Biology subjects

Chia, S. Y.

Publications and source records attributed to Chia, S. Y..

3 recordsLinked to original sources

bioRxiv2026

Intraspecific trait variation shapes macro-scale patterns ofniche breadth and range size

Morphological variation within species may promote adaptation across ecological and geographic space, perhaps reflecting evolutionary plasticity and adaptability. Based on this concept, species with greater intraspecific variation in morphological traits may be expected to occupy broader ecological niches and larger geographic ranges. However, even in the age of global trait datasets, intraspecific morphological variation remains poorly quantified at broad taxonomic and geographic scales, limiting our understanding of how trait flexibility shapes ecological and biogeographic patterns. Focusing on 161 species of bulbuls, a widespread avian family containing some of the most abundant bird species in the world, along with some of the rarest and most restricted in range, we conducted global-scale sampling of morphological traits. These included beak shape, tarsus length and wing length, associated with dietary niche, foraging strategy and dispersal, respectively. Using phylogenetic models, we tested whether ecological niche breadth and geographical range size are predicted by intraspecific morphological variation quantified from 8,251 museum specimens and 5,627 live captures. Our results demonstrate that morphological trait variation predicts both ecological niche breadth and geographic range size. Furthermore, widespread species exhibit greater morphological variation than restricted-range species even when comparisons are constrained to equivalent geographic extents, consistent with the hypothesis that intraspecific trait variation facilitates range expansion rather than simply accumulating as a consequence of occupying a larger range. These results identify intraspecific morphological variation as a potentially important, yet largely overlooked, predictor of ecological traits and biogeographic distributions in birds.

ecology↗

bioRxiv2025

Mitoxantrone Hydrochloride Targets APP and LRRK2 to Improve Neurodegeneration in Parkinson's Models

BackgroundParkinsons disease (PD) is the second common neurodegenerative disorder, driven by the loss of dopaminergic neurons and pathological -synuclein protein accumulation. Currently, there is no disease-modifying therapy that can halt PD progression. Our previous study uncovered a critical pathogenic feed-forward loop between amyloid precursor protein (APP) and leucine-rich repeat kinase 2 (LRRK2), in which the two proteins mutually enhance each others expression, ultimately leading to mitochondrial dysfunction and neurotoxicity. Targeting this vicious cycle represents a promising therapeutic strategy for PD. MethodsTo discover novel inhibitors targeting this axis, we performed high-throughput screening of an FDA-approved drug library using a fluorescence-based biosensor system. We identified Mitoxantrone hydrochloride (MH), an antineoplastic agent, as a lead compound that inhibits both APP and LRRK2 expression. Its efficacy was validated in cellular models, including patient induced pluripotent stem cell (iPSC)-derived dopaminergic neurons and human peripheral blood mononuclear cells (PBMCs). Motor behavioural and safety assessments were subsequently conducted in PD mouse models. ResultsWe demonstrated that MH suppresses both APP and LRRK2 expression in various cell types in a dosage-dependent manner. In addition, MH also inhibits phosphorylation of LRRK2 and its downstream substrate Rab10. We further showed MH inhibits LRRK2 activity through direct binding to its kinase domain. Critically, MH treatment rescued dopaminergic neuron loss and reversed motor deficits in both 6-Hydroxydopamine (6-OHDA)-induced and LRRK2G2019S genetic PD mouse models. Moreover, we found that oral administration of MH is therapeutically effective, providing superior neuroprotection and behavioral recovery without detectable cardiotoxicity or gastrointestinal damage. ConclusionsOur findings demonstrate MH as a compelling, repurposable therapeutic candidate capable of disrupting a core pathogenic mechanism in PD.

neuroscience↗

bioRxiv2025

Birds that don't exist: niche pre-emption as a constraint on morphological evolution in the Passeroidea

Understanding why some viable body forms never evolve can reveal how ecological and evolutionary forces shape biodiversity. We investigate this question in the Passeroidea, a large group of songbirds, by analyzing their morphological trait space using topological data analysis and ancestral state reconstruction. We identify a long-standing morphological gap densely surrounded by extant species but unoccupied throughout passeroid diversification. The gap patterns deviate from neutral expectations and show no evidence of past occupation, rendering neutral evolution and extinction unlikely. Similar morphologies exist in other bird lineages, ruling out intrinsic constraints or niche absence. Geographic distributions and traits of passeroids versus non-passeroid gap occupants point to competitive exclusion as the plausible explanation: early-colonizing territorial specialists outside the Passeroidea may have preemptively occupied key habitats, limiting evolutionary opportunities for later-arriving lineages. We demonstrate how historical contingency can shape macroevolutionary outcomes, and introduce a generalizable framework for investigating structural gaps in trait evolution.

ecology↗