Biology subjects

Peters, J.

Publications and source records attributed to Peters, J..

At least 55 records · Page 3Linked to original sources

bioRxiv2022

Erotic cue exposure increases physiological arousal, biases choices towards immediate rewards and attenuates model-based reinforcement learning

Computational psychiatry focuses on identifying core cognitive processes that appear altered across a broad range of psychiatric disorders. Temporal discounting of future rewards and model-based control during reinforcement learning have proven as two promising candidates. Despite its trait-like stability, temporal discounting has been suggested to be at least partly under contextual control. For example, highly arousing cues such as erotic pictures were shown to increase discounting, although overall evidence to date remains somewhat mixed. Whether model-based reinforcement learning is similarly affected by arousing cues is unclear. Here we tested cue-reactivity effects (erotic pictures) on subsequent temporal discounting and model-based reinforcement learning in a within-subjects design in n=39 healthy male participants. Self-reported and physiological arousal (cardiac activity and pupil dilation) were assessed before and during cue exposure. Arousal was increased during exposure of erotic vs. neutral cues both on the subjective and autonomic level. Erotic cue exposure nominally increased discounting as reflected by reduced choices of delayed options. Hierarchical drift diffusion modeling (DDM) linked increased discounting to a shift in the starting point bias of evidence accumulation towards immediate options. Model-based control during reinforcement learning was reduced following erotic cues according to model-agnostic analysis. Notably, DDM linked this effect to attenuated forgetting rates of unchosen options, leaving the model-based control parameter unchanged. Our findings replicate previous work on cue-reactivity effects in temporal discounting and for the first time show similar effects in model-based reinforcement learning. Our results highlight how environmental cues can impact core human decision processes and reveal that comprehensive drift diffusion modeling approaches can yield novel insights in reward-based decision processes.

neuroscience↗

bioRxiv2022

Imaging the columnar functional organization of human area MT+ to axis-of-motion stimuli using VASO at 7 Tesla

Cortical columns of direction-selective neurons in the motion sensitive area (MT) have been successfully established as a microscopic feature of the neocortex in animals. The same property has been investigated at mesoscale (<1 mm) in the homologous brain area (hMT+, V5) in living humans by using ultra-high field functional magnetic resonance imaging (fMRI). Despite the reproducibility of the selective response to axis-of-motion stimuli, clear quantitative evidence for the columnar organization of hMT+ is still lacking. Using cerebral blood volume (CBV)-sensitive fMRI at 7 Tesla with submillimeter resolution and high spatial specificity to microvasculature, we investigate the columnar functional organization of hMT+ in 5 participants perceiving axis-of-motion stimuli for both blood oxygenation level dependent (BOLD) and vascular space occupancy (VASO) contrast mechanisms provided by the used Slab-Selective Slice Inversion (SS-SI)-VASO sequence. With the development of a new searchlight algorithm for column detection, we provide the first quantitative columnarity map that characterizes the entire 3D hMT+ volume. Using voxel-wise measures of sensitivity and specificity, we demonstrate the advantage of using CBV-sensitive fMRI to detect mesoscopic cortical features by revealing higher specificity of axis-of-motion cortical columns for VASO as compared to BOLD contrast. These voxel-wise metrics also provide further insights on how to mitigate the highly debated draining veins effect. We conclude that using CBV-VASO fMRI together with voxel-wise measurements of sensitivity, specificity and columnarity offers a promising avenue to quantify the mesoscopic organization of hMT+ with respect to axis-of-motion stimuli. Furthermore, our approach and methodological developments are generalizable and applicable to other human brain areas where similar mesoscopic research questions are addressed.

neuroscience↗

bioRxiv2022

Between fishing and farming: palaeogenomic analyses reveal cross-cultural interactions triggered by the arrival of the Neolithic in the Danube Gorges

While early Neolithic populations in Europe were largely descended from early Aegean farmers, there is also evidence of episodic gene flow from local Mesolithic hunter-gatherers into early Neolithic communities. Exactly how and where this occurred is still unknown. Here we report direct evidence for admixture between the two groups at the Danube Gorges in Serbia. Analysis of palaeogenomes recovered from skeletons revealed that second-generation mixed individuals were buried amidst individuals whose ancestry was either exclusively Aegean Neolithic or exclusively local Mesolithic. The mixed ancestry is also reflected in a corresponding mosaic of grave goods. With its deep sequence of occupation and its unique dwellings that suggest at least semi-sedentary occupation since the late Mesolithic, the area of the Danube Gorges has been at the center of the debate about the contribution of Mesolithic societies to the Neolithisation of Europe. As suggested by our data, which were processed exclusively with uncertainty-aware bioinformatic tools, it may have been precisely in such contexts that close interactions between these societies were established, and Mesolithic ancestry and cultural elements were assimilated.

