Biology subjects

Jordan, A.

Publications and source records attributed to Jordan, A..

31 records · Page 2Linked to original sources

bioRxiv2023

Imaging analysis of six human histone H1 variants reveals universal enrichment of H1.2, H1.3, and H1.5 at the nuclear periphery and nucleolar H1X presence

Histone H1 participates in chromatin condensation and regulates nuclear processes. Human somatic cells may contain up to seven histone H1 variants, although their functional heterogeneity is not fully understood. Here, we have profiled the differential nuclear distribution of the somatic H1 repertoire in human cells through imaging techniques including super-resolution microscopy. H1 variants exhibit characteristic distribution patterns in both interphase and mitosis. H1.2, H1.3, and H1.5 are universally enriched at the nuclear periphery in all cell lines analyzed and co-localize with compacted DNA. H1.0 shows a less pronounced peripheral localization, with apparent variability among different cell lines. On the other hand, H1.4 and H1X are distributed throughout the nucleus, being H1X universally enriched in high-GC regions and abundant in the nucleoli. Interestingly, H1.4 and H1.0 show a more peripheral distribution in cell lines lacking H1.3 and H1.5. The differential distribution patterns of H1 suggest specific functionalities in organizing lamina-associated domains or nucleolar activity, which is further supported by a distinct response of H1X or phosphorylated H1.4 to the inhibition of rDNA transcription. Moreover, H1 variants depletion affects chromatin structure in a variant-specific manner. Concretely, H1.2 knock-down, either alone or combined, triggers a global chromatin decompaction. Overall, imaging has allowed us to distinguish H1 variants distribution beyond the segregation in two groups denoted by previous ChIP-seq determinations. Our results support H1 variants heterogeneity and suggest that variant-specific functionality can be shared between different cell types.

cell biology↗

bioRxiv2022

A novel bacteriocin produced by Bifidobacterium longum subsp. infantis has dual antimicrobial and immunomodulatory activity

Bacteriocins are ribosomally-synthesized antimicrobial peptides produced by bacteria with either narrow or broad spectrum activity. Many genome mining studies have indicated that bacteriocin gene clusters are widespread within certain gut microbiota members. In early life, Bifidobacterium comprise the dominant microbiota genus in vaginally delivered and breast-fed infants, with high levels associated with improved health. However, in many cases the mechanisms underlying these beneficial effects are unknown, although a limited number of studies have suggested that bacteriocin production by Bifidobacterium may represent a key mechanism for preventing pathogen over-growth. Here, we used BAGEL4 and antiSMASH to identify putative bacteriocin sequences in the whole genome sequences of 33 Bifidobacterium strains isolated from infants participating in two clinical studies. We identified a novel non-lantibiotic bacteriocin from Bifidobacterium longum subsp. infantis LH_664, with 40% sequence homology to Lactococcin 972 from Lactococcus lactis subsp. lactis. The putative bacteriocin (Bifidococcin_664) was chemically synthesized and studied for antimicrobial and immune-modulatory activities. We determined it has discrete activity against Clostridium perfringens and it appears to have novel immune stimulatory activities, promoting macrophage phagocytosis and specific cytokine release. These data highlight strain-specific beneficial properties in the early life genus Bifidobacterium, and suggest avenues for development of novel and highly specific dual action antimicrobials, and possible probiotic strains, that are active against clinically important bacterial pathogens. Data summarySamples LH_9 to LH_666 were previously sequenced and deposited to ENA under accession numbers ERS2658025-ERS2658043. Samples LH_986 to LH_1052 are newly sequenced and deposited to NCBI under accession numbers SAMN24838598-SAMN24838611. Additionally, previously assembled publicly available sequences (n=7) were retrieved online from NCBI Genomes database. See Supplementary Table S1 for further details.

microbiology↗

bioRxiv2022

The rates of adult neurogenesis and oligodendrogenesis are linked to cell cycle regulation through p27-dependent gene repression of SOX2

Cell differentiation involves profound changes in global gene expression that often have to occur in coordination with cell cycle exit. Because cyclin-dependent kinase inhibitor p27 reportedly regulates proliferation of neural progenitor cells in the subependymal neurogenic niche of the adult mouse brain, but can also have effects on gene expression, we decided to molecularly analyze its role in adult neurogenesis and oligodendrogenesis. At the cell level, we show that p27 restricts residual cyclin-dependent kinase activity after mitogen withdrawal to antagonize cycling, but it is not essential for cell cycle exit. Contrasting gene expression with chromatin accessibility, we find that p27 is coincidentally necessary to globally repress many genes involved in the transit from multipotentiality to differentiation, including those coding for neural progenitor transcription factors SOX2, OLIG2, and ASCL1. Our data reveal both direct association of p27 with regulatory sequences in the three genes and an additional hierarchical relationship where p27 repression of the Sox2 gene leads to reduced levels of SOX2-downstream targets Olig2 and Ascl1. In vivo, p27 is also required for the regulation of the proper level of SOX2 necessary for neuroblasts and oligodendroglial progenitor cells to timely exit cell cycle in a lineage-dependent manner.

