Biology subjects

Jacob, V.

Publications and source records attributed to Jacob, V..

10 recordsLinked to original sources

bioRxiv2026

Lack of co-ordination of stomatal, hydraulic and leaf browning traits in 16 perennial Australian grass species of differing climate origins

Grasslands are vulnerable to increasing drought with global warming, but process-based models lack the mechanistic knowledge required to predict the magnitude of drought impacts. While a plant hydraulics framework has been successful in advancing process understanding of drought responses in trees, and how drought responses vary across rainfall gradients, similar approaches have rarely been applied to grasses. Here, we quantified the progression of key drought response processes in sixteen dominant perennial grasses (seven C3 and nine C4) with differing climatic origins across eastern Australia. We found that stomatal closure, hydraulic impairment and leaf browning occurred concurrently, in contrast to the progressive sequence typically observed in trees. We also found that drought response traits were not correlated with species climate of origin. The early impairment of leaf hydraulic conductance and leaf browning along with the lack of correlation with climate of origin suggest that grasses may employ fundamentally different strategies to adapt to low water availability than trees. These results highlight the need for grass-specific parameterization of drought responses in process-based models.

ecology↗

bioRxiv2026

Loss of 7-Dehydrocholesterol Reductase-mediated cholesterol biosynthesis activates IRF3 and inhibits control of Mycobacterium marinum infection

Cholesterol immunometabolism is a critical controller of immunopathology in respiratory infections such as tuberculosis. Smith-Lemli-Opitz syndrome (SLOS) patients are affected by a loss of 7-dehydrocholesterol reductase (DHCR7) function and have elevated 7-dehydrocholesterol (7DHC) and reduced cholesterol. Increased 7DHC has been found to be protective against viral infections in a range of infection models however SLOS patients have a higher susceptibility to respiratory infection. Here we use the zebrafish-Mycobacterium marinum infection model to demonstrate a compromised innate immune response to bacterial infection in the absence of dhcr7. We correlate increased 7DHC with increased activation of the IRF3/type I interferon axis and demonstrate Irf3 is a targetable signaling node to restore anti-bacterial immunity in a dhcr7-depleted background. Plain English summaryLoss of 7-dehydrocholesterol reductase causes Smith-Lemli-Opitz syndrome. One of the metabolic features of Smith-Lemli-Opitz syndrome is increased 7-dehydrocholesterol (7DHC). We find increased 7DHC inhibits the ability of zebrafish to control mycobacterial infection by mis-activating an antiviral immune response at the expense of a protective anti-bacterial immune response. Our study suggests the susceptibility to respiratory infections and increased neuroinflammation in Smith-Lemli-Opitz syndrome could be treated by targeting the antiviral protein IRF3.

immunology↗

bioRxiv2026

Deciphering sepsis molecular subtypes using large-scale data to identify subtype-specific drug repurposing

Sepsis is a life-threatening dysregulated response to infection, the heterogeneity of which precludes effective targeted therapies. To address this, we created a transcriptomic atlas of publicly available adult sepsis data, on which we performed molecular subtyping and identified potential subtype-specific drug repurposing opportunities. In total, we harmonized data from 3,713 samples across 28 datasets, of which 2,251 were from sepsis patients. Using this data, we identified four molecular subtypes of sepsis (C1 - C4) by clustering the sepsis samples based on expression differences in immune-and lipid-related genes. We next identified gene signatures unique to each molecular subtype. Pathway analysis of these signatures revealed patterns of immune exhaustion and metabolic dysregulation in C1, suggesting potential benefit from corticosteroid treatment. C2 had the youngest patient population and the lowest mortality, and C2 expression patterns were often anti-correlated with those of C1. C3 was enriched for inflammatory and cellular stress pathways, while the highest mortality subtype, C4, showed evidence of immunosuppression and metabolic reprogramming. Gene and pathway-level analysis of our molecular subtypes statistically correlated with results from analysis of 28-day mortality, with the best (C2) and worst subtypes (C4) exhibiting similar molecular dysregulation as survivors and non-survivors, respectively. For each subtype, we then evaluated potential targeted therapies. Using a large-scale pharmacogenomics database, we identified drugs targeting the subtype gene signatures and assessed the potential clinical impacts of these drugs. We identified several potential candidate therapies for each molecular subtype, including possible responsiveness to Methylene Blue therapy for patients from our highest mortality subtype, C4. Notably, our drug repurposing analysis revealed a significant representation of anti-inflammatory monoclonal antibody therapies across molecular subtypes. The anti-correlated signatures in C1 and C2 suggest that monoclonal antibody therapies may not be effective for patients in both subtypes, which may explain why prior clinical trials have been unsuccessful. Altogether, our detailed molecular subtyping and analysis identify potential drug targets within each molecular subtype, with implications for future precision medicine for sepsis.

