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7,228 results for “Modules”
Social immunity modulates competition between coinfecting pathogens
<p>Coinfections with multiple pathogens can result in complex within-host dynamics affecting virulence and transmission. Whilst multiple infections are intensively studied in solitary hosts, it is so far unresolved how social host interactions interfere with pathogen competition, and if this depends on coinfection diversity. We studied how the collective disease defenses of ants – their social immunity – influence pathogen competition in coinfections of same or different fungal pathogen species. Social immunity reduced virulence for all pathogen combinations, but interfered with spore production only in different-species coinfections. Here, it decreased overall pathogen sporulation success, whilst simultaneously increasing co-sporulation on individual cadavers and maintaining a higher pathogen diversity at the community-level. Mathematical modeling revealed that host sanitary care alone can modulate competitive outcomes between pathogens, giving advantage to fast-germinating, thus less grooming-sensitive ones. Host social interactions can hence modulate infection dynamics in coinfected group members, thereby altering pathogen communities at the host- and population-level.</p>
Figure 3 from: Nocheva H, Sabit Z, Bakalov D, Grigorov E (2021) Interactions between the cannabinoid and the serotonergic systems in modulation of pain perception. Pharmacia 68(1): 109-115. https://doi.org/10.3897/pharmacia.68.e49219
Figure 3 Bidirectional effects of (A) DPAT, (B) AEA, and (C) AEA+DPAT in intact animals and after 1h HS.
Figure 2 from: Nocheva H, Sabit Z, Bakalov D, Grigorov E (2021) Interactions between the cannabinoid and the serotonergic systems in modulation of pain perception. Pharmacia 68(1): 109-115. https://doi.org/10.3897/pharmacia.68.e49219
Figure 2 Effects of CB1-agonist (AEA) and 5НТ1А-agonists (DPAT) alone administration on nociceptive (PP) thresholds in (A) intact animals (int) and (B) animals subjected to 1 hour of heat stress (1h HS) without and after pretreatment with CB1- and 5НТ1А-antagonists (AM and NAN, respectively). PP-thresholds are represented as mean values ± S.E.M. in arbitrary units (AU). ***p < 0.001, **p < 0.01, *p < 0.05 vs. controls. A. +++p < 0.001, ++p < 0.01 vs. int+AEA+DPAT. int+NAN+DPAT were compared to int+DPAT – xxxp < 0.001, xxp < 0.01; int+AM+AEA were compared to int+AEA – $$$ p < 0.001. B. +++p < 0.001, ++p < 0.01 vs. 1h HS; xxxp < 0.001, xxp < 0.01 vs. 1h HS+AEA+DPAT. 1h HS+NAN+DPAT were compared to 1h HS+DPAT – $$$p < 0.001, $$p < 0.01; 1h HS+AM+AEA were compared to 1h HS+AEA – &&&p < 0.001.
Figure 1 from: Nocheva H, Sabit Z, Bakalov D, Grigorov E (2021) Interactions between the cannabinoid and the serotonergic systems in modulation of pain perception. Pharmacia 68(1): 109-115. https://doi.org/10.3897/pharmacia.68.e49219
Figure 1 Effects of CB1- and 5НТ1А-agonists (AEA+DPAT) administration on nociceptive (PP) thresholds in (A) intact animals (int) and (B) animals subjected to 1 hour of heat stress (1 h HS) without and after pretreatment with CB1- and 5НТ1А-antagonists (AM and NAN, respectively). PP-thresholds are represented as mean values ± S.E.M. in arbitrary units (AU). ***p < 0.001, **p < 0.01 vs. controls. A. +++p < 0.001, ++p < 0.01 vs. int+AEA+DPAT. B. +++p < 0.001 vs. 1 h HS; xxxp < 0.001, xxp < 0.01 vs. 1 h HS+AEA+DPAT.
