The Experts below are selected from a list of 285 Experts worldwide ranked by ideXlab platform
Jessica E Messier - One of the best experts on this subject based on the ideXlab platform.
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stxbp1 munc18 1 haploinsufficiency in mice recapitulates key features of stxbp1 encephalopathy and impairs cortical inhibition
bioRxiv, 2019Co-Authors: Eugene S Chao, Hsiaotuan Chao, Jessica E Messier, Hongmei Chen, Wu Yi-chenAbstract:Abstract Mutations in genes encoding synaptic proteins cause many neurodevelopmental disorders, but the underlying pathogeneses are poorly understood. Syntaxin-binding protein 1 (STXBP1) is an essential component of the neurotransmitter release machinery. Its de novo heterozygous mutations are among the most frequent causes of neurodevelopmental disorders including intellectual disabilities and epilepsies. These disorders, collectively referred to as STXBP1 encephalopathy, affect a broad spectrum of neurological and neuropsychiatric features common among neurodevelopmental disorders. To gain insight into STXBP1 encephalopathy Pathogenesis, we generated new Stxbp1 null alleles in mice and found that Stxbp1 haploinsufficiency impaired cognitive, psychiatric, and motor functions and caused cortical hyperexcitability and seizures. Surprisingly, Stxbp1 haploinsufficiency reduced neurotransmission from cortical parvalbumin- and somatostatin-expressing GABAergic interneurons by differentially decreasing the synaptic strength and connectivity, respectively. These results demonstrate that Stxbp1 haploinsufficient mice recapitulate key features of STXBP1 encephalopathy and indicate that inhibitory dysfunction is likely a key contributor to the disease Pathogenesis.
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Stxbp1/Munc18-1 haploinsufficiency in mice recapitulates key features of STXBP1 encephalopathy and impairs cortical inhibition
bioRxiv, 2019Co-Authors: Wu Yi-chen, Eugene S Chao, Hsiaotuan Chao, Jessica E Messier, Huda Y. Zoghbi, Hongmei Chen, Jianrong TangAbstract:Abstract Mutations in genes encoding synaptic proteins cause many neurodevelopmental disorders, but the underlying pathogeneses are poorly understood. Syntaxin-binding protein 1 (STXBP1) is an essential component of the neurotransmitter release machinery. Its de novo heterozygous mutations are among the most frequent causes of neurodevelopmental disorders including intellectual disabilities and epilepsies. These disorders, collectively referred to as STXBP1 encephalopathy, affect a broad spectrum of neurological and neuropsychiatric features common among neurodevelopmental disorders. To gain insight into STXBP1 encephalopathy Pathogenesis, we generated new Stxbp1 null alleles in mice and found that Stxbp1 haploinsufficiency impaired cognitive, psychiatric, and motor functions and caused cortical hyperexcitability and seizures. Surprisingly, Stxbp1 haploinsufficiency reduced neurotransmission from cortical parvalbumin- and somatostatin-expressing GABAergic interneurons by differentially decreasing the synaptic strength and connectivity, respectively. These results demonstrate that Stxbp1 haploinsufficient mice recapitulate key features of STXBP1 encephalopathy and indicate that inhibitory dysfunction is likely a key contributor to the disease Pathogenesis.
Rita R. Colwell - One of the best experts on this subject based on the ideXlab platform.
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Vibrio ecology, Pathogenesis and evolution - Vibrio ecology, Pathogenesis, and evolution.
