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Jingmin Zhu, Xiao Huang, Hui Jiang, Lingling Hu, Jennifer J Michal, Zhihua Jiang, Huahong Shi
Evidence has shown that triphenyltin (TPT) triggers severe malformations in Xenopus tropicalis embryos, partly due to activation of PPARγ (peroxisome proliferator activated receptor γ) protein. In the present study, we investigated how abundance of pparγ and TPT exposure interact and affect X. tropicalis embryonic development. We observed pparγ expression signals appeared in the neural crest and neural fold, as well as in the brain, eyes and spinal cord organs. Both pparγ overexpression and its Morpholino (MO) knockdown inhibited pax6 (paired box 6) expression, a marker of eye development, and significantly up- and down-regulated lipid and glucose homeostasis related genes, such as lpl (lipoprotein lipase), slc2a4 (solute carrier family 2 (facilitated glucose transporter), member 4) and pck1 (phosphoenolpyruvate carboxykinase 1, cytosolic), thus inducing eye phenotypes...
August 15, 2018: Science of the Total Environment
Gustavo Cabral-Miranda, Ana R Cardoso, Luis C S Ferreira, M Goreti F Sales, Martin F Bachmann
Zika virus (ZIKV) recently emerged as a global threat subsequent to its global spread because it induces microencephaly and other brain damages in infants born to infected mothers. Epidemiological monitoring of infection has been hampered by the absence of reliable serological tests capable to distinguish between ZIKV and other Flavivirus infections, in particular Dengue virus (DENV). As both viruses are transmitted by the same mosquito-species, their distributions largely overlap and reliable serological distinction between the viruses is essential...
May 1, 2018: Biosensors & Bioelectronics
Ankita Thawani, Devika Sirohi, Richard J Kuhn, Donna M Fekete
Zika virus (ZIKV) is associated with severe neurodevelopmental impairments in human fetuses, including microencephaly. Previous reports examining neural progenitor tropism of ZIKV in organoid and animal models did not address whether the virus infects all neural progenitors uniformly. To explore this, ZIKV was injected into the neural tube of 2-day-old chicken embryos, resulting in nonuniform periventricular infection 3 days later. Recurrent foci of intense infection were present at specific signaling centers that influence neuroepithelial patterning at a distance through secretion of morphogens...
April 17, 2018: Cell Reports
P J Wichgers Schreur, L van Keulen, D Anjema, J Kant, J Kortekaas
Zika virus (ZIKV) is a mosquito-borne flavivirus that became associated with microcephaly in newborns and Guillain-Barré syndrome in adults after its emergence in the Pacific and the Americas in 2015. Newly developed rodent and nonhuman primate models have already revealed important insights into ZIKV-induced neuropathology. Nonhuman primates are phylogenetically closely related to humans and are therefore preferred human surrogates in ZIKV research. However, the use of nonhuman primates, particularly during gestation, raises ethical issues...
March 29, 2018: Emerging Microbes & Infections
Magdalena Sanz Cortes, Ana Maria Rivera, Mayel Yepez, Carolina V Guimaraes, Israel Diaz Yunes, Alexander Zarutskie, Ivan Davila, Anil Shetty, Arun Mahadev, Saray Maria Serrano, Nicolas Castillo, Wesley Lee, Gregory Valentine, Michael Belfort, Guido Parra, Carrie Mohila, Kjersti Aagaard, Miguel Parra Saavedra
BACKGROUND: Congenital Zika virus (ZIKV) infection can be detected in both the presence and absence of microcephaly and manifests as a number of signs and symptoms that are detected clinically and by neuroimaging. However, to date, qualitative and quantitative measures for the purpose of diagnosis and prognosis are limited. OBJECTIVES: Main objectives of this study conducted on fetuses and infants with confirmed congenital Zika virus infection and detected brain abnormalities were (1) to assess the prevalence of microcephaly and the frequency of the anomalies that include a detailed description based on ultrasound and magnetic resonance imaging in fetuses and ultrasound, magnetic resonance imaging, and computed tomography imaging postnatally, (2) to provide quantitative measures of fetal and infant brain findings by magnetic resonance imaging with the use of volumetric analyses and diffusion-weighted imaging, and (3) to obtain additional information from placental and fetal histopathologic assessments and postnatal clinical evaluations...
April 2018: American Journal of Obstetrics and Gynecology
Nadia Rachdaoui, Ling Li, Belinda Willard, Takhar Kasumov, Stephen Previs, Dipak Sarkar
BACKGROUND: Alcohol consumption during pregnancy is a significant public health problem and can result in a continuum of adverse outcomes to the fetus known as fetal alcohol spectrum disorders (FASD). Subjects with FASD show significant neurological deficits, ranging from microencephaly, neurobehavioral, and mental health problems to poor social adjustment and stress tolerance. Neurons are particularly sensitive to alcohol exposure. The neurotoxic action of alcohol, i.e., through ROS production, induces DNA damage and neuronal cell death by apoptosis...
