RACK1 MARylation regulates translation and stress granules in ovarian cancer cells.

Mono(ADP-ribosyl)ation (MARylation) is emerging as a critical regulator of ribosome function and translation. Herein, we demonstrate that RACK1, an integral component of the ribosome, is MARylated by the mono(ADP-ribosyl) transferase (MART) PARP14 in ovarian cancer cells. MARylation of RACK1 is required for stress granule formation and promotes the colocalization of RACK1 in stress granules with G3BP1, eIF3η, and 40S ribosomal proteins.

Nocturnal camouflage through background matching against moonlight.

Camouflage is often considered a daytime phenomenon based on light and shade. Nocturnal camouflage can also occur, but its mechanistic basis remains unclear. Here, we analyze the conditions for background matching (BM) of avian predators against the night sky.

An SH3-binding allosteric modulator stabilizes the global conformation of the AML-associated Src-family kinase, Hck.

While ATP-site inhibitors for protein-tyrosine kinases are often effective drugs, their clinical utility can be limited by off-target activity and acquired resistance mutations due to the conserved nature of the ATP-binding site. However, combining ATP-site and allosteric kinase inhibitors can overcome these shortcomings in a double-drugging framework. Here we explored the allosteric effects of two pyrimidine diamines, PDA1 and PDA2, on the conformational dynamics and activity of the Src-family tyrosine kinase Hck, a promising drug target for acute myeloid leukemia.

Omega-3 supplementation attenuates doxorubicin-induced cardiotoxicity but is not related to the ceramide pathway.

Cardiotoxicity is the serious side effect of doxorubicin treatment. Ceramides are formed from the degradation of sphingolipids in cell membranes and play an important role in signaling and modulating biological processes. There is evidence that omega-3 fatty acid administration can act on this pathway.

The Composition of the HDL Particle and Its Capacity to Remove Cellular Cholesterol Are Associated with a Reduced Risk of Developing Active Inflammatory Rheumatoid Arthritis.

In rheumatoid arthritis (RA), the risk of cardiovascular death is 50% higher compared to the general population. This increased risk is partly due to the systemic inflammation characteristic of RA and changes in the lipoprotein profiles. This study investigated plasma lipid levels, lipid ratios, and the composition and functionality of high-density lipoprotein (HDL) in control individuals and RA subjects based on the disease's inflammatory score (DAS28).

Cutoff Values of Aldosterone and the Aldosterone-Renin Ratio for Predicting Primary Aldosteronism in Patients with Resistant Hypertension: A Real-Life Study.

Primary aldosteronism (PA) is commonly associated with resistant hypertension. Biochemical tests can be clinically useful in the screening and diagnosis of primary aldosteronism. This study aimed to identify the cutoff values of aldosterone levels (A) and the aldosterone-renin ratio (ARR) for an accurate prediction of PA in patients with apparent resistant hypertension in a real-life scenario.

MHC Class II Supertypes Affect Survival and Lifetime Reproductive Success in a Migratory Songbird.

The major histocompatibility complex (MHC) plays a critical role in the immune response against pathogens. Its high polymorphism is thought to be mainly the consequence of host-pathogen co-evolution, but elucidating the mechanism(s) driving MHC evolution remains challenging for natural populations. We investigated the diversity of MHC class II genes in a wild population of pied flycatchers Ficedula hypoleuca and tested its associations with two key components of individual fitness: lifetime reproductive success and survival.

In-Center Hemodialysis Experiences Among Latinx Adults: A Qualitative Study.

Rationale & Objective: Latinx individuals are more likely to start and remain receiving in-center hemodialysis, over home dialysis, than non-Latinx White individuals. The objective of our study was to understand the drivers of sustained in-center dialysis and deterrents of switching to home dialysis use for Latinx individuals receiving in-center dialysis.

Study Design: This qualitative study used semistructured one-on-one interviews.

Oxidative Stress in the Murine Model of Extraparenchymal Neurocysticercosis.

