Biology subjects

Frank, C.

Publications and source records attributed to Frank, C..

9 recordsLinked to original sources

bioRxiv2026

Unveiling the taxonomic diversity and unprecedented biosynthetic treasure of the phylum Myxococcota

Natural products remain vital sources of therapeutics, particularly anti-infectives, and members of the phylum Myxococcota constitute an especially rich reservoir for their discovery. Based on decades of microbiological efforts, we present 154 new Myxococcota genomes and propose a revised taxonomy expanding the number of described families from 11 to 28 and genera from 32 to 90. Comparison with an equivalent set from the prime source Actinomycetota shows that Myxococcota possess a comparable biosynthetic diversity, underscoring their promise for large-scale isolation and sequencing efforts. The vast untapped potential reflected in 2,387 uncharacterized gene cluster families is highlighted by genome mining efforts, yielding four validated compounds exhibiting novel chemistry, including myxolutamids and myxopentacins. We show that many Myxococcota-derived natural products, such as myxolutamid A and two new sorangicin derivatives, are conserved within taxonomic lineages. New described families thus bear high biosynthetic potential underpinning the importance of precise taxonomic classification guiding targeted drug discovery.

microbiology↗

bioRxiv2025

Forward Engineering Organ Development and Cancer Therapeutics with Optogenetics

Robust growth control is an essential requirement for the survival of living organisms, while its dysregulation results in diseases such as cancer. However, a significant knowledge gap exists in understanding how precise organ growth control is achieved. The growing arsenal of optogenetic toolkits allows precise, noninvasive control of cellular signaling in vivo, enabling research into how bioelectrical and chemical cues regulate organ growth. Here, we used the red-light-activated channelrhodopsin, CsChrimson, to stimulate intracellular calcium signaling dynamics in the wing epithelium of Drosophila melanogaster, an established model system for investigating organ size control. By varying light intensity and activation dynamics systematically, we identified a biphasic regulation of final organ size. Illumination of CsChrimson depolarizes cells and stimulates spikes of cytosolic calcium concentrations, a phenomenon explained by a computational model that incorporates the inclusion of both gap junction closure and voltage-gated calcium channel activation. This calcium regulation tunes downstream effectors involved in growth regulation and apoptosis. In particular, we found that prolonged bright red light exposure (100 lux/12 hours) increased cell death in wing imaginal discs and caused severe morphological abnormalities in adult wings, with phenotypic severity dependent on stimulation parameters defined by illumination intensity and period of activation. Strikingly, an optimum level of dim, pulsatile light (5 lux, 1 minute on/off pulse train) resulted in overgrown organs and significantly upregulated cell proliferation. We also co-expressed an oncogene, RasV12, with CsChrimson and showed that experimental optical simulation parameters can be exploited to control the morphology of tumorous tissues and initiate targeted remission of tumorous growth. Our findings and approach provide a powerful framework to dissect the role of dynamic physiological signaling events in organogenesis and offer translational insights into new therapeutic strategies with applications in cancer and regenerative medicine.

bioengineering↗

bioRxiv2024

Examining perfluorohexane sulfonate (PFHxS) impacts on sensorimotor and circadian rhythm development

Perfluorohexane sulfonate (PFHxS) is a ubiquitous perfluoroalkyl substance known for its environmental persistence and potential toxicity. This study investigated PFHxSs impact on zebrafish embryos, focusing on sensorimotor behavior, circadian rhythm disruption, and underlying molecular mechanisms. Under 24 hr dark incubations, PFHxS exposure induced concentration-dependent hyperactivity within larval photomotor response, characterized by the distinctive "O-bend" response, strong light-phase hyperactive movement and seizure-like movements. It appears that PFHxS-treated embryos cannot sense light cues in a normal manner. Similar hyperactivity was seen for acoustic startle response assay, suggesting that the response is not merely visual, but sensorimotor. LC-MS studies confirmed detectable uptake of PFHxS into embryos. We then conducted mRNA-sequencing across multiple time points (48 and 120 hpf) and concentrations (0.00025, 0.0025 and 25 {micro}M). Data at the 25 {micro}M (2-120 hpf) exposure showed disrupted pathways associated with DNA and cell cycle. Interestingly, data at 0.00025 {micro}M - an environmentally relevant concentration- at 48 hpf showed disruption of MAPK and other signaling pathways. Immunohistochemistry of eyes showed reduced retinal stem cell proliferation, consistent with observed DNA replication pathway disruptions. To assess if these impacts were driven by circadian rhythm development, we manipulated light/dark cycles during PFHxS incubation; this manipulation altered behavioral patterns, implicating circadian rhythm modulation as a target of PFHxS. Since circadian rhythm is modulated by the pineal gland, we ablated the gland using metronidazole; this ablation partially rescued hyperactivity, indicating the glands role in driving the phenotype. Collectively, these findings underscore proclivity of PFHxS to cause neurodevelopmental toxicity, necessitating further mechanistic exploration and environmental health assessments.

pharmacology and toxicology↗

bioRxiv2023

The microbiome of an amphibious plant shifts dramatically across the host life cycle.

