Morphological Anomalies Research Articles

Are There Common Mechanisms Between the Hutchinson-Gilford Progeria Syndrome and Natural Aging?

The Hutchinson–Gilford progeria syndrome (HGPS) is a premature aging disease caused by mutations of the LMNA gene leading to increased production of a partially processed form of the nuclear fibrillar protein lamin A – progerin. Progerin acts as a dominant factor that leads to multiple morphological anomalies of cell nuclei and disturbances in heterochromatin organization, mitosis, DNA replication and repair, and gene transcription. Progerin-positive cells are present in primary fibroblast cultures obtained from the skin of normal donors at advanced ages. These cells display HGPS-like defects in nuclear morphology, decreased H3K9me3 and HP1, and increased histone H2AX phosphorylation marks of the DNA damage loci. Inhibition of progerin production in cells of aged non-HGPS donors in vivo increases the proliferative activity, H3K9me3, and HP1, and decreases the senescence markers p21, IGFBP3, and GADD45B to the levels of young donor cells. Thus, progerin-dependent mechanisms act in natural aging. Excessive activity of the same mechanisms may well be the cause of premature aging in HGPS. Telomere attrition is widely regarded to be one of the primary hallmarks of aging. Progerin expression in normal human fibroblasts accelerates the loss of telomeres. Changes in lamina organization may directly affect telomere attrition resulting in accelerated replicative senescence and progeroid phenotypes. The chronological aging in normal individuals and the premature aging in HGPS patients are mediated by similar changes in the activity of signaling pathways, including downregulation of DNA repair and chromatin organization, and upregulation of ERK, mTOR, GH-IGF1, MAPK, TGFβ, and mitochondrial dysfunction. Multiple epigenetic changes are common to premature aging in HGPS and natural aging. Recent studies showed that epigenetic systems could play an active role as drivers of both forms of aging. It may be suggested that these systems translate the effects of various internal and external factors into universal molecular hallmarks, largely common between natural and accelerated forms of aging. Drugs acting at both natural aging and HGPS are likely to exist. For example, vitamin D3 reduces the progerin production and alleviates most HGPS features, and also slows down epigenetic aging in overweight and obese non-HGPS individuals with suboptimal vitamin D status.

The Treatment of a Dental Morphological Anomaly Type Dens in Dente A challenge

Dens in dente or the amelo-dentinal invagination is met rarely and involves, almost in exclusivity, the upper lateral incisisors, usually unilateral, being an invagination in glove finger of the enamel in dentine, on the level of a tooth often dismorphic. The radiologic aspect is of candle flame, occupying the central part of an upper lateral incisor.

Hexavalent chromium-induced toxic effects on the antioxidant levels, histopathological alterations and expression of Nrf2 and MT2 genes in the branchial tissue of Ctenopharyngodon idellus

Ability of hexavalent chromium to accumulate and induce oxidative stress has been studied in the gills of Ctenopharyngodon idellus, with the resulting damage in the form of altered endogenous antioxidant enzyme activity and, histopathology in the tissue. The fish were exposed to 5.3 (C1) and 10.63 mg/L (C2) of hexavalent chromium and were scrutinised on 15th, 30th and 45th day of toxicant exposure. Oxidative stress studied in terms of lipid peroxidation and glutathione levels and the antioxidant enzymes activity also exhibited alterations. The histopathological modifications in gills announced lesions in the form of hyperplasia, aneurysm, lamellar fusion, focal proliferation, epithelial degeneration and necrosis with loss of lamellae, bringing irreversible damage on 45th day with mean degree of tissue change value of 100.35 ± 10.69. Bioaccumulation of chromium, and increased anomalies in branchial tissue exhibited damage in concentration and time-dependent manner. The ultrastructural anomalies in the cellular morphology in the epithelial cells of filaments and lamellae, exhibited pleomorphic nuclei, swollen mitochondria, extensive vacuolation and loss of microridges in pavement cells. The tissue also displayed altered regulation of Nrf2 and Mt2 following Cr(VI) exposure with maximum downregulation on 45th day by 61 and 53%, respectively. PCA generated two principal components, PC1 (GSH, GST, CAT and SOD) and PC2 (DTC, MDA and Cr(VI) concentration). Thus, it can be concluded that accumulation of Cr(VI) induces alteration in the gene expression of Nrf2 and Mt2 leading to the development of oxidative stress, ensuing various pathological changes creating hindrance in fish survival.

