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PubMed2024

Tailored UPRE2 variants for dynamic gene regulation in yeast.

Genetic elements are foundational in synthetic biology serving as vital building blocks. They enable programming host cells for efficient production of valuable chemicals and recombinant proteins. The unfolded protein response (UPR) is a stress pathway in which the transcription factor Hac1 interacts with the upstream unfolded protein response element (UPRE) of the promoter to restore endoplasmic reticulum (ER) homeostasis. Here, we created a UPRE2 mutant (UPRE2m) library. Several rounds of screening identified many elements with enhanced responsiveness and a wider dynamic range. The most active element m84 displayed a response activity 3.72 times higher than the native UPRE2. These potent elements are versatile and compatible with various promoters. Overexpression of HAC1 enhanced stress signal transduction, expanding the signal output range of UPRE2m. Through molecular modeling and site-directed mutagenesis, we pinpointed the DNA-binding residue Lys60 in Hac1(Hac1-K60). We also confirmed that UPRE2m exhibited a higher binding affinity to Hac1. This shed light on the mechanism underlying the Hac1-UPRE2m interaction. Importantly, applying UPRE2m for target gene regulation effectively increased both recombinant protein production and natural product synthesis. These genetic elements provide valuable tools for dynamically regulating gene expression in yeast cell factories.

Saccharomyces cerevisiae↗

PubMed2026

ER proteostasis failure in HYOU1 deficiency alters B cells, neutrophils, and interferon signalling.

Hypoxia upregulated 1 (HYOU1) is a stress-inducible ER chaperone. We investigated 2 unrelated patients carrying biallelic HYOU1 variants and presenting with primary immunodeficiency. Patient 1, homozygous for p.Pro444His, displayed failure to thrive, hypoglycemia, B cell lymphopenia, and neutropenia. Patient 2, compound heterozygous for p.Arg262Gln and p.Pro757_Glu758insAla, exhibited recurrent infections, enteropathy, and hypogammaglobulinemia. In Patient 1, while HYOU1 transcription was preserved, the protein was severely reduced. Tunicamycin treatment of dermal fibroblasts showed a blunted unfolded protein response and defective induction of ER stress-responsive genes. Immunophenotyping showed near-absence of circulating B cells, and single-cell RNA sequencing of bone marrow identified an arrest at the pro-B cell stage. Neutrophils displayed hypogranulation and dysregulated IFN- and apoptosis-associated transcriptional signatures, unresponsive to G-CSF. HYOU1 deficiency hence results in ER stress-induced proteostasis failure that simultaneously impairs adaptive immunity through B cell developmental arrest and innate immunity through neutrophil dysfunction and IFN pathway imbalance. This work expands the spectrum of HYOU1 deficiency and further identifies ER proteostasis as a central determinant of immune homeostasis.

Journal Article↗

PubMed2026

Proteome analyses reveal endoplasmic reticulum stress-induced changes in protein abundance associated with Ube2j2 deficiency in human cell culture.

The unfolded protein response (UPR) helps reinstate cellular proteostasis upon an accumulation of misfolded proteins in the endoplasmic reticulum (ER), in part through ER-associated degradation (ERAD). Ube2j2 is an ER-localized E2 ubiquitin-conjugating enzyme that participates in ERAD. We used mass spectrometry analysis of cultured U2OS cells to investigate how the loss of Ube2j2 affects the cellular proteome in response to tunicamycin-induced ER stress. We constructed a network of twelve statistically distinct modules of protein abundance profiles across conditions. We describe the gene ontology annotations for each module along with the "hub gene" proteins whose abundance levels most closely adhere to each module's protein abundance profile. Our analysis identifies known Ube2j2-associated pathways (eg the UPR and ERAD) and cellular functions that were previously unassociated with Ube2j2 (eg RNA metabolism, ER-Golgi transport, and cell-cycle progression). These data are available via ProteomeXchange with identifier PXD076153 and provide avenues for further investigation into the cellular functions of Ube2j2 under basal and ER-stressed conditions.

