Latent Autoimmune Diabetes in Adults Associated with Von Recklinghausen’s Disease (Neurofibromatosis Type 1)

Introduction: Endocrine disorders during Von Recklinghausen’s Disease or neurofibromatosis type 1 (NF1) are rare and particularly observed in children. However, autoimmune diabetes mellitus (DM) remains exceptional and unusual during this phacomatosis. We report an original case of Latent Autoimmune Diabetes in Adults (LADA) associated with NF1.Case Report: A 32-year-old Tunisian male, known to have NF1 since childhood, was admitted for significant recent weight loss (10 kg in one month) with high blood glucose levels. The biological tests confirmed the diagnosis of DM with marked ketoacidosis: fast blood glucose at 16 mmol/l, postprandial glucose at 21 mmol/l, and HbA1c at 9.9%. Radiological and endoscopic investigations did not indicate pancreatic and/or duodenal tumors. Anti-GAD and anti-IA2 autoantibodies were positively confirming the diagnosis of LADA. The assessment of degenerative complications and screening for possible other autoimmune diseases were negative. The evolution was favorable under intensive insulinotherapy.Conclusion: The association of DM type 1 with NF1 remains exceptional and only four cases are found in the literature, all pediatrics. Our observation is, to our knowledge, the first reporting this association in adult (LADA with NF1)

Biomarcadores de estrés oxidativo en las branquias del bivalvo Mactra stultorum expuesto a acrilamida

Acrylamide (ACR) is among the most deleterious pollutants in the environment and presents a serious risk to humans and ecosystems. The purpose of this study was to assess its effects when administered at different concentrations (5, 10 and 20 mg L–1) to evaluate antioxidant status in the gills of Mactra stultorum. Our results showed, after five days of treat­ment, an increase in malondialdehyde (MDA), lipid hydroperoxides (LOOH), advanced oxidation protein products (AOPP), reduced glutathione (GSH), ascorbic acid (Vit C) and metallothionein (MDA) levels in gills of treated clams compared with controls. Moreover, an increase in superoxide dismutase (SOD) and a significant decrease in glutathione peroxidase (GPx) activities were also observed. Acrylamide induced neurotoxicity, as evidenced by the inhibition of acetylcholinesterase (AChE) activity in a dose-dependent manner. Overall, our results indicated that oxidative stress may be considered one of the mechanisms behind acrylamide toxicity in bivalves, although the subject requires more research.La acrilamida (ACR) es uno de los contaminantes más perjudiciales en el medio ambiente y presenta un grave riesgo para los seres humanos y los ecosistemas. El objetivo de este estudio es evaluar los efectos del ACR administrado a diferentes concentraciones (5, 10 y 20 mg L–1) con el fin de evaluar el estado antioxidante en las branquias de Mactra stulto­rum. Nuestros resultados mostraron, después de 5 días de tratamiento, un aumento en los niveles de malondialdehído (MDA), hidroperóxidos lipídicos (LOOH), proteínas de oxidación avanzada (AOPP), glutatión reducido (GSH), ácido ascórbico (vit C) y metalotioneínas (MTs) en las branquias de las almejas tratadas en comparación con los controles. Además, también se observó un aumento en la superóxidodismutasa (SOD) y una disminución significativa en las actividades de glutatión pero­xidasa (GPx). La acrilamida indujo neurotoxicidad como lo demuestra la inhibición de la actividad de la acetilcolinesterasa (AChE) de una manera dependiente de la dosis. En general, nuestros resultados indicaron que el estrés oxidativo puede con­siderarse como uno de los mecanismos detrás de la toxicidad por ACR en los bivalvos, aunque el tópico debería beneficiarse de más investigaciones

AVALIAÇÃO DA CAPTAÇÃO DE OLIGOELEMENTOS NO CARANGUEJO INVASIVO PORTUNUS SEGNIS HEPATOPANCREAS USANDO UMA ABORDAGEM BIOQUÍMICA MULTIVARIADA