Severe Scoliosis and Fin Deformities in Three Fish Species Collected from Jubail Vicinity, Saudi Arabia, Arabian Gulf

The anomalies in fish fall into two main categories: severe ones that affect their fitness, and less severe ones that don’t impact survival and may occur as a result of various external and internal factors. Abnormally developed fish can be used as indicators of water pollution because of their high incidence in polluted areas. The objectives of the present study were to report and describe for the first time severe cases of scoliosis and fin deformities in fish from Saudi Arabia. Morphological anomalies, in general, can reduce the weight of fish and, more importantly, impact the value per kg sold. Therefore, the fisheries industries should conduct research into the various etiological causes of the deformities before any management policy can be chosen.

Antidepressant and Neuroprotective Effects of Naringenin via Sonic Hedgehog-GLI1 Cell Signaling Pathway in a Rat Model of Chronic Unpredictable Mild Stress.

Depression is one of the most prevalent and crucial public health problem connected to significant mortality and co-morbidity. Recently, numerous studies suggested that dietary flavanones exhibit neuroprotective and antidepressant effects against various psycho-physiological conditions including depression. The present study is focused on the antidepressant and neuroprotective effects of naringenin (NAR) and the involvement of sonic hedgehog (Shh) signaling in the chronic unpredictable mild stress (CUMS)-induced depression. Twenty-four male Wistar rats were randomly assigned into four groups: CON group (saline s.c.), NAR group (NAR 50mg/kg, p.o.), CUMS group (subjected to CUMS along with saline p.o.), and CUMS + NAR group (NAR 50mg/kg p.o. along with CUMS) for 28days including 1-week pre-treatment with NAR. The results showed that NAR was found to inhibit behavioral abnormalities including increased despair in force swim test, and reduced locomotor activity caused by CUMS in open field test. Moreover, Morris water maze revealed that NAR also mitigates CUMS-associated cognitive impairment. In addition to the antidepressant-like effect, NAR mitigates morphological anomalies in the hippocampal CA1 region and cortex. Furthermore, we observed brain-derived neurotrophic factor (BDNF), Shh, GLI1, NKX2.2, and PAX6 were downregulated in the hippocampus of CUMS-exposed rats, which can be upregulated by NAR pre-treatment. GLI1 is main downstream signaling component of Shh signaling cascade, which further regulates the expression of homeodomain transcription factors PAX6 and NKX2.2.

A humanized mouse model, demonstrating progressive hearing loss caused by MYO6 p.C442Y, is inherited in a semi-dominant pattern

Myosin VI is an actin-associated molecular motor vital for auditory and vestibular function. It is encoded by MYO6 located on chromosome 6q13 in human. Pathogenic variants in MYO6 have been associated with both dominant and recessive forms of hearing loss. However, the molecular mechanisms remain unclear. We established a humanized knock-in mouse model, Myo6-C442Y, to mimic the p.C442Y missense variant identified in human patients with autosomal dominant nonsyndromic hearing loss designated as DFNA22. We characterized hearing and inner ear morphologies of Myo6-C442Y and wild-type control mice. We found that both homozygous and heterozygous Myo6-C442Y mice exhibited hearing loss from three weeks after birth that rapidly progressed to profound deafness by six to nine weeks of age. The hearing loss corresponded to the degeneration of hair cells in the organ of Corti. We also observed disorganized stereocilia with irregular morphological features by immunohistochemistry and scanning electron microscopy. Additionally, hearing loss and inner-ear morphological anomalies were more pronounced and deteriorated more drastically in homozygous than in heterozygous Myo6-C442Y mice, indicating a semi-dominant inheritance pattern. Heterozygous Myo6-C442Y mice recapitulated the progressive postlingual sensorineural deafness in human, thus providing a useful model for elucidating the role myosin VI plays in the mammalian auditory system. Furthermore, the late-onset hearing loss of this mouse model may provide a therapeutic window for the emerging gene therapy, a promising strategy to treat certain forms of genetic deafness.

Response of Chironomidae to environmental disturbances in a high mountain lake in Patagonia during the last millennium

AbstractThrough the last millennium, Patagonia has been affected by changing climate conditions and successive volcanic eruptions. Lake Tonček is a high-altitude lake in the Southern Volcanic Zone in the northern Patagonian Andes. We documented the responses of the subfossil chironomid community to the effects of successive volcanic and different conditions in a sedimentary sequence from this lake comprising the last 900 years. The community composition and structure (abundance, diversity, and richness) and the development of morphological anomalies in the chironomid mouthparts were evaluated throughout the core. Both climatic conditions and volcanism affected the chironomid community differentially. The chironomid community changed following short-term climate change patterns, being affecting not only by temperature changes but also by variations in the regional precipitation regime. Decreases in abundance and diversity were only observed in coarse volcanic layers. In these samples, we recorded a high percentage of damaged chironomid mouthparts caused by mechanical wear, breakage or abrasion, possibly due to the increase of mineral particles. Our results represent important baseline data about the responses of chironomid communities to environmental disturbances in high-altitude lakes over long time frames.

