Gene module reconstruction identifies cellular differentiation processes and the regulatory logic of specialized secretion in zebrafish.

During differentiation, cells become structurally and functionally specialized, but comprehensive views of the underlying remodeling processes are elusive. Here, we leverage single-cell RNA sequencing (scRNA-seq) developmental trajectories to reconstruct differentiation using two secretory tissues as models-the zebrafish notochord and hatching gland. First, we integrated expression and functional similarities to identify gene modules, revealing dozens of modules representing known and newly associated differentiation processes and their dynamics.

Germ cell progression through zebrafish spermatogenesis declines with age.

Vertebrate spermatogonial stem cells maintain sperm production over the lifetime of an animal, but fertility declines with age. Although morphological studies have informed our understanding of typical spermatogenesis, the molecular and cellular mechanisms underlying the maintenance and decline of spermatogenesis are not yet understood. We used single-cell RNA sequencing to generate a developmental atlas of the aging zebrafish testis.

Metal-free alkyne annulation enabling π-extension of boron-doped polycyclic aromatic hydrocarbons.

A C-H functionalizing annulation reaction of boron-doped polycyclic aromatic hydrocarbons (PAHs) with alkynes is described. This metal-free π-extension provides a new synthetic route to fusion atom B-doped polycyclic aromatic hydrocarbons (PAHs) that is demonstrated with the synthesis of a family of new, functionalized, structurally constrained 6a,15a-diborabenzo[]naphtho[2,1-]picenes. These annulation products exhibit deep LUMO energy levels, strong visible-range absorptions, and sterically accessible π-systems that can adopt herringbone or π-stacked solid-state structures based on choice of substituents.

Cell-type-specific mRNA transcription and degradation kinetics in zebrafish embryogenesis from metabolically labeled single-cell RNA-seq.

During embryonic development, pluripotent cells assume specialized identities by adopting particular gene expression profiles. However, systematically dissecting the relative contributions of mRNA transcription and degradation to shaping those profiles remains challenging, especially within embryos with diverse cellular identities. Here, we combine single-cell RNA-Seq and metabolic labeling to capture temporal cellular transcriptomes of zebrafish embryos where newly-transcribed (zygotic) and pre-existing (maternal) mRNA can be distinguished.

Triple -substitution reactions of B(CF) and [(CF)PF] with P(SiMe).

-Substitution reactions on CF rings of Lewis acids have been exploited to achieve triply substituted derivatives. The reaction of B(CF) with P(SiMe) ultimately affords the Lewis acid B(CFP(SiMe))1. This species binds Lewis bases affording the adducts LB(CFP(SiMe)) (L = MeCN 2, OPEt3, PMe4, PBu5) and reacts with LiMe to give the salt [Li][MeB(CFP(SiMe))]·3THF 6.

Diboraperylene Diborinic Acid Self-Assembly on Ag(111)-Kagome Flat Band Localized States Imaged by Scanning Tunneling Microscopy and Spectroscopy.

Replacement of sp-hybridized carbon in polycyclic aromatic hydrocarbons (PAHs) by boron affords electron-deficient π-scaffolds due to the vacant p-orbital of three-coordinate boron with the potential for pronounced electronic interactions with electron-rich metal surfaces. Using a diboraperylene diborinic acid derivative as precursor and a controlled on-surface non-covalent synthesis approach, we report on a self-assembled chiral supramolecular kagome network on an Ag(111) surface stabilized by intermolecular hydrogen-bonding interactions at low temperature. Scanning tunneling microscopy (STM) and spectroscopy (STS) reveal a flat band at ca.

Gene module reconstruction elucidates cellular differentiation processes and the regulatory logic of specialized secretion.

During differentiation, cells become structurally and functionally specialized, but comprehensive views of the underlying remodeling processes are elusive. Here, we leverage scRNA-seq developmental trajectories to reconstruct differentiation using two secretory tissues as a model system - the zebrafish notochord and hatching gland. First, we present an approach to integrate expression and functional similarities for gene module identification, revealing dozens of gene modules representing known and newly associated differentiation processes and their temporal ordering.

Single-cell analysis of shared signatures and transcriptional diversity during zebrafish development.

During development, animals generate distinct cell populations with specific identities, functions, and morphologies. We mapped transcriptionally distinct populations across 489,686 cells from 62 stages during wild-type zebrafish embryogenesis and early larval development (3-120 h post-fertilization). Using these data, we identified the limited catalog of gene expression programs reused across multiple tissues and their cell-type-specific adaptations.