neuroscience↗

bioRxiv2021

Histone H1 regulates non-coding RNA turnover on chromatin in a m6A-dependent manner

Linker histones are highly abundant chromatin-associated proteins with well-established structural roles in chromatin and as general transcriptional repressors. In addition, it has been long proposed that histone H1 exerts context-specific effects on gene expression. Here, we have identified a new function of histone H1 in chromatin structure and transcription using a range of genomic approaches. We show that histone H1-depleted cells accumulate nascent non-coding RNAs on chromatin, suggesting that histone H1 prevents non-coding RNA transcription and regulates non-coding transcript turnover on chromatin. Accumulated non-coding transcripts have reduced levels of m6A modification and cause replication-transcription conflicts. Accordingly, altering the m6A RNA methylation pathway rescues the replicative phenotype of H1 loss. This work unveils unexpected regulatory roles of histone H1 on non-coding RNA turnover and m6A deposition, highlighting the intimate relationship between chromatin conformation, RNA metabolism and DNA replication to maintain genome performance.

molecular biology↗

bioRxiv2021

Profiling of histone H1 variants and changes on genome architecture and gene expression upon histone H1 depletion in breast cancer cells

Up to seven members of the histone H1 family may contribute to chromatin compaction and its regulation in human somatic cells. In breast cancer cells, knock-down of multiple H1 variants deregulates many genes, promotes the appearance of genome-wide accessibility sites and triggers an interferon response via activation of heterochromatic repeats. However, how these changes in the expression profile relate to the re-distribution of H1 variants as well as to genome conformational changes have not been yet studied. Here, we combined ChIP-seq of five endogenous H1 variants with Chromosome Conformation Capture analysis in wild-type and H1 knock-down T47D cells. The results indicate that H1 variants coexist in the genome in two large groups depending on the local DNA GC content and that their distribution is robust with respect to multiple H1 depletion. Despite the small changes in H1 variants distribution, knock-down of H1 translated into more isolated but de-compacted chromatin structures at the scale of Topologically Associating Domains or TADs. Such changes in TAD structure correlated with a coordinated gene expression response of their resident genes. This is the first report describing simultaneous profiling of five endogenous H1 variants within a cell line and giving functional evidence of genome topology alterations upon H1 depletion in human cancer cells.

genomics↗

bioRxiv2021

Dynamics on the web: spiders use physical rules to solve complex tasks in mate search and competition

A long-standing question in animal behaviour is how organisms solve complex tasks. Here we explore how the dynamics of animal behaviour in the ubiquitous tasks of mate-search and competition can arise from a physics-based model of effective interactions. Male orb-weaving spiders of the genus Trichonephila are faced with the daunting challenge of entering the web of a much larger and potentially cannibalistic female, approaching her, and fending off rival males. The interactions that govern the dynamics of males within the confined two-dimensional arena of the females web are dominated by seismic vibrations. This unifying modality allows us to describe the spiders as interacting active particles, responding only to effective forces of attraction and repulsion due to the female and rival males. Our model is based on a detailed analysis of experimental spider trajectories, obtained during the approach of males towards females, and amidst their interactions with rival males of different sizes. The dynamics of spider particles that emerges from our theory allows us to explain a puzzling relationship between the density of males on the web and the reproductive advantages of large males. Our results provide strong evidence that the simple physical rules at the basis of our model can give rise to complex fitness related behaviours in this system.

animal behavior and cognition↗

bioRxiv2020

Towards understanding the regulation of histone H1 somatic subtypes with OMICs.

BackgroundHistone H1 is involved in the regulation of chromatin higher-order structure and compaction. In humans, histone H1 is a multigene family with seven subtypes differentially expressed in somatic cells. Which are the regulatory mechanisms that determine the variability of the H1 complement is a long-standing biological question regarding histone H1. We have used a new approach based on the integration of OMICs data to address this question. ResultsWe have examined the 3D-chromatin structure, the binding of transcription factors (TFs), and the expression of somatic H1 genes in human cell lines, using data from public repositories, such as ENCODE. Analysis of Hi-C, ChIP-seq, and RNA-seq data, have shown that transcriptional control has a greater impact on H1 regulation than previously thought. Somatic H1 genes located in TADs show higher expression than in boundaries. H1 genes are targeted by a variable number of transcription factors including cell cycle-related TFs, and tissue-specific TFs, suggesting a finetuned, subtype-specific transcriptional control. We describe, for the first time, that all H1 somatic subtypes are under transcriptional co-regulation. The replication-independent subtypes, which are encoded in different chromosomes, isolated from other histone genes are also co-regulated with the rest of the somatic H1 genes, indicating that transcriptional co-regulation extends beyond the histone cluster. ConclusionsTranscriptional control and transcriptional co-regulation explain, at least in part, the variability of H1 complement, the fluctuations of H1 subtypes during development, and also the compensatory effects observed, in model systems, after perturbation of one or more H1 subtypes.

