Biology subjects

Kramer, J.

Publications and source records attributed to Kramer, J..

28 records · Page 2Linked to original sources

bioRxiv2021

An intranasally administrated SARS-CoV-2 beta variant subunit booster vaccine prevents beta variant viral replication in rhesus macaques

Emerging of SARS-CoV-2 variants and waning of vaccine/infection-induced immunity poses threats to curbing the COVID-19 pandemic. An effective, safe, and convenient booster vaccine will be needed. We hypothesized that a variant-modified mucosal booster vaccine might induce local immunity to prevent SARS-CoV-2 infection at the port of entry. The beta-variant is hardest to cross-neutralize. Herein we assessed the protective efficacy of an intranasal booster composed of beta variant-spike protein S1 with IL-15 and TLR agonists in previously immunized macaques. The macaques were first vaccinated with Wuhan strain S1 with the same adjuvant. One year later, negligibly detectable SARS-CoV-2-specific antibody remained. Nevertheless, the booster induced vigorous humoral immunity including serum- and bronchoalveolar lavage (BAL)-IgG, secretory nasal- and BAL-IgA, and neutralizing antibody against the original strain and/or beta variant. Beta-variant S1-specifc CD4+ and CD8+ T cell responses were also elicited in PBMC and BAL. Following SARS-CoV-2 beta variant challenge, the vaccinated group demonstrated significant protection against viral replication in the upper and lower respiratory tracts, with almost full protection in the nasal cavity. The fact that one intranasal beta-variant booster administrated one year after the first vaccination provoked protective immunity against beta variant infections may inform future SARS-CoV-2 booster design and administration timing.

immunology↗

bioRxiv2021

Siderophores drive invasion dynamics in bacterial communities through their dual role as public good versus public bad

Microbial invasions can compromise ecosystem services and spur dysbiosis and disease in hosts. Nevertheless, the mechanisms determining invasion outcomes often remain unclear. Here, we examine the role of iron-scavenging siderophores in driving invasions of Pseudomonas aeruginosa into resident communities of environmental pseudomonads. Siderophores can be "public goods" by delivering iron to individuals possessing matching receptors; but they can also be "public bads" by withholding iron from competitors lacking these receptors. Accordingly, siderophores should either promote or impede invasion, depending on their dual effects on invader and resident growth. Using supernatant feeding and invasion assays, we show that invasion success indeed decreased when the invader was inhibited (public bad) rather than stimulated (public good) by the residents siderophores. Conversely, invasion success often increased when the invader could use its siderophore to inhibit the residents. Our findings identify siderophores as a major driver of invasion dynamics in bacterial communities.

ecology↗

bioRxiv2020

Local adaptation, geographical distance and phylogenetic relatedness: assessing the drivers of siderophore-mediated social interactions in natural bacterial communities

In heterogenous, spatially structured habitats, individuals within populations can become adapted to the prevailing conditions in their local environment. Such local adaptation has been reported for animals and plants, and for pathogens adapting to hosts. There is increasing interest in applying the concept of local adaptation to microbial populations, especially in the context of microbe-microbe interactions. Here, we tested whether cooperation and cheating on cooperation can spur patterns of local adaptation in soil and pond communities of Pseudomonas bacteria, collected across a geographical scale of 0.5 to 50 meters. We focused on the production of pyoverdines, a group of secreted iron-scavenging siderophores that often differ among pseudomonads in their chemical structure and the receptor required for their uptake. A combination of supernatant-feeding and competition assays between isolates from four distance categories revealed tremendous variation in the extent to which pyoverdine non- and low-producers can benefit from pyoverdines secreted by producers. However, this variation was not explained by geographical distance, but primarily depended on the phylogenetic relatedness between interacting isolates. A notable exception occurred in local pond communities, where the effect of phylogenetic relatedness was eroded in supernatant assays, probably due to the horizontal transfer of receptor genes. While the latter result could be a signature of local adaptation, our results overall indicate that common ancestry and not geographical distance is the main predictor of siderophore-mediated social interactions among pseudomonads.

evolutionary biology↗

bioRxiv2019

Systems analysis of blood transcriptomes in dementia patients reveals an innate immune response shared across disorders