Humans↗

PubMed2026

Exercise elicits mitonuclear protein imbalance and UPRmt in the liver of mice with obesity.

Mitochondrial dysfunction plays a critical role in the development of metabolic dysfunction-associated steatotic liver disease (MASLD). It has been proposed that mitochondrial unfolded-protein response (UPRmt) activation improves mitochondrial function in the liver. Growing evidence demonstrates that physical exercise effectively prevents and treats MASLD. However, the effects of exercise on UPRmt activation in the liver are unknown. Thus, we investigated the impact of aerobic training on the mechanisms involved in mitochondrial quality control in the liver in a mouse model of obesity. Liver transcript data from a genetic reference panel of BXD isogenic mice revealed a negative correlation between UPRmt-related genes and hepatic triacylglycerol content. In addition, the liver UPRmt markers were strongly associated with several mitochondrial-related genes in the hepatic tissue of BXD mice and humans. Notably, 4 weeks of aerobic exercise strongly impacted the liver metabolism, preventing intrahepatic lipid accumulation in HFD-fed mice. Physical exercise boosted the NAD-biosynthesis pathway, elicited the mitonuclear protein imbalance, stimulated the protein content of UPRmt-markers, including CLpP, Lonp1, and Yme1L1, and improved the mitochondrial proteostasis and function in the liver in HFD-fed mice. Thus, our findings link the mitonuclear protein imbalance and UPRmt activation in the liver to mitochondrial proteostasis and MASLD prevention in response to physical exercise.

Animals↗

PubMed2025

Defining the host dependencies and the transcriptional landscape of RSV infection and bystander activation.

Respiratory syncytial virus (RSV) is a globally prevalent pathogen, causes severe disease in older adults, and is the leading cause of bronchiolitis and pneumonia in the United States for children during their first year of life [1]. Despite its prevalence worldwide, RSV-specific treatments remain unavailable for most infected patients. Here, we leveraged a combination of genome-wide CRISPR knockout screening and single-cell RNA sequencing to improve our understanding of the host determinants of RSV infection and the host response in both infected cells, and uninfected bystanders. These data reveal temporal transcriptional patterns that are markedly different between RSV infected and bystander activated cells. Our data show that expression of interferon-stimulated genes is primarily observed in bystander activated cells, while genes implicated in the unfolded protein response and cellular stress are upregulated specifically in RSV infected cells. Furthermore, genome-wide CRISPR screens identified multiple host factors important for viral infection, findings which we contextualize relative to 29 previously published screens across 17 additional viruses. These unique data complement and extend prior studies that investigate the proinflammatory response to RSV infection, and juxtaposed to other viral infections, provide a rich resource for further hypothesis testing.

CRISPR screen↗

PubMed2026

Integrated physiological and transcriptomic analyses reveal coordinated gill responses to heat stress in pikeperch (Sander lucioperca).

Climate change-driven warming of aquatic environments has made thermal stress an increasingly important factor influencing fish physiological homeostasis. Given their central roles in respiration and osmoregulation, gills are particularly responsive to variations in ambient temperature. Histological examination, physiological measurements, and transcriptome profiling were integrated to investigate the mechanisms associated with heat stress-induced gill injury in pikeperch (Sander lucioperca). Histological analysis revealed that exposure to 29 °C directly caused structural damage to the gills of pikeperch. Oxidative status was evaluated by measuring malondialdehyde (MDA) levels and the activities of antioxidant enzymes, including superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT). MDA accumulation was significantly enhanced under heat stress, while antioxidant enzyme activities (SOD, POD, and CAT) displayed a transient increase followed by a subsequent decline. Transcriptome profiling showed marked enrichment of the protein processing in endoplasmic reticulum pathway after heat stress, suggesting activation of endoplasmic reticulum (ER) stress in pikeperch gills. With increasing stress duration, the unfolded protein response (UPR) appeared unable to re-establish ER homeostasis, shifting ire1 and atf6 toward a pro-apoptotic state. Protein-protein interaction (PPI) analysis further highlighted hub genes potentially involved in heat stress-induced ER stress and apoptosis. TUNEL staining and western blotting collectively confirmed that heat stress triggered apoptosis in pikeperch gill tissue. Overall, this study provides new insights into the physiological and molecular responses of pikeperch gills to heat stress and enhances our understanding of thermal stress adaptation in cold-water aquaculture species under climate change.

