Biology subjects

Williams, D. R.

Publications and source records attributed to Williams, D. R..

14 recordsLinked to original sources

bioRxiv2026

From chromosome-scale assembly to the mappable genome of rubber dandelion: chromosome reorganization, rubber-pathway coordination, and domestication traits

Natural rubber supply depends almost entirely on one tropical tree, motivating development of temperate alternatives. Rubber dandelion (Taraxacum kok-saghyz Rodin) is the leading candidate, with comparatively well characterized rubber biosynthesis pathways, but its large, repeat-rich genome has left breeding genomics far behind pathway biology. In response, we assembled OSU TarKok 3.0, a 1.19-Gb nuclear reference in which eight chromosome-scale scaffolds contain 98% of the sequence. Continuity within chromosomes improved markedly, with contig N50 rising from 1.3 to 37.8 Mb, and conserved gene-space recovery improved accordingly. Macrosynteny showed strong chromosome conservation within Taraxacum and, when compared to lettuce, displayed four nearly intact and four composite chromosomes, a signature compatible with descending dysploidy accompanied by rearrangement rather than a single end-to-end fusion. Across nine Cichorieae genomes, none of six surveyed rubber-related gene families was uniquely enlarged in rubber dandelion. Instead, a cis-prenyltransferase locus, a rubber transferase activator, and three small rubber particle protein genes were enriched in underground tissues and grouped with rubber elongation factor in a latex-associated co-expression module, favoring coordinated pathway deployment over species-specific family expansion. Intersecting uniquely mappable and nonrepetitive sequence defined the mappable genome, approximately 210 Mb or 18% of the assembly, within which markers can be interpreted allelically. Mapping in an independent F2 family of 83 plants identified a chromosome 1 locus for filled-seed production under restricted cross-pollination, whereas herbicide response yielded no significant locus in this design. OSU TarKok 3.0 links chromosome reorganization, pathway deployment, and domestication traits into one framework for improving an outcrossing crop.

plant biology↗

bioRxiv2025

Phase diversity improves retinal image quality in adaptive optics scanning light ophthalmoscopy

The quality of retinal images is compromised by aberrations that remain uncorrected even in confocal adaptive optics imaging. This study demonstrates phase diversity (PD), a computational imaging technique, to address residual aberrations and enhance image quality in adaptive optics scanning laser ophthalmoscopy (AOSLO). By using images of the same object obtained with and without deliberately added aberrations, PD computes and compensates for the effects of existing residual aberrations beyond those corrected by a closed-loop AO system. Experimental validation demonstrates that PD improves visualization of retinal microstructures, including cone mosaics and dendrites of fluorescently labeled retinal ganglion cells (RGCs).

neuroscience↗

bioRxiv2025

Predicting the responses of the world's bird species to increases in agricultural production

The intensification and expansion of croplands are among the greatest threats to biodiversity, but the likely responses to these changes remain unknown for most species. Using data on responses of 862 bird species to changes in yields of arable crops, we extrapolate vulnerability to agriculture for the worlds other terrestrial birds based on their traits and taxonomy. We estimate that 74-78% of terrestrial bird species globally suffer population declines where natural habitats are replaced by croplands, and that over half cannot persist in cropland at even the lowest current yields. Past impacts of agriculture on birds have been greatest in the tropics, particularly in coastal forest regions of Central and South America and West Africa and in southern and South-East Asia. Using these estimates to model the impacts of future scenarios of agricultural change, we find that continuing current rates of cropland expansion and yield increases (i.e., extrapolating business-as-usual trends to 2050) is expected to have more negative impacts on birds (particularly in Central and South America, Eastern Europe, sub-Saharan Africa and South and East Asia) than a potential alternative of a targeted strategy of closing yield gaps while limiting cropland expansion. However, we also identify biodiverse regions of the world where closing yield gaps may have more severe impacts on birds than business-as-usual, such as the Pampas of South America and parts of the Sahel region in West Africa. The strategy of least impact for a particular area can be predicted from the response characteristics of the communities of species present there, offering opportunities to take account of regional context for designing less damaging global food production systems.

ecology↗

bioRxiv2024

Asymmetric Activation of Retinal ON and OFF Pathways by AOSLO Raster-Scanned Visual Stimuli