bioinformatics↗

bioRxiv2026

Trait - climate relations in Themeda triandra: a widely distributed C4 grass and crop wild relative

O_LIQuantifying relationships between traits and climate using plants collected from diverse climatic origins, grown under common conditions, potentially provides valuable insights into climate adaptation. C_LIO_LIWe report on fifteen accessions of kangaroo grass (Themeda triandra), a C4 species distributed across Australia, Asia, the Middle East and Africa from the Andropogoneae clade of grasses that is vital to global agriculture. Plants were grown to maturity in glasshouses under two thermal regimes, with ample water supplied. Numerous physiological, "economic" and developmental traits were characterised. C_LIO_LIAs expected, plants grown at 20{degrees}C maxima had lower photosynthetic rates (Asat) and dark respiration rates, reduced leaf expansion, and delayed flowering compared with plants grown at 30{degrees}C. However, surprisingly few traits varied with climate-of-origin: accessions from colder climates had higher Asat alongside lower leaf mass per area, but only when grown at 20{degrees}C; flowering time showed the strongest correlation with site climate, with plants from wetter, warmer or less variable climates taking longer to flower. C_LIO_LIOur findings highlight remarkable phenotypic flexibility in key traits of T. triandra; this flexibility is likely key to its wide distribution. The strong relationship between flowering time and climate-of-origin underscores the importance of reproductive phenology as an adaptive trait. C_LI

ecology↗

bioRxiv2025

Radiotherapy Enhancement by Gold Nanocluster-functionalized Nanoliposomes Using Polychromatic Orthovoltage X-ray Irradiation

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers, as the most effective chemoradiation therapies achieve unsatisfactory outcomes while associated with high toxicity. Nanoliposomal drug delivery systems are widely used to improve chemotherapy safety, yet passive release of amphiphilic drugs may still associate with adverse toxicity. To address this, we previously developed nanoliposomes functionalized with hydrophobic gold nanoclusters, demonstrating radiocatalytic activity and enhanced chemoradiotherapy effects in 3D PDAC microtumors under synchrotron irradiation. In this study, gold nanocluster-functionalized nanoliposomes (AuLPs) were optimized and evaluated under 220 kVp orthovoltage X-ray irradiation, widely used in preclinical irradiation systems. AuLPs containing 0.2 mol% gold nanoclusters produced 1.5-fold more reactive oxygen species than unloaded liposomes. However, higher molar ratios were necessary to improve radiotherapy outcomes in 3D PDAC microtumor models following 4 and 8 Gy irradiation. Pharmacokinetics and biodistribution evaluations showed a modest increase in tumor gold content 24 hours post-injection in orthotopic PDAC models. Altogether, these results underscore the potential of gold-radiotherapy-responsive liposomes while highlighting critical formulation challenges, which must be resolved for full therapeutic potential.

bioengineering↗

bioRxiv2025

Drought, thermal response and climate-patterning in cuticular conductance of the widespread C4 grass, Themeda triandra

