Biology subjects

Almeida, J.

Publications and source records attributed to Almeida, J..

29 records · Page 2Linked to original sources

bioRxiv2023

The FIBRILLIN multigene family in tomato, their roles in plastoglobuli structure and metabolism

Plastoglobuli (PG) are plant lipoprotein compartments, present in plastid organelles. They are involved in the formation and/or storage of lipophilic metabolites. FIBRILLINs (FBN) are one of the main PG-associated proteins and are particularly abundant in carotenoid-enriched chromoplasts found in ripe fruits and flowers. To address the contribution of different FBNs to isoprenoid sequestration and PG function, a multiplex gene editing approach was undertaken. Analysis of single and high-order fbn mutants for the major PG-related FBNs in tomato, namely SlFBN1, SlFBN2a, SlFBN4, SlFBN7a, revealed functional redundancy. High order fbn mutants displayed phenotypes associated with abnormal isoprenoid accumulation, and aberrant PG formation and morphology. Lipidomic analysis highlighted broader changes in lipid metabolism. Paralog-specific roles were also observed and included the regulation of specific isoprenoids (e.g., plastochromanol) and control of plastidial esterification capability by SlFBN7a. Collectively, the results support both structural and regulatory roles of SlFBNs in PGs. Our findings expose fundamental aspects of metabolic compartmentalisation in plant cells and the importance of lipoprotein particles for their plastid metabolism/physiology. Significance statementIn the chromoplast of ripe tomato fruit and flower, plastoglobuli (PGs) are associated with several important biotechnological traits, due to their functional involvement in metabolism, developmental transitions, and environmental adaption. FIBRILLINS (FBN) are a multigene family of proteins that are collectively major components of the PG. Using a multiplex CRISPR-Cas9 approach single and high-order fbn mutants have been developed. Functional redundancy amongst the members of the FBN multigene family was evident, but also paralog specific functions/influence. Aberrant plastoglobuli formation and altered lipid metabolism are evident among fbn mutants. Characterisation of this resource has shed light on the functional role of FBN and their role in PG formation. This strategy offers new potential for the development of nutritional enhanced and climate resilient crops.

plant biology↗

bioRxiv2022

A Cdh3-Lam332 signaling axis in a leader cell subpopulation controls protrusion dynamics and tumor organoid collective migration

Carcinoma dissemination can occur when heterogeneous tumor and tumor stromal cells clusters migrate together via collective migration. Cells at the front lead and direct collective migration, yet how these leader cells form and interact with the microenvironment to direct migration are not fully appreciated. From live videos of primary mouse and human breast tumor organoids in a 3D microfluidic system that mimics the native breast tumor microenvironment, we developed 3D computational models which hypothesize that leader cells generate high protrusive forces and overcome extracellular matrix (ECM) resistance. Using single cell sequencing, we reveal leader cells are heterogeneous, and identify and isolate a unique Cadherin-3 (Cdh3) positive leader cell subpopulation that is necessary and sufficient to lead migration. Cdh3 controls leader cell protrusion dynamics through the local production of Laminin-332 which is required for integrin/focal adhesion function. Our findings highlight how a subset of leader cells interact with the microenvironment to direct collective migration. TeaserHigher protrusions of Cdh3+ leader cells polarize tumor organoids that then invade collagen via Lam332 adhesion feedback.

cancer biology↗

bioRxiv2022

Mechanically primed cells transfer memory to fibrous matrices for persistent invasion

In disease and development, cells sense and migrate across mechanically dissimilar environments. We investigated whether mechanical memory of past environments empowers cells to navigate new, three-dimensional environments. Here, we show that cells primed by stiff matrices apply higher forces, compared to soft-primed cells, to accumulate and align collagen fibers towards sustained invasion. This priming advantage persists in dense or stiffened collagen. Through an energy-minimization model, we elucidate how memory-laden cells overcome mechanosensing of softer or challenging environments via a cell-matrix transfer of memory. Consistent with model predictions, depletion of -catenin and YAP hamper coordinated forces and cellular memory required for collagen remodeling before invasion. We release tension in collagen fibers via laser ablation and disable fiber remodeling by lysyl-oxidase inhibition; both of which disrupt cell-to-matrix transfer of memory and reduce invasion. These results have implications for cancer, fibrosis, and aging, where potential matrix memory may generate prolonged cellular response. One-Sentence SummaryCell invasion across mechanically dissimilar environments is mediated by force-based storage and extraction of cell and matrix memory.

biophysics↗

bioRxiv2022

The way of the light: how visual information reaches the auditory cortex in congenitally deaf adults

Human and animal studies on cross-modal plasticity under congenital deafness suggest that early auditory cortex plays a significant role in the processing of visual information when congenitally deprived from its typical (auditory) input. However, the pathway by which early auditory cortex is fed with visual information is still understudied. Here we focused on addressing how visual information reaches the auditory cortex under congenital deafness. We put forth a mechanistic model that proposes that different corticocortical and subcortical connections play a central role in rerouting visual information to the early auditory cortex of congenitally deaf individuals. Specifically, we show, using Representational Connectivity Analysis (RCA) and Dynamic Causal Modeling (DCM), that connections from the right superior colliculus to the right inferior colliculus, as well as connections from right early visual cortical regions to the right early auditory cortex play a role in rerouting visual information to early auditory cortex in congenitally deaf individuals. These findings shed light on how visual information reaches the early auditory cortex of deaf individuals - specifically, they suggest that neuroplasticity reshapes subcortical connections in order to re-route visual information to the auditory stream.