Adaptive optics scanning light ophthalmoscopy (AOSLO) enables high-resolution retinal imaging, eye tracking, and stimulus delivery in the living eye. AOSLO-mediated visual stimuli are created by temporally modulating the excitation light as it scans across the retina. As a result, each location within the field of view receives a brief flash of light during each scanner cycle (every 33-40 ms). Here we used in vivo calcium imaging with AOSLO to investigate the impact of this intermittent stimulation on the retinal ON and OFF pathways. Raster-scanned backgrounds exaggerated existing ON-OFF pathway asymmetries leading to high baseline activity in ON cells and increased response rectification in OFF cells.

neuroscience↗

bioRxiv2024

Targeting phosphatase DUSP22 ameliorates skeletal muscle wasting via Akt independent JNK-FOXO3a repression

Skeletal muscle wasting results from numerous conditions, such as sarcopenia, glucocorticoid therapy or intensive care. It prevents independent living in the elderly, predisposes to secondary diseases, and ultimately reduces lifespan. There is no approved drug therapy and the major causative mechanisms are not fully understood. Dual specificity phosphatase 22 (DUSP22) is a pleiotropic signaling molecule that plays important roles in immunity and cancer. However, the role of DUSP22 in skeletal muscle wasting is unknown. In this study, DUSP22 was found to be upregulated in sarcopenia patients and models of skeletal muscle wasting. DUSP22 knockdown or pharmacological inhibition prevented multiple forms of muscle wasting. Mechanistically, targeting DUSP22 suppressed FOXO3a, a master regulator of skeletal muscle wasting, via downregulation of the stress-activated kinase JNK, which occurred independently of aberrant Akt activation. DUSP22 targeting was also effective in human skeletal muscle cells undergoing atrophy. In conclusion, phosphatase DUSP22 is a novel target for preventing skeletal muscle wasting. The DUSP22-JNK-FOXO3a axis could be exploited to treat sarcopenia or related aging disorders.

cell biology↗

bioRxiv2023

Cone-opponent ganglion cells in the primate fovea tuned to non-cardinal color directions

A long-standing question in vision science is how the three cone photoreceptor types - long (L), medium (M) and short (S) wavelength sensitive - combine to generate our perception of color. Hue perception can be described along two opponent axes: red-green and blue-yellow. Psychophysical measurements of color appearance indicate that the cone inputs to the red-green and blue-yellow opponent axes are M vs. L+S and L vs. M+S, respectively. However, the "cardinal directions of color space" revealed by psychophysical measurements of color detection thresholds following adaptation are L vs. M and S vs. L+M. These cardinal directions match the most common cone-opponent retinal ganglion cells (RGCs) in the primate retina. Accordingly, the cone opponency necessary for color appearance is thought to be established in cortex. However, small populations with the appropriate M vs. L+S and L vs. M+S cone-opponency have been reported in large surveys of cone inputs to primate RGCs and their projections to the lateral geniculate nucleus (LGN), yet their existence continues to be debated. Resolving this long-standing open question is necessary because a complete account of the coneopponency in the retinal output is critical for efforts to understand how downstream neural circuits process color. Here, we performed adaptive optics calcium imaging to longitudinally, noninvasively measure foveal RGC light responses in the living macaque eye. We confirm the presence of L vs. M+S and M vs. L+S neurons with non-cardinal coneopponency and demonstrate that cone-opponent signals in the retinal output are more diverse than classically thought.

neuroscience↗

bioRxiv2023

Real-time PCR detection of mixed Plasmodium ovale curtisi and wallikeri species infections in human and mosquito hosts

