Biology subjects

Esposito, F.

Publications and source records attributed to Esposito, F..

At least 19 recordsLinked to original sources

bioRxiv2026

Single-vector AAV delivery of En-ISPmu1 and donor DNA for in vivo targeted genome integration

TnpBs are compact RNA-guided nucleases ideally suited for in vivo delivery. By screening novel TnpBs identified from large metagenomic datasets, ISPmu1 was discovered and its protein and {omega}RNA were engineered to generate En-ISPmu1, which achieved editing efficiencies exceeding 65% across 12 human loci. Owing to its compact size, En-ISPmu1 was delivered together with a donor DNA in a single AAV vector, yielding up to 12.7% targeted integration in mouse liver. These findings establish En-ISPmu1 as a promising versatile platform for in vivo therapeutic genome editing applications.

bioengineering↗

bioRxiv2026

Learned Audiovisual Predictability Modulates Depth-Resolved Hippocampal-Cortical Functional Coupling

Perception reflects the dynamic integration of prior expectations, uncertainty, and incoming sensory evidence, but the neural circuitry supporting these computations remains debated. Current theories implicate coordinated interactions between the hippocampus and neocortex, potentially at the level of hippocampal subfields and cortical layers. Evidence in humans has come primarily from the visual domain, while less is known about how these interactions support learned auditory predictions. Using submillimetre 7T fMRI, we investigated depth-resolved functional coupling between hippocampal subfields and temporal and frontal cortical regions during audiovisual associative prediction. Participants learned deterministic associations between visual cues and auditory syllables, allowing us to compare auditory processing in predictable and unpredictable contexts. Predictability-related connectivity changes showed a spatially structured pattern involving DG/CA3-pSTG and CA1-inferior frontal regions, with significant edge-wise effects resolved across cortical depths. These findings provide fine-grained evidence that learned auditory predictability modulates hippocampal-cortical functional interactions across temporo-frontal systems.

neuroscience↗

bioRxiv2026

A comparison of continuous-wave fNIRS with quantitative fMRI-derived indices of brain function in the visual cortex

Functional near-infrared spectroscopy (fNIRS) and functional magnetic resonance imaging (fMRI) both rely on the phenomenon of neurovascular coupling (NVC) to probe brain activity through their sensitivity to cerebral blood oxygenation. However, the relationship between fNIRS chromophores (oxy- and deoxyhaemoglobin, HbO and HbR), and fMRI (Blood Oxygen Level Dependent and Arterial Spin Labeling, BOLD and ASL) measurements, and whether this relationship remains consistent across subjects and physiological conditions, has only been partially characterised.. We acquired concurrent continuous-wave fNIRS and gradient-echo (GE) and spin-echo (SE) BOLD-ASL fMRI in healthy adults (n = 10) during visual stimulation. By applying calibrated fMRI methodology, we examined the relationships between fNIRS-derived haemoglobin modulations and fMRI-derived modulations in macrovascular (GE-) and microvascular (SE-) BOLD signals, cerebral blood flow (CBF), and oxygen metabolism (CMRO2). Group-level results showed strong temporal cross-modal agreement, with HbO and HbR tightly mirroring all fMRI signal time-courses (|r| > 0.8). A quantitative analysis of trial-by-trial modulations revealed distinct state-dependent behaviours: HbO maintained a stable relationship with the fMRI-derived metrics across conditions, whereas cross-modal relationships between HbR and fMRI-derived metrics substantially strengthened at higher flow-metabolism coupling (FMC), the ratio of CBF to CMRO2 change, an index of the strength of NVC. Both HbO and HbR were more strongly associated with GE-BOLD than with SE-BOLD. These findings provide a rigorous physiological grounding for fNIRS signal interpretation, demonstrating its utility as a surrogate marker for specific haemodynamic and metabolic parameters.