The role of peripheral inflammation in dementia is an important but complex topic. We present here the largest cohort of peripheral blood gene expression data ever assembled from patients with dementia and matching controls. Importantly, this cohort includes individuals from a diverse set of dementia disorders, including Alzheimers Disease (AD), mild cognitive impairment (MCI), and multiple disorders within the frontotemporal dementia (FTD) spectrum. We found strong transcriptional evidence of an innate immune inflammatory response, mediated by monocytes and neutrophils, in AD, MCI, and two FTD subtypes, PSP and nfvPPA. This transcriptional inflammatory response is enriched for genetic risk for AD, in part because it is also enriched for microglial genes, which have previously been implicated in AD risk. Finally, we show that this transcriptional response is strongly enriched for binding of the transcription factors PU.1 and RELA, which have previously been linked to AD risk and progression.

bioinformatics↗

bioRxiv2019

State and trait characteristics of anterior insula time-varying functional connectivity

The human anterior insula (aINS) is a topographically organized brain region, in which ventral portions contribute to socio-emotional function through limbic and autonomic connections, whereas the dorsal aINS contributes to cognitive processes through frontal and parietal connections. Open questions remain, however, regarding how aINS connectivity varies over time. We implemented a novel approach combining seed-to-whole-brain sliding-window functional connectivity MRI and k-means clustering to assess time-varying functional connectivity of aINS subregions. We studied three independent large samples of healthy participants and longitudinal datasets to assess inter- and intra-subject stability, and related aINS time-varying functional connectivity profiles to dispositional empathy. We identified four robust aINS time-varying functional connectivity modes that displayed both "state" and "trait" characteristics: while modes featuring connectivity to sensory regions were modulated by eye closure, modes featuring connectivity to higher cognitive and emotional processing regions were stable over time and related to empathy measures.

neuroscience↗

bioRxiv2019

Salience network atrophy links neuron type-specific degeneration to loss of empathy in frontotemporal dementia

Each neurodegenerative syndrome reflects a stereotyped pattern of cellular, regional, and large-scale brain network degeneration. In behavioral variant frontotemporal dementia (bvFTD), a disorder of social-emotional function, von Economo neurons (VENs) and fork cells are among the initial neuronal targets. These large layer 5 projection neurons are concentrated in the anterior cingulate and frontoinsular (FI) cortices, regions that anchor the salience network, a large-scale system linked to social-emotional function. Here, we studied patients with bvFTD, amyotrophic lateral sclerosis (ALS), or both, given that these syndromes share common pathobiological and genetic factors. Our goal was to determine how neuron type-specific TAR DNA-binding protein of 43 kDa (TDP-43) pathobiology relates to atrophy in specific brain structures and to loss of emotional empathy, a cardinal feature of bvFTD. We combined questionnaire-based empathy assessments, in vivo structural MR imaging, and quantitative histopathological data from 16 patients across the bvFTD/ALS spectrum. We show that TDP-43 pathobiology within right FI VENs and fork cells is associated with salience network atrophy spanning insular, medial frontal, and thalamic regions. Gray matter degeneration within these structures mediated loss of emotional empathy, suggesting a chain of influence linking the cellular, regional/network, and behavioral levels in producing signature bvFTD clinical features.

neuroscience↗

bioRxiv2018

Pervasive positive linkage between bacterial social traits suggests the predominance of competitive interactions in natural Pseudomonas communities

Bacteria frequently cooperate by sharing secreted metabolites such as enzymes and siderophores. The expression of different public good traits can be interdependent, and studies on laboratory systems have shown that such trait linkage affects eco-evolutionary dynamics within bacterial communities. Here, we examine whether linkage among social traits occurs in natural Pseudomonas communities by examining investment levels and correlations between five public goods: biosurfactants, biofilm components, proteases, pyoverdines, and toxic compounds. Our phenotypic assays involving 315 isolates from soil and freshwater communities revealed that their social trait expression profiles varied dramatically, and that correlations between traits were frequent, exclusively positive, and sometimes habitat-specific. Our results indicate that Pseudomonas communities are dominated by isolates lying on a continuum between a social type producing multiple public goods, and an asocial type showing low investment into social traits. This segregation into different social types could reflect local adaptation to different microhabitats, or emerge from competition between different (social) strategies. Moreover, our results show that isolates with specialized trait repertoires are rare, suggesting limited scope for the mutual exchange of different public goods between isolates. Overall, our work indicates that complex interdependencies among social traits influence the evolution of microbial lifestyles in nature.

