Humanized Foxp2 accelerates learning by enhancing transitions from declarative to procedural performance

The acquisition of language and speech is uniquely human, but how genetic changes might have adapted the nervous system to this capacity is not well understood. Two human-specific amino acid substitutions in the transcription factor forkhead box P2 (FOXP2) are outstanding mechanistic candidates, as they could have been positively selected during human evolution and as FOXP2 is the sole gene to date firmly linked to speech and language development. When these two substitutions are introduced into the endogenous Foxp2 gene of mice (Foxp2[superscript hum]), cortico-basal ganglia circuits are specifically affected. Here we demonstrate marked effects of this humanization of Foxp2 on learning and striatal neuroplasticity. Foxp2[superscript hum/hum] mice learn stimulus–response associations faster than their WT littermates in situations in which declarative (i.e., place-based) and procedural (i.e., response-based) forms of learning could compete during transitions toward proceduralization of action sequences. Striatal districts known to be differently related to these two modes of learning are affected differently in the Foxp2[superscript hum/hum] mice, as judged by measures of dopamine levels, gene expression patterns, and synaptic plasticity, including an NMDA receptor-dependent form of long-term depression. These findings raise the possibility that the humanized Foxp2 phenotype reflects a different tuning of corticostriatal systems involved in declarative and procedural learning, a capacity potentially contributing to adapting the human brain for speech and language acquisition.Nancy Lurie Marks Family FoundationSimons Foundation (Autism Research Initiative Grant 137593)National Institutes of Health (U.S.) (Grant R01 MH060379)Wellcome Trust (London, England) (Grant 075491/Z/04)Wellcome Trust (London, England) (Grant 080971)Fondation pour la recherche medicaleMax Planck Society for the Advancement of Scienc

Drift estimation in sparse sequential dynamic imaging, with application to nanoscale fluorescence microscopy.

A major challenge in many modern superresolution fluorescence microscopy techniques at the nanoscale lies in the correct alignment of long sequences of sparse but spatially and temporally highly resolved images. This is caused by the temporal drift of the protein structure, e.g. due to temporal thermal inhomogeneity of the object of interest or its supporting area during the observation process. We develop a simple semiparametric model for drift correction in single-marker switching microscopy. Then we propose an M-estimator for the drift and show its asymptotic normality. This is used to correct the final image and it is shown that this purely statistical method is competitive with state of the art calibration techniques which require the incorporation of fiducial markers in the specimen. Moreover, a simple bootstrap algorithm allows us to quantify the precision of the drift estimate and its effect on the final image estimation. We argue that purely statistical drift correction is even more robust than fiducial tracking, rendering the latter superfluous in many applications. The practicability of our method is demonstrated by a simulation study and by a single-marker switching application. This serves as a prototype for many other typical imaging techniques where sparse observations with high temporal resolution are blurred by motion of the object to be reconstructed

Annotation of primate miRNAs by high throughput sequencing of small RNA libraries

BACKGROUND: In addition to genome sequencing, accurate functional annotation of genomes is required in order to carry out comparative and evolutionary analyses between species. Among primates, the human genome is the most extensively annotated. Human miRNA gene annotation is based on multiple lines of evidence including evidence for expression as well as prediction of the characteristic hairpin structure. In contrast, most miRNA genes in non-human primates are annotated based on homology without any expression evidence. We have sequenced small-RNA libraries from chimpanzee, gorilla, orangutan and rhesus macaque from multiple individuals and tissues. Using patterns of miRNA expression in conjunction with a model of miRNA biogenesis we used these high-throughput sequencing data to identify novel miRNAs in non-human primates. RESULTS: We predicted 47 new miRNAs in chimpanzee, 240 in gorilla, 55 in orangutan and 47 in rhesus macaque. The algorithm we used was able to predict 64% of the previously known miRNAs in chimpanzee, 94% in gorilla, 61% in orangutan and 71% in rhesus macaque. We therefore added evidence for expression in between one and five tissues to miRNAs that were previously annotated based only on homology to human miRNAs. We increased from 60 to 175 the number miRNAs that are located in orthologous regions in humans and the four non-human primate species studied here. CONCLUSIONS: In this study we provide expression evidence for homology-based annotated miRNAs and predict de novo miRNAs in four non-human primate species. We increased the number of annotated miRNA genes and provided evidence for their expression in four non-human primates. Similar approaches using different individuals and tissues would improve annotation in non-human primates and allow for further comparative studies in the future

Self-Sabotage Workshop: a starting point to unravel sabotaging of instruments as a design practice

Within the music improvisation and jazz scenes, playing a wrong note may be seen as a source of creativity and novelty, where an initially undesired factor (the mistaken note) invites the musician to leverage their skills to transform it into new musical material. How does this idea, however, translate into more experimental scenes like NIME, where control and virtuosity are not necessarily the performance's aim? Moreover, within NIME communities the addition of randomness or constraints to musical instruments is often an intended aesthetic decision rather than a source of mistakes. To explore this contrast, we invited four NIME practitioners to participate in the Self-Sabotage Workshop, where each practitioner had to build their own sabotaging elements for their musical instruments and to give a short demonstration with them. We gathered participants' impressions of self-sabotating in a focus group, inquiring about control and musicality, and also the strategies they developed for coping with the self-sabotaged instruments. We discuss the emergent ideas of planned and unplanned sabotaging, and we propose a starting point towards the idea of self-sabotaging as a continuous design and musical process where designers/musicians try to overcome barriers that they impose upon themselves