SUN-521 Intracranial Calcifications Outside the Basal Ganglia at Presentation of Barakat Syndrome

Hypoparathyroidism-sensorineural Deafness-Renal dysgenesis (HDR, or Barakat) syndrome is an uncommon cause of hypoparathyroidism, representing fewer than 200 documented cases in the literature worldwide. Individuals with HDR have variable penetrance and a range of phenotypes. While basal ganglia calcifications are known to occur with chronic hypoparathyroidism, they are less common in children and intracranial calcifications outside the basal ganglia, to our knowledge, have not been documented in HDR syndrome. Case presentation: A 10 year-old boy with a history of sensorineural deafness and attention deficit hyperactivity disorder presented after a new-onset seizure during a basketball game. His initial total serum calcium level of 5.9 mg/dl with an albumin level of 4.4 mg/dl, serum phosphorus was 7.0 mg/dl, and normal creatinine for age. PTH level was 2 pg/ml. He was started on calcitriol and calcium supplementation. There was no prior personal nor family history of hypocalcemia, nephrolithiasis, deafness nor renal problems. A head CT showed calcifications in the basal ganglia as well as at the temporal and frontoparietal gray-white matter junction and thalamus. Parathyroid antibody testing was negative. Subsequent genetic analysis of the GATA3 gene indicated heterozygosity for c.790T>C causing a missense mutation (p.Cys264Arg), that has been reported to cause HDR due to altered DNA binding affinity of the zinc finger component of GATA3. On renal ultrasound kidneys were in the 8th-13th percentile for size, raising the possibility of mild hypoplasia. Post-treatment urine Calcium-to-Creatinine ratio was 0.105. We describe a case of HDR in childhood who presented with seizures and very rare pediatric finding of calcifications in the basal ganglia as well as additional intracranial calcification in the thalamus and temporal and frontoparietal gray-white matter junction, which to our knowledge have not previously been described with HDR Syndrome. This case highlights important features of this disorder including severe intracranial calcifications and morphologic renal anomalies. HDR patients are at high risk for renal impairment, which is a key prognostic factor. Thus, careful monitoring of renal function, avoidance of nephrotoxins and of excessive calciuria during hypoparathyroidism management are necessary.

Salicylic acid induces amelioration of chromium toxicity and affects antioxidant enzyme activity in Sorghum bicolor L.

Aim: Chromium (Cr(VI)) would inflict serious morphological, metabolic, and physiological anomalies in plants ranging from chlorosis of shoot to lipid peroxidation and protein degradation. Cr(VI) toxicity is often associated with oxidative stress, caused by the excessive formation of reactive oxygen species (ROS). In response, plants are equipped with a repertoire of mechanisms to counteract heavy metal (HM) toxicity. Salicylic acid (SA) plays a key role in the signal transduction pathways of various stress responses, demonstrating the protective effect of SA against abiotic stress factors. So, the present investigation was carried out to study the amelioration of pernicious effects of different concentration of Cr(VI) (0.0, 2.0, and 4.0 mg Cr(VI) kg−1 soil in the form of potassium dichromate) by treatments of salicylic acid solution viz. pretreatment and foliar spray via antioxidative enzymes and their metabolites.Results: With different treatments of salicylic acid solution, the reinstatement from ill effects of Cr(VI) toxicity was contemplated but the most conspicuous effect was observed when salicylic acid solution was supplied through the foliar spray (0.50 mM). This was accompanied with an increase in ascorbate peroxidase activity and hydrogen peroxide content and decrease in peroxidase activity and ascorbic acid content.Significance of the study: This study suggests that salicylic acid when applied through pre-treatment of seeds or through a foliar spray can be used to ameliorate the toxic effects of chromium (VI). Salicylic acid has the great potential for reducing the toxicity of heavy metals without negatively impacting the growth of the plants.

Small Animal Review

Introduction: In dogs, the presence of anaemia combined with three or more erythrocyte morphological anomalies, particularly eccentrocytes, increases the clinical suspicion of lymphoma, compared with inflammatory bowel disease.