Interactions between plants and their associated microbiomes are thought to enhance the capacity of the host plant to overcome extreme conditions, yet the significance of microbially mediated stress tolerance in most plant species and ecosystems remains unknown. For the first time, we examined the microbiome of the amphibious plant Eryngium castrense (Apiaceae) inhabiting Mediterranean climate ephemeral wetlands in California. Eryngium castrense has the capacity to survive as both an aquatic and terrestrial plant, thereby living under contrasting extremes of water stress. Whether plant-associated microbial communities are also affected by such changes, and what ecological role they play while inhabiting amphibious plants, is an underexplored topic of plant-microbial interactions in natural and artificial systems. We amplified and sequenced 16S rRNA genes from bacteria and archaea to examine microbial communities associated with roots and shoots over the plants full life cycle. We observed that the microbiome changes from the aquatic stage to the terrestrial stage, and that roots and shoots represent distinct habitats within the plant host ecosystem. When compared with soil and water column samples, plant samples retained a unique, differentiated core microbiome. Taxa located in the roots during the terrestrial stage were linked with potential functions such as nitrogen acquisition, sulfur assimilation, and resistance to heavy metals, whereas aquatic roots held potential phythoparasites. Overall, our results provide new insights into symbiotic relationships in plants subject to stress-related to water saturation and deficiency.

microbiology↗

bioRxiv2023

Loss of thymocyte competition underlies the tumor suppressive functions of the E2a transcription factor in T lymphocyte acute lymphoblastic leukemia.

T lymphocyte acute lymphoblastic leukemia (T-ALL) is frequently associated with increased expression of the E protein transcription factor inhibitors TAL1 and LYL1. In mouse models, ectopic expression of Tal1 or Lyl1 in T cell progenitors or inactivation of E2a, is sufficient to predispose mice to develop T-ALL. How E2a suppresses thymocyte transformation is currently unknown. Here, we show that early deletion of E2a, prior to the DN3 stage, was required for robust leukemogenesis and was associated with alterations in thymus cellularity, T cell differentiation, and gene expression in immature CD4+CD8+ thymocytes. Introduction of wild-type thymocytes into mice with early deletion of E2a prevented leukemogenesis, or delayed disease onset, and impacted the expression of multiple genes associated with transformation and genome instability. Our data indicate that E2a suppresses leukemogenesis by promoting T cell development and enforcing inter-thymocyte competition, a mechanism that is emerging as a safeguard against thymocyte transformation. These studies have implications for understanding how multiple essential regulators of T cell development suppress T-ALL and support the hypothesis that thymus cellularity is a determinant of leukemogenesis.

cancer biology↗

bioRxiv2022

TGF-β promotes the postselection thymic development and peripheral function of interferon-γ-producing iNKT cells

Interferon-{gamma} producing invariant natural killer T (iNKT1) cells are lipid reactive innate-like lymphocytes that are resident in the thymus and peripheral tissues where they protect against pathogenic infection. The thymic functions of iNKT1 cells are not fully elucidated but subsets of thymic iNKT cells modulate CD8 T cell, dendritic cell, B cell and thymic epithelial cell numbers or function. Here we show that a subset of thymic iNKT1 cells require transforming growth factor (TGF)-{beta} induced signals for their development and for expression of residency associated adhesion receptors. Liver and spleen iNKT1 cells do not share this TGF-{beta} gene signature but nonetheless TGF-{beta} is required for optimal liver iNKT1 cell function. Our findings provide insight into the heterogeneity of mechanisms guiding iNKT1 cell development in different tissues and suggest a close association between a subset of iNKT1 cells and TGF-{beta} producing cells in the thymus.

immunology↗

bioRxiv2022

The effects of combined action observation and motor imagery on corticospinal excitability and movement outcomes: A meta-analysis

