Biology subjects

Altmann, J.

Publications and source records attributed to Altmann, J..

5 recordsLinked to original sources

bioRxiv2025

An organotypic in vitro model of human papillomavirus-associated precancerous lesions allowing automated cell quantification for preclinical drug testing

Summary and graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=176 SRC="FIGDIR/small/661539v1_ufig1.gif" ALT="Figure 1"> View larger version (69K): org.highwire.dtl.DTLVardef@11e0c27org.highwire.dtl.DTLVardef@1affaf8org.highwire.dtl.DTLVardef@85c10forg.highwire.dtl.DTLVardef@145d491_HPS_FORMAT_FIGEXP M_FIG C_FIG O_LIA durable organotypic epithelial raft culture was established as a model of cervical precancer. C_LIO_LIPlausible time- and dose-dependent effects of cisplatin, 5-FU, and sinecatechins treatment were observed on keratinocytes and HPV-transformed cells. C_LIO_LITreatment effects were reliably quantified using machine learning-based cell classification. C_LIO_LIThis model may serve as a platform for preclinical investigation of topical and systemic treatment. C_LI Oncogenic human papillomaviruses (HPV) are causally responsible for invasive cancers and precancerous lesions. These lesions represent a considerable disease burden worldwide, yet no causally effective treatments are available. The development of HPV tumor models realistically reflecting the in vivo treatment situation is necessary for finding new effective and tissue-sparing treatments. This study aimed to establish an in vitro model of HPV-induced precancerous lesions for preclinical drug testing and to provide an automated method for quantifying cell counts to assess treatment effects in this model. To establish organotypic epithelial raft cultures (OTCs) as a model of HPV-induced precancerous lesions, we cultivated HPV-transformed cervical cancer cell lines SiHa, CaSki, HeLa, and SW756 in conjunction with primary human keratinocytes on a dermal equivalent and evaluated the impact of different cultivation variables. To demonstrate suitability of our model for preclinical drug application studies, we applied 5-fluorouracil, sinecatechins, and cisplatin either onto the air-exposed surface or to the growth medium, mimicking topical and systemic drug administration routes. We then developed a machine learning-based approach to quantify cell counts reflecting treatment effects in the established OTCs. We successfully optimized a durable in vitro model of HPV-induced precancerous lesions. The model enabled monitoring of treatment effects in a three-dimensional context with differentiated consideration of the targeted HPV-transformed cells and surrounding normal epithelium. We demonstrated that extreme gradient boosted tree classifiers (XGBoost) can be successfully used to distinguish the number of tumor cells, normal keratinocytes, and degraded cells with high accuracy (81.8{+/-}8%; P=2x10-6). Critically, quantification results plausibly reflected microscopical observations and gave a fine-grained picture of time- and dose-dependent treatment effects. The established model in combination with automated cell quantification can serve as a valuable tool in analyzing major preclinical endpoints in in vitro studies, such as target cell treatment efficacy, potential side effects, and treatment schedule optimization.

cancer biology↗

bioRxiv2022

Five decades of data yield no support for adaptive biasing of offspring sex ratio in wild baboons (Papio cynocephalus)

Over the past 50 years, a wealth of testable, often conflicting, hypotheses have been generated about the evolution of offspring sex ratio manipulation by mothers. Several of these hypotheses have received support in studies of invertebrates and some vertebrate taxa. However, their success in explaining sex ratios in mammalian taxa, and especially in primates, has been mixed. Here, we assess the predictions of four different hypotheses about the evolution of biased offspring sex ratios in the well-studied baboons of the Amboseli basin in Kenya: the Trivers-Willard, female rank enhancement, local resource competition, and local resource enhancement hypotheses. Using the largest sample size ever analyzed in a primate population (n = 1372 offspring), we test the predictions of each hypothesis. Overall, we find no support for adaptive biasing of sex ratios. Offspring sex is not consistently related to maternal dominance rank or biased towards the dispersing sex, nor it is predicted by group size, population growth rates, or their interaction with maternal rank. Because our sample size confers power to detect even subtle biases in sex ratio, including modulation by environmental heterogeneity, these results suggest that adaptive biasing of offspring sex does not occur in this population.

evolutionary biology↗

bioRxiv2020

Beyond orphaned infants: novel effects of maternal death in wild primates

Primate offspring often depend on their mothers well beyond the age of weaning, and offspring that experience maternal death in early life can suffer substantial reductions in fitness across the lifespan. Here we leverage data from eight wild primate populations (seven species) to examine two underappreciated pathways linking early maternal death and offspring fitness that are distinct from direct effects of orphaning on offspring survival. First, we show that, for five of the seven species, offspring face reduced survival during the years immediately preceding maternal death, while the mother is still alive. Second, we identify an intergenerational effect of early maternal loss in three species (muriquis, baboons, and blue monkeys), such that early maternal death experienced in one generation leads to reduced offspring survival in the next. Our results have important implications for the evolution of slow life histories in primates, as they suggest that maternal condition and survival are more important for offspring fitness than previously realized.

evolutionary biology↗

bioRxiv2020

Comparing proportional and ordinal dominance ranks reveals multiple competitive landscapes in an animal society

Across group-living animals, linear dominance hierarchies lead to disparities in access to resources, health outcomes, and reproductive performance. Studies of how dominance rank affects these outcomes typically employ one of several dominance rank metrics without examining the assumptions each metric makes about its underlying competitive processes. Here we compare the ability of two dominance rank metrics--ordinal rank and proportional or standardized rank--to predict 20 distinct traits in a well-studied wild baboon population in Amboseli, Kenya. We propose that ordinal rank best predicts outcomes when competition is density-dependent, while proportional rank best predicts outcomes when competition is density-independent. We found that for 75% (15/20) of the traits, one of the two rank metrics performed better than the other. Strikingly, all male traits were better predicted by ordinal than by proportional rank, while female traits were evenly split between being better predicted by proportional or ordinal rank. Hence, male and female traits are shaped by different competitive regimes: males competitive environments are largely driven by density-dependent resource access (e.g., access to estrus females), while females competitive environments are shaped by both density-independent resource access (e.g. distributed food resources) and density-dependent resource access. However, traits related to competition for social and mating partners are an exception to this sex-biased pattern: these traits were better predicted by ordinal rank than by proportional rank for both sexes. We argue that this method of comparing how different rank metrics predict traits of interest can be used as a way to distinguish between different competitive processes operating in animal societies.

animal behavior and cognition↗

bioRxiv2019

Intergenerational effects of early adversity on survival in wild baboons

In humans and nonhuman animals, early life adversity can affect an individuals health, survival, and fertility for many years after the adverse experience. However, whether early life adversity also imposes intergenerational effects on the exposed individuals offspring is not well understood. Here, we fill this gap by leveraging prospective, longitudinal data on a wild, long-lived primate. We find that juveniles whose mothers experienced early life adversity exhibit high mortality before age 4, and this effect is independent of the juveniles own experience of early adversity. Furthermore, our results point towards a strong role for classic parental effects in driving these effects: mothers that experienced early life adversity displayed reduced viability in adulthood, which in turn led to reductions in offspring survival. Importantly, these mothers juvenile offspring often preceded them in death by 1 to 2 years, indicating that, for high adversity mothers, the quality of maternal care declines near the end of life. While we cannot exclude direct effects of a parents environment on offspring quality (e.g., transgenerational epigenetic changes), our results are most consistent with a classic parental effect, in which the environment experienced by a parent affects its future phenotype and therefore its offsprings phenotype. Together, our findings demonstrate that adversity experienced by individuals in one generation can have strong effects on the survival of offspring in the next generation, even if those offspring did not themselves experience early adversity.

zoology↗