How informative is the mouse for human gut microbiota research?

The microbiota of the human gut is gaining broad attention owing to its association with a wide range of diseases, ranging from metabolic disorders (e.g. obesity and type 2 diabetes) to autoimmune diseases (such as inflammatory bowel disease and type 1 diabetes), cancer and even neurodevelopmental disorders (e.g. autism). Having been increasingly used in biomedical research, mice have become the model of choice for most studies in this emerging field. Mouse models allow perturbations in gut microbiota to be studied in a controlled experimental setup, and thus help in assessing causality of the complex host-microbiota interactions and in developing mechanistic hypotheses. However, pitfalls should be considered when translating gut microbiome research results from mouse models to humans. In this Special Article, we discuss the intrinsic similarities and differences that exist between the two systems, and compare the human and murine core gut microbiota based on a meta-analysis of currently available datasets. Finally, we discuss the external factors that influence the capability of mouse models to recapitulate the gut microbiota shifts associated with human diseases, and investigate which alternative model systems exist for gut microbiota research.KEY WORDS: Gut microbiota, Humanized mouse models, Mouse core gut microbiota, Mouse models, Mouse pan-gut microbiota     

How acidic is the lumen?

Proton motive force (pmf), established across the thylakoid membrane by photosynthetic electron transfer, functions both to drive the synthesis of ATP and initiate processes that down-regulate photosynthesis. At the same time, excessively low lumen pH can lead to the destruction of some lumenal components and sensitization of the photosynthetic apparatus to photoinhibition. Therefore, in order to understand the energy budget of photosynthesis, its regulation and responses to environmental stresses, it is essential to know the magnitude of pmf, its distribution between pH and the electric field () as well as the relationships between these parameters and G_ATP, and down-regulatory and inhibitory processes. We review past estimates of lumen pH and propose a model that can explain much of the divergent data in the literature. In this model, in intact plants under permissive conditions, photosynthesis is regulated so that lumen pH remains mod erate (between 5.8 and 6.5), where it modulates the activity of the violaxanthin deepoxidase, does not significantly restrict the turnover of the cytochrome b₆f complex, and does not destabilize the oxygen evolving complex. Only under stressed conditions, where light input exceeds the capacity of both photosynthesis and down-regulatory processes, does lumen pH decrease below 5, possibly contributing to photoinhibition. A value of n = 4 for the stoichiometry of protons pumped through the ATP synthase per ATP synthesized, and a minor contribution of to pmf, will allow moderate lumen pH to sustain the observed levels of G_ATP.     

Why is the house mouse karyotype so variable?

rates of robertsonian chromosomal evolution in the Western European house mouse are about two orders of magnitude greater than for most other mammals. This has resulted in a remarkable diversity of karyotypic races in a very short period of time. Recent studies are beginning to shed light on the relative contributions of mutation, drift, selection and meiotic drive in producing this pattern.     

Nucleosome positioning: How is it established, and why does it matter?

Packaging of eukaryotic genomes into chromatin affects every process that occurs on DNA. The positioning of nucleosomes on underlying DNA plays a key role in the regulation of these processes, as the nucleosome occludes underlying DNA sequences. Here, we review the literature on mapping nucleosome positions in various organisms, and discuss how nucleosome positions are established, what effect nucleosome positioning has on control of gene expression, and touch on the correlations between chromatin packaging, sequence evolution, and the evolution of gene expression programs.     

How local is the local field potential?

Local field potentials (LFPs) are of growing importance in neurophysiological investigations. LFPs supplement action potential recordings by indexing activity relevant to EEG, magnetoencephalographic, and hemodynamic (fMRI) signals. Recent reports suggest that LFPs reflect activity within very small domains of several hundred micrometers. We examined this conclusion by comparing LFP, current source density (CSD), and multiunit activity (MUA) signals in macaque auditory cortex. Estimated by frequency tuning bandwidths, these signals' "listening areas" differ systematically with an order of MUA?< CSD?< LFP. Computational analyses confirm that observed LFPs receive local contributions. Direct measurements indicate passive spread of LFPs to sites more than a centimeter from their origins. These findings appear to be independent of the frequency content of the LFP. Our results challenge the idea that LFP recordings typically integrate over extremely circumscribed local domains. Rather, LFPs appear as a mixture of local potentials with "volume conducted" potentials from distant sites.     