Germ cells do not progress through spermatogenesis in the infertile zebrafish testis.

Vertebrate spermatogonial stem cells maintain sperm production over the lifetime of an animal but fertility declines with age. While morphological studies have greatly informed our understanding of typical spermatogenesis, the molecular and cellular mechanisms underlying spermatogenesis are not yet understood, particularly with respect to the onset of fertility. We used single-cell RNA sequencing to generate a developmental atlas of the zebrafish testis.

Single-cell temporal dynamics reveals the relative contributions of transcription and degradation to cell-type specific gene expression in zebrafish embryos.

During embryonic development, pluripotent cells assume specialized identities by adopting particular gene expression profiles. However, systematically dissecting the underlying regulation of mRNA transcription and degradation remains a challenge, especially within whole embryos with diverse cellular identities. Here, we collect temporal cellular transcriptomes of zebrafish embryos, and decompose them into their newly-transcribed (zygotic) and pre-existing (maternal) mRNA components by combining single-cell RNA-Seq and metabolic labeling.

Differentiation trajectories of the nervous system reveal transcriptional regulators of neuronal fate.

The small freshwater cnidarian polyp uses adult stem cells (interstitial stem cells) to continually replace neurons throughout its life. This feature, combined with the ability to image the entire nervous system (Badhiwala et al., 2021; Dupre & Yuste, 2017) and availability of gene knockdown techniques (Juliano, Reich, et al.

Single-cell analysis of shared signatures and transcriptional diversity during zebrafish development.

During development, animals generate distinct cell populations with specific identities, functions, and morphologies. We mapped transcriptionally distinct populations across 489,686 cells from 62 stages during wild-type zebrafish embryogenesis and early larval development (3-120 hours post-fertilization). Using these data, we identified the limited catalog of gene expression programs reused across multiple tissues and their cell-type-specific adaptations.

12b,24b-Diborahexabenzo[a,c,fg,l,n,qr]pentacene: A Low-LUMO Boron-Doped Polycyclic Aromatic Hydrocarbon.

Herein we devise and execute a new synthesis of a pristine boron-doped nanographene. Our target boron-doped nanographene was designed based on DFT calculations to possess a low LUMO energy level and a narrow band gap derived from its precise geometry and B-doping arrangement. Our synthesis of this target, a doubly B-doped hexabenzopentacene (B -HBP), employs six net C-H borylations of an alkene, comprising consecutive hydroboration/electrophilic borylation/dehydrogenation and BBr /AlCl /2,6-dichloropyridine-mediated C-H borylation steps.

Interventional Radiology Education for Improving Primary Care Provider Awareness.

To evaluate the effectiveness of a lecture series in increasing awareness and knowledge about common interventional radiology (IR) procedures amongst emergency medicine and internal medicine residents at a tertiary care academic medical center.A series of two 60-minute lectures was presented at both the Emergency and Internal Medicine weekly didactic conferences for the respective residency programs. The lectures covered the indications, contraindications, imaging, pre-procedure preparation, complications, and follow-up of common IR procedures, including both didactics as well as interactive question and answer segments.

Emergence of Neuronal Diversity during Vertebrate Brain Development.

Neurogenesis comprises many highly regulated processes including proliferation, differentiation, and maturation. However, the transcriptional landscapes underlying brain development are poorly characterized. We describe a developmental single-cell catalog of ∼220,000 zebrafish brain cells encompassing 12 stages from embryo to larva.

Reactions of carbene-stabilized borenium cations.

In this paper we probe the reactivity of the borenium cations [CH(NCHCH)(NCHPh)BH][B(CF)] 2 and [CH(NCHCH)B][B(CF)] 3. The reactions of 2 with cyclohexene or 3,3-dimethyl-1-butene gave the alkyl-aryl borenium salts [PhCH(CHN)CCHCHBR][B(CF)] (R = Cy 4, CHCHtBu 5) while the corresponding reactions with diphenylacetylene, 1-hexyne and 1-phenyl-1-propyne gave the aryl-alkenyl borenium cation salts [PhCH(CHN)CCHCHBC(R)C(H)R][B(CF)] (R = R = Ph 6, R = H, R = CH7, R = Me, R = Ph 8a, R = Ph, R = Me 8b). In contrast, the reaction of 2 with ethynyldiphenylphosphane or 2-vinylpyridine lead to the formation of the adducts, [PhCH(CHN)CCHCHB(H)P(Ph)CCH][B(CF)] 9, [PhCH(CHN)CCHCHB(H)NCHC(H)CH][B(CF)] 10, respectively, while the more bulky donor HC[double bond, length as m-dash]C(Ph)PMes gave 1,2-hydroboration of the phosphinoalkene affording [PhCH(CHN)CCHCHBCHCH(Ph)PMes][B(CF)] 11.

