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PubMed2025

CLADES: A Programmable Cascade of Genes for Cell Lineage Analysis and Manipulation.

In the Drosophila brain, neuronal diversity originates from approximately 100 neural stem cells, each dividing asymmetrically. Precise mapping of cell lineages at the single-cell resolution is crucial for understanding the mechanisms that direct neuronal specification. However, existing methods for high-resolution lineage tracing are notably time-consuming and labor-intensive. Here, we outline the best practices for lineage tracing using CLADES (cell lineage access driven by an edition sequence), a revolutionary approach to neuronal lineage tracing that addresses the limitations of previous methods. CLADES effectively traces the birth order of neurons using approximately 100 samples. The technique relies on a genetic cascade of reporter activations and deactivations that delineate lineage progression through color-coded markers. This system not only facilitates the detailed mapping of neuronal lineages but also holds the potential to be applied to tracking biological events and producing cell types for therapeutic purposes.

Animals↗

PubMed2024

Family genetic risk communication and reverse cascade testing in the BabySeq project.

PURPOSE: Genomic sequencing of newborns can initiate disease surveillance and therapy for children and may identify at-risk relatives through reverse cascade testing. We explored genetic risk communication and reverse cascade testing among families of newborns who underwent exome sequencing and were identified as having a risk for an autosomal dominant disease. METHODS: We conducted semistructured interviews with parents of newborns enrolled in the BabySeq Project who had a pathogenic or likely pathogenic variant associated with an autosomal dominant childhood- and/or adult-onset disease returned. We used directed content analysis to derive themes. RESULTS: From 11 families, all first-degree relatives (n = 32, 100%), 29 second-degree relatives (76%), and 26 third-degree relatives (43%) were informed of their risk. All parents (n = 22, 69% of first-degree relatives), 4 (11%) second-degree relatives, and 1 (2%) third-degree relatives underwent cascade testing. Most parents preferred to handle risk communication themselves. Parents with positive cascade testing but no associated symptoms were less inclined to share findings with relatives but highly motivated to share results if the variant's associated disease severity was high, as perceived with adult-onset conditions. One new subtheme, family member traits, was identified and defined as a relative's propensity to anxiety/concern after risk communications but did not diminish risk communication. CONCLUSION: Findings can inform more effective notification and testing practices for families of newborns at risk for hereditary genetic conditions.

Humans↗

PubMed2026

Interpreting cancer genetics through a two-step "evolutionary cascade hypothesis": bridging neutral and selective perspectives.

BACKGROUND: DNA mutations are the fundamental engines of cancer, driving its initiation and progression. The forces that fuel malignancy are also the architects of evolution, shaping life through genetic variations. Mutations, in fact, can emerge naturally from endogenous processes, such as oxidative DNA damage or errors in replication, as well as induced by external factors, including cosmic radiation and chemical carcinogens. MAIN BODY: A key question in cancer research is whether tumor evolution is primarily governed by selective bottlenecks, neutral evolution, or dynamic genetic plasticity. In this work, we examine cancer as a disease driven by evolutionary processes rooted in fundamental biological requirements, including sustained proliferation and nutrient utilization. We hypothesize that the accumulation of mutations activates an evolutionary switch, enabling tumor cells to acquire an enhanced capacity for survival, adaptation, and growth at rates far exceeding typical evolutionary timescales. We propose the "evolutionary cascade hypothesis," a unifying framework that integrates these models into a coherent sequence. At its core lies the failure of DNA repair mechanisms, representing a critical transition in cancer progression. This shift marks the transition from an initial non-Darwinian, neutral phase to a Darwinian, more deterministic phase. CONCLUSIONS: As predictive models of tumor evolution advance through genomic big data and artificial intelligence-driven analysis, the future of cancer treatment may extend beyond targeting individual mutations to disrupting the underlying evolutionary mechanisms that sustain malignancy. This paradigm shift could redefine therapeutic strategies and ultimately improve patient outcomes.

Humans↗

PubMed2026

Challenges of genomic testing for patients and clinicians in Latin America: Foundations of a qualitative multi-country study.