bioengineering↗

bioRxiv2025

Chemosensitive brainstem and diencephalic components in breath-hold fMRI

ObjectiveThe knowledge on breathing control and central chemoreception, key subcortical functions involved in several neuropathologies, is still mainly based on animal studies. In humans, functional MRI (fMRI) offers the needed spatio-temporal resolution and non-invasiveness, but the lack of specific tools and preprocessing solutions hinders its use in brainstem studies. We hereby propose an original fMRI analysis pipeline aimed at unravelling central chemoreception mechanisms, by integrating acquisition, spatial coregistration, noise removal and a novel data-driven analysis solution to compare network activation levels across tasks or conditions in fMRI. ApproachNovel analysis methodologies are integrated with the optimization of known preprocessing approaches to physiological noise correction and brainstem-focused coregistration. We couple independent components of fMRI data, separately estimated from healthy subjects during Free Breathing (FB) and Breath Hold (BH), by means of spatial correlation. We then identify statistically significant differences between BH and FB in CO2-dependent components by means of voxel-wise comparisons of components percent signal change. Components were localized using the Brainstem Navigator Atlas for enhancing network interpretability. Main ResultsUsing the pipeline we characterized CO2-related BOLD oscillations within the central control system of breathing. We corroborated the primary chemoreceptive role of medullary raphe in healthy subjects. We observed that BH over-activated ascending sensory-motor projections through the postero-lateral thalamus, descending projections through the putamen, and peripheral sensations entry points in the dorsal medulla. We highlighted the role of latero-dorsal tegmentum in the response to hypercapnia-induced aversive effects. SignificanceOur method allows to non-invasively locate primary chemoreception and related arousal triggers, characterizing alterations and therefore fostering the identification of therapeutic targets in abnormal breathing. Moreover, the proposed strategy addresses the issues of inter-task comparison among homologous independent sources, of their characterization and interpretation. Its extension could benefit all similarly challenging brainstem-focused studies, including those on Parkinsons and Alzheimers diseases.

bioengineering↗

bioRxiv2025

The molecular chaperone TRAP1 promotes translation of Luc7l3 mRNA to enhance ovarian cancer cell proliferation

Heat shock proteins have been increasingly identified in RNA-interactomes, suggesting potential roles beyond their canonical functions. Among those, the cancer-linked chaperone TRAP1 has been mainly characterized for its regulatory role on respiratory complex activity and protein synthesis, while its specific function as an RNA-binding protein (RBP) remains unclear. In this study, we confirmed the RNA-binding activity of TRAP1 in living cells using both protein- and RNA-centric approaches and demonstrated that multiple TRAP1 regions cooperate in such binding. Enhanced cross-linking and immunoprecipitation (eCLIP) in high-grade serous ovarian cancer cells revealed that TRAP1 primarily binds cytosolic protein-coding genes, with the majority coding for splicing-related factors. Notably, among TRAP1 most significantly bound transcripts, we identified the splicing factor LUC7L3, a U1 snRNP component involved in cell proliferation. We confirmed TRAP1 binding to Luc7l3 transcript by RIP-qPCR and showed that TRAP1 promotes Luc7l3 mRNA translation. Furthermore, we demonstrated that TRAP1 enhances ovarian cancer cell proliferation through LUC7L3 translational regulation. In summary, our findings provide the first comprehensive characterization of TRAP1 as an RBP and identify a critical target for ovarian cancer cell proliferation, offering new insights into its multifaceted roles in tumor biology.

