Biology subjects

Ott, S. R.

Publications and source records attributed to Ott, S. R..

5 recordsLinked to original sources

bioRxiv2026

MTAP deficiency is a novel biomarker in neuroendocrine neoplasms of the lung

IntroductionMTAP emerges as potential predictive biomarker for MTA-cooperative PRMT5-inhibitors. Although MTAP attracts increasing attention in non-small cell lung cancer, its role in pulmonary neuroendocrine neoplasms (NENs) remains largely unexplored. MethodsHere, we assessed the prevalence of MTAP deficiency in 209 pulmonary NENs using immunohistochemistry (IHC). Additionally, we performed fluorescence in situ hybridization (FISH), whole exome sequencing (WES), deep proteomic profiling, transcriptomic, and methylation analyses of selected MTAP deficient and proficient carcinoids to further elucidate the underlying mechanisms of MTAP expression pattern. ResultsMTAP deficiency by IHC was detected in all neuroendocrine precursor lesions (n=17), 92% of typical carcinoids (n=51), 86% of atypical carcinoids (n=21), and 10% of large cell neuroendocrine carcinomas (LCNEC) (n=30). In contrast, all small cell lung cancers (SCLC) were MTAP proficient (n=90). In MTAP deficient carcinoids, FISH and WES did not detect homozygous 9p21 deletions, and methylation analysis showed no evidence of MTAP promoter hypermethylation. Comparing MTAP deficient and MTAP proficient carcinoids, proteomic data showed a clear separation between the two groups. Further, there was an inverse correlation between the expression of MTAP and OTP (orthopedia homeobox protein), which is known as a strong prognostic marker in pulmonary carcinoids. DiscussionMTAP deficiency is a novel hallmark of neuroendocrine precursors and most pulmonary carcinoids, clearly distinguishing the latter from SCLC and most LCNEC. It is neither caused by 9p21 deletion, nor by MTAP promoter hypermethylation. MTAP deficiency is a group-defining feature of carcinoids that might pave the way for new therapeutic approaches.

pathology↗

bioRxiv2024

A neural correlate of learning fails to predict foraging efficiency in Bombus terrestris.

The mushroom bodies (MB) are integrative structures in the insect brain that, in social bees, contribute to both visual and olfactory learning. Changes in the density of presynaptic boutons (or microglomeruli) within the calyx region of the MB have been repeatedly linked to various aspects of foraging, including forms of learning that are thought to be key to support foraging efficiency. Here we set out to directly test the relationship between foraging efficiency and microglomerulus density in a bumblebee model, Bombus terrestris. We found no evidence that microglomerulus density predicted real-world foraging performance, nor any relationship with foraging experience. Instead, our data suggest a potential non-linear relationship between individual age, independent of foraging experience, and microglomerulus density in the lip region of the calyx, which is associated with olfactory processing. Our findings suggest that in real-world scenarios there is no simple direct relationship between microglomerular density, learning ability and foraging efficiency in bumblebees, highlighting the gap in knowledge regarding the relationships between learning abilities, neuroanatomy and foraging efficiency.

animal behavior and cognition↗

bioRxiv2020

Plasticity of behavioural variability reflects conflicting selection in group-living and solitary desert locusts