genomics↗

bioRxiv2022

Fatty acid synthesis knockdown promotes biofilm wrinkling and inhibits sporulation in Bacillus subtilis

Many bacterial species typically live in complex three-dimensional biofilms, yet little is known about systematic changes to gene function between non-biofilm and biofilm lifestyles. Here, we created a CRISPRi library of knockdown strains covering all known essential genes in the biofilm-forming Bacillus subtilis strain 3610. We show that gene essentiality is largely conserved between liquid and surface growth and between two media. We developed an image analysis algorithm to quantify biofilm colony wrinkling, which identified strains with high or low levels of wrinkling that were uncorrelated with extracellular matrix gene expression. We also designed a high-throughput screen for sensitive quantification of sporulation efficiency and performed the first screens of sporulation during essential gene knockdown. We found that all basal knockdowns of essential genes were competent for sporulation in a sporulation-inducing medium, but certain strains exhibited reduced sporulation efficiency in LB, a medium with generally lower levels of sporulation. Knockdown of fatty acid synthesis increased wrinkling and inhibited sporulation. These results highlight the importance of essential genes in biofilm structure and sporulation/germination and suggest a previously unappreciated and multifaceted role for fatty acid synthesis in bacterial lifestyles and developmental processes. Abstract ImportanceFor many bacteria, life typically involves growth in dense, three-dimensional communities called biofilms that contain cells with differentiated roles and are held together by extracellular matrix. To examine how gene function varies between non-biofilm and biofilm growth, we created a comprehensive library of strains using CRISPRi to knockdown expression of each essential gene in the model species Bacillus subtilis 3610, which can develop into a wrinkled biofilm structure or a spore capable of surviving harsh environments. This library enabled us to determine when gene essentiality depends on growth conditions. We also developed high-throughput assays and computational algorithms to identify essential genes involved in biofilm wrinkling and sporulation. Knockdown of fatty acid synthesis increased the density of wrinkles, and also inhibited sporulation in a medium with generally lower sporulation levels. These findings indicate that essential processes such as fatty acid synthesis can play important and multifaceted roles in bacterial development.

microbiology↗

bioRxiv2022

Unravelling the mechanisms of adaptation to high pressure in proteins

Life is thought to have appeared in the depth of the sea, under high hydrostatic pressure. Nowadays, it is known that the deep biosphere hosts a myriad of life forms thriving under high pressure conditions. However, the evolutionary mechanisms leading to their adaptation are still not known. Here we show the molecular bases of these mechanisms through a neutron scattering study of two orthologous proteins. We observed that pressure adaptation involves the decoupling of protein-water dynamics and the elimination of cavities in the protein core. This is achieved by an enrichment of acidic residues on the protein surface and by the use of bulkier hydrophobic residues in the core. These findings will be the starting point in the search of a complete genomic model explaining high pressure adaptation.

biophysics↗

bioRxiv2022

The dynamical Matryoshka model: 3. Diffusive nature of the atomic motions contained in a new dynamical model for deciphering local lipid dynamics

In accompanying papers [Bicout et al., BBA - Biomembr. Submitted; Cisse et al., BBA - Biomembr. Submitted], a new model called Matryoshka model has been proposed to describe the geometry of atomic motions in phospholipid molecules in bilayers and multilamellar vesicles based on their quasielastic neutron scattering (QENS) spectra. Here, in order to characterize the relaxational aspects of this model, the energy widths of the QENS spectra of the samples were analyzed first in a model-free way. The spectra were decomposed into three Lorentzian functions, which are classified as slow, intermediate, and fast motions depending on their widths. The analysis provides the diffusion coefficients, residence times, and geometrical parameters for the three classes of motions. The results corroborate the parameter values such as the amplitudes and the mobile fractions of atomic motions obtained by the application of the Matryoshka model to the same samples. Since the current analysis was carried out independently of the development of the Matryoshka model, the present results enhance the validity of the model. The model will serve as a powerful tool to decipher the dynamics of lipid molecules not only in model systems, but also in more complex systems such as mixtures of different kinds of lipids or natural cell membranes.

