PDGFRA is a conserved HAND2 effector during early cardiac development.

The basic helix-loop-helix transcription factor HAND2 has multiple roles during vertebrate organogenesis, including cardiogenesis. However, much remains to be uncovered about its mechanism of action. Here, we show the generation of several hand2 mutant alleles in zebrafish and demonstrate that dimerization-deficient mutants display the null phenotype but DNA-binding-deficient mutants do not.

Perspectives on Codebook: sequence specificity of uncharacterized human transcription factors.

We describe an effort ("Codebook") to determine the sequence specificity of 332 putative and largely uncharacterized human transcription factors (TFs), as well as 61 control TFs. Nearly 5,000 independent experiments across multiple and assays produced motifs for just over half of the putative TFs analyzed (177, or 53%), of which most are unique to a single TF. The data highlight the extensive contribution of transposable elements to TF evolution, both in and , and identify tens of thousands of conserved, base-level binding sites in the human genome.

Cross-platform DNA motif discovery and benchmarking to explore binding specificities of poorly studied human transcription factors.

A DNA sequence pattern, or "motif", is an essential representation of DNA-binding specificity of a transcription factor (TF). Any particular motif model has potential flaws due to shortcomings of the underlying experimental data and computational motif discovery algorithm. As a part of the Codebook/GRECO-BIT initiative, here we evaluated at large scale the cross-platform recognition performance of positional weight matrices (PWMs), which remain popular motif models in many practical applications.

GHT-SELEX demonstrates unexpectedly high intrinsic sequence specificity and complex DNA binding of many human transcription factors.

A long-standing challenge in human regulatory genomics is that transcription factor (TF) DNA-binding motifs are short and degenerate, while the genome is large. Motif scans therefore produce many false-positive binding site predictions. By surveying 179 TFs across 25 families using >1,500 cyclic selection experiments with fragmented, naked, and unmodified genomic DNA - a method we term GHT-SELEX (Genomic HT-SELEX) - we find that many human TFs possess much higher sequence specificity than anticipated.

Extensive binding of uncharacterized human transcription factors to genomic dark matter.

Most of the human genome is thought to be non-functional, and includes large segments often referred to as "dark matter" DNA. The genome also encodes hundreds of putative and poorly characterized transcription factors (TFs). We determined genomic binding locations of 166 uncharacterized human TFs in living cells.

Reconstructing the sequence specificities of RNA-binding proteins across eukaryotes.

RNA-binding proteins (RBPs) are key regulators of gene expression. Here, we introduce EuPRI (Eukaryotic Protein-RNA Interactions) - a freely available resource of RNA motifs for 34,736 RBPs from 690 eukaryotes. EuPRI includes binding data for 504 RBPs, including newly collected RNAcompete data for 174 RBPs, along with thousands of reconstructed motifs.

Fibroblast activation protein inhibitor PET/CT as an emerging diagnostic modality in interstitial lung disease and other fibrotic conditions.

Interstitial lung diseases (ILD) encompass a wide range of disorders characterized by alveolar inflammation and fibrotic tissue remodeling, marked by significant morbidity and mortality. Systemic sclerosis (SSc), among other connective tissue diseases, is a frequent cause of ILD. Assessment of pulmonary fibrosis is frequently constrained by the delayed manifestations of profibrotic activation of fibroblasts, which results in late macroscopic alterations detectable by standard imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) scans.

Distinct mechanisms regulate ventricular and atrial chamber wall formation.

Tissues undergo distinct morphogenetic processes to achieve similarly shaped structures. In the heart, cardiomyocytes in both the ventricle and atrium build internal structures for efficient contraction. Ventricular wall formation (trabeculation) is initiated by cardiomyocyte delamination.

Mechanical forces remodel the cardiac extracellular matrix during zebrafish development.

