Enhancing quality and yield of recombinant secretory IgA antibodies in Nicotiana benthamiana by endoplasmic reticulum engineering.

The production of complex multimeric secretory immunoglobulins (SIgA) in Nicotiana benthamiana leaves is challenging, with significant reductions in complete protein assembly and consequently yield, being the most important difficulties. Expanding the physical dimensions of the ER to mimic professional antibody-secreting cells can help to increase yields and promote protein folding and assembly. Here, we expanded the ER in N.

SUMO2 rescues neuronal and glial cells from the toxicity of P301L Tau mutant.

Introduction: Abnormal intracellular accumulation of Tau aggregates is a hallmark of Alzheimer's disease (AD) and other Tauopathies, such as Frontotemporal dementia (FTD). Tau deposits primarily affect neurons, but evidence indicates that glial cells may also be affected and contribute distinctively to disease progression. Cells can respond to toxic insults by orchestrating global changes in posttranslational modifications of their proteome.

Emissions of HFC-23 do not reflect commitments made under the Kigali Amendment.

HFC-23 (trifluoromethane) is a potent greenhouse gas released to the atmosphere primarily as a by-product of HCFC-22 (chlorodifluoromethane) synthesis. Since 2020, the Kigali Amendment to the Montreal Protocol has required Parties to destroy their HFC-23 emissions to the extent possible. Here, we present updated HFC-23 emissions estimated from atmospheric observations.

TNIK: A redox sensor in endothelial cell permeability.

Dysregulation of endothelial barrier integrity can lead to vascular leak and potentially fatal oedema. TNF-α controls endothelial permeability during inflammation and requires the actin organizing Ezrin-Radixin-Moesin (ERM) proteins. We identified TRAF2 and NCK-interacting kinase (TNIK) as a kinase directly phosphorylating and activating ERM, specifically at the plasma membrane of primary human endothelial cells.

Carotenoid composition and sequestration in cassava (Manihot esculentum Crantz) roots.

Cassava (Manihot esculentum Crantz) is a staple food source for many developing countries. Its edible roots are high in starch but lack micronutrients such as β-carotene. In the present study, analysis of pedigree breeding populations has led to the identification of cassava accessions with enhanced β-carotene contents up to 40 μg/g DW.

Unexplained high and persistent methyl bromide emissions in China.

Methyl bromide (CHBr) is an important ozone-depleting substance whose use is regulated under the Montreal Protocol. Quantifying emissions on the national scale is required to assess compliance with the Montreal Protocol and thereby ensure the timely recovery of the ozone layer. However, the spatial-temporal patterns of China's national CHBr emissions remain unclear.

Maximizing saffron apocarotenoid production in varied tomato fruit carotenoid contexts.

Saffron spice owes its commercial appreciation to its specific apocarotenoids: crocins, picrocrocin, and safranal. In Crocus sativus, these compounds are biosynthesized from zeaxanthin through oxidative cleavage by the carotenoid cleavage dioxygenase 2 (CCD2). Transgenic tomato plants expressing CsCCD2 in the fruit, named Tomaffron, accumulate high levels of saffron apocarotenoids despite the low substrate availability for CsCCD2.

HMGA1 orchestrates chromatin compartmentalization and sequesters genes into 3D networks coordinating senescence heterogeneity.

HMGA1 is an abundant non-histone chromatin protein that has been implicated in embryonic development, cancer, and cellular senescence, but its specific role remains elusive. Here, we combine functional genomics approaches with graph theory to investigate how HMGA1 genomic deposition controls high-order chromatin networks in an oncogene-induced senescence model. While the direct role of HMGA1 in gene activation has been described previously, we find little evidence to support this.

SARS-CoV-2 Nucleocapsid Protein Induces Tau Pathological Changes That Can Be Counteracted by SUMO2.

Neurologic manifestations are an immediate consequence of SARS-CoV-2 infection, the etiologic agent of COVID-19, which, however, may also trigger long-term neurological effects. Notably, COVID-19 patients with neurological symptoms show elevated levels of biomarkers associated with brain injury, including Tau proteins linked to Alzheimer's pathology. Studies in brain organoids revealed that SARS-CoV-2 alters the phosphorylation and distribution of Tau in infected neurons, but the mechanisms are currently unknown.

Biochemical characterisation of a cassava (Manihot esculenta crantz) diversity panel for post-harvest physiological deterioration; metabolite involvement and environmental influence.

Cassava (Manihot esculenta Crantz) produces edible roots, a major carbohydrate source feeding more than 800 million people in Africa, Latin America, Oceania and Asia. Post-harvest physiological deterioration (PPD) renders harvested cassava roots unpalatable and unmarketable. Decades of research on PPD have elucidated several genetic, enzymatic and metabolic processes involved.

Synthesis and Characterization of Click Chemical Probes for Single-Cell Resolution Detection of Epichaperomes in Neurodegenerative Disorders.

Neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's disease (PD), represent debilitating conditions with complex, poorly understood pathologies. Epichaperomes, pathologic protein assemblies nucleated on key chaperones, have emerged as critical players in the molecular dysfunction underlying these disorders. In this study, we introduce the synthesis and characterization of clickable epichaperome probes, PU-TCO, positive control, and PU-NTCO, negative control.