molecular biology↗

bioRxiv2019

Regulation of hippocampal memory by mTORC1 in somatostatin interneuron

Translational control of long-term synaptic plasticity via Mechanistic Target Of Rapamycin Complex 1 (mTORC1) is crucial for hippocampal learning and memory. The role of mTORC1 is well-characterized in excitatory principal cells but remains largely unaddressed in inhibitory interneurons. Here we used cell type-specific conditional knockout strategies to alter mTORC1 function selectively in somatostatin (SOM) inhibitory interneurons (SOM-INs). We found that up- and down-regulation of SOM-IN mTORC1 activity bi-directionally regulates contextual fear and spatial memory consolidation. Moreover, contextual fear learning induced a metabotropic glutamate receptor type 1 (mGluR1) mediated long-term potentiation (LTP) of excitatory input synapses onto hippocampal SOM-INs, that was dependent on mTORC1. Finally, the induction protocol for mTORC1-mediated late-LTP in SOM-INs regulated Schaffer collateral pathway LTP in pyramidal neurons. Thus, mTORC1 activity in somatostatin interneurons contributes to learning-induced persistent plasticity of their excitatory synaptic inputs and hippocampal memory consolidation, uncovering a role of mTORC1 in inhibitory circuits for memory.

neuroscience↗

bioRxiv2019

A low-cost, open-source framework for tracking and behavioural analysis of animals in aquatic ecosystems

Although methods for tracking animals underwater exist, they frequently involve costly infrastructure investment, or capture and manipulation of animals to affix or implant tags. These practical concerns limit the taxonomic coverage of aquatic movement ecology studies and implementation in areas where high infrastructure investment is impossible. Here we present a method based on deep-learning and structure-from-motion, with which we can accurately determine the 3D location of animals, the structure of the environment in which they are moving. Further behavioural decomposition of the body position and contour of animals subsequently allow quantifying the behavioural states of each interacting animal. This approach can be used with minimal infrastructure and without confining animals to to a fixed area, or capturing and interfering with them in any way. With this approach, we are able to track single individuals (Conger Eel, Conger oceanus), small heterospecific groups (Mullus surmuletus, Diplodus sp.), and schools of animals (Tanganyikan cichlids Lamprologus callipterus) in freshwater and marine systems, and in habitats ranging in environmental complexity. Positional information was highly accurate, with errors as low as 1.67% of body length. Tracking data was embedded in 3D environmental models that could be used to examine collective decision making, obstacle avoidance, and visual connectivity of groups. By analyzing body contour and position, we were also able to use unsupervised classification to quantify the kinematic behavioural states of each animal. The proposed framework allows us to understand animal behaviour in aquatic systems at an unprecedented resolution and a fraction of the cost of established methodologies, with minimal domain expertise at the data acquisition or analysis phase required. Implementing this method, research can be conducted in a wide range of field contexts to collect laboratory standard data, vastly expanding both the taxonomic and environmental coverage of quantitative animal movement analysis with a low-cost, open-source solution.

animal behavior and cognition↗

bioRxiv2018

Taking a deeper look: Quantifying the differences in fish assemblages between shallow and mesophotic temperate rocky reefs

The spatial distribution of a species assemblage is often determined by habitat and climate. In the marine environment, depth can become an important factor as degrading light leads to changes in the biological habitat structure. To date, much of the focus of ecological fish research has been based on reefs in less than 40 m with little research on the ecological role of mesophotic reefs. We deployed baited remote underwater stereo video systems (stereo-BRUVS) on temperate reefs in two depth categories: shallow (20-40m) and mesophotic (80-120m), off Port Stephens, Australia. Sites were selected using data collected by swath acoustic sounder to ensure stereo-BRUVS were deployed on reef. The sounder also provided rugosity, slope and relief data for each stereo-BRUVS deployment. Multivariate analysis indicates that there are significant differences in the fish assemblages between shallow and mesophotic reefs, primarily driven by Ophthalmolepis lineolatus and Notolabrus gymnogenis only occurring on shallow reefs and schooling species of fish that were unique to each depth category: Atypichthys strigatus on shallow reefs and Centroberyx affinis on mesophotic reefs. While shallow reefs had a greater species richness and abundance of fish when compared to mesophotic reefs, mesophotic reefs hosted the same species richness of fishery targeted species. Chrysophrys auratus (pink snapper) and Nemodactylus douglassii (grey morwong) are two highly targeted species in this region. While C. auratus was numerically more abundant on shallow reefs, mesophotic reefs provide habitat for larger fish. In comparison, N. douglassii were evenly distributed across all sites sampled. Generalized linear models revealed that depth and habitat type provided the most parsimonious model for predicting the distribution of C. auratus, while habitat type alone best predicted the distribution of N. douglassii. These results demonstrate the importance of mesophotic reefs to fishery targeted species and therefore have implications for informing the management of these fishery resources on shelf rocky reefs.

ecology↗

bioRxiv2018

Cleaner wrasse pass the mark test. What are the implications for consciousness and self-awareness testing in animals?