neuroscience↗

bioRxiv2021

Disentangling hand and tool processing: distal effects of neuromodulation

The neural processing within a brain region that responds to more than one object category can be separated by looking at the horizontal modulations established by that region, which suggests that local representations can be affected by connections to distal areas, in a category-specific way. Here we first wanted to test whether by applying transcranial direct current stimulation (tDCS) to a region thatre sponds both to hands and tools (posterior middle temporal gyrus; pMTG), while participants performed either a hand- or tool-related training task, we would be able to specifically target the trained category, and thereby dissociate the overlapping neural processing. Second, we wanted to see if these effects were limited to the target area or extended to distal but functionally connected brain areas. After each combined tDCS and training session, participants therefore viewed images of tools, hands, and animals, in an fMRI scanner. Using multivoxel pattern analysis, we found that tDCS stimulation to pMTG indeed improved the classification accuracy between tools vs. animals, but only when combined with a tool training task (not a hand training task). However, surprisingly, tDCS stimulation to pMTG also improved the classification accuracy between hands vs. animals when combined with a tool training task (not a hand training task). Our findings suggest that overlapping but functionally-specific networks can be separated by using a category-specific training task together with tDCS - a strategy that can be applied more broadly to other cognitive domains using tDCS - and demonstrates the importance of horizontal modulations in objectcategory representations.

neuroscience↗

bioRxiv2021

Stable brain PET metabolic networks using a multiple sampling scheme

The human brains interregional communication is vital for its proper functioning. A promising direction for investigating how these regions communicate relies on the assumption that the brain is a complex network. In this context, images derived from positron emission tomography (PET) have been proposed as a potential source for understanding brain networks. However, such networks are often assembled via direct computation of inter-subject correlations, neglecting variabilities between subjects and jeopardizing the construction of group representative networks. Here, we used [18F]FDG-PET data from 1027 individuals at different syndromal stages (352 CU, 621 MCI and 234 AD) to develop a novel method for constructing stable (i.e. resilient to spurious data points) metabolic brain networks. Our multiple sampling (MS) scheme generates brain networks with higher stability when compared to the conventional approach. In addition, the proposed method is robust to imbalanced datasets and requires 50% fewer subjects to achieve stability than the conventional approach. Our method has the potential to considerably boost PET data reutilization and advance our understating of human brain network patterns in health and disease.

neuroscience↗

bioRxiv2021

High-level representations in human occipito-temporal cortex are indexed by distal connectivity

Human object recognition is dependent on occipito-temporal cortex, but a complete understanding of the complex functional architecture of this area must account for how it is connected to the wider brain. Converging functional magnetic resonance imaging evidence shows that univariate responses to different categories of information (e.g. faces, bodies, & non-human objects) are strongly related to, and potentially shaped by, functional and structural connectivity to the wider brain. However, to date, there have been no systematic attempts to determine how distal connectivity and complex local high-level responses in occipito-temporal cortex (i.e. multivoxel response patterns) are related. Here, we show that distal functional connectivity is related to, and can reliably index, high-level representations for several visual categories (i.e. tools, faces, & places) within occipito-temporal cortex; that is, voxels sets that are strongly connected to distal brain areas show higher pattern discriminability than less well-connected sets do. We further show that, in several cases, pattern discriminability is higher in sets of well-connected voxels than sets defined by local activation (e.g. strong amplitude responses to faces in fusiform face area). Together, these findings demonstrate the important relationship between the complex functional organization of occipito-temporal cortex and wider brain connectivity. Significance statementHuman object recognition relies strongly on occipito-temporal cortex (OTC), yet responses in this broad area are often considered in relative isolation to the rest of the brain. We employ a novel connectivity-guided voxel selection approach with functional MRI data to show higher sensitivity to information (i.e. higher multivoxel pattern discriminability) in voxel sets that share strong connectivity to distal brain areas, relative to: 1) voxel sets that are less-strongly connected; and in several cases 2) voxel sets that are defined by strong local response amplitude. These findings underscore the importance of distal contributions to local processing in OTC.

neuroscience↗

bioRxiv2019

Offline tDCS modulates prefrontal cortical-subcortical cerebellar fear pathways in delayed fear extinction