Animals↗

PubMed2026

Schisantherin B mitigates cisplatin-induced ototoxicity by modulating the CNPY2-PERK/CHOP signaling axis.

Irreversible cisplatin-induced hearing loss (CIHL) is a refractory chemotherapy-related adverse effect with limited clinical treatments. Schisantherin B (STB), a lignan isolated from Schisandra chinensis, is widely recognized for its neuroprotective properties, while its role in auditory injury remains unclear. Herein, we found that STB alleviated cisplatin-induced ototoxicity in House Ear Institute Organ of Corti 1 (HEI-OC1) cells and guinea pig models, protecting cochlear hair cells, synaptic ribbons and spiral ganglion neurons, and partially restoring auditory brainstem response (ABR) thresholds. Furthermore, combined drug affinity responsive target stability (DARTS) assay, the cellular thermal shift assay (CETSA), and the surface plasmon resonance (SPR) assay, we confirmed STB directly binds to the canopy FGF signaling regulator 2 (CNPY2), a key initiator of endoplasmic reticulum (ER) stress. Notably, consistent dual in vitro and in vivo validation confirmed that STB exerts no regulatory effect on CNPY2 protein abundance, yet suppressed the downstream Protein kinase R-like endoplasmic reticulum kinase / C/EBP homologous protein (PERK/CHOP) signaling cascade and ER stress-mediated apoptosis. Moreover, molecular docking and co-immunoprecipitation (co-IP) validated the physical binding of STB to CNPY2 and the endogenous interaction between CNPY2 and PERK. Additionally, CNPY2 overexpression and shRNA knockdown further verified this functional relationship. Integrated proteomic and transcriptomic analyses showed STB partially reversed cisplatin-triggered inflammation and excessive ER stress. Collectively, our results suggest STB may serve as a potential otoprotective agent. The CNPY2-PERK/CHOP axis is closely linked to cisplatin-induced cochlear damage and offers a feasible target for intervention against CIHL. Abbreviations: CIHL, cisplatin-induced hearing loss; STB, Schisantherin B; HEI-OC1, house ear institute organ of corti 1; ABR, auditory brainstem response; DARTS, drug affinity responsive target stability; CETSA, cellular thermal shift assay; SPR, surface plasmon resonance; CNPY2, canopy FGF signaling regulator 2; ER, endoplasmic reticulum; PERK, protein kinase R-like endoplasmic reticulum kinase; CHOP, C/EBP homologous protein; co-IP, co-immunoprecipitation; STA, Schisantherin A; STC, Schisantherin C; dB SPL, decibels sound pressure level; EDTA, ethylenediaminetetraacetic acid; dB SPL, decibels sound pressure level; SGN, spiral ganglion neuron; IHCs, inner hair cells; OHCs, outer hair cells; CCK-8, Cell Counting Kit-8; OD, optical density; ODb, blank sample, ODc, control sample; NC, negative control; PVDF, polyvinylidene difluoride; RT, room temperature; LC-MS/MS, liquid chromatography tandem mass spectrometry; MS, mass spectrometry; DMSO, dimethyl sulfoxide; KDs, equilibrium dissociation constants; SP, standard precision; SEM, standard error of the mean; HSD, honestly significant difference; Ctrl, control group; CV, cell viability; Kd, dissociation rate constant; Ka, association rate constant; STS, sodium thiosulfate; UPR, unfolded protein response; BLB, blood-labyrinth barrier.

Apoptosis↗

PubMed2026

Human Monocytic Models Reveal Genotype-Dependent Inflammatory Programs in VEXAS Syndrome.

