Fission yeast essential nuclear pore protein Nup211 regulates the expression of genes involved in cytokinesis.

Nuclear pore proteins control nucleocytoplasmic transport; however, certain nucleoporins play regulatory roles in activities such as transcription and chromatin organization. The fission yeast basket nucleoporin Nup211 is implicated in mRNA export and is essential for cell viability. Nup211 preferentially associates with heterochromatin, however, it is unclear whether it plays a role in regulating transcription.

Transcriptome-scale RNA-targeting CRISPR screens reveal essential lncRNAs in human cells.

Mammalian genomes host a diverse array of RNA that includes protein-coding and noncoding transcripts. However, the functional roles of most long noncoding RNAs (lncRNAs) remain elusive. Using RNA-targeting CRISPR-Cas13 screens, we probed how the loss of ∼6,200 lncRNAs impacts cell fitness across five human cell lines and identified 778 lncRNAs with context-specific or broad essentiality.

De novo antibody discovery in human blood from full-length single B cell transcriptomics and matching haplotyped-resolved germline assemblies.

Immunoglobulin (IGH, IGK, IGL) loci in the human genome are highly polymorphic regions that encode the building blocks of the light and heavy chain IG proteins that dimerize to form antibodies. The processes of V(D)J recombination and somatic hypermutation in B cells are responsible for creating an enormous reservoir of highly specific antibodies capable of binding a vast array of possible antigens. However, the antibody repertoire is fundamentally limited by the set of variable (V), diversity (D), and joining (J) alleles present in the germline IG loci.

Precise date for the Laacher See eruption synchronizes the Younger Dryas.

The Laacher See eruption (LSE) in Germany ranks among Europe's largest volcanic events of the Upper Pleistocene. Although tephra deposits of the LSE represent an important isochron for the synchronization of proxy archives at the Late Glacial to Early Holocene transition, uncertainty in the age of the eruption has prevailed. Here we present dendrochronological and radiocarbon measurements of subfossil trees that were buried by pyroclastic deposits that firmly date the LSE to 13,006 ± 9 calibrated years before present (BP; taken as AD 1950), which is more than a century earlier than previously accepted.

Profiling the genetic determinants of chromatin accessibility with scalable single-cell CRISPR screens.

CRISPR screens have been used to connect genetic perturbations with changes in gene expression and phenotypes. Here we describe a CRISPR-based, single-cell combinatorial indexing assay for transposase-accessible chromatin (CRISPR-sciATAC) to link genetic perturbations to genome-wide chromatin accessibility in a large number of cells. In human myelogenous leukemia cells, we apply CRISPR-sciATAC to target 105 chromatin-related genes, generating chromatin accessibility data for ~30,000 single cells.

Securing timelines in the ancient Mediterranean using multiproxy annual tree-ring data.

Calendar-dated tree-ring sequences offer an unparalleled resource for high-resolution paleoenvironmental reconstruction. Where such records exist for a few limited geographic regions over the last 8,000 to 12,000 years, they have proved invaluable for creating precise and accurate timelines for past human and environmental interactions. To expand such records across new geographic territory or extend data for certain regions further backward in time, new applications must be developed to secure "floating" (not yet absolutely dated) tree-ring sequences, which cannot be assigned single-calendar year dates by standard dendrochronological techniques.

Subfossil trees suggest enhanced Mediterranean hydroclimate variability at the onset of the Younger Dryas.

Nearly 13,000 years ago, the warming trend into the Holocene was sharply interrupted by a reversal to near glacial conditions. Climatic causes and ecological consequences of the Younger Dryas (YD) have been extensively studied, however proxy archives from the Mediterranean basin capturing this period are scarce and do not provide annual resolution. Here, we report a hydroclimatic reconstruction from stable isotopes (δO, δC) in subfossil pines from southern France.

Contrasting Rates of LINE-1 Amplification among New World Primates of the Atelidae Family.

