Skip to main content

Publications search

Found 37443 matches. Displaying 1511-1520
Bartsch TF, Villasante CM, Hengel FE, Toure A, Firester DM, Oswald A, Hudspeth AJ
Show All Authors

Measurement of hindered diffusion in complex geometries for high-speed studies of single-molecule forces (opens in new window)

SCIENTIFIC REPORTS 2021 JAN 26; 11(1):? Article 2196
Show Abstract
In a high-speed single-molecule experiment with a force probe, a protein is tethered between two substrates that are manipulated to exert force on the system. To avoid nonspecific interactions between the protein and nearby substrates, the protein is usually attached to the substrates through long, flexible linkers. This approach precludes measurements of mechanical properties with high spatial and temporal resolution, for rapidly exerted forces are dissipated into the linkers. Because mammalian hearing operates at frequencies reaching tens to hundreds of kilohertz, the mechanical processes that occur during transduction are of very short duration. Single-molecule experiments on the relevant proteins therefore cannot involve long tethers. We previously characterized the mechanical properties of protocadherin 15 (PCDH15), a protein essential for human hearing, by tethering an individual monomer through very short linkers between a probe bead held in an optical trap and a pedestal bead immobilized on a glass coverslip. Because the two confining surfaces were separated by only the length of the tethered protein, hydrodynamic coupling between those surfaces complicated the interpretation of the data. To facilitate our experiments, we characterize here the anisotropic and position-dependent diffusion coefficient of a probe in the presence of an effectively infinite wall, the coverslip, and of the immobile pedestal.
Bastard P, Manry J, Chen J, Rosain J, Seeleuthner Y, AbuZaitun O, Lorenzo L, Khan T, Hasek M, Hernandez N, Bigio B, Zhang P, Levy R, Shrot S, Reino EJG, Lee YS, Boucherit S, Aubart M, Gijsbers R, Beziat V, Li Z, Pellegrini S, Rozenberg F, Marr N, Meyts I, Boisson B, Cobat A, Bustamante J, Zhang Q, Jouangy E, Abel L, Somech R, Casanova JL, Zhang SY
Show All Authors

Herpes simplex encephalitis in a patient with a distinctive form of inherited IFNAR1 deficiency (opens in new window)

JOURNAL OF CLINICAL INVESTIGATION 2021 JAN 4; 131(1):? Article e139980
Show Abstract
Inborn errors of TLR3-dependent IFN-alpha/beta- and IFN-lambda-mediated immunity in the CNS can underlie herpes simplex virus 1 (HSV-1) encephalitis (HSE). The respective contributions of IFN-alpha/beta and IFN-lambda are unknown. We report a child homozygous for a genomic deletion of the entire coding sequence and part of the 3'-UTR of the last exon of IFNAR1, who died of HSE at the age of 2 years. An older cousin died following vaccination against measles, mumps, and rubella at 12 months of age, and another 17-year-old cousin homozygous for the same variant has had other, less severe, viral illnesses. The encoded IFNAR1 protein is expressed on the cell surface but is truncated and cannot interact with the tyrosine kinase TYK2. The patient's fibroblasts and EBV-B cells did not respond to IFN-alpha 2b or IFN-beta, in terms of STAT1, STAT2, and STAT3 phosphorylation or the genome-wide induction of IFN-stimulated genes. The patient's fibroblasts were susceptible to viruses, including HSV-1, even in the presence of exogenous IFN-alpha 2b or IFN-beta. HSE is therefore a consequence of inherited complete IFNAR1 deficiency. This viral disease occurred in natural conditions, unlike those previously reported in other patients with IFNAR1 or IFNAR2 deficiency. This experiment of nature indicates that IFN-alpha/beta are essential for anti-HSV-1 immunity in the CNS.
Chandler JA, Cabrera LY, Doshi P, Fecteau S, Fins JJ, Guinjoan S, Hamani C, Herrera-Ferra K, Honey CM, Illes J, Kopell BH, Lipsman N, McDonald PJ, Mayberg HS, Nadler R, Nuttin B, Oliveira-Maia AJ, Rangel C, Ribeiro R, Salles A, Wu HM
Show All Authors

International Legal Approaches to Neurosurgery for Psychiatric Disorders (opens in new window)

FRONTIERS IN HUMAN NEUROSCIENCE 2021 JAN 13; 14(?):? Article 588458
Show Abstract
Neurosurgery for psychiatric disorders (NPD), also sometimes referred to as psychosurgery, is rapidly evolving, with new techniques and indications being investigated actively. Many within the field have suggested that some form of guidelines or regulations are needed to help ensure that a promising field develops safely. Multiple countries have enacted specific laws regulating NPD. This article reviews NPD-specific laws drawn from North and South America, Asia and Europe, in order to identify the typical form and contents of these laws and to set the groundwork for the design of an optimal regulation for the field. Key challenges for this design that are revealed by the review are how to define the scope of the law (what should be regulated), what types of regulations are required (eligibility criteria, approval procedures, data collection, and oversight mechanisms), and how to approach international harmonization given the potential migration of researchers and patients.
Schureck MA, Darling JE, Merk A, Shao JF, Daggupati G, Srinivasan P, Olinares PDB, Rout MP, Chait BT, Wollenberg K, Subramaniam S, Desai SA
Show All Authors