O_LIBackground and Aims: Grasslands underpin global biodiversity, carbon storage, and ecosystem resilience, yet are increasingly threatened by rising temperatures and water scarcity. Understanding how key physiological traits respond to drought and heat is essential for ensuring grassland function under future conditions. Here, we investigated intraspecific variation in leaf cuticular traits--specifically minimum cuticular conductance after stomatal closure (gmin) and its response to temperature--in six Australian accessions of Themeda triandra spanning a wide climatic gradient. We asked whether gmin and its response to drought reflect climate-of-origin and whether the cuticle shows a thermal threshold (Tp) beyond which conductance rises sharply. C_LIO_LIMethods: Plants from six accessions were grown under well-watered (control) glasshouse conditions and then exposed to drought. We measured gmin in both control and drought treatments and assessed the response of gmin to increasing temperature (30-55 {degrees}C) using fresh fully hydrated leaves (control). Climatic data for each site of origin were used to explore trait-environment relationships. C_LIO_LIKey results: Under well-watered conditions, gmin showed no link to climate-of-origin. Under drought, however, gmin displayed clearer climate-linked patterns: accessions from cooler, wetter regions had lower values, contrary to expectations. Drought responses varied strongly among accessions, ranging from marked reductions to significant increases in gmin. With increasing temperature, gmin declined gradually and no accession exhibited a distinct phase transition, indicating a thermally stable cuticle. C_LIO_LIConclusions: Themeda triandra shows considerable intraspecific diversity in gmin and its response to drought. The clearer alignment between climate of origin and gmin measured under drought conditions suggests drought stress is an important filter for gmin expression. These findings provide a physiological basis for identifying genotypes with enhanced resilience for use in grassland conservation and restoration under a warming, drying climate. C_LI

ecology↗

bioRxiv2025

Dabigatran prevents lipopolysaccharide mediated apoptosis in zebrafish through a thrombin independent mechanism

Endotoxemia is a feature of sepsis pathogenesis and has also been found to mediate the pathophysiology of multiple inflammatory conditions. In this work, we use a lipopolysaccharide (LPS) induced endotoxemia model in zebrafish to identify novel mediators of LPS toxicity. We performed transcriptomic studies on LPS-treated larvae, followed by in silico analysis, which revealed associations between the signatures of LPS-treated embryos and those of drugs involving diverse pathways. In parallel, we performed an in vivo screen using >1,500 FDA-approved compounds and identified multiple novel small molecules that reduced inflammation and prevented LPS toxicity. We focused on the direct thrombin inhibitor dabigatran, which was identified through both the in vivo and in silico analyses. We found that dabigatran co-administration significantly reduced the expression of inflammatory cytokines and completely protected zebrafish from endotoxemic death due to LPS. Surprisingly, we found that this protection occurs in prothrombin mutant fish, proving that protection from endotoxemia occurs independently of the anticoagulant function of dabigatran. We additionally found that dabigatran administration significantly decreased nitric oxide production and apoptosis compared to LPS treatment alone, suggesting possible mechanisms by which protection from endotoxemia is achieved. In summary, we identify several novel small molecules that prevent LPS-induced endotoxemia and show that one such small molecule, dabigatran, exerts a thrombin-independent effect on nitric oxide production and apoptosis. This and the other identified small molecules warrant further exploration in inflammatory conditions including sepsis.

pharmacology and toxicology↗

bioRxiv2024

Olfaction in Tephritidae: a balance between detection and discrimination

Phytophagous insects are capable of detecting and locating suitable hosts, which emit volatile compounds. Polyphagous species appear to have a complex olfactory strategy given that their numerous hosts have diverse emission profiles. In particular, their hosts volatile emissions share some of the same compounds, providing chemical bridges between them. However, the behavioural plasticity observed in insect host selection suggests that other volatiles have a complementary role. Here we explore how the specialization of polyphagous Tephritidae fruit fly in detecting and discriminating between host fruits has driven their chemical selectivity. The volatile emissions from intact or mechanically damaged fruit of 28 different species were analysed using gas chromatography-mass spectrometry and fed into a neuronal model of an olfactory system. We predicted in silico a functional trade-off between the two tasks, with optimal performance depending on detecting a higher proportion of shared fruit compounds, but with lower sensitivity compared to unshared compounds, or vice-versa. Using triple point electroantennography and a behavioural assay, we studied the olfactory response of Tephritidae fruit fly species that oviposit on fruit. Amplitude of the olfactory responses of eight species were negatively correlated with the compounds degree of sharedness among fruit emissions, while response probability was previously shown to correlate positively with a similar metric. A dose-dependent switch in the flys preference confirmed the ecological importance of both shared and unshared fruit compounds. Thus, we propose that insect olfactory systems are chemically tuned to detect suitable hosts and accurately discriminate between them.

