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1.
Neurotrophins and FGF2 contribute to formation of the cochlea, but their roles in cochlear nucleus development are unknown. The effects of these factors may differ in the cochlea and cochlear nucleus, which may influence each other's development. It is important to analyze the effects of these factors on cellular structures at well‐defined steps in the normal morphogenetic sequence. The present study used immunohistochemistry to localize factors in situ and to test hypotheses about their roles in an in vitro model. Specific antibody staining revealed that TrkC, the NT3 receptor, is present in neural precursors prior to embryonic day E11 until after birth. NT3 appeared in precursor cells during migration (E13–E15) and disappeared at birth. TrkC and NT3 occurred in the same structures, including growing axons, terminals, and their synaptic targets. Thus, NT3 tracks the migration routes and the morphogenetic sequences within a window defined by TrkC. In vitro, the cochlear nucleus anlage was explanted from E11 embryos. Cultures were divided into groups fed with defined medium, with or without FGF2, BDNF, and NT3 supplements, alone or in combinations, for 7 days. When neuroblasts migrated and differentiated, immunostaining was used for locating NT3 and TrkC in the morphogenetic sequence, bromodeoxyuridine for proliferation, and synaptic vesicle protein for synaptogenesis. By time‐lapse imaging and quantitative measures, the results support the hypothesis that FGF2 promotes proliferation and migration. NT3 interacts with FGF2 and BDNF to promote neurite outgrowth, fasciculation, and synapse formation. Factors and receptors localize to the structural sites undergoing critical changes. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 相似文献
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Victoria L. Wyckelsma Tomas Venckunas Peter J. Houweling Maja Schlittler Volker M. Lauschke Chrystal F. Tiong Harrison D. Wood Niklas Ivarsson Henrikas Paulauskas Nerijus Eimantas Daniel C. Andersson Kathryn N. North Marius Brazaitis Håkan Westerblad 《American journal of human genetics》2021,108(3):446-457
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Claire Z. Larter Chrystal Inglis Michael A. Silverman Geoffrey C. Farrell Michel R. Leroux 《Developmental neurobiology》2013,73(1):1-13
Primary cilia are ubiquitous cellular antennae whose dysfunction collectively causes various disorders, including vision and hearing impairment, as well as renal, skeletal, and central nervous system anomalies. One ciliopathy, Alström syndrome, is closely related to Bardet–Biedl syndrome (BBS), sharing amongst other phenotypic features morbid obesity. As the cellular and molecular links between weight regulation and cilia are poorly understood, we used the obese mouse strain foz/foz, bearing a truncating mutation in the Alström syndrome protein (Alms1), to help elucidate why it develops hyperphagia, leading to early onset obesity and metabolic anomalies. Our in vivo studies reveal that Alms1 localizes at the base of cilia in hypothalamic neurons, which are implicated in the control of satiety. Alms1 is lost from this location in foz/foz mice, coinciding with a strong postnatal reduction (~70%) in neurons displaying cilia marked with adenylyl cyclase 3 (AC3), a signaling protein implicated in obesity. Notably, the reduction in AC3‐bearing cilia parallels the decrease in cilia containing two appetite‐regulating proteins, Mchr1 and Sstr3, as well as another established Arl13b ciliary marker, consistent with progressive loss of cilia during development. Together, our results suggest that Alms1 maintains the function of neuronal cilia implicated in weight regulation by influencing the maintenance and/or stability of the organelle. Given that Mchr1 and Sstr3 localization to remaining cilia is maintained in foz/foz animals but known to be lost from BBS knockout mice, our findings suggest different molecular etiologies for the satiety defects associated with the Alström syndrome and BBS ciliopathies. © 2012 Wiley Periodicals, Inc. Develop Neurobiol, 2013 相似文献
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There is controversy as to whether dyslexic children present systematic postural deficiency. Clinicians use a combination of ophthalmic prisms and proprioceptive soles to improve postural performances. This study examines the effects of convergent prisms and spherical lenses on posture. Fourteen dyslexics (13–17 years-old) and 11 non dyslexics (13–16 years-old) participated in the study. Quiet stance posturography was performed with the TechnoConcept device while subjects fixated a target at eye-level from a distance of 1_m. Four conditions were run: normal viewing; viewing the target with spherical lenses of −1 diopter (ACCOM1) over each eye; viewing with −3 diopters over each eye (ACCOM3); viewing with a convergent prism of 8 diopters per eye. Relative to normal viewing, the −1 lenses increased the surface of body sway significantly whereas the −3 diopter lenses only resulted in a significant increase of antero-posterior body sway. Thus, adolescents would appear to cope more effectively with stronger