Genomic medicine is expanding across Latin America (LATAM), yet access to essential ancillary services such as genetic counselling remains limited. 'Latin-SEQ' is a study that provides whole exome sequencing (WES) for neuromuscular diseases across 18 countries, aiming to improve diagnostic rates and generate region-specific genetic insights. However, funding constraints exclude genetic counselling and cascade testing, raising concerns about equitable and harm-free care. This paper reports early findings from 'Latin-SEQ Plus,' a mixed-methods study exploring patient and healthcare practitioner (HCP) perspectives on WES and genetic counselling. Data were generated via surveys with patients and HCPs, and participatory workshops with HCPs across six countries. We found that patients strongly valued genetic testing for diagnostic clarity, improved care, and family planning. HCPs acknowledged the diagnostic benefits of WES but highlighted absence of local genetic counselling services, inconsistent pre and post-test practices, and uncertainty in managing incidental findings and variants of uncertain significance (VUS). Psychological impacts related to WES results are not always addressed, underscoring risks of psychological and emotional harm for patients. Access to WES and genetic counselling is limited in LATAM due to financial hardship and the absence of a clear genetic counselling infrastructure. Our findings also reveal a mismatch between patient expectations and HCPs' capacity to deliver comprehensive genomic care. We argue for urgent investment in genetic counselling infrastructure, HCP training, culturally tailored resources, and policy frameworks to support equitable implementation of genomic medicine in LATAM.

Humans↗

PubMed2026

Guidelines for Genetic Testing of Peripheral Nerve Disorders.

Inherited peripheral neuropathies (IPNs) comprise a clinically and genetically heterogeneous group of disorders affecting approximately 1 in 2500 individuals and represent one of the most common inherited neurologic diseases. The rapidly expanding identification of disease-causing genes and the widespread implementation of next-generation sequencing (NGS) have fundamentally transformed the diagnostic evaluation of these disorders. Contemporary molecular testing has substantially increased diagnostic yield, shortened the diagnostic delay, refined disease classification, and strengthened genotype-phenotype correlations. In the United States, NGS-based multigene panels have become the most cost-effective first-line molecular diagnostic approach for most patients with suspected inherited neuropathies, whereas phenotype-directed single-gene testing remains appropriate in selected clinical circumstances and in healthcare systems in which access to comprehensive sequencing is limited. Despite these advances, challenges continue to affect diagnostic accuracy, including interpretation of variants of uncertain significance, detection of copy number variants and repeat expansions, technical limitations associated with highly homologous genomic regions such as SORD, and variability in gene content and analytic performance among commercially available testing platforms. Accurate diagnosis therefore requires integration of clinical phenotype, electrodiagnostic findings, family history, and molecular data. Establishing a precise genetic diagnosis has become increasingly important because it improves prognostic accuracy, guides genetic counseling and cascade testing, identifies patients with treatable hereditary neuropathies such as transthyretin amyloidosis, and facilitates enrollment in gene-specific clinical trials and emerging precision therapies. An evidence-based, phenotype-driven approach that incorporates contemporary molecular technologies is essential to maximize diagnostic efficiency while recognizing the strengths and limitations of currently available genetic testing strategies.

Charcot–Marie–tooth disease↗

PubMed2026

A Novel SLC25A4 Variant Causing Mitochondrial Dysfunction, Myopathy and Cardiomyopathy: A Functional and Molecular Characterization.

SLC25A4, solute carrier family 25 member 4, gene is a member of the mitochondrial carrier subfamily within the solute carrier protein family. Pathogenic variants in SLC25A4 are associated with a spectrum of mitochondrial disorders that exhibit variable inheritance patterns and clinical manifestations. Specifically, dominantly inherited variants are typically associated with progressive external ophthalmoplegia with mitochondrial DNA deletions, recessively inherited variants are linked to myopathy and cardiomyopathy, and de novo variants can result in early-onset fatal disease presentations. In this study, we aimed to identify and characterize the disease-causing mutation(s) in a nine-year-old female patient from a consanguineous Saudi family. The patient was asymptomatic until the age of 3 years, when she presented with cardiomyopathy and myopathy. Comprehensive genetic analysis inclusive of whole exome sequencing and segregation analysis using Sanger sequencing identified an SLC25A4 variant (NM_001151.4: exon 2: c.112-1G>C) as the most likely cause of the disease. To assess transcript-level effects, we performed RT-PCR on RNA extracted from the patient's cultured lymphoblast cell lines (LCLs) and fibroblast cell lines (FCLs). RT-PCR analysis demonstrated that the variant causes aberrant splicing, resulting in a 6 bp in-frame deletion (p.Gln37_Val38del) in the ANT1 protein. Quantitative RT-PCR demonstrated reduced SLC25A4 transcript levels in both FCLs and LCLs. Quantitative PCR analysis of mitochondrial DNA demonstrated a trend toward increased mtDNA copy number in patient-derived FCLs compared with controls, suggesting a possible compensatory response to mitochondrial dysfunction. Furthermore, Seahorse assays revealed marked reductions in both oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) in patient-derived FCLs compared with controls. These findings expand the molecular and functional spectrum of SLC25A4-associated disease and may inform clinical practice, including genetic interventions such as preimplantation genetic diagnosis, premarital genetic screening, targeted genetic counseling, and cascade testing of at-risk family members.

