Neuropilin 1 signaling guides neural crest cells to coordinate pathway choice with cell specification

Neural crest cells (NCCs) are highly motile embryonic stem cells that delaminate from the neuroectoderm early during vertebrate embryogenesis and differentiate at defined target sites into various essential cell types. To reach their targets, NCCs follow 1 of 3 sequential pathways that correlate with NCC fate. The firstborn NCCs travel ventrally alongside intersomitic blood vessels to form sympathetic neuronal progenitors near the dorsal aorta, while the lastborn NCCs migrate superficially beneath the epidermis to give rise to melanocytes. Yet, most NCCs enter the somites to form the intermediate wave that gives rise to sympathetic and sensory neurons. Here we show that the repulsive guidance cue SEMA3A and its receptor neuropilin 1 (NRP1) are essential to direct the intermediate wave NCC precursors of peripheral neurons from a default pathway alongside intersomitic blood vessels into the anterior sclerotome. Thus, loss of function for either gene caused excessive intersomitic NCC migration, and this led to ectopic neuronal differentiation along both the anteroposterior and dorsoventral axes of the trunk. The choice of migratory pathway did not affect the specification of NCCs, as they retained their commitment to differentiate into sympathetic or sensory neurons, even when they migrated on an ectopic dorsolateral path that is normally taken by melanocyte precursors. We conclude that NRP1 signaling coordinates pathway choice with NCC fate and therefore confines neuronal differentiation to appropriate locations

Lupus Myelopathy in a Child

A 5-year-old female developed, after a 7-month period of fever, anorexia, weight loss, and a transitory cutaneous erythematous eruption, a severe acute transverse myelopathy, with a partial recovery of motor and sensory function. She had positive antinuclear and antidouble-stranded DNA antibodies but no antiphospholipid antibodies. Six months later she had massive proteinuria and restarted treatment with steroids and cyclophosphamide. Our patient is one of the youngest reported with lupus myelopathy. We discuss the clinical presentation, the magnetic resonance imaging findings, and other relevant laboratory studies of this rare but serious complication of systemic lupus erythematosus

Neuropilin 1 and 2 control cranial gangliogenesis and axon guidance through neural crest cells

Neuropilin (NRP) receptors and their class 3 semaphorin (SEMA3) ligands play well-established roles in axon guidance, with loss of NRP1, NRP2, SEMA3A or SEMA3F causing defasciculation and errors in growth cone guidance of peripherally projecting nerves. Here we report that loss of NRP1 or NRP2 also impairs sensory neuron positioning in the mouse head, and that this defect is a consequence of inappropriate cranial neural crest cell migration. Specifically, neural crest cells move into the normally crest-free territory between the trigeminal and hyoid neural crest streams and recruit sensory neurons from the otic placode; these ectopic neurons then extend axons between the trigeminal and facioacoustic ganglia. Moreover, we found that NRP1 and NRP2 cooperate to guide cranial neural crest cells and position sensory neurons; thus, in the absence of SEMA3/NRP signalling, the segmentation of the cranial nervous system is lost. We conclude that neuropilins play multiple roles in the sensory nervous system by directing cranial neural crest cells, positioning sensory neurons and organising their axonal projections

Metastatic small bowel occlusion as initial presentation of squamous cell carcinoma of the lung

info:eu-repo/semantics/publishedVersio

Fatty acid production by four strains of Mucor hiemalis grown in plant oil and soluble carbohydrates

Four Mucor hiemalis strains (M1, M2, M3 and M4), isolated from soil at a depth of 0 - 15 cm in the Juréia- Itatins Ecology Station (JIES), in the state of São Paulo, Brazil and were evaluated for the production of-linolenic (GLA) and other unsaturated fatty acids. Five growth variables (temperature, pH, carbon source, nitrogen source, and vegetable oils) were studied. Liquid media containing 2% vegetable oil (palm oil, canola oil, soybean oil, sesame oil, or sunflower oil) or 2% carbohydrate (fructose, galactose, glycerol, glucose, lactose, maltose, sucrose, sorbitol or xylose) and 1% yeast extract as a nitrogen source were used. The greatest biomass production was observed with M3 and M4 strains in palm oil (91.5 g l-1) and sunflower oil (68.3 g l-1) media, respectively. Strain M4 produced greater quantities of polyunsaturated acids in medium containing glucose. The GLA production in the M4 biomass was 1,132.2 mg l-1 in glucose medium. Plant oils were inhibitors of fatty acid production by these strains