Animals living in groups tend to express less variable behaviour than animals living alone. It is widely assumed that this difference reflects, at least in part, an adaptive response to contrasting selection pressures: group-living should favour the evolution of more uniform behaviour whereas lone-living should favour behaviour that is less predictable. Empirical evidence linking these contrasting selection pressures to intrinsic differences in behavioural variability is, however, largely lacking. The desert locust, Schistocerca gregaria, manifests in two very distinct eco-phenotypes, a lone-living cryptic "solitarious phase" and a swarming "gregarious phase" that aggregates into very large and dense groups. This "phase polyphenism" has evolved in response to contrasting selection pressures that change rapidly and unpredictably. Phase differences in mean behaviour are well-characterised, but no previous study has considered differences in variability. Here we used locust phase polyphenism to test the hypothesis that group living leads to the evolution of reduced intrinsic variability in behaviour. We measured two behaviours in both phenotypes: locomotor activity in the presence of conspecifics, and locomotor hesitation in approaching food when alone. We assayed each individual repeatedly and estimated variability relative to the mean in log-normal mixed-effects models that explicitly account for the means-variance dependency in the behavioural measures. Our results demonstrate that relative behavioural variability differs between the two phases in line with predictions from ecological theory: both within-individual and between-individual variability were lower in the group-living gregarious phenotype. This contrasts with previous studies on social niche construction in spiders and crickets, and highlights the importance of social ecology: in animals that form non-social collectives, such as locusts, reduced individual behavioural variability is key for coherent collective behaviour. The differences in variability persisted when gregarious locusts were tested in isolation and solitarious locusts were tested in groups, indicating that they arise not simply as flexible reactions to different social contexts, but are intrinsic to the individual animals of each phase. This "variance polyphenism" in locusts provides empirical evidence that evolutionary adaptation for group living has driven a reduction in within- and between-individual behavioural variability.

ecology↗

bioRxiv2019

Malpighamoeba infection compromises fluid secretion and P-glycoprotein detoxification in Malpighian tubules

Malpighian tubules, analogous to vertebrate nephrons, play a key role in insect osmoregulation and detoxification. Tubules can become infected with a protozoan, Malpighamoeba, which damages their epithelial cells, potentially compromising their function. Here we used a modified Ramsay assay to quantify the impact of Malpighamoeba infection on fluid secretion and P-glycoprotein-dependent detoxification by desert locust Malpighian tubules. Infected tubules have a greater surface area and a higher fluid secretion rate than uninfected tubules. Infection also impairs P-glycoprotein-dependent detoxification by reducing the net rhodamine extrusion per surface area. However, due to the increased surface area and fluid secretion rate, infected tubules have similar total net extrusion per tubule to uninfected tubules. Increased fluid secretion rate of infected tubules likely exposes locusts to greater water stress and increased energy costs. Coupled with reduced efficiency of P-glycoprotein detoxification per surface area, Malpighamoeba infection is likely to reduce insect survival in natural environments.

physiology↗

bioRxiv2017

Regressions Fit for Purpose: Models of Locust Phase State Must Not Conflate Morphology With Behaviour

Locusts are defined by their capacity to transform between two very distinct integrated phenotypes or phases in response to changes in population density: a solitarious phase, which occurs when densities are low, and a gregarious phase, which arises as a consequence of crowding and can form very large and economically damaging swarms. The two phases differ fundamentally in their behaviour, physiology and morphology. A large body of work on the mechanistic basis of behavioural phase transitions has relied on multivariate logistic regression (LR) models to estimate the probability of behavioural gregariousness from multiple behavioural variables. Martin-Blazquez and Bakkali (2017, Entomologia Experimentalis et Applicata 163, 9-25) have recently proposed standardised LR models for estimating an overall gregariousness level from a combination of behavioural and, unusually, morphometric variables. Here I develop a detailed argument to demonstrate that the premise of such an overall gregariousness level is fundamentally flawed. Since locust phase transformations intrinsically entail a decoupling of behaviour and morphology, phase state cannot meaningfully be conflated onto a single axis. LR models that do so are therefore of very limited value for any analysis of phase transitions. I furthermore show why behavioural predictor variables should not be adjusted by measures of body size that themselves differ between phases. I discuss the models fitted by Martin-Blazquez and Bakkali (2017) to highlight potential pitfalls in statistical methodology that must be avoided when applying LR to the analysis of behavioural phase state. Finally, I reject the idea that standardised models provide a valid shortcut to estimating phase state across different developmental stages, strains or species. The points addressed here are pertinent to any research on transitions between complex phenotypes and behavioural syndromes.

animal behavior and cognition↗