Biology subjects

Murdoch, H.

Publications and source records attributed to Murdoch, H..

5 recordsLinked to original sources

bioRxiv2026

Ardisia mela (Primulaceae) a new threatened, herbaceous species of Ardisia subgen. Kamardisia from the forest of the Crystal Mts, Gabon.

Ardisia mela is formally described from the forests of the Crystal Mts, Gabon based on a specimen collected in 1968 and informally described in 1979 by Taton as Species 2. Despite the proximity of the collection to a road, and a resurgence of botanical surveys in the Crystal Mts in recent years, the species appears not to have been refound, and as it occurs in a logging concession and areas of cleared forest can be seen in the vicinity of the collection site, the species is considered threatened and provisionally assessed as Critically Endangered using the 2012 IUCN standard.

plant biology↗

bioRxiv2026

A Taxonomic Revision of the Monocaul Phanerophyte Ardisia (Primulaceae) of Gabon

Monocaul Ardisia (Primulaceae) have a single, vertical, woody stem and spiral phyllotaxy. They range from 30 cm to 100 cm tall. Three species of this architectural group, Ardisia mayumbensis, A. hallei and A. bracteata, have been recorded from Gabon hitherto. In this taxonomic revision we show that A. mayumbensis does not occur in Gabon, and we describe three new species. Two of these, Ardisia doudou sp. nov.and A. mica sp.nov., are endemic to Gabon and one, A. litterbin sp.nov, is found in both Gabon and Republic of the Congo. Ardisia hallei and A. bracteata are redescribed. All five species have a litter-gathering habit with a terminal funnel of leaves, and two of these species, Ardisia doudou and Ardisia litterbin, also possess adventitious roots in the distal part of the stem, a well-established strategy found in litter-gathering forest species of other plant families in tropical Africa. We provisionally assess the conservation status of all five taxa using the 2012 IUCN standard, finding that all monocaul Ardisia in Gabon fall within threatened categories. Two of the species, Ardisia bracteata and A. mica, are known from single collections and have not been seen for 164 and 63 years respectively and are conceivably extinct although further surveys are needed to establish this. We employ new characters in delineating and describing African Ardisia using leaf thickness and oil gland data.

Plant Biology↗

bioRxiv2025

Mycobacterium tuberculosis growth arrest on propionate at acidic pH is suppressed by mutations in phoPR and pyrazinamide treatment

Mycobacterium tuberculosis (Mtb) arrests its growth at acidic pH, when grown on specific single carbon sources, including propionate. However, Mtb grows well on propionate at pH 7.0, supporting that propionate can support growth as a sole carbon source. To understand the basis of the propionate-driven growth arrest at acidic pH, we performed a forward genetic selection for mutants that enable growth on propionate at pH 5.7. All the selected mutants had insertions in the two-component regulatory genes phoR or phoP. We hypothesized that growth arrest at acidic pH is caused by PhoPR diverting carbon from central carbon metabolism towards lipid anabolism and that when PhoPR is inactivated, growth is promoted through metabolizing propionate by the methyl citrate cycle (MCC) into pyruvate, a permissive carbon source for growth at acidic pH. Using chemical inhibition and mutants of the MCC pathway, we demonstrate that the enhanced growth is dependent on the MCC. Furthermore, stimulating lipid synthesis via the methylmalonyl-CoA pathway by adding vitamin B12 restricts growth in the{Delta} phoPR mutant and, conversely, restricting lipid anabolism by inhibiting the triacylglycerol (TAG) synthase tgs1 enhances growth of the{Delta} phoPR mutant. Notably, CoA pools increased in the{Delta} phoPR mutant grown on propionate, directly supporting our model. Given the role of CoA metabolism in pyrazinamide sensitivity, we examined Mtb sensitivity to pyrazinamide on propionate at acidic pH and, surprisingly, observed that pyrazinamide treatment of WT Mtb suppresses growth arrest on propionate at acidic pH. In contrast, the phoPR mutant has enhanced sensitivity to pyrazinamide. Together, these findings support that propionate-driven growth arrest at acidic pH is caused by metabolic remodeling that is regulated by PhoPR and is associated with pyrazinamide sensitivity. ImportanceWhen grown on certain single carbon sources, such as propionate, Mtb arrests its growth at acidic pH and establishes a state of non-replicating persistence (NRP). To understand the genetic basis of this growth restriction, a genetic selection was performed to identify mutants unable to arrest growth at acidic pH with propionate as a sole carbon source. The selection exclusively identified mutants in the PhoPR two-component regulatory system, which functions to modulate cell envelope lipids and redox homeostasis through the upregulation of lipid synthesis at acidic pH. Using genetic and chemical inhibition studies, we demonstrate that PhoPR arrests growth at acidic pH by diverting carbon away from the methyl citrate cycle towards lipid anabolism. Surprisingly, treatment of Mtb with pyrazinamide at acidic pH on propionate, also enabled growth. Therefore, this study defines new mechanisms by which Mtb integrates environmental signaling to regulate growth, metabolism, and drug susceptibility. These findings are relevant to pathogenesis, as PhoPR is essential for growth in macrophages and animals, environments with varying pH and carbon source availability, depending on immune pressures. These data suggest that drug susceptibility may be impacted by enhanced growth and metabolic capacity of Mtb in acidic and propionate-rich environments, such as the within the macrophage or the granuloma.