Plasmodium ovale curtisi (Poc) and Plasmodium ovale wallikeri (Pow) represent distinct non-recombining malaria species that are increasing in prevalence in sub-Saharan Africa. Though they circulate sympatrically, co-infection within human and mosquito hosts has rarely been described. Separate 18S rRNA real-time PCR assays that detect Poc and Pow were modified to allow species determination in parallel under identical cycling conditions. The lower limit of detection was 0.6 plasmid copies/L (95% CI 0.4-1.6) for Poc and 4.5 plasmid copies/L (95% CI 2.7-18) for Pow, or 0.1 and 0.8 parasites/L, respectively, assuming 6 copies of 18s rRNA per genome. However, the assays showed cross-reactivity at concentrations greater than 103 plasmid copies/L (roughly 200 parasites/L). Mock mixtures were used to establish criteria for classifying mixed Poc/Pow infections that prevented false-positive detection while maintaining sensitive detection of the minority ovale species down to 100 copies/L (<1 parasite/L). When the modified real-time PCR assays were applied to field-collected blood samples from Tanzania and Cameroon, species identification by real-time PCR was concordant with nested PCR, but additionally detected two mixed Poc/Pow infections where nested PCR detected a single Po species. When real-time PCR was applied to 14 oocyst-positive Anopheles midguts saved from mosquitoes fed on P. ovale-infected persons, mixed Poc/Pow infections were detected in 11 (79%). Based on these results, 8/9 P. ovale carriers transmitted both P. ovale species to mosquitoes, though both Po species could only be detected in the blood of two carriers. The described real-time PCR approach can be used to identify the natural occurrence of mixed Poc/Pow infections in human and mosquito hosts and reveals that such co-infections and co-transmission are likely more common than appreciated. AUTHOR SUMMARYPlasmodium ovale, one of five species of malaria known to infect humans, in fact represents two distinct species, P. ovale curtisi (Poc) and wallikeri (Pow), that can only be distinguished using molecular diagnostics. Though Poc and Pow circulate in the same regions in Africa and Asia, mixed infections, where both are found in the same human host, have rarely been described. In this study, we modified existing real-time PCR assays targeting 18S rRNA and developed an algorithm to detect mixed Poc/Pow infections. We then applied these assays to field-collected samples from Tanzania and Cameroon, including blood samples from P. ovale-infected persons and P. ovale-positive mosquito midguts saved from mosquito feeding assays. We detected both Poc and Pow in roughly 10% of human P. ovale blood-stage infections, and surprisingly, in a majority of blood-fed mosquitoes. This suggests that Poc and Pow co-infect the same hosts more frequently than previously realized.

microbiology↗

bioRxiv2022

Intracytoplasmic membranes develop in Geobacter sulfurreducens under thermodynamically limiting conditions

Geobacter sulfurreducens is an electroactive bacterium capable of reducing metal oxides in the environment and electrodes in engineered systems1,2. Geobacter sp. are the keystone organisms in electrogenic biofilms, as their respiration consumes fermentation products produced by other organisms and reduces a terminal electron acceptor e.g. iron oxide or an electrode. To respire extracellular electron acceptors with a wide range of redox potentials, G. sulfurreducens has a complex network of respiratory proteins, many of which are membrane-bound3-5. We have identified intracytoplasmic membrane (ICM) structures in G. sulfurreducens. This ICM is an invagination of the inner membrane that has folded and organized by an unknown mechanism, often but not always located near the tip of a cell. Using confocal microscopy, we can identify that at least half of the cells contain an ICM when grown on low potential anode surfaces, whereas cells grown at higher potential anode surfaces or using fumarate as electron acceptor had significantly lower ICM frequency. 3D models developed from cryo-electron tomograms show the ICM to be a continuous extension of the inner membrane in contact with the cytoplasmic and periplasmic space. The differential abundance of ICM in cells grown under different thermodynamic conditions supports the hypothesis that it is an adaptation to limited energy availability, as an increase in membrane-bound respiratory proteins could increase electron flux. Thus, the ICM provides extra inner-membrane surface to increase the abundance of these proteins. G. sulfurreducens is the first Thermodesulfobacterium or metal-oxide reducer found to produce ICMs.

microbiology↗

bioRxiv2022

Inhibiting 5-lipoxygenase prevents skeletal muscle atrophy by targeting organogenesis signaling and insulin-like growth factor-1

