Biology subjects

Hale, L.

Publications and source records attributed to Hale, L..

9 recordsLinked to original sources

bioRxiv2025

Reversible Dissociation of Mitochondrial Complex V Balances Anabolic and Energy-Generating Needs in Cancer

Cancer cell metabolic re-programming provides the excess energy and anabolic precursors necessary to sustain uncontrolled growth. This is partly mediated by the Warburg effect, whereby glucose is converted into ATP and a subset of these anabolic substrates. Concurrently, mitochondrial mass and ATP production decline in most tumors. This raises the question of how increased supplies of glycolysis-derived anabolic substrates can be balanced with those generated by the TCA cycle. Using primary murine liver cancers and cell lines, we show that this can be explained by the dissociation of mitochondrial Complex V (CV or ATP synthase) into its component and functionally-independent Fo and F1 domains. This occurs as a result of marked reductions in MT-ATP6, a CV subunit that stabilizes the Fo-F1 association. Serving as a proton pore, Fo maintains a normal mitochondrial membrane potential without generating ATP, thus allowing the TCA cycle, electron transport chain and anaplerotic reactions to function at high levels. Concurrently, free F1 functions as an ATPase to prevent excessive ATP accumulation. The uncoupling of TCA cycle-derived anabolic substrate production from membrane hyperpolarization and ATP synthesis by a smaller population of more efficient mitochondria allows TCA cycle-generated anabolic precursors to match those generated via glycolysis.

cancer biology↗

bioRxiv2025

Genetic and phenotypic diversity of wine-associated Hanseniaspora species

The genus Hanseniaspora includes apiculate yeasts commonly found in fruit- and fermentation-associated environments. Their genetic diversity and evolutionary adaptations remain largely unexplored despite their ecological and enological significance. This study investigated the phylogenetic relationships, genome structure, selection patterns, and phenotypic diversity of Hanseniaspora species isolated from wine environments, focusing on Hanseniaspora uvarum, the most abundant non-Saccharomyces yeast in wine fermentation. A total of 151 isolates were sequenced, including long-read genomes for representatives of the main phylogenetic clades. Comparative genomics revealed ancestral chromosomal rearrangements between the slow- (SEL) and fast-evolving (FEL) lineages that could have contributed to their evolutionary split, as well as significant loss of genes associated with mRNA splicing, chromatid segregation and signal recognition particle protein targeting specifically in the FEL lineage. Pangenome analysis within H. uvarum identified extensive copy number variation (CNV), particularly in genes related to xenobiotic tolerance, nutrient transport and metabolism. Investigation into the selective landscape following the FEL/SEL divergence identified diversifying selection in 229 genes in the Hanseniaspora FEL lineage, with significant enrichment in genes within the lysine biosynthetic pathway, suggesting a key role for this amino acid in early FEL adaptation. In H. uvarum, signatures of recent positive selection were detected in genes linked to sulphur assimilation, sterol biosynthesis and glycerol production, indicating potential adaptation to the stresses imposed by grape and wine fermentation. Furthermore, phenotypic screening of 113 isolates revealed substantial intraspecific diversity, with specific species exhibiting enhanced ethanol, osmotic, copper, SO2, and cold tolerance. These findings provide novel insights into the genomic evolution and functional diversity of Hanseniaspora, expanding our understanding of yeast adaptation to wine fermentation and laying the foundation for targeted gene investigations within this important genus.

microbiology↗

bioRxiv2024

Temporal and spatial dynamics within the fungal microbiome of grape fermentation

Wine fermentation is a highly complex and competitive environment, imposing harsh selective pressures on fungal community ecology and diversity. The composition of fungal communities inhabiting the surface of grapes will directly impact fermentation progression, wine quality, and contribute to the distinctiveness between wines from different geographical regions. Despite this, the extent of microbial community diversity between geographies, termed microbial terroir, remains highly debated. We amassed a large survey of grape spontaneous ferments over six years, encompassing 3105 fungal microbiomes across 14 geographically separated grape-growing regions, and nine grape cultivars. Investigation into the biodiversity of these ferments identified that few high abundance genera form the core of the initial grape microbiome. In line with previous studies, various consistent taxa were linked to specific geographical locations and grape varieties. However, these taxa accounted for a small portion of the overall diversity in the dataset. Through unsupervised clustering, we identified three distinct community types in the grape fungal microbiome, each exhibiting variations in the abundance of key genera. Analysing ferments across temporal and spatial scales revealed significant differences in species richness and compositional heterogeneity between wineries and grape growing regions. However, microbial communities were transient between years in the same winery, regularly transitioning between the three broad community types. We then investigated microbial community composition throughout the fermentative process and observed that initial microbial community composition is predictive of the diversity during the early stages of fermentation, with Hanseniaspora uvarum detected as the main non-Saccharomyces species within this large cohort of samples. Our results help to formulate a clear understanding of the spatial and temporal characteristics of the grape juice fungal microbiome and suggest that these communities are mainly defined by the grape niche and in a minor way shaped by local environmental conditions.

microbiology↗

bioRxiv2023

Do native and introduced cover crops differ in their ability to suppress weeds and reduce seedbanks? A Case study in a Table Grape Vineyard.