biophysics↗

bioRxiv2022

High temperature molecular motions within a model protomembrane architecture

Modern phospholipid membranes are known to be in a functional, physiological state, corresponding to the liquid crystalline phase, only under very precise external conditions. The phase is characterised by specific lipid motions, which seem mandatory to permit sufficient flexibility and stability for the membrane. It can be assumed that similar principles hold for proto-membranes at the origin of life although they were likely composed of simpler, single chain fatty acids and alcohols. In the present study we investigated molecular motions of four types of model membranes to shed light on the variations of dynamics and structure as a function of temperature as protocells might have existed close to hot vents. We find a clear hierarchy among the flexibilities of the samples, where some structural parameters seem to depend on the lipids used while others do not.

biophysics↗

bioRxiv2022

The dynamical Matryoshka model: 2. Modeling of local lipid dynamics at the sub-nanosecond timescale in phospholipid membranes

Biological membranes are generally formed by lipids and proteins. Often, the membrane properties are studied through model membranes formed by phospholipids only. They are molecules composed by a hydrophilic head group and hydrophobic tails, which can present a panoply of various motions, including small localized movements of a few atoms up to the diffusion of the whole lipid or collective motions of many of them. In the past, efforts were made to measure these motions experimentally by incoherent neutron scattering and to quantify them, but with upcoming modern neutron sources and instruments, such models can now be improved. In the present work, we expose a quantitative and exhaustive study of lipid dynamics on DMPC and DMPG membranes, using the Matryoshka model recently developed by our group. The model is confronted here to experimental data collected on two different membrane samples, at three temperatures and two instruments. Despite such complexity, the model describes reliably the data and permits to extract a series of parameters. The results compare also very well to other values found in the literature. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/486370v1_fig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@374f9corg.highwire.dtl.DTLVardef@14ba37eorg.highwire.dtl.DTLVardef@dae67corg.highwire.dtl.DTLVardef@151f721_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1:C_FLOATNO Graphical abstract. C_FIG Highlights- The Matryoshka model brings a new general description of local lipid dynamics. - Phospholipid membranes on various conditions are compared in this novel framework. - Effects of main phase transition, membrane geometry or motion direction are probed. - Despite high number of parameters, overfitting is avoided by a global fit strategy.

biophysics↗

bioRxiv2022

Longer metaphase and fewer chromosome segregation errors in modern human than Neandertal brain development

Since the ancestors of modern humans separated from those of Neandertals, around one hundred amino acid substitutions spread to essentially all modern humans. The biological significance of these changes is largely unknown. Here, we examine all six such amino acid substitutions in the three proteins known to have key roles in kinetochore function and chromosome segregation and to be highly expressed in the stem cells of the developing neocortex. When we introduce these modern human-specific substitutions in the mouse, three substitutions in two of these proteins, KIF18a and KNL1, cause a prolongation of metaphase and a reduction in chromosome segregation errors in apical progenitors of the developing neocortex. Conversely, the ancestral substitutions cause a reduction in metaphase length and an increase in chromosome segregation errors in human brain organoids. Our data also show that, in these aspects, Neandertals were more similar to chimpanzees than to modern humans. Thus, the fidelity of chromosome segregation during neocortex development improved in modern humans after their divergence from Neandertals.

neuroscience↗

bioRxiv2022

A single dose of the catecholamine precursor Tyrosine reduces physiological arousal and decreases decision thresholds in reinforcement learning and temporal discounting