BackgroundSkeletal muscle atrophy can occur in response to numerous factors, such as aging and certain medications, and produces a major socioeconomic burden. At present, there are no approved drugs for treating skeletal muscle atrophy. Arachidonate 5-lipoxygenase (Aox5) is a drug target for a number of diseases. However, pharmacological targeting of Alox5, and its role in skeletal muscle atrophy, is unclear. MethodsThe potential effects of gene knockdown and pharmacological targeting of Alox5 on skeletal muscle atrophy was investigated using cell-based models, animal models, and human skeletal muscle tissue cultures. Malotilate, a clinically safe drug developed for enhancing liver regeneration and Alox5 inhibitor, was investigated as a repurposing candidate. Mechanism(s) of action in skeletal muscle atrophy were assessed by measuring the expression level or activation status of key regulatory pathways, and validated using gene knockdown and RNA sequencing. ResultsMyotubes treated with the atrophy-inducing glucocorticoid, dexamethasone, were protected from catabolic responses by treatment with malotilate (+41.29%, P < 0.01). Similar anti-atrophy effects were achieved by gene knockdown of Alox5 (+30.4%, P < 0.05). Malotilate produced anti-atrophy effects without affecting the myogenic differentiation program. In an in vivo model of skeletal muscle atrophy, malotilate treatment enhanced muscle performance (Grip strength: +35.72%, Latency to fall: +553.1%, P < 0.05), increased mass and fiber cross sectional area (Quadriceps: +23.72%, Soleus: +33.3%, P < 0.01), and down-regulated atrogene expression (Atrogin-1: -61.58%, Murf-1: -66.06%, P < 0.01). Similar, beneficial effects of malotilate treatment were observed in an aging muscle, which also showed the preservation of fast twitch fibers (Type 2a: +56.48%, Type 2b: +37.32%, P < 0.01). Leukotrine B4, a product of Alox5 activity with inflammatory and catabolic functions, was found to be elevated in skeletal muscle undergoing atrophy (Quadriceps: +224.4%, P < 0.001). Cellular transcriptome analysis showed that targeting Alox5 upregulated biological processes regulating organogenesis and increased the expression of insulin-like growth factor-1, a key anti-atrophy hormone (+226.5%, P < 0.05). Interestingly, these effects were restricted to the atrophy condition and not observed in normal skeletal muscle cultures with Alox5 inhibition. Human skeletal muscle tissue was also protected from atrophy by pharmacological targeting of Alox5 (+23.68%, P < 0.05). ConclusionThese results shed new light on novel drug targets and mechanisms underpinning skeletal muscle atrophy. Alox5 is a regulator and drug target for muscle atrophy, and malotilate is an attractive compound for repurposing studies to treat this disease.

cell biology↗

bioRxiv2022

In vivo physiology of foveal retinal ganglion cells in Macaca fascicularis

The primate fovea is specialized for high acuity chromatic vision, with the highest density of cone photoreceptors and a disproportionately large representation in visual cortex. The unique visual properties conferred by the fovea are conveyed to the brain by retinal ganglion cells, the somas of which lie at the margin of the foveal pit. Microelectrode recordings of these centermost retinal ganglion cells have been challenging due to the fragility of the fovea in the excised retina. Here we overcome this challenge by combining high resolution fluorescence adaptive optics ophthalmoscopy with calcium imaging to optically record functional responses of foveal retinal ganglion cells in the living eye. We use this approach to study the chromatic responses and spatial transfer functions of retinal ganglion cells using spatially uniform fields modulated in different directions in color space and monochromatic drifting gratings. We recorded from over 350 cells across three Macaca fascicularis primates over a time period of weeks to months. We find that the majority of the L vs. M cone opponent cells serving the most central foveolar cones have spatial transfer functions that peak at high spatial frequencies (20-40 c/deg), reflecting strong surround inhibition that sacrifices sensitivity at low spatial frequencies but preserves the transmission of fine detail in the retinal image. In addition, we fit to the drifting grating data a detailed model of how ganglion cell responses draw on the cone mosaic to derive receptive field properties of L vs. M cone opponent cells at the very center of the foveola. The fits are consistent with the hypothesis that foveal midget ganglion cells are specialized to preserve information at the resolution of the cone mosaic. By characterizing the functional properties of retinal ganglion cells in vivo through adaptive optics, we characterize the response characteristics of these cells in situ.

neuroscience↗

bioRxiv2021

Divergence in dimerization and activity of primate APOBEC3C

The APOBEC3 (A3) family of single-stranded DNA cytidine deaminases are host restriction factors that inhibit lentiviruses, such as HIV-1, in the absence of the Vif protein that causes their degradation. Deamination of cytidine in HIV-1 (-)DNA forms uracil that causes inactivating mutations when uracil is used as a template for (+)DNA synthesis. For APOBEC3C (A3C), the chimpanzee and gorilla orthologues are more active than human A3C, and the Old World Monkey A3C from rhesus macaque (rh) is not active against HIV-1. Multiple integrated analyses determined why rhA3C was not active against HIV-1 and how to increase this activity. Biochemical, virological, and coevolutionary analyses combined with molecular dynamics simulations showed that the key amino acids needed to promote rhA3C antiviral activity also promoted dimerization. Although rhA3C shares a similar dimer interface with hominid A3C, the key amino acid contacts were different. Overall, our results determine the basis for why rhA3C is less active than human A3C, establish the amino acid network for dimerization and increased activity, and track the loss and gain of A3C antiviral activity in primates. The coevolutionary analysis of the A3C dimerization interface provides a basis from which to analyze dimerization interfaces of other A3 family members.

biochemistry↗

bioRxiv2020

Dynamic Changes in Fecal Bacterial Microbiota of Dairy Cattle across the Production Line