The Basic Requirement of Tight Junction Proteins in Blood-Brain Barrier Function and Their Role in Pathologies.

This review addresses the role of tight junction proteins at the blood-brain barrier (BBB). Their expression is described, and their role in physiological and pathological processes at the BBB is discussed. Based on this, new approaches are depicted for paracellular drug delivery and diagnostics in the treatment of cerebral diseases.

Evaluation of the biodistribution and preliminary safety profile of a novel brain-targeted manganese dioxide-based nanotheranostic system for Alzheimer's disease.

A novel brain-targeted and reactive oxygen species-activatable manganese dioxide containing nanoparticle system functionalized with anti-amyloid-β antibody (named aAβ-BTRA-NC) developed by our group has shown great promise as a highly selective magnetic resonance imaging (MRI) contrast agent for early detection and multitargeted disease-modifying treatment of Alzheimer's disease (AD). To further evaluate the suitability of the formulation for future clinical application, we investigated the safety, biodistribution, and pharmacokinetic profile of aAβ-BTRA-NC in a transgenic TgCRND8 mouse AD model, wild type (WT) littermate, and CD-1 mice. Dose-ascending studies demonstrated that aAβ-BTRA-NC was well-tolerated by the animals up to 300 μmol Mn/kg body weight [b.

Transient Receptor Potential Canonical 5 (TRPC5): Regulation of Heart Rate and Protection against Pathological Cardiac Hypertrophy.

TRPC5 is a non-selective cation channel that is expressed in cardiomyocytes, but there is a lack of knowledge of its (patho)physiological role in vivo. Here, we examine the role of TRPC5 on cardiac function under basal conditions and during cardiac hypertrophy. Cardiovascular parameters were assessed in wild-type (WT) and global TRPC5 knockout (KO) mice.

Non-targeted discovery of high-value bio-products in Nicotiana glauca L: a potential renewable plant feedstock.

The evaluation of plant-based feedstocks is an important aspect of biorefining. Nicotiana glauca is a solanaceous, non-food crop that produces large amounts of biomass and is well adapted to grow in suboptimal conditions. In the present article, compatible sequential solvent extractions were applied to N.

Activation of the native PHYTOENE SYNTHASE 1 promoter by modifying near-miss cis-acting elements induces carotenoid biosynthesis in embryogenic rice callus.

Modification of silent latent endosperm-enabled promoters (SLEEPERs) allows the ectopic activation of non-expressed metabolic genes in rice callus Metabolic engineering in plants typically involves transgene expression or the mutation of endogenous genes. An alternative is promoter modification, where small changes in the promoter sequence allow genes to be switched on or off in particular tissues. To activate silent genes in rice endosperm, we screened native promoters for near-miss cis-acting elements that can be converted to endosperm-active regulatory motifs.

p53 rapidly restructures 3D chromatin organization to trigger a transcriptional response.

Activation of the p53 tumor suppressor triggers a transcriptional program to control cellular response to stress. However, the molecular mechanisms by which p53 controls gene transcription are not completely understood. Here, we uncover the critical role of spatio-temporal genome architecture in this process.

Aging and brain free cholesterol concentration on amyloid-β peptide accumulation in guinea pigs.

Alzheimer's disease is a complex multifactorial neurodegenerative disorder wherein age is a major risk factor. The appropriateness of the Hartley guinea pig (GP), which displays high sequence homologies of its amyloid-β (Aβ and Aβ) peptides, Mdr1 and APP (amyloid precursor protein) and similarity in lipid handling to humans, was appraised among 9-40 weeks old guinea pigs. Protein expression levels of P-gp (Abcb1) and Cyp46a1 (24(S)-hydroxylase) for Aβ, and Aβ efflux and cholesterol metabolism, respectively, were decreased with age, whereas those for Lrp1 (low-density lipoprotein receptor related protein 1), Rage (receptor for advanced glycation endproducts) for Aβ efflux and influx, respectively, and Abca1 (the ATP binding cassette subfamily A member 1) for cholesterol efflux, were unchanged among the ages examined.

Quantitative comparison of presenilin protein expression reveals greater activity of PS2-γ-secretase.

γ-secretase processing of amyloid precursor protein (APP) has long been of interest in the pathological progression of Alzheimer's disease (AD) due to its role in the generation of amyloid-β. The catalytic component of the enzyme is the presenilins of which there are two homologues, Presenilin-1 (PS1) and Presenilin-2 (PS2). The field has focussed on the PS1 form of this enzyme, as it is typically considered the more active at APP processing.

Integrative transcriptomics reveals association of abscisic acid and lignin pathways with cassava whitefly resistance.

Background: Whiteflies are a global threat to crop yields, including the African subsistence crop cassava (Manihot esculenta). Outbreaks of superabundant whitefly populations throughout Eastern and Central Africa in recent years have dramatically increased the pressures of whitefly feeding and virus transmission on cassava. Whitefly-transmitted viral diseases threaten the food security of hundreds of millions of African farmers, highlighting the need for developing and deploying whitefly-resistant cassava.