Supplementation with the catecholamine precursor L-Tyrosine might enhance cognitive performance, but overall findings are mixed. Here, we investigate the effect of a single dose of tyrosine (2g) vs. placebo on two key aspects of catecholamine-dependent decision-making: model-based reinforcement learning (2-step task) and temporal discounting, using a double-blind, placebo-controlled, within-subject design (n=28 healthy male participants). We leveraged drift diffusion models in a hierarchical Bayesian framework to jointly model participants choices and response times in both tasks. Furthermore, comprehensive autonomic monitoring (heart rate, heart rate variability, pupillometry, spontaneous eye-blink rate) was performed both pre- and post-supplementation, to explore potential physiological effects of supplementation. Across tasks, tyrosine consistently reduced participants RTs without deteriorating task-performance. Diffusion modeling linked this effect to attenuated decision-thresholds in both tasks and further revealed increased model-based control (2-step task) and (if anything) attenuated temporal discounting. On the physiological level, participants pupil dilation was predictive of the individual degree of temporal discounting. Tyrosine supplementation reduced physiological arousal as revealed by increases in pupil dilation variability and reductions in hear rate. Supplementation-related changes in physiological arousal predicted individual changes in temporal discounting. Our findings provide first evidence that tyrosine supplementation might impact psychophysiological parameters, and suggest that modeling approaches based on sequential sampling models can yield novel insights into latent cognitive processes modulated by amino-acid supplementation.

neuroscience↗

bioRxiv2021

A Marmoset Model for Mycobacterium avium Complex Pulmonary Disease

RationaleMycobacterium avium complex, is the most common nontuberculous mycobacterial respiratory pathogen in humans. Disease mechanisms are poorly understood due to the absence of a reliable animal model for M. avium complex pulmonary disease. ObjectiveAssess the susceptibility, immunologic and histopathologic responses of the common marmoset (Callithrix jacchus) to M. avium complex pulmonary infection. Methods7 adult female marmosets underwent endobronchial inoculation with 108 colony-forming units of M. intracellulare and were monitored for 30 or 60 days. Prior to infection, chest radiograph and serum cytokines were assessed; serum cytokines were also monitored weekly for 30 days. At sacrifice 30 days (3 animals) or 60 days (4 animals) after infection, chest radiograph, serum and bronchoalveolar lavage cytokines, histopathology, and cultures of the bronchoalveolar lavage, lungs, liver, and kidney were analyzed. Measurements and Main ResultsFive of seven animals (two at 30 days and three at 60 days of infection) had positive lung cultures for M. intracellulare. Extra-pulmonary cultures were positive in three animals. All animals appeared healthy throughout the study. All five animals with positive lung cultures had radiographic changes consistent with pneumonitis. At 30 days, those with M. intracellulare lung infection showed granulomatous inflammation while at 60 days there was less inflammatory change, but bronchiectasis was noted. The cytokine response in the bronchoalveolar lavage fluid was uniformly greater in the animals with positive M. intracellulare cultures than those without a productive infection with greater levels at 30-days compared to 60-days. Similarly, serum cytokines were more elevated in the animals that had positive M. intracellulare cultures compared to those without a productive infection, peaking 14-21 days after inoculation. ConclusionEndobronchial instillation of M. intracellulare resulted in pulmonary mycobacterial infection in marmosets with a differential immune response, radiographic and histopathologic abnormalities, and an indolent course consistent with M. avium complex lung infection in humans.

microbiology↗

bioRxiv2021

Motor response vigour and fixations reflect subjective preferences during intertemporal choice

Value-based decision-making is of central interest in cognitive neuroscience and psychology, as well as in the context of neuropsychiatric disorders characterised by decision-making impairments. Studies examining (neuro-)computational mechanisms underlying choice behaviour typically focus on participants decisions. However, there is increasing evidence that option valuation might also be reflected in motor response vigour and eye movements, implicit measures of subjective utility. To examine motor response vigour and visual fixation correlates of option valuation in intertemporal choice, we set up a task where the participants selected an option by pressing a grip force transducer, simultaneously tracking fixation shifts between options. As outlined in our preregistration (https://osf.io/k6jct), we used hierarchical Bayesian parameter estimation to model the choices assuming hyperbolic discounting, compared variants of the softmax and drift diffusion model, and assessed the relationship between response vigour and the estimated model parameters. The behavioural data were best explained by a drift diffusion model specifying a non-linear scaling of the drift rate by the subjective value differences. Replicating previous findings (Green et al., 1997; Wagner et al., 2020), we found a magnitude effect for temporal discounting, such that higher rewards were discounted less. This magnitude effect was further reflected in response vigour, such that stronger forces were exerted in the high vs. the low magnitude condition. Bayesian hierarchical linear regression further revealed higher grip forces, faster response times and a lower number of fixation shifts for trials with higher subjective value differences. Our data suggest that subjective utility or implicit valuation is reflected in response vigour during intertemporal choice. Taking into account response vigour might thus provide deeper insight into decision-making, reward valuation and maladaptive changes in these processes, e.g. in the context of neuropsychiatric disorders.

