Adaptive evolution of molecular phenotypes

Molecular phenotypes link genomic information with organismic functions, fitness, and evolution. Quantitative traits are complex phenotypes that depend on multiple genomic loci. In this paper, we study the adaptive evolution of a quantitative trait under time-dependent selection, which arises from environmental changes or through fitness interactions with other co-evolving phenotypes. We analyze a model of trait evolution under mutations and genetic drift in a single-peak fitness seascape. The fitness peak performs a constrained random walk in the trait amplitude, which determines the time-dependent trait optimum in a given population. We derive analytical expressions for the distribution of the time-dependent trait divergence between populations and of the trait diversity within populations. Based on this solution, we develop a method to infer adaptive evolution of quantitative traits. Specifically, we show that the ratio of the average trait divergence and the diversity is a universal function of evolutionary time, which predicts the stabilizing strength and the driving rate of the fitness seascape. From an information-theoretic point of view, this function measures the macro-evolutionary entropy in a population ensemble, which determines the predictability of the evolutionary process. Our solution also quantifies two key characteristics of adapting populations: the cumulative fitness flux, which measures the total amount of adaptation, and the adaptive load, which is the fitness cost due to a population's lag behind the fitness peak.Comment: Figures are not optimally displayed in Firefo

Towards Auditory Profile-Based Hearing-Aid Fittings:BEAR Rationale and Clinical Implementation

(1) Background: To improve hearing-aid rehabilitation, the Danish ‘Better hEAring Rehabilitation’ (BEAR) project recently developed methods for individual hearing loss characterization and hearing-aid fitting. Four auditory profiles differing in terms of audiometric hearing loss and supra-threshold hearing abilities were identified. To enable auditory profile-based hearing-aid treatment, a fitting rationale leveraging differences in gain prescription and signal-to-noise (SNR) improvement was developed. This report describes the translation of this rationale to clinical devices supplied by three industrial partners. (2) Methods: Regarding the SNR improvement, advanced feature settings were proposed and verified based on free-field measurements made with an acoustic mannikin fitted with the different hearing aids. Regarding the gain prescription, a clinically feasible fitting tool and procedure based on real-ear gain adjustments were developed. (3) Results: Analyses of the collected real-ear gain and SNR improvement data confirmed the feasibility of the clinical implementation. Differences between the auditory profile-based fitting strategy and a current ‘best practice’ procedure based on the NAL-NL2 fitting rule were verified and are discussed in terms of limitations and future perspectives. (4) Conclusion: Based on a joint effort from academic and industrial partners, the BEAR fitting rationale was transferred to commercially available hearing aids

Auditory Tests for Characterizing Hearing Deficits in Listeners With Various Hearing Abilities: The BEAR Test Battery

The Better hEAring Rehabilitation (BEAR) project aims to provide a new clinical profiling tool—a test battery—for hearing loss characterization. Although the loss of sensitivity can be efficiently measured using pure-tone audiometry, the assessment of supra-threshold hearing deficits remains a challenge. In contrast to the classical “attenuation-distortion” model, the proposed BEAR approach is based on the hypothesis that the hearing abilities of a given listener can be characterized along two dimensions, reflecting independent types of perceptual deficits (distortions). A data-driven approach provided evidence for the existence of different auditory profiles with different degrees of distortions. Ten tests were included in a test battery, based on their clinical feasibility, time efficiency, and related evidence from the literature. The tests were divided into six categories: audibility, speech perception, binaural processing abilities, loudness perception, spectro-temporal modulation sensitivity, and spectro-temporal resolution. Seventy-five listeners with symmetric, mild-to-severe sensorineural hearing loss were selected from a clinical population. The analysis of the results showed interrelations among outcomes related to high-frequency processing and outcome measures related to low-frequency processing abilities. The results showed the ability of the tests to reveal differences among individuals and their potential use in clinical settings

