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Biology subjects

Jennings, L.

Publications and source records attributed to Jennings, L..

10 recordsLinked to original sources

Effects of the nemertean egg predator Carcinonemertes carcinophila (Carcinonemertidae: Monostilifera) on the reproductive output and fecundity of the Florida Atlantic blue crab Callinectes sapidus.

The blue crab, Callinectes sapidus, is an important crab fishery in Florida, valued at approximately $14.5 M in 2023. However, female blue crabs are host to the nemertean worm Carcinonemertes carcinophila, which preys upon its eggs. Other nemerteans from this genus have been linked to the collapse of fisheries, such as the Dungeness crab fishery in the 1960s and 1970s and the red king crab fishery in the 1980s. In 2022, the newly-discovered nemertean Carcinonemertes conanobrieni was found to parasitize the egg masses of female Caribbean spiny lobsters, Panulirus argus, and has had drastic impacts on the reproductive output and fecundity of this species. We hypothesized that nemertean egg parasites might have similar impacts on blue crabs. To investigate this, we collected 52 ovigerous female blue crabs from Jacksonville and Ormond Beach, 61.5% of which were infested with C. carcinophila. Infestation status did not significantly affect fecundity or reproductive output; instead, body mass and embryo stage were the strongest predictors. Infestation was more prevalent in crabs with late-stage embryos, consistent with nemertean life cycle timing. While most hosts carried few worms, a subset showed high infestation intensity, and both infestation status and nemertean density were significant predictors of embryo loss. This is a positive sign for the Florida blue crab fishery, as it suggests that the blue crab nemertean might not be as impactful to that fishery as others.

ecology↗

The fluctuation-based regime of thalamocortical circuitry

Neocortical neurons in primary visual cortex (V1) integrate excitatory inputs from both thalamic and cortical sources to generate selectivity for orientation, direction and disparity. Feedforward models have posited that thalamocortical input can drive these selectivities, but the relative sparsity of thalamic synapses raises questions about the sufficiency of this input. To determine whether thalamic drive is sufficient to evoke cortical responses, we quantified the current threshold required to evoke action potentials in vivo using whole-cell recordings in mouse V1. We then isolated thalamic input via optogenetic cortical silencing and compared its strength to the measured spiking threshold. We find that although average thalamic input is below the threshold for action potential generation, trial-by-trial fluctuations in thalamic drive are sufficient to evoke visually driven action potentials. These results demonstrate that thalamic excitation alone can drive cortical spiking, but its effectiveness depends on fluctuations in synaptic input.

neuroscience↗

Setting priorities for the acquisition of primary plant occurrence data

AimEffective implementation of the Global Biodiversity Framework and Global Strategy for Plant Conservation depends on accurate species distribution data. Current vascular plant distribution data, while crucial for understanding terrestrial ecosystems, is often sparse and biased and requires significant expansion. This study developed a scalable approach to prioritize areas for plant occurrence data acquisition, adaptable to national priorities and providing a framework for botanical institutions to coordinate efforts and allocate resources. LocationGlobal. MethodsUsing a Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) analysis, we prioritized areas based on: (a) ecosystem service value; (b) floristic value threatened by climate or land-use change; and (c) uncertainty in species richness estimates, stratified by biome and region. Regional prioritization maps for Africa & Madagascar; East, South and Southeast Asia; Siberia and the Russian Far East; South America; and North & Central America were reviewed by botanical experts for validation. Scalability was assessed by comparing regional and global analyses. ResultsData-driven priority maps, divided into tree-dominated and grassland/deforested areas, largely received expert support. High similarity between global and regional maps demonstrated scalability. Main conclusionsOur approach provides a framework for supporting national implementation of the Global Biodiversity Framework. Variables and their weights can be tailored to national or local needs. The methods flexibility and adaptability extend to other taxonomic groups and objectives, such as protected area selection By prioritizing data acquisition, whether field-based or digital, this research promotes the efficient use of resources. A key advantage of this approach is its capacity to systematically translate expert opinion into explicit and quantitative criteria, which in turn facilitates clear communication with policymakers and funders.