Humans↗

PubMed2026

Multi-omic characterization of the Hispanic/Latino blood lipidome reveals an additional locus and attenuated genetic prediction.

While lipids have been extensively investigated, genetic regulation of the circulating lipidome in diverse populations remains poorly understood. We conducted a lipidome-wide genome-wide association study (GWAS) of 830 lipid species in 2,287 Hispanic/Latino participants and performed predictive modeling across omics layers. We identified 7,593 genome-wide significant SNPs mapping to 208 genes. Conditional analysis disentangled the long-range linkage disequilibrium artifacts from the pleiotropic FADS1/2/3 cluster. Separately, we discovered an association at the GPLD1 locus for a circulating ceramide. Colocalization revealed shared genetic architecture with conventional lipids alongside distinct, species-specific pathways. Incorporating Native/Indigenous American expression quantitative trait loci (eQTLs) within a multi-omic framework uncovered 62 likely regulatory genes missed by European-centric gene expression models. Finally, genetically regulated predictive models demonstrated performance declining from transcriptomics to proteomics to lipidomics, reflecting increased distance from gene action along the molecular cascade. Our study provides a genetic landscape of lipid metabolism in a highly burdened population and highlights the challenges in predicting lipid abundance.

Hispanic/Latino population↗

PubMed2025

MYC Regulates a DNA Repair Gene Expression Program in Small Cell Carcinoma of the Ovary, Hypercalcemic Type.

BACKGROUND/OBJECTIVES: SCCOHT is an aggressive and often fatal cancer that belongs to the ~20% of cancers defined by mutations to subunits of the SWI/SNF chromatin remodeling complex. In SCCOHT, mutations to the SMARCA4 gene, which encodes the SWI/SNF ATPase BRG1, are sufficient to impair SWI/SNF function. This single genetic lesion leads to a cascade of events that promote tumorigenesis, some of which may involve the intersection of SWI/SNF with oncogenic pathways such as those regulated by the MYC oncogene. In SCCOHT tumors and other cancers marked by SWI/SNF subunit mutation, MYC target genes are recurrently activated, pointing to a relationship between SWI/SNF and MYC that has yet to be fully explored. METHODS: In this study, we investigate the contribution of MYC to SCCOHT biology by performing a combination of chromatin binding and transcriptome assays in genetically engineered SCCOHT cell lines, with subsequent validation using patient tumor expression data. RESULTS: We find that MYC binds to thousands of active promoters in the BIN-67 SCCOHT cell line and that the depletion of MYC results in a broad range of gene expression changes with a notable effect on the expression of genes related to DNA repair. We uncover an MYC-regulated DNA repair gene expression program in BIN-67 cells that is antagonized by BRG1 reintroduction. Finally, we identify a DNA repair gene signature that is upregulated in SCCOHT tumors and in tumors defined by loss of the SWI/SNF subunit SNF5. CONCLUSIONS: Collectively, these data implicate MYC as a robust regulator of DNA repair gene expression in SCCOHT and lay a foundation for future studies focused on interrogating the relationship between BRG1 and MYC.

ATR↗

PubMed2026

Incidental MSH6 Germline Pathogenic Variant Identified through Tumor-only Comprehensive Genomic Profiling in a Patient with Small Cell Lung Cancer.

A 55-year-old woman was diagnosed with limited-disease small cell lung cancer (LD-SCLC) after incidental detection of a lung nodule. First-line chemotherapy achieved partial response, but recurrence occurred after one year. During second-line therapy, comprehensive genomic profiling (CGP) revealed a germline MSH6 frameshift mutation. Although lung tumor immunohistochemistry showed the retained expression of mismatch repair (MMR) protein, a prior colon cancer specimen showed the loss of MSH6 expression and deficient MMR expression. Germline genetic testing confirmed Lynch syndrome. Cascade testing identified the same mutation in her daughter. This case outlines a tumor-to-germline workflow with testing of at-risk relatives and highlights the importance of prudent interpretation of presumed germline variants.