Frontiers in microbiology, 2014Co-Authors: Daniela Ceccarelli, Rita R. ColwellAbstract:This Research Topic brings together 24 articles that highlight the most recent research findings concerning the biology of the genus Vibrio and covers pathogenicity and host interaction, genome plasticity and evolution, and the dynamics of factors influencing the ecology of vibrios. Vibrio comprises one of the most diverse marine bacterial genera (Gomez-Gil et al., 2014), and its diversity is emphasized in two of the articles opening this set of Research Topic papers. Sawabe et al. (2013) present a molecular phylogeny of 86 Vibrio species based on genome sequencing that provides insight into Vibrio biodiversity and evolutionary history. In a study of more than 300 Vibrio genome sequences, Lukjancenko and Ussery (2014) conclude that the Vibrio pan-genome comprises 17,000 gene families, differentially present and/or expressed in any given species. A remarkable feature of all Vibrio species is an highly plastic genome, a feature examined in five papers. The two chromosomes are shaped by horizontal gene transfer involving, among others, antibiotic resistance, virulence, and niche adaptation (Rowe-Magnus et al., 2001; Kirkup et al., 2010). V. vulnificus biotype 3 is a notable example. Efimov et al. (2013) suggest biotype 3 evolved from biotype 1 by acquisition of unique genes from other bacterial species, such as Shewanella, sharing the same ecological niche. Carraro et al. (2014) employ molecular and functional characterization of pVCR94, to identify the role of IncA/C plasmids in antibiotic resistance in a Rwandan V. cholerae isolate. A retrospective analysis of epidemic V. cholerae in Angola is reported by Valia et al. (2013), showing unexpected genomic variability among variants, highlighting the role of genomic islands, phages, and integrative conjugative elements in the genetic diversity of V. cholerae in a single epidemic. Rivas et al. (2013) describe acquisition by Photobacterium damselae subsp. damselae of virulence plasmid pPHDD1 that encodes pore-forming toxins and hemolysins which play a key role in virulence for both fish and humans. A review by Rapa and Labbate (2013) describes the role of integrons in Vibrio species for which gene cassettes comprise approximately 1–3% of the entire genome and are very likely involved in bacterial adaptation and evolution. Nine of the manuscripts analyze Vibrio pathogenicity, disease development, specificity, and adaptation in both human and animal hosts. Tan et al. (2014) deciphered the biosynthetic network of the siderophore vulnibactin, essential in iron uptake from host proteins, the importance of which in V. vulnificus pathogenicity has been clinically demonstrated. Inhibition/resistance mechanisms developed by V. salmonicida, the causative agent of hemorrhagic septicemia in Atlantic salmon, is described by Bjelland et al. (2013), who show that it overcomes the salmon innate immune system to a point where the infection overwhelms the host. The role in bacterial virulence of diverse extracellular proteolytic enzymes secreted by human pathogenic Vibrio species is the focus of a review by Miyoshi (2013). The engagement of type VI secretion systems by V. cholerae is suggested as a means of intra- and inter-species predation and nutrient acquisition, inducing rapid multiplication in the human host (Pukatzki and Provenzano, 2013). The bioluminescent marine bacterium V. campbellii is used by Wang et al. (2013) to analyze the pyomelanin-pigmented phenotype, known to provide Vibrio species with greater UV and oxidative stress resistance and enhanced intestine colonization. The relationship between pathogenicity and motility in Vibrio species and the contribution of flagella to adhesion and biofilm formation are discussed by Zhu et al. (2013). The largely unexplored V. fluvialis mechanisms of Pathogenesis, survival and fitness are reviewed by Ramamurthy et al. (2014). Twenty new Vibrio species associated with molluscans are described and their pathogenic potential for molluscs elucidated by Romalde et al. (2014). The exquisite bacteria–host interaction between V. fisheri and its squid host, Euprymna scolopes, is described in detail, as are the molecular pathways of biofilm formation, motility, and