Biology subjects

Law, C.

Publications and source records attributed to Law, C..

At least 19 recordsLinked to original sources

bioRxiv2026

Sexual Dimorphism and Geographic Variation in Washington Bobcat (Lynx rufus) Skulls

Sexual dimorphism is a well-studied phenomenon in which males and females of a species exhibit different phenotypic characteristics. However, the degree of sexual dimorphism within a species may vary among populations and may be influenced by geographic factors such as seasonality, prey availability, and population density. In this study, we examined the effects of sexual dimorphism and geographic region on the craniomandibular morphology of bobcats (Lynx rufus) in Washington State. Using digital calipers, we measured 13 craniomandibular traits from 35 males and 42 females. We found that the degree of skull dimorphism does not differ between the eastern and western side of the Cascade Mountains. However, we found significant effects of sex and geographic region on craniomandibular morphology. Across the geographic regions, males were significantly larger than females in most craniomandibular traits, excluding postorbital constriction breadth (POC). After correcting for expected size differences, only condylobasal length (CBL) was disproportionately longer in males, indicating subtle shape dimorphism within this trait, that is largely unexplained by allometry. Mechanical advantage (MA) of the temporalis and masseter muscles did not differ between the sexes at the canine or the molar bite points. Comparisons between populations east and west of the Cascade Range revealed that while sex remains the primary indicator of overall size, there is a small regional effect on size as western bobcats are slightly larger than eastern bobcats. These regional differences highlight how environmental pressures including local prey availability and severe winter conditions may influence functional skull design. Future ecological and behavioral studies are needed to further clarify how these localized environmental drivers shape phenotypic variation across populations.

evolutionary biology↗

bioRxiv2026

Gut immunity and the bacterial and eukaryotic microbiome of wild house mice.

It is well established that the microbiome can have major effects on animal biology. Here we have investigated the composition of the bacterial and eukaryotic gut microbiome of wild mice from three sample sites and sought to understand what affects its composition. We find that the bacterial and eukaryotic microbiome differs among mice from different sites. Among mouse traits, we found that only gut inflammation and the concentration of faecal immunoglobulin A affected the microbiome diversity. However, the microbiome diversity was more commonly affected by the microbiome composition itself, both within-bacterial and within-eukaryotic, but also by cross bacterial-eukaryotic effects. We found that most hosts produce IgA that binds some of their gut bacteria, though mice are largely idiosyncratic in which taxa they bind with IgA, with a few taxa commonly IgA-bound. The eukaryotic microbiome was dominated by fungal taxa, and included Eimeria infection that was particularly common at one of the sites. At the high Eimeria prevalence site, mice had comparatively marked caecal inflammation and significantly greater IgA responses. Our results emphasise the substantial among-individual mouse differences in gut microbiome composition, gut physiology and immunology, and the biological significance of the bacterial-eukaryotic effects that we suggest requires further study.

ecology↗

bioRxiv2025

Long-fuse evolution of carnivoran skeletal phenomes through the Cenozoic

Climatic change is hypothesized to promote phenotypic diversification. While neontological analyses are often used to test this hypothesis, extant data only captures time-averaged signals of surviving lineages. More nuanced tests require paired and longitudinal climatic and organismal data. Here, we developed the most comprehensive phenomic dataset to-date of pan-carnivorans to test hypotheses that Cenozoic climatic change influenced the evolution of the cranial, appendicular, and axial skeleton. We found support for the hypothesis that a hierarchical progression of ecological diversification across the Cenozoic significantly influenced the establishment of modern carnivorans. Specifically, extinctions during the Eocene-Oligocene Transition released crown carnivorans from a constrained adaptive zone to interfamilial skeletal diversification. Intrafamilial skeletal diversification did not occur for another 20 million years until after the Mid-Miocene Climate Transition. Our work demonstrates the essential role of macroevolutionary data from the fossil record for revealing how major global climatic events steered the evolutionary trajectories of modern skeletal phenomes.