In the current investigation, we evaluated the biological consequences of trace elements contamination in the two Tunisian gulfs (Gabes gulf and Tunis gulf) on the blue swimming crabs hepatopancreas (Portunus segnis). The concentrations of three trace elements (cadmium, copper, and lead) in the hepatopancreas P.segnis were evaluated. Additionally, acetylcholinesterase (AChE), metallothioneins (MTs), hydroxide peroxidase (H2O2) and advanced oxidation protein products (AOPP) levels, were chosen as measurements to evaluate the environmental effects on the two crabs’ populations from different gulfs. Macromolecular (lipids, proteins, and DNA) were also determined in P.segnis hepatopancreas. The results of trace elements bioaccumulation in soft P. segnis hepatopancreas showed a high pollution in the Gabes gulf as evidence by significant accumulation of cadmium, cooper, and lead. These findings were confirmed by significant increases of metal pollution index (MPI) and metallothioneins (MTs) levels in the hepatopancreas of P. segnis from Gabes gulf than these from Tunis gulf. Consequently, the trace elements accumulation in P.segnis from Gabes gulf conduct to the generation of lipid peroxidation processes as documented by the high levels of H2O2and LOOH. A significant decrease of AChE activity was recorded in crabs collected from Gabes gulf as compared to these from Tunis gulf. The present study revealed depletion of proteins and lipids contents, while DNA showed significant degradation on crab hepatopancreas collected from Gabes gulf comparing to Tunis gulf. These evidences must be taken in consideration when using P. segnis as an ecological indicator species in the biomonitoring programs.Na investigação atual, avaliamos as consequências biológicas da contaminação por oligoelementos nos dois golfos tunisinos (Golfo de Gabes e Golfo de Tunísia) sobre os caranguejos nados azuis hepatopâncreas (Portunus segnis). Foram avaliadas as concentrações de três oligoelementos (cádmio, cobre e chumbo) no hepatopâncreas P.segnis. Além disso, os níveis de acetilcolinesterase (AChE), metalotioninas (MTs), peroxidase hidróxida (H2O2) e produtos de proteína de oxidação avançada (AOPP) foram escolhidos como medidas para avaliar os efeitos ambientais nas populações dos dois caranguejos de diferentes golfos. Macromoleculares (lipídios, proteínas e DNA) também foram determinados em P.segnis hepatopâncreas. Os resultados da bioacumulação de elementos vestigiais em P. segnis hepatopancreas mole mostraram uma alta poluição no Golfo de Gabes como evidência pelo acúmulo significativo de cádmio, cobre e chumbo. Estes resultados foram confirmados por aumentos significativos do índice de poluição de metais (MPI) e dos níveis de metalotioninas (MTs) no hepatopâncreas de P. segnis do Golfo de Gabes do que estes do Golfo de Tunísia. Consequentemente, o acúmulo de elementos vestigiais em P.segnis do Golfo de Gabes conduz à geração de processos de peroxidação lipídica, como documentado pelos altos níveis de H2O2e LOOH. Uma diminuição significativa da atividade de AChE foi registrada em caranguejos coletados do Golfo de Gabes em comparação com estes do Golfo de Tunísia. O presente estudo revelou esgotamento de proteínas e conteúdo de lipídios, enquanto o DNA mostrou degradação significativa no hepatopâncreas de caranguejo coletado do Golfo de Gabes em comparação com o Golfo de Tunísia. Estas evidências devem ser levadas em consideração ao utilizar P. segnis como uma espécie indicadora ecológica nos programas de biomonitoramento

Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma.

We collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of >1,000 cases. We identified co-segregating mutations in histone-mutant subgroups including loss of FBXW7 in H3.3G34R/V, TOP3A rearrangements in H3.3K27M, and BCOR mutations in H3.1K27M. Histone wild-type subgroups are refined by the presence of key oncogenic events or methylation profiles more closely resembling lower-grade tumors. Genomic aberrations increase with age, highlighting the infant population as biologically and clinically distinct. Uncommon pathway dysregulation is seen in small subsets of tumors, further defining the molecular diversity of the disease, opening up avenues for biological study and providing a basis for functionally defined future treatment stratification

Functional diversity and co-operativity between subclonal populations of paediatric glioblastoma and diffuse intrinsic pontine glioma cells