Data from: Comparative transcriptome atlases reveal altered gene expression modules between two Cleomaceae C3 and C4 plant species
C4 photosynthesis outperforms the ancestral C3 state in a wide range of natural and agro-ecosystems by affording higher water-use and nitrogen-use efficiencies. It therefore represents a prime target for engineering novel, high-yielding crops by introducing the trait into C3 backgrounds. However, the genetic architecture of C4 photosynthesis remains largely unknown. To define the divergence in gene expression modules between C3 and C4 photosynthesis during leaf ontogeny, we generated comprehensive transcriptome atlases of two Cleomaceae species, Gynandropsis gynandra (C4) and Tarenaya hassleriana (C3), by RNA sequencing. Overall, the gene expression profiles appear remarkably similar between the C3 and C4 species. We found that known C4 genes were recruited to photosynthesis from different expression domains in C3, including typical housekeeping gene expression patterns in various tissues as well as individual heterotrophic tissues. Furthermore, we identified a structure-related module recruited from the C3 root. Comparison of gene expression patterns with anatomy during leaf ontogeny provided insight into genetic features of Kranz anatomy. Altered expression of developmental factors and cell cycle genes is associated with a higher degree of endoreduplication in enlarged C4 bundle sheath cells. A delay in mesophyll differentiation apparent both in the leaf anatomy and the transcriptome allows for extended vein formation in the C4 leaf.
Data from: HS1BP3 negatively regulates autophagy by modulation of phosphatidic acid levels
A fundamental question is how autophagosome formation is regulated. Here we show that the PX domain protein HS1BP3 is a negative regulator of autophagosome formation. HS1BP3 depletion increased the formation of LC3-positive autophagosomes and degradation of cargo both in human cell culture and in zebrafish. HS1BP3 is localized to ATG16L1- and ATG9-positive autophagosome precursors and we show that HS1BP3 binds phosphatidic acid (PA) through its PX domain. Furthermore, we find the total PA content of cells to be significantly upregulated in the absence of HS1BP3, as a result of increased activity of the PA-producing enzyme phospholipase D (PLD) and increased localization of PLD1 to ATG16L1-positive membranes. We propose that HS1BP3 regulates autophagy by modulating the PA content of the ATG16L1-positive autophagosome precursor membranes through PLD1 activity and localization. Our findings provide key insights into how autophagosome formation is regulated by a novel negative-feedback mechanism on membrane lipids.
Data from: Speed dependency in α-motoneuron activity and locomotor modules in human locomotion: indirect evidence for phylogenetically conserved spinal circuits
Coordinated locomotor muscle activity is generated by the spinal central pattern generators (CPGs). Vertebrate studies have demonstrated the following two characteristics of the speed control mechanisms of the spinal CPGs: (i) rostral segment activation is indispensable for achieving high-speed locomotion; and (ii) specific combinations between spinal interneuronal modules and motoneuron (MN) pools are sequentially activated with increasing speed. Here, to investigate whether similar control mechanisms exist in humans, we examined spinal neural activity during varied-speed locomotion by mapping the distribution of MN activity in the spinal cord and extracting locomotor modules, which generate basic MN activation patterns. The MN activation patterns and the locomotor modules were analysed from multi-muscle electromyographic recordings. The reconstructed MN activity patterns were divided into the following three patterns depending on the speed of locomotion: slow walking, fast walking and running. During these three activation patterns, the proportion of the activity in rostral segments to that in caudal segments increased as locomotion speed increased. Additionally, the different MN activation patterns were generated by distinct combinations of locomotor modules. These results are consistent with the speed control mechanisms observed in vertebrates, suggesting phylogenetically conserved spinal mechanisms of neural control of locomotion.