OBJECTIVES: VEXAS syndrome is a severe X-linked autoinflammatory disorder caused by somatic mutations in ubiquitin-like modifier activating enzyme 1 (UBA1), with clinical outcomes that vary by UBA1 genotype. We aimed to elucidate genotype-specific inflammatory programs and identify potential therapeutic targets. METHODS: We conducted longitudinal deep phenotyping, including whole-blood RNA sequencing (RNA-seq) and clinical activity assessment. Peripheral blood samples were analyzed by single-cell RNA-seq. Human monocytic cell lines harboring each major UBA1 mutation (p.Met41Val, p.Met41Thr, or p.Met41Leu) were generated and subjected to transcriptomic and functional analyses. RESULTS: Thirteen patients with VEXAS syndrome contributed a total of 79 RNA-seq samples. Among genes upregulated in VEXAS syndrome, RNASE1 showed the strongest correlation with longitudinal disease activity (r = 0.70, FDR < 0.05) and was upregulated in patients' monocytes. In UBA1-mutant monocytic cell lines, genotype-dependent ubiquitination defects were observed in a graded manner (p.Met41Val > p.Met41Thr > p.Met41Leu), even in the absence of exogenous stimuli. These defects were accompanied by unfolded protein response activation, increased pro-inflammatory cytokine production, progressive cell death, and RNASE1 upregulation, all following the same graded pattern, recapitulating patient genotype-phenotype associations. Transcriptomic analyses demonstrated enrichment of pro-inflammatory, interferon, and necroptosis signatures in more severe genotypes. Notably, inhibition of receptor-interacting protein kinase 3 (RIPK3) markedly attenuated all pathological features, including RNASE1 upregulation. CONCLUSIONS: Our UBA1-mutant monocytic cell-line models, representing three distinct genotypes, recapitulate genotype-dependent inflammatory phenotypes that can be modulated by RIPK3 inhibition, providing a translational platform for mechanistic investigation and precision therapy development in VEXAS syndrome.

Journal Article↗

PubMed2026

Endothelial PERK restricts lymphoid regeneration by reducing DLL4-NOTCH3 signaling at the Pre-B niche.

Delayed immune recovery after hematopoietic stem cell (HSC) transplantation is associated with a poor clinical outcome. We study the role of unfolded protein response (ER stress) in hematopoietic regeneration within the bone marrow (BM) microenvironment. We reveal that BM endothelium PERK activation is a prominent feature of patients with leukemia and is a hallmark response in mice following ionizing irradiation. Ablating endothelial Perk boosts NOTCH ligand DLL4 expression and promotes DLL4-dependent early HSC and B progenitor regeneration. Single-cell analysis reveals that endothelial DLL4 activates NOTCH3 expressed by mesenchymal stroma cells, and that the PERK-DLL4 axis coordinates the regulation of lymphoid commitment. NOTCH3 is critical for the upregulation of IL7 following irradiation and the expansion of lymphoid progenitors. These findings not only unveil an ER stress-controlled vascular-stroma signaling mechanism in regenerative hematopoiesis but also highlight PERK blockade as a promising strategy to improve immune recovery after myeloablative transplantation.

CP: cell biology↗

PubMed2026

Circular RNAs in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive loss of motor neurons, with most cases lacking a clear genetic basis. Emerging evidence highlights the involvement of non-coding RNAs, particularly circular RNAs (circRNAs), in disease onset and progression. Here, we investigated circRNAs implicated in ALS and related motor neuron diseases (MNDs). Here, we provide a general overview of circular RNA metabolism and cellular functions. We then present our systematic literature review that identified ALS-associated circRNAs, followed by in silico analyses of 15 circular RNA candidates that were selected based on the most compelling data regarding ALS. Our results revealed that several circular RNAs regulate ALS-related genes, such as unfolded protein response, oxidative stress, cell cycle regulation, and apoptosis. Protein-RNA interaction analysis further showed that ALS-related circRNAs can sponge 20 RNA-binding proteins. Additionally, molecular docking analysis demonstrated that ALS-associated FUS variants significantly alter its binding affinity to circular RNAs. RNA-seq data from ALS patients confirmed significant alterations in the expression of host genes of ALS-related circRNAs and hub proteins in ALS-affected CNS tissues. Collectively, our findings identify circRNAs as potential key contributors to ALS pathogenesis.

