A new class of natural anthelmintics targeting lipid metabolism.

Parasitic helminths are a major global health threat, infecting nearly one-fifth of the human population and causing significant losses in livestock and crops. Resistance to the few anthelmintic drugs is increasing. Here, we report a set of avocado fatty alcohols/acetates (AFAs) that exhibit nematocidal activity against four veterinary parasitic nematode species: Brugia pahangi, Teladorsagia circumcincta and Heligmosomoides polygyrus, as well as a multidrug resistant strain (UGA) of Haemonchus contortus.

TeloSearchLR: an algorithm to detect novel telomere repeat motifs using long sequencing reads.

Telomeres are eukaryotic chromosome end structures that guard against sequence loss and aberrant chromosome fusions. Telomeric repeat motifs (TRMs), the minimal repeating unit of a telomere, vary from species to species, with some evolutionary clades experiencing a rapid sequence divergence. To explore the full scope of this evolutionary divergence, many bioinformatic tools have been developed to infer novel TRMs using repetitive sequence search on short sequencing reads.

Assessing nanobody interaction with SARS-CoV-2 Nsp9.

The interaction between SARS-CoV-2 non-structural protein Nsp9 and the nanobody 2NSP90 was investigated by NMR spectroscopy using the paramagnetic perturbation methodology PENELOP (Paramagnetic Equilibrium vs Nonequilibrium magnetization Enhancement or LOss Perturbation). The Nsp9 monomer is an essential component of the replication and transcription complex (RTC) that reproduces the viral gRNA for subsequent propagation. Therefore preventing Nsp9 recruitment in RTC would represent an efficient antiviral strategy that could be applied to different coronaviruses, given the Nsp9 relative invariance.

The Caenorhabditis elegans TDRD5/7-like protein, LOTR-1, interacts with the helicase ZNFX-1 to balance epigenetic signals in the germline.

LOTUS and Tudor domain containing proteins have critical roles in the germline. Proteins that contain these domains, such as Tejas/Tapas in Drosophila, help localize the Vasa helicase to the germ granules and facilitate piRNA-mediated transposon silencing. The homologous proteins in mammals, TDRD5 and TDRD7, are required during spermiogenesis.

NMR-Based Analysis of Nanobodies to SARS-CoV-2 Nsp9 Reveals a Possible Antiviral Strategy Against COVID-19.

Following the entry into the host cell, SARS-CoV-2 replication is mediated by the replication transcription complex (RTC) assembled through a number of nonstructural proteins (Nsps). A monomeric form of Nsp9 is particularly important for RTC assembly and function. In the present study, 136 unique nanobodies targeting Nsp9 are generated.

Novel LOTUS-domain proteins are organizational hubs that recruit Vasa to germ granules.

We describe MIP-1 and MIP-2, novel paralogous germ granule components that interact with the intrinsically disordered MEG-3 protein. These proteins promote P granule condensation, form granules independently of MEG-3 in the postembryonic germ line, and balance each other in regulating P granule growth and localization. MIP-1 and MIP-2 each contain two LOTUS domains and intrinsically disordered regions and form homo- and heterodimers.

A Genome-Wide RNAi Screen for Enhancers of a Germline Tumor Phenotype Caused by Elevated GLP-1/Notch Signaling in .

Stem cells are tightly controlled Both the balance between self-renewal and differentiation and the rate of proliferation are often regulated by multiple factors. The hermaphrodite germ line provides a simple and accessible system for studying stem cells In this system, GLP-1/Notch activity prevents the differentiation of distal germ cells in response to ligand production from the nearby distal tip cell, thereby supporting a stem cell pool. However, a delay in germline development relative to somatic gonad development can cause a pool of undifferentiated germ cells to persist in response to alternate Notch ligands expressed in the proximal somatic gonad.

Tissue- and sex-specific small RNAomes reveal sex differences in response to the environment.

RNA interference (RNAi) related pathways are essential for germline development and fertility in metazoa and can contribute to inter- and trans-generational inheritance. In the nematode Caenorhabditis elegans, environmental double-stranded RNA provided by feeding can lead to heritable changes in phenotype and gene expression. Notably, transmission efficiency differs between the male and female germline, yet the underlying mechanisms remain elusive.

Comparative Epigenomics Reveals that RNA Polymerase II Pausing and Chromatin Domain Organization Control Nematode piRNA Biogenesis.

Piwi-interacting RNAs (piRNAs) are important for genome regulation across metazoans, but their biogenesis evolves rapidly. In Caenorhabditis elegans, piRNA loci are clustered within two 3-Mb regions on chromosome IV. Each piRNA locus possesses an upstream motif that recruits RNA polymerase II to produce an ∼28 nt primary transcript.

Developmental dynamics of gene expression and alternative polyadenylation in the Caenorhabditis elegans germline.

Background: The 3' untranslated regions (UTRs) of mRNAs play a major role in post-transcriptional regulation of gene expression. Selection of transcript cleavage and polyadenylation sites is a dynamic process that produces multiple transcript isoforms for the same gene within and across different cell types. Using LITE-Seq, a new quantitative method to capture transcript 3' ends expressed in vivo, we have characterized sex- and cell type-specific transcriptome-wide changes in gene expression and 3'UTR diversity in Caenorhabditis elegans germline cells undergoing proliferation and differentiation.

Genome Architecture and Evolution of a Unichromosomal Asexual Nematode.

Asexual reproduction in animals, though rare, is the main or exclusive mode of reproduction in some long-lived lineages. The longevity of asexual clades may be correlated with the maintenance of heterozygosity by mechanisms that rearrange genomes and reduce recombination. Asexual species thus provide an opportunity to gain insight into the relationship between molecular changes, genome architecture, and cellular processes.

