Vertical selection for nuclear and mitochondrial genomes shapes gut microbiota and modifies risks for complex diseases

Here we postulate that the heritability of complex disease traits previously ascribed solely to the inheritance of the nuclear and mitochondrial genomes is broadened to encompass a third component of the holobiome, the microbiome. To test this, we expanded on the selectively bred low capacity runner/high capacity runner (LCR/HCR) rat exercise model system into four distinct rat holobiont model frameworks including matched and mismatched host nuclear and mitochondrial genomes. Vertical selection of varying nuclear and mitochondrial genomes resulted in differential acquisition of the microbiome within each of these holobiont models. Polygenic disease risk of these novel models were assessed and subsequently correlated with patterns of acquisition and contributions of their microbiomes in controlled laboratory settings. Nuclear-mitochondrial-microbiotal interactions were not for exercise as a reporter of health, but significantly noted for increased adiposity, increased blood pressure, compromised cardiac function, and loss of long-term memory as reporters of disease susceptibility. These findings provide evidence for coselection of the microbiome with nuclear and mitochondrial genomes as an important feature impacting the heritability of complex diseases.

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Evidence for a single mechanism gating perceptual and long-term memory information into working memory

10.31234/osf.io/3m7up ◽

2020 ◽

Author(s):

Sam Verschooren ◽

Yoav Kessler ◽

Tobias Egner

Keyword(s):

Working Memory ◽

Long Term Memory ◽

Sources Of Information ◽

Term Memory ◽

Source Selection ◽

Single Mechanism ◽

Gating Mechanism ◽

Opening And Closing ◽

Selection Of

An influential view of working memory (WM) holds that its’ contents are controlled by a selective gating mechanism that allows for relevant perceptual information to enter WM when opened, but shields WM contents from interference when closed. In support of this idea, prior studies using the reference-back paradigm have established behavioral costs for opening and closing the gate between perception and WM. WM also frequently requires input from long-term memory (LTM), but it is currently unknown whether a similar gate controls the selection of LTM representations into WM, and how WM gating of perceptual vs. LTM sources of information relate to each other. To address these key theoretical questions, we devised a novel version of the reference-back paradigm, where participants switched between gating perceptual and LTM information into WM. We observed clear evidence for gate opening and closing costs in both cases. Moreover, the pattern of costs associated with gating and source-switching indicated that perceptual and LTM information is gated into WM via a single gate, and rely on a shared source-selection mechanism. These findings extend current models of WM gating to encompass LTM information, and outline a new functional WM architecture.

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Optimum selection intensities in artificial selection programmes: an experimental evaluation

Genetics Research ◽

10.1017/s0016672300017535 ◽

1977 ◽

Vol 30 (2) ◽

pp. 115-119 ◽

Cited By ~ 4

Author(s):

R. Frankham

Keyword(s):

Experimental Evaluation ◽

Selection Intensity ◽

Effective Population ◽

Term Selection ◽

Optimum Selection ◽

Selection For ◽

Selection Intensities ◽

Selection Of ◽

Better Than

SUMMARYAn experimental evaluation of Robertson's (1970) theory concerning optimum intensities of selection for selection of varying durations has been carried out using published results from a long term selection study in Drosophila. Agreement of predicted rankings of treatments with expectations was excellent for low values of t/T (generations/total number scored) but poor for larger values of t/T. This was due to the 20% selection intensity treatments responding worse than expected and the 40% treatments relatively better than expected. Several possible reasons for the discrepancies exist but the most likely explanation is considered to be the greater reduction in effective population size due to selection in treatments with more intense selection.