Motor simulation interventions involving motor imagery (MI) and action observation (AO) have received considerable interest in the behavioral sciences. A growing body of research has focused on using AO and MI simultaneously, termed combined action observation and motor imagery (AOMI). The current paper includes two meta-analyses that quantify changes in corticospinal excitability and motor skill performance for AOMI compared to AO, MI and control conditions. Specifically, the first meta-analysis collated and synthesized existing motor evoked potential (MEP) amplitude data from transcranial magnetic stimulation studies and the second meta-analysis collated and synthesized existing movement outcome data from behavioral studies. AOMI had a positive effect compared to control and AO but not MI conditions for both MEP amplitudes and movement outcomes. No methodological factors moderated the effects of AOMI, indicating a robust effect of AOMI across the two outcome variables. The results of the meta-analyses are discussed in relation to existing literature on motor simulation and skill acquisition, before providing viable directions for future research on this topic. HighlightsO_LIMotor imagery (MI) and action observation (AO) can be combined (AOMI) C_LIO_LIThis paper synthesizes neurophysiological and behavioral evidence for AOMI C_LIO_LIAOMI had increased corticospinal excitability compared to AO and control but not MI C_LIO_LIAOMI led to improved movement outcomes compared to AO and control but not MI C_LIO_LIThe reported effects of AOMI were maintained across all moderators C_LI

neuroscience↗

bioRxiv2021

Losses and gains of fallows drive farmland bird populations over three funding periods of the EU Common Agricultural Policy

O_LIFallow land provides habitat for threatened and declining farmland biodiversity. Policy change under the EUs Common Agricultural Policy (CAP) has been driving the area of fallows over the past decades and influenced trends in farmland biodiversity. C_LIO_LIWe analyzed the relationships between fallow land area across Germany over three CAP funding periods and species richness and abundance of farmland birds. We examined whether the strength of the relationships with fallow land area were moderated by species habitat preferences and landscape configurational complexity (edge density). We combined spatial data on fallow land area from three agricultural censuses in Germany (2007, 2010 and 2016) with country-wide farmland bird monitoring data. C_LIO_LIFarmland bird species richness and the abundance of the majority of the studied farmland bird species were positively related to increases in fallows across three CAP funding periods. The relationship of fallows with bird richness was strongest at intermediate levels of edge density. There was generally little support for a moderating effect of edge density on the relations between fallows and bird abundance. C_LIO_LIWe conclude that the loss of fallows in the period 2007 to 2016 resulted in strong declines of farmland birds. We predict that a future increase of the proportion of fallow land to 4% of the arable land, as envisaged in the German 2023-2027 CAP strategic plans, or to 10%, as foreseen in the EU Biodiversity Strategy, will lead to increases in farmland bird species richness and abundance depending on the landscape context and species-specific habitat preferences. C_LI Policy implicationsIncreasing the proportion of fallow land will likely be a key lever to stabilize and revert negative farmland bird population trends. An increase of fallow area in all but the least complex landscapes will boost farmland bird richness and abundance. Increasing the proportion of fallow land to 4% should bring farmland bird richness and abundance back to the levels observed in 2007 acknowledging that farmland bird populations were already severely depleted in 2007. A more ambitious expansion of fallow land towards 10% should be targeted towards areas that experienced the strongest loss of fallows and towards landscapes with intermediate levels of edge density.

ecology↗

bioRxiv2020

Model-based integration of citizen-science data from disparate sources increases the precision of bird population trends

AimTimely and accurate information on population trends is a prerequisite for effective biodiversity conservation. Structured biodiversity monitoring programs have been shown to track population trends reliably, but require large financial and time investment. The data assembled in a large and growing number of online databases are less structured and suffer from bias, but the number of observations is much higher compared to structured monitoring programs. Model-based integration of data from these disparate sources could capitalize on their respective strengths. LocationGermany. MethodsAbundance data for 26 farmland bird species were gathered from the standardized Common Breeding Bird Survey (CBBS) and three online databases that varied with regard to their degree of survey standardization. Population trends were estimated with a benchmark model that included only CBBS data, and five Bayesian hierarchical models integrating all data sources in different combinations. Across models, we compared consistency and precision of the predicted population trends, and the accuracy of the models. Bird species body mass, prevalence in the dataset and abundance were tested as potential predictors of the explored quantities. ResultsConsistency in predicted annual abundance indices was generally high especially when comparing the benchmark models to the integrated models without unstructured data. The accuracy of the estimated population changes was higher in the hierarchical models compared to the benchmark model but this was not related to data-integration. Precision of the predicted population trends increased as more data sources were integrated. Main conclusionsModel-based integration of data from different sources can lead to improved precision of bird population trend estimates. This opens up new opportunities for conservation managers to identify declining populations earlier. Integrating data from online databases could substantially increase sample size and thus allowing to derive trends for currently not well-monitored species, especially at sub-national scales.

ecology↗