microbiology↗

bioRxiv2018

Systematic functional characterization of the intellectual disability-associated SWI/SNF complex reveals distinct roles for the BAP and PBAP complexes in post-mitotic memory forming neurons of the Drosophila mushroom body

Technology has led to rapid progress in the identification of genes involved in neurodevelopmental disorders like intellectual disability (ID), but our functional understanding of the causative genes is lagging. Here, we show that the SWI/SNF chromatin remodeling complex is one of the most overrepresented cellular components disrupted in ID. We systematically investigated the role of individual subunits of this large protein complex in post-mitotic memory forming neurons of the Drosophila mushroom body (MB). Using this approach, we have identified novel differential roles for the two prominent conformations of the Drosophila SWI/SNF complex, known as BAP and PBAP. The PBAP conformation is required post-mitotically for remodeling of the MB {gamma} neurons during morphogenesis and is essential for both short and long-term memory. In contrast, the BAP conformation appears to preferentially effect long-term memory and is associated with {gamma} neuron survival. Our results suggest that different subunits of the SWI/SNF complex may influence learning and memory through diverse and distinct roles in regulating structural plasticity, survival, and functionality of post-mitotic neurons. This study provides novel insight into the neuronal function of individual SWI/SNF subunits and will serve as a basis for understanding SWI/SNF-mediated gene regulatory mechanisms in post-mitotic neurons.

neuroscience↗

bioRxiv2018

Environmental determinants of pyoverdine production, exploitation and competition in natural Pseudomonas communities

Many bacteria rely on the secretion of siderophores to scavenge iron from the environment. Laboratory studies revealed that abiotic and biotic factors together determine how much siderophores bacteria make, and whether siderophores can be exploited by non-producing cheaters or be deployed by producers to inhibit competitors. Here, we explore whether these insights apply to natural communities, by comparing the production of the siderophore pyoverdine among 930 Pseudomonas strains from 48 soil and pond communities. We found that pH, iron content, carbon concentration, and community diversity determine pyoverdine production levels, and the extent to which strains are either stimulated or inhibited by heterologous (non-self) pyoverdines. While pyoverdine non-producers occurred in both habitats, their prevalence was higher in soils. Environmental and genetic analysis suggest that non-producers can evolve as cheaters, exploiting heterologous pyoverdine, but also due to pyoverdine disuse in environments with increased iron availability. Overall, we found that environmental factors explained between-strain variation in pyoverdine production much better in soils than in ponds, presumably because high strain mixing in ponds prevents local adaption. Our study sheds light on the complexity of natural bacterial communities, and provides first insights into the multivariate nature of siderophore-based iron acquisition and competition among environmental pseudomonads.

microbiology↗

bioRxiv2017

The evolution of social life in family groups

Family life forms an integral part of the life-history of species across the animal kingdom, and plays a crucial role in the evolution of animal sociality. Our current understanding of family life, however, is almost exclusively based on studies that (i) focus on parental care and associated family interactions (such as those arising from sibling rivalry and parent-offspring conflict), and (ii) investigate these phenomena in the advanced family systems of mammals, birds, and eusocial insects. Here, we argue that these historical biases have fostered the neglect of key processes shaping social life in ancestral family systems, and thus profoundly hamper our understanding of the (early) evolution of family life. Based on a comprehensive survey of the literature, we first illustrate that the strong focus on parental care in advanced social systems has deflected scrutiny of other important social processes such as sibling cooperation, parent-offspring competition and offspring assistance. We then show that accounting for these neglected processes - and their changing role in the course of evolution - could profoundly change our understanding of the evolutionary origin and subsequent consolidation of family life. Finally, we outline how this diachronic perspective on the evolution of family living could provide novel insights into general processes driving social evolution. Overall, we infer that the explicit consideration of thus far neglected facets of family life, together with their study across the whole diversity of family systems, are crucial to advance our understanding of the processes that shape the evolution of social life.

evolutionary biology↗