plant biology↗

Selective reduction of KCNA4 in vulnerable glutamatergic-serotonin neurons of the dorsal raphe nucleus in Alzheimers Disease

INTRODUCTIONWe previously demonstrated that htau mice recapitulate many neuropsychiatric features of early Alzheimers disease (AD), and that the dorsal raphe nucleus (DRN) contains distinct subregions. Herein, we investigate vulnerability of the centromedial DRN to pathologically-phosphorylated tau (pTau), a region composed predominantly of dually serotonergic/glutamatergic (5HT/glut) neurons. METHODSWe use computational, molecular, biophysical, and behavioral techniques to assess the centromedial DRN across preclinical and post-mortem settings. RESULTSThe centromedial DRN contains 5HT/glut neurons that differentially express ion-channel genes in the htau mouse. 5HT/glut neurons exhibit increased excitability, which we demonstrate may dually promote pTau accumulation and the severity of depressive-like behaviors in htau mice. At Braak 2, KCNA4 is reduced in 5HT/glut neurons in AD, which are especially vulnerable to pTau compared to 5HT-nonglut neurons. DISCUSSIONTau-mediated dysfunction of the DRN may be driven by changes in ion channel activity that concomitantly promote the spread of pTau in Braak progression.

neuroscience↗

Community Challenge towards Consensus on Characterization of Biological Tissue: C4Bios First Findings

This study investigates methodological variability across various expert laboratories worldwide, with regards to characterizing the mechanical properties of biological tissues. Two testing rounds were conducted on the specific use case of uniaxial tensile testing of porcine aorta. In the first round, 24 labs were invited to apply their established methods to assess inter-laboratory variability. This revealed significant methodological diversity and associated variability in the stress-stretch results, underscoring the necessity for a standardized approach. In the second round, a consensus protocol was collaboratively developed and adopted by 19 labs in an attempt to minimize variability. This involved standardized sample preparation and uniformity in testing protocol, including the use of a common cutting and thickness measurement tool. Despite protocol harmonization, significant variability persisted across labs, which could not be solely attributed to inherent biological differences in tissue samples. These results illustrate the challenges in unifying testing methods across different research settings, underlining the necessity for further refinement of testing practices. Enhancing consistency in biomechanical experiments is pivotal when comparing results across studies, as well as when using the resulting material properties for in silico simulations in medical research.

bioengineering↗

Biomarker Identification by Proteomic Analysis of Vitreous Humor and Plasma in Diabetic Retinopathy

