159 research outputs found
Balancing family with a successful career in neuroscience.
After years of hard work as a student and postdoc, stressful negotiations and restless nights of agony regarding your academic future, you managed to secure a Principal Investigator (PI) position and establish your own laboratory. And just when you thought you could relax a bit and enjoy some time with your family, or start a family, you find yourself facing massive levels of responsibility added to your research, that demand most of your time and energy. The challenge to balance a successful career with a happy family life is not a trivial one.The FENSâKavli Network of Excellence is supported by FENS, the Kavli Foundation, Alzheimer's Research UK, the European Molecular Biology Organization (EMBO) and Roche. P.P. acknowledges funding from the European Research Council (StG 311435 dEMORY). J.G. is supported by the European Research Council (StG 678832 REMOTE MEMORY TRACES), an MQ fellow award, the Swiss National Science Foundation, the National Competence Center for Research in Switzerland SYNAPSY, the SYNAPSIS Foundation, the BĂŠatrice EdererâWeber Stiftung, the Alzheimer's Association as well as by an Independent Investigator Award from the Brain and Behavior Research Foundation. I.H.âO. is supported by the ERC Consolidator Grant CoG 681577 PSYCHOCELL. D.B. is supported by the Wellcome Trust. G.L.âB. is supported by the European Research Council, ERCâ2014âCoG 647012 and the Spanish MINECO BFU2012â34298 grant
Evidence That Descending Cortical Axons Are Essential for Thalamocortical Axons to Cross the Pallial-Subpallial Boundary in the Embryonic Forebrain
Developing thalamocortical axons traverse the subpallium to reach the cortex located in the pallium. We tested the hypothesis that descending corticofugal axons are important for guiding thalamocortical axons across the pallial-subpallial boundary, using conditional mutagenesis to assess the effects of blocking corticofugal axonal development without disrupting thalamus, subpallium or the pallial-subpallial boundary. We found that thalamic axons still traversed the subpallium in topographic order but did not cross the pallial-subpallial boundary. Co-culture experiments indicated that the inability of thalamic axons to cross the boundary was not explained by mutant cortex developing a long-range chemorepulsive action on thalamic axons. On the contrary, cortex from conditional mutants retained its thalamic axonal growth-promoting activity and continued to express Nrg-1, which is responsible for this stimulatory effect. When mutant cortex was replaced with control cortex, corticofugal efferents were restored and thalamic axons from conditional mutants associated with them and crossed the pallial-subpallial boundary. Our study provides the most compelling evidence to date that cortical efferents are required to guide thalamocortical axons across the pallial-subpallial boundary, which is otherwise hostile to thalamic axons. These results support the hypothesis that thalamic axons grow from subpallium to cortex guided by cortical efferents, with stimulation from diffusible cortical growth-promoting factors
Mouse Embryonic Retina Delivers Information Controlling Cortical Neurogenesis
The relative contribution of extrinsic and intrinsic mechanisms to cortical development is an intensely debated issue and an outstanding question in neurobiology. Currently, the emerging view is that interplay between intrinsic genetic mechanisms and extrinsic information shape different stages of cortical development [1]. Yet, whereas the intrinsic program of early neocortical developmental events has been at least in part decoded [2], the exact nature and impact of extrinsic signaling are still elusive and controversial. We found that in the mouse developing visual system, acute pharmacological inhibition of spontaneous retinal activity (retinal waves-RWs) during embryonic stages increase the rate of corticogenesis (cell cycle withdrawal). Furthermore, early perturbation of retinal spontaneous activity leads to changes of cortical layer structure at a later time point. These data suggest that mouse embryonic retina delivers long-distance information capable of modulating cell genesis in the developing visual cortex and that spontaneous activity is the candidate long-distance acting extrinsic cue mediating this process. In addition, these data may support spontaneous activity to be a general signal coordinating neurogenesis in other developing sensory pathways or areas of the central nervous system
Language impairment in a case of a complex chromosomal rearrangement with a breakpoint downstream of FOXP2
BACKGROUND:
We report on a young female, who presents with a severe speech and language disorder and a balanced de novo complex chromosomal rearrangement, likely to have resulted from a chromosome 7 pericentromeric inversion, followed by a chromosome 7 and 11 translocation.
RESULTS:
Using molecular cytogenetics, we mapped the four breakpoints to 7p21.1-15.3 (chromosome position: 20,954,043-21,001,537, hg19), 7q31 (chromosome position: 114,528,369-114,556,605, hg19), 7q21.3 (chromosome position: 93,884,065-93,933,453, hg19) and 11p12 (chromosome position: 38,601,145-38,621,572, hg19). These regions contain only non-coding transcripts (ENSG00000232790 on 7p21.1 and TCONS_00013886, TCONS_00013887, TCONS_00014353, TCONS_00013888 on 7q21) indicating that no coding sequences are directly disrupted. The breakpoint on 7q31 mapped 200 kb downstream of FOXP2, a well-known language gene. No splice site or non-synonymous coding variants were found in the FOXP2 coding sequence. We were unable to detect any changes in the expression level of FOXP2 in fibroblast cells derived from the proband, although this may be the result of the low expression level of FOXP2 in these cells.