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Temporal–prefrontal cortical network for discrimination of valuable objects in long-term memory

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1707695115 ◽

2018 ◽

Vol 115 (9) ◽

pp. E2135-E2144 ◽

Cited By ~ 13

Author(s):

Ali Ghazizadeh ◽

Whitney Griggs ◽

David A. Leopold ◽

Okihide Hikosaka

Keyword(s):

Functional Connectivity ◽

Resting State ◽

High Capacity ◽

Long Term Memory ◽

Gaze Behavior ◽

Resting State Functional Connectivity ◽

Term Memory ◽

Term Retention ◽

Long Term Retention

Remembering and discriminating objects based on their previously learned values are essential for goal-directed behaviors. While the cerebral cortex is known to contribute to object recognition, surprisingly little is known about its role in retaining long-term object–value associations. To address this question, we trained macaques to arbitrarily associate small or large rewards with many random fractal objects (>100) and then used fMRI to study the long-term retention of value-based response selectivity across the brain. We found a pronounced long-term value memory in core subregions of temporal and prefrontal cortex where, several months after training, fractals previously associated with high reward (“good” stimuli) elicited elevated fMRI responses compared with those associated with low reward (“bad” stimuli). Similar long-term value-based modulation was also observed in subregions of the striatum, amygdala, and claustrum, but not in the hippocampus. The value-modulated temporal–prefrontal subregions showed strong resting-state functional connectivity to each other. Moreover, for areas outside this core, the magnitude of long-term value responses was predicted by the strength of resting-state functional connectivity to the core subregions. In separate testing, free-viewing gaze behavior indicated that the monkeys retained stable long-term memory of object value. These results suggest an implicit and high-capacity memory mechanism in the temporal–prefrontal circuitry and its associated subcortical regions for long-term retention of object-value memories that can guide value-oriented behavior.

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The magical number 4 limits selection of object categories for encoding into visual long-term memory

Journal of Vision ◽

10.1167/18.10.831 ◽

2018 ◽

Vol 18 (10) ◽

pp. 831

Author(s):

Derek McClellan ◽

D. Alexander Varakin ◽

Amanda Renfro ◽

Jason Hays

Keyword(s):

Long Term Memory ◽

Term Memory ◽

Magical Number ◽

Object Categories ◽

Selection Of

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Some Memories Never Fade: Inferring Multi-Scale Memory Effects on Habitat Selection of a Migratory Ungulate Using Step-Selection Functions

Frontiers in Ecology and Evolution ◽

10.3389/fevo.2021.702818 ◽

2021 ◽

Vol 9 ◽

Author(s):

Helena Rheault ◽

Charles R. Anderson ◽

Maegwin Bonar ◽

Robby R. Marrotte ◽

Tyler R. Ross ◽

...

Keyword(s):

Habitat Selection ◽

Mule Deer ◽

Space Use ◽

Long Term Memory ◽

Environmental Covariates ◽

Short And Long Term ◽

Step Selection Functions ◽

Step Selection ◽

Selection Of

Understanding how animals use information about their environment to make movement decisions underpins our ability to explain drivers of and predict animal movement. Memory is the cognitive process that allows species to store information about experienced landscapes, however, remains an understudied topic in movement ecology. By studying how species select for familiar locations, visited recently and in the past, we can gain insight to how they store and use local information in multiple memory types. In this study, we analyzed the movements of a migratory mule deer (Odocoileus hemionus) population in the Piceance Basin of Colorado, United States to investigate the influence of spatial experience over different time scales on seasonal range habitat selection. We inferred the influence of short and long-term memory from the contribution to habitat selection of previous space use within the same season and during the prior year, respectively. We fit step-selection functions to GPS collar data from 32 female deer and tested the predictive ability of covariates representing current environmental conditions and both metrics of previous space use on habitat selection, inferring the latter as the influence of memory within and between seasons (summer vs. winter). Across individuals, models incorporating covariates representing both recent and past experience and environmental covariates performed best. In the top model, locations that had been previously visited within the same season and locations from previous seasons were more strongly selected relative to environmental covariates, which we interpret as evidence for the strong influence of both short- and long-term memory in driving seasonal range habitat selection. Further, the influence of previous space uses was stronger in the summer relative to winter, which is when deer in this population demonstrated strongest philopatry to their range. Our results suggest that mule deer update their seasonal range cognitive map in real time and retain long-term information about seasonal ranges, which supports the existing theory that memory is a mechanism leading to emergent space-use patterns such as site fidelity. Lastly, these findings provide novel insight into how species store and use information over different time scales.

