Global distribution of mcr gene variants in 214,095 metagenomic samples

Since the initial discovery of a mobilized colistin resistance gene (mcr-1), several other variants have been reported, some of which might have circulated a while before being discovered. Metagenomic data provides an opportunity to re-analyze available older data to understand the evolutionary history of recently discovered antimicrobial resistance genes (ARGs). Here, we present a large-scale metagenomic study of 442 Tbp of sequencing reads from 214,095 samples to identify the host and geographical distribution and genomic context of nine mcr gene variants (mcr-1 to mcr-9). Our results show that the dissemination of each variant is not uniform. Instead, the source and location play a role in the spread. Despite the very diverse distribution, the genomic background of the mcr genes remains unchanged as the same mobile genetic elements and plasmid replicons occur. This work emphasizes the importance of sharing genomic data for surveillance of ARGs in our fight against antimicrobial resistance.

BALLCOURT REPRESENTATIONS IN QUIECHAPA, OAXACA, MEXICO: RITUAL OFFERING, FERTILITY, AND LIFE

During an archaeological survey in the municipality of San Pedro Mártir Quiechapa, Oaxaca, Mexico, archaeologists from the Proyecto Arqueológico de Quiechapa (PAQuie) encountered and documented a number of carved stone elements. Of particular interest are the 30 representations of ballcourts carved into natural rock outcrops at two sites in the region. This is the highest density in which this type of ballcourt representation occurs throughout Mesoamerica. After their initial discovery, members of PAQuie documented the carved stone ballcourts using structure-from-motion (SfM) photogrammetry, a quick and affordable technique to collect 3D spatial, quantitative, and visual data of stone carvings. In this article, I report on the carved stone ballcourt representations documented in the Quiechapa region and offer some preliminary interpretations. I first provide some description of the broader archaeological context in which the carvings were found. Then I describe the methods used to record the stone carvings, followed by a presentation of the data. Finally, in dialogue with extant literature, I explore some possibilities as to why these carved stone ballcourt representations were created, how they may have been used, and what they may symbolize.

Omicron variant of SARS-CoV-2 harbors a unique insertion mutation of putative viral or human genomic origin

The emergence of a heavily mutated SARS-CoV-2 variant (B.1.1.529, Omicron) and it’s spread to 6 continents within a week of initial discovery has set off a global public health alarm. Characterizing the mutational profile of Omicron is necessary to interpret its shared or distinctive clinical phenotypes with other SARS-CoV-2 variants. We compared the mutations of Omicron with prior variants of concern (Alpha, Beta, Gamma, Delta), variants of interest (Lambda, Mu, Eta, Iota and Kappa), and all 1523 SARS-CoV-2 lineages constituting 5.4 million SARS-CoV-2 genomes. Omicron’s Spike protein has 26 amino acid mutations (23 substitutions, two deletions and one insertion) that are distinct compared to other variants of concern. Whereas the substitution and deletion mutations have appeared in previous SARS-CoV-2 lineages, the insertion mutation (ins214EPE) has not been previously observed in any SARS-CoV-2 lineage other than Omicron. The nucleotide sequence encoding for ins214EPE could have been acquired by template switching involving the genomes of other viruses that infect the same host cells as SARS-CoV-2 or the human transcriptome of host cells infected with SARS-CoV-2. For instance, given recent clinical reports of co-infections in COVID-19 patients with seasonal coronaviruses (e.g. HCoV-229E), single cell RNA-sequencing data showing co-expression of the SARS-CoV-2 and HCoV-229E entry receptors (ACE2 and ANPEP) in respiratory and gastrointestinal cells, and HCoV genomes harboring sequences homologous to the nucleotide sequence that encodes ins214EPE, it is plausible that the Omicron insertion could have evolved in a co-infected individual. There is a need to understand the function of the Omicron insertion and whether human host cells are being exploited by SARS-CoV-2 as an ‘evolutionary sandbox’ for host-virus and inter-viral genomic interplay.

