A conserved chronobiological complex times development.

The mammalian PAS-domain protein PERIOD (PER) and its orthologue LIN-42 have been proposed to constitute an evolutionary link between two distinct, circadian and developmental, timing systems. However, while the function of PER in animal circadian rhythms is well understood molecularly and mechanistically, this is not true for LIN-42's function in timing rhythmic development. Here, using targeted deletions, we find that the LIN-42 PAS domains are dispensable for the protein's function in timing molts.

Dynamics of miRNA accumulation during C. elegans larval development.

Temporally and spatially controlled accumulation underlies the functions of microRNAs (miRNAs) in various developmental processes. In Caenorhabditis elegans, this is exemplified by the temporal patterning miRNAs lin-4 and let-7, but for most miRNAs, developmental expression patterns remain poorly resolved. Indeed, experimentally observed long half-lives may constrain possible dynamics.

Suppression and Control of Bipolar Powder Charging by Turbulence.

Current models predict particles of the same material but different sizes to charge bipolar upon contacts; the resulting charge peaks endanger process safety. However, we found wall-bounded turbulence to suppress the powder's electrostatic charging. Aerodynamic forces skew the collision frequency and narrow the charge distribution's bandwidth.

Airborne virus transmission: Increased spreading due to formation of hollow particles.

The globally supported social distancing rules to prevent airborne transmission of COVID-19 assume small saliva droplets evaporate fast and large ones, which contain most viral copies, fall fast to the ground. However, during evaporation, solutes distribute non-uniformly within the droplets. We developed a numerical model to predict saliva droplet drying in different environments.

Convergence of multiple RNA-silencing pathways on GW182/TNRC6.

The RNA-binding protein TRIM71/LIN-41 is a phylogenetically conserved developmental regulator that functions in mammalian stem cell reprogramming, brain development, and cancer. TRIM71 recognizes target mRNAs through hairpin motifs and silences them through molecular mechanisms that await identification. Here, we uncover that TRIM71 represses its targets through RNA-supported interaction with TNRC6/GW182, a core component of the miRNA-induced silencing complex (miRISC).

C. elegans molting requires rhythmic accumulation of the Grainyhead/LSF transcription factor GRH-1.

C. elegans develops through four larval stages that are rhythmically terminated by molts, that is, the synthesis and shedding of a cuticular exoskeleton. Each larval cycle involves rhythmic accumulation of thousands of transcripts, which we show here relies on rhythmic transcription.

A specific type of Argonaute phosphorylation regulates binding to microRNAs during C. elegans development.

Argonaute proteins are at the core of the microRNA-mediated gene silencing pathway essential for animals. In C. elegans, the microRNA-specific Argonautes ALG-1 and ALG-2 regulate multiple processes required for proper animal developmental timing and viability.

Coupling of growth rate and developmental tempo reduces body size heterogeneity in C. elegans.

Animals increase by orders of magnitude in volume during development. Therefore, small variations in growth rates among individuals could amplify to a large heterogeneity in size. By live imaging of C.

H3K9me selectively blocks transcription factor activity and ensures differentiated tissue integrity.

The developmental role of histone H3K9 methylation (H3K9me), which typifies heterochromatin, remains unclear. In Caenorhabditis elegans, loss of H3K9me leads to a highly divergent upregulation of genes with tissue and developmental-stage specificity. During development H3K9me is lost from differentiated cell type-specific genes and gained at genes expressed in earlier developmental stages or other tissues.

Gene expression oscillations in C. elegans underlie a new developmental clock.

During C. elegans larval development, thousands of genes, accounting for >20% of the transcriptome, exhibit oscillatory expression with large amplitudes. The time of peaking varies for different genes, but expression generally peaks once per larval stage, with both the oscillation period and larval stage duration varying in concert with temperature.

Protease-mediated processing of Argonaute proteins controls small RNA association.

Small RNA pathways defend the germlines of animals against selfish genetic elements, yet pathway activities need to be contained to prevent silencing of self genes. Here, we reveal a proteolytic mechanism that controls endogenous small interfering (22G) RNA activity in the Caenorhabditis elegans germline to protect genome integrity and maintain fertility. We find that DPF-3, a P-granule-localized N-terminal dipeptidase orthologous to mammalian dipeptidyl peptidase (DPP) 8/9, processes the unusually proline-rich N termini of WAGO-1 and WAGO-3 Argonaute (Ago) proteins.

Developmental function and state transitions of a gene expression oscillator in Caenorhabditis elegans.

Gene expression oscillators can structure biological events temporally and spatially. Different biological functions benefit from distinct oscillator properties. Thus, finite developmental processes rely on oscillators that start and stop at specific times, a poorly understood behavior.

Primary melanotic tumors of the nervous system: a consecutive case series.

Background And Purpose: Primary melanotic tumors of the nervous system (PMTNS) are thought to be an exceedingly rare group of tumors not captured by tumor registries. We aimed to determine relative incidence, clinical presentation, diagnostic findings, patient management, and outcome.

Methods: We retrospectively searched the database of the Section of Neuro-Oncology at the Yale Cancer Center for patients with primary or metastatic melanotic lesions of the nervous system.

Neuronal Calcium Sensor 1 is up-regulated in response to stress to promote cell survival and motility in cancer cells.

Changes in intracellular calcium (Ca ) signaling can modulate cellular machinery required for cancer progression. Neuronal calcium sensor 1 (NCS1) is a ubiquitously expressed Ca -binding protein that promotes tumor aggressiveness by enhancing cell survival and metastasis. However, the underlying mechanism by which NCS1 contributes to increased tumor aggressiveness has yet to be identified.

A branched heterochronic pathway directs juvenile-to-adult transition through two LIN-29 isoforms.

Robust organismal development relies on temporal coordination of disparate physiological processes. In , the heterochronic pathway controls a timely juvenile-to-adult (J/A) transition. This regulatory cascade of conserved proteins and small RNAs culminates in accumulation of the transcription factor LIN-29, which triggers coordinated execution of transition events.

The RNA hairpin binder TRIM71 modulates alternative splicing by repressing MBNL1.

TRIM71/LIN-41, a phylogenetically conserved regulator of development, controls stem cell fates. Mammalian TRIM71 exhibits both RNA-binding and protein ubiquitylation activities, but the functional contribution of either activity and relevant primary targets remain poorly understood. Here, we demonstrate that TRIM71 shapes the transcriptome of mouse embryonic stem cells (mESCs) predominantly through its RNA-binding activity.

coordinates the transition to adulthood through a single primary and four secondary targets.

The juvenile-to-adult (J/A) transition, or puberty, is a period of extensive changes of animal body morphology and function. The onset of puberty is genetically controlled, and the miRNA temporally regulates J/A transition events in nematodes and mammals. Here, we uncover the targets and downstream pathways through which controls male and female sexual organ morphogenesis and skin progenitor cell fates.

Timing mechanism of sexually dimorphic nervous system differentiation.

The molecular mechanisms that control the timing of sexual differentiation in the brain are poorly understood. We found that the timing of sexually dimorphic differentiation of postmitotic, sex-shared neurons in the nervous system of the male is controlled by the temporally regulated miRNA and its target , a translational regulator. acts through an isoform of a conserved Zn finger transcription factor, expressed in a subset of sex-shared neurons only in the male.

Neuronal calcium sensor 1 (NCS1) promotes motility and metastatic spread of breast cancer cells in vitro and in vivo.

Increased levels of the calcium-binding protein neuronal calcium sensor 1 (NCS1) predict an unfavorable patient outcome in several aggressive cancers, including breast and liver tumors. Previous studies suggest that NCS1 overexpression facilitates metastatic spread of these cancers. To investigate this hypothesis, we explored the effects of NCS1 overexpression on cell proliferation, survival, and migration patterns in vitro in 2- and 3-dimensional (2/3-D).

An interplay of miRNA abundance and target site architecture determines miRNA activity and specificity.

MicroRNAs often occur in families whose members share an identical 5' terminal 'seed' sequence. The seed is a major determinant of miRNA activity, and family members are thought to act redundantly on target mRNAs with perfect seed matches, i.e.

Evolutionary plasticity of the NHL domain underlies distinct solutions to RNA recognition.

RNA-binding proteins regulate all aspects of RNA metabolism. Their association with RNA is mediated by RNA-binding domains, of which many remain uncharacterized. A recently reported example is the NHL domain, found in prominent regulators of cellular plasticity like the C.

Two distinct transcription termination modes dictated by promoters.

Transcription termination determines the ends of transcriptional units and thereby ensures the integrity of the transcriptome and faithful gene regulation. Studies in yeast and human cells have identified the exoribonuclease XRN2 as a key termination factor for protein-coding genes. Here we performed a genome-wide investigation of RNA polymerase II (Pol II) transcription termination in XRN2-deficient and observed two distinct modes of termination.