Disfunção tiróidea e amiodarona

Although most patients remain clinically euthyroid, some develop amiodarone-induced hyperthyroidism (HPEAI) or hypothyroidism (HPOAI). The authors present a retrospective analysis of ten patients with amiodarone-induced thyroid dysfunction. Six patients were female and mean amiodarone intake was 17.7 months. HPOIA was more common (six patients). From all the patients with HPEAI, two had type 2, one had type 1, and one had type 3 hyperthyroidism. Symptoms suggestive of thyroid dysfunction occurred in five patients, most of them with HPOAI. In HPEAI, the most frequent symptom was exacerbation of arrhythmia (three patients). Discontinuation of amiodarone and treatment with levothyroxine was chosen in 83.3% of the HPOAI cases, while thyonamide treatment with corticosteroids and without amiodarone was the option in 75% of the HPEAI cases. There were three deaths, all in patients with HPEAI. HPEAI is potentially fatal. The clinical picture may be vague, so the thyroid monitoring is mandatory

TERTp mutations and p53 expression in head and neck cutaneous basal cell carcinomas with different aggressive features

Cutaneous basal cell carcinoma (cBCC) is an economic burden to health services, due to its great morbidity and increasing incidence in old people. Infiltrative cBCCs and cBCCs with micronodular pattern are considered as more aggressive. The role of p53 expression and TERTp mutation on cBCC behavior remains to be clarified. We aimed to assess TERTp mutations and p53 expression in relation to the cBCC histological subtype in a cohort of patients referred to an ENT Department of a tertiary Hospital of Northern Portugal. We performed a retrospective clinicopathological and histological review of the head and neck cBCCs followed-up at the otorhinolaryngology department of Trás-os-Montes e Alto Douro hospital (January 2007–June 2018). We assessed TERTp mutations in 142 cBCCs and p53 protein expression, through immunohistochemistry, in 157 cBCCs. We detected TERTp mutations in 43.7% of cBCCs and p53 overexpression in 60.5% of cBCCs. We spotted association of p53 overexpression and TERTp mutation with necrosis. In the infitrative-growth pattern cBCCs, there was no significant association with the clinical and histological features evaluated, except for necrosis. In the indolent-growth cBCCs, we identified a significant association of TERTp mutation status with female sex, necrosis, multiple cBCCs, and p53 positive expression. Our results suggest that TERTp mutation may be useful to identify more aggressive features in the indolent-growth pattern cBCCs (nodular and superficial subtypes). Further studies with larger cohorts are warranted to clarify the relevance of TERTp mutation in cBCCs.This study was supported by FCT, the Portuguese Foundation for Science and Technology through a Ph.D. Grant to SM (SFRH/BD/137802/2018). This work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT-Fundação para a Ciência e a Tecnolo-gia/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274). Additional funding by the European Regional Development Fund (ERDF) through the Operational Programme for Competitiveness and Internationalization—COMPETE2020, and Portuguese national funds via FCT, under project POCI-01-0145-FEDER-016390: CANCEL STEM and from the FCT, under the project POCI-01-0145-FEDER-031438: The other faces of telomerase: Looking beyond tumour immortalization (PDTC/MED-ONC/31438/2017)

Giant cell glioblastoma: review of the literature and illustrated case

Giant cell glioblastoma is an infrequent variety of glioblastoma (5% of the cases). It has deserved a separate category in the World Health Organization classification of grade IV tumors. The clinical, imaging, histological and immunohistochemical characteristics, and the genetic alterations are reviewed. Treatment and prognosis are discussed and updated. The case of a patient that survived 19 months and died of spinal leptomeningeal metastases is illustrated

Mechanical study of PLA-PCL fibers during in vitro degradation

The aliphatic polyesters are widely used in biomedical applications since they are susceptible to hydrolytic and/or enzymatic chain cleavage, leading to alpha-hydroxyacids, generally metabolized in the human body. This is particularly useful for many biomedical applications, especially, for temporary mechanical supports in regenerative medical devices. Ideally, the degradation should be compatible with the tissue recovering. In this work, the evolution of mechanical properties during degradation is discussed based on experimental data. The decrease of tensile strength of PLA-PCL fibers follows the same trend as the decrease of molecular weight, and so it can also be modeled using a first order equation. For each degradation stage, hyperelastic models such as Neo-Hookean, Mooney-Rivlin and second reduced order, allow a reasonable approximation of the material behavior. Based on this knowledge, constitutive models that describe the mechanical behavior during degradation are proposed and experimentally validated. The proposed theoretical models and methods may be adapted and used in other biodegradable materials, and can be considered fundamental tools in the design of regenerative medical devices where strain energy is an important requirement, such as, for example, ligaments, cartilage and stents