Amyotrophic Lateral Sclerosis↗

PubMed2012

Crohn's disease.

Crohn's disease is a relapsing systemic inflammatory disease, mainly affecting the gastrointestinal tract with extraintestinal manifestations and associated immune disorders. Genome wide association studies identified susceptibility loci that--triggered by environmental factors--result in a disturbed innate (ie, disturbed intestinal barrier, Paneth cell dysfunction, endoplasmic reticulum stress, defective unfolded protein response and autophagy, impaired recognition of microbes by pattern recognition receptors, such as nucleotide binding domain and Toll like receptors on dendritic cells and macrophages) and adaptive (ie, imbalance of effector and regulatory T cells and cytokines, migration and retention of leukocytes) immune response towards a diminished diversity of commensal microbiota. We discuss the epidemiology, immunobiology, amd natural history of Crohn's disease; describe new treatment goals and risk stratification of patients; and provide an evidence based rational approach to diagnosis (ie, work-up algorithm, new imaging methods [ie, enhanced endoscopy, ultrasound, MRI and CT] and biomarkers), management, evolving therapeutic targets (ie, integrins, chemokine receptors, cell-based and stem-cell-based therapies), prevention, and surveillance.

Colonic Diseases↗

PubMed2025

Transcriptional profiling of Hutchinson-Gilford Progeria patients identifies primary target pathways of progerin.

Hutchinson Gilford Progeria Syndrome (HGPS) is an ultra-rare pediatric premature aging disorder. The disease is caused by a point mutation in the LMNA gene leading to the production of the dominant-negative progerin isoform of the nuclear envelope protein lamin A. Disease severity and progression amongst the population of ~140 known patients is variable. Most of the mechanistic insights into the disease have come from studies using cellular or mouse models of HGPS. To probe the clinical relevance of previously implicated cellular pathways and to address the extent of gene expression heterogeneity between patients, we have performed transcriptomic analysis of a comprehensive set of HGPS patients. We find misexpression of several cellular pathways across the patient population, particularly of multiple signaling pathways as well as the Unfolded Protein Response (UPR) and mesodermal cell fate specification. Variability amongst individual patients was limited, with misregulation of the major pathways observed in most patients. Comparing the transcriptome of patients with an inducible HGPS cell model, we distinguished immediate-early cellular response pathways from secondary adaptive pathways and identified mTORC1, the UPR, UV response, apoptosis and TNFα signaling via NF-κB as primary targets of the disease-causing progerin protein.

Hutchinson-Gilford Progeria Syndrome↗

PubMed2025

Gfa1 (glutamine fructose-6-phosphate aminotransferase) is essential for Aspergillus fumigatus growth and virulence.

BACKGROUND: Aspergillus fumigatus, the primary etiological agent of invasive aspergillosis, causes over 1.8 million deaths annually. Targeting cell wall biosynthetic pathways offers a promising antifungal strategy. Gfa1, a rate-limiting enzyme in UDP-GlcNAc synthesis, plays a pivotal role in the hexosamine biosynthetic pathway (HBP). RESULTS: Deletion of gfa1 (Δgfa1) results in auxotrophy for glucosamine (GlcN) or N-acetylglucosamine (GlcNAc). Under full recovery (FR) conditions, where minimal medium is supplemented with 5 mM GlcN as the sole carbon source, the Δgfa1 mutant shows growth comparable to the wild-type (WT). However, when supplemented with 5 mM GlcN and 55 mM glucose, growth is partially repressed, likely due to carbon catabolite repression, a condition termed partial repression (PR). Under PR conditions, Δgfa1 exhibits compromised growth, reduced conidiation, defective germination, impaired cell wall integrity, and increased sensitivity to endoplasmic reticulum (ER) stress and high temperatures. Additionally, Δgfa1 demonstrates disruptions in protein homeostasis and iron metabolism. Transcriptomic analysis of the mutant under PR conditions reveals significant alterations in carbohydrate and amino acid metabolism, unfolded protein response (UPR) processes, and iron assimilation. Importantly, Gfa1 is essential for A. fumigatus virulence, as demonstrated in Caenorhabditis elegans and Galleria mellonella infection models. CONCLUSIONS: These findings underscore the critical role of Gfa1 in fungal pathogenicity and suggest its potential as a therapeutic target for combating A. fumigatus infections.