ImportanceIdentify detectable plasma and/or vitreous signals to potentially predict diabetic retinopathy (DR) progression for earlier disease intervention. ObjectiveTo determine the mediators and potential disease progression biomarkers of DR in vitreous humor (VH) and plasma samples using the SomaScan proteome profiling platform. DesignDifferential expression analysis was conducted on VH and plasma samples using the SomaScan Assay. SettingA non-interventional study conducted to collect and analyze VH and plasma samples from patients with diabetic retinopathy. ParticipantsSamples from DR (60 nonproliferative diabetic retinopathy/NPDR, 60 proliferative diabetic retinopathy/PDR) and 60 control patients were collected. Main outcomes and MeasuresDifferentially expressed proteins between disease and control groups were identified. Pathway enrichment analysis was conducted to identify significantly perturbed pathways in DR. Finally, a random forest model was used to identify predictive biomarkers of disease progression. ResultsSomaScan v3 is a pooled aptamer hybridization assay using 5080 SOMAmers to probe over 4100 proteoforms in VH and plasma samples from 3 groups (control, NPDR, and PDR). The most profound protein content change was observed in the VH samples of PDR patients, while minimal changes were measured in plasma samples, highlighting the regionality of PDR pathogenesis. Many key molecules and molecular pathways such as VEGF-A, erythropoietin, and inflammation-associated proteins implicated in DR were significantly affected in the VH of PDR patients. In addition to the classic pathways (hypoxia, immune response, mTORC1 signaling) known to be involved in PDR, novel signaling pathways, including HEME metabolism and adipogenesis, were identified in VH samples. Application of a machine learning algorithm identified a panel of plasma PDR predictive biomarkers and revealed SCARA5 as the top one based on the largest average Gini decrease in the model. ConclusionOur study identified profound alteration of protein expression and molecular pathways in the VH of PDR patients, supporting the key role of local pathogenic changes in DR progression compared to systemic factors. Although the systemic changes related to DR were small, a few disease progression predictive candidate biomarkers (SCARA5, PTK7, FAM3Band FAM3D) were identified, prompting further investigation. Key PointsQuestion: Are plasma/ vitreous humor (VH) proteins predictive of diabetic retinopathy (DR) progression? Findings: This study identifies substantial protein changes in the VH of proliferative diabetic retinopathy (PDR) patients, while early nonproliferative DR (NPDR) patients show minimal change. We identify multiple proteins linked to angiogenesis, inflammation, immune cells (microglia/macrophage/neutrophil), and leukostasis associated with PDR and reveal a potential plasma panel of disease progression (from NPDR to PDR) biomarkers (SCARA5, PTK7, FAM3B, FAM3D). Meaning: Identified disease progression predictive biomarkers permits potential development of prognostic tools to identify individuals most at risk for PDR progression and offering reduced disease burden by earlier intervention.

physiology↗

Proteomic profile analysis of plasma and aqueous humor from glaucoma and non-glaucomatous patients

PurposeGlaucoma, a multifactorial ocular neuropathy, can lead to irreversible vision loss. Diagnosis involves assessing optic cupping (increased cup-to-disc ratios) and structural changes (like retinal nerve fiber layer thinning) through clinical imaging. Elevated intraocular pressure (IOP) is commonly associated with glaucoma, but not always. However, understanding disease progression is hindered by limited access to donor ocular tissue and consistent clinical data. We hypothesize that the proteome of aqueous humor and plasma may be altered in disease and correlates with clinical parameters such as IOP and cup-to-disc ratios. MethodsAqueous humor (AH) and plasma samples were collected from 36 glaucoma patients (17 male, 19 female), and 35 non-glaucomatous control patients (16 male, 19 female) undergoing cataract surgery. The protein profile was compared using the SOMAscan(R) assay system for proteome profiling. From glaucomatous donors, correlations between IOP and cup- to-disc ratios to proteome differences were determined. ResultsOverall proteomics profiles between both AH and plasma were compared by combining all samples (glaucoma and non-glaucoma) and then performing correlation analyses. This study revealed similar protein abundance in the two biological fluids. Additionally, it identified different abundance of proteins in plasma and AH between glaucoma and non- glaucoma samples. The differential proteins identified were involved in pathways related to vascular integrity, inflammation, immune response, cell adhesion, and complement activation. Generally, glaucomatous AH showed higher protein levels. Neurofilament light chain (NEFL) protein correlated with elevated IOP and inflammatory markers, but not with cup-to-disc ratios. ConclusionsTogether, our data demonstrate that the proteins identified in this study from glaucomatous donors correspond to markers of neurodegeneration and those that may inhibit cell proliferation or disrupt vascular integrity.

cell biology↗

Application of Cancer Cell Line Encyclopedia for Measuring Correlation Between Transcriptomics and Proteomics as a Guide for System-level Insights