Transcranial direct current stimulation (tDCS) has been studied to enhance extinction-based treatments for anxiety disorders. However, the field shows conflicting results about the anxiolytic effect of tDCS and only a few studies have previously observed the extinction of consolidated memories. Off-line tDCS modulates subsequent fear response (fear recall and fear extinction) neural activity and connectivity, throughout changes in the fear pathway that is critically involved in the pathogenesis of anxiety disorders. Thirty-four women participated in a two-day fear conditioning procedure. On day 1, women were randomly assigned to the control group (n=18) or the tDCS group (n=16) and went through a fear acquisition procedure. On day 2, the tDCS group received 20min tDCS at 1mA [cathode - F4; anode - contralateral deltoid] immediately before extinction and while inside the MRI scanner. The control group completed the extinction procedure only. fMRI whole brain contrast analysis showed stimulation dependent activity patterns with the tDCS group showing decreased neural activity during the processing of the CS+ and increased activity during the processing of the CS, in prefrontal, postcentral and paracentral regions, during late extinction. PPI analysis showed tDCS impact on the connectivity between the left dorsolateral prefrontal cortex and three clusters along the cortical-amygdalo-hippocampal- cerebellar pathway, during the processing of the CS+ in late extinction (TFCE corrected at p <.05). The increased neuronal activity during the processing of safety cues and the stronger coupling during the processing of threat cues might well be the mechanisms by which tDCS contributes to stimuli discrimination. HighlightsO_LIThe anxiolytic effect of cathodal tDCS is controversial. C_LIO_LIWe show cathodal tDCS modulatory effect on delayed extinction of the fear response. C_LIO_LICathodal tDCS modulates the processing of safe and threatening cues. C_LIO_LICathodal tDCS modulates the activity and connectivity of the fear network. C_LI

neuroscience↗

bioRxiv2019

Mozambican genetic variation provides new insights into the Bantu expansion

The Bantu expansion, which started in West Central Africa around 5,000 BP, constitutes a major migratory movement involving the joint spread of peoples and languages across sub-Saharan Africa. Despite the rich linguistic and archaeological evidence available, the genetic relationships between different Bantu-speaking populations and the migratory routes they followed during various phases of the expansion remain poorly understood. Here, we analyze the genetic profiles of southwestern and southeastern Bantu-speaking peoples located at the edges of the Bantu expansion by generating genome-wide data for 200 individuals from 12 Mozambican and 3 Angolan populations using [~]1.9 million autosomal single nucleotide polymorphisms. Incorporating a wide range of available genetic data, our analyses confirm previous results favoring a \"late split\" between West and East Bantu speakers, following a joint passage through the rainforest. In addition, we find that Bantu speakers from eastern Africa display genetic substructure, with Mozambican populations forming a gradient of relatedness along a North-South cline stretching from the coastal border between Kenya and Tanzania to South Africa. This gradient is further associated with a southward increase in genetic homogeneity, and involved minimum admixture with resident populations. Together, our results provide the first genetic evidence in support of a rapid North-South dispersal of Bantu peoples along the Indian Ocean Coast, as inferred from the distribution and antiquity of Early Iron Age assemblages associated with the Kwale archaeological tradition.

genetics↗

bioRxiv2019

The effect of cathodal tDCS on fear extinction: a cross-measures study

Extinction-based procedures are often used to inhibit maladaptive fear responses. However, because extinction procedures show efficacy limitations, transcranial direct current stimulation (tDCS) has been suggested as a promising add-on enhancer. In this study, we tested the effect of cathodal tDCS over extinction, to unveil the processes at play that boost the effectiveness of extinction procedures and its translational potential to the treatment of anxiety disorders. We implemented a fear conditioning procedure whereby 41 healthy women (mean age = 20.51 {+/-} 5.0) were assigned to either cathodal tDCS (n=27) or sham tDCS (n=16). Fear responses were measured with self-reports, autonomic responses, and implicit avoidance tendencies. Cathodal tDCS shows no statistically significant effect in extinction, according to self-reports, and seems to even negatively affect fear conditioned skin conductance responses. However, implicit avoidance tendencies, assessed one-to-three months after the tDCS session and extinction, reveal a group difference in the avoidance tendencies towards the neutral stimuli (F (1, 41) = 12.04, p = .001,{eta} p2 = .227), with the active cathodal tDCS groups showing a positive bias but not the sham group. This suggests a decreased generalization effect in the tDCS group with a moderate effect size. That is, cathodal tDCS may have enhanced long-term distinctiveness between threatening cues and perceptively similar neutral cues through a disambiguation process of the value of the neutral stimuli - a therapeutic target in anxiety disorders. Future studies should confirm these results and extend the study of cathodal tDCS effect on short term avoidance tendencies.

neuroscience↗

bioRxiv2018

Transcranial direct current stimulation alters functional network structure in humans

Transcranial direct current stimulation (tDCS) is routinely used in basic and clinical research, but its efficacy has been challenged on a methodological and statistical basis recently. The arguments against tDCS derive from insufficient understanding of how this technique interacts with brain processes physiologically. Because of its potential as a central tool in neuroscience, it is important to clarify whether and how tDCS affects neuronal activity. Here, we investigate influences of offline tDCS on network architecture measured by functional magnetic resonance imaging. Our results reveal a tDCS-induced reorganisation of a functionally-defined network that is dependent on whether we are exciting or inhibiting a node within this network, confirming in a functioning brain, and in a bias free and independent fashion that tDCS influences neuronal activity. Moreover, our results suggest that network-specific connectivity has an important role in defining the effects of tDCS and the relationship between brain states and behaviour.

neuroscience↗