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Rubin, G.

Publications and source records attributed to Rubin, G..

3 recordsLinked to original sources

Evolutionary trade-offs between growth and reproduction under obesogenic conditions: sex-biased skeletal and gonadal maturation in mice

Adolescence is a brief period during which finite energy resources are reallocated from linear growth toward reproductive maturation. Rising childhood obesity and earlier onset of puberty suggest that modern, energy rich diets may distort these evolved energy allocation rules, but causal mechanisms remain unclear. Here, we expose male and female wild-type and leptin receptor deficient (Db/Db) to either high fat or normal chow diets. We longitudinally analyze metabolic, skeletal, gonadal, endocrine and insulin-receptor phenotypes from 4-10 weeks of age (sexual maturation window in mice). In WT males, HFDs increased adiposity and impaired glucose tolerance, and selectively remodeled joint morphology, advanced gonadal maturation, and shifted insulin receptor expression from growth plates to testes. Together, these changes indicate a rebalancing of energy use toward reproduction at the expense of skeletal and metabolic health. WT females showed subtler systemic metabolic disruption but clear diet-responsive changes in growth plate and ovarian maturation. Our findings indicate that energy-rich diets during adolescence shift evolved allocation rules to prioritize reproductive readiness over skeletal robustness in a sex-dependent manner, with potential consequences for precocious puberty and bone health in humans.

evolutionary biology↗

Early-life microbiota disruption by antibiotics elicits fitness trade-offs that differ by sex

Exposure to early-life antibiotics (ELA) promotes adult obesity across diverse species, often more strongly in males than females1-3. However, the physiological and evolutionary mechanisms driving ELA-mediated developmental plasticity and their consequences for fitness remain unclear3. Here, treating young mice with high- or low-dose ampicillin altered the gut microbiome and elicited reduced lean mass and energy expenditure in males to promote increased adult visceral adiposity. High-dose ELA constrained energy availability during treatment, evidenced by reduced growth and cecal short-chain fatty acids, raising the possibility that developmental plasticity under ELA could be adaptive in energy-limited environments. Adult ELA-treated males had reduced fitness under free-fed conditions -- driven by smaller body size, fat stores, and impaired immunity -- but were buffered against fitness reductions under caloric restriction, consistent with predictive adaptive response models of development4,5. Strikingly, ELA-treated females exhibited none of the proximate metabolic responses observed in males, with adult body size and composition indistinguishable from controls. In the absence of similar developmental plasticity, ELA-treated females exhibited exacerbated fitness reductions under caloric restriction, including lower energetic investments in reproduction and immunity. Our results suggest that ELA exposure elicits sexually dimorphic developmental responses that engender long-term health and fitness consequences dependent on adult nutritional conditions.

evolutionary biology↗

Neurogenetic dissection of the Drosophila innate olfactory processing center

Animals exhibit innate behaviours in response to a variety of sensory stimuli such as olfactory cues. In Drosophila, a higher olfactory centre called the lateral horn (LH) is implicated in innate behaviour. However, our knowledge of the structure and function of the LH is scant, due to the lack of sparse neurogenetic tools for this brain region. Here we generate a collection of split-GAL4 driver lines providing genetic access to 82 LH cell-types. We identify the neurotransmitter and axo-dendritic polarity for each cell-type. Using these lines were create an anatomical map of the LH. We found that [~]30% of LH projections converge with outputs from the mushroom body, the site of olfactory learning and memory. Finally, using optogenetic activation of small groups of LH neurons. We identify cell-types that drive changes in either valence or specific motor programs, such as turning and locomotion. In summary we have generated a resource for manipulating and mapping LH neurons in both light and electron microscopy and generated insights into the anatomy and function of the LH.

neuroscience↗