Humans↗

PubMed2025

What Should a Clinical Cardiologist Know About Cardiogenetics?

Inherited cardiovascular diseases are becoming increasingly prominent in clinical practice, significantly impacting diagnosis, risk assessment, and family screening strategies. Progress in genetic testing has broadened access to cardiogenetic evaluations, while also presenting new challenges in interpreting variants and incorporating findings into clinical care. This narrative review explores 20 essential questions that clinical cardiologists may face when dealing with suspected or confirmed inherited cardiac conditions. Organized as a practical, question-driven guide, it outlines when to consider a genetic cause, how to choose and interpret genetic tests, and how to manage patients regardless of their genetic test results. The review emphasizes variant classification based on American College of Medical Genetics and Genomics criteria, the importance of clinical context in interpreting uncertain results, and the principles behind family cascade screening. Particular attention is given to the management of relatives who carry a genetic variant but show no symptoms, and to the current limitations of genetic testing technologies (eg, performance). Ethical considerations, including the appropriate timing of testing in children minors, are also discussed. By connecting genetic insights with clinical cardiology, this review aims to support practical, informed decision making and promote effective collaboration with cardiogenetic specialists.

Humans↗

PubMed2025

Genetic Downregulation of Interleukin-6 Signaling, Coagulation Function, and Risk of Thromboembolic Disease.

BACKGROUND: Although genetic evidence supports IL-6 (interleukin-6) signaling inhibition as protective against atherosclerotic disease, its potential effects on thromboembolic outcomes are not well established. We conducted a Mendelian randomization analysis to investigate the association of genetically proxied IL-6 signaling inhibition with venous thromboembolism, cardioembolic stroke, and coagulation cascade protein levels. METHODS: IL-6 signaling inhibition was proxied using the rs2228145 IL6R missense variant, which impairs classical IL-6 signaling and lowers CRP (C-reactive protein) levels. Genetic associations with thromboembolic disease outcomes were obtained from genome-wide association studies of venous thromboembolism (81 190 cases) and cardioembolic stroke (10 804 cases). As atherosclerotic comparator traits, we included coronary artery disease (181 522 cases) and large-artery atherosclerotic stroke (6399 cases). Genetic associations with 35 coagulation cascade protein levels were obtained from the UK Biobank (n=6218) and deCODE cohorts (n=35 559). Mendelian randomization estimates were derived using the Wald ratio method, scaled per 1-unit decrease in natural log-transformed CRP levels. RESULTS: Genetically proxied IL-6 signaling inhibition was associated with increased risk of venous thromboembolism (odds ratio [OR], 1.31 [95% CI, 1.16-1.47], P=6.5×10-6) but not with cardioembolic stroke (OR, 1.25 [95% CI, 0.73-2.14], P=0.42). Conversely, protective associations were observed for both coronary artery disease and large-artery atherosclerotic stroke. Proteomic analyses demonstrated significant reductions in levels of 5 procoagulant and 7 anticoagulant or antifibrinolytic proteins. CONCLUSIONS: These findings suggest that IL-6 signaling inhibition dysregulates coagulation homeostasis and increases venous thromboembolism risk. Further experimental, translational, and epidemiologic studies are warranted to delineate underlying mechanisms and to evaluate thromboembolic safety in pharmacologic IL-6 signaling inhibition.

Humans↗

PubMed2026

Rare genetic variant risks in patients with sepsis-associated acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a complex, heterogeneous, and deadly condition often resulting from pulmonary lesions due to sepsis, among other causes. There is a lack of targeted therapies to specifically treat the patients. Common genetic factors in the population (frequency > 1%) have been associated with ARDS susceptibility, but systematic genetic screens of the role of rare genetic variants are lacking. We used the network of known molecular interactions to identify ARDS risks from clusters of biologically related genes containing qualifying variants (QVs) with frequency < 1% likely affecting function. METHODS: We conducted whole-exome sequencing in sepsis patients from the GEN-SEP cohort (n = 822, of which 272 developed ARDS). A network-based heterogeneity clustering algorithm was used to discover significant gene clusters (p < 1 × 10–5). Gene-set enrichment analysis and logistic regression models aggregating QVs were used for cross-verification to confirm consistency and deepen understanding of the effect sizes of gene clusters. RESULTS: We identified 19 significant clusters (plowest = 3.29 × 10–10), each containing an average of 102 genes (11.6% mean similarity). QVs in nine gene clusters were associated with sepsis-associated ARDS (plowest = 1 × 10–5) but were not associated with 28-day survival. Clusters were enriched in several biological pathways, notably the Toll-like receptor cascades. CONCLUSIONS: These results support a marked genetic heterogeneity underlying ARDS susceptibility and the presence of rare risk variants involving multiple biological processes that are associated with sepsis outcomes. Particularly, they underscore the importance of rare variants in genes of the Toll-like receptor cascades in the risk for sepsis-associated ARDS.

