Biology, Volume 12, Issue 8 (August 2023) – 112 articles

Cognitive impairment (CI) shares common cardiovascular risk factors with acute myocardial infarction (AMI), and is increasingly prevalent in our ageing population. Whilst AMI is associated with increased rates of CI, CI remains underreported and infrequently identified in patients with AMI. In this review, we discuss the evidence surrounding AMI and its links to dementia and CI, including pathophysiology, risk factors, management and interventions. Vascular dysregulation plays a major role in CI, with atherosclerosis, platelet activation, microinfarcts and perivascular inflammation resulting in neurovascular unit dysfunction, disordered homeostasis and a dysfunctional neurohormonal response. This subsequently affects perfusion pressure, resulting in enlarged periventricular spaces and hippocampal sclerosis. The increased platelet activation seen in coronary artery disease (CAD) can also result in inflammation and amyloid-β protein deposition which is associated with Alzheimer’s Dementia. Post-AMI, reduced blood pressure and reduced left ventricular ejection fraction can cause chronic cerebral hypoperfusion, cerebral infarction and failure of normal circulatory autoregulatory mechanisms. Patients who undergo coronary revascularization (percutaneous coronary intervention or bypass surgery) are at increased risk for post-procedure cognitive impairment, though whether this is related to the intervention itself or underlying cardiovascular risk factors is debated. Mortality rates are higher in dementia patients with AMI, and post-AMI CI is more prevalent in the elderly and in patients with post-AMI heart failure. Medical management (antiplatelet, statin, renin-angiotensin system inhibitors, cardiac rehabilitation) can reduce the risk of post-AMI CI; however, beta-blockers may be associated with functional decline in patients with existing CI. The early identification of those with dementia or CI who present with AMI is important, as subsequent tailoring of management strategies can potentially improve outcomes as well as guide prognosis. Full article

Introduction: Hypertension, a leading cause of death, was investigated in this study to understand the role of specific brain regions in regulating blood pressure. The lateral parabrachial nucleus (LPBN), Kolliker-fuse nucleus (KF), and periductal grey matter (PAG) were examined for their involvement in hypertension. Methods: Lentiviral vectors were used to alter the activity of these brain regions in hypertensive rats. Over a 75-day period, blood pressure, heart rate, reflex responses, and heart rate variability were measured. Results: Decreasing the activity in the LPBN resulted in a reduced sympathetic outflow, lowering the blood pressure and heart rate. In the KF, the sympathetic activity decreased and chemoreflex variation was attenuated, without affecting the blood pressure. Silencing the PAG had no significant impact on blood pressure or sympathetic tone, but decreased cardiac baroreflex gain. Discussion: These findings highlight the significant role of the LPBN in hypertension-related sympathetic activation. Additionally, LPBN and KF neurons appear to activate mechanisms that control respiration and sympathetic outflow during chemoreceptor activation. Conclusions: The study provided insights into the contribution of the midbrain and pontine regions to neurogenic hypertension and offers potential avenues for future genetic interventions and developing novel treatment approaches. Full article

Our search of existing cancer databases aimed to assess the current landscape and identify key needs. We analyzed 71 databases, focusing on genomics, proteomics, lipidomics, and glycomics. We found a lack of cancer-related lipidomic and glycomic databases, indicating a need for further development in these areas. Proteomic databases dedicated to cancer research were also limited. To assess overall progress, we included human non-cancer databases in proteomics, lipidomics, and glycomics for comparison. This provided insights into advancements in these fields over the past eight years. We also analyzed other types of cancer databases, such as clinical trial databases and web servers. Evaluating user-friendliness, we used the FAIRness principle to assess findability, accessibility, interoperability, and reusability. This ensured databases were easily accessible and usable. Our search summary highlights significant growth in cancer databases while identifying gaps and needs. These insights are valuable for researchers, clinicians, and database developers, guiding efforts to enhance accessibility, integration, and usability. Addressing these needs will support advancements in cancer research and benefit the wider cancer community. Full article

