Search bioRxiv⌕ Search

Biology subjects

Lambert, S.

Publications and source records attributed to Lambert, S..

25 records · Page 2Linked to original sources
bioRxiv2021

Influence of age on functional memory T cell diversity

Memory T cells exhibit considerable diversity that determines their ability to be protective and their durability. Here, we examined whether changes in T cell heterogeneity contribute to the age-associated failure of immune memory. By screening for age-dependent T cell surface markers, we have identified CD4 and CD8 memory T cell subsets that are unrelated to previously defined subsets of central and effector memory cells. Memory T cells expressing the ecto-5-nucleotidase CD73 constitute a functionally distinct subset of memory T cells that declines with age. They exhibit many features favorable for immune protection, including longevity and polyfunctionality. They have a low turnover, but are poised to display effector functions and to develop into cells resembling tissue-resident memory T cells (TRM). Upstream regulators of differential chromatin accessibility and transcriptomes include transcription factors that are characteristic for conferring these superior memory features as well as facilitating CD73 expression. CD73 is not just a surrogate marker of these regulatory networks but is directly involved in T cell survival and TRM differentiation Interventions preventing the decline of this T cell subset or increasing CD73 expression have the potential to improve immune memory in older adults.

immunology↗
bioRxiv2021

In situ community dynamics influences the temperature- and light- dependent succession of seasonal phytoplankton

Temperature and light play a crucial role in regulating phytoplankton blooms in the Ocean. To assess the importance of these two parameters experimentally, microcosms were conducted on seven picoplankton communities (<3 m) sampled in December, March, June and September 2015 and 2016 in the North Western Mediterranean Sea. Each community was exposed to 4 realistic seasonal conditions (December, March, June and September). Metabarcoding was used to investigate the eukaryotic diversity in the 56 microcosms experiments in parallel to high-frequency monitoring of environmental diversity in the sea. The three major lineages identified were the Stramenopiles, Alveolata and Archaeplastida. Overall, the five-day incubations were not sufficient to reshape the initial microbial communities completely. The microcosm outcome was strongly influenced by the dynamics of phytoplankton starting communities. In pre-bloom conditions, phytoplanktonic species were the most sensitive to temperature and light conditions. During a bloom, species belonging to diatoms or Chlorodendrophyceae usually did not respond to light and temperature in microcosms and continued to bloom independently of the applied seasonal condition. Together, these results suggest that light and temperature seasonal conditions play a crucial role in regulating phytoplankton dynamics in pre-bloom conditions and biotic interactions may be preponderant in bloom and post-bloom conditions.

ecology↗
bioRxiv2020

Measuring stimulus-evoked neurophysiological differentiation in distinct populations of neurons in mouse visual cortex

Despite significant progress in understanding neural coding, it remains unclear how the coordinated activity of large populations of neurons relates to what an observer actually perceives. Since neurophysiological differences must underlie differences among percepts, differentiation analysis--quantifying distinct patterns of neurophysiological activity--is an "inside out" approach that addresses this question. We used two-photon calcium imaging in mice to systematically survey stimulus-evoked neurophysiological differentiation in excitatory populations across 3 cortical layers (L2/3, L4, and L5) in each of 5 visual cortical areas (primary, lateral, anterolateral, posteromedial, and anteromedial) in response to naturalistic and phase-scrambled movie stimuli. We find that unscrambled stimuli evoke greater neurophysiological differentiation than scrambled stimuli specifically in L2/3 of the anterolateral and anteromedial areas, and that this effect is modulated by arousal state and locomotion. Contrariwise, decoding performance was far above chance and did not vary substantially across areas and layers. Differentiation also differed within the unscrambled stimulus set, suggesting that differentiation analysis may be used to probe the ethological relevance of individual stimuli.

neuroscience↗
bioRxiv2020

Immunization with Mycobacterium vaccae NCTC 11659 prevents the development of PTSD- like sleep and behavioral phenotypes after sleep disruption and acute stress in mice

Because regular sleep disruption can increase vulnerability to stress-related psychiatric disorders, there is a need to explore novel countermeasures to increase stress resilience after inadequate sleep. In this study, we explored the impact of 5 days of intermittent sleep disruption on vulnerability to acute social defeat stress in mice, and investigated the ability of the environmental, immunomodulatory bacterium Mycobacterium vaccae NCTC 11659 (MV) to promote stress resilience in that context. We found that mice receiving sleep disruption plus acute stress developed sleep and behavioral phenotypes that had some features of human posttraumatic stress disorder (PTSD) including reduced NREM delta power and increased NREM beta power in post-stress sleep EEG, persistent increases in sleep fragmentation and the REM:Sleep ratio, and behavioral changes. Importantly, immunization with heat-killed MV prevented the development of this phenotype. These results support further research into novel, microbial-based countermeasures to improve health and increase resilience to sleep disruption.

neuroscience↗
bioRxiv2019

Topoisomerase IIα Prevents, But Does Not Resolve, Ultrafine Anaphase Bridges By Two Mechanisms

Topoisomerase II (Topo II), a well-conserved double-stranded DNA (dsDNA)-specific decatenase, processes dsDNA catenanes resulting from DNA replication during mitosis. Topo II defects lead to an accumulation of ultrafine anaphase bridges (UFBs), a type of chromosome non-disjunction. Topo II has been reported to resolve DNA anaphase threads, possibly accounting for the increase in UFB frequency upon Topo II inhibition. We hypothesized that the excess UFBs might also result, at least in part, from an impairment of the prevention of UFB formation by Topo II. We found that Topo II inhibition promotes UFB formation without affecting UFB resolution during anaphase. Moreover, we showed that Topo II inhibition promotes the formation of two types of UFBs depending on cell-cycle phase. Topo II inhibition during S-phase compromises complete DNA replication, leading to the formation of UFB-containing unreplicated DNA, whereas Topo II inhibition during mitosis impedes DNA decatenation at metaphase-anaphase transition, leading to the formation of UFB-containing DNA catenanes. Thus, Topo II activity is essential to prevent UFB formation in a cell-cycle dependent manner, but dispensable for UFB resolution during anaphase.

cell biology↗
bioRxiv2017

The non-homologous end joining factor Ku orchestrates replication fork resection and fine-tunes Rad51-mediated fork restart

Replication requires Homologous Recombination (HR) to stabilize and restart terminally-arrested forks. HR-mediated fork processing requires single stranded DNA (ssDNA) gaps and not necessarily Double Strand Breaks. We used genetic and molecular assays to investigate fork-resection and restart at dysfunctional, unbroken forks in Schizosaccharomyces pombe. We found that fork-resection is a two-step process coordinated by the non-homologous end joining factor Ku. An initial resection mediated by MRN/Ctp1 removes Ku from terminally-arrested forks, generating ~ 110 bp sized gaps obligatory for subsequent Exo1-mediated long-range resection and replication restart. The lack of Ku results in slower fork restart, excessive resection, and impaired RPA recruitment. We propose that terminally-arrested forks undergo fork reversal, providing a single DNA end for Ku binding which primes RPA-coated ssDNA. We uncover an unprecedented role for Ku in orchestrating resection of unbroken forks and in fine-tuning HR-mediated replication restart.\n\nO_LIKu orchestrates a two-steps DNA end-resection of terminally-arrested and unbroken forks\nC_LIO_LIMRN/Ctp1 removes Ku from terminally-arrested forks to initiate fork-resection\nC_LIO_LIa ~110 bp sized ssDNA gap is sufficient and necessary to promote fork restart.\nC_LIO_LIThe lack of Ku decreases ssDNA RPA-coating, and slows down replication fork restart.\nC_LI

genetics↗