Humans↗

PubMed2026

Plant nitrogen nutrition: enhancing plant resilience to abiotic stresses.

Nitrogen (N) is not only an essential macronutrient for plant growth and development but also functions as a pivotal signaling molecule that orchestrates adaptive responses to various abiotic stresses, including acidic stress, aluminum toxicity, salinity, drought, and extreme temperatures. This review synthesizes recent advances in our understanding of the molecular mechanisms by which N signaling, mediated by different N forms (e.g., NH4+ and NO3-), integrates with core stress-response pathways. We specifically discuss the genetic crosstalk between N sensing and key signaling cascades, including abscisic acid (ABA) signaling, the salt overly sensitive (SOS) pathway, and reactive oxygen species (ROS) homeostasis. The review details how this integration modulates physiological and transcriptional reprogramming through central regulators such as NIN-like proteins (NLPs), calcineurin B-like protein (CBL)-interacting protein kinase (CIPK), and the target of rapamycin (TOR) kinase, ultimately optimizing the trade-off between growth and tolerance. By establishing a unified genetic and molecular framework, this review aims to provide a theoretical basis for developing novel strategies in precision N management and molecular breeding to synergistically enhance N use efficiency (NUE) and abiotic stress tolerance in crops.

Nitrogen↗

PubMed1977

Urticaria. An updated review.

Urticaria can result from many different stimuli, and numerous factors, both immunologic and nonimmunologic, are involved in its pathogenesis. Most commonly considered of immunologic mechanisms is the type I hypersensitivity state mediated by IgE. Another immunologic mechanism involves the activation of the complement cascade, which produces anaphylatoxins that can release histamine. Immunologic, nonimmunologic, genetic, and modulating factors converge on mast cells and basophils to release mediators capable of producing urticarial lesions. In addition to the clinical and laboratory diagnosis and treatment regimens, we review such mediators as histamine, kinins, serotonin, slow-reacting substance of anaphylaxis, prostaglandins, acetylcholine, fibrin degradation products, and anaphylatoxins that increase vascular permeability and can thereby produce wheals. Special consideration is given to histamine and the factors that regulate is secretory release from mast cells and basophils, including the modulating role of intracellular levels of cyclic adenosine monophosphate.

Bites and Stings↗

PubMed2026

Sitosterolemia: evolving strategies for earlier diagnosis.

PURPOSE OF REVIEW: Sitosterolemia is a rare autosomal recessive lipid disorder caused by biallelic pathogenic variants in ABCG5 or ABCG8 , resulting in excessive intestinal absorption and impaired biliary excretion of plant sterols. Although historically considered exceptionally rare, recent genetic studies suggest the disorder is substantially underdiagnosed, with marked phenotypic heterogeneity ranging from xanthomas and premature atherosclerosis to hematologic abnormalities, and frequently mimics familial hypercholesterolemia. This review summarizes recent advances in the clinical, biological, and genetic diagnosis of sitosterolemia, with a focus on strategies that may facilitate earlier detection. RECENT FINDINGS: Phytosterol quantification, particularly sitosterol, campesterol, and stigmasterol, remains indispensable for accurate diagnosis. Hematologic abnormalities, including hemolytic anemia, stomatocytosis, and macrothrombocytopenia, are increasingly recognized as valuable diagnostic clues complementing the biochemical approach. Expanded variant catalogs for ABCG5/ABCG8 and genome-wide association studies have revealed potentially polygenic contributions to phytosterol metabolism extending beyond these two genes. However, no specific guidelines have yet been established for cascade screening. SUMMARY: Earlier diagnosis requires integration of clinical, biochemical, hematologic, and genetic data. Plasma phytosterol measurement remains the diagnostic cornerstone. Improved disease awareness, broader access to sterol testing, and expanded genetic screening may reduce diagnostic delays and enable timely management, including ezetimibe and dietary phytosterol restriction.