Serpúlidos (Annelida, Serpulidae) colectados en las campañas oceanográficas de Fauna Ibérica

Se han identificado las colecciones de poliquetos de la familia Serpulidae (Annelida) recolectados en las campañas oceanográficas de Fauna Ibérica, las cuales se encuentran depositadas en el Museo Nacional de Ciencias Naturales de Madrid (MNCN), en el marco del Proyecto Fauna Ibérica. Se estudiaron algo más de 100 muestras, que fueron recolectadas en el ámbito íbero-balear desde profundidades someras hasta más de 700 m de profundidad. Se han identificado un total de 24 especies pertenecientes a 15 géneros; se han observado algunas anomalías morfológicas, como por ejemplo características intermedias entre dos especies de Serpula o quimeras bioperculadas en Hydroides. También se ha profundizado en el estudio de los complejos de géneros Apomatus-Protula y Filograna-Salmacina.

Retrospective evaluation of anemia and erythrocyte morphological anomalies in dogs with lymphoma or inflammatory bowel disease.

OBJECTIVE To assess the prevalences of anemia and various RBC anomalies in dogs with lymphoma versus inflammatory bowel disease (IBD) and to evaluate potential relationships between these variables and the severity of lymphoma. DESIGN Retrospective cross-sectional study. ANIMALS 82 client-owned dogs. PROCEDURES Medical records and blood smears were reviewed for dogs in which IBD or lymphoma had been diagnosed between January 1, 2006, and December 31, 2014, and for healthy dogs evaluated during that time frame. Hematologic data were analyzed, and results were compared among groups of healthy dogs, dogs with IBD, and dogs with lymphoma. Results were also compared within the lymphoma group between dogs further grouped on the basis of lymphoma clinical stage, substage, and cell size. RESULTS Prevalence of anemia was significantly higher in dogs with lymphoma (17/32 [53%]) than in dogs with IBD (5/23 [22%]). The total number of different RBC anomalies was significantly higher in dogs with lymphoma than in dogs that were healthy or had IBD. A cutoff of 3 different RBC anomalies/dog enabled differentiation between lymphoma and IBD, with a sensitivity and specificity of 71% and 70%, respectively (area under the fitted curve, 0.7239 ± 0.0727). The presence of eccentrocytes was the only individual RBC anomaly significantly more common in dogs with lymphoma (8/28 [29%]) versus dogs with IBD (1/23 [4%]). CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that detection of anemia combined with ≥ 3 RBC morphological anomalies, particularly eccentrocytes, on blood smears should increase the clinical suspicion of lymphoma, compared with IBD, in dogs.

MapB, the Brucella suis TamB homologue, is involved in cell envelope biogenesis, cell division and virulence

Brucella species are Gram-negative, facultative intracellular pathogens responsible for a worldwide zoonosis. The envelope of Brucella exhibits unique characteristics that make these bacteria furtive pathogens and resistant to several host defence compounds. We have identified a Brucella suis gene (mapB) that appeared to be crucial for cell envelope integrity. Indeed, the typical resistance of Brucella to both lysozyme and the cationic lipopeptide polymyxin B was markedly reduced in a ∆mapB mutant. MapB turned out to represent a TamB orthologue. This last protein, together with TamA, a protein belonging to the Omp85 family, form a complex that has been proposed to participate in the translocation of autotransporter proteins across the outer membrane (OM). Accordingly, we observed that MapB is required for proper assembly of an autotransporter adhesin in the OM, as most of the autotransporter accumulated in the mutant cell periplasm. Both assessment of the relative amounts of other specific outer membrane proteins (OMPs) and a proteome approach indicated that the absence of MapB did not lead to an extensive alteration in OMP abundance, but to a reduction in the relative amounts of a protein subset, including proteins from the Omp25/31 family. Electron microscopy revealed that ∆mapB cells exhibit multiple anomalies in cell morphology, indicating that the absence of the TamB homologue in B. suis severely affects cell division. Finally, ∆mapB cells were impaired in macrophage infection and showed an attenuated virulence phenotype in the mouse model. Collectively, our results indicate that the role of B. suis TamB homologue is not restricted to participating in the translocation of autotransporters across the OM but that it is essential for OM stability and protein composition and that it is involved in cell envelope biogenesis, a process that is inherently coordinated with cell division.