Single-Center Longitudinal Implementation of Lecture Series Based on the American College of Radiology Appropriateness Criteria for Emergency Medicine Provider Education.

Rationale And Objectives: The purpose of our study was to improve awareness and knowledge of the American College of Radiology Appropriateness Criteria (ACR-AC) among Emergency Medicine (EM) residents and to assess the long-term effectiveness of this ACR-AC lecture-based series.

Materials And Methods: Ten lectures-based on the ACR-AC were given to EM residents at an academic medical center. Four of these lectures were subsequently repeated in the subsequent academic year.

Biliary Endoscopy for Benign and Malignant Biliary Strictures.

Percutaneous endoscopy operated by interventional radiologists has the potential to become an effective tool to both help diagnose and treat benign and malignant biliary strictures. This is particularly true in cases where endoscopic retrograde cholangiopancreatography fails or is not feasible due to surgically-altered anatomy. Both preoperative clinical and technical procedural factors must be taken into consideration when pursuing percutaneous endoscopy.

A Highly Warped Heptagon-Containing sp Carbon Scaffold via Vinylnaphthyl π-Extension.

A new strategy is demonstrated for the synthesis of warped, negatively curved, all-sp -carbon π-scaffolds. Multifold C-C coupling reactions are used to transform a polyaromatic borinic acid into a saddle-shaped polyaromatic hydrocarbon (2) bearing two heptagonal rings. Notably, this Schwarzite substructure is synthesized in only two steps from an unfunctionalized alkene.

Stem cell differentiation trajectories in resolved at single-cell resolution.

The adult polyp continually renews all of its cells using three separate stem cell populations, but the genetic pathways enabling this homeostatic tissue maintenance are not well understood. We sequenced 24,985 single-cell transcriptomes and identified the molecular signatures of a broad spectrum of cell states, from stem cells to terminally differentiated cells. We constructed differentiation trajectories for each cell lineage and identified gene modules and putative regulators expressed along these trajectories, thus creating a comprehensive molecular map of all developmental lineages in the adult animal.

Tunable Low-LUMO Boron-Doped Polycyclic Aromatic Hydrocarbons by General One-Pot C-H Borylations.

Boron-doping has long been recognized as a promising LUMO energy-lowering modification of graphene and related polycyclic aromatic hydrocarbons (PAHs). Unfortunately, synthetic difficulties have been a significant bottleneck for the understanding, optimization, and application of precisely boron-doped PAHs for optoelectronic purposes. Herein, a facile one-pot hydroboration electrophilic borylation cascade/dehydrogenation approach from simple alkene precursors is coupled with postsynthetic B-substitution to give access to ten ambient-stable core- and periphery-tuned boron-doped PAHs.

Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis.

During embryogenesis, cells acquire distinct fates by transitioning through transcriptional states. To uncover these transcriptional trajectories during zebrafish embryogenesis, we sequenced 38,731 cells and developed URD, a simulated diffusion-based computational reconstruction method. URD identified the trajectories of 25 cell types through early somitogenesis, gene expression along them, and their spatial origin in the blastula.

Synthesis of a Doubly Boron-Doped Perylene through NHC-Borenium Hydroboration/C-H Borylation/Dehydrogenation.

Reaction of an N-heterocyclic carbene (NHC)-borenium ion with 9,10-distyrylanthracene forms four B-C bonds through two selective, tandem hydroboration-electrophilic C-H borylations to yield an isolable, crystallographically characterizable polycyclic diborenium ion as its [NTf ] salt (1). Dehydrogenation of 1 with TEMPO radical followed by acidic workup yields a 3,9-diboraperylene as its corresponding borinic acid (2). This sequence can be performed in one pot to allow the facile, metal-free conversion of an alkene into a small molecule containing a boron-doped graphene substructure.

Incidence and interventions for post-thrombotic syndrome.

Post-thrombotic syndrome (PTS) is a venous stress disorder that develops from long-term effects from a previous deep venous thrombosis (DVT). The morbidity associated with PTS may be significant and patients can present with edema, chronic pain, swelling, skin changes, and heaviness of the affected limb. PTS can eventually lead to a decreased quality of life and to a marked burden for the healthcare system.