chemotaxis (Norsworthy and Visick, 2013). The capacity of Vibrio species to persist in the aquatic environment, their ecology and association with abiotic and biotic factors, as well as environmental surveillance for public health (Lipp et al., 2002; Grimes et al., 2009; Johnson, 2013) comprise a section in the Research Topic that opens with a review by Lutz et al. (2013) elucidating complex mechanisms enabling V. cholerae to withstand starvation, temperature fluctuation, salinity variation, and predation. Haley et al. (2014) report water temperature increase can be correlated with rise of a diverse population of V. parahaemolyticus, some of which carry pandemic markers, in water and plankton along the Georgian coast of the Black Sea. V. parahaemolyticus and V. vulnificus populations associated with oyster, sediment, and surface water related to a hurricane event in the Chesapeake Bay are concluded to be influenced by wave energy and sediment resuspension (Shaw et al., 2014). Canesi et al. (2013) show the serum of Mytilus galloprovincialis promotes phagocytosis and killing by hemocytes of both V. cholerae O1 and non-O1/non-O139 in edible bivalves. Chakraborty et al. (2013) evaluate a sensitive and specific dipstick test to detect toxigenic V. cholerae in water, validating a simple, inexpensive method for use in areas at risk of cholera. Three articles addressing Vibrio environmental diversity and dynamics complete this Research Topic. Mansergh and Zehr (2014) suggest that the natural shift of Vibrio populations in Monterey Bay is affected by larger oceanographic conditions (flow velocities and wind patterns), rather than individual environmental factors. Meta-analysis of environmental variables and Vibrio association with plants, algae, zooplankton, and animals are reviewed by Takemura et al. (2014). As a final point concerning environmental distribution, Constantin De Magny et al. (2014) propose temporal shifts, zooplankton community variability, and occurrence of V. cholerae in the aquatic environment are related to cholera dynamics. These factors, analyzed by metagenomics, permit greater understanding of community structure, function, and competition. In summary, the collection of manuscripts provided in this Research Topic offers a comprehensive exploration of Vibrio biology, from the single gene to the bacterial community, elucidating Vibrio molecular pathways and evolutionary history. This special issue shows the significant progress achieved in understanding the complex biology of the genus Vibrio and should both stimulate discussion and offer a challenge to researchers in microbial ecology and evolution.
Wu Yi-chen - One of the best experts on this subject based on the ideXlab platform.
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stxbp1 munc18 1 haploinsufficiency in mice recapitulates key features of stxbp1 encephalopathy and impairs cortical inhibition
bioRxiv, 2019Co-Authors: Eugene S Chao, Hsiaotuan Chao, Jessica E Messier, Hongmei Chen, Wu Yi-chenAbstract:Abstract Mutations in genes encoding synaptic proteins cause many neurodevelopmental disorders, but the underlying pathogeneses are poorly understood. Syntaxin-binding protein 1 (STXBP1) is an essential component of the neurotransmitter release machinery. Its de novo heterozygous mutations are among the most frequent causes of neurodevelopmental disorders including intellectual disabilities and epilepsies. These disorders, collectively referred to as STXBP1 encephalopathy, affect a broad spectrum of neurological and neuropsychiatric features common among neurodevelopmental disorders. To gain insight into STXBP1 encephalopathy Pathogenesis, we generated new Stxbp1 null alleles in mice and found that Stxbp1 haploinsufficiency impaired cognitive, psychiatric, and motor functions and caused cortical hyperexcitability and seizures. Surprisingly, Stxbp1 haploinsufficiency reduced neurotransmission from cortical parvalbumin- and somatostatin-expressing GABAergic interneurons by differentially decreasing the synaptic strength and connectivity, respectively. These results demonstrate that Stxbp1 haploinsufficient mice recapitulate key features of STXBP1 encephalopathy and indicate that inhibitory dysfunction is likely a key contributor to the disease Pathogenesis.