conflicts rather than subtle ones. The prism condition resulted in a significant increase in both the surface and the antero-posterior body sway. Importantly, all of these effects were similar for the two groups. Wavelet analysis (time frequency domain) revealed high spectral power of antero-posterior sway for the prism condition in both groups. In the ACCOM3 condition, the spectral power of antero-posterior sway decreased for non dyslexics but increased for dyslexics suggesting that dyslexics encounter more difficulty with accommodation. The cancelling time for medium range frequency (believed to be controlled by the cerebellum), was shorter in dyslexics, suggesting fewer instances of optimal control. We conclude that dyslexics achieve similar postural performances albeit less efficiently. Prisms and lenses destabilize posture for all teenagers. Thus, contrary to adults, adolescents do not seem to use efferent, proprioceptive ocular motor signals to improve their posture, at least not immediately when confronted to convergence accommodation conflict. 相似文献
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In the United States, disease screening is offered to the public as a consumer service. It has been proposed that the act
of “consumption” is a manifestation of agency and that the decision to consume is an exercise of autonomy. The enthusiasm
of the American public for disease screening and the expansion in the demand for all sorts of disease screening in recent
years can be viewed as an expression of such autonomy. Here, we argue that the enthusiasm for disease screening witnessed
in the American public today may be more a reflection of the constraint on autonomy than its facilitation. It is our opinion
that the articulation of socio-historical processes has contributed to a moral imperative which is reflected in the decision
making of individuals around disease screening. We suggest medical and health professionals have a responsibility to facilitate
the exercise of individual autonomy in health care decision making as an integral component of professional obligation. These
professionals need to problematise healthcare activities that constrain individual autonomy. 相似文献
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Chavda S Liu Y Babu B Davis R Sielaff A Ruprich J Westrate L Tronrud C Ferguson A Franks A Tzou S Adkins C Rice T Mackay H Kluza J Tahir SA Lin S Kiakos K Bruce CD Wilson WD Hartley JA Lee M 《Biochemistry》2011,50(15):3127-3136
With the aim of incorporating a recognition element that acts as a fluorescent probe upon binding to DNA, three novel pyrrole (P) and imidazole (I)-containing polyamides were synthesized. The compounds contain a p-anisylbenzimidazolecarboxamido (Hx) moiety attached to a PP, IP, or PI unit, giving compounds HxPP (2), HxIP (3), and HxPI (4), respectively. These fluorescent hybrids were tested against their complementary nonfluorescent, non-formamido tetraamide counterparts, namely, PPPP (5), PPIP (6), and PPPI (7) (cognate sequences 5'-AAATTT-3', 5'-ATCGAT-3', and 5'-ACATGT-3', respectively). The binding affinities for both series of polyamides for their cognate and noncognate sequences were ascertained by surface plasmon resonance (SPR) studies, which revealed that the Hx-containing polyamides gave binding constants in the 10(6) M(-1) range while little binding was observed for the noncognates. The binding data were further compared to the corresponding and previously reported formamido-triamides f-PPP (8), f-PIP (9), and f-PPI (10). DNase I footprinting studies provided additional evidence that the Hx moiety behaved similarly to two consecutive pyrroles (PP found in 5-7), which also behaved like a formamido-pyrrole (f-P) unit found in distamycin and many formamido-triamides, including 8-10. The biophysical characterization of polyamides 2-7 on their binding to the abovementioned DNA sequences was determined using thermal melts (ΔT(M)), circular dichroism (CD), and isothermal titration calorimetry (ITC) studies. Density functional calculations (B3LYP) provided a theoretical framework that explains the similarity between PP and Hx on the basis of molecular electrostatic surfaces and dipole moments. Furthermore, emission studies on polyamides 2 and 3 showed that upon excitation at 322 nm binding to their respective cognate sequences resulted in an increase in fluorescence at 370 nm. These low molecular weight polyamides show promise for use as probes for monitoring DNA recognition processes in cells. 相似文献
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Reed JS Sidney J Piaskowski SM Glidden CE León EJ Burwitz BJ Kolar HL Eernisse CM Furlott JR Maness NJ Walsh AD Rudersdorf RA Bardet W McMurtrey CP O'Connor DH Hildebrand WH Sette A Watkins DI Wilson NA 《Immunogenetics》2011,63(12):789-807