evolutionary biology↗

bioRxiv2025

Characterization of ORF19.7608 (PPP1), a Biofilm-induced Gene of Candida albicans

The opportunistic human pathogen Candida albicans is an important cause of nosocomial infections, in large part because of its propensity to form biofilms on indwelling medical devices such as catheters. The formation of these biofilms is controlled by a complex transcriptional network and involves over a thousand genes, many of which are uncharacterized. We have investigated three genes (ORF19.4654, ORF19.7608, and PBR1), found only in C. albicans and closely related species, that are highly induced under biofilm conditions and encode small proteins with N-terminal signal sequences. Through the construction of fluorescent protein fusions, we have examined the location of the encoded proteins in both planktonic and biofilm cells. Orf19.4654-Scarlet and Pbr1-Scarlet were localized to the vacuole under both conditions. In contrast, the Orf19.7608-GFP fusion generated a punctate pattern only under biofilm conditions and was designated Ppp1 (Punctate Pattern Protein 1). The Ppp1-GFP puncta were similar in location, stability, and size to those formed by the eisosome subunit Sur7, but co-localization studies suggest that Ppp1 and Sur7 define separate elements. The PPP1 mutation does not cause a distinct phenotype under various stress conditions or in the presence of antifungals and does not impact biofilm formation and biomass. These data suggest that while the expression and cellular localization of Ppp1 appear controlled by conditions generating biofilms, and define a unique subcellular localization pattern, Ppp1 protein function is not essential for biofilm formation. IMPORTANCEBiofilm formation is a virulence factor of medical importance in C. albicans. Identifying the biological function and cellular localization of biofilm-related proteins can help in their characterization and understanding of the biofilm network. Microscopy was employed to identify the subcellular localization of putative biofilm proteins, aiming to provide insight into their possible functions. Prb1 and Orf19.4654 localized to the vacuole, while Orf19.7608 (Ppp1) formed puncta. Phenotypic assays to investigate the uniqueness of PPP1 revealed that it does not play a major role in the stress response pathways or antifungal activity. Overall, our study provides insight into the localization of the products of Candida-specific biofilm genes.

microbiology↗

bioRxiv2024

Growth patterns of theoretical bite force and jaw musculature in southern sea otters (Enhydra lutris nereis)

The transition from milk to solid food requires drastic changes in the morphology of the feeding apparatus and its performance. As durophagous mammals, southern sea otters exhibit significant ontogenetic changes in cranial and mandibular morphology to presumably enable them to feed on a variety of hard-shelled invertebrate prey. Juvenile sea otters begin feeding independently by 6 -8 months of age, but how quickly they reach sufficient maturity in biting performances remains unknown. Here, I found that theoretical bite force of southern sea otters does not reach full maturation until during the adult stage at 3.6 and 5.0 years of age in females and males, respectively. The slow maturation of biting performance can be directly attributed to the slow growth and development of the cranium and the primary jaw adductor muscle (i.e., the temporalis) and may ultimately impact the survival of newly weaned juveniles by limiting their ability to process certain hard-shelled prey. Alterative foraging behaviors such as tool use, however, may mitigate the disadvantages of delayed maturation of biting performance. In analyses of sexual dimorphism, I found that female otters reached bite force maturation earlier whereas male otters exhibit initial rapid growth in bite force-to quickly reach sufficient biting performances needed to process prey early in life-followed by a slower growth phase towards bite force maturation that coincides with sexual maturity. This biphasic growth in bite force suggests that male to male competition for resources and mates exhibits strong selection in the growth and development of skull form and function in male otters. Overall, this study demonstrates how the analysis of anatomical data can provide insight on the foraging ecologies and life histories of sea otters across ontogeny.

developmental biology↗

bioRxiv2024

The carnivoran adaptive landscape reveals trade-offs among functional traits in the skull, appendicular, and axial skeleton