Data from: Complex spike synchrony dependent modulation of rat deep cerebellar nuclear activity
The rules determining cerebellar output are not fully understood, but must involve Purkinje cell activity (PCs), as PCs are the major input to deep cerebellar nuclear (DCN) cells (which form the majority of cerebellar output). Here, the influence of PC complex spikes (CSs) was investigated by simultaneously recording DCN activity with CSs from PC arrays in anesthetized rats. Crosscorrelograms were used to identify PCs that were presynaptic to recorded DCN cells (presynaptic PCs). Such PCs were located within rostrocaudal cortical strips and displayed synchronous CS activity. CS-associated modulation of DCN activity included a short-latency post-CS inhibition and long-latency excitations before and after the CS. The amplitudes of the post-CS responses correlated with the level of synchronization among presynaptic PCs. A temporal precision of {less than or equal to} 10 ms was generally required for CSs to be maximally effective. The results suggest that CS synchrony is a key control parameter of cerebellar output.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).
Data from: Modulation frequency as a cue for auditory speed perception
Unlike vision, the mechanisms underlying auditory motion perception are poorly understood. Here we describe an auditory motion illusion revealing a novel cue to auditory speed perception: the temporal frequency of amplitude modulation (AM-frequency), typical for rattling sounds. Naturally, corrugated objects sliding across each other generate rattling sounds whose AM-frequency tends to directly correlate with speed. We found that AM-frequency modulates auditory speed perception in a highly systematic fashion: moving sounds with higher AM-frequency are perceived as moving faster than sounds with lower AM-frequency. Even more interestingly, sounds with higher AM-frequency also induce stronger motion aftereffects. This reveals the existence of specialized neural mechanisms for auditory motion perception, which are sensitive to AM-frequency. Thus, in spatial hearing, the brain successfully capitalizes on the AM-frequency of rattling sounds to estimate the speed of moving objects. This tightly parallels previous findings in motion vision, where spatio-temporal frequency of moving displays systematically affects both speed perception and the magnitude of the motion aftereffects. Such an analogy with vision suggests that motion detection may rely on canonical computations, with similar neural mechanisms shared across the different modalities.
Data from: Head shape modulates diversification of a classic cichlid pharyngeal jaw innovation
Functional innovations are often invoked to explain the uneven distribution of ecological diversity. Innovations may provide access to new adaptive zones by expanding available ecological opportunities and may serve as catalysts of adaptive radiation. However, diversity is often unevenly distributed within clades that share a key innovation, highlighting the possibility that the impact of the innovation is mediated by other traits. Pharyngognathy is a widely recognized innovation of the pharyngeal jaws that enhances the ability to process hard and tough prey in several major radiations of fishes, including marine wrasses and freshwater cichlids. We explored diversification of lower pharyngeal jaw shape, a key feature of pharyngognathy, and the extent to which it is influenced by head shape in Neotropical cichlids. While pharyngeal jaw shape was unaffected by either head length or head depth, its disparity declined dramatically with increasing head width. Head width also predicted the rate of pharyngeal jaw evolution such that higher rates were associated with narrow heads. Wide heads are associated with exploiting prey that require intense processing by pharyngeal jaws that have expanded surfaces for the attachment of enlarged muscles. However, we show that a wide head constrains access to adaptive peaks associated with several trophic roles. A constraint on the independent evolution of pharyngeal jaw and head shape may explain the uneven distribution of ecological diversity within a clade that shares a major functional innovation.
Figure 1 from: Merkhan M, Mohammad J, Fathi Z, Younis Z, Mahmood S, Mohammed M (2021) Silent hyperlipidaemia modulated vascular endothelial markers. Pharmacia 68(2): 479-484. https://doi.org/10.3897/pharmacia.68.e67959
Figure 1 Lipid profile is higher in patient group compared to healthy individuals. LDL=low density lipoprotein, VLDL= very low-density lipoprotein. Data expressed as mean±SD, *p<0.001.