Malaria parasites use a soluble RhopH complex for erythrocyte invasion and an integral form for nutrient uptake (opens in new window)

ELIFE 2021 JAN 4; 10(?):? Article e65282
Show Abstract
Malaria parasites use the RhopH complex for erythrocyte invasion and channel-mediated nutrient uptake. As the member proteins are unique to Plasmodium spp., how they interact and traffic through subcellular sites to serve these essential functions is unknown. We show that RhopH is synthesized as a soluble complex of CLAG3, RhopH2, and RhopH3 with 1:1:1 stoichiometry. After transfer to a new host cell, the complex crosses a vacuolar membrane surrounding the intracellular parasite and becomes integral to the erythrocyte membrane through a PTEX translocon-dependent process. We present a 2.9 angstrom single-particle cryo-electron microscopy structure of the trafficking complex, revealing that CLAG3 interacts with the other subunits over large surface areas. This soluble complex is tightly assembled with extensive disulfide bonding and predicted transmembrane helices shielded. We propose a large protein complex stabilized for trafficking but poised for host membrane insertion through large-scale rearrangements, paralleling smaller two-state pore-forming proteins in other organisms.
Toubiana J, Cohen JF, Brice J, Poirault C, Bajolle F, Curtis W, Moulin F, Matczak S, Leruez M, Casanova JL, Chalumeau M, Taylor M, Allali S
Show All Authors

Distinctive Features of Kawasaki Disease Following SARS-CoV-2 Infection: a Controlled Study in Paris, France (opens in new window)

JOURNAL OF CLINICAL IMMUNOLOGY 2021; 41(3):526-535
Show Abstract
Background An outbreak of multisystem inflammatory syndrome in children, including Kawasaki disease (KD), emerged during COVID-19 pandemic. We explored whether Kawasaki-like disease (KD), when associated with confirmed SARS-CoV-2 infection, has specific characteristics. Methods We included children and adolescents with KD criteria admitted in the department of general pediatrics of a university hospital in Paris, France, between January 1, 2018, and May 26, 2020. The incidence of KD was compared between the outbreak and a pre-outbreak control period (January 1, 2018, to April 25). Characteristics of patients with positive SARS-CoV-2 testing (KD-SARS-CoV-2) were compared to those of the pre-outbreak period (classic KD). Results A total of 30 and 59 children with KD were admitted during the outbreak and pre-outbreak periods, respectively (incidence ratio 13.2 [8.3-21.0]). During the outbreak, 23/30 (77%) children were diagnosed as KD-SARS-CoV-2. When compared with patients with classic KD, those with KD-SARS-CoV-2 were more frequently of sub-Saharan African ancestry (OR 4.4 [1.6-12.6]) and older (median 8.2 vs. 4.0 years, p < 0.001), had more often initial gastrointestinal (OR 84 [4.9-1456]) and neurological (OR 7.3 [1.9-27.7] manifestations, and shock syndrome (OR 13.7 [4.2-45.1]). They had significantly higher CRP and ferritin levels. Noticeably, they had more frequently myocarditis (OR 387 [38-3933]). Conclusions Children and adolescents with KD-SARS-CoV-2 have specific features when compared with those with classic KD. These findings should raise awareness and facilitate the study of their pathogenesis.
Sani I, Stemmann H, Caron B, Bullock D, Stemmler T, Fahle M, Pestilli F, Freiwald WA
Show All Authors

The human endogenous attentional control network includes a ventro-temporal cortical node (opens in new window)

NATURE COMMUNICATIONS 2021 JAN 15; 12(1):? Article 360
Show Abstract
Endogenous attention is the cognitive function that selects the relevant pieces of sensory information to achieve goals and it is known to be controlled by dorsal fronto-parietal brain areas. Here we expand this notion by identifying a control attention area located in the temporal lobe. By combining a demanding behavioral paradigm with functional neuroimaging and diffusion tractography, we show that like fronto-parietal attentional areas, the human posterior inferotemporal cortex exhibits significant attentional modulatory activity. This area is functionally distinct from surrounding cortical areas, and is directly connected to parietal and frontal attentional regions. These results show that attentional control spans three cortical lobes and overarches large distances through fiber pathways that run orthogonally to the dominant anterior-posterior axes of sensory processing, thus suggesting a different organizing principle for cognitive control. Endogenous attention is known to be controlled by dorsal fronto-parietal brain areas. Here the authors identify a control attention area located in the temporal lobe, which is functionally distinct from surrounding areas, and is directly connected to parietal and frontal attentional regions.
Imanaka Y, Taniguchi M, Doi T, Tsumura M, Nagaoka R, Shimomura M, Asano T, Kagawa R, Mizoguchi Y, Karakawa S, Arihiro K, Imai K, Morio T, Casanova JL, Puel A, Ohara O, Kamei K, Kobayashi M, Okada S
Show All Authors