neuroscience↗

bioRxiv2021

Parameter and model recovery of reinforcement learning models for restless bandit problems

Multi-armed restless bandit tasks are regularly applied in psychology and cognitive neuroscience to assess exploration and exploitation behavior in structured environments. These models are also readily applied to examine effects of (virtual) brain lesions on performance, and to infer neurocomputational mechanisms using neuroimaging or pharmacological approaches. However, to infer individual, psychologically meaningful parameters from such data, computational cognitive modeling is typically applied. Recent studies indicate that softmax (SM) decision rule models that include a representation of environmental dynamics (e.g. the Kalman Filter) and additional parameters for modeling exploration and perseveration (Kalman SMEP) fit human bandit task data better than competing models. Parameter and model recovery are two central requirements for computational models: parameter recovery refers to the ability to recover true data-generating parameters; model recovery refers to the ability to correctly identify the true data generating model using model comparison techniques. Here we comprehensively examined parameter and model recovery of the Kalman SMEP model as well as nested model versions, i.e. models without the additional parameters, using simulation and Bayesian inference. Parameter recovery improved with increasing trial numbers, from around .8 for 100 trials to around .93 for 300 trials. Model recovery analyses likewise confirmed acceptable recovery of the Kalman SMEP model. Model recovery was lower for nested Kalman filter models as well as delta rule models with fixed learning rates. Exploratory analyses examined associations of model parameters with model-free performance metrics. Random exploration, captured by the inverse softmax temperature, was associated with lower accuracy and more switches. For the exploration bonus parameter modeling directed exploration, we confirmed an inverse-U-shaped association with accuracy, such that both an excess and a lack of directed exploration reduced accuracy. Taken together, these analyses underline that the Kalman SMEP model fulfills basic requirements of a cognitive model.

neuroscience↗

bioRxiv2021

The dynamical Matryoshka model: 1. Incoherent neutron scattering functions for lipid dynamics in bilayers

Fluid lipid bilayers are the building blocks of biological membranes. Although there is a large amount of experimental data using inconsistent quasi-elastic neutron scattering (QENS) techniques to study membranes, very little theoretical works have been developed to study the local dynamics of membranes. The main objective of this work is to build a theoretical framework to study and describe the local dynamics of lipids and derive analytical expressions of inconsistent diffusion functions (ISF) for QENS. As results, we developed the dynamical Matryoshka model which describes the local dynamics of lipid molecules in membrane layers as a nested hierarchical convolution of three motional processes: (i) individual motions described by the vibrational motions of H-atoms; (ii) internal motions including movements of the lipid backbone, head groups and tails, and (iii) molecule movements of the lipid molecule as a whole. The analytical expressions of the ISF associated with these movements are all derived. For use in analyzing the QENS experimental data, we also derived an analytical expression for the aggregate ISF of the Matryoshka model which involves an elastic term plus three inelastic terms of well-separated time scales and whose amplitudes and rates are functions of the lipid motions. And as an illustrative application, we used the aggregated ISF to analyze the experimental QENS data on a lipid sample of multilamellar bilayers of DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine). It is clear from this analysis that the dynamical Matryoshka model describes very well the experimental data and allow extracting the dynamical parameters of the studied system.

biophysics↗

bioRxiv2021

The aging lung mucosa: A proteomics study

The elderly population is at increased risk of acute and chronic respiratory infections and other pulmonary diseases, and it is estimated that this population will double in the next 30 years. Biochemical changes in the lung alveolar mucosa and lung cells alter local immune response as we age, creating opportunities for invading pathogens to establish successful infections. Indeed, the lungs of the elderly are a pro-inflammatory, pro-oxidative, dysregulated environment but this environment has remained understudied. We performed a comprehensive, quantitative proteomic profile of the lung mucosa in the elderly, developing insight into the molecular fingerprints, pathways, and regulatory networks that characterize the lung in old age. We identified neutrophils in the lungs of elderly individuals as possible contributors to dysregulated lung tissue environment. This study establishes a baseline for future investigations to develop strategies to mitigate susceptibility to respiratory infections in the elderly.

systems biology↗

bioRxiv2021

Increased temporal discounting and reduced model-based control in problem gambling are not substantially modulated by exposure to virtual gambling environments.