Renal Dysfunction in Patients With Direct Infiltration by B-Cell Lymphoma

BackgroundB-cell lymphoproliferative disorders with renal involvement are relatively frequent, but remain poorly described. A kidney biopsy is usually required to detect the renal lesions that are often missed using other diagnostic tools.MethodsWe retrospectively identified 34 patients with renal lymphoma diagnosed by percutaneous kidney biopsy (PKB) at Rennes University Hospital and its affiliated hospital centers between January 1, 2004, and May 1, 2016. Clinical, biological, radiological, and histological characteristics were collected at biopsy time.ResultsThe included patients had Waldenström macroglobulinemia (n = 12; 35.3%), chronic lymphocytic leukemia/lymphocytic lymphoma (n = 10; 29.5%), high-grade B-cell lymphoma (n = 6; 17.6%), and low-grade B-cell lymphoma (n = 6; 17.6%). The median follow-up was 29 months. Renal involvement led to renal function impairment in 29 patients (85.3%), among whom 20 had acute kidney injury (70%), and to nephrotic syndrome in 4 patients (11.8%). Only 13 patients (38.2%) presented morphological kidney anomalies among whom 5 showed bilateral infiltration. Histologically, interstitial infiltrate (97.1%) was the most common kidney lesion, and 9 patients (26.5%) had specific lymphomatous intraglomerular lesions. After hematological treatment (n = 29), a renal response was observed only in 8 patients (27.6%).ConclusionRenal involvement in the context of B-cell lymphoproliferative disorders is not uncommon. PKB is the best method to confirm this diagnosis. It should be performed early to rapidly initiate the hematological treatment to preserve kidney function.

Taurodontism part 1: history, aetiology and molecular signalling, epidemiology and classification

Abstract: Taurodontism is a developmental morphological anomaly that affects the internal anatomy of the multi-rooted teeth; hence, it is difficult to distinguish from a normal tooth structure based only on external appearance. In this defect, the teeth have elongated and cylindrical pulp cavities, a deep furcation and short roots. This article aims to address an important problem related to the cause of taurodontism. Although it is a well-held belief that taurodontism is caused by delayed or failed invagination of Hertwig's Epithelial Root Sheath (HERS), the molecular mechanism that signals this delay or failure had not been well understood until recently. This article discusses the history, aetiology, prevalence and classification of this morphological disorder, whereas part 2 of this 2-part series will discuss the biomechanics of taurodontic teeth, differential diagnosis and congenital disorders that mimic taurodontism, relevant syndromes, clinical implications and management. CPD/Clinical Relevance: In order to treat cases presenting taurodontism, it is essential to understand this anomaly along with its history, aetiology and associated epidemiology. This will provide clinicians with a deeper understanding when they encounter a relatively unnoticeable anomaly.

Production of deuterated biomass by cultivation of Lemna minor (duckweed) in D2O.

Common duckweed Lemna minor was cultivated in 50% D2O to produce biomass with 50-60% deuterium incorporation containing cellulose with degree of polymerization close (85%) to that of H2O-grown controls. The small aquatic plant duckweed, particularly the genus Lemna, widely used for toxicity testing, has been proposed as a potential source of biomass for conversion into biofuels as well as a platform for production of pharmaceuticals and specialty chemicals. Ability to produce deuterium-substituted duckweed can potentially extend the range of useful products as well as assist process improvement. Cultivation of these plants under deuterating conditions was previously been reported to require addition of kinetin to induce growth and was hampered by anomalies in cellular morphology and protein metabolism. Here, we report the production of biomass with 50-60% deuterium incorporation by long-term photoheterotrophic growth of common duckweed Lemna minor in 50% D2O with 0.5% glucose. L. minor grown in 50% D2O without addition of kinetin exhibited a lag phase twice that of H2O-grown controls, before start of log phase growth at 40% of control rates. Compared to continuous white fluorescent light, growth rates increased fivefold for H2O and twofold for 50% D2O when plants were illuminated at higher intensity with a metal halide lamp and a diurnal cycle of 12-h light/12-h dark. Deuterium incorporation was determined by a combination of 1H and 2H nuclear magnetic resonance (NMR) to be 40-60%. The cellulose from the deuterated plants had an average-number degree of polymerization (DPn) and polydispersity index (PDI) close to that of H2O-grown controls, while Klason lignin content was reduced. The only major gross morphological change noted was root inhibition.