Analyses of form-function relationships are widely used to understand links between morphology, ecology, and adaptation across macroevolutionary scales. However, few have investigated functional trade-offs and covariance within and between the skull, limbs, and vertebral column simultaneously. In this study, we investigated the adaptive landscape of skeletal form and function in carnivorans to test how functional trade-offs between these skeletal regions contribute to ecological adaptations and the topology of the landscape. We found that morphological proxies of function derived from carnivoran skeletal regions exhibit trade-offs and covariation across their performance surfaces, particularly in the appendicular and axial skeletons. These functional trade-offs and covariation correspond as adaptations to different adaptive landscapes when optimized by various factors including phylogeny, dietary ecology, and, in particular, locomotor mode. Lastly, we found that the topologies of the optimized adaptive landscapes and underlying performance surfaces are largely characterized as a single gradual gradient rather than as rugged, multipeak landscapes with distinct zones. Our results suggest that carnivorans may already occupy a broad adaptive zone as part of a larger mammalian adaptive landscape that masks the form and function relationships of skeletal traits.

evolutionary biology↗

bioRxiv2024

Skull evolution and lineage diversification in endemic Malagasy carnivorans

Madagascar is one of the worlds foremost biodiversity hotspots with more than 90% of its species endemic to the island. Malagasy carnivorans are one of only four extant terrestrial mammalian clades endemic to Madagascar. Although there are only eight extant species, these carnivorans exhibit remarkable phenotypic and ecological diversity that is often hypothesized to have diversified through an adaptive radiation. Here, we investigated the evolution of skull diversity in Malagasy carnivorans and tested if they exhibited characteristics of convergence and an adaptive radiation. We found that their skull disparity exceeds that of any other feliform family, as their skulls vary widely and strikingly capture a large amount of the morphological variation found across all feliforms. We also found evidence of shared adaptive zones in cranial shape between euplerid subclades and felids, herpestids, and viverrids. Lastly, contrary to predictions of adaptive radiation, we found that Malagasy carnivorans do not exhibit rapid lineage diversification and only marginally faster rates of mandibular shape evolution, and to a lesser extent cranial shape evolution, compared to other feliforms. These results reveal that exceptional diversification rates are not necessary to generate the striking phenotypic diversity that evolved in carnivorans after their dispersal to and isolation on Madagascar.

evolutionary biology↗

bioRxiv2023

Endogenous tagging using split mNeonGreen in human iPSCs for live imaging studies

Endogenous tags have become invaluable tools to visualize and study native proteins in live cells. However, generating human cell lines carrying endogenous tags is difficult due to the low efficiency of homology-directed repair. Recently, an engineered split mNeonGreen protein was used to generate a large-scale endogenous tag library in HEK293 cells. Using split mNeonGreen for large-scale endogenous tagging in human iPSCs would open the door to studying protein function in healthy cells and across differentiated cell types. We engineered an iPS cell line to express the large fragment of the split mNeonGreen protein (mNG21-10) and showed that it enables fast and efficient endogenous tagging of proteins with the short fragment (mNG211). We also demonstrate that neural network-based image restoration enables live imaging studies of highly dynamic cellular processes such as cytokinesis in iPSCs. This work represents the first step towards a genome-wide endogenous tag library in human stem cells.

cell biology↗

bioRxiv2022

Scaling patterns of body plans differ among squirrel ecotypes

Body size is often hypothesized to facilitate or constrain morphological diversity in the cranial, appendicular, and axial skeletons. However, how overall body shape scales with body size (i.e., body shape allometry) and whether these scaling patterns differ between ecological groups remains poorly investigated. Here, we test whether and how the relationships between body shape, body size, and limb lengths differ among species with different locomotory specializations, and describe the underlying morphological components that contribute to body shape variation among squirrel (Sciuridae) ecotypes. We quantified the body size and shape of 87 squirrel species from osteological specimens held at museum collections. Using phylogenetic comparative methods on these data, we found that 1) body shape and its underlying morphological components scale allometrically with body size, but these allometric patterns differ among squirrel ecotypes; 2) only ground squirrels exhibit a relationship between forelimb length and body shape, where more elongate species exhibit relatively shorter forelimbs; and 3) the relative length of the ribs and elongation or shortening of the thoracic region contributes the most to body shape variation across squirrels. Overall, our work contributes to the growing understanding of mammalian body shape evolution and how it is influenced by body size and locomotor ecology, in this case from robust subterranean to gracile gliding squirrels.

