Biology subjects

Maggi, S.

Publications and source records attributed to Maggi, S..

10 recordsLinked to original sources

bioRxiv2026

Modeling human embryo adhesion using a microfluidic platform

Embryo adhesion represents the first step of implantation, yet understanding this process has been hindered by the lack of human in vitro platforms that replicate endometrial physiology. Here, we present a dual-channel microfluidic platform containing organoid-derived endometrial epithelium and primary stromal cells. Our model recapitulates important endometrial hallmarks including epithelial polarization, stromal decidualization, extracellular vesicle release, and hormone-induced receptivity. We tested its function by introducing mouse and human blastocysts and showed that embryos displayed features of initial adhesion. These included establishment of embryo-epithelial contacts initiated via the polar trophectoderm, inner cell mass repositioning, and lineage segregation. Moreover, human embryos secreted {beta}hCG indicating a functional trophoblast. Thus, this work provides a platform to study key features of embryo adhesion and endometrial receptivity, and disorders affecting embryo-endometrium interactions. TeaserEndometrium-on-a-chip shows detailed human embryo adhesion dynamics.

molecular biology↗

bioRxiv2025

Electron Cryo-Tomography Reveals the Caulobacter vibrioidesTight Adherence Pilus Architecture

The type IV filament superfamily is a widespread group of molecular machines involved in natural transformation, motility, adhesion, nutrient uptake, and secretion of a wide spectrum of protein substrates. The gram-negative bacterium Caulobacter vibrioides expresses the tight adherence (Tad) pilus, a type IV machine involved in surface colonization. Here we investigated the proteins involved in Tad pilus production by {Phi}CbK resistance screening and the order of machine assembly and its polar remnant by fluorescence tagging. Using electron cryo-tomography and subtomogram averaging of wild-type and mutant strains, we resolved the Tad pilus machine architecture and built an integrative model of its structure. The resulting model suggests the individual roles of multiple Tad proteins. Together the data also reveals the Tad pilus machines assembly order.

cell biology↗

bioRxiv2025

Integrative Structure and Function of the Vibrio cholerae Competence Pilus Machine

Type IV pili are hair-like, surface-exposed polymers involved in many fundamental biological processes. The competence pilus (CP) is responsible for natural transformation, the ability to acquire exogenous DNA. Here we purified the Vibrio cholerae CP and used electron cryo-microscopy (cryo-EM) to obtain a 3.3 [A] map of the fiber by helical reconstruction. We then used electron cryo-tomography (cryo-ET) to reveal the in-situ architecture of the competence pilus machine (CPM). Compared to other type IVa pilus machines, the CPM has unique characteristics including multiple conformational states, a ring-like density formed by PilQs C-terminal domain absent in the previously solved SPA structure, and the presence of a double ATPase ring in the cytoplasm. Using integrative modeling with the cryo-ET map as an envelope, we generated a full-length pseudoatomic model of the CPM. Molecular dynamics (MD) simulations of the entire CPM embedded within realistic bacterial membranes and the peptidoglycan cell wall revealed that the model demonstrates structural integrity under physiological conditions. Steered MD simulations of pilus extension and retraction through PilQ revealed gate-opening mechanisms and demonstrated the channels mechanical resistance and flexibility during translocation.

cell biology↗

bioRxiv2025

MotorBench: A Cryo-Electron Tomography Dataset of Bacterial Flagellar Motors for Testing Detection Algorithms

Understanding bacterial nanomachines like flagellar motors, which are crucial for pathogenic bacteria motility, is vital for microbiological and therapeutic research. Cryogenic electron tomography (cryo-ET) enables visualization of these structures within cells at near-native conditions. But manual identification remains challenging due to low contrast, limited resolution, and crowded in vivo environments. To address this, we introduce MotorBench, an expert-annotated dataset of bacterial flagellar motors that has been curated as part of a Kaggle competition BYU - Locating Bacterial Flagellar Motors 2025, engaging data scientists globally to create automated detection algorithms. MotorBench and its accompanying tools are intended to serve as a benchmark for evaluating and comparing future algorithms in automated cryo-ET analysis.

molecular biology↗

bioRxiv2023

Shotgun proteomic analysis of the caterpillar Lonomia obliqua (Lepitoptera, Saturniidae) hemolymph and effects in rat hippocampal neurons culture

Study of substances with potentially neuroprotective has been one of the research focus on drugs development. Toxic proteins of Lonomia obliqua caterpillars, which have caused several accidents in southern Brazil, were identified in the hemolymph with anti-apoptotic activity. This study aims the evaluation of the protein profile and the hemolymph effect on cell viability of rats primary cultured hippocampal neurons after apoptosis induction. Semi-quantitative shotgun proteomics approach was used to evaluate the protein profile of 3 caterpillars lots of different origin. Were identified a total of 76 proteins, 71 in hemolymph and 40 in fractions. Antiviral protein predominated in crude hemolymph, following by serine proteases, hemolins and protease inhibitors. In fractions were identified hemolins, serine proteases and protease inhibitors. The treatment of rats primary cultured hippocampal neurons with the chromatographic fraction at concentration of 0.05 and 0.10% (v/v) for 24 hours, with subsequently apoptosis induction was able to maintain cell viability significantly higher than positive control. Hemolymph protein composition can show qualitative and quantitative variations intra species when compared different origins animals and consequently exposed to various environmental factors. The results shown on this study may contribute to the identification of proteins with potential use as neuroprotective in degenerative conditions.