2017: Clinical Epigenetics
Maia Delaine, Anne-Sophie Weingertner, Antoine Nougairede, Quentin Lepiller, Samira Fafi-Kremer, Romain Favre, Rémi Charrel
We report congenital microencephaly caused by infection with lymphocytic choriomeningitis virus in the fetus of a 29-year-old pregnant women at 23 weeks' gestation. The diagnosis was made by ultrasonography and negative results for other agents and confirmed by a positive PCR result for lymphocytic choriomeningitis virus in an amniotic fluid sample.
September 2017: Emerging Infectious Diseases
Jørgen S Agerholm, Fintan J McEvoy, Steffen Heegaard, Carole Charlier, Vidhya Jagannathan, Cord Drögemüller
BACKGROUND: Surveillance for bovine genetic diseases in Denmark identified a hitherto unreported congenital syndrome occurring among progeny of a Holstein sire used for artificial breeding. A genetic aetiology due to a dominant inheritance with incomplete penetrance or a mosaic germline mutation was suspected as all recorded cases were progeny of the same sire. Detailed investigations were performed to characterize the syndrome and to reveal its cause. RESULTS: Seven malformed calves were submitted examination...
August 2, 2017: BMC Genetics
Megan C Mladinich, John Schwedes, Erich R Mackow
Zika virus (ZIKV) is a mosquito-borne Flavivirus that has emerged as the cause of encephalitis and fetal microencephaly in the Americas. ZIKV uniquely persists in human bodily fluids for up to 6 months, is sexually transmitted, and traverses the placenta and the blood-brain barrier (BBB) to damage neurons. Cells that support persistent ZIKV replication and mechanisms by which ZIKV establishes persistence remain enigmatic but central to ZIKV entry into protected neuronal compartments. The endothelial cell (EC) lining of capillaries normally constrains transplacental transmission and forms the BBB, which selectively restricts access of blood constituents to neurons...
July 11, 2017: MBio
Bor Luen Tang
Zika virus (ZIKV) infection has been associated with congenital microcephaly and peripheral neuropathy. The ongoing epidemic has triggered swift responses in the scientific community, and a number of recent reports have now confirmed a causal relationship between ZIKV infection and birth defect. In particular, ZIKV has been shown to be capable of compromising and crossing the placental barrier and infect the developing fetal brain, resulting in the demise and functional impairment of neuroprogenitor cells critical for fetal cortex development...
September 2016: Archives of Microbiology
Pablo Martínez de Salazar, Anna Suy, Adrián Sánchez-Montalvá, Carlota Rodó, Fernando Salvador, Israel Molina
Zika fever is an arboviral systemic disease that has recently become a public health challenge of global concern after its spread through the Americas. This review highlights the current understanding on Zika virus epidemiology, its routes of transmission, clinical manifestations, diagnostic tests, and the current management, prevention and control strategies. It also delves the association between Zika infection and complications, such as microencephaly or Guillem-Barré syndrome.
April 2016: Enfermedades Infecciosas y Microbiología Clínica
Clare J Wilhelm, Marina Guizzetti
Alcohol consumption during pregnancy can produce a variety of central nervous system (CNS) abnormalities in the offspring resulting in a broad spectrum of cognitive and behavioral impairments that constitute the most severe and long-lasting effects observed in fetal alcohol spectrum disorders (FASD). Alcohol-induced abnormalities in glial cells have been suspected of contributing to the adverse effects of alcohol on the developing brain for several years, although much research still needs to be done to causally link the effects of alcohol on specific brain structures and behavior to alterations in glial cell development and function...
2015: Frontiers in Integrative Neuroscience
Amanjot Kaur Riar, Madhusudhanan Narasimhan, Mary Latha Rathinam, George I Henderson, Lenin Mahimainathan
BACKGROUND: Developing brain is a major target for alcohol's actions and neurological/functional abnormalities include microencephaly, reduced frontal cortex, mental retardation and attention-deficits. Previous studies have shown that ethanol altered the lateral ventricular neuroepithelial cell proliferation. However, the effect of ethanol on subventricular basal progenitors which generate majority of the cortical layers is not known. METHODS: We utilized spontaneously immortalized rat brain neuroblasts obtained from cultures of 18-day-old fetal rat cerebral cortices using in vitro ethanol exposures and an in utero binge model...
