Postmitotic Hoxa5 Expression Specifies Pontine Neuron Positional Identity and Input Connectivity of Cortical Afferent Subsets

The mammalian precerebellar pontine nucleus (PN) has a main role in relaying cortical information to the cerebellum. The molecular determinants establishing ordered connectivity patterns between cortical afferents and precerebellar neurons are largely unknown. We show that expression of Hox5 transcription factors is induced in specific subsets of postmitotic PN neurons at migration onset. Hox5 induction is achieved by response to retinoic acid signaling, resulting in Jmjd3-dependent derepression of Polycomb chromatin and 3D conformational changes. Hoxa5 drives neurons to settle posteriorly in the PN, where they are monosynaptically targeted by cortical neuron subsets mainly carrying limb somatosensation. Furthermore, Hoxa5 postmigratory ectopic expression in PN neurons is sufficient to attract cortical somatosensory inputs regardless of position and avoid visual afferents. Transcriptome analysis further suggests that Hoxa5 is involved in circuit formation. Thus, Hoxa5 coordinates postmitotic specification, migration, settling position, and subcircuit assembly of PN neuron subsets in the cortico-cerebellar pathway.Peer reviewe

Histone H3.3 beyond cancer: Germline mutations in Histone 3 Family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients

Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported. We analyze 46 patients bearing de novo germline mutations in histone 3 family 3A (H3F3A) or H3F3B with progressive neurologic dysfunction and congenital anomalies without malignancies. Molecular modeling of all 37 variants demonstrated clear disruptions in interactions with DNA, other histones, and histone chaperone proteins. Patient histone posttranslational modifications (PTMs) analysis revealed notably aberrant local PTM patterns distinct from the somatic lysine mutations that cause global PTM dysregulation. RNA sequencing on patient cells demonstrated up-regulated gene expression related to mitosis and cell division, and cellular assays confirmed an increased proliferative capacity. A zebrafish model showed craniofacial anomalies and a defect in Foxd3-derived glia. These data suggest that the mechanism of germline mutations are distinct from cancer-associated somatic histone mutations but may converge on control of cell proliferation

Is child speech intelligible? The case of cochlear implanted (CI) vs normal-hearing (NH) children

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Immobilized-cell physiology: current data and the potentialities of proteomics

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Proteomics of Biofilm Bacteria

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Realisation of voicing by French-speaking CI children after long-term implant use: An acoustic study

International audienceStudies of speech production in French-speaking cochlear-implanted (CI) children are very scarce. Yet, difficulties in speech production have been shown to impact the intelligibility of these children. The goal of this study is to understand the effect of long-term use of cochlear implant on speech production, and more precisely on the coordination of laryngeal-oral gestures in stop production. The participants were all monolingual French children: 13 6;6- to 10;7-year-old CI children and 20 age-matched normally hearing (NH) children. We compared /p/, /t/, /k/, /b/, /d/ and /g/ in word-initial consonant-vowel sequences, produced in isolation in two different tasks, and we studied the effects of CI use, vowel context, task and age factors (i.e. chronological age, age at implantation and duration of implant use). Statistical analyses show a difference in voicing production between groups for voiceless consonants (shorter Voice Onset Times for CI children), with significance reached only for /k/, but no difference for voiced consonants. Our study indicates that in the long run, use of CI seems to have limited effects on the acquisition of oro-laryngeal coordination needed to produce voicing, except for specific difficulties located on velars. In a follow-up study, further acoustic analyses on vowel and fricative production by the same children reveal more difficulties, which suggest that cochlear implantation impacts frequency-based features (second formant of vowels and spectral moments of fricatives) more than durational cues (voicing)

Front. Microbiol.,

Enterohaemorrhagic Escherichia coli, such as serotype O157:H7, are a leading cause of food-associated outbreaks. While the primary reservoir is associated with cattle, plant foods have been associated as sources of human infection. E. coli is able to grow in the tissue of food plants such as spinach. While fecal contamination is the primary suspect, soil has been underestimated as a potential reservoir. Persistence of bacterial populations in open systems is the product of growth, death, predation, and competition. Here we report that E. coli O157:H7 can grow using the soluble compounds in soil, and characterize the effect of soil growth on the stationary phase proteome. E. coli 933D (stxII(-)) was cultured in Soil Extracted Soluble Organic Matter (SESOM) and the culturable count determined for 24d. The proteomes of exponential and stationary phase populations were characterized by 2D gel electrophoresis and protein spots were identified by MALDI-TOF mass spectrometry. While LB controls displayed a death phase, SESOMgrown population remained culturable for 24d, indicating an altered physiological state with superior longevity. This was not due to decreased cell density on entry to stationary phase as 24 h SESOM populations concentrated 10-fold retained their longevity. Principal component analysis showed that stationary phase proteomes from SESOM and LB were different. Differences included proteins involved in stress response, motility, membrane and wall composition, nutrient uptake, translation and protein turnover, and anabolic and catabolic pathways, indicating an altered physiological state of soil-grown cells entering stationary phase. The results suggest that E. coli may be a soil commensal that, in absence of predation and competition, maintains stable populations in soil

Growth and extended survival of Escherichia coli O157 : H7 in soil organic matter

Enterohaemorrhagic Escherichia coli such as serotype O157:H7 are a leading cause of food-associated outbreaks. While the primary reservoir is associated with cattle, plant foods have been associated as sources of human infection. E. coli is able to grow in the tissue of food plants such as spinach. While fecal contamination is the primary suspect, soil has been underestimated as a potential reservoir. Persistence of bacterial populations in open systems is the product of growth, death, predation, and competition. Here we report that E. coli O157:H7 can grow using the soluble compounds in soil, and characterize the effect of soil growth in the stationary phase proteome. E. coli 933D (stxII-) was cultured in Soil Extracted Soluble Organic Matter (SESOM) and the culturable count determined for 24 d. The proteomes of exponential and stationary phase populations were characterized by 2D gel electrophoresis and protein spots were identified by MALDI-TOF mass spectrometry. While LB controls displayed a death phase, SESOM grown population remained culturable for 24 d, indicating an altered physiological state with superior longevity. This was not due to decreased cell density on entry to stationary phase as 24h SESOM populations concentrated 10-fold retained their longevity. Principal component analysis showed that stationary phase proteomes from SESOM and LB were different. Differences included proteins involved in stress response, motility, membrane and wall composition, nutrient uptake, translation and protein turnover, and anabolic and catabolic pathways, indicating an altered physiological state of soil-grown cells entering stationary phase. The results suggest that E. coli may be a soil commensal that in absence of predation and competition maintains stable populations in soil.We thank David Francis for donating E. coli O157:H7 933D, and Birgit Voigt of the Institute for Microbiology, Ernst Moritz Arndt University, Greifswald, Germany for protein identification. GN and AC were supported by the South Dakota Agricultural Experiment Station. This research was supported by the South Dakota Agricultural Experiment Station. We acknowledge use of the SDSU-FGCF supported in part by NSF/EPSCoR Grant No. 0091948 and by the State of South Dakota.http://www.frontiersin.org/Microbiologyam2018BiochemistryGeneticsMicrobiology and Plant Patholog

Proteomic analysis of agar gel-entrappedPseudomonas aeruginosa

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Comparative proteomic analysis of planktonic and immobilized Pseudomonas aeruginosa cells: a multivariate statistical approach

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