Aspergillus fumigatus↗

PubMed2025

Investigating the miRNA-mRNA interactome of human trabecular meshwork cells treated with TGF-β1 provides insights into the pathogenesis of pseudoexfoliation glaucoma.

Pseudoexfoliation glaucoma is a severe form of secondary open angle glaucoma and is associated with activation of the TGF-β pathway by TGF-β1. MicroRNAs (miRNAs) are small non-coding RNA species that are involved in regulation of mRNA expression and translation. To investigate what glaucomatous changes occur in the trabecular meshwork and how these changes may be regulated by miRNAs, we performed a bioinformatics analysis resulting in a miRNA-mRNA interactome. Primary human trabecular meshwork cells originating from normal donors were treated with TGF-β1 at 5 ng/mL for 24h; total RNA was extracted followed by RNA-Seq and miRNA-Seq. For both mRNA and miRNA species, differential expression was determined using a bioinformatics pipeline consisting of FastQC, STAR, FeatureCounts, edgeR (for miRNA) and DESeq2 (for mRNA). Putative mRNA-miRNA interactions between differentially expressed mRNA and miRNA species were determined using interaction databases miRWalk, miRTarBase, TarBase and TargetScan. To classify mRNA species by function and pathway, gene enrichment was performed using Enrichr. The resulting miRNA-mRNA interactome consisted of 1202 interactions. Some highly connected microRNAs were hsa-let-7e-5p, hsa-miR-20a-5p, hsa-miR-122-5p, and hsa-miR-29c-3p. Most differentially expressed genes were indicated to be regulated by miRNAs. The sub-interactomes of genes involved in specific pseudoexfoliation glaucoma related enrichment terms such as oxidative stress, unfolded protein response, signal molecules and ECM remodelling were determined. This is the first study to present a genome-wide microRNA-mRNA regulatory network for human trabecular meshwork cells treated with TGF-β1 and may serve to generate unbiased hypotheses about regulatory functions and mRNA targets of miRNAs in pseudoexfoliation glaucoma and may help to develop miRNA-based therapeutics.

Humans↗

PubMed1977

Induction of neutralizing antibodies and immunity in vaccinated guinea pigs by cyanogen bromide-peptides of VP3 of foot-and-mouth disease virus.

The specificity of guinea pig antisera against large cyanogen bromide-cleaved peptides of the virus capsid protein VP3 of foot-and-mouth disease virus type O1, strain Kaufbeuren has been characterized by double immunodiffusion, virus neutralization and protection tests. Antibodies to purified 146S particles and the cleavage peptides of VP3 showed an incomplete cross-section against VP3 peptide antigen when reacted in immunodiffusion tests, indicating that new antigenic determinants are exhibited by the peptides which are not recognized by the antiserum against the native virus proteins. The immune response against the reduced, unfolded chain constituents of VP3 was lower in comparison to that of native virus particles but still some immunological determinants remained actively capable of inducing virus-neutralizing antibodies in immunized guinea pigs.

Animals↗

PubMed2026

Mining the sHSP20 (small heat-shock protein) gene family in finger millet (Eleusine coracana (L.) Gaertn.): structural, evolutionary and predicted abiotic-stress-responsive insights.

