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Biology subjects

Robertson, C.

Publications and source records attributed to Robertson, C..

9 recordsLinked to original sources

Motivational trade-offs in a cockroach: impact of conditions, injury, and development

The ability to flexibly trade off access between competing or antagonistic stimuli ("motivational trade-offs") is a key criterion for assessing whether animals can feel pain. However, in some commonly farmed, exterminated, and studied insect orders such as Blattodea (cockroaches and termites), the ability to make motivational trade-offs is unconfirmed, which makes it difficult to assess their welfare needs. Here we gave cockroaches (Blaptica dubia) a choice between access to shelter or to nutrition across a series of linked experiments to assess whether they are capable of motivational trade-offs and if they are flexibly adjusted due to external conditions and/or injury and develop across ontogeny. We found cockroaches avoided a food reward when it was exposed to light (a behavioural trade-off), but they did not adjust their preference flexibly in response to lighting intensity or increased hunger level (no motivational trade-off). We did find that injury reduces willingness to accept light exposure when accessing nutrition, which is consistent with the idea of the sensation of pain reducing risk-taking behaviour. Finally, we showed that juvenile cockroaches match adults in not making a motivational trade-off. All together our results provide much-needed evidence for criteria of whether insects feel pain and suggest upper limits to cognitive complexity and flexibility in Blattodea. These findings can be integrated with other neurological and behavioural measures to help us judge how we treat insects and other invertebrates in our care.

animal behavior and cognition↗

Supergene control of chiral development in mirror-image flowers

How genes determine the left-versus right-handed development of chiral structures is a fascinating question. The reciprocal placement of female and male organs on opposite sides of the midline in mirror-image flowers limits selfing and promotes efficient cross-pollination. Here we identify the molecular and developmental basis of floral handedness in butterfly lilies. Female and male organs deflect by a combination of genetically controlled chirality and gravitropism, orienting left and right with respect to an external rather than internal reference axis. Coordinated organ placement is controlled by a hemizygous supergene containing two causal loci, MIR156-R and YUCCA-R, responsible for opposite female and male organ orientation, respectively. This genomic architecture results in differential placement of the supergene alleles on the pollinators and maintenance of the reproductive polymorphism.

plant biology↗

Style deflection is determined by the handedness of phyllotaxis and differential cell elongation in a species with mirror-image flowers

Many animals and plants show left-right (LR) asymmetry. In some animal systems, handedness has a simple genetic basis, which has allowed identifying how handedness is determined at the molecular level, even if its functional relevance often remains unclear. Mirror-image flowers represent an example of LR asymmetry of clear functional significance, with the reciprocal placement of male and female organs in left- versus right-handed flowers promoting cross-pollination. Here, we use the South African geophyte Cyanella alba to study how handedness of its mirror-image flowers is determined and elaborated during development. Inflorescences of C. alba produce flowers with a largely consistent handedness. However, we find that this handedness has no simple genetic basis, and individual plants can switch their predominant handedness between years. Rather, it is the direction of the phyllotactic spiral that determines floral handedness. Cellular analysis combined with biophysical modelling demonstrates that style deflection is driven by increased cell expansion in the adaxial carpel facing the next oldest flower compared to the other adaxial carpel. The more expanding carpel shows transcriptional signatures of increased auxin signaling compared to the less expanding one, and auxin application to the latter can reverse the orientation of style deflection. We propose that a recently described inherent LR auxin asymmetry in the initiating organs of spiral phyllotaxis determines handedness in C. alba, representing a conserved non-genetic mechanism for creating a stable floral polymorphism. This mechanism links chirality across different levels of plant development and exploits a developmental constraint in a core patterning process to produce morphological variation of ecological relevance.

plant biology↗

Microbiota-dependent indole production is required for the development of collagen-induced arthritis

Altered tryptophan catabolism has been identified in inflammatory diseases like rheumatoid arthritis (RA) and spondyloarthritis (SpA), but the causal mechanisms linking tryptophan metabolites to disease are unknown. Using the collagen-induced arthritis (CIA) model we identify alterations in tryptophan metabolism, and specifically indole, that correlate with disease. We demonstrate that both bacteria and dietary tryptophan are required for disease, and indole supplementation is sufficient to induce disease in their absence. When mice with CIA on a low-tryptophan diet were supplemented with indole, we observed significant increases in serum IL-6, TNF, and IL-1{beta}; splenic ROR{gamma}t+CD4+ T cells and ex vivo collagen-stimulated IL-17 production; and a pattern of anti-collagen antibody isotype switching and glycosylation that corresponded with increased complement fixation. IL-23 neutralization reduced disease severity in indole-induced CIA. Finally, exposure of human colon lymphocytes to indole increased expression of genes involved in IL-17 signaling and plasma cell activation. Altogether, we propose a mechanism by which intestinal dysbiosis during inflammatory arthritis results in altered tryptophan catabolism, leading to indole stimulation of arthritis development. Blockade of indole generation may present a novel therapeutic pathway for RA and SpA.

immunology↗

Aging-associated augmentation of gut microbiome virulence capability drives sepsis severity.