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Starters and Bacteriophages in Lactic Acid Casein Manufacture

Journal of Milk and Food Technology ◽

10.4315/0022-2747-38.5.275 ◽

1975 ◽

Vol 38 (5) ◽

pp. 275-278 ◽

Cited By ~ 7

Author(s):

T. D. THOMAS ◽

R. J. LOWRIE

Keyword(s):

Lactic Acid ◽

New Zealand ◽

Acid Production ◽

Continuous Selection ◽

Streptococcus Cremoris ◽

Selection For ◽

The Individual ◽

First Time ◽

Selection Of

A controlled starter system was used for the first time in commercial lactic acid casein manufacture in New Zealand. Multiple starters of up to four components were constructed from 18 recently derived Streptococcus cremoris isolates which were not lysed by any of the phages in the collection of the New Zealand Dairy Research Institute. During the first season of casein manufacture, phages attacking 17 isolates were detected in the casein whey. Of these, 12 prevented adequate acid production by the appropriate host even at levels below 1 phage per 10 to 1000 ml in the milk before starter addition. In contrast, the first detected phages attacking the other five isolates did not significantly influence the rate of acid development; use of these starters continued until phages which eliminated acid production appeared. An alternative starter system based on the continuous selection of “phage-tolerant” cultures was investigated. Regular addition of whey, from previous manufacture, to the individual mother cultures of each component permitted long-term use of the multiple starter. This procedure of continued selection for phage-tolerant organisms has been used successfully for a complete season in a major casein factory.

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Exploring the impact of complex diseases on non-diseased human tissue transcriptomes

10.21203/rs.3.rs-317782/v1 ◽

2021 ◽

Author(s):

Chi-Lam Poon ◽

Cho-Yi Chen

Keyword(s):

Gene Expression ◽

Spinal Cord ◽

Human Body ◽

Complex Disease ◽

Association Studies ◽

Genetic Effect ◽

Complex Diseases ◽

Functional Enrichment ◽

The Impact

Abstract Background The development of complex diseases is contributed by the combination of multiple factors and complicated interactions between them. Inflammation has recently been associated with many complex diseases and may cause long-term damage to the human body. In this study, we examined whether two types of complex disease systematically altered the transcriptomes of non-diseased human tissues and whether inflammation was linked to identifiable molecular signatures, using post-mortem samples from the Genotype-Tissue Expression (GTEx) project. Results Following a series of differential expression (DE) analyses, dozens to hundreds of DE genes were identified in multiple tissues between subjects with and without a history of cerebrovascular disease (CVD) or major depression (MD). DE genes from these disease-associated tissues—the visceral adipose, tibial artery, caudate, and spinal cord for CVD; and the hypothalamus, putamen, and spinal cord for MD—were further analyzed for functional enrichment. Many pathways associated with immunological events were positively enriched in the DEGs of the CVD-associated tissues, as were the neurological and metabolic pathways in the MD-associated tissues. Eight gene–tissue pairs were found to overlap with those prioritized by our transcriptome-wide association studies (TWAS), indicating a potential genetic effect on gene expression for circulating cytokine phenotypes. Conclusions Complex diseases like CVD and MD may cause observable changes in the gene expression of non-diseased tissues, suggesting that a long-term impact of diseases, lifestyles and environmental factors may together contribute to the appearance of transcriptomic “scars” on the human body. Furthermore, inflammation is probably one of the systemic and long-lasting effects of cerebrovascular events.

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The Effect of the Colour Selection for Internal Surfaces on Non-Visual Daylight Human Response

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.1057.231 ◽

2014 ◽

Vol 1057 ◽

pp. 231-240

Author(s):

Peter Hartman ◽

Peter Hanuliak ◽

Lucia Maňková ◽

Jozef Hraška

Keyword(s):

Visual System ◽

Spectral Composition ◽

Light Conditions ◽

Basic Principles ◽

Health And Wellbeing ◽

System A ◽

Internal Surfaces ◽

Selection For ◽

Selection Of

Nowadays lighting criterions for internal spaces can be widened; because there is need to not only stimulate properly the human visual system but also to entrain the non-visual system of users or inhabitants. Since the medical discoveries in the field of light influence of circadian system, a system that controls our daily body rhythms, gave us basic principles how it works, we can use advanced methods how to evaluate internal light climate in the buildings. We focused on the colours of wall finishes, which influence the spectral composition of the light that enters the eye of inhabitants in specified locations. A set of specified applied colors were compared to the neutrally coloured walls. Also the effect of external shading obstruction was examined in this study. This observation, based on the spectral examination of light conditions, may provide more complex overview on selection of internal surfaces colours in long-term occupied spaces, taking health and wellbeing into consideration.