Figure 2 from: Merkhan M, Mohammad J, Fathi Z, Younis Z, Mahmood S, Mohammed M (2021) Silent hyperlipidaemia modulated vascular endothelial markers. Pharmacia 68(2): 479-484. https://doi.org/10.3897/pharmacia.68.e67959
Figure 2 Hyperlipidaemia associated with modulation of vascular endothelial markers. Comparison between result analysed from serum of healthy and patient group indicated that Hyperlipidaemia reduced arylesterase (AE) and nitric oxide (NO) together with increase peroxidae (PO), arginase (AG), metalloendopeptidase (MEP), myeloperoxidase (MPO), and peroxynitrite (PN). Data expressed as mean±SD, *p<0.001.
Data from: Surface color and predictability determine contextual modulation of V1 firing and gamma oscillations
The integration of direct bottom-up inputs with contextual information is a core feature of neocortical circuits. In area V1, neurons may reduce their firing rates when their receptive field input can be predicted by spatial context. Gamma-synchronized (30–80 Hz) firing may provide a complementary signal to rates, reflecting stronger synchronization between neuronal populations receiving mutually predictable inputs. We show that large uniform surfaces, which have high spatial predictability, strongly suppressed firing yet induced prominent gamma synchronization in macaque V1, particularly when they were colored. Yet, chromatic mismatches between center and surround, breaking predictability, strongly reduced gamma synchronization while increasing firing rates. Differences between responses to different colors, including strong gamma-responses to red, arose from stimulus adaptation to a full-screen background, suggesting prominent differences in adaptation between M- and L-cone signaling pathways. Thus, synchrony signaled whether RF inputs were predicted from spatial context, while firing rates increased when stimuli were unpredicted from context.
Data from: All-trans retinoic acid disrupts development in ex vivo cultured fetal rat testes. II: modulation of mono-(2-ethylhexyl) phthalate toxicity
Humans are universally exposed to low levels of phthalate esters (phthalates), which are used to plasticize polyvinyl chloride. Phthalates exert adverse effects on the development of seminiferous cords in the fetal testis through unknown toxicity pathways. To investigate the hypothesis that phthalates alter seminiferous cord development by disrupting retinoic acid signaling in the fetal testis, gestational day 15 fetal rat testes were exposed for 1-3 days to 10-6 M all-trans retinoic acid (ATRA) alone or in combination with 10-6 to 10-4 M mono-(2-ethylhexyl) phthalate (MEHP) in ex vivo culture. As previously reported, exogenous ATRA reduced seminiferous cord number. This effect was attenuated in a concentration-dependent fashion by MEHP co-exposure. ATRA and MEHP-exposed testes were depleted of DDX4-positive germ cells but not Sertoli cells. MEHP alone enhanced the expression of the retinoic acid receptor target Rbp1 and the ovary development-associated genes Wnt4 and Nr0b1, and suppressed expression of the Leydig cell marker, Star, and the germ cell markers, Ddx4 and Pou5f1. In co-exposures, MEHP predominantly enhanced the gene expression effects of ATRA, but the Wnt4 and Nr0b1 concentration-responses were non-linear. Similarly, ATRA increased the number of cells expressing the granulosa cell marker FOXL2 in testis cultures, but this induction was attenuated by addition of MEHP. These results indicate that MEHP can both enhance and inhibit actions of ATRA during fetal testis development and provide evidence that retinoic acid signaling is a target for phthalate toxicity in the fetal testis.
