Nuclear F-actin assembly on damaged chromatin is regulated by DYRK1A and Spir1 phosphorylation.

Nuclear actin-based movements support DNA double-strand break (DSB) repair. However, molecular determinants that promote filamentous actin (F-actin) formation on the damaged chromatin remain undefined. Here we describe the DYRK1A kinase as a nuclear activity that promotes local F-actin assembly to support DSB mobility and repair, accomplished in part by its targeting of actin nucleator spire homolog 1 (Spir1).

S-Adenosylmethionine (SAMe) as an adjuvant therapy for patients with depression: An updated systematic review and meta-analysis.

Background: Major depressive disorder (MDD) is an intractable disease requiring long-term treatment. S-adenosyl-L-methionine (SAMe), a natural substance, has antidepressant effects, but the exact effect remains unclear. This study examines the evidence concerning the efficacy of SAMe as a monotherapy or in combination with antidepressants.

Diversification of the Carbodicarbene Class by Embedding an Anionic Component in its Scaffold.

Carbodicarbene (CDC) has become an emerging ligand in many fields due to its strong σ-donating ability. View Article and Find Full Text PDF

Evaluation of the determinants for improved pluripotency induction and maintenance by engineered SOX17.

An engineered SOX17 variant with point mutations within its DNA binding domain termed SOX17FNV is a more potent pluripotency inducer than SOX2, yet the underlying mechanism remains unclear. Although wild-type SOX17 was incapable of inducing pluripotency, SOX17FNV outperformed SOX2 in mouse and human pluripotency reprogramming. In embryonic stem cells, SOX17FNV could replace SOX2 to maintain pluripotency despite considerable sequence differences and upregulated genes expressed in cleavage-stage embryos.

Binuclear Macrocyclic Silver(I) Complex of a Bis(carbone) Pincer Ligand: Synthesis and Application as a Carbone-Transfer Agent.

A facile synthesis of a binuclear Ag complex of a bis(carbone) ligand and its application as a carbone-transfer agent for the generation of other transition-metal complexes of Au (), Ni (), and Pd () is presented. Complex was synthesized through multiple synthetic routes under mild reaction conditions using the tetracationic [H][OTf·Cl] precursor salt, the dicationic [H][OTf] ylide salt, and the free ligand . The first two synthesis routes require no prior isolation of the air-, moisture-, and temperature-sensitive free ligand , thus affording complex with high yield and purity.

FACI is a novel clathrin adaptor protein 2-binding protein that facilitates low-density lipoprotein endocytosis.

Background: Cholesterol plays a vital role in multiple physiological processes. Cellular uptake of cholesterol is mediated primarily through endocytosis of low-density lipoprotein (LDL) receptor. New modifiers of this process remain to be characterized.

Effectiveness of Oil Pulling for Improving Oral Health: A Meta-Analysis.

The effect of oil pulling on oral health has not yet been fully demonstrated. Therefore, we performed a meta-analysis to investigate the effect of oil pulling on oral health. We searched PubMed, the Cochrane Library, and the EMBASE database, limiting the search to human patients and articles written in English and published before 31 July 2022.

A conserved Trp residue in HwBR contributes to its unique tolerance toward acidic environments.

Bacteriorhodopsin (BR) is a light-driven outward proton pump found mainly in halophilic archaea. A BR from an archaeon Haloquadratum walsbyi (HwBR) was found to pump protons under more acidic conditions compared with most known BR proteins. The atomic structural study on HwBR unveiled that a pair of hydrogen bonds between the BC and FG loop in its periplasmic region may be a factor in such improved pumping capability.

Pressure and stiffness sensing together regulate vascular smooth muscle cell phenotype switching.

Vascular smooth muscle cells (VSMCs) play a central role in the progression of atherosclerosis, where they switch from a contractile to a synthetic phenotype. Because of their role as risk factors for atherosclerosis, we sought here to systematically study the impact of matrix stiffness and (hemodynamic) pressure on VSMCs. Thereby, we find that pressure and stiffness individually affect the VSMC phenotype.

A Bis-(carbone) Pincer Ligand and Its Coordinative Behavior toward Multi-Metallic Configurations.

Carbones are divalent carbon(0) species that contain two lone pairs of electrons. Herein, we have prepared the first known stable and isolable free bis-(carbone) pincer framework with a well-defined solid-state structure. This bis-(carbone) ligand is an effective scaffold for forming monometallic (Ni and Pd) and trinuclear heterometallic complexes with Au-Pd-Au, Au-Ni-Au, and Cu-Ni-Cu configurations.

Bayesian spatiotemporal modeling on complex-valued fMRI signals via kernel convolutions.

We propose a model-based approach that combines Bayesian variable selection tools, a novel spatial kernel convolution structure, and autoregressive processes for detecting a subject's brain activation at the voxel level in complex-valued functional magnetic resonance imaging (CV-fMRI) data. A computationally efficient Markov chain Monte Carlo algorithm for posterior inference is developed by taking advantage of the dimension reduction of the kernel-based structure. The proposed spatiotemporal model leads to more accurate posterior probability activation maps and less false positives than alternative spatial approaches based on Gaussian process models, and other complex-valued models that do not incorporate spatial and/or temporal structure.

FACI Is a Novel CREB-H-Induced Protein That Inhibits Intestinal Lipid Absorption and Reverses Diet-Induced Obesity.

Background & Aims: CREB-H is a key liver-enriched transcription factor governing lipid metabolism. Additional targets of CREB-H remain to be identified and characterized. Here, we identified a novel fasting- and CREB-H-induced (FACI) protein that inhibits intestinal lipid absorption and alleviates diet-induced obesity in mice.

Bayesian inference for stationary points in Gaussian process regression models for event-related potentials analysis.