The ability to perceive and recognise a reflected mirror image as self (mirror self-recognition, MSR) is considered a hallmark of cognition across species. Although MSR has been reported in mammals and birds, it is not known to occur in any other major taxon. A factor potentially limiting the ability to test for MSR is that the established assay for MSR, the mark test, shows an interpretation bias towards animals with the dexterity (or limbs) required to touch a mark. Here, we show that the cleaner wrasse fish, Labroides dimidiatus, passes through all phases of the mark test: (i) social reactions towards the reflection, (ii) repeated idiosyncratic behaviours towards the mirror (contingency testing), and (iii) frequent observation of their reflection. When subsequently provided with a coloured tag, individuals attempt to remove the mark in the presence of a mirror but show no response towards transparent marks, or to coloured marks in the absence of a mirror. This remarkable finding presents a challenge to our interpretation of the mark test - do we accept that these behavioural responses in the mark test, which are taken as evidence of self-recognition in other species, mean that fish are self-aware? Or do we conclude that these behavioural patterns have a basis in a cognitive process other than self-recognition? If the former, what does this mean for our understanding of animal intelligence? If the latter, what does this mean for our application and interpretation of the mark test as a metric for animal cognitive abilities?

animal behavior and cognition↗

bioRxiv2018

Using Network Analysis to Localize the Epileptogenic Zone from Invasive EEG Recordings in Intractable Focal Epilepsy

Treatment of medically intractable focal epilepsy (MIFE) by surgical resection of the epileptogenic zone (EZ) is often effective provided the EZ can be reliably identified. Even with the use of invasive recordings, the clinical differentiation between the EZ and normal brain areas can be quite challenging, mainly in patients without MRI detectable lesions. Consequently, despite relatively large brain regions being removed, surgical success rates barely reach 60-65%. Such variable and unfavorable outcomes associated with high morbidity rates are often caused by imprecise and/or inaccurate EZ localization. We developed a localization algorithm that uses network-based data analytics to process invasive EEG recordings. This network algorithm analyzes the centrality signatures of every contact electrode within the recording network and characterizes contacts into susceptible EZ based on the centrality trends over time. The algorithm was tested in a retrospective study that included 42 patients from four epilepsy centers. Our algorithm had higher agreement with EZ regions identified by clinicians for patients with successful surgical outcomes and less agreement for patients with failed outcomes. These findings suggest that network analytics and a network systems perspective of epilepsy may be useful in assisting clinicians in more accurately localizing the EZ.\n\nAUTHOR SUMMARYEpilepsy is a disease that results in abnormal firing patterns in parts of the brain that comprise the epileptogenic network, known as the epileptogenic zone (EZ). Current methods to localize the EZ for surgical treatment often requires observations of hundreds of thousands of EEG data points measured from many electrodes implanted in a patients brain. In this paper, we used network science to show that EZ regions may exhibit specific network signatures before, during and after seizure events. Our algorithm computes the likelihood of each electrode being in the EZ and tends to agree more with clinicians during successful resections and less during failed surgeries. These results suggest that a networked analysis approach to EZ localization may be valuable in a clinical setting.

neuroscience↗

bioRxiv2017

Characterization and Validation of a Novel Group of Type V, Class 2 Nucleases for in vivo Genome Editing

CRISPR-based genome editing is an enabling technology with potential to dramatically transform multiple industries. Identification of additional editing tools will be imperative for broad adoption and application of this technology. A novel Type V, Class 2 CRISPR nuclease system was identified from Microgenomates and Smithella bacterial species (CRISPR from Microgenomates and Smithella, Cms1). This system was shown to efficiently generate indel mutations in the major crop plant rice (Oryza sativa). Cms1 are distinct from other Type V nucleases, are smaller than most other CRISPR nucleases, do not require a tracrRNA, and have an AT-rich protospacer-adjacent motif site requirement. A total of four novel Cms1 nucleases across multiple bacterial species were shown to be functional in a eukaryotic system. This is a major expansion of the Type V CRISPR effector protein toolbox and increases the diversity of options available to researchers.

molecular biology↗