Cover cropping is considered a valuable tool for integrated weed management. However, weed suppression by cover crops can be inconsistent. We hypothesized that a native cover crop species may have greater capacity to suppress weeds than an introduced species owing to adaptive advantages. A study was conducted from 2020 to 2022 in a newly-established Autumn King tablegrape vineyard in Parlier, CA. Two cover crop treatments, a native plant species, phacelia (Phacelia tanacetifolia), or an introduced species, rye (Secale cereale L. Merced), were compared to a no cover crop, herbicide-managed control for impacts on weed control. Cover crops were sown in 2019 in the center 1.8 m of the 3.6 m space between the grapevine rows. The experimental design was a randomized complete block with four replications. Percent cover, weed density, and weed biomass in different seasons were assessed in the inter-row spaces and the vine rows. Soil samples were collected in 2021 from the grape row and interrow spaces to assess the weed seedbank. After the cover crops were terminated, percent weed cover was lower in the interrow of the phacelia compared to the no cover crop plots at two sampling times. When cover crops were actively growing (winter/spring), phacelia plots had a 7-fold higher cover crop to weed biomass ratio compared to that of the rye plots, thus indicating greater weed suppression. However, weed seedling emergence from the seedbank samples of the cover crop plots were 2- to 4-fold greater (in the phacelia and rye, respectively) than from the no cover crop plots. In summary, phacelia suppressed weeds more than rye; however, they both resulted in a bigger weed seedbank size compared to the herbicide-managed no cover crop plots, so additional management practices will be needed for long term weed management with cover crops in vineyards.

ecology↗

bioRxiv2020

Conversion of marginal land into switchgrass conditionally accrues soil carbon and reduces methane consumption

Switchgrass (Panicum virgatum L.) is a perennial C4 grass native to tallgrass prairies of the Central US, and a promising bioenergy feedstock. Switchgrass can be cultivated on soils with low nutrient contents and its rooting depth, of up to 2 m, has brought attention to the crop as a potential mechanism to sequester and build soil carbon (C). Switchgrass, therefore, offers multifaceted benefits on degraded soils by enhancing soil organic matter content. However, to evaluate the sustainability of switchgrass-based biofuel production, it is crucial to understand the impacts of land conversion and switchgrass establishment on biotic/abiotic characteristics of various soils. In this study, we characterized the ecosystem-scale consequences of switchgrass growing at two highly-eroded, Dust Bowl remnant field sites from Oklahoma US, with silt-loam (SL) or clay-loam (CL) soil textures having low nitrogen (N), phosphorus (P), and C contents. Paired plots at each site, including fallow control and switchgrass-cultivated, were assessed. Our results indicated that switchgrass significantly increased soil C at the SL site and reduced microbial diversity at the CL site. The CL site exhibited significantly higher CO2 flux and higher respiration from switchgrass plots. Strikingly, switchgrass significantly reduced the CH4 consumption by an estimated 39% for the SL site and 47% for the CL site. Structural equation modeling identified soil temperature, P content, and soil moisture levels as the most influential factors regulating both CO2 and CH4 fluxes. CO2 flux was also influenced by microbial biomass while CH4 flux was influenced by microbial diversity. Together, our results suggest that site selection by soil type is a crucial factor in improving soil C stocks and mitigating greenhouse gas (GHG) fluxes, especially considering our finding that switchgrass reduced methane consumption, implying that carbon balance considerations should be accounted for to fully evaluate the sustainability of switchgrass cultivation.

molecular biology↗

bioRxiv2020

Lower Soil Carbon Loss Due to Persistent Microbial Adaptation to Climate Warming

Soil microbial respiration is an important source of uncertainty in projecting future climate and carbon (C) cycle feedbacks. Despite intensive studies for two decades, the magnitude, direction, and duration of such feedbacks are uncertain, and their underlying microbial mechanisms are still poorly understood. Here we examined the responses of soil respiration and microbial community structure to long-term experimental warming in a temperate grassland ecosystem. Our results indicated that the temperature sensitivity of soil microbial respiration (i.e., Q10) persistently decreased by 12.0{+/-}3.7% across 7 years of warming. Integrated metagenomic and functional analyses showed that microbial community adaptation played critical roles in regulating respiratory acclimation. Incorporating microbial functional gene abundance data into a microbially-enabled ecosystem model significantly improved the modeling performance of soil microbial respiration by 5-19%, compared to the traditional non-microbial model. Model parametric uncertainty was also reduced by 55-71% when gene abundances were used. In addition, our modeling analyses suggested that decreased temperature sensitivity could lead to considerably less heterotrophic respiration (11.6{+/-}7.5%), and hence less soil C loss. If such microbially mediated dampening effects occur generally across different spatial and temporal scales, the potential positive feedback of soil microbial respiration in response to climate warming may be less than previously predicted.