The cardiac extracellular matrix (cECM) is fundamental for organ morphogenesis and maturation, during which time it undergoes remodeling, yet little is known about whether mechanical forces generated by the heartbeat regulate this remodeling process. Using zebrafish as a model and focusing on stages when cardiac valves and trabeculae form, we found that altering cardiac contraction impairs cECM remodeling. Longitudinal volumetric quantifications in wild-type animals revealed region-specific dynamics: cECM volume decreases in the atrium but not in the ventricle or atrioventricular canal.

Control of cardiac contractions using Cre-lox and degron strategies in zebrafish.

Cardiac contractions and hemodynamic forces are essential for organ development and homeostasis. Control over cardiac contractions can be achieved pharmacologically or optogenetically. However, these approaches lack specificity or require direct access to the heart.

AI Evaluation of Imaging Factors in the Evolution of Stage-Treated Metastases Using Gamma Knife.

Background: The study investigated whether three deep-learning models, namely, the CNN_model (trained from scratch), the TL_model (transfer learning), and the FT_model (fine-tuning), could predict the early response of brain metastases (BM) to radiosurgery using a minimal pre-processing of the MRI images. The dataset consisted of 19 BM patients who underwent stereotactic-radiosurgery (SRS) within 3 months. The images used included axial fluid-attenuated inversion recovery (FLAIR) sequences and high-resolution contrast-enhanced T1-weighted (CE T1w) sequences from the tumor center.

Dispersoids in Al-Mg-Si Alloy AA 6086 Modified by Sc and Y.

The aluminium alloy AA 6086 attains the highest room temperature strength among Al-Mg-Si alloys. This work studies the effect of Sc and Y on the formation of dispersoids in this alloy, especially L1-type ones, which can increase its high-temperature strength. A comprehensive investigation was carried out using light microscopy (LM), scanning (SEM), and transmission (TEM) electron microscopy, energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and dilatometry to obtain the information regarding the mechanisms and kinetics of dispersoid formation, particularly during isothermal treatments.

RNA-binding proteins that lack canonical RNA-binding domains are rarely sequence-specific.

Thousands of RNA-binding proteins (RBPs) crosslink to cellular mRNA. Among these are numerous unconventional RBPs (ucRBPs)-proteins that associate with RNA but lack known RNA-binding domains (RBDs). The vast majority of ucRBPs have uncharacterized RNA-binding specificities.

Effect of Heat Treatment on Osteoblast Performance and Bactericidal Behavior of Ti6Al4V(ELI)-3at.%Cu Fabricated by Laser Powder Bed Fusion.

Cu addition to alloys for biomedical applications has been of great interest to reduce bacterial growth. In situ-alloyed Ti6Al4V(ELI)-3at.%Cu was successfully manufactured by laser powder bed fusion (L-PBF).

Reconstruction of full-length LINE-1 progenitors from ancestral genomes.

Sequences derived from the Long INterspersed Element-1 (L1) family of retrotransposons occupy at least 17% of the human genome, with 67 distinct subfamilies representing successive waves of expansion and extinction in mammalian lineages. L1s contribute extensively to gene regulation, but their molecular history is difficult to trace, because most are present only as truncated and highly mutated fossils. Consequently, L1 entries in current databases of repeat sequences are composed mainly of short diagnostic subsequences, rather than full functional progenitor sequences for each subfamily.

Thermoacidophilic Bioleaching of Industrial Metallic Steel Waste Product.

The continuous deposition of hazardous metalliferous wastes derived from industrial steelmaking processes will lead to space shortages while valuable raw metals are being depleted. Currently, these landfilled waste products pose a rich resource for microbial thermoacidophilic bioleaching processes. Six thermoacidophilic archaea (, and ) were cultivated on metal waste product derived from a steelmaking process to assess microbial proliferation and bioleaching potential.

Study of Nanoporosity Evolution during Dealloying AgAu and CoPd by Grazing-Incidence Small-Angle X-ray Scattering.

