Biology subjects

Lim, B. K.

Publications and source records attributed to Lim, B. K..

6 recordsLinked to original sources

bioRxiv2026

Ancient DNA perspectives on North American cervids identify dispersal waves and fluctuations in diversity

North American fauna has experienced major changes over the last two million years. Glacial cycles, animal migrations, peopling waves, and, more recently, European colonisation, caused demographic fluctuations, divergence, and wildlife extinctions. Caribou (Rangifer tarandus), moose (Alces alces), wapiti (Cervus canadensis), white-tailed (Odocoileus virginianus) and mule deer (O. hemionus) are the five extant cervids in Northern America, with unique dispersal patterns and conservation statuses. Here, we used DNA analysis of ancient, historical and modern individuals of these Cervidae to retrace evolutionary processes through time. We show that present-day eastern Canada caribou share ancestry with a 30-thousand-year-old sample from western Canada consistent with the species' complex dispersal history as suggested by literature. Our results suggest rapid expansion of moose following their arrival on the continent ~15 thousand years ago. Data on wapiti shows a recent loss of diversity consistent with its large-scale extirpation after European colonisation. Results on Odocoileus species are in line with their recognised mito-nuclear discordance. Our results exemplify the utility of chronological sampling to gain a better understanding of how external pressures drive genomic changes.

evolutionary biology↗

bioRxiv2024

Detection of intra-tumoral microbiota from transcriptomic sequencing of Asian breast cancer

The human microbiome has garnered significant interest in recent years as an important driver of human health and disease. Likewise, it has been suggested that the intra-tumoral microbiome may be associated with specific features of cancer such as tumour progression and metastasis. However, additional research is needed to validate these findings in diverse populations. In this study, we characterized the intra-tumoral microbiota of 883 Malaysian breast cancer patients using transcriptomic data from bulk tumours and investigated their association with clinical variables and immune scores. We found that the tumour microbiome was not associated with breast cancer molecular subtype, cancer stage, tumour grade, or patient age, but was weakly associated with immune scores. We also found that the tumour microbiome was able to predict immune scores in our cohort using random forest models, suggesting the possibility of an interaction between the tumour microbiome and the tumour immune microenvironment in Asian breast cancer.

microbiology↗

bioRxiv2021

Gene losses in the common vampire bat illuminate molecular adaptations to blood feeding

Feeding exclusively on blood, vampire bats represent the only obligate sanguivorous lineage among mammals. To uncover genomic changes associated with adaptations to this unique dietary specialization, we generated a new haplotype-resolved reference-quality genome of the common vampire bat (Desmodus rotundus) and screened 26 bat species for genes that were specifically lost in the vampire bat lineage. We discovered previously-unknown gene losses that relate to metabolic and physiological changes, such as reduced insulin secretion (FFAR1, SLC30A8), limited glycogen stores (PPP1R3E), and a distinct gastric physiology (CTSE). Other gene losses likely reflect the biased nutrient composition (ERN2, CTRL) and distinct pathogen diversity of blood (RNASE7). Interestingly, the loss of REP15 likely helped vampire bats to adapt to high dietary iron levels by enhancing iron excretion and the loss of the 24S-hydroxycholesterol metabolizing enzyme CYP39A1 could contribute to their exceptional cognitive abilities. Finally, losses of key cone phototransduction genes (PDE6H, PDE6C) suggest that these strictly-nocturnal bats completely lack cone-based vision. These findings enhance our understanding of vampire bat biology and the genomic underpinnings of adaptations to sanguivory.

