoration has the potential to return many ecosystem functions and services. Although culture‐based approaches have allowed researchers to learn about the biology, physiology, and cultivation of biocrusts, transferring this knowledge to field implementation has been more challenging. A large amount of research has amassed to improve our understanding of biocrust restoration, leaving us at an opportune time to learn from one another and to join approaches for maximum efficacy. The articles in this special issue improve the state of our current knowledge in biocrust restoration, highlighting efforts to effectively restore biocrusts through a variety of different ecosystems, across scales and utilizing a variety of lab and field methods. This collective work provides a useful resource for the scientific community as well as land managers.     

Burn‐in Free Nonfullerene‐Based Organic Solar Cells

Organic solar cells that are free of burn‐in, the commonly observed rapid performance loss under light, are presented. The solar cells are based on poly(3‐hexylthiophene) (P3HT) with varying molecular weights and a nonfullerene acceptor (rhodanine‐benzothiadiazole‐coupled indacenodithiophene, IDTBR) and are fabricated in air. P3HT:IDTBR solar cells light‐soaked over the course of 2000 h lose about 5% of power conversion efficiency (PCE), in stark contrast to [6,6]‐Phenyl C61 butyric acid methyl ester (PCBM)‐based solar cells whose PCE shows a burn‐in that extends over several hundreds of hours and levels off at a loss of ≈34%. Replacing PCBM with IDTBR prevents short‐circuit current losses due to fullerene dimerization and inhibits disorder‐induced open‐circuit voltage losses, indicating a very robust device operation that is insensitive to defect states. Small losses in fill factor over time are proposed to originate from polymer or interface defects. Finally, the combination of enhanced efficiency and stability in P3HT:IDTBR increases the lifetime energy yield by more than a factor of 10 when compared with the same type of devices using a fullerene‐based acceptor instead.