cancer biology↗

bioRxiv2025

Bodily perception links memory and self: a case study of an amnesic patient

Episodic autobiographical memory (EAM) is a building block of self-consciousness, involving recollection and subjective re-experiencing of personal past experiences. Any life episode is originally encoded by a subject within a body. This raises the possibility that memory encoding is shaped by bodily self-consciousness (BSC), a basic form of self-consciousness arising from the multisensory and sensorimotor perceptual signals from the body. Recent studies in healthy subjects showed that embodied encoding improves EAM, with the involvement of the hippocampus. However, there are only few imaging studies to date, hippocampal data are not consistent, and the role of hippocampal damage is not understood. We investigated how different BSC states during encoding, modulate later EAM retrieval, in a patient with severe amnesia caused by rare bilateral hippocampal damage. We performed three separate behavioral experiments using immersive virtual reality. The patient showed consistently more difficulties recollecting information encoded in embodied vs. disembodied states, particularly when asked to recall her perspective experienced at encoding. These results contrasted with the usual beneficial effect of BSC on EAM, and significantly differed from controls. These data provide consistent evidence that BSC impacts encoding and later reliving, and shows that the hippocampus is not just a critical structure for EAM, but also for effects of embodiment on memory. Additional fMRI data extend these findings by revealing that hippocampal-parietal connectivity mediates BSC-EAM coupling. Our findings plead for an important role of BSC in EAM, mediated by the hippocampus and its connectivity, leading to embodied memories that are experienced as belonging to the self. HighlightsO_LIWe studied a patient with memory deficits caused by bilateral hippocampal atrophy C_LIO_LIMultisensory stimulation modulated embodiment during episode encoding C_LIO_LIAcross three studies the patient showed stronger memory deficits for embodied episodes C_LIO_LIMultisensory bodily perception impacts bodily self-consciousness and episodic memory C_LIO_LIOur findings link the bodily self to episodic memory and the hippocampus C_LI

neuroscience↗

bioRxiv2024

DNA damage response defects induced by the formation of TDP-43 and mutant FUS cytoplasmic inclusions and their pharmacological rescue.

Formation of cytoplasmic inclusions (CIs) of TDP-43 and FUS, along with DNA damage accumulation, is a hallmark of affected motor neurons in Amyotrophic Lateral Sclerosis (ALS). However, the impact of CIs on DNA damage response (DDR) and repair in this pathology remains unprobed. Here, we show that CIs of TDP-43 and FUSP525L, co-localizing with stress granules, lead to a dysfunctional DDR activation associated with physical DNA breakage. Inhibition of the activity of the DDR kinase ATM, but not of ATR, abolishes DDR signaling, indicating that DNA double-strand breaks (DSBs) are the primary source of DDR activation. In addition, cells with TDP-43 and FUSP525L CIs exhibit reduced DNA damage-induced RNA synthesis at DSBs. We previously showed that the two endoribonucleases DROSHA and DICER, also known to interact with TDP-43 and FUS during small RNA processing, contribute to DDR signaling at DSBs. Treatment with enoxacin, which stimulates DDR and repair by boosting the enzymatic activity of DICER, restores a proficient DDR and reduces DNA damage accumulation in cultured cells with CIs and in vivo in a murine model of ALS. In Drosophila melanogaster, Dicer-2 overexpression rescues TDP-43-mediated retinal degeneration. In summary, our results indicate that the harmful effects caused by TDP-43 and FUS proteinopathies include genotoxic stress and that the pharmacological stimulation of the DNA damage signaling and repair counteracts it.

molecular biology↗

bioRxiv2024

DROSHA, DICER and Damage-Induced long ncRNA control BMI1-dependent transcriptional repression at DNA double-strand break

Genome integrity is safeguarded by the DNA damage response (DDR). Controlled transcriptional dampening of genes surrounding DNA double-strand breaks (DSBs) has been shown to facilitate DNA repair. This phenomenon, defined as DSB-induced silencing in cis (DISC), involves the DDR apical kinase ATM and the Polycomb Repressive Complex 1 (PRC1). Conversely, DSBs have also been reported to induce de novo transcription of damaged-induced long non-coding RNAs (dilncRNAs) in a MRE11-RAD50-NBS1 (MNR) complex-dependent manner. MRN also controls the recruitment to DSB of the ribonuclease DROSHA, which together with DICER, stimulates DDR signaling and DNA repair. Here, we reconcile these apparently contrasting observations by showing that dilncRNA, together with DROSHA and DICER, but not GW182-like proteins required for miRNA-mediated gene silencing, controls DISC. Indeed, similarly to ATM, MRN inhibition abolishes DISC while pharmacological enhancement of DICER ribonuclease activity by Enoxacin improves DISC. Importantly, Enoxacin administration restores DISC upon ATM inhibition, demonstrating that DICER promotes DISC independently from ATM. Differently, Enoxacin does not restore DISC upon MRN inhibition, suggesting that DICER acts downstream to dilncRNA biogenesis and DROSHA recruitment. Mechanistically, we show that DROSHA and DICER control the recruitment of the PRC1 component BMI1 at DSBs and the consequent H2A-K119 ubiquitination. Upon DSBs formation, BMI1 and DROSHA interact in an RNA-dependent manner. Indeed, BMI1 associates to dilncRNA and do so in a DROSHA- and DICER-dependent manner. Importantly, inhibition of dilncRNA function by antisense oligonucleotides or Cas13-mediated targeting is sufficient to reduce BMI1 recruitment and DISC at individual loci. We propose that dilncRNAs together with DROSHA and DICER control DISC at genomic DSB by supporting PRC1 recruitment and chromatin ubiquitination.