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Stxbp1/Munc18-1 haploinsufficiency in mice recapitulates key features of STXBP1 encephalopathy and impairs cortical inhibition
bioRxiv, 2019Co-Authors: Wu Yi-chen, Eugene S Chao, Hsiaotuan Chao, Jessica E Messier, Huda Y. Zoghbi, Hongmei Chen, Jianrong TangAbstract:Abstract Mutations in genes encoding synaptic proteins cause many neurodevelopmental disorders, but the underlying pathogeneses are poorly understood. Syntaxin-binding protein 1 (STXBP1) is an essential component of the neurotransmitter release machinery. Its de novo heterozygous mutations are among the most frequent causes of neurodevelopmental disorders including intellectual disabilities and epilepsies. These disorders, collectively referred to as STXBP1 encephalopathy, affect a broad spectrum of neurological and neuropsychiatric features common among neurodevelopmental disorders. To gain insight into STXBP1 encephalopathy Pathogenesis, we generated new Stxbp1 null alleles in mice and found that Stxbp1 haploinsufficiency impaired cognitive, psychiatric, and motor functions and caused cortical hyperexcitability and seizures. Surprisingly, Stxbp1 haploinsufficiency reduced neurotransmission from cortical parvalbumin- and somatostatin-expressing GABAergic interneurons by differentially decreasing the synaptic strength and connectivity, respectively. These results demonstrate that Stxbp1 haploinsufficient mice recapitulate key features of STXBP1 encephalopathy and indicate that inhibitory dysfunction is likely a key contributor to the disease Pathogenesis.
Michael M. Paparella - One of the best experts on this subject based on the ideXlab platform.
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Otological Perspectives and Pathogenesis
Auris Nasus Larynx, 1996Co-Authors: Michael M. PaparellaAbstract:Abstract All the major developments in clinical otology are prologue to future knowledge, some of which we cannot yet anticipate. The foundation for research, education, and clinical care is understanding the pathogeneses of diseases. Research on this grows from clinical observations by individuals, who should publish. We need to understand and treat disease-processes, not just their surface signs. Education (communicating with colleagues) should aim at teaching approaches to Pathogenesis, not just demonstrating “vocational” techniques; it should continue throughout a physician's lifetime; and it should make use of increasingly available mechanisms for global communication, to benefit patients. Four clinical problems for which we now better understand the Pathogenesis will illustrate how understanding of their Pathogenesis, developed in research and communicated in education, can affect clinical care. The illustrations are: sensorineural hearing loss, otitis media, Meniere's disease, and diseases manifesting interactions between middle ear and inner ear. Understanding and sometimes altering Pathogenesis can allow prevention, not just treatment and rehabilitation of disease.
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Pathogenesis of tympanosclerosis
Otolaryngology-Head and Neck Surgery, 1993Co-Authors: Mahesh H Bhaya, Patricia A. Schachern, Tetsuo Morizono, Michael M. PaparellaAbstract:In spite of the wealth of information on the clinical, histologic, and pathologic aspects of tympanosclerosis, the Pathogenesis of tympanosclerosis is still unclear. In an attempt to understand the Pathogenesis, 319 human temporal bones from 196 individuals with otitis media were studied. The extent and nature of tympanosclerosis and the characteristics of the otitis media associated with it were studied. Forty-five temporal bones from 35 individuals with otitis media were found to have tympanosclerosis, giving an incidence of 14.1%. It was seen most commonly in individuals over 40 years of age (86.7%). The male-to-female ratio was 1.6:1. The most common site of occurrence was the tympanic membrane (88.9%). Tympanosclerosis was seen more often in the anterior and posterior inferior quadrants of the tympanic membrane and that, too, in a central position. Tympanosclerosis was seen more commonly in temporal bones with irreversible inflammatory changes, and in this group, late plaques were more commonly seen ...
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Pathogenesis of tympanosclerosis.