Oxidative stress is associated with several infectious diseases, as well as the severity of inflammatory reactions. The control of inflammation during parasite destruction is a target of neurocysticercosis treatment, as inflammation is strongly related to symptom severity. In this study, we investigated the presence of malondialdehyde and protein carbonyl, two by-products of reactive oxygen species (ROS), in an experimental model of extraparenchymal neurocysticercosis.

Relaxin Modulates the Genomic Actions and Biological Effects of Estrogen in the Myometrium.

Estradiol (E2) and relaxin (Rln) are steroid and polypeptide hormones, respectively, with important roles in the female reproductive tract, including myometrium. Some actions of Rln, which are mediated by its membrane receptor RXFP1, require or are augmented by E2 signaling through its cognate nuclear steroid receptor, estrogen receptor alpha (ERα). In contrast, other actions of Rln act in opposition to the effects of E2.

RBN-2397, a PARP7 Inhibitor, Synergizes with Paclitaxel to Inhibit Proliferation and Migration of Ovarian Cancer Cells.

Objectives: Mono(ADP-ribosyl)ation (MARylation), a post translational modification of proteins, is emerging as an important regulator of the biology of cancer cells. PARP7 (TiPARP), a mono (ADP-ribosyl) transferase (MART), MARylates its substrate α-tubulin in ovarian cancer cells, promoting destabilization of microtubules, cell growth, and migration. Recent development of RBN-2397, a potent inhibitor that selectively acts on PARP7, has provided a new tool for exploring the role of PARP7 catalytic activity in biological processes.

Adapting the Baseline Resilience Indicators for Communities (BRIC) Framework for England: Development of a Community Resilience Index.

Community resilience results from complex interactions between people, places, and environments. Measuring community resilience aligns with policy objectives to enhance resilience to adverse events and address spatial disparities. The Baseline Resilience Indicators for Communities (BRIC) is a composite index used to measure resilience.

Protein Hydrolysates from Salmon Heads and Cape Hake By-Products: Comparing Enzymatic Method with Subcritical Water Extraction on Bioactivity Properties.

Fish by-products can be converted into high-value-added products like fish protein hydrolysates (FPHs), which have high nutritional value and are rich in bioactive peptides with health benefits. This study aims to characterise FPHs derived from salmon heads (HPSs) and Cape hake trimmings (HPHs) using Alcalase for enzymatic hydrolysis and Subcritical Water Hydrolysis (SWH) as an alternative method. All hydrolysates demonstrated high protein content (70.

Development and characterization of recombinant ADP-ribose binding reagents that allow simultaneous detection of mono and poly ADP-ribose.

ADP-ribosylation (ADPRylation) is a post-translational modification (PTM) of proteins mediated by the activity of a variety of ADP-ribosyltransferase (ART) enzymes, such as the Poly (ADP-ribose) Polymerase (PARP) family of proteins. This PTM is diverse in both form and biological functions, which makes it a highly interesting modification, but difficult to study due to limitations in reagents available to detect the diversity of ADPRylation. Recently we developed a set of recombinant antibody-like ADP-ribose (ADPR) binding proteins using naturally occurring ADPR binding domains (ARBDs), including macrodomains and WWE domains, functionalized by fusion to the constant "Fc" region of rabbit immunoglobulin.

Environmental conditions influence host-parasite interactions and host fitness in a migratory passerine.

The study of host-parasite co-evolution is a central topic in evolutionary ecology. However, research is still fragmented and the extent to which parasites influence host life history is debated. One reason for this incomplete picture is the frequent omission of environmental conditions in studies analyzing host-parasite dynamics, which may influence the exposure to or effects of parasitism.

Design, Synthesis, and Structure-Activity Relationships of Novel Peptide Derivatives of the Severe Acute Respiratory Syndrome-Coronavirus-2 Spike-Protein that Potently Inhibit Nicotinic Acetylcholine Receptors.