molecular biology↗

bioRxiv2024

Exploring the impacts of human breast milk functional lipidome on infant health and growth outcomes in early life using lipid bioinformatics

Human breast milk lipidome is complex, and how changes in the functional lipid metabolism converge systematically to alter infants health outcomes is poorly understood. We used human breast milk and infant-mother dyads as a test system to demonstrate how the application of improved lipid bioinformatics can be effective in discerning systematic changes in functional lipid metabolism providing novel discoveries of how lactational programming in early life can influence infant health and growth outcomes. The study consisted of 40 mother-infant dyads where breast milk, maternal diet, infant anthropometrics [fat mass index (FMI), length z score, BMI z score, fat-free mass index (FFMI)], and infant atopic disease outcome (ear infection, cold, wheezing, diarrhea, and eczema) were collected at one and four months postpartum. Integrated Lipid Bioinformatics analyses were conducted using XLSTAT, Metaboanalyst 5.0. R software, Lipid Search, Xcalibur, and Cytoscape software. The results showed breast milk lipidome ordinated into distinct clusters based on maternal BMI status, and differences in developmental and atopic disease outcomes following redundancy analysis. Specifically, lipids from obese mothers clustered with FMI and eczema, while lipids from non-obese mothers clustered with FFM and wheezing. Receiver operating analysis was effective in identifying potential lipid biomarkers that were significantly associated with infant FMI, FFMI, and eczema during early life. Sphingolipid and glycerophospholipid pathways were significantly associated with the altered breast milk lipidome impacting infant development and atopic disease outcome during the first year of life. The findings following the advanced lipid bioinformatics suggest that the breastmilk functional lipid metabolism appears to play a key role in lipid-mediated lactational programming influencing development and atopic disease outcome, and present opportunities for potential dietary intervention in early life.

bioinformatics↗

bioRxiv2023

Resolving the pharmacological redox-sensitivity of SARS-CoV-2 PLpro in drug repurposing screening enabled identification of the competitive GRL-0617 binding site inhibitor CPI-169

The SARS CoV-2 Papain-Like protease has multiple roles in the viral replication cycle, related to both its polypeptide cleavage function and its capacity to antagonize host immune response. Targeting PLpro function is recognized as a promising mechanism to modulate viral replication whilst supporting host immune responses. However, development of PLpro specific inhibitors remains challenging. Upcoming studies revealed the limitation of reported inhibitors by profiling them through a pipeline of enzymatic, binding and cellular activity assays showing unspecific activity. GRL-0617 remained the only validated molecule with demonstrated anti-viral activity in cells. In this study we refer to the pitfalls of redox-sensitivity of PLpro. Using a screening-based approach to identify inhibitors of PLpro proteolytic activity, we made extensive efforts to validate the active compounds over a range of conditions and readouts, emphasising the need for comprehensive orthogonal data when profiling putative PLpro inhibitors. The remaining active compound CPI-169, showed to compete with GRL-0617 in NMR-based experiments, suggesting to share a similar binding mode, opening novel design opportunities for further developments as antiviral agents. Author summaryThe increasing knowledge about SARS-CoV-2 allowed the development of multiple strategies to contain the spread of COVID-19 infection. Nevertheless, effective antiviral pharmacological treatments are still rare and viral evolution allowed a fast adaptation and escape from available containment methods. The papain like protease (PLpro) has now become the next most promising SARS-CoV-2 therapeutic due to its multiple functions in virus replication cycle and antagonization of host immune response. However, due to inherent flexibility and sensitivity of this enzyme specific inhibitors are rare. Here we report on a screening strategy using repurposing of known drugs that takes into account PLpro characteristics to identify new inhibitors, showing the success of the approach by identifying CPI-169 that competitive targets the well described GRL-0617 inhibitor binding pocket of PLpro and helping to design further antiviral agents.