A novel small molecule that disrupts a key event during the oocyte-to-embryo transition in C. elegans.

The complex cellular events that occur in response to fertilization are essential for mediating the oocyte-to-embryo transition. Here, we describe a comprehensive small-molecule screen focused on identifying compounds that affect early embryonic events in Caenorhabditis elegans We identify a single novel compound that disrupts early embryogenesis with remarkable stage and species specificity. The compound, named C22, primarily impairs eggshell integrity, leading to osmotic sensitivity and embryonic lethality.

Identification of Conserved MEL-28/ELYS Domains with Essential Roles in Nuclear Assembly and Chromosome Segregation.

Nucleoporins are the constituents of nuclear pore complexes (NPCs) and are essential regulators of nucleocytoplasmic transport, gene expression and genome stability. The nucleoporin MEL-28/ELYS plays a critical role in post-mitotic NPC reassembly through recruitment of the NUP107-160 subcomplex, and is required for correct segregation of mitotic chromosomes. Here we present a systematic functional and structural analysis of MEL-28 in C.

In Vivo Interaction Proteomics in Caenorhabditis elegans Embryos Provides New Insights into P Granule Dynamics.

Studying protein interactions in whole organisms is fundamental to understanding development. Here, we combine in vivo expressed GFP-tagged proteins with quantitative proteomics to identify protein-protein interactions of selected key proteins involved in early C. elegans embryogenesis.

Wild worm embryogenesis harbors ubiquitous polygenic modifier variation.

Embryogenesis is an essential and stereotypic process that nevertheless evolves among species. Its essentiality may favor the accumulation of cryptic genetic variation (CGV) that has no effect in the wild-type but that enhances or suppresses the effects of rare disruptions to gene function. Here, we adapted a classical modifier screen to interrogate the alleles segregating in natural populations of Caenorhabditis elegans: we induced gene knockdowns and used quantitative genetic methodology to examine how segregating variants modify the penetrance of embryonic lethality.

Comparative validation of the D. melanogaster modENCODE transcriptome annotation.

Accurate gene model annotation of reference genomes is critical for making them useful. The modENCODE project has improved the D. melanogaster genome annotation by using deep and diverse high-throughput data.

Global characterization of the oocyte-to-embryo transition in Caenorhabditis elegans uncovers a novel mRNA clearance mechanism.

The oocyte-to-embryo transition (OET) is thought to be mainly driven by post-transcriptional gene regulation. However, expression of both RNAs and proteins during the OET has not been comprehensively assayed. Furthermore, specific molecular mechanisms that regulate gene expression during OET are largely unknown.

Uncovering buffered pleiotropy: a genome-scale screen for mel-28 genetic interactors in Caenorhabditis elegans.

mel-28 (maternal-effect-lethal-28) encodes a conserved protein required for nuclear envelope function and chromosome segregation in Caenorhabditis elegans. Because mel-28 is a strict maternal-effect lethal gene, its function is required in the early embryo but appears to be dispensable for larval development. We wanted to test the idea that mel-28 has postembryonic roles that are buffered by the contributions of other genes.

A compendium of RNA-binding motifs for decoding gene regulation.

RNA-binding proteins are key regulators of gene expression, yet only a small fraction have been functionally characterized. Here we report a systematic analysis of the RNA motifs recognized by RNA-binding proteins, encompassing 205 distinct genes from 24 diverse eukaryotes. The sequence specificities of RNA-binding proteins display deep evolutionary conservation, and the recognition preferences for a large fraction of metazoan RNA-binding proteins can thus be inferred from their RNA-binding domain sequence.

DevStaR: high-throughput quantification of C. elegans developmental stages.

We present DevStaR, an automated computer vision and machine learning system that provides rapid, accurate, and quantitative measurements of C. elegans embryonic viability in high-throughput (HTP) applications. A leading genetic model organism for the study of animal development and behavior, C.

High-throughput fluorescence-based isolation of live C. elegans larvae.

For the nematode Caenorhabditis elegans, automated selection of animals of specific genotypes from a mixed pool has become essential for genetic interaction or chemical screens. To date, such selection has been accomplished using specialized instruments. However, access to such dedicated equipment is not common.

RNAi methods and screening: RNAi based high-throughput genetic interaction screening.

Expanding on decades of mutational analyses, numerous genome-scale RNAi screens have now been performed in C. elegans, leading to estimates that the majority of genes with essential functions that can be revealed by single-gene perturbations have already been identified in this organism. To build on this basic foundation and uncover condition-dependent or combinatorial effects of non-essential genes will require even higher-scale screening.

A model of cytoplasmically driven microtubule-based motion in the single-celled Caenorhabditis elegans embryo.

We present a model of cytoplasmically driven microtubule-based pronuclear motion in the single-celled Caenorhabditis elegans embryo. In this model, a centrosome pair at the male pronucleus initiates stochastic microtubule (MT) growth. These MTs encounter motor proteins, distributed throughout the cytoplasm, that attach and exert a pulling force.

A high-resolution C. elegans essential gene network based on phenotypic profiling of a complex tissue.

High-content screening for gene profiling has generally been limited to single cells. Here, we explore an alternative approach-profiling gene function by analyzing effects of gene knockdowns on the architecture of a complex tissue in a multicellular organism. We profile 554 essential C.

Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project.

We systematically generated large-scale data sets to improve genome annotation for the nematode Caenorhabditis elegans, a key model organism. These data sets include transcriptome profiling across a developmental time course, genome-wide identification of transcription factor-binding sites, and maps of chromatin organization. From this, we created more complete and accurate gene models, including alternative splice forms and candidate noncoding RNAs.