Virus-specific CD8(+) T cells play an important role in controlling HIV/SIV replication. These T cells recognize intracellular pathogen-derived peptides displayed on the cell surface by individual MHC class I molecules. In the SIV-infected rhesus macaque model, five Mamu class I alleles have been thoroughly characterized with regard to peptide binding, and a sixth was shown to be uninvolved. In this study, we describe the peptide binding of Mamu-A1*007:01 (formerly Mamu-A*07), an allele present in roughly 5.08% of Indian-origin rhesus macaques (n?=?63 of 1,240). We determined a preliminary binding motif by eluting and sequencing endogenously bound ligands. Subsequently, we used a positional scanning combinatorial library and panels of single amino acid substitution analogs to further characterize peptide binding of this allele and derive a quantitative motif. Using this motif, we selected and tested 200 peptides derived from SIV(mac)239 for their capacity to bind Mamu-A1*007:01; 33 were found to bind with an affinity of 500?nM or better. We then used PBMC from SIV-infected or vaccinated but uninfected, A1*007:01-positive rhesus macaques in IFN-γ Elispot assays to screen the peptides for T-cell reactivity. In all, 11 of the peptides elicited IFN-γ(+) T-cell responses. Six represent novel A1*007:01-restricted epitopes. Furthermore, both Sanger and ultradeep pyrosequencing demonstrated the accumulation of amino acid substitutions within four of these six regions, suggestive of selective pressure on the virus by antigen-specific CD8(+) T cells. Thus, it appears that Mamu-A1*007:01 presents SIV-derived peptides to antigen-specific CD8(+) T cells and is part of the immune response to SIV(mac)239. 相似文献
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Laura C. Harrington Andrew Fleisher Diego Ruiz-Moreno Francoise Vermeylen Chrystal V. Wa Rebecca L. Poulson John D. Edman John M. Clark James W. Jones Sangvorn Kitthawee Thomas W. Scott 《PLoS neglected tropical diseases》2014,8(8)
Background
Mosquito biting frequency and how bites are distributed among different people can have significant epidemiologic effects. An improved understanding of mosquito vector-human interactions would refine knowledge of the entomological processes supporting pathogen transmission and could reveal targets for minimizing risk and breaking pathogen transmission cycles.Methodology and principal findings
We used human DNA blood meal profiling of the dengue virus (DENV) vector, Aedes aegypti, to quantify its contact with human hosts and to infer epidemiologic implications of its blood feeding behavior. We determined the number of different people bitten, biting frequency by host age, size, mosquito age, and the number of times each person was bitten. Of 3,677 engorged mosquitoes collected and 1,186 complete DNA profiles, only 420 meals matched people from the study area, indicating that Ae. aegypti feed on people moving transiently through communities to conduct daily business. 10–13% of engorged mosquitoes fed on more than one person. No biting rate differences were detected between high- and low-dengue transmission seasons. We estimate that 43–46% of engorged mosquitoes bit more than one person within each gonotrophic cycle. Most multiple meals were from residents of the mosquito collection house or neighbors. People ≤25 years old were bitten less often than older people. Some hosts were fed on frequently, with three hosts bitten nine times. Interaction networks for mosquitoes and humans revealed biologically significant blood feeding hotspots, including community marketplaces.Conclusion and significance
High multiple-feeding rates and feeding on community visitors are likely important features in the efficient transmission and rapid spread of DENV. These results help explain why reducing vector populations alone is difficult for dengue prevention and support the argument for additional studies of mosquito feeding behavior, which when integrated with a greater understanding of human behavior will refine estimates of risk and strategies for dengue control. 相似文献10.
Elena Maklashina Sany Rajagukguk Chrystal A. Starbird W. Hayes McDonald Anna Koganitsky Michael Eisenbach Tina M. Iverson Gary Cecchini 《The Journal of biological chemistry》2016,291(6):2904-2916
Escherichia coli harbors two highly conserved homologs of the essential mitochondrial respiratory complex II (succinate:ubiquinone oxidoreductase). Aerobically the bacterium synthesizes succinate:quinone reductase as part of its respiratory chain, whereas under microaerophilic conditions, the quinol:fumarate reductase can be utilized. All complex II enzymes harbor a covalently bound FAD co-factor that is essential for their ability to oxidize succinate. In eukaryotes and many bacteria, assembly of the covalent flavin linkage is facilitated by a small protein assembly factor, termed SdhE in E. coli. How SdhE assists with formation of the covalent flavin bond and how it binds the flavoprotein subunit of complex II remain unknown. Using photo-cross-linking, we report the interaction site between the flavoprotein of complex II and the SdhE assembly factor. These data indicate that SdhE binds to the flavoprotein between two independently folded domains and that this binding mode likely influences the interdomain orientation. In so doing, SdhE likely orients amino acid residues near the dicarboxylate and FAD binding site, which facilitates formation of the covalent flavin linkage. These studies identify how the conserved SdhE assembly factor and its homologs participate in complex II maturation. 相似文献