Data from: Inhibition of Smurf2 translation by miR-322/503 protects from ischemia reperfusion injury by modulating EZH2/Akt/GSK3β signaling
BACKGROUND: myocardial ischemia/reperfusion (I/R) is a common and lethal disease that threatens people's life worldwide. The underlying mechanisms are under intensive study and yet remain unclear. Here, we explored the function of miR-322/503 in myocardial I/R injury. METHODS: We used isolated rat perfused heart as an in vivo model and H9c2 cells subjected with the oxygen and glucose deprivation followed by reperfusion (OGD/R) as in vitro model to study myocardial I/R injury. TTC staining was used to measure the infarct size and TUNEL staining was used to examine apoptosis. qRT-PCR and western blot were used to determine expression levels of miR-322/503, Smurf2, EZH2, p-Akt, p-GSK3β. RESULTS: Overexpression of miR-322/503 decreased infarct size, inhibited cell apoptosis and promoted cell proliferation through up-regulation of p-Akt and p-GSK3β. Thus, the expression of miR-322/503 was reduced during I/R process. On the molecular level, miR-322/503 directly bound Smurf2 mRNA and suppressed its translation. Smurf2 ubiquitinated EZH2 and degraded EZH2 which could activate Akt/GSK3β signaling. CONCLUSIONS: Our study demonstrates that miR-322/503 plays a beneficial role in myocardial I/R injury. By inhibition of Smurf2 translation, miR-322/503 induces EZH2 expression and activates Akt/GSK3β pathway, thereby protecting cells from ischemia reperfusion injury.
Data from: Modulation of the cutaneous silent period in the upper-limb with whole-body instability
The silent period induced by cutaneous electrical stimulation of the digits has been shown to be task-dependent, at least in the grasping muscles of the hand. However, it is unknown if the cutaneous silent period is adaptable throughout muscles of the entire upper limb, in particular when the task requirements are substantially altered. The purpose of the present study was to examine the characteristics of the cutaneous silent period in several upper limb muscles when introducing increased whole-body instability. The cutaneous silent period was evoked in 10 healthy individuals with electrical stimulation of digit II of the right hand when the subjects were seated, standing, or standing on a wobble board while maintaining a background elbow extension contraction with the triceps brachii of ~5% of maximal voluntary contraction (MVC) strength. The first excitatory response (E1), first inhibitory response (CSP), and second excitatory response (E2) were quantified as the percent change from baseline and by their individual durations. The results showed that the level of CSP suppression was lessened (47.7 ± 7.7% to 33.8 ± 13.2% of baseline, p = 0.019) and the duration of the CSP inhibition decreased (p = 0.021) in the triceps brachii when comparing the seated and wobble board tasks. For the wobble board task the amount of cutaneous afferent inhibition of EMG activity in the triceps brachii decreased; which is proposed to be due to differential weighting of cutaneous feedback relative to the corticospinal drive, most likely due to presynaptic inhibition, to meet the demands of the unstable task.
Data from: Mating affects resource selection and modulates associational effects between neighbouring resources
Associational effects occur when the attack rate on a resource depends on neighbouring resources in the environment. These effects are predicted to result from mismatches experienced by the consumer organism in resource selection along hierarchical search levels. As resource selection depends on sensory information used during search behaviour, we expected that different physiological states of an insect might modulate the outcome of associational effects due to differences in resource selection. We used Drosophila melanogaster, as a model organism for olfactory-guided behaviour in insects, to study the effects of mating induced behavioural changes on associational effects between two alternative resources. We found that mating has no effect on the ability of D. melanogaster to locate resource patches, but rather affects the perception of the resources within the patch. Consequently, we only found associational effects in the experiments with unmated females and not in the experiments with mated females. Our results suggest that the lack of associational effects for mated females resulted from changes in the use of short-range olfactory cues, leading to random selection among the resources. In conclusion, our results suggest that the physiological state of an insect modulates associational effects by affecting resource selection rates within the patch.