evolutionary biology↗

bioRxiv2021

Chloroplast-localized translation for protein targeting in Chlamydomonas reinhardtii

Translation is localized within cells to target proteins to their proper locations. We asked whether translation occurs on the chloroplast surface in Chlamydomonas and, if so, whether it is involved in co-translational protein targeting, aligned spatially with localized translation by the bacterial-type ribosomes within this organelle, or both. Our results reveal a domain of the chloroplast envelope which is bound by translating ribosomes. Purified chloroplasts retained ribosomes and mRNAs encoding two chloroplast proteins specifically on this "translation domain", but not a mRNA encoding a cytoplasmic protein. Ribosomes clusters were seen on this domain by electron tomography. Activity of the chloroplast-bound ribosomes is supported by results of the ribopuromycylation and puromycin-release assays. Co-translational chloroplast protein import is supported by nascent polypeptide dependency of the ribosome-chloroplast associations. This cytoplasmic translation domain aligns localized translation by organellar bacterial-type ribosomes in the chloroplast. This juxtaposition the dual translation systems facilitates the targeting and assembly of the polypeptide products. One-Sentence SummaryTranslation is localized to a domain of the chloroplast envelope for co-translational protein targeting in Chlamydomonas.

cell biology↗

bioRxiv2021

Polarization and cell-fate decision facilitated by the adaptor Ste50 in Saccharomyces cerevisiae

In response to pheromone, many proteins localize on the plasma membrane of yeast cell to reform it into a polarized shmoo structure. The adaptor protein Ste50, long known as a pheromone signal enhancer critical for shmoo polarization, has never been explored systematically for its localization and function in the polarization process. Time-lapse single-cell imaging and quantitation shown here characterizes Ste50p involvement in the establishment of cell polarity. We found early localization of Ste50p patches on the cell cortex that mark the point of shmoo initiation, these polarity sites move, and patches remain associated with the growing shmoo tip in a pheromone concentration timedependent manner until shmoo maturation. By quantitative analysis we show that polarization corelates with the rising levels of Ste50p, enabling rapid individual cell responses to pheromone that corresponds to a critical level of Ste50p at the initial G1 phase. We exploited the quantitative differences in the pattern of Ste50p expression to corelate with the cell-cell phenotypic heterogeneity showing Ste50p involvement in the cellular differentiation choice. Taken together, these findings present spatiotemporal localization of Ste50p during yeast polarization, suggesting that Ste50p is a component of the polarisome, and plays a critical role in regulating the polarized growth of shmoo during pheromone response.

cell biology↗

bioRxiv2021

A deep learning approach to capture the essence of Candida albicans morphologies

We present deep learning-based approaches for exploring the complex array of morphologies exhibited by the opportunistic human pathogen C. albicans. Our system entitled Candescence automatically detects C. albicans cells from Differential Image Contrast microscopy, and labels each detected cell with one of nine vegetative, mating-competent or filamentous morphologies. The software is based upon a fully convolutional one-stage object detector and exploits a novel cumulative curriculum-based learning strategy that stratifies our images by difficulty from simple vegetative forms to more complex filamentous architectures. Candescence achieves very good performance on this difficult learning set which has substantial intermixing between the predicted classes. To capture the essence of each C. albicans morphology, we develop models using generative adversarial networks and identify subcomponents of the latent space which control technical variables, developmental trajectories or morphological switches. We envision Candescence as a community meeting point for quantitative explorations of C. albicans morphology.