Prior research has focused on host factors as mediators of exaggerated sepsis-associated morbidity and mortality in older adults. This focus on the host, however, has failed to identify therapies that improve sepsis outcomes in the elderly. We hypothesized that the increased susceptibility of the aging population to sepsis is not only a function of the host, but also reflects longevity-associated changes in the virulence of gut pathobionts. We utilized two complementary models of gut microbiota-induced experimental sepsis to establish the aged gut microbiome as a key pathophysiologic driver of heightened disease severity. Further murine and human investigations into these polymicrobial bacterial communities demonstrated that age was associated with only subtle shifts in ecological composition, but an overabundance of genomic virulence factors that have functional consequence on host immune evasion. One Sentence SummaryThe severity of sepsis in the aged host is in part mediated by longevity-associated increases in gut microbial virulence.

microbiology↗

Investigating the growth of an engineered strain of Cyanobacteria with an Agent-Based Model and a Recurrent Neural Network

A computational framework combining Agent-Based Models (ABMs) and Deep Learning techniques was developed to help design microbial communities that convert light and CO2 into useful bioproducts. An ABM that accounts for CO2, light, sucrose export rate and cell-to-cell mechanical interactions was used to investigate the growth of an engineered sucrose-exporting strain of Synechococcus elongatus PCC 7942. The ABM simulations produced population curves and synthetic images of colony growth. The curves and the images were analyzed, and growth was correlated to nutrients availability and colonies initial spatial distribution. To speed up the ABM simulations, a metamodel based on a Recurrent Neural Network, RNN, was trained on the synthetic images of growth. This metamodel successfully reproduced the population curves and the images of growth at a lower computational cost. The computational framework presented here paves the road towards designing microbial communities containing sucrose-exporting Synechococcus elongatus PCC 7942 by exploring the solution space in silico first.

microbiology↗

Nanolipoprotein mediated Her2 protein transfection induces malignant transformation in human breast acinar cultures

Her2 overexpression is associated with an aggressive form of breast cancer and malignant transformation. We sought to determine if a nano-carrier system could introduce Her2 protein to non-malignant cells and determine the effects on cell phenotype and transcriptome. With stimulation with Her2-NLPs, we observed uptake of Her2 protein and a decreased probability of individual non-malignant cells forming polar growth arrested acinar-like structures. The NLP delivery system alone or Her2-NLPs plus trastuzumab showed no effect on acinar organization rate. Transcriptomics revealed essentially no effect of empty NLPs versus untreated cells whereas Her2-NLPs versus either untreated or empty NLP treated cells revealed upregulation of several factors associated with breast cancer. Pathway analysis also suggested that known nodes downstream of Her2 were activated in response to Her2-NLP treatment. This suggests that Her2-NLPs are sufficient for malignant transformation of non-malignant cells and that this system offers a new model for studying cell surface receptor signaling without genomic modification or transformation techniques.

cancer biology↗

The human UDP-galactose 4’-epimerase (GALE) is required for cell surface glycome structure and function

Glycan biosynthesis relies on nucleotide-sugars (NS), abundant metabolites that serve as monosaccharide donors for glycosyltransferases. In vivo, signal-dependent fluctuations in NS levels are required to maintain normal cell physiology and are dysregulated in disease, but how mammalian cells regulate NS levels and pathway flux remains largely uncharacterized. To address this knowledge gap, we examined uridine diphosphate (UDP)-galactose 4-epimerase (GALE), which interconverts two pairs of essential NSs. GALE deletion in human cells triggered major imbalances in its substrate NSs and consequent dramatic changes in glycolipids and glycoproteins, including a subset of integrins and the Fas death receptor. NS dysregulation also directly impacted cell signaling, as GALE-/- cells exhibit Fas hypoglycosylation and hypersensitivity to Fas ligand-induced apoptosis. Our results reveal a new role for GALE-mediated NS regulation in supporting death receptor signaling and may have implications for the molecular etiology of illnesses characterized by NS imbalances, including galactosemia and metabolic syndrome.

cell biology↗

The microstructure of laminin-111 compensates for dystroglycan loss in functional differentiation of mammary epithelial cells

AbstractLaminin-111, an extracellular matrix (ECM) glycoprotein found in the basement membrane of mammary gland epithelia, is essential for lactation. In mammary epithelial cells, dystroglycan (Dg) is believed to be necessary for polymerization of laminin-111 into networks, thus we asked whether correct polymerization could compensate for Dg loss. Artificially polymerized laminin-111 and the laminin-glycoprotein mix Matrigel, both formed branching, spread networks with fractal dimensions from 1.7-1.8, whereas laminin-111 in media formed small aggregates without fractal properties (a fractal dimension of 2). In Dg knockout cells, either polymerized laminin-111 or Matrigel readily attached to the cell surface, whereas aggregated laminin-111 did not. In contrast, polymerized and aggregated laminin-111 bound similarly to Dg knock-ins. Both polymerized laminin-111 and Matrigel promoted cell rounding, clustering, formation of tight junctions, and expression of milk proteins, whereas aggregated Ln-1 did not attach to cells or promote functional differentiation. HighlightsO_LILaminin assembles into a fractal network when in presence of either the cell surface receptor dystroglycan or acidic glycoproteins or an acidic buffer. C_LIO_LIWhen this microstructure is recreated with an acidic treatment, laminin binds readily to dystroglycan null cells and induces functional differentiation of mammary epithelial cells. C_LI

bioengineering↗