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Stable differentiation and clonality of murine long-term hematopoiesis after extended reduced-intensity selection for MGMT P140K transgene expression

Blood ◽

10.1182/blood-2006-11-053710 ◽

2007 ◽

Vol 110 (6) ◽

pp. 1779-1787 ◽

Cited By ~ 10

Author(s):

Claudia R. Ball ◽

Ingo H. Pilz ◽

Manfred Schmidt ◽

Sylvia Fessler ◽

David A. Williams ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem ◽

In Vivo Selection ◽

Cell Clones ◽

Selection For ◽

The Impact ◽

Reduced Intensity ◽

Selection Of

AbstractEfficient in vivo selection increases survival of gene-corrected hematopoietic stem cells (HSCs) and protects hematopoiesis, even if initial gene transfer efficiency is low. Moreover, selection of a limited number of transduced HSCs lowers the number of cell clones at risk of gene activation by insertional mutagenesis. However, a limited clonal repertoire greatly increases the proliferation stress of each individual clone. Therefore, understanding the impact of in vivo selection on proliferation and lineage differentiation of stem-cell clones is essential for its clinical use. We established minimal cell and drug dosage requirements for selection of P140K mutant O6-methylguanine-DNA-methyltransferase (MGMT P140K)–expressing HSCs and monitored their differentiation potential and clonality under long-term selective stress. Up to 17 administrations of O6-benzylguanine (O6-BG) and 1,3-bis(2-chloroethyl)-1-nitroso-urea (BCNU) did not impair long-term differentiation and proliferation of MGMT P140K–expressing stem-cell clones in mice that underwent serial transplantation and did not lead to clonal exhaustion. Interestingly, not all gene-modified hematopoietic repopulating cell clones were efficiently selectable. Our studies demonstrate that the normal function of murine hematopoietic stem and progenitor cells is not compromised by reduced-intensity long-term in vivo selection, thus underscoring the potential value of MGMT P140K selection for clinical gene therapy.

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Parameters and determinants of responses to selection in antibody libraries

PLoS Computational Biology ◽

10.1371/journal.pcbi.1008751 ◽

2021 ◽

Vol 17 (3) ◽

pp. e1008751

Author(s):

Steven Schulz ◽

Sébastien Boyer ◽

Matteo Smerlak ◽

Simona Cocco ◽

Rémi Monasson ◽

...

Keyword(s):

Affinity Maturation ◽

Response To Selection ◽

Evolutionary Potential ◽

Term Evolution ◽

A Genome ◽

Antibody Libraries ◽

Selection For ◽

The Impact ◽

Selection Of

The sequences of antibodies from a given repertoire are highly diverse at few sites located on the surface of a genome-encoded larger scaffold. The scaffold is often considered to play a lesser role than highly diverse, non-genome-encoded sites in controlling binding affinity and specificity. To gauge the impact of the scaffold, we carried out quantitative phage display experiments where we compare the response to selection for binding to four different targets of three different antibody libraries based on distinct scaffolds but harboring the same diversity at randomized sites. We first show that the response to selection of an antibody library may be captured by two measurable parameters. Second, we provide evidence that one of these parameters is determined by the degree of affinity maturation of the scaffold, affinity maturation being the process by which antibodies accumulate somatic mutations to evolve towards higher affinities during the natural immune response. In all cases, we find that libraries of antibodies built around maturated scaffolds have a lower response to selection to other arbitrary targets than libraries built around germline-based scaffolds. We thus propose that germline-encoded scaffolds have a higher selective potential than maturated ones as a consequence of a selection for this potential over the long-term evolution of germline antibody genes. Our results are a first step towards quantifying the evolutionary potential of biomolecules.

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