Electrochemical dealloying has become a standard technique to produce nanoporous network structures of various noble metals, exploiting the selective dissolution of one component from an alloy. While achieving nanoporosity during dealloying has been intensively studied for the prime example of nanoporous Au from a AgAu alloy, dealloying from other noble-metal alloys has been rarely investigated in the scientific literature. Here, we study the evolution of nanoporosity in the electrochemical dealloying process for both CoPd and AgAu alloys using a combination of grazing-incidence small-angle X-ray scattering (GISAXS), kinetic Monte Carlo (KMC) simulations, and scanning transmission electron microscopy (STEM).

High-Resolution Microstructure Characterization of Additively Manufactured X5CrNiCuNb17-4 Maraging Steel during Ex and In Situ Thermal Treatment.

Powder and selective laser melting (SLM) additively manufactured parts of X5CrNiCuNb17-4 maraging steel were systematically investigated by electron microscopy to understand the relationship between the properties of the powder grains and the microstructure of the printed parts. We prove that satellites, irregularities and superficial oxidation of powder particles can be transformed into an advantage through the formation of nanoscale (AlMnSiTiCr) oxides in the matrix during the printing process. The nano-oxides showed extensive stability in terms of size, spherical morphology, chemical composition and crystallographic disorder upon in situ heating in the scanning transmission electron microscope up to 950 °C.

Development of photo-crosslinkable collagen hydrogel building blocks for vascular tissue engineering applications: A superior alternative to methacrylated gelatin?

The present work targets the development of collagen-based hydrogel precursors, functionalized with photo-crosslinkable methacrylamide moieties (COL-MA), for vascular tissue engineering (vTE) applications. The developed materials were physico-chemically characterized in terms of crosslinking kinetics, degree of modification/conversion, swelling behavior, mechanical properties and in vitro cytocompatibility. The collagen derivatives were benchmarked to methacrylamide-modified gelatin (GEL-MA), due to its proven track record in the field of tissue engineering.

Assessment of the aortic wall histological changes with ageing.

Aim: The authors aimed to quantitatively assess the variation with age of three of the main components of the aortic wall, namely elastic fibers (FE) and collagen fibers [FC(COL)], and smooth muscle cells (SMCs).

Materials And Methods: Four aortic cross sections (base, cross, thoracic, abdominal) were collected during autopsy from 90 cases of all ages, processed using the classical histopathological (HP) technique (formalin fixation and paraffin embedding) and stained with Orcein and Goldner's trichrome. The obtained histological slides were transformed into virtual slides.

Surgical Treatment in a High-Risk Pulmonary Embolism: Case Report.

We present the case of a 35-year-old woman who had a high-risk pulmonary embolism (according to ESC risk stratification for pulmonary embolism) after she had undergone a Caesarion section. Postoperatively, she presented with acute left lower limb pain, swelling and erythema. A diagnosis was made of deep vein thrombosis (DVT) of the ilio-femoral and popliteal veins.

An In Situ Synchrotron Dilatometry and Atomistic Study of Martensite and Carbide Formation during Partitioning and Tempering.

Precipitation hardened and tempered martensitic-ferritic steels (TMFSs) are used in many areas of our daily lives as tools, components in power generation industries, or in the oil and gas (O&G) industry for creep and corrosion resistance. In addition to the metallurgical and forging processes, the unique properties of the materials in service are determined by the quality heat treatment (HT). By performing a quenching and partitioning HT during an in situ high energy synchrotron radiation experiment in a dilatometer, the evolution of retained austenite, martensite laths, dislocations, and carbides was characterized in detail.

Hsa-miR-125b Therapeutic Role in Colon Cancer Is Dependent on the Mutation Status of the TP53 Gene.

Colon cancer is the third most common cancer type worldwide and is highly dependent on DNA mutations that progressively appear and accumulate in the normal colon epithelium. Mutations in the gene appear in approximately half of these patients and have significant implications in disease progression and response to therapy. miR-125b-5p is a controversial microRNA with a dual role in cancer that has been reported to target specifically in colon adenocarcinomas.