molecular biology↗

bioRxiv2023

Embodiment in episodic memory through premotor-hippocampal coupling

Episodic memory (EM) allows us to remember and relieve past events and experiences, depending on cortical-hippocampal reinstatement involved during encoding. Although it has been claimed that EM is fundamental to establish a sense of self across time, this has never been shown experimentally. Here we combine immersive virtual reality and fMRI and report stronger hippocampal reinstatement for scenes encoded under preserved sense of self, reflecting later recall performance. We further link the sense of self to EM showing that hippocampal reinstatement is coupled with reinstatement in premotor cortex, a key sense of self region. We extend these findings in a severe amnesic patient (caused by bilateral hippocampal damage), whose memory and re-experiencing lacked the normal dependency on the sense of self. Premotor-hippocampal coupling in EM describes how the self at encoding is neurally reinstated during the retrieval of past episodes, enabling a sense of self across time. TeaserPremotor-hippocampal coupling reveals how the self is reinstated when retrieving past episodes.

neuroscience↗

bioRxiv2023

Cytosolic and mitochondrial translation elongation are coordinated through the molecular chaperone TRAP1 for the synthesis and import of mitochondrial proteins

A complex interplay between mRNA translation and cellular respiration has been recently unveiled, but its regulation in humans is poorly characterized in either health or disease. Cancer cells radically reshape both biosynthetic and bioenergetic pathways to sustain their aberrant growth rates. In this regard, we have shown that the molecular chaperone TRAP1 not only regulates the activity of respiratory complexes, behaving alternatively as an oncogene or a tumor suppressor, but also plays a concomitant moonlighting function in mRNA translation regulation. Herein we identify the molecular mechanisms involved, demonstrating that TRAP1: i) binds both mitochondrial and cytosolic ribosomes as well as translation elongation factors, ii) slows down translation elongation rate, and iii) favors localized translation in the proximity of mitochondria. We also provide evidence that TRAP1 is coexpressed in human tissues with the mitochondrial translational machinery, which is responsible for the synthesis of respiratory complex proteins. Altogether, our results show an unprecedented level of complexity in the regulation of cancer cell metabolism, strongly suggesting the existence of a tight feedback loop between protein synthesis and energy metabolism, based on the demonstration that a single molecular chaperone plays a role in both mitochondrial and cytosolic translation, as well as in mitochondrial respiration.

biochemistry↗

bioRxiv2022

Nirmatrelvir treatment blunts the development of antiviral adaptive immune responses in SARS-CoV-2 infected mice

Alongside vaccines, antiviral drugs are becoming an integral part of our response to the SARS-CoV-2 pandemic. Nirmatrelvir - an orally available inhibitor of the 3-chymotrypsin-like cysteine protease - has been shown to reduce the risk of progression to severe COVID-19. However, the impact of nirmatrelvir treatment on the development of SARS-CoV-2-specific adaptive immune responses is unknown. Here, by using a mouse model of SARS-CoV-2 infection, we show that nirmatrelvir administration early after infection blunts the development of SARS-CoV-2-specific antibody and T cell responses. Accordingly, upon secondary challenge, nirmatrelvir-treated mice recruited significantly fewer memory T and B cells to the infected lungs and to mediastinal lymph nodes, respectively. Together, the data highlight a potential negative impact of nirmatrelvir treatment with important implications for clinical management and might help explain the virological and/or symptomatic relapse after treatment completion reported in some individuals.

immunology↗

bioRxiv2021

Thalamo-hippocampal pathway regulates incidental memory load: insights from sex differences