Small heat-shock proteins (sHSPs, the HSP20 family) are ATP-independent molecular chaperones that hold partially unfolded substrates and protect the proteome during heat and other abiotic stresses; every member is defined by a conserved α-crystallin domain (ACD). Finger millet (Eleusine coracana) is a climate-resilient, calcium-rich allotetraploid cereal of the semi-arid tropics whose HSP20 repertoire had not been catalogued. The present study is an entirely computational (in silico) analysis of the chromosome-scale reference genome of finger millet (NCBI GenBank assembly GCA_032690845.1, cultivar KNE 796-S). Mining the predicted proteome with the ACD profile (Pfam PF00011) and confirming every candidate by NCBI CD-search recovered 76 non-redundant ACD-bearing HSP20 genes (EcHSP20-1-EcHSP20-76). Based on phylogeny and TargetP-predicted localization, the members were classified into ten subfamilies: seven cytosolic/nuclear classes (C-I to C-VII, 60 members) together with chloroplastic (11), mitochondrial (3) and endoplasmic-reticulum (2) groups. The proteins ranged from 110 to 355 amino acids (12.1-39.2 kDa) with theoretical pI of 4.85-9.69. The 76 loci were distributed over 14 of the 18 chromosomes and were conspicuously absent from chromosomes 8 A, 8B, 9 A and 9B, with pronounced clustering on chromosomes 1, 2, 3 and 6. Duplication analysis detected 149 paralogous pairs (49 homoeologous, 80 segmental/dispersed and 18 tandem); 147 of 148 pairs for which substitution rates could be calculated returned Ka/Ks < 1 (mean 0.20), indicating strong purifying selection consistent with retention after whole-genome/allopolyploid duplication. Promoter analysis (PlantCARE) revealed enrichment of abscisic-acid-responsive (ABRE), MYB/MYC drought-related, STRE, DRE, low-temperature (LTR) and methyl-jasmonate/salicylic-acid elements, whereas canonical heat-shock elements (HSE) were not recovered. Expression profiling against a public drought transcriptome (SRP081350) showed that about half of the genes (39 of 76) are transcribed in leaf tissue, the expressed fraction being dominated by the cytosolic class C-I. This first finger-millet HSP20 catalogue provides a verified, reproducible framework and nominates computationally predicted candidate genes for future functional work on thermotolerance in cereals.

Allotetraploid↗

PubMedDate not supplied

General considerations of coagulation proteins.

The coagulation system is part of the continuum of host response to injury and is thus intimately involved with the kinin, complement and fibrinolytic systems. In fact, as these multiple interrelationships have unfolded, it has become difficult to define components as belonging to just one system. With this limitation in mind, an attempt has been made to present the biochemistry and physiology of those factors which appear to have a dominant role in the coagulation system. Coagulation proteins in general are single chain glycoprotein molecules. The reactions which lead to their activation are usually dependent on the presence of an appropriate surface, which often is a phospholipid micelle. Large molecular weight cofactors are bound to the surface, frequently by calcium, and act to induce a favorable conformational change in the reacting molecules. These molecules are typically serine proteases which remove small peptides from the clotting factors, converting the single chain species to two chain molecules with active site exposed. The sequence of activation is defined by the enzymes and substrates involved and eventuates in fibrin formation. Multiple alternative pathways and control mechanisms exist throughout the normal sequence to limit coagulation to the area of injury and to prevent interference with the systemic circulation.

Antithrombins↗

PubMed1975

Stabilization of the globular structure of ferricytochrome c by chloride in acidic solvents.

Increasing concentrations of chloride were found to increase the resolution between two visible absorbance spectral transitions associated with acidification of ferricytochrome c. Analysis of a variety of spectral and viscosity measurements indicates that protonation of a single group having an apparent pK of 2.1 +/- 0.2 and an intrinsic pK of about 5.3 displaces the methionine ligand without significantly perturbing the native globular conformation. Analysis of methylated ferricytochrome c suggests that protonation of a carboxylate ion, most likely a heme propionate residue, is responsible for displacement of the methionine ligand. Addition of a proton to a second group having an apparent pK of 1.2 +/- 0.1 displaces the histidine ligand and unfolds the protein from a globular conformation into a random coil. It is most likely that the second protonation occurs on the imidazole ring of the histidine ligand itself. Chloride is proposed to perturb these transitions by ligation in the fifth coordination position of the heme ion. Such ligation stabilizes a globular conformation of ferricytochrome c at pH 0.0 and 25 degrees.

Animals↗