How important is it to consider lineage diversification heterogeneity in macroevolutionary studies? Lessons from the lizard family Liolaemidae

Macroevolutionary and biogeographical studies commonly apply multiple models to test state-dependent diversification. These models track the association between states of interest along a phylogeny, although many of them do not consider whether different clades might be evolving under different evolutionary drivers. Yet, they are still commonly applied to empirical studies without careful consideration of possible lineage diversification heterogeneity along the phylogenetic tree. A recent biogeographic study has suggested that orogenic uplift of the southern Andes has acted as a species pump, driving diversification of the lizard family Liolaemidae (307 described species), native to temperate southern South America. Here, we argue against the Andean uplift as main driver of evolution in this group. We show that there is a clear pattern of heterogeneous diversification in the Liolaemidae, which biases state- and environment-dependent analyses in, respectively, the GeoSSE and RPANDA programs. We show here that there are two shifts to accelerated speciation rates involving two clades that have both been classified as having “Andean” distributions. We incorporated the Geographic Hidden-State Speciation and Extinction model (GeoHiSSE) to accommodate unrelated diversification shifts, and also re-analyzed the data in RPANDA program after splitting biologically distinct clades for separate analyses, as well as including a more appropriate set of models. We demonstrate that the “Andean uplift” hypothesis is not supported when the heterogeneous diversification histories among these lizards is considered. We use the Liolaemidae as an ideal system to demonstrate potential risks of ignoring clade-specific differences in diversification patterns in macroevolutionary studies. We also implemented simulations to show that, in agreement with previous findings, the HiSSE approach can effectively and substantially reduce the level of distribution-dependent models receiving the highest AIC weights in such scenarios. However, we still find a relatively high rate (15%) of distribution-dependent models receiving the highest AIC weights, and provide recommendations related to the set of models included in the analyses that reduce these rates by half. Finally, we demonstrate that trees including clades following different dependent-drivers affect RPANDA analyses by producing different outcomes, ranging from partially correct models to completely misleading results. We provide recommendations for the implementation of both programs.     

What is a schizophrenic mouse?

In this issue of Neuron, Clapcote et al. examine mice containing missense mutations of the DISC1 gene, a locus associated with major mental illness in at least one large Scottish family. Genetic manipulation of mouse homologs of genes implicated in the etiology of psychiatric disorders is a promising avenue of research, but also one that is fraught with interpretative difficulties.     

How is a seita fitted to the body?

A seita is a carrier frame for backpacking used in Nishiki-cho, Yamaguchi Prefecture, Japan. In this mountainous district, people make their living by agriculture and forestry and carry everything on their backs with seita. In this study, we investigated the relationships between the sizes of a body and the dimensions of a seita. This survey was conducted on 30 subjects (mean +/- SD; 68.1 +/- 9.0 years old) at three mountain villages. We measured some anthropometric sizes and seita dimensions and found that the correlation between height and sum of shoulder-lumbar-nuki distance (back length of a seita) and shoulder strap length is significant. In additional surveys, we took photographs with some markers on iliocristale, trochanterion, and so on, when the subjects carried seita in two load conditions. The photographs indicate that the load-supporting points in 16 of 23 subjects were between the iliocristale and trochanterion (i.e., on the sacrum). It is important to note that nobody showed that point above the iliocristale (i.e., on the lumbar vertebra). These data lead to the conclusion that when people in Nishik-icho carry loads with seita, they support loads not on the lumbar vertebrae but on the sacrum, and that they adjust the perimeter consisting of the back part and shoulder strap of the seita.     

How random is the toss of a coin?

Background

The toss of a coin has been a method used to determine random outcomes for centuries. It is still used in some research studies as a method of randomization, although it has largely been discredited as a valid randomization method. We sought to provide evidence that the toss of a coin can be manipulated.

Methods

We performed a prospective experiment involving otolaryngology residents in Vancouver, Canada. The main outcome was the proportion of “heads” coin tosses achieved (out of 300 attempts) by each participant. Each of the participants attempted to flip the coin so as to achieve a heads result.

Results

All participants achieved more heads than tails results, with 7 of the 13 participants having significantly more heads results (p ≤ 0.05). The highest proportion of heads achieved was 0.68 (95% confidence interval 0.62–0.73, p < 0.001).