Reproductive Characteristics of Male Rabbits ( Oryctolagus cuniculus ) Fed on Spirulina ( Spirulina platensis ) Hydro - Ethanolic Extract

Spirulina , a filamentous cyanobacteri um, possesses diverse biological activities and nutritional significance due to high concentration of natural nutrients . This work aimed to evaluate the effects of hydro - ethanolic extract (HEE) of Spirulina platensis on organ weights, sperm characteristics , reproductive hormones and fertility index in male rabbits. 30 male rabbits were randomly distributed into 5 groups (6 rabbits/group). For 120 days, group 1 animals (control) were orally given distilled water, those of group 2 were treated with 100 mg/kg bw of vitamin E, while groups 3, 4 and 5 received respectively 100, 200 and 400 mg/kg bw of spirulina extract. The results showed that the relative weights of the vas deferens and sexual glands increased significantly (p<0.05) in the HEE groups compared to the control, whereas no significant (p>0.05) difference was noticed in the weights of testes and epididymis, sperm mobility and membrane integrity. Sperm count was significantly (p<0.05) higher in animals given 400 mg/kg bw of HEE of spirulina with refere nce to all other treatments. The sperm morphological anomalies declined significantly (p<0.05) in HEE - treated rabbits compared to distilled water and vitamin E - given animals. The serum concentration of FSH decreased significantly (p<0.05) in rabbits receiv ing 400 mg/kg bw of HEE of spirulina compared to those of other groups. Meanwhile, that of LH did not show any significant (p>0.05) difference among treatments. The serum content in testosterone increased significantly (p<0.05) in spirulina extract - treated and vitamin E groups with reference to the control group. The litter size and the sex ratio did not present any significant (p>0.05) difference among treatments. The kid weight at birth and the litter size at weaning increased significantly (p<0.05) in sp irulina extract - treated and vitamin E groups with the reference to the control group. The viability rates at weaning were significantly (p<0.05) higher in spirulina extract - treated groups referring to the vitamin E and distilled water groups. In conclusion , the administration of hydro - ethanolic extract of spirulina enhanced the sexual organ weights, sperm characteristics, reproductive hormone levels and performances in male rabbit.

Role of Oocyte Morphological Abnormality Rates on the Embryo Development and Implantation

OBJECTIVE: The aim of this study was to assess the impact of some oocyte morphological abnormality rates on embryo development and implantation.STUDY DESIGN: Oocyte morphological abnormalities including oocyte size, elliptical shape, vacuole, plain polar body, fragmented polar body, large perivitellin space, perivitellin debris, central granulation, dense central granulation, inclusion body, thick zona pellucida, clusters of smooth endoplasmic reticulum, easy needle insertion and dark cytoplasm were determined for each oocyte. Rates of these oocyte morphological anomalies were determined for each case and the impact of rates on the cycle outcome was analyzed.RESULTS: Similar oocyte morphology abnormality rates were observed between cycles with and without successful embryo implantation. On the other hand, both fragmented polar body and vacuole rates were found to be significantly higher in cycles with Grade 2 embryo transfer. These rate differences were remained significant after adjustment for the age and basal FSH level.CONCLUSION: None of the oocyte morphological features was found to have significant impact on ART outcome.

High MYC Levels Favour Multifocal Carcinogenesis.

The term “field cancerisation” describes the formation of tissue sub-areas highly susceptible to multifocal tumourigenesis. In the earlier stages of cancer, cells may indeed display a series of molecular alterations that allow them to proliferate faster, eventually occupying discrete tissue regions with irrelevant morphological anomalies. This behaviour recalls cell competition, a process based on a reciprocal fitness comparison: when cells with a growth advantage arise in a tissue, they are able to commit wild-type neighbours to death and to proliferate at their expense. It is known that cells expressing high MYC levels behave as super-competitors, able to kill and replace less performant adjacent cells; given MYC upregulation in most human cancers, MYC-mediated cell competition is likely to pioneer field cancerisation. Here we show that MYC overexpression in a sub-territory of the larval wing epithelium of Drosophila is sufficient to trigger a number of cellular responses specific to mammalian pre-malignant tissues. Moreover, following induction of different second mutations, high MYC-expressing epithelia were found to be susceptible to multifocal growth, a hallmark of mammalian pre-cancerous fields. In summary, our study identified an early molecular alteration implicated in field cancerisation and established a genetically amenable model which may help study the molecular basis of early carcinogenesis.

Corrigendum: Homozygous missense mutation L673P in adenylate kinase 7 (AK7) leads to primary male infertility and multiple morphological anomalies of the flagella but not to primary ciliary dyskinesia.

Corrigendum: Homozygous missense mutation L673P in adenylate kinase 7 (AK7) leads to primary male infertility and multiple morphological anomalies of the flagella but not to primary ciliary dyskinesia.