evolutionary biology↗

bioRxiv2020

The mouse cortico-basal ganglia-thalamic network

The cortico-basal ganglia-thalamic loop is one of the fundamental network motifs in the brain. Revealing its structural and functional organization is critical to understanding cognition, sensorimotor behavior, and the natural history of many neurological and neuropsychiatric diseases. Classically, the basal ganglia is conceptualized to contain three primary information output channels: motor, limbic, and associative. However, given the roughly 65 cortical areas and two dozen thalamic nuclei that feed into the dorsal striatum, a three-channel view is overly simplistic for explaining the myriad functions of the basal ganglia. Recent works from our lab and others have subdivided the dorsal striatum into numerous functional domains based on convergent and divergent inputs from the cortex and thalamus. To complete this work, we generated a comprehensive data pool of [~]700 injections placed across the striatum, external globus pallidus (GPe), substantia nigra pars reticulata (SNr), thalamic nuclei, and cortex. We identify 14 domains of SNr, 36 in the GPe, and 6 in the parafascicular and ventromedial thalamic nuclei. Subsequently, we identify 6 parallel cortico-basal ganglia-thalamic subnetworks that sequentially transduce specific subsets of cortical information with complex patterns of convergence and divergence through every elemental node of the entire cortico-basal ganglia loop. These experiments reveal multiple important novel features of the cortico-basal ganglia network motif. The prototypical sub-network structure is characterized by a highly interconnected nature, with cortical information processing through one or more striatal nodes, which send a convergent output to the SNr and a more parallelized output to the GPe; the GPe output then converges with the SNr. A domain of the thalamus receives the nigral output, and is interconnected with both the striatal domains and the cortical areas that filter into its nigral input source. This study provides conceptual advancement of our understanding of the structural and functional organization of the classic cortico-basal ganglia network.

neuroscience↗

bioRxiv2020

A characterization of the electrophysiological, morphological and input domains of vasoactive intestinal peptide (VIP) interneurons in the medial entorhinal cortex (MEC)

Circuit interactions within the medial entorhinal cortex (MEC) translate movement into a coherent code for spatial location. Entorhinal principal cells are subject to strong lateral inhibition, suggesting that a disinhibitory mechanism may drive their activation. Cortical Vasoactive Intestinal Peptide (VIP) expressing inhibitory neurons predominantly contact interneurons, providing a local disinhibitory mechanism. Here, we investigate the electrophysiological and morphological properties of VIP cells using in vitro whole-cell patch clamp recordings and use rabies-mediated circuit tracing to discover long-range inputs that may modulate this population in mice. We report physiological and morphological properties of VIP cells that differ across lamina and along the dorsal-ventral MEC axis. Furthermore, we reveal long-range inputs to VIP neurons from regions known to encode proprioceptive and auditory information, including the mesencephalic trigeminal nucleus and superior para-olivary nuclei, respectively. These results characterize the properties of VIP cells and reveal sensory modalities that could drive disinhibition in the MEC.

neuroscience↗

bioRxiv2018

Brainstem control of urethral sphincter relaxation and scent marking behavior

Urination may occur either reflexively in response to a full bladder or deliberately irrespective of immediate need. Voluntary control is desired because it ensures that waste is expelled when consciously desired and socially appropriate1,2. Urine release requires two primary components: bladder pressure and urethral relaxation1-3. Although the bladder contracts during urination, its slow smooth muscle is not under direct voluntary control and its contraction alone is not sufficient for voiding. The decisive action of urination is at the urethral sphincter, where striated muscle permits fast control. This sphincter is normally constricted, but relaxes to enable urine flow. Barringtons nucleus (Bar, or pontine micturition center) in the brainstem is known to be essential for the switch from urine storage to elimination4-7, and a subset of Bar neurons expressing corticotropin releasing hormone (BarCRH) have recently been shown to promote bladder contraction8-10. However, Bar neurons that relax the urethral sphincter to enable urination behavior have not been identified. Here we describe novel brainstem neurons that control the external urethral sphincter. We find that scent marking behavior in male mice depends upon a subpopulation of spatially clustered Bar neurons that express high levels of estrogen receptor 1 (BarESR1). These neurons are glutamatergic, project to urinary nuclei in the spinal cord with a bias towards sphincter-inhibiting interneurons, and their activity correlates with natural urination. Optogenetic stimulation of BarESR1 neurons rapidly initiates sphincter bursting and efficient voiding in absence of sensory cues in anesthetized and behaving animals. Conversely, inhibiting the activity of these neurons prevents olfactory cues from promoting scent marking behavior. The identification of BarESR1 cells provides an expanded model for the supraspinal control of urination and its dysfunction.

neuroscience↗