Genetic evidence of human adaptation to a cooked diet

Humans have been argued to be biologically adapted to a cooked diet, but this hypothesis has not been tested at the molecular level. Here, we combine controlled feeding experiments in mice with comparative primate genomics to show that consumption of a cooked diet influences gene expression and that affected genes bear signals of positive selection in the human lineage. Liver gene expression profiles in mice fed standardized diets of meat or tuber were affected by food type and cooking, but not by caloric intake or consumer energy balance. Genes affected by cooking were highly correlated with genes known to be differentially expressed in liver between humans and other primates, and more genes in this overlap set show signals of positive selection in humans than would be expected by chance. Sequence changes in the genes under selection appear before the split between modern humans and two archaic human groups, Neandertals and Denisovans, supporting the idea that human adaptation to a cooked diet had begun by at least 275,000 years ago

P250306E_USS0073_TWIP DefPub Freeform- Phase-value - Parametermatrix for Sending/Receiving Array

The invention relates to an ultrasonic measurement system comprising: a phased-array transmit antenna (1) comprising a plurality of ultrasonic transducers (PMUTs), a phased-array receive antenna (2), wherein the receive antenna (2) is distinct from the 5 transmit antenna (1), a control unit (3) configured to assign to each transducer of the transmit antenna (1) a signal with an individually adjustable phase value, wherein the phase values are defined by a transmit parameter matrix (P_TX), wherein the control unit (3) is further configured to transmit multiple orthogonal codes 10 (C₁, C₂, ..., Cₙ) simultaneously superimposed on the same frequency band, with each code assigned to a directional channel (K₁, K₂, ..., Kₙ), wherein the receive antenna (2) is configured to process received signals using a receive parameter matrix (P_RX) and to calculate for each directional channel a cross-correlation function (CCF) or a matched filter, 15 wherein the position of a reflecting object is determined from the plurality of CCFs

P250307E_USS0068_TWIP DefPub SAWs as ACF, Matched Filter, and Phase Detection

This invention presents a method and device for real-time analog signal processing using Surface Acoustic Wave (SAW) technology. The system performs three core functions without digital conversion: (1) Autocorrelation Function (ACF) for time-frequency transformation, (2) Matched Filtering for pattern recognition, and (3) Phase Detection of modulated signals. A SAW chip with interdigital transducers (IDTs) on a piezoelectric substrate decomposes input signals into parallel frequency channels ( frequency bins ). Envelope detection of each channel’s output generates an analog spectrogram. Weighting these outputs with predefined coded patterns (via analog operational circuits) enables instantaneous cross-correlation, acting as a matched filter. For phase-sensitive detection, in-phase/quadrature (I/Q) decomposition supports complex-valued processing of modulation schemes (e.g., QPSK, OFDM)

Measurement of the F2 structure function in deep inelastic e+^{+}p scattering using 1994 data from the ZEUS detector at HERA

We present measurements of the structure function \Ft\ in e^+p scattering at HERA in the range 3.5\;\Gevsq < \qsd < 5000\;\Gevsq. A new reconstruction method has allowed a significant improvement in the resolution of the kinematic variables and an extension of the kinematic region covered by the experiment. At \qsd < 35 \;\Gevsq the range in x now spans 6.3\cdot 10^{-5} < x < 0.08 providing overlap with measurements from fixed target experiments. At values of Q^2 above 1000 GeV^2 the x range extends to 0.5. Systematic errors below 5\perc\ have been achieved for most of the kinematic urray, W

Design and testing of a co-rotating vibration excitation system

A vibration excitation system (VES) in a form of an active coupling is proposed, designed and manufactured. The system is equipped with a set of piezoelectric stack actuators uniformly distributed around the rotor axis and positioned parallel to each other. The actuator arrangement allows an axial displacement of the coupling halves as well as their rotation about any transverse axis. Through the application of the VES an aimed vibration excitation is realised in a co-rotating coordinate system, which enables a non-invasive and precise modal analysis of rotating components. As an example, the VES is applied for the characterisation of the structural dynamic behaviour of a generic steel rotor at different rotational speeds. The first results are promising for both stationary and rotating conditions

Neandertal introgression partitions the genetic landscape of neuropsychiatric disorders and associated behavioral phenotypes

Despite advances in identifying the genetic basis of psychiatric and neurological disorders, fundamental questions about their evolutionary origins remain elusive. Here, introgressed variants from archaic humans such as Neandertals can serve as an intriguing research paradigm. We compared the number of associations for Neandertal variants to the number of associations of frequency-matched non-archaic variants with regard to human CNS disorders (neurological and psychiatric), nervous system drug prescriptions (as a proxy for disease), and related, non-disease phenotypes in the UK biobank (UKBB). While no enrichment for Neandertal genetic variants were observed in the UKBB for psychiatric or neurological disease categories, we found significant associations with certain behavioral phenotypes including pain, chronotype/sleep, smoking and alcohol consumption. In some instances, the enrichment signal was driven by Neandertal variants that represented the strongest association genome-wide. SNPs within a Neandertal haplotype that was associated with smoking in the UKBB could be replicated in four independent genomics datasets