Inherited CARD9 Deficiency in a Child with Invasive Disease Due to Exophiala dermatitidis and Two Older but Asymptomatic Siblings (opens in new window)

JOURNAL OF CLINICAL IMMUNOLOGY 2021; ?(?):?
Show Abstract
Purpose Autosomal recessive CARD9 deficiency predisposes patients to invasive fungal disease. Candida and Trichophyton species are major causes of fungal disease in these patients. Other CARD9-deficient patients display invasive diseases caused by other fungi, such as Exophiala spp. The clinical penetrance of CARD9 deficiency regarding fungal disease is surprisingly not complete until adulthood, though the age remains unclear. Moreover, the immunological features of genetically confirmed yet asymptomatic individuals with CARD9 deficiency have not been reported. Methods Identification of CARD9 mutations by gene panel sequencing and characterization of the cellular phenotype by quantitative PCR, immunoblot, luciferase reporter, and cytometric bead array assays were performed. Results Gene panel sequencing identified compound heterozygous CARD9 variants, c.1118G>C (p.R373P) and c.586A>G (p.K196E), in a 4-year-old patient with multiple cerebral lesions and systemic lymphadenopathy due to Exophiala dermatitidis. The p.R373P is a known disease-causing variant, whereas the p.K196E is a private variant. Although the patient's siblings, a 10-year-old brother and an 8-year-old sister, were also compound heterozygous, they have been asymptomatic to date. Normal CARD9 mRNA and protein expression were found in the patient's CD14(+) monocytes. However, these cells exhibited markedly impaired pro-inflammatory cytokine production in response to fungal stimulation. Monocytes from both asymptomatic siblings displayed the same cellular phenotype. Conclusions CARD9 deficiency should be considered in previously healthy patients with invasive Exophiala dermatitidis disease. Asymptomatic relatives of all ages should be tested for CARD9 deficiency. Detecting cellular defects in asymptomatic individuals is useful for diagnosing CARD9 deficiency.
Bagert JD, Mitchener MM, Patriotis AL, Dul BE, Wojcik F, Nacev BA, Feng LJ, Allis CD, Muir TW
Show All Authors

Oncohistone mutations enhance chromatin remodeling and alter cell fates (opens in new window)

NATURE CHEMICAL BIOLOGY 2021; 17(4):403-411
Show Abstract
Whole-genome sequencing data mining efforts have revealed numerous histone mutations in a wide range of cancer types. These occur in all four core histones in both the tail and globular domains and remain largely uncharacterized. Here we used two high-throughput approaches, a DNA-barcoded mononucleosome library and a humanized yeast library, to profile the biochemical and cellular effects of these mutations. We identified cancer-associated mutations in the histone globular domains that enhance fundamental chromatin remodeling processes, histone exchange and nucleosome sliding, and are lethal in yeast. In mammalian cells, these mutations upregulate cancer-associated gene pathways and inhibit cellular differentiation by altering expression of lineage-specific transcription factors. This work represents a comprehensive functional analysis of the histone mutational landscape in human cancers and leads to a model in which histone mutations that perturb nucleosome remodeling may contribute to disease development and/or progression.
Alavi A, Lowes MA, Lu JD, Xu ZL, Habel M, Guo RF, Piguet V
Show All Authors

Elevated Plasma Complement Proteins in Palmoplantar Pustulosis: A Potential Therapeutic Target (opens in new window)

JOURNAL OF CUTANEOUS MEDICINE AND SURGERY 2021; ?(?):? Article 1203475421995180
Show Abstract
Karayol R, Medrihan L, Warner-Schmidt JL, Fait BW, Rao MN, Holzner EB, Greengard P, Heintz N, Schmidt EF
Show All Authors

Serotonin receptor 4 in the hippocampus modulates mood and anxiety (opens in new window)

MOLECULAR PSYCHIATRY 2021; ?(?):?
Show Abstract
Serotonin receptor 4 (5-HT4R) plays an important role in regulating mood, anxiety, and cognition, and drugs that activate this receptor have fast-acting antidepressant (AD)-like effects in preclinical models. However, 5-HT4R is widely expressed throughout the central nervous system (CNS) and periphery, making it difficult to pinpoint the cell types and circuits underlying its effects. Therefore, we generated a Cre-dependent 5-HT4R knockout mouse line to dissect the function of 5-HT4R in specific brain regions and cell types. We show that the loss of functional 5-HT4R specifically from excitatory neurons of hippocampus led to robust AD-like behavioral responses and an elevation in baseline anxiety. 5-HT4R was necessary to maintain the proper excitability of dentate gyrus (DG) granule cells and cell type-specific molecular profiling revealed a dysregulation of genes necessary for normal neural function and plasticity in cells lacking 5-HT4R. These adaptations were accompanied by an increase in the number of immature neurons in ventral, but not dorsal, dentate gyrus, indicating a broad impact of 5-HT4R loss on the local cellular environment. This study is the first to use conditional genetic targeting to demonstrate a direct role for hippocampal 5-HT4R signaling in modulating mood and anxiety. Our findings also underscore the need for cell type-based approaches to elucidate the complex action of neuromodulatory systems on distinct neural circuits.