Data from: Non-monotonic temporal-weighting indicates a dynamically modulated evidence-integration mechanism
Perceptual decisions are thought to be mediated by a mechanism of sequential sampling and integration of noisy evidence whose temporal weighting profile affects the decision quality. To examine temporal weighting, participants were presented with two brightness-fluctuating disks for 1, 2 or 3 seconds and were requested to choose the overall brighter disk at the end of each trial. By employing a signal-perturbation method, which deploys across trials a set of systematically controlled temporal dispersions of the same overall signal, we were able to quantify the participants' temporal weighting profile. Results indicate that, for intervals of 1 or 2 sec, participants exhibit a primacy-bias. However, for longer stimuli (3-sec) the temporal weighting profile is non-monotonic, with concurrent primacy and recency, which is inconsistent with the predictions of previously suggested computational models of perceptual decision-making (drift-diffusion and Ornstein-Uhlenbeck processes). We propose a novel, dynamic variant of the leaky-competing accumulator model as a potential account for this finding, and we discuss potential neural mechanisms.
Data from: Pre-basic molt, feather quality and modulation of the adrenocortical response to stress in two populations of Rufous-collared sparrows, Zonotrichia capensis
Molt is an energetically expensive process in which birds may allocate 25% or more of their body protein mass to the production of new feathers. Stressful events can interfere with feather growth via the adrenal hormone corticosterone, which is released in response to environmental stress. Corticosterone release, in turn, regulates gluconeogenesis which could directly inhibit protein synthesis and deposition during molt when feathers are growing, which potentially could reduce feather quality dramatically. Thus, many species suppress the adrenocortical stress response, and therefore maintain lower corticosterone levels during molt. In this study we assessed the relationship between plasma corticosterone levels and feather quality in rufous-collared sparrow inhabiting the valleys of the Atacama Desert – one of the most stable and aseasonal environments in the world, and in the semiarid and seasonal Fray Jorge National Park in the north of Chile. We tested two hypotheses; i) feather quality is positively related to the amount of corticosterone suppression during molt, relative to corticosterone levels during other life history stages; and, ii) feather quality is negatively related to the absolute levels of corticosterone. We found negative associations between corticosterone levels and feather quality. However, these effects were stronger in the Atacama Desert where birds showed minimal corticosterone suppression and overall low feather quality. Although we found better feather quality in Fray Jorge, corticosterone suppression in these birds was relatively low in comparison with other species inhabiting higher latitudes. It is possible that birds in a highly variable environment face a stronger trade-off between feather quality and the stress-response. Our results suggest that the strength of the trade-off between feather quality and corticosterone levels could be dependent on energetic demands, seasonality, and unpredictable events.
A new mechanism for a familiar mutation – bovine DGAT1 K232A modulates gene expression through multi-junction exon splice enhancement
<p>The <i>DGAT1</i> gene encodes an enzyme responsible for catalysing the terminal reaction in mammary triglyceride synthesis, and underpins a well-known pleiotropic quantitative trait locus (QTL) with a large influence on milk composition phenotypes. Since first described over 15 years ago, a protein-coding variant K232A has been assumed as the causative variant underlying these effects, following <i>in-vitro</i> studies that demonstrated differing levels of triglyceride synthesis between the two protein isoforms. In the current study, we used a large RNAseq dataset to re-examine the underlying mechanisms of this large milk production QTL, and hereby report novel expression-based functions of the chr14 g.1802265AA>GC variant that encodes the <i>DGAT1 </i>K232A substitution. Using expression QTL (eQTL) mapping, we demonstrate a highly-significant mammary eQTL for <i>DGAT1, </i>where the K232A mutation appears as one of the top associated variants for this effect. By conducting <i>in vitro</i> expression and splicing experiments in bovine mammary cell culture, we further show modulation of splicing efficiency by this mutation, likely through disruption of an exon splice enhancer as a consequence of the allele encoding the 232A variant. Although the relative contributions of the enzymatic and transcription-based mechanisms now attributed to K232A remain unclear, these results suggest that transcriptional impacts contribute to the diversity of lactation effects observed at this locus.</p>
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Allen Brain Atlas
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Annotated Behaviour and Observability Dataset (ABODe)
ABODe is a University of Edinburgh DataShare dataset for behavior classification in group-housed mice using home-cage video, identities, bounding boxes, ground-plate positions, and annotator labels.
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