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2

Analysis of the formation of memory and place cells in the hippocampus

Ein weit verbreitetes Modell postuliert, dass Gedächtnisinhalte (repräsentiert als neuronale Aktivitätsmuster im entorhinalem Kortex) in der hippocampalen Subregion CA3 abgespeichert werden und dass diese Region als ein autoassociatives Netzwerk funktioniert. Seit Kurzem ist jedoch bekannt, dass viele Neurone im entorhinalem Kortex, die sogenannten Gitterzellen, in einer speziellen Weise feuern. Wir untersuchen ob das Modell auch Muster speichern kann, welche die Aktivität von Gitterzellen wiederspiegeln und finden heraus, dass ein autoassociatives CA3 Netzwerk schädlich ist für Gedächtnisbildung. Wir präsentieren stattdessen ein alternatives Modell, welches Muster effektiver speichern kann. Des Weiteren zeigen wir, dass in einem vorwärtsgerichtetem Netzwerk realistische Ortszellen nicht allein aus Gitterzellen erzeugt werden können, sondern schlagen vielmehr vor, dass Ortszellen aus allen verschieden entorhinalen Zelltypen generiert werden.One widely accepted model postulates that memories (represented as patterns of neuronal activity in the entorhinal cortex) are stored in the hippocampal CA3 subregion and that this region functions as an auto-associative network. Recently, it is known that many neurons in the entorhinal cortex, the so-called grid cells, fire in a special way. We investigate whether the model can store patterns, which reflect the activity of grid cells and we find out that an auto-associative CA3 network is detrimental to memory formation. We instead present an alternative model which can store patterns more effectively. Furthermore, we show that in a feedforward network place cells cannot be produced solely by grid cells. We suggest instead that place cells are generated by all different cell types that are present in the entorhinal cortex

Comparing headphone- and loudspeaker-playback using spatial scene analysis in virtual audio-visual reverberant environments

In multi-talker situations, listeners face the challenge of having to identify a target speech source out of a mixture of interfering sources. To test these realistic situations in the laboratory it is common to employ arrays with many loudspeakers. Allowing clinics to use such experimental paradigms, headphone playback can be an alternative. However, headphone reproduction often leads to different outcomes because of the lack of individual head-related transfer functions (HRTFs). Here, we investigated how normal-hearing listeners analyze virtual audio-visual scenes that differed in terms of the number of concurrent talkers and the amount of reverberation using either head-tracked headphones using generic HRTFs or via a loudspeaker-array. Listeners were asked to identify and locate an ongoing story in a mixture of other stories. The visual components of the scenarios were reproduced via virtual reality headset. Differences between loudspeaker and headphone-based reproduction were evaluated using the response time and the localization accuracy. The number of talkers as well as the amount of reverberation affected the ability to analyze an audio-visual scene, in terms of response time and localization error. Preliminary data suggest only slightly elevated response times when employing headphone reproduction compared to loudspeakers, making them a valid tool for clinical research.</p

Memory storage fidelity in the hippocampal circuit: the role of subregions and input statistics.

In the last decades a standard model regarding the function of the hippocampus in memory formation has been established and tested computationally. It has been argued that the CA3 region works as an auto-associative memory and that its recurrent fibers are the actual storing place of the memories. Furthermore, to work properly CA3 requires memory patterns that are mutually uncorrelated. It has been suggested that the dentate gyrus orthogonalizes the patterns before storage, a process known as pattern separation. In this study we review the model when random input patterns are presented for storage and investigate whether it is capable of storing patterns of more realistic entorhinal grid cell input. Surprisingly, we find that an auto-associative CA3 net is redundant for random inputs up to moderate noise levels and is only beneficial at high noise levels. When grid cell input is presented, auto-association is even harmful for memory performance at all levels. Furthermore, we find that Hebbian learning in the dentate gyrus does not support its function as a pattern separator. These findings challenge the standard framework and support an alternative view where the simpler EC-CA1-EC network is sufficient for memory storage

From grid cells to place cells with realistic field sizes.

While grid cells in the medial entorhinal cortex (MEC) of rodents have multiple, regularly arranged firing fields, place cells in the cornu ammonis (CA) regions of the hippocampus mostly have single spatial firing fields. Since there are extensive projections from MEC to the CA regions, many models have suggested that a feedforward network can transform grid cell firing into robust place cell firing. However, these models generate place fields that are consistently too small compared to those recorded in experiments. Here, we argue that it is implausible that grid cell activity alone can be transformed into place cells with robust place fields of realistic size in a feedforward network. We propose two solutions to this problem. Firstly, weakly spatially modulated cells, which are abundant throughout EC, provide input to downstream place cells along with grid cells. This simple model reproduces many place cell characteristics as well as results from lesion studies. Secondly, the recurrent connections between place cells in the CA3 network generate robust and realistic place fields. Both mechanisms could work in parallel in the hippocampal formation and this redundancy might account for the robustness of place cell responses to a range of disruptions of the hippocampal circuitry