ecology↗

bioRxiv2019

Microbial extracellular polysaccharide production and aggregate stability controlled by Switchgrass (Panicum virgatum) root biomass and soil water potential

Deep-rooting perennial grasses are promising feedstock for biofuel production, especially in marginal soils lacking organic material, nutrients, and/or that experience significant water stress. Perennial grass roots can alter surrounding soil conditions and influence microbial activities, particularly the production of extracellular polymeric substances composed primarily of extracellular polysaccharides (EPS). These polymers can alleviate cellular moisture and nutrient stress, and enhance soil characteristics through improved water retention and aggregate stability, the latter of which may in turn enhance carbon persistence. In this study we used a 13CO2 tracer greenhouse experiment to examine the effect of switchgrass cultivation on the production and origin of EPS in a marginal soil with five fertilization/water treatments (control, +N, +NP, +P, low water). Soils with both added nitrogen and phosphorus had the highest root biomass, EPS and percentage of water-stable soil aggregates. Multiple linear regression analyses revealed root biomass was the most important determinant for soil EPS production, potentially by controlling carbon supply and diurnal changes in soil water potential. Path analysis highlighted the role of soil water potential were and EPS on with water-stable soil aggregates, indicating that EPS concentration and soil aggregation have similar drivers in this soil. High mannose content confirmed the microbial origin of EPS. 13CO2 labeling indicated that 0.18% of newly fixed plant carbon was incorporated into EPS. Analysis of field samples suggests that EPS is significantly enhanced under long-term switchgrass cultivation. Our results demonstrate that switchgrass cultivation can promote microbial production of EPS, providing a mechanism to enhance sustainability of marginal soils.

microbiology↗

bioRxiv2019

Century long fertilization reduces stochasticity controlling grassland microbial community succession

Determining the drivers underlying ecological succession is a fundamental goal of ecological research and essential for predicting ecosystem functioning in response to human-induced environmental changes. Although various studies have examined the impacts of nitrogen (N) addition on plant and microbial community diversity, structure and activities, it remains unknown how long-term anthropogenic fertilization affects the ecological succession of microbial functional guilds and its underlying community assembly mechanisms. Here, using archived soils, we examined more than a centurys succession in soil microbial functional communities (from 1870 to 2008) from the Park Grass Experiment at Rothamsted Experimental Station, the longest running ecological experiment in the world. Long-term fertilization was found to significantly alter soil functional community structure and led to increasingly convergent succession of soil microbial communities. Meta-analysis indicated that microbial temporal turnover (w) was highly time scale-dependent, and the w value threshold was estimated as 0.0025 with a threshold time point of approximately 160 years. In addition, the importance of stochastic assembly varied greatly in regulating the succession of different microbial guilds. Fertilization had large to medium effects on reducing ecological stochasticity for microbial guilds involved in carbon (C) fixation and degradation, N fixation and mineralization, and denitrification. This century long-term study elucidated the differing influences of assembly mechanisms on soil microbial functional communities involved in C and N cycling, which could not be derived from taxonomic or phylogenetic approaches.

ecology↗

bioRxiv2017

Transcriptional evaluation of the developmental accuracy, reproducibility and robustness of kidney organoids derived from human pluripotent stem cells

We have previously reported a protocol for the directed differentiation of human induced pluripotent stem cells to kidney organoids comprised of nephrons, proximal and distal epithelium, vasculature and surrounding interstitial elements. The utility of this protocol for applications such as disease modelling will rely implicitly on the developmental accuracy of the model, technical robustness of the protocol and transferability between iPSC lines. Here we report extensive transcriptional analyses of the sources of variation across the timecourse of differentiation from pluripotency to complete kidney organoid, focussing on repeated differentiations to day 18 organoid. Individual organoids generated within the same differentiation experiment show Spearmans correlation coefficients of >0.99. The greatest source of variation was seen between experimental batch, with the enrichment for genes that also varied temporally between day 10 and day 25 organoids implicating nephron maturation as contributing to transcriptional variance between individual differentiation experiments. A morphological analysis revealed a transition from renal vesicle to capillary loop stage nephrons across the same time period. Distinct iPSC clones were also shown to display congruent transcriptional programs with inter-experimental and inter-clonal variation most strongly associated with nephron patterning. Even epithelial cells isolated from organoids showed transcriptional alignment with total organoids of the same day of differentiation. This data provides a framework for managing experimental variation, thereby increasing the utility of this approach for personalised medicine and functional genomics.

bioinformatics↗