Stationary points embedded in the derivatives are often critical for a model to be interpretable and may be considered as key features of interest in many applications. We propose a semiparametric Bayesian model to efficiently infer the locations of stationary points of a nonparametric function, which also produces an estimate of the function. We use Gaussian processes as a flexible prior for the underlying function and impose derivative constraints to control the function's shape via conditioning.

Polypeptide organic radical batteries.

In only a few decades, lithium-ion batteries have revolutionized technologies, enabling the proliferation of portable devices and electric vehicles, with substantial benefits for society. However, the rapid growth in technology has highlighted the ethical and environmental challenges of mining lithium, cobalt and other mineral ore resources, and the issues associated with the safe usage and non-hazardous disposal of batteries. Only a small fraction of lithium-ion batteries are recycled, further exacerbating global material supply of strategic elements.

PI(3,4)P-mediated membrane tubulation promotes integrin trafficking and invasive cell migration.

Invadopodia are integrin-mediated adhesions with abundant PI(3,4)P However, the functional role of PI(3,4)P in adhesion signaling remains unclear. Here, we find that the PI(3,4)P biogenesis regulates the integrin endocytosis at invadopodia. PI(3,4)P is locally produced by PIK3CA and SHIP2 and is concentrated at the trailing edge of the invadopodium arc.

A DYRK1B-dependent pathway suppresses rDNA transcription in response to DNA damage.

DNA double-strand breaks (DSBs) at ribosomal gene loci trigger inhibition of ribosomal DNA (rDNA) transcription and extensive nucleolar reorganization, including the formation of nucleolar caps where rDNA DSBs engage with canonical DSB signaling and repair factors. While these nucleolar responses underlie maintenance of rDNA stability, the molecular components that drive each of these events remain to be defined. Here we report that full suppression of rRNA synthesis requires the DYRK1B kinase, a nucleolar DSB response that can be uncoupled from ATM-mediated DSB signaling events at the nucleolar periphery.

Redox Communication between Two Diarylamido/Bis(phosphine) (PNP)M Moieties Bridged by Ynediyl Linkers (M = Ni, Pd, Pt).

A series of binuclear homo- and heterobimetallic complexes of the general type (PNP)M-[linker]-M(PNP) have been prepared (M = Ni, Pd, Pt; PNP = a diarylamido/bis(phosphine) pincer ligand; -[linker]- = -C≡C-, -C≡CC≡C-, -C≡CCHC≡C-). Each (PNP)M site can be oxidized by one electron, and this work reports the investigation of the mixed-valence behavior in terms of the communication between the two redox sites and the degree of the delocalization in the monooxidized cation. The compounds were evaluated using cyclic voltammetry, UV-vis-NIR and EPR spectroscopy, X-ray crystallography, and DFT calculations.

Screen identifies DYRK1B network as mediator of transcription repression on damaged chromatin.

DNA double-strand breaks (DSBs) trigger transient pausing of nearby transcription, an emerging ATM-dependent response that suppresses chromosomal instability. We screened a chemical library designed to target the human kinome for new activities that mediate gene silencing on DSB-flanking chromatin, and have uncovered the DYRK1B kinase as an early respondent to DNA damage. We showed that DYRK1B is swiftly and transiently recruited to laser-microirradiated sites, and that genetic inactivation of DYRK1B or its kinase activity attenuated DSB-induced gene silencing and led to compromised DNA repair.

Abl-mediated PI3K activation regulates macrophage podosome formation.

Podosomes play crucial roles in macrophage adhesion and migration. Wiskott-Aldrich syndrome protein (WASP; also known as WAS)-mediated actin polymerization is one of the key events initiating podosome formation. Nevertheless, membrane signals to trigger WASP activation at macrophage podosomes remain unclear.

Podosome formation promotes plasma membrane invagination and integrin-β3 endocytosis on a viscous RGD-membrane.

Integrin receptors orchestrate cell adhesion and cytoskeletal reorganization. The endocytic mechanism of integrin-β3 receptor at the podosome remains unclear. Using viscous RGD-membrane as the model system, here we show that the formation of podosome-like adhesion promotes Dab2/clathrin-mediated endocytosis of integrin-β3.

Tail domains of myosin-1e regulate phosphatidylinositol signaling and F-actin polymerization at the ventral layer of podosomes.

During podosome formation, distinct phosphatidylinositol 3,4,5-trisphosphate lipid (PI(3,4,5)P3) production and F-actin polymerization take place at integrin-mediated adhesions. Membrane-associated actin regulation factors, such as myosin-1, serve as key molecules to link phosphatidylinositol signals to podosome assembly. Here, we report that long-tailed myosin-1e (Myo1e) is enriched at the ventral layer of the podosome core in a PI(3,4,5)P3-dependent manner.

Nucleolar residence of the seckel syndrome protein TRAIP is coupled to ribosomal DNA transcription.

The RING finger protein TRAIP protects genome integrity and its mutation causes Seckel syndrome. TRAIP encodes a nucleolar protein that migrates to UV-induced DNA lesions via a direct interaction with the DNA replication clamp PCNA. Thus far, mechanistically how UV mobilizes TRAIP from the nucleoli remains unknown.

RNF169 limits 53BP1 deposition at DSBs to stimulate single-strand annealing repair.

Unrestrained 53BP1 activity at DNA double-strand breaks (DSBs) hampers DNA end resection and upsets DSB repair pathway choice. RNF169 acts as a molecular rheostat to limit 53BP1 deposition at DSBs, but how this fine balance translates to DSB repair control remains undefined. In striking contrast to 53BP1, ChIP analyses of ASI-induced DSBs unveiled that RNF169 exhibits robust accumulation at DNA end-proximal regions and preferentially targets resected, RPA-bound DSBs.