The failure to develop effective therapies for pediatric glioblastoma (pGBM) and diffuse intrinsic pontine glioma (DIPG) is in part due to their intrinsic heterogeneity. We aimed to quantitatively assess the extent to which this was present in these tumors through subclonal genomic analyses and to determine whether distinct tumor subpopulations may interact to promote tumorigenesis by generating subclonal patient-derived models in vitro and in vivo. Analysis of 142 sequenced tumors revealed multiple tumor subclones, spatially and temporally coexisting in a stable manner as observed by multiple sampling strategies. We isolated genotypically and phenotypically distinct subpopulations that we propose cooperate to enhance tumorigenicity and resistance to therapy. Inactivating mutations in the H4K20 histone methyltransferase KMT5B (SUV420H1), present in <1% of cells, abrogate DNA repair and confer increased invasion and migration on neighboring cells, in vitro and in vivo, through chemokine signaling and modulation of integrins. These data indicate that even rare tumor subpopulations may exert profound effects on tumorigenesis as a whole and may represent a new avenue for therapeutic development. Unraveling the mechanisms of subclonal diversity and communication in pGBM and DIPG will be an important step toward overcoming barriers to effective treatments

Investigating otolith mass asymmetry in six benthic and pelagic fish species (Actinopterygii) from the Gulf of Tunis

Otolith mass asymmetry can significantly affect the vestibular system functionalities; usually, the X values of mass asymmetry vary between −0.2 and + 0.2 (−0.2 < X < + 0.2). These values can change during a fish life and therefore they are not related to the fish total length. We collected a total of 404 fish specimens from the Gulf of Tunis, including three pelagic species: Sardina pilchardus (Walbaum, 1792) (74 otolith pairs), Trachurus mediterraneus (Steindachner, 1868) (66 otolith pairs), and Chelon auratus (Risso, 1810) (60 otolith pairs) and three benthic species: Gobius niger Linnaeus, 1758 (77 otolith pairs), Mullus barbatus Linnaeus, 1758 (60 otolith pairs), and Trachinus draco Linnaeus, 1758 (67 otolith pairs). The relation between the total length and the otolith mass asymmetry was first calculated and compared, and then was evaluated. The comparison of the otolith mass asymmetry between benthic and pelagic species showed a significant difference (P < 0.05), where the absolute mean value of X does not exceed the critical value (0.2) for all the studied species. No relation has been found between the magnitude of the otolith mass asymmetry and the length in both benthic and pelagic specimens. Environmental factors have an indirect effect on somatic growth and otolith accretion. The significant difference found in this study can be due to the difference between the benthic and pelagic environments

Discovery of a Missing Link: First Observation of the HONO–Water Complex

International audienceThe still unexplained daytime HONO concentration in the Earth’s atmosphere and the impact of water on the HONO chemistry have been a mystery for decades. Several pathways and many modeling methods have failed to reproduce the atmospheric measurements. We reveal in this study the first spectroscopic observation and characterization of the complex of HONO with water observed through its rotational signature. Under the experimental conditions, HONO–water is stable, particularly straightforward to form, and features intense absorption signals. This could explain both the influence of water on the HONO chemistry and the missing HONO sources, as well as the missing contribution of many other molecules of atmospheric relevance that skew the accuracy of field measurements and the full account of partitioning species in the atmosphere

Functional diversity and cooperativity between subclonal populations of pediatric glioblastoma and diffuse intrinsic pontine glioma cells

The failure to develop effective therapies for pediatric glioblastoma (pGBM) and diffuse intrinsic pontine glioma (DIPG) is in part due to their intrinsic heterogeneity. We aimed to quantitatively assess the extent to which this was present in these tumors through subclonal genomic analyses and to determine whether distinct tumor subpopulations may interact to promote tumorigenesis by generating subclonal patient-derived models in vitro and in vivo. Analysis of 142 sequenced tumors revealed multiple tumor subclones, spatially and temporally coexisting in a stable manner as observed by multiple sampling strategies. We isolated genotypically and phenotypically distinct subpopulations that we propose cooperate to enhance tumorigenicity and resistance to therapy. Inactivating mutations in the H4K20 histone methyltransferase KMT5B (SUV420H1), present in <1% of cells, abrogate DNA repair and confer increased invasion and migration on neighboring cells, in vitro and in vivo, through chemokine signaling and modulation of integrins. These data indicate that even rare tumor subpopulations may exert profound effects on tumorigenesis as a whole and may represent a new avenue for therapeutic development. Unraveling the mechanisms of subclonal diversity and communication in pGBM and DIPG will be an important step toward overcoming barriers to effective treatments