Interpretation

Certain people are able to successfully manipulate the toss of a coin. This throws into doubt the validity of using a coin toss to determine a chance result.The toss or flip of a coin to randomly assign a decision traditionally involves throwing a coin into the air and seeing which side lands facing up. This method may be used to resolve a dispute, see who goes first in a game or determine which type of treatment a patient receives in a clinical trial. There are only 2 possible outcomes, “heads” or “tails,” although, in theory, landing on an edge is possible. (Research suggests that when the coin is allowed to fall onto a hard surface, the chance of this happening is in the order of 1 in 6000 tosses.¹)When a coin is flipped into the air, it is supposedly made to rotate about an axis parallel to its flat surfaces. The coin is initially placed on a bent forefinger, and the thumb is released from under the coin surface, where it has been held under tension. The thumbnail strikes the part of the coin unsupported by the index finger, sending it rotating upward. All this is done with an upward movement of the hand and forearm. The coin may be allowed to fall to the floor or other surface or it may be caught by the “tosser” and sometimes turned onto the back of the opposite hand and then revealed. The catching method should not matter, provided it is consistent for each toss. The opponent often calls the toss when the coin is airborne, although in the case of randomization for clinical trials, this is unnecessary because one is simply looking for an outcome.Open in a separate windowThe appeal of the coin toss that it is a simple, seemingly unbiased, method of deciding between 2 options. Although the outcome of a coin toss should be at even odds, the outcome may well not be. Historically, the toss of a coin before a duel reputedly decided which person had his back to the sun — an obvious advantage when taking aim! In medical trials, a simple statistical manipulation can have a dramatic effect on the treatment a patient receives. Our hypothesis is that with minimal training, the outcome of the toss can be weighted heavily to the call of the tosser, thus abolishing the 50:50 chance result that is expected and allowing for manipulation of an apparently random event.     

How costly is the honest signaling of need?

ESS models of biological signaling have shown that costly signals can provide honest information. In the context of parent-offspring conflict over the allocation of resources by parents to their young, the theory explains costly offspring solicitation behavior as an accurate signal of offspring need to parents who cannot assess offspring condition directly. In this paper, we provide a simple but general characterization of the honest signaling of need in models of parent-offspring conflict: the offspring's signaling cost is proportional to the parent's fitness loss from satisfying the offspring's resource requirement. The factor of proportionality is given by a measure of the extent of parent-offspring conflict that depends only on coefficients of relatedness. These results hold for interbrood conflict with uniparental investment even if the relationship between offspring condition and resource requirement is not monotonic, and extend to cases of biparental care, uncertainty concerning the parent's condition, and intra-brood conflict. Copyright 1999 Academic Press.     

Just How Emergent is the Emergence of Semiosis?

Studying the origin of semiosis is a task obscured by terminological and metaphysical issues which create an ambiguous set of definitions for biosemiotics when referring to the concept of emergence. The question is, how emergent can semiosis be? And what are the conditions for semiosis to be an emergent of a certain type? This paper will attempt to briefly deal with the general terminology of emergence from a philosophical point of view and will discuss the characterization of semiosis as an emergent phenomenon based on the distinctions made by Bedau, Kim and Chalmers. Accordingly, we will consider the possibility of strong and weak emergence in an attempt to bring some clarity to what it means for something in biosemiotics to be an emergent and how the philosophical concepts play out when applied to biosemiotic research. In inquiring into the metaphysical status of semiosis, we change our semiotic theories to correspond to the assumptions contained in the elementary objects of our theories. This being the case, the way semiosis–the constitutive element that it is for semiotics–is taken to be with regards to its possible ontology, will conduct to different research objects for the long-term investigation of its origins and necessary conditions.     

COMMENTARY: How cryptic is the Scandinavian lynx?

A reanalysis of the existing genotypic data shows that they are compatible with the hypothesis that the present-day Scandinavian lynx represents a recent expansion from a single source. This contradicts earlier conclusions. The difference arises when it is assumed that the expansion and colonization have been stochastic processes and that the populations may not be at a drift-migration equilibrium.     

How is the individuality of a face recognized?

A familiar face is instantly recognized in a crowd. This cannot be achieved through a feature by feature comparison of the observed face with either an average face (norm-based model of face recognition) or with a set of similarly constructed faces stored in memory (exemplar-based model of face recognition). A modified norm-based model is thus proposed. Instead of memorizing an average face, the normal variations for each facial feature are used to construct a multidimensional volume of face-space devoid of unusual features, here defined as features whose metrics lie below the 5th or above the 95th percentiles for that feature. A face consisting of 100 independently variable features will thus have, on average, 10 unusual features. Face identification then becomes exception-reporting. It requires only 10 such rare features to render a given face a one in 10¹³ faces (P=0.05¹⁰=9.8×10⁻¹⁴). In a world containing 6.7×10⁹ people, such a face would be unique. Faces remembered in this way can have their unusual features exaggerated or attenuated without loss of identity. This is the basis of caricatures and anti-caricatures. It also means that individuals belonging to a foreign race, possessing several features with modes beyond the “usual range” of the own-race population, will all look alike. Features that render a face unique in the own-race population are now shared by everyone in the foreign race.Average faces are more beautiful than the faces used in the averaging process. This makes evolutionary sense. Natural selection increases the frequency of fit features at the expense of maladaptive features. “Usual features” are therefore fitter than “unusual features”, and play an important role in mate selection. Such an existing fundamental sexual attribute could easily have been harnessed for the fast and efficient recognition of individuals in the community.