January 19, 2016: Journal of Biomedical Science
Diana Le Duc, Ana Spataru, Mihai Ceanga, Leon Zagrean, Torsten Schöneberg, Emil C Toescu, Ana-Maria Zagrean
Prenatal alcohol exposure is associated with microencephaly, cognitive and behavioral deficits, and growth retardation. Some of the mechanisms of ethanol-induced injury, such as high level oxidative stress and overexpression of pro-apoptotic genes, can increase the sensitivity of fetal neurons towards hypoxic/ischemic stress associated with normal labor. Thus, alcohol-induced sequelae may be the cumulative result of direct ethanol toxicity and increased neuronal vulnerability towards metabolic stressors, including hypoxia...
July 21, 2015: Brain Research
Jason Howitt, Ley-Hian Low, Ulrich Putz, Anh Doan, Jenny Lackovic, Choo-Peng Goh, Jenny Gunnersen, John Silke, Seong-Seng Tan
Pten controls a signaling axis that is implicated to regulate cell proliferation, growth, survival, migration, and metabolism. The molecular mechanisms underlying the specificity of Pten responses to such diverse cellular functions are currently poorly understood. Here we report the control of Pten activity and signaling specificity during the cell cycle by Ndfip1 regulation of Pten spatial distribution. Genetic deletion of Ndfip1 resulted in a loss of Pten nuclear compartmentalization and increased cell proliferation, despite cytoplasmic Pten remaining active in regulating PI3K/Akt signaling...
April 2015: Journal of Molecular Cell Biology
Bahri Karacay, Jo Mahoney, Jeffrey Plume, Daniel J Bonthius
BACKGROUND: Prenatal alcohol exposure can kill developing neurons, leading to microencephaly and mental retardation. However, not all fetuses are equally vulnerable to alcohol's neurotoxic effects. While some fetuses are severely affected and are ultimately diagnosed with fetal alcohol syndrome (FAS), others have no evidence of neuropathology and are behaviorally normal. These widely different outcomes among alcohol-exposed fetuses are likely due, in part, to genetic differences. Some fetuses possess genotypes that make them much more vulnerable than others to alcohol's teratogenic effects...
February 2015: Alcoholism, Clinical and Experimental Research
Daniel J Bonthius, Zachary Winters, Bahri Karacay, Samantha Larimer Bousquet, Daniel J Bonthius
The cerebellum is a major target of alcohol-induced damage in the developing brain. However, the cerebella of some children are much more seriously affected than others by prenatal alcohol exposure. As a consequence of in utero alcohol exposure, some children have substantial reductions in cerebellar volume and corresponding neurodevelopmental problems, including microencephaly, ataxia, and balance deficits, while other children who were exposed to similar alcohol quantities are spared. One factor that likely plays a key role in determining the impact of alcohol on the fetal cerebellum is genetics...
January 2015: Neurotoxicology
Yumi Okoshi, Masaharu Hayashi, Sachiko Kanda, Toshiyuki Yamamoto
We reported a 64-year-old autopsy case, showing a unique combination of disorders in visceral organs and brain. She had developmental delay, microencephaly, and facial dysmorphism. She developed sick sinus syndrome and liver cirrhosis. There were no abnormalities in laboratory tests for congenital metabolic errors or anomaly syndromes, including activities of lysosomal enzymes, isoelectric focusing of serum transferrin or array comparative genomic hybridization. She died of cardiorespiratory failure. At autopsy she showed liver cirrhosis and mesangial proliferation...
September 2014: Brain & Development
Joseph D Tingling, Shameena Bake, Rhonda Holgate, Jeremy Rawlings, Phillips P Nagsuk, Jayashree Chandrasekharan, Sarah L Schneider, Rajesh C Miranda
BACKGROUND: Ethanol is a potent teratogen. Its adverse neural effects are partly mediated by disrupting fetal neurogenesis. The teratogenic process is poorly understood, and vulnerable neurogenic stages have not been identified. Identifying these is a prerequisite for therapeutic interventions to mitigate effects of teratogen exposures. METHODS: We used flow cytometry and qRT-PCR to screen fetal mouse-derived neurosphere cultures for ethanol-sensitive neural stem cell (NSC) subpopulations, to study NSC renewal and differentiation...
2013: PloS One
Azam Ramezani, Iran Goudarzi, Taghi Lashkarboluki, Mohammad Taghi Ghorbanian, Kataneh Abrari, Mahmoudi Elahdadi Salmani
OBJECTIVE(S): The purpose of this study was to investigate the role of oxidative stress in Purkinje cell neurotoxicity of ethanol-treated rat. MATERIALS AND METHODS: Male rat pups 4-day-old was used in this study. Ethanol was administered to rat pups at a dose of 6 g/kg from postnatal days (PDs) 4 to 5. Pups were killed 90 min after the second alcohol treatment on PD 5 by decapitation and the brain was immediately removed. The cerebellum was dissected for analyzing the oxidative stress parameters and histological study...
July 2012: Iranian Journal of Basic Medical Sciences
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