High-performance virtual reality (VR) technology has opened new possibilities for the examination of the reactivity towards addiction-related cues (cue-reactivity) in addiction. In this preregistered study (https://osf.io/4mrta), we investigated the subjective, physiological, and behavioral effects of gambling-related VR environment exposure in participants reporting frequent or pathological gambling (n=31) as well as non-gambling controls (n=29). On two separate days, participants explored two rich and navigable VR-environments (neutral: cafe vs. gambling-related: casino/sports-betting facility), while electrodermal activity and heart rate were continuously measured using remote sensors. Within VR, participants performed a temporal discounting task and a sequential decision-making task designed to assess model-based and model-free contributions to behavior. Replicating previous findings, we found strong evidence for increased temporal discounting and reduced model-based control in participants reporting frequent or pathological gambling. Although VR gambling environment exposure increased subjective craving, there was if anything inconclusive evidence for further behavioral or physiological effects. Instead, VR exposure substantially increased physiological arousal (electrodermal activity), across groups and conditions. VR is a promising tool for the investigation of context effects in addiction, but some caution is warranted since effects of real gambling environments might not generally replicate in VR. Future studies should delineate how factors such as cognitive load and ecological validity could be balanced to create a more naturalistic VR experience.

neuroscience↗

bioRxiv2021

Incidental reinstatement of faces and scenes in medial temporal lobe subregions during word recognition

During associative retrieval, the brain reinstates neural representations that were present during encoding. The human medial temporal lobe (MTL) with its subregions hippocampus (HC), perirhinal cortex (PRC), and parahippocampal cortex (PHC) plays a central role in neural reinstatement. Previous studies have given compelling evidence for reinstatement in the MTL during explicitly instructed associative retrieval. High-confident recognition may be similarly accompanied by recollection of associated information from the encoding context. It is unclear, however, whether high-confident recognition memory elicits reinstatement in the MTL even in the absence of an explicit instruction to retrieve associated information. Here, we addressed this open question using high-resolution fMRI. Twenty-eight male and female human volunteers engaged in a recognition memory task for words that they had previously encoded together with faces and scenes. Using complementary uni- and multivariate approaches, we show that MTL subregions including the PRC, PHC, and HC differentially reinstate category-specific representations during high-confident word recognition, even though no explicit instruction to retrieve the associated category was given. This constitutes novel evidence that high-confident recognition memory is accompanied by incidental reinstatement of associated category information in MTL subregions, and supports a functional model of the MTL that emphasises content-sensitive representations during both encoding and retrieval.

neuroscience↗

bioRxiv2021

Host- and age-dependent transcriptional changes in Mycobacterium tuberculosis cell envelope biosynthesis genes after exposure to human alveolar lining fluid

Tuberculosis (TB) infection, caused by the airborne pathogen Mycobacterium tuberculosis (M.tb), resulted in almost 1.4 million deaths in 2019 and the number of deaths is predicted to increase by 20% over the next 5 years due to the COVID-19 pandemic. Upon reaching the alveolar space, M.tb comes in close contact with the lung mucosa before and after its encounter with host alveolar compartment cells. Our previous studies show that homeostatic innate soluble components of the alveolar lining fluid (ALF) can quickly alter the cell envelope surface of M.tb upon contact, defining subsequent M.tb-host cell interactions and infection outcomes in vitro and in vivo. We also demonstrated that ALF from 60+ year old elders (E-ALF) vs. healthy 18- to 45-year-old adults (A-ALF) is dysfunctional with loss of homeostatic capacity and impaired innate soluble responses linked to high local oxidative stress. In this study, a targeted transcriptional assay demonstrates that M.tb exposure to human ALF alters the expression of its cell envelope genes. Specifically, our results indicate that A-ALF-exposed M.tb upregulates cell envelope genes associated with lipid, carbohydrate, and amino acid metabolism, as well as genes associated with redox homeostasis and transcriptional regulators. Conversely, M.tb exposure to E-ALF shows lesser transcriptional response, with most of the M.tb genes unchanged or downregulated. Overall, this study indicates that M.tb responds and adapts to the lung alveolar environment upon contact, and that the host ALF status determined by factors such as age might play an important role in determining infection outcome.

molecular biology↗