Linking Phosphoinositides to Proteins: A Novel Signaling PIPeline.

Phosphoinositide (PIP) signaling plays pivotal roles in myriad biological processes and is altered in many diseases including cancer. Canonical PIP signaling involves membrane-associated PIP lipid second messengers that modulate protein recruitment and activity at membrane focal points. In the nucleus, PIP signaling operates separately from membranous compartments defining the paradigm of non-canonical PIP signaling.

Peptain-1 blocks ischemia/reperfusion-induced retinal capillary degeneration in mice.

Introduction: Neurovascular degeneration results in vascular dysfunction, leakage, ischemia, and structural changes that can lead to significant visual impairment. We previously showed the protective effects of peptain-1, a 20 amino acid peptide derived from the αB-crystallin core domain, on retinal ganglion cells in two animal models of glaucoma. Here, we evaluated the ability of peptain-1 to block apoptosis of human retinal endothelial cells (HRECs) and retinal capillary degeneration in mice subjected to retinal ischemia/reperfusion (I/R) injury.

Aryl Hydrocarbon Receptor Knockout Accelerates PanIN Formation and Fibro-Inflammation in a Mutant Kras -Driven Pancreatic Cancer Model.

Objectives: The pathogenesis of pancreas cancer (PDAC) remains poorly understood, hindering efforts to develop a more effective therapy for PDAC. Recent discoveries show the aryl hydrocarbon receptor (AHR) plays a crucial role in the development of several cancers and can be targeted for therapeutic effect. However, its involvement in the pathogenesis of PDAC remains unclear.

The extremophilic Andean isolate Acinetobacter sp. Ver3 expresses two ferredoxin-NADP reductase isoforms with different catalytic properties.

Ferredoxin/flavodoxin-NADPH reductases (FPRs) catalyze the reversible electron transfer between NADPH and ferredoxin/flavodoxin. The Acinetobacter sp. Ver3 isolated from high-altitude Andean lakes contains two isoenzymes, FPR1 and FPR2.

Introduction of a terminal electron sink in chloroplasts decreases leaf cell expansion associated with higher proteasome activity and lower endoreduplication.

Foliar development involves successive phases of cell proliferation and expansion that determine the final leaf size, and is characterized by an early burst of reactive oxygen species generated in the photosynthetic electron transport chain (PETC). Introduction of the alternative PETC acceptor flavodoxin in tobacco chloroplasts led to a reduction in leaf size associated to lower cell expansion, without affecting cell number per leaf. Proteomic analysis showed that the biogenesis of the PETC proceeded stepwise in wild-type leaves, with accumulation of light-harvesting proteins preceding that of electron transport components, which might explain the increased energy and electron transfer to oxygen and reactive oxygen species build-up at this stage.

Environmental pollutants and phosphoinositide signaling in autoimmunity.

Environmental pollution stands as one of the most critical challenges affecting human health, with an estimated mortality rate linked to pollution-induced non-communicable diseases projected to range from 20% to 25%. These pollutants not only disrupt immune responses but can also trigger immunotoxicity. Phosphoinositide signaling, a pivotal regulator of immune responses, plays a central role in the development of autoimmune diseases and exhibits high sensitivity to environmental stressors.

Heme biosynthesis regulates BCAA catabolism and thermogenesis in brown adipose tissue.

With age, people tend to accumulate body fat and reduce energy expenditure . Brown (BAT) and beige adipose tissue dissipate heat and increase energy expenditure via the activity of the uncoupling protein UCP1 and other thermogenic futile cycles . The activity of brown and beige depots inversely correlates with BMI and age , suggesting that promoting thermogenesis may be an effective approach for combating age-related metabolic disease .

Regulation of NRF2 by Phosphoinositides and Small Heat Shock Proteins.

Unlabelled: Reactive oxygen species (ROS) are generated by aerobic metabolism, and their deleterious effects are buffered by the cellular antioxidant response, which prevents oxidative stress. The nuclear factor erythroid 2-related factor 2 (NRF2) is a master transcriptional regulator of the antioxidant response. Basal levels of NRF2 are kept low by ubiquitin-dependent degradation of NRF2 by E3 ligases, including the Kelch-like ECH-associated protein 1 (KEAP1).

Comparison of inpatient psychiatric medication management in gender diverse youth with cisgender peers.

Introduction: The primary objective was to determine if gender diverse (GD) youth receive different psychotropic prescribing compared with cisgender (CG) peers with the same diagnosis. Secondary objectives include evaluation of readmission rates and the effect of gender-affirming hormone therapy (GAHT) on psychiatric outcomes in transgender (TG) patients.

Methods: A total of 255 GD youth patients were retrospectively matched to CG controls based on age, primary discharge diagnosis, and year of admission.

NERNST: a genetically-encoded ratiometric non-destructive sensing tool to estimate NADP(H) redox status in bacterial, plant and animal systems.