Robust and reliable proteome measurements provide mechanistic insights in biomedical research. SOMAmer (Slow Off-rate Modified Aptamer) reagents are modified, DNA-based, affinity reagents that measure defined target proteins with reproducibility and accuracy similar to monoclonal antibodies. Applying SOMAmer reagent technology, we developed SomaScan, a clinical proteome profiling platform with capability to measure 7,523 proteoforms for 6,594 human proteins by UniprotID in small sample volumes (e.g., 55l plasma or serum). We evaluated the platform by profiling the proteome of a panel of well characterized Cell Line Encyclopedia (CCLE) cancer models. Unsupervised machine learning analyses demonstrate the SomaScan assay distinguishing cell lines on the basis of their proteome signatures, and identifying both tissue-specific and oncogenic pathways. The proteome measured by SomaScan correlates with published CCLE transcriptome at a level comparable to other published transcript to proteome studies. Taken together, we demonstrate that the SomaScan platform is a technically reproducible system suitable for biomedical and clinical applications that reliably illuminates underlying biomolecular mechanisms.

systems biology↗

FBH1 deficiency sensitizes cells to WEE1 inhibition by promoting mitotic catastrophe

WEE1 kinase phosphorylates CDK1 and CDK2 to regulate origin firing and mitotic entry. Inhibition of WEE1 has become an attractive target for cancer therapy due to the simultaneous induction of replication stress and inhibition of the G2/M checkpoint. WEE1 inhibition in cancer cells with high levels of replication stress results in induction of replication catastrophe and mitotic catastrophe. To increase potential as a single agent chemotherapeutic, a better understanding of genetic alterations that impact cellular responses to WEE1 inhibition is warranted. Here, we investigate the impact of loss of the helicase, FBH1, on the cellular response to WEE1 inhibition. FBH1-deficient cells have a reduction in ssDNA and double strand break signaling indicating FBH1 is required for induction of replication stress response in cells treated with WEE1 inhibitors. Despite the defect in the replication stress response, FBH1-deficiency sensitizes cells to WEE1 inhibition by increasing mitotic catastrophe. We propose loss of FBH1 is resulting in replication-associated damage that requires the WEE1-dependent G2 checkpoint for repair.

cell biology↗

Metal-organic framework (MOF) nanomedicine preparations of sildenafil designed for the future treatment of pulmonary arterial hypertension

Pulmonary Arterial Hypertension (PAH) is an aggressive disease with poor prognosis, no available cure, and low survival rates. Currently, there are several classes of vasodilator drugs that are widely used as treatment strategies for PAH. These include (i) endothelin-1 receptor antagonists, (ii) phosphodiesterase type 5 inhibitors, (iii) prostacyclin analogues, and (iv) soluble guanylate cyclase activators. Despite their clinical benefits, these therapies are hindered by their systemic side effects. This limitation could be overcome by controlled drug release, with future modifications for targeted drug delivery, using a nanomedicine approach. In the current study, we have evaluated one particular nanomedicine platform (the highly porous iron-based metal-organic framework (MOF) commonly referred to as MIL-89) as a carrier of the PAH drug sildenafil. We have previously shown that MIL-89 is relatively non-toxic in a range of human cell types and well tolerated in vivo. Here we prepared a nano-formulation of MIL-89 (nanoMIL-89) and then successfully charged it with a payload of sildenafil (sil@nanoMIL-891). sil@nanoMIL-89 was then shown to release sildenafil in a biphasic manner with an initial rapid release over 6 hours followed by a more sustained release over 72 hours. Both nanoMIL-89 and sil@nanoMIL-89 were relatively non-toxic when incubated with human endothelial cells for 24 hours. Finally, the vasodilator effect of sil@nanoMIL-89 was measured over 8 hours using isolated mouse aorta. Consistent with drug release kinetics, sil@nanoMIL-89 induced vasodilation after a lag phase of >4 hours. Thus, in sil@nanoMIL-89, we have produced a nano-formulation of sildenafil displaying delayed drug release corresponding to vasodilator activity. Further pharmacological assessment of sil@nanoMIL-89, including in PAH models, is now required and constitutes the subject of ongoing investigation.

pharmacology and toxicology↗