Incidental memory can be challenged by increasing either the retention delay or the memory load. The dorsal hippocampus (dHP) appears to help with both consolidation from short-term (STM) to long-term memory (LTM), and higher memory loads, but the mechanism is not fully understood. Here we find that female mice, despite having the same STM capacity of 6 objects and higher resistance to distraction in our different object recognition task (DOT), when tested over 1h or 24h delays appear to transfer to LTM only 4 objects, whereas male mice have an STM capacity of 6 objects in this task. In male mice the dHP shows greater activation (as measured by c-Fos expression), whereas female mice show greater activation of the ventral midline thalamus (VMT). Optogenetic inhibition of the VMT-dHP pathway during off-line memory consolidation enables 6-object LTM retention in females, while chemogenetic VMT-activation impairs it in males. Thus, removing or enhancing sub-cortical inhibitory control over the hippocampus, leads to differences in incidental memory. One Sentence SummaryThe sex-dependent recruitment of a subcortical pathway regulates how many items are spontaneously memorized in mice.

neuroscience↗

bioRxiv2020

Identification of inhibitors of SARS-CoV-2 3CL-Pro enzymatic activity using a small molecule in-vitro repurposing screen

Compound repurposing is an important strategy for the identification of effective treatment options against SARS-CoV-2 infection and COVID-19 disease. In this regard, SARS-CoV-2 main protease (3CL-Pro), also termed M-Pro, is an attractive drug target as it plays a central role in viral replication by processing the viral polyproteins pp1a and pp1ab at multiple distinct cleavage sites. We here report the results of a repurposing program involving 8.7 K compounds containing marketed drugs, clinical and preclinical candidates, and small molecules regarded as safe in humans. We confirmed previously reported inhibitors of 3CL-Pro, and have identified 62 additional compounds with IC50 values below 1 M and profiled their selectivity towards Chymotrypsin and 3CL-Pro from the MERS virus. A subset of 8 inhibitors showed anti-cytopathic effect in a Vero-E6 cell line and the compounds thioguanosine and MG-132 were analysed for their predicted binding characteristics to SARS-CoV-2 3CL-Pro. The X-ray crystal structure of the complex of myricetin and SARS-Cov-2 3CL-Pro was solved at a resolution of 1.77 [A], showing that myricetin is covalently bound to the catalytic Cys145 and therefore inhibiting its enzymatic activity. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=154 SRC="FIGDIR/small/422677v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@17ca2aeorg.highwire.dtl.DTLVardef@19c5159org.highwire.dtl.DTLVardef@1a0adf6org.highwire.dtl.DTLVardef@1fd05cd_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOAbstract Figure.C_FLOATNO Workflow for identification and profiling of inhibitors of SARS-CoV-2 3CL-Pro using a large scale repurposing and bioactive compound collection (rhs). Primary assay principle based on quenched FRET peptide substrate of SARS-CoV-2 3CL-Pro (lhs). Inhibiting compounds reduce fluorescence signal relative to DMSO controls. Hit profiling using X-ray. C_FIG

molecular biology↗

bioRxiv2020

Towards Semantic fMRI Neurofeedback: Navigating among Mental States using Real-time Representational Similarity Analysis

ObjectiveReal-time functional magnetic resonance imaging neurofeedback (rt-fMRI-NF) is a non-invasive MRI procedure allowing examined participants to learn to self-regulate brain activity by performing mental tasks. A novel two-step rt-fMRI-NF procedure is proposed whereby the feedback display is updated in real-time based on high level (semantic) representations of experimental stimuli via real-time representational similarity analysis of multi-voxel patterns of brain activity. ApproachIn a localizer session, the stimuli become associated with anchored points on a two-dimensional representational space where distances approximate between-pattern (dis)similarities. In the NF session, participants modulate their brain response, displayed as a movable point, to engage in a specific neural representation. The developed method pipeline is verified in a proof-of-concept rt-fMRI-NF study at 7 Tesla using imagery of concrete objects. The dependence on noise is more systematically assessed on artificial fMRI data with similar (simulated) spatio-temporal structure and variable (injected) signal and noise. A series of brain activity patterns from the ventral visual cortex is evaluated via on-line and off-line analyses and the performances of the method are reported under different noise conditions. Main resultsThe participant in the proof-of-concept study exhibited robust activation patterns in the localizer session and managed to control the neural representation of a stimulus towards the selected target, in the NF session. The offline analyses validated the rt-fMRI-NF results, showing that the rapid convergence to the target representation is noise-dependent. SignificanceOur proof-of-concept study demonstrates the potential of semantic NF designs where the participant navigates among different mental states. Compared to traditional NF designs (e.g. using a thermometer display to set the level of the neural signal), the proposed approach provides content-specific feedback to the participant and extra degrees of freedom to the experimenter enabling real-time control of the neural activity towards a target brain state without suggesting a specific mental strategy to the subject.