microbiology↗

bioRxiv2025

DISC1-PML protein interaction for congenital CMV infection-induced cortical neural progenitor deficit: perturbance of host signaling via viral IE1

Congenital CMV infection is the most common perinatal infection, affecting up to 0.5% of infants. This elicits long-term disabilities that include neuropsychiatric manifestations, such as intellectual disability, microcephaly. Despite its high prevalence, the underlying mechanism of how congenitally acquired CMV infection causes brain pathology remains unknown. Here we discovered the molecular interplay of key host (DISC1 and PML) and viral (IE1) proteins within the neural progenitor cells, which underlay an attenuated neural progenitor proliferation. Abolishing the viral IE1 protein by delivering IE1-targeting CRISPR/Cas9 to fetal brain rescued this progenitor cell deficit, a key pathology in congenital CMV infection. A selective targeting to a viral-specific protein by the CRISPR/Cas9 system is minimal in off-target effects. Therefore, we believe that a pivotal role of IE1 in an attenuated neural progenitor proliferation in the developing cortex through its interfering with interaction between host DISC1 and PML proteins.

developmental biology↗

bioRxiv2018

DISC1 regulates N-Methyl-D-Aspartate receptor dynamics: Abnormalities induced by a Disc1 mutation modelling a translocation linked to major mental illness

The neuromodulatory gene DISC1 is disrupted by a t(1;11) translocation that is highly penetrant for schizophrenia and affective disorders, but how this translocation affects DISC1 function is incompletely understood. N-Methyl-D-Aspartate receptors (NMDAR) play a central role in synaptic plasticity and cognition, and are implicated in the pathophysiology of schizophrenia through genetic and functional studies. We show that the NMDAR subunit GluN2B complexes with DISC1-associated trafficking factor TRAK1, while DISC1 interacts with the GluN1 subunit and regulates dendritic NMDAR motility in cultured mouse neurons. Moreover, in the first mutant mouse that models DISC1 disruption by the translocation, the pool of NMDAR transport vesicles and surface/synaptic NMDAR expression are increased. Since NMDAR cell surface/synaptic expression is tightly regulated to ensure correct function, these changes in the mutant mouse are likely to affect NMDAR signalling and synaptic plasticity. Consistent with these observations, RNASeq analysis of translocation carrier-derived human neurons indicates abnormalities of excitatory synapses and vesicle dynamics. RNASeq analysis of the human neurons also identifies many differentially expressed genes previously highlighted as putative schizophrenia and/or depression risk factors through large-scale genome-wide association and copy number variant studies, indicating that the translocation triggers common disease pathways that are shared with unrelated psychiatric patients. Altogether our findings suggest that translocation-induced disease mechanisms are likely to be relevant to mental illness in general, and that such disease mechanisms include altered NMDAR dynamics and excitatory synapse function. This could contribute to the cognitive disorders displayed by translocation carriers.

neuroscience↗