biochemistry↗

bioRxiv2023

Structure and Function of the Dot/Icm T4SS

The Legionella pneumophila Dot/Icm type IV secretion system (T4SS) delivers effector proteins into host cells during infection. Despite its significance as a potential drug target, our current understanding of its atomic structure is limited to isolated subcomplexes. In this study, we used subtomogram averaging and integrative modeling to construct a nearly-complete model of the Dot/Icm T4SS accounting for seventeen protein components. We locate and provide insights into the structure and function of six new components including DotI, DotJ, DotU, IcmF, IcmT, and IcmX. We find that the cytosolic N-terminal domain of IcmF, a key protein forming a central hollow cylinder, interacts with DotU, providing insight into previously uncharacterized density. Furthermore, our model, in combination with analyses of compositional heterogeneity, explains how the cytoplasmic ATPase DotO is connected to the periplasmic complex via interactions with membrane-bound DotI/DotJ proteins. Coupled with in situ infection data, our model offers new insights into the T4SS-mediated secretion mechanism.

biochemistry↗

bioRxiv2022

Tracking subject's strategies in behavioural choice experiments at trial resolution

Investigating how, when, and what subjects learn during decision-making tasks requires tracking their choice strategies on a trial-by-trial basis. Here we present a simple but effective probabilistic approach to tracking choice strategies at trial resolution using Bayesian evidence accumulation. We show this approach identifies both successful learning and the exploratory strategies used in decision tasks performed by humans, non-human primates, rats, and synthetic agents. Both when subjects learn and when rules change the exploratory strategies of win-stay and lose-shift, often considered complementary, are consistently used independently. Indeed, we find the use of lose-shift is strong evidence that subjects have latently learnt the salient features of a new rewarded rule. Our approach can be extended to any discrete choice strategy, and its low computational cost is ideally suited for real-time analysis and closed-loop control.

neuroscience↗

bioRxiv2022

Dynamic structural adaptations enable the endobiotic predation of bdellovibrio bacteriovorus

Bdellovibrio bacteriovorus is an endobiotic microbial predator that offers promise as a living antibiotic for its ability to kill Gram-negative bacteria, including human pathogens. Even after six decades of study, fundamental details of its predation cycle remain mysterious. Here, we used cryo-electron tomography to comprehensively image the lifecycle of B. bacteriovorus at nanometer-scale resolution. In addition to providing the first high-resolution images of predation in a native (hydrated, unstained) state, we also discover several surprising features of the process, including novel macromolecular complexes involved in prey attachment/invasion and a flexible portal structure lining a hole in the prey peptidoglycan that tightly seals the prey outer membrane around the predator during entry. Unexpectedly, we find that B. bacteriovorus does not shed its flagellum during invasion, but rather resorbs it into its periplasm for degradation. Finally, following replication and division in the bdelloplast, we observe a transient and extensive ribosomal lattice on the condensed B. bacteriovorus nucleoid. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/496000v1_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@35da74org.highwire.dtl.DTLVardef@19923f1org.highwire.dtl.DTLVardef@106a616org.highwire.dtl.DTLVardef@181f2fb_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2019

Independent population coding of the present and the past in prefrontal cortex during learning

Medial prefrontal cortex (mPfC) activity represents information about the state of the world, including present behaviour, such as decisions, and the immediate past, such as short-term memory. Unknown is whether information about different states of the world are represented in the same mPfC neural population and, if so, how they are kept distinct. To address this, we analyse here mPfC population activity of rats learning rules in a Y-maze, with self-initiated choice trials to an arm-end followed by a self-paced return during the inter-trial interval (ITI). We find that trial and ITI population activity from the same population fall into different low-dimensional subspaces. These subspaces encode different states of the world: multiple features of the task can be decoded from both trial and ITI activity, but the decoding axes for the same feature are roughly orthogonal between the two task phases, and the decodings are predominantly of features of the present during the trial but features of the preceding trial during the ITI. These subspace distinctions are carried forward into sleep, where population activity is preferentially reactivated in post-training sleep, but differently for activity from the trial and ITI subspaces. Our results suggest that the problem of interference when representing different states of the world is solved in mPfC by population activity occupying different subspaces for the world states, which can be independently decoded by downstream targets and independently addressed by upstream inputs. Significance statementActivity in the medial prefrontal cortex plays a roles in representing the current and past states of the world. We show that during a maze task the activity of a single population in medial prefrontal cortex represents at least two different states of the world. These representations were sequential and sufficiently distinct that a downstream population could separately read out either state from that activity. Moreover, the activity representing different states is differently reactivated in sleep. Different world states can thus be represented in the same medial prefrontal cortex population, but in such a way that prevents potentially catastrophic interference between them.

neuroscience↗

bioRxiv2017

An ensemble code in medial prefrontal cortex links prior events to outcomes during learning

The prefrontal cortex is implicated in learning the rules of an environment through trial and error. But it is unclear how such learning is related to the prefrontal cor-texs role in short-term memory. Here we asked if the encoding of short-term memory in prefrontal cortex was used by rats learning decision rules in a Y-maze task. We found that a similar pattern of neural ensemble activity was selectively recalled after reinforcement for a correct decision. This reinforcement-selective recall only reliably occurred immediately before the abrupt behavioural transitions indicating successful learning of the current rule, and faded quickly thereafter. We could simultaneously decode multiple, retrospective task events from the ensemble activity, suggesting the recalled ensemble activity had multiplexed encoding of prior events. Our results suggest that successful trial-and-error learning is dependent on reinforcement tagging the relevant features of the environment to maintain in prefrontal cortex short-term memory.

neuroscience↗