microbiology↗

bioRxiv2021

The ubiquitous terpene geosmin is a warning chemical

Known as the smell of earth after rain, geosmin is an odorous terpene detectable by humans at picomolar concentrations. Geosmin production is heavily conserved in actinobacteria, myxobacteria, cyanobacteria, and some fungi, but its biological activity is poorly understood. We theorized that geosmin was an aposematic signal used to indicate the unpalatability of toxin-producing microbes, discouraging predation by eukaryotes. Consistent with this hypothesis we found that geosmin and the related terpene 2-methylisoborneol reduced predation of Streptomyces coelicolor and Myxococcus xanthus by the bacteriophagous Caenorhabditis elegans. Predation was restored by the removal of both terpene biosynthetic pathways or deletion of the C. elegans ASE sensory neuron, and resulted in the death of the nematodes. Geosmin itself was non-toxic. This is the first warning chemical to be identified in bacteria or fungi, and suggests molecular signalling affects microbial predator-prey interactions in a manner similar to the well-studied visual markers of poisonous animal prey.

microbiology↗

bioRxiv2021

Tumor expressed CD95 causes suppression of anti-tumor activity of NK cells in a model of triple negative breast cancer

The apoptosis inducing receptor CD95/Fas has multiple tumorigenic activities. Stimulation by its cognate ligand CD95L on many cancer cells increases their growth, motility, ability to invade and/or their cancer stemness. Using genetically engineered mouse models of ovarian and liver cancer, we previously reported that deletion of CD95 in the tumor cells strongly reduced their ability to grow in vivo [1, 2]. Using a combination of immune-deficient and immune-competent mouse models, we now establish that loss of CD95 in metastatic triple negative breast cancer cells prevents tumor growth by modulating the immune landscape. CD95 deficient but not wild-type tumors barely grow in an immune-competent environment and show an increase in immune infiltrates into the tumor. This growth reduction is caused by NK cells and does not involve CD8+ T cells. On the other hand, in immune compromised mice CD95 k.o. cells are not growth inhibited, but they fail to form metastases. In summary, we demonstrate that in addition to its tumor and metastasis promoting activities, CD95 expression by tumor cells can exert immune suppressive activities providing a new target for immune therapy.

cancer biology↗

bioRxiv2021

The Ran pathway uniquely regulates cytokinesis in cells with different fates in the early C. elegans embryo

Cytokinesis occurs at the end of mitosis and occurs due to the ingression of a contractile ring that cleaves the daughter cells. This process is tightly controlled to prevent cell fate changes or aneuploidy, and the core machinery is highly conserved among metazoans. Multiple mechanisms regulate cytokinesis, but their requirement in different cell types is not known. Here, we show that differently fated AB and P1 cells in the early C. elegans embryo have unique cytokinesis kinetics supported by distinct levels and cortical patterning of myosin. Through perturbation of polarity regulators and the generation of stable tetraploid strains, we demonstrate that these differences depend on both cell fate and size. Additionally, these parameters could influence the Ran pathway, which coordinates the contractile ring with chromatin position, and controls cytokinesis differently in AB and P1 cells. Our findings demonstrate the need to consider multiple parameters when modeling ring kinetics.

cell biology↗

bioRxiv2020

Multi-tissue patterning drives anterior morphogenesis of the C. elegans embryo

Complex structures derived from multiple tissue types are challenging to study in vivo, and our knowledge of how cells from different tissues are coordinated is limited. Model organisms have proven invaluable for improving our understanding of how chemical and mechanical cues between cells from two different tissues can govern specific morphogenetic events. Here we used Caenorhabditis elegans as a model system to show how cells from three different tissues are coordinated to give rise to the anterior lumen. This poorly understood process has remained a black box for embryonic morphogenesis. Using various microscopy and software approaches, we describe the movements and patterns of epidermal cells, neuroblasts and pharyngeal cells that contribute to lumen formation. The anterior-most pharyngeal cells (arcade cells) may provide the first marker for the location of the future lumen and facilitate the patterning of the surrounding neuroblasts. These neuroblast patterns control the rate of migration of the anterior epidermal cells, whereas the epidermal cells ultimately reinforce and control the position of the future lumen, as they must join with the pharyngeal cells for their epithelialization. Our studies are the first to characterize anterior morphogenesis in C. elegans in detail and should lay the framework for identifying how these different patterns are controlled at the molecular level.