ecology↗

bioRxiv2020

Pastures and Climate Extremes: Impacts of warming and drought on the productivity and resilience of key pasture species in a field experiment

Shifts in the timing, intensity and/or frequency of climate extremes, such as severe drought and heatwaves, can generate sustained shifts in ecosystem function with important ecological and economic impacts for rangelands and managed pastures. The Pastures and Climate Extremes experiment (PACE) in Southeast Australia was designed to investigate the impacts of a severe winter/spring drought (60% rainfall reduction) and, for a subset of species, a factorial combination of drought and elevated temperature (ambient +3 {degrees}C) on pasture productivity. The experiment included nine common pasture and Australian rangeland species from three plant functional groups (C3 grasses, C4 grasses and legumes) planted in monoculture. Winter/spring drought resulted in productivity declines of 45% on average and up to 74% for the most affected species (Digitaria eriantha) during the 6-month treatment period, with eight of the nine species exhibiting significant yield reductions. Despite considerable variation in species sensitivity to drought, C4 grasses were more strongly affected by this treatment than C3 grasses or legumes. Warming also had negative effects on cool-season productivity, associated at least partially with exceedance of optimum growth temperatures in spring and indirect effects on soil water content. The combination of winter/spring drought and year-round warming resulted in the greatest yield reductions. We identified responses that were either additive such that there was only as significant warming effect under drought (Festuca), or less-than-additive, where there was no drought effect under warming (Medicago), compared to ambient plots. Results from this study highlight the sensitivity of diverse pasture species to increases in winter and spring drought severity similar to those predicted for this region, and that anticipated benefits of cool-season warming are unlikely to be realised. Overall, the substantial negative impacts on productivity suggest that future, warmer, drier climates will result in shortfalls in cool-season forage availability, with profound implications for the livestock industry and natural grazer communities.

ecology↗

bioRxiv2017

Olfactory coding in the turbulent realm

Long-distance olfactory search behaviors depend on odor detection dynamics. Due to turbulence, olfactory signals travel as bursts of variable concentration and spacing and are characterized by long-tail distributions of odor/no-odor events, challenging the computing capacities of olfactory systems. How animals encode complex olfactory scenes to track the plume far from the source remains unclear. Here we focus on the coding of the plume temporal dynamics in moths. We compare responses of olfactory receptor neurons (ORNs) and antennal lobe projection neurons (PNs) to sequences of pheromone stimuli either with white-noise patterns or with realistic turbulent temporal structures simulating a large range of distances (8 to 64 m) from the odor source. For the first time, we analyze what information is extracted by the olfactory system at large distances from the source. Neuronal responses are analyzed using linear-nonlinear models fitted with white-noise stimuli and used for predicting responses to turbulent stimuli. We found that neuronal firing rate is less correlated with the dynamic odor time course when distance to the source increases because of improper coding during long odor and no-odor events that characterize large distances. Rapid adaptation during long puffs does not preclude however the detection of puff transitions in PNs. Individual PNs but not individual ORNs encode the onset and offset of odor puffs for any temporal structure of stimuli. A higher spontaneous firing rate coupled to an inhibition phase at the end of PN responses contributes to this coding property. This allows PNs to decode the temporal structure of the odor plume at any distance to the source, an essential piece of information moths can use in their tracking behavior.\n\nAuthor SummaryLong-distance olfactory search is a difficult task because atmospheric turbulence erases global gradients and makes the plume discontinuous. The dynamics of odor detections is the sole information about the position of the source. Male moths successfully track female pheromone plumes at large distances. Here we show that the moth olfactory system encodes olfactory scenes simulating variable distances from the odor source by characterizing puff onsets and offsets. A single projection neuron is sufficient to provide an accurate representation of the dynamic pheromone time course at any distance to the source while this information seems to be encoded at the population level in olfactory receptor neurons.

neuroscience↗