NADP(H) is a central metabolic hub providing reducing equivalents to multiple biosynthetic, regulatory and antioxidative pathways in all living organisms. While biosensors are available to determine NADP or NADPH levels in vivo, no probe exists to estimate the NADP(H) redox status, a determinant of the cell energy availability. We describe herein the design and characterization of a genetically-encoded ratiometric biosensor, termed NERNST, able to interact with NADP(H) and estimate E.

Lipid transfer proteins and a PI 4-kinase initiate nuclear phosphoinositide signaling.

Unlabelled: Phosphoinositide (PIP ) messengers are present in non-membranous regions of nuclei, where they are assembled into a phosphatidylinositol (PI) 3-kinase (PI3K)/Akt pathway that is distinct from the cytosolic membrane-localized pathway. In the nuclear pathway, PI kinases/phosphatases bind the p53 tumor suppressor protein (wild-type and mutant) to generate p53-PIP complexes that regulate Akt activation. However, this pathway is dependent on poorly characterized nuclear PIP pools.

Porcine fungal mock community analyses: Implications for mycobiome investigations.

Introduction: The gut microbiome is an integral partner in host health and plays a role in immune development, altered nutrition, and pathogen prevention. The mycobiome (fungal microbiome) is considered part of the rare biosphere but is still a critical component in health. Next generation sequencing has improved our understanding of fungi in the gut, but methodological challenges remain.

Aryl hydrocarbon receptor knockout accelerates PanIN formation and fibro-inflammation in a mutant -driven pancreatic cancer model.

Objectives: The pathogenesis of pancreas cancer (PDAC) remains poorly understood, hindering efforts to develop a more effective therapy for PDAC. Recent discoveries show the aryl hydrocarbon receptor (AHR) plays a crucial role in the pathogenesis of several cancers, and can be targeted for therapeutic effect. However, its involvement in PDAC remains unclear.

COVID-19 and risk assessment room for public health in four Colombian crossborder territories.

Introduction: Public health risk management in Colombia is led by the Instituto Nacional de Salud. In the face of the COVID-19 emergency, response actions centered on the implementation of risk analysis rooms and the strengthening of surveillance at points of entry into the country. Objective: To analyze the implementation and maintenance phases of the COVID-19 risk analysis rooms in four border departments of Colombia.

Ultrasonography and X-ray micro-computed tomography characterization of the effects caused by carrageenin in the muscle of gilthead seabream (Sparus aurata).

The current work aimed to carry out an in vivo study of the λ-carrageenin-induced inflammation in the skin of gilthead seabream (Sparus aurata). The fish were injected intramuscularly with phosphate-buffered saline (PBS, as control) or λ-carrageenin (1% in PBS), and the injection zone was evaluated by real-time ultrasonography (Vevo Lab, VisualSonics) at 1.5, 3, 6, 12, and 24 h post-injection (p.

The chloroplast redox-responsive transcriptome of solanaceous plants reveals significant nuclear gene regulatory motifs associated to stress acclimation.

Transcriptomes of solanaceous plants expressing a plastid-targeted antioxidant protein were analysed to identify chloroplast redox networks modulating the expression of nuclear genes associated with stress acclimation. Plastid functions depend on the coordinated expression of nuclear genes, many of them associated to developmental and stress response pathways. Plastid-generated signals mediate this coordination via retrograde signaling, which includes sensing of chloroplast redox state and levels of reactive oxygen species (ROS), although it remains a poorly understood process.

Holistic idealization: An artifactual standpoint.

Idealization is commonly understood as distortion: representing things differently than how they actually are. In this paper, we outline an alternative artifactual approach that does not make misrepresentation central for the analysis of idealization. We examine the contrast between the Hodgkin-Huxley (1952a, b, c) and the Heimburg-Jackson (2005, 2006) models of the nerve impulse from the artifactual perspective, and argue that, since the two models draw upon different epistemic resources and research programs, it is often difficult to tell which features of a system the central assumptions involved are supposed to distort.

Engineering Climate-Change-Resilient Crops: New Tools and Approaches.

Environmental adversities, particularly drought and nutrient limitation, are among the major causes of crop losses worldwide. Due to the rapid increase of the world's population, there is an urgent need to combine knowledge of plant science with innovative applications in agriculture to protect plant growth and thus enhance crop yield. In recent decades, engineering strategies have been successfully developed with the aim to improve growth and stress tolerance in plants.

Safety and efficacy of N-acetylmannosamine (ManNAc) in patients with GNE myopathy: an open-label phase 2 study.

Purpose: To evaluate the safety and efficacy of N-acetylmannosamine (ManNAc) in GNE myopathy, a genetic muscle disease caused by deficiency of the rate-limiting enzyme in N-acetylneuraminic acid (Neu5Ac) biosynthesis.

Methods: We conducted an open-label, phase 2, single-center (NIH, USA) study to evaluate oral ManNAc in 12 patients with GNE myopathy (ClinicalTrials.gov NCT02346461).