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery, 1993Co-Authors: Mahesh H Bhaya, Patricia A. Schachern, Tetsuo Morizono, Michael M. PaparellaAbstract:In spite of the wealth of information on the clinical, histologic, and pathologic aspects of tympanosclerosis, the Pathogenesis of tympanosclerosis is still unclear. In an attempt to understand the Pathogenesis, 319 human temporal bones from 196 individuals with otitis media were studied. The extent and nature of tympanosclerosis and the characteristics of the otitis media associated with it were studied. Forty-five temporal bones from 35 individuals with otitis media were found to have tympanosclerosis, giving an incidence of 14.1%. It was seen most commonly in individuals over 40 years of age (86.7%). The male-to-female ratio was 1.6:1. The most common site of occurrence was the tympanic membrane (88.9%). Tympanosclerosis was seen more often in the anterior and posterior inferior quadrants of the tympanic membrane and that, too, in a central position. Tympanosclerosis was seen more commonly in temporal bones with irreversible inflammatory changes, and in this group, late plaques were more commonly seen than early or intermediate plaques. Audiometric charts failed to show any direct relationship between extent of tympanosclerosis and the severity of hearing loss. The only audiometric finding of any consequence was a mixed hearing loss in the presence of middle ear tympanosclerosis.
Eugene S Chao - One of the best experts on this subject based on the ideXlab platform.
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stxbp1 munc18 1 haploinsufficiency in mice recapitulates key features of stxbp1 encephalopathy and impairs cortical inhibition
bioRxiv, 2019Co-Authors: Eugene S Chao, Hsiaotuan Chao, Jessica E Messier, Hongmei Chen, Wu Yi-chenAbstract:Abstract Mutations in genes encoding synaptic proteins cause many neurodevelopmental disorders, but the underlying pathogeneses are poorly understood. Syntaxin-binding protein 1 (STXBP1) is an essential component of the neurotransmitter release machinery. Its de novo heterozygous mutations are among the most frequent causes of neurodevelopmental disorders including intellectual disabilities and epilepsies. These disorders, collectively referred to as STXBP1 encephalopathy, affect a broad spectrum of neurological and neuropsychiatric features common among neurodevelopmental disorders. To gain insight into STXBP1 encephalopathy Pathogenesis, we generated new Stxbp1 null alleles in mice and found that Stxbp1 haploinsufficiency impaired cognitive, psychiatric, and motor functions and caused cortical hyperexcitability and seizures. Surprisingly, Stxbp1 haploinsufficiency reduced neurotransmission from cortical parvalbumin- and somatostatin-expressing GABAergic interneurons by differentially decreasing the synaptic strength and connectivity, respectively. These results demonstrate that Stxbp1 haploinsufficient mice recapitulate key features of STXBP1 encephalopathy and indicate that inhibitory dysfunction is likely a key contributor to the disease Pathogenesis.
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Stxbp1/Munc18-1 haploinsufficiency in mice recapitulates key features of STXBP1 encephalopathy and impairs cortical inhibition
bioRxiv, 2019Co-Authors: Wu Yi-chen, Eugene S Chao, Hsiaotuan Chao, Jessica E Messier, Huda Y. Zoghbi, Hongmei Chen, Jianrong TangAbstract:Abstract Mutations in genes encoding synaptic proteins cause many neurodevelopmental disorders, but the underlying pathogeneses are poorly understood. Syntaxin-binding protein 1 (STXBP1) is an essential component of the neurotransmitter release machinery. Its de novo heterozygous mutations are among the most frequent causes of neurodevelopmental disorders including intellectual disabilities and epilepsies. These disorders, collectively referred to as STXBP1 encephalopathy, affect a broad spectrum of neurological and neuropsychiatric features common among neurodevelopmental disorders. To gain insight into STXBP1 encephalopathy Pathogenesis, we generated new Stxbp1 null alleles in mice and found that Stxbp1 haploinsufficiency impaired cognitive, psychiatric, and motor functions and caused cortical hyperexcitability and seizures. Surprisingly, Stxbp1 haploinsufficiency reduced neurotransmission from cortical parvalbumin- and somatostatin-expressing GABAergic interneurons by differentially decreasing the synaptic strength and connectivity, respectively. These results demonstrate that Stxbp1 haploinsufficient mice recapitulate key features of STXBP1 encephalopathy and indicate that inhibitory dysfunction is likely a key contributor to the disease Pathogenesis.