Biliary pancreatic malignancy has an occultic onset, a high degree of malignancy, and a poor prognosis. Most clinical patients miss the opportunity for surgical resection of the tumor. Systemic chemotherapy is still one of the important methods for the treatment of biliary pancreatic malignancies. Many chemotherapy regimens are available, but their efficacy is not satisfactory, and the occurrence of chemotherapy resistance is a major reason leading to poor prognosis. With the advancement of studies on intestinal flora, it has been found that intestinal flora is correlated with and plays an important role in chemotherapy resistance. The application of probiotics and other ways to regulate intestinal flora can improve this problem. This paper aims to review and analyze the research progress of intestinal flora in the chemotherapy resistance of biliary pancreatic malignancies to provide new ideas for treatment. Full article

Several elasmobranch species undergo shifts in body proportions during their ontogenetic growth. Such morphological changes could reflect variation in diet, locomotion, or, more broadly, in the species’ interactions with their environment. However, to date, only a few studies have been conducted on this topic, and most of them focused on particular body regions. In the present study, the ontogenetic growth of five different demersal shark species was investigated by using both traditional linear morphometry of the entire body and shape analysis of the caudal fin. A total of 449 sharks were analysed: 95 little gulper sharks, 80 longnose spurdogs, 103 kitefin sharks, 124 velvet belly lanternsharks, and 47 angular roughsharks. From each specimen, 36 linear morphometric measurements were taken. While a first canonical analysis of principal coordinates ruled out the possibility of different growth patterns between males and females, the same analysis statistically discriminated between small and large individuals in every species based on their morphology. A Similarity Percentage analysis revealed that the most important measurements in distinguishing these two groups were those related to body lengths, indicating that large individuals are more elongated than small individuals. The shape analysis of caudal fins revealed allometric growth during ontogenetic development, with adult individuals having a wider fin (discriminant analysis, p < 0.05). These findings could be related to changes in predatory skills, supporting the hypothesis of a shift in the ecological role that these sharks play in their environment, thus providing new essential information for their conservation. Full article

The excessive use of synthetic pesticides has caused environmental problems and human health risks and increased the development of resistance in several organisms. Allelochemicals, secondary metabolites produced as part of the defense mechanisms in plants and microorganisms, are an attractive alternative to replace synthetic pesticides to remediate these problems. Microalgae are natural producers of a wide range of allelochemicals. Thus, they provide new opportunities to identify secondary metabolites with pesticide activities and an alternative approach to discover new modes of action and circumvent resistance. We screened 10 green microalgae strains belonging to the Chlorophyta phylum for their potential to inhibit the growth of photosynthetic and nonphotosynthetic organisms. Bioassays were established to assess microalgae extracts’ effectiveness in controlling the growth of Chlorella sorokiniana, Arabidopsis thaliana, Amaranthus palmeri, and the model nematode Caenorhabditis elegans. All tested strains exhibited herbicidal, nematocidal, or algicidal activities. Importantly, methanol extracts of a Chlamydomonas strain effectively controlled the germination and growth of a glyphosate-resistant A. palmeri biotype. Likewise, some microalgae extracts effectively killed C. elegans L1 larvae. Comprehensive metabolic profiling using LC-MS of extracts with pesticide activities showed that the metabolite composition of Chlamydomonas, Chlorella, and Chloroidium extracts is diverse. Molecules such as fatty acids, isoquinoline alkaloids, aldehydes, and cinnamic acids were more abundant, suggesting their participation in the pesticide activities. Full article

Regression models are extensively used to explore the relationship between a dependent variable and its covariates. These models work well when the dependent variable is categorical and the data are supposedly independent, as is the case with generalized linear models (GLMs). However, trait data from related species do not operate under these conditions due to their shared common ancestry, leading to dependence that can be illustrated through a phylogenetic tree. In response to the analytical challenges of count-dependent variables in phