Biology subjects

Bustamante, S.

Publications and source records attributed to Bustamante, S..

5 recordsLinked to original sources

bioRxiv2026

Aging disrupts cumulus-oocyte NAD homeostasis

The age-related decline in oocyte nicotinamide adenine dinucleotide (NAD) is associated with reduced developmental potential and female infertility. Despite the extraordinary longevity of the female germline, the mechanism for maintaining oocyte NAD remains unresolved. Here, we used stable isotope tracing to identify a new mechanism for shared, intercellular NAD biosynthesis, whereby somatic-germline metabolic coupling between the oocyte and its surrounding cumulus cells is critical to maintain oocyte NAD homeostasis. We show that this coupling deteriorates with reproductive aging, identifying altered NAD metabolism in cumulus cells from mice and women of advancing reproductive age. This cumulus-oocyte metabolic coupling of NAD biosynthesis contributes to protection against the age-related increases in oocyte reactive oxygen species (ROS). In intact complexes, restoring NAD through supplementation with the precursor nicotinamide mononucleotide (NMN) increased glutathione, reduced ROS and improved mitochondrial membrane potential in oocytes from aged mice and in oocytes exposed to oxidative insult. Importantly, the ability of NMN to resolve elevated ROS depends on the presence of cumulus cells. Together, this new model of somatic-germline metabolic coupling of NAD biosynthesis places an age-related deterioration in cumulus cell-mediated metabolic support as a key driver of impaired oocyte NAD levels and redox dysregulation with aging.

cell biology↗

bioRxiv2024

The Interplay of Ecological Opportunity and Adult Foraging Strategies in Juvenile Sparrow Individual Specialization

Temporal variation in resource availability, amplified by global change, may have strong impacts on species breeding at temperate and high latitudes that cue their reproduction to exploit seasonal resource pulses. This study examines how resource availability and parental care influence niche partitioning between and within age classes in the rufous-collared sparrow, which provides extensive parental care. We hypothesized juveniles would exhibit narrower niches focused on high-quality resources compared to adults, regardless of resource availability. We used stable isotope analysis to quantify individual and population niches in juveniles and adults across the breeding season in two cohorts experiencing contrasting resource landscapes. Contrary to our initial hypothesis, juveniles exhibited greater among individual diet variation and smaller total niche widths (i.e., higher levels of individual specialization) during periods of high food availability in comparison to periods of food scarcity. Interestingly, total niche width and individual specialization of adults remained stable across seasons despite a shift in trophic level, highlighting their potential role in providing a consistent diet for their young. These findings reveal a dynamic interplay between resource availability, parental care, and individual specialization, with important implications for understanding population resilience under variable resource scenarios. The study also suggests that adult sparrows modify their provisioning strategies based on resources, potentially buffering offspring from environmental fluctuations. Understanding age-specific responses to resource variation is crucial for predicting species responses to ecological conditions, particularly in regions like central Chile where seasonal resource limitation is expected to become more variable in response to climate change.

ecology↗

bioRxiv2022

Oocyte and cumulus cell cooperativity and metabolic plasticity under the direction of oocyte paracrine factors

Mammalian oocytes develop and mature in a mutually dependent relationship with surrounding cumulus cells. The oocyte actively regulates cumulus cell differentiation and function by secreting soluble paracrine oocyte-secreted factors (OSFs). We characterized the molecular mechanisms by which two model OSFs, cumulin and BMP15, regulate oocyte maturation and cumulus-oocyte cooperativity. Exposure to these OSFs during maturation altered the proteomic and multispectral autofluorescence profiles of both the oocyte and cumulus cells. In oocytes, cumulin significantly upregulated proteins involved in nuclear function. In cumulus cells, both OSFs elicited marked upregulation of a variety of metabolic processes (mostly anabolic), including lipid, nucleotide, and carbohydrate metabolism, while mitochondrial metabolic processes were downregulated. The mitochondrial changes were validated by functional assays confirming altered mitochondrial morphology, respiration, and content, whilst maintaining ATP homeostasis. Collectively, these data demonstrate that OSFs remodel cumulus cell metabolism during oocyte maturation in preparation for ensuing fertilization and embryonic development. HIGHLIGHTSO_LIDuring oocyte maturation, oocyte-secreted factors promote cell cooperativity between the oocyte and cumulus cells by altering the molecular composition of both cell types. C_LIO_LIOocyte-secreted factors downregulate protein catabolic processes, and upregulate DNA binding, translation, and ribosome assembly in oocytes. C_LIO_LIOocyte-secreted factors alter mitochondrial number, morphology, and function in cumulus cells. C_LIO_LIOocyte-secreted factors further enhance metabolic plasticity in cumulus cells by upregulating anabolic pathways for macromolecules and small molecule organics. C_LIO_LIThe oocyte, via oocyte-secreted factors, instructs cumulus cells to increase metabolic workload on its behalf, thereby subduing oocyte metabolism. C_LI

developmental biology↗

bioRxiv2022

Neuronal growth regulator 1 (NEGR1) promotes synaptic targeting of glutamic acid decarboxylase 65 (GAD65)

Neuronal growth regulator 1 (NEGR1) is a glycosylphosphatidylinositol-anchored cell adhesion molecule encoded by an obesity susceptibility gene. We demonstrate that NEGR1 accumulates in GABAergic inhibitory synapses in hypothalamic neurons, a GABA-synthesizing enzyme GAD65 attaches to the plasma membrane, and NEGR1 promotes clustering of GAD65 at the synaptic plasma membrane. GAD65 is removed from the plasma membrane with newly formed vesicles. The association of GAD65 with vesicles results in increased GABA synthesis. In NEGR1 deficient mice, the synaptic targeting of GAD65 is decreased, the GABAergic synapse densities are reduced, and the reinforcing effects of food rewards are blunted. In mice fed a high fat diet, levels of NEGR1 are increased and GAD65 abnormally accumulates at the synaptic plasma membrane. Our results indicate that NEGR1 regulates a previously unknown step required for synaptic targeting and functioning of GAD65, which can be affected by bidirectional changes in NEGR1 levels causing disruptions in the GABAergic signaling controlling feeding behavior.

neuroscience↗

bioRxiv2020

Desert Dingo (Canis lupus dingo) genome provides insights into their role in the Australian ecosystem.

The dingo is Australias iconic top-order predator and arrived on the continent between 5,000-8,000 years ago. To provide an unbiased insight into its evolutionary affiliations and biological interactions, we coupled long-read DNA sequencing with a multiplatform scaffolding approach to produce an ab initio genome assembly of the desert dingo (85X coverage) we call CanLup_DDS. We compared this genome to the Boxer (CanFam3.1) and German Shepherd dog (CanFam_GSD) assemblies and characterized lineage-specific and shared genetic variation ranging from single- to megabase pair-sized variants. We identified 21,483 dingo-specific and 16,595 domestic dog-specific homozygous structural variants mediating genic and putative regulatory changes. Comparisons between the dingo and domestic dog builds detected unique inversions on Chromosome 16, structural variations in genes linked with starch metabolism, and seven differentially methylated genes. To experimentally assess genomic differences 17 dingoes and 15 German Shepherd dogs were fed parallel diets for 14 days. In dingoes, low AMY2B copy number and serum amylase levels are linked with high cholesterol and LDL levels. Gut microbiome analyses revealed enrichment of the family Clostridiaceae, which can utilize complex resistant starch, while scat metabolome studies identified high phenylethyl alcohol concentrations that we posit are linked with territory marking. Our study provides compelling genomic, microbiome, and metabolomic links showing the dingo has distinct physiology from domestic breed dogs with a unique role in the ecosystem.

genomics↗