CONCLUSIONS:
We conclude that the phenotype observed in this patient either arises from a subtle change in FOXP2 regulation due to the disruption of a downstream element controlling its expression, or from the direct disruption of non-coding RNAs
Optimization of interneuron function by direct coupling of cell migration and axonal targeting
Neural circuit assembly relies on the precise synchronization of developmental processes, such as cell migration and axon targeting, but the cell-autonomous mechanisms coordinating these events remain largely unknown. Here we found that different classes of interneurons use distinct routes of migration to reach the embryonic cerebral cortex. Somatostatin-expressing interneurons that migrate through the marginal zone develop into Martinotti cells, one of the most distinctive classes of cortical interneurons. For these cells, migration through the marginal zone is linked to the development of their characteristic layer 1 axonal arborization. Altering the normal migratory route of Martinotti cells by conditional deletion of Mafbâa gene that is preferentially expressed by these cellsâcell-autonomously disrupts axonal development and impairs the function of these cells in vivo. Our results suggest that migration and axon targeting programs are coupled to optimize the assembly of inhibitory circuits in the cerebral cortex
Quasi-Monte Carlo rules for numerical integration over the unit sphere
We study numerical integration on the unit sphere using equal weight quadrature rules, where the weights are such
that constant functions are integrated exactly.
The quadrature points are constructed by lifting a -net given in the
unit square to the sphere by means of an area
preserving map. A similar approach has previously been suggested by Cui and
Freeden [SIAM J. Sci. Comput. 18 (1997), no. 2].
We prove three results. The first one is that the construction is (almost)
optimal with respect to discrepancies based on spherical rectangles. Further we
prove that the point set is asymptotically uniformly distributed on
. And finally, we prove an upper bound on the spherical cap
-discrepancy of order (where denotes the
number of points). This slightly improves upon the bound on the spherical cap
-discrepancy of the construction by Lubotzky, Phillips and Sarnak [Comm.
Pure Appl. Math. 39 (1986), 149--186]. Numerical results suggest that the
-nets lifted to the sphere have spherical cap
-discrepancy converging with the optimal order of
Common variation near ROBO2 is associated with expressive vocabulary in infancy
Twin studies suggest that expressive vocabulary at ~24 months is modestly heritable. However, the genes influencing this early linguistic phenotype are unknown. Here we conduct a genome-wide screen and follow-up study of expressive vocabulary in toddlers of European descent from up to four studies of the EArly Genetics and Lifecourse Epidemiology consortium, analysing an early (15â18 months, âone-word stageâ, NTotal=8,889) and a later (24â30 months, âtwo-word stageâ, NTotal=10,819) phase of language acquisition. For the early phase, one single-nucleotide polymorphism (rs7642482) at 3p12.3 near âROBO2, encoding a conserved axon-binding receptor, reaches the genome-wide significance level (P=1.3 Ă 10â8) in the combined sample. This association links language-related common genetic variation in the general population to a potential autism susceptibility locus and a linkage region for dyslexia, speech-sound disorder and reading. The contribution of common genetic influences is, although modest, supported by genome-wide complex trait analysis (meta-GCTA h215â18-months=0.13, meta-GCTA h224â30-months=0.14) and in concordance with additional twin analysis (5,733 pairs of European descent, h224-months=0.20)
Point sets on the sphere with small spherical cap discrepancy
In this paper we study the geometric discrepancy of explicit constructions of
uniformly distributed points on the two-dimensional unit sphere. We show that
the spherical cap discrepancy of random point sets, of spherical digital nets
and of spherical Fibonacci lattices converges with order . Such point
sets are therefore useful for numerical integration and other computational
simulations. The proof uses an area-preserving Lambert map. A detailed analysis
of the level curves and sets of the pre-images of spherical caps under this map
is given
Molecular and Electrophysiological Characterization of GFP-Expressing CA1 Interneurons in GAD65-GFP Mice
The use of transgenic mice in which subtypes of neurons are labeled with a fluorescent protein has greatly facilitated modern neuroscience research. GAD65-GFP mice, which have GABAergic interneurons labeled with GFP, are widely used in many research laboratories, although the properties of the labeled cells have not been studied in detail. Here we investigate these cells in the hippocampal area CA1 and show that they constitute âź20% of interneurons in this area. The majority of them expresses either reelin (70Âą2%) or vasoactive intestinal peptide (VIP; 15Âą2%), while expression of parvalbumin and somatostatin is virtually absent. This strongly suggests they originate from the caudal, and not the medial, ganglionic eminence. GFP-labeled interneurons can be subdivided according to the (partially overlapping) expression of neuropeptide Y (42Âą3%), cholecystokinin (25Âą3%), calbindin (20Âą2%) or calretinin (20Âą2%). Most of these subtypes (with the exception of calretinin-expressing interneurons) target the dendrites of CA1 pyramidal cells. GFP-labeled interneurons mostly show delayed onset of firing around threshold, and regular firing with moderate frequency adaptation at more depolarized potentials
Jugoslavija u meÄunarodnoj trgovini ribom, ribljim proizvodima i preraÄevinama
Sulfonamides
are profoundly important in pharmaceutical design.
CâN cross-coupling of sulfonamides is an effective method for
fragment coupling and structureâactivity relationship (SAR)
mining. However, cross-coupling of the important <i>N</i>-arylsulfonamide pharmacophore has been notably unsuccessful. Here,
we present a solution to this problem via oxidative Cu-catalysis (ChanâLam
cross-coupling). Mechanistic insight has allowed the discovery and
refinement of an effective cationic Cu catalyst to facilitate the
practical and scalable ChanâLam <i>N</i>-arylation
of primary and secondary <i>N</i>-arylsulfonamides at room
temperature. We also demonstrate utility in the large scale synthesis
of a key intermediate to a clinical hepatitis C virus treatment
- âŚ