developmental biology↗

bioRxiv2020

The zinc cluster transcription factor Rha1 is a positive filamentation regulator in Candida albicans

Zinc cluster transcription factors are essential fungal specific regulators of gene expression. In the dimorphic pathogen Candida albicans, they control processes ranging from metabolism and stress adaptation to mating, virulence, and antifungal resistance. Here, we have identified the gene CaORF19.1604 as encoding a zinc cluster transcription factor that acts as a regulator of filament development. Hyperactivation of CaORF19.1604, which we have named RHA1 for Regulator of Hyphal Activity, leads to a wrinkled colony morphology under non-hyphal growth conditions, to pseudohyphal growth and filament formation, to invasiveness and enhanced biofilm formation. Cells with activated Rha1 are sensitive to cell wall modifying agents such as Congo red and the echinocandin drug caspofungin but show normal sensitivity to fluconazole. RNA-sequencing-based transcriptional profiling of the activated Rha1 strain reveals the up-regulation of genes for core filamentation and cell-wall-adhesion-related proteins such as Als1, Als3, Ece1, and Hwp1. Upregulation is also seen for the genes for the hyphal-inducing transcription factors Brg1 and Ume6 and genes encoding several enzymes involved in arginine metabolism, while downregulation is seen for the hyphal repressor Nrg1. The deletion of BRG1 blocks the filamentation caused by activated Rha1, while null mutants of UME6 result in a partial block. Deletion of RHA1 can partially reduce healthy hyphal development triggered by environmental conditions such as Spider medium or serum at 37{degrees}C. In contrast to the limited effect of either single mutant, the double rha1 ume6 deletion strain is totally defective in both serum and Spider medium stimulated hyphal development. While the loss of Brg1 function blocks serum-stimulated hyphal development, this block can be significantly bypassed by Rha1 hyperactivity, and the combination of Rha1 hyperactivity and serum addition can generate significant polarization in even brg1 ume6 double mutants. Our results thus suggest that in response to external signals, Rha1 functions to facilitate the switch from an Nrg1 controlled yeast state to a Brg1/Ume6 regulated hyphal state. Author SummaryCandida albicans is the predominant human fungal pathogen, generating a mortality rate of 40% in systemically infected patients. The ability of Candida albicans to change its morphology is a determinant of its tissue penetration and invasion in response to variant host-related stimuli. The regulatory mechanism for filamentation includes a complex network of transcription factors that play roles in regulating hyphae associated genes. We identify here a new regulator of filamentation from the zinc cluster transcription factor family. We present evidence suggesting that this transcription factor assists the Nrg1/Brg1 switch regulating hyphal development.

microbiology↗

bioRxiv2018

Small interfering RNAs based on huntingtin trinucleotide repeats are highly toxic to cancer cells

Trinucleotide repeat (TNR) expansions in the genome cause a number of degenerative diseases. A prominent TNR expansion involves the triplet CAG in the huntingtin (HTT) gene responsible for Huntingtons disease (HD). Pathology is caused by protein and RNA generated from the TNR regions including small siRNA-sized repeat fragments. An inverse correlation between the length of the repeats in HTT and cancer incidence has been reported for HD patients. We now show that siRNAs based on the CAG TNR are toxic to cancer cells by targeting genes that contain long reverse complimentary TNRs in their open reading frames. Of the 60 siRNAs based on the different TNRs, the 6 members in the CAG/CUG family of related TNRs are the most toxic to both human and mouse cancer cells. siCAG/CUG TNR-based siRNAs induce cell death in vitro in all tested cancer cell lines and slow down tumor growth in a preclinical mouse model of ovarian cancer with no signs of toxicity to the mice. We propose to explore TNR-based siRNAs as a novel form of anti-cancer reagents.

cancer biology↗