The clinical advances of proteolysis targeting chimeras in oncology

Proteolysis targeting chimeras (PROTACs) are a class of small molecules designed to target proteins for degradation. Their novel and unique modes of action provide PROTACs with the potential for their application in the management of both solid and hematologic malignancies. Since its initial discovery, the technology of targeted protein degradation, especially in the form of PROTACs, has had significant advances. A number of PROTACs have entered a late stage of preclinical development. Several of them are either in phase 1/2 clinical trials or approaching approval for initial clinical evaluation. This article discusses the preclinical and clinical findings of PROTACs of clinically relevant protein targets in cancer.

The Palermo Stone and its Associated Fragments: New Discoveries on the Oldest Royal Annals of Ancient Egypt

Historical royal sources concerning Old Kingdom Egypt are rather scarce. One of the most important is a group of seven inscribed stone fragments also known as royal annals, the most famous of which is certainly the so-called Palermo Stone. These annals have been the subject of countless studies over more than a century since their initial discovery. However, the reading and interpretation of the hieroglyphic inscriptions engraved on them is still partial and often obscure. In recent years, however, the annals underwent a complete re-examination by means of the most up-to date technologies of 3D photographic documentation and reproduction – first of all, the so-called ‘Reflectance Transformation Imaging’ (RTI). In this article we will provide some insights on the new reading of selected parts of the fragments, especially the two major pieces: the Palermo Stone and the so-called ‘Cairo Fragment 1’.

The promise of microRNA-based therapies in Alzheimer’s disease: challenges and perspectives

Multi-pathway approaches for the treatment of complex polygenic disorders are emerging as alternatives to classical monotarget therapies and microRNAs are of particular interest in that regard. MicroRNA research has come a long way from their initial discovery to the cumulative appreciation of their regulatory potential in healthy and diseased brain. However, systematic interrogation of putative therapeutic or toxic effects of microRNAs in (models of) Alzheimer’s disease is currently missing and fundamental research findings are yet to be translated into clinical applications. Here, we review the literature to summarize the knowledge on microRNA regulation in Alzheimer’s pathophysiology and to critically discuss whether and to what extent these increasing insights can be exploited for the development of microRNA-based therapeutics in the clinic.

Tadpole-transporting frogs use stagnant water odor to find pools in the rainforest

Breeding sites are often a limited and ephemeral resource for rainforest frogs. This resource limitation has driven the evolution of diverse reproductive strategies that increase offspring survival. For example, poison frogs shuttle their tadpoles from terrestrial clutches to aquatic rearing sites, using various cues to assess pool suitability. Yet, how frogs find new pools is unknown. We tested the role of odor cues in the process of finding tadpole deposition sites by the poison frog Allobates femoralis. We created 60 artificial pools grouped into three conditions: stagnant water, tadpole water, and clean water control. Fifteen pools were discovered within six days, with more tadpoles and more frogs directly observed at pools with stagnant odor cues. Our findings suggest that frogs use odor cues associated with stagnant water for the initial discovery of new breeding pools. These cues may be good indicators of pool stability and increased likelihood of tadpole survival.

The history and typification of Lilium humboldtii J.H.Krelage (Liliaceae)

The history of the Californian Lilium humboldtii J.H.Krelage, its initial discovery and confusion in literature over its collection, distribution and naming are discussed. Neotypes are designated for the names Lilium humboldtii and Lilium bloomerianum Kellogg. Lectotypes are designated for the names Lilium canadense var. puberulum Torr. and L. bloomerianum var. ocellatum Kellogg.

Musings from the Tribbles Research and Innovation Network

This commentary integrates historical and modern findings that underpin our understanding of the cell-specific functions of the Tribbles (TRIB) proteins that bear on tumorigenesis. We touch on the initial discovery of roles played by mammalian TRIB proteins in a diverse range of cell-types and pathologies, for example, TRIB1 in regulatory T-cells, TRIB2 in acute myeloid leukaemia and TRIB3 in gliomas; the origins and diversity of TRIB1 transcripts; microRNA-mediated (miRNA) regulation of TRIB1 transcript decay and translation; the substantial conformational changes that ensue on binding of TRIB1 to the transcription factor C/EBPα; and the unique pocket formed by TRIB1 to sequester its C-terminal motif bearing a binding site for the E3 ubiquitin ligase COP1. Unashamedly, the narrative is relayed through the perspective of the Tribbles Research and Innovation Network, and its establishment, progress and future ambitions: the growth of TRIB and COP1 research to hasten discovery of their cell-specific contributions to health and obesity-related cancers.