The spike-protein of SARS-CoV-2 has a distinctive amino-acid sequence (RRARS) that forms a cleavage site for the enzyme furin. Strikingly, the structure of the spike-protein loop containing the furin cleavage site bears substantial similarity to neurotoxin peptides found in the venoms of certain snakes and marine cone snails. Leveraging this relationship, we designed and synthesized disulfide-constrained peptides with amino-acid sequences corresponding to the furin cleavage-sites of wild-type (B.

Development and Characterization of Recombinant ADP-Ribose Binding Reagents that Allow Simultaneous Detection of Mono and Poly ADP-Ribose.

ADP-ribosylation (ADPRylation) is a post-translational modification (PTM) of proteins mediated by the activity of a variety of ADP-ribosyltransferase (ART) enzymes, such as the Poly (ADP-ribose) Polymerase (PARP) family of proteins. This PTM is diverse in both form and biological functions, which makes it a highly interesting modification, but difficult to study due to limitations in reagents available to detect the diversity of ADP-ribosylation. Recently we developed a set of recombinant antibody-like ADP-ribose binding proteins, using naturally occurring ADPR binding domains (ARBDs) that include macrodomains and WWE domains, that have been functionalized by fusion to the constant "Fc" region of rabbit immunoglobulin.

The association between family dynamics and Positive Youth Development in secondary education students.

Introduction: The Positive Youth Development (PYD) framework is a strengths-based approach to adolescence that states that adolescents will thrive if nurtured by the right developmental assets. The family is one of the most important developmental assets, but studies about the relationship between family dynamics and the overall PYD of adolescents are scarce.

Objective: The present study aims to examine the associations between five family dynamics indicators and PYD, while taking into account the role of gender.

The nightjar and the ant: Intercontinental migration reveals a cryptic interaction.

Birds and ants co-occur in most terrestrial ecosystems and engage in a range of interactions. Competition, mutualism and predation are prominent examples of these interactions, but there are possibly many others that remain to be identified and characterized. This study provides quantitative estimates of the frequency of toe amputations resulting from ant bites in a population of migratory red-necked nightjars () monitored for 15 years (2009-2023) in S Spain, and identifies the attacker(s) based on taxonomic analyses of ant-mandible remains found on injured toes.

Nucleolar Localization of the RNA Helicase DDX21 Predicts Survival Outcomes in Gynecologic Cancers.

Unlabelled: Cancer cells with DNA repair defects (e.g., BRCA1/2 mutant cells) are vulnerable to PARP inhibitors (PARPi) due to induction of synthetic lethality.

A Targetable Self-association Surface of the Huntingtin exon1 Helical Tetramer Required for Assembly of Amyloid Pre-nucleation Oligomers.

Polyglutamine (polyQ) sequences undergo repeat-length dependent formation of disease-associated, amyloid-like cross-β core structures with kinetics and aggregate morphologies often influenced by the flanking sequences. In Huntington's disease (HD), the htt segment on the polyQ's N-terminal flank enhances aggregation rates by changing amyloid nucleation from a classical homogeneous mechanism to a two-step process requiring an ɑ-helix-rich oligomeric intermediate. A folded, helix-rich htt tetrameric structure suggested to be this critical intermediate was recently reported.

Novel FOXM1 inhibitor STL001 sensitizes human cancers to a broad-spectrum of cancer therapies.

Forkhead box protein M1 (FOXM1) is often overexpressed in human cancers and strongly associated with therapy resistance and less good patient survival. The chemotherapy options for patients with the most aggressive types of solid cancers remain very limited because of the acquired drug resistance, making the therapy less effective. NPM1 mutation through the inactivation of FOXM1 via FOXM1 relocalization to the cytoplasm confers more favorable treatment outcomes for AML patients, confirming FOXM1 as a crucial target to overcome drug resistance.

Time Savings and Safety of EMS Administration of Antibiotics for Open Fractures.

Introduction: Early administration of antibiotics for open fractures reduces serious bone and soft tissue infections. The effectiveness of antibiotics in reducing these infections is time-dependent, with various surgical associations recommending administration within one hour of injury, or within one hour of patient arrival to the emergency department (ED). The extent to which prehospital antibiotic administration in these situations might reduce the time to treatment has not been previously reported.