Humans↗

PubMed2026

The transcription factor SbWRKY6 confers cadmium tolerance via activating SbPLAC8-17 expression in sorghum.

Cadmium (Cd) is a widespread environmental pollutant that severely threatens crop productivity and food safety. However, the regulatory mechanisms underlying Cd detoxification and tolerance in sorghum remain largely elusive. Herein, we functionally characterized SbWRKY6, a Cd‑induced WRKY transcription factor that localizes to the nucleus and functions as a transcriptional activator. Stable overexpression of SbWRKY6 significantly enhanced Cd tolerance in sorghum, as evidenced by improved growth performance, mitigated oxidative damage, and decreased Cd concentration in plant tissues, whereas silencing of SbWRKY6 resulted in a Cd-hypersensitive phenotype with exacerbated toxicity symptoms. Mechanistically, we identified SbPLAC8-17, a member of the Plant Cadmium Resistance (PCR)/PLAC8 family, as a critical downstream target of SbWRKY6. Heterologous expression of SbPLAC8-17 functionally complemented the Cd‑sensitive phenotype of the yeast mutant ∆ycf1 and reduced intracellular Cd accumulation. Further yeast one-hybrid (Y1H), electrophoretic mobility shift assay (EMSA), and dual-luciferase reporter (Dual-LUC) assays confirmed that SbWRKY6 directly binds to the SbPLAC8-17 promoter and transcriptionally activates its expression. In vivo silencing of SbPLAC8-17 significantly impaired cellular Cd²⁺ efflux and aggravated Cd toxicity in sorghum. Additionally, the rapid Cd-induced transcriptional upregulation of SbMPK3 and its direct physical interaction with SbWRKY6 suggest a potential upstream regulatory module that remains to be functionally validated. Collectively, this study elucidates a novel SbWRKY6‑SbPLAC8-17 transcriptional cascade that positively regulates Cd tolerance by facilitating Cd²⁺ efflux, providing promising genetic targets for phytoremediation and molecular breeding of safe sorghum cultivars for Cd-contaminated fields.

Sorghum↗

PubMed2025

Exploring Potential Causality and Molecular Mechanisms between Heart Failure and Renal Failure: Insights from Mendelian Randomization Studies, the MIMIC-IV Database and the Gene Expression Omnibus Database.

UNLABELLED: Introduction: Heart failure (HF) and renal failure (RF) frequently coexist as cardiorenal syndrome, but their underlying causal mechanisms remain poorly defined. METHODS: This study applied Mendelian randomization (MR) using genome-wide association study (GWAS) datasets to investigate the causal effect of HF on RF. The inverse variance weighted method assessed causality, and summary-data-based MR (SMR) was used to identify therapeutic targets. Additional analyses included 211 gut microbiota traits and 1,400 serum metabolites. Validation was performed using the MIMIC-IV database. Transcriptomic data were analyzed to identify differentially expressed genes (DEGs) and key transcription factors (TFs). RESULTS: This study found that HF significantly increases the risk of RF (OR = 1.54, 95% CI: 1.07-2.23, p = 0.020). SMR analysis identified SURF1 and MAP3K11 as potential therapeutic targets for HF and RF. One gut microbiota genus and one serum metabolite showed causal associations with both diseases. MIMIC-IV data supported the HF-RF association (OR = 2.94, 95% CI: 2.81-3.07, p < 0.001). A total of 11 overlapping DEGs were enriched in the MAPK cascade, with RELA identified as a key TF. CONCLUSION: This study provides genetic and molecular evidence supporting a causal role of HF in RF, highlighting microbial, metabolic, and immune mechanisms as potential therapeutic targets. .

Humans↗

PubMed1975

Phenol oxidase activation in Drosophila: a cascase of reactions.

Our earlier evidence concerning the complexity of the activation process for Drosophila phenol oxidase has been confirmed by separation and purification of six proteins involved. This is a minimal number required in a reaction series or cascade to yield active enzyme, and at least two more proteins are known to be involved. A simpler system involving only the last step with one precursor and one activation as has been reported in the literature is consistent with the cascade picture, but the whole complex system must be considered when dealing with genetic and developmental regulation of pigmentation and sclerotization. Details are given for partial or complete purification of six of the proteins involved and evidence for their modes of interaction is presented.

Animals↗