Bacteria play important roles in the gastrointestinal tract (GIT) of dairy cattle as the communities are responsible for host health, growth and production performance. However, a systematic characterization and comparison of microbial communities in the GIT of cattle housed in different management units on a modern dairy are still lacking. In this study, we used 16S rRNA sequencing to evaluate the fecal bacterial communities of 90 dairy cattle raised and housed in 12 clearly defined management units on a modern dairy farm. We found that -diversity differed between several pairs of management units, especially between the hutch calves (management unit 1) and the other units except post weaned heifers (management unit 2). Although {beta}-diversity revealed that most of the samples did not cluster according to their management unit membership except management unit 1, in which the samples grouped and separated from others, we observed three major clusters. Besides the hutch calves (management unit 1), most samples from the other 11 units formed two distinct clusters and the relative abundance of Patescibacteria might be the reason for the separation. Moreover, we identified 212 amplicon sequence variants (ASVs) with relative abundances > 0.1% in more than 10% of the total samples that had significantly different abundances in these units. Furthermore, we found that, as the calves aged, 19 ASVs that were exclusively detected in unit 1, gradually degraded and never reoccurred in other management units. Lastly, we recognized 181 pairs of interactions between 61 ASVs with possibly strong synergistic or antagonistic relationships. These results suggest the enteric microbial communities of dairy cattle housed in different management units are quite dynamic. IMPORTANCEBacterial communities of GIT are crucial for ruminants, such as dairy cattle since they contribute to not only the cattles physiology and health but also milk production and food safety that are closely related to human health. Both scientifically and agriculturally, it is necessary to have deep insights into the composition and changes of the bacteria on modern dairy farms. In this study, we provided the profiles of fecal bacterial communities of dairy cattle in each management unit on a modern dairy and described how the enteric microbial communities changed across these management units. The findings have implications for improving animal health, dairy production, farm management, and food safety.

microbiology↗

bioRxiv2020

Poor availability of context-specific evidence hampers decision-making in conservation

Evidence-based conservation relies on robust and relevant evidence. Practitioners often prefer locally relevant studies whose results are more likely to be transferable to the context of planned conservation interventions. To quantify the availability of relevant evidence for amphibian and bird conservation we reviewed Conservation Evidence, a database of quantitative tests of conservation interventions. Studies were geographically clustered and found at extremely low densities - fewer than one study was present within a 2,000 km radius of a given location. The availability of relevant evidence was extremely low when we restricted studies to those studying biomes or taxonomic orders containing high percentages of threatened species, compared to the most frequently studied biomes and taxonomic orders. Further constraining the evidence by study design showed that only 17-20% of amphibian and bird studies used robust designs. Our results highlight the paucity of evidence on the effectiveness of conservation interventions, and the disparity in evidence for local contexts that are frequently studied and those where conservation needs are greatest. Addressing the serious global shortfall in context-specific evidence requires a step change in the frequency of testing conservation interventions, greater use of robust study designs and standardized metrics, and methodological advances to analyze patchy evidence bases.

ecology↗

bioRxiv2019

The challenge of heterogeneous evidence in conservation

Conservation efforts to tackle the current biodiversity crisis need to be as efficient and effective as possible. To inform decision-makers of the most effective conservation actions, it is important to identify biases and gaps in the conservation literature to prioritize future evidence generation. We assessed the state of this global literature base using the Conservation Evidence database, a comprehensive collection of quantitative tests of conservation actions (interventions) from the published literature. For amphibians and birds, we investigated the nature of Conservation Evidence spatially and taxonomically, as well as by biome, effectiveness metrics, and study design. Studies were heavily concentrated in Western Europe and North America for birds and particularly amphibians. Studies that used the most robust study designs - Before-After Control-Impact and Randomized Controlled Trials - were also the most geographically restricted. Furthermore, there was no relationship between the number of studies in each 1x1 degree grid cell and the number of species, threatened species or data-deficient species. Taxonomic biases and gaps were apparent for amphibians and birds - some orders were absent from the evidence base and others were poorly represented relative to the proportion of threatened species they contained. Temperate forest and grassland biomes were highly represented, which reinforced observed geographic biases. Various metrics were used to evaluate the effectiveness of a given conservation action, potentially making studies less directly comparable and evidence synthesis more difficult. We also found that the least robust study designs were the most commonly used; studies using robust designs were scarce. Future research should prioritize testing conservation actions on threatened species outside of Western Europe and North America. Standardizing metrics and improving the robustness of study designs used to test conservation actions would also improve the quality of the evidence base for synthesis and decision-making.

ecology↗