neuroscience↗

bioRxiv2020

Area per player in small-sided games to replicate the external load and estimated physiological match demands in elite soccer players

The current study determined the area-per-player during small- or large-sided games with or without goalkeeper that replicates the relative (m{middle dot}min-1) total distance, high-intensity running distance, sprint distance and metabolic power covered during official matches. Time-motion analysis was performed on twenty-five elite soccer-players during 26 home-matches. A total of 2565 individual samples for SSGs using different pitch sizes and different number of players were collected and classified as SSGs with (SSG-G) or without goalkeeper (SSG-P). A between-position comparison was also performed. The area-per-player needed to replicate the official match demands was largely greater in SSG-G vs SSG-P for total distance [187{+/-}53 vs 115{+/-}35 m2, effect size (ES): 1.60 95%CI 0.94/2.21], high-intensity running distance [262{+/-}72 vs 166{+/-}39 m2, ES: 1.66(0.99/2.27)] and metabolic power [177{+/-}42 vs 94{+/-}40, ES: 1.99(1.31/2.67)], but similar for sprint distance [(316{+/-}75 vs 295{+/-}99 m2, ES: 0.24(-0.32/0.79)] with direction of larger area-per-player for sprint distance > high-intensity running > total distance {cong} metabolic power for both SSG-G and SSG-P. In SSG-G, forwards required greater area-per-player than central-defenders [ES: 2.96(1.07/4.35)], wide-midfielders [ES: 2.45(0.64/3.78)] and wide-defenders [ES: 3.45(1.13/4.99)]. Central-midfielders required greater area-per-player than central-defenders [ES: 1.69(0.20/2.90)] and wide-midfielders [ES: 1.35(-0.13/2.57)]. In SSG-P, central defenders need smaller area-per-player (ES: -6.01/-0.92) to overall replicate the match demands compared to all other positions. The current results highlight that soccer players need a specific area-per-player during the small-side games with or without goalkeeper to replicate the overall match demands, especially to perform high-intensity running or sprint distance. Additionally, central defenders, central midfielders and forwards need to be trained with tailored area-per-player or specific rules/additional exercises.

physiology↗

bioRxiv2019

α-synuclein in the retina leads to degeneration of dopamine amacrine cells impairing vision

Introduction-synuclein aggregates have been identified in the retina of Parkinsons disease patients associated to vision impairment. In this study, we sought to determine the effects of -synuclein overexpression on the survival and function of dopaminergic (DA) amacrine cells in the retina.\n\nMethodsAdult mice were intravitreally injected with an adeno-associated viral (AAV) vector to overexpress human wild-type -synuclein in the inner retina. Following systemic injections of levodopa (L-DOPA), retinal responses and visual acuity driven behavior were measured by electroretinography (ERG) and water maze task, respectively. Amacrine cells and ganglion cells were counted at 1, 2 and 3 months post-injection.\n\nResults-synuclein led to an early loss of DA cells, which was associated with the decrease of light-adapted ERG responses and visual acuity. Systemic injections of L-DOPA rescued these retinal and visual abnormalities.\n\nConclusionsThe data show that -synuclein affects dopamine neurons in the retina. The approach provides a novel accessible mode of modeling the underlying mechanisms implicated in synucleinophaties pathogenesis and for testing novel treatments.

neuroscience↗