LINE-1 (L1) retrotransposons constitute the dominant category of transposons in mammalian genomes. L1 elements are active in the vast majority of mammals, and only a few cases of L1 extinction have been documented. The only possible case of extinction in primates was suggested for South American spider monkeys.

Contrasted patterns of evolution of the LINE-1 retrotransposon in perissodactyls: the history of a LINE-1 extinction.

Background: LINE-1 (L1) is the dominant autonomously replicating non-LTR retrotransposon in mammals. Although our knowledge of L1 evolution across the tree of life has considerably improved in recent years, what we know of L1 evolution in mammals is biased and comes mostly from studies in primates (mostly human) and rodents (mostly mouse). It is unclear if patterns of evolution that are shared between those two groups apply to other mammalian orders.

The Evolution of LINE-1 in Vertebrates.

The abundance and diversity of the LINE-1 (L1) retrotransposon differ greatly among vertebrates. Mammalian genomes contain hundreds of thousands L1s that have accumulated since the origin of mammals. A single group of very similar elements is active at a time in mammals, thus a single lineage of active families has evolved in this group.

Measuring (210) Pb by accelerator mass spectrometry: a study of isobaric interferences of (204,205,208) Pb and (210) Pb.

Rationale: The measurement of (210) Pb provides an assessment of the risk an individual faces of developing lung cancer as a result of their exposure to radon and radon decay products. Existing radiometric techniques are not sensitive enough to detect (210) Pb in many exposures. This report describes the further development of a method of measuring (210) Pb using Accelerator Mass Spectrometry (AMS).

Energy drink usage among university students in a Caribbean country: Patterns of use and adverse effects.

Objective: There has been little inquiry addressing whether or not concerns about adverse effects of energy drink usage are relevant in the Caribbean. This survey investigated energy drink usage and adverse consequences among tertiary level students in Trinidad and Tobago.

Methods: A cross-sectional survey of 1994 students from eight institutions was conducted using a de novo questionnaire based on findings from a focus group of students.

BxPC3 pancreatic cancer cells express a truncated Smad4 protein upon PI3K and mTOR inhibition.

Smad4 is a critical regulator of transforming growth factor (TGF)-β signaling and is defective in numerous human cancers. In total, 30% of pancreatic cancers harbor a homozygous deletion of Smad4. The human pancreatic cancer cell line, BxPC3, has been reported to be Smad4-null due to a homozygous deletion and has been widely used as a Smad4-null model.

Long-term analyses of innervation and neuromuscular integrity in the Trembler-J mouse model of Charcot-Marie-Tooth disease.

A large fraction of hereditary demyelinating neuropathies, classified as Charcot-Marie-Tooth disease type 1A, is associated with misexpression of peripheral myelin protein 22. In this study, we characterized morphologic and biochemical changes that occur with diseaseprogression in neuromuscular tissue of Trembler-J mice, a spontaneous rodent model of Charcot-Marie-Tooth disease type 1A. Using age-matched, 2- and 10-month-old, wild-type and Trembler-J mice, we observed neuromuscular deficits that progress from distal to proximal regions.

Suppression of AKT phosphorylation restores rapamycin-based synthetic lethality in SMAD4-defective pancreatic cancer cells.

mTOR has been implicated in survival signals for many human cancers. Rapamycin and TGF-β synergistically induce G1 cell-cycle arrest in several cell lines with intact TGF-β signaling pathway, which protects cells from the apoptotic effects of rapamycin during S-phase of the cell cycle. Thus, rapamycin is cytostatic in the presence of serum/TGF-β and cytotoxic in the absence of serum.

Revisiting the evolution of mouse LINE-1 in the genomic era.

Background: LINE-1 (L1) is the dominant category of transposable elements in placental mammals. L1 has significantly affected the size and structure of all mammalian genomes and understanding the nature of the interactions between L1 and its mammalian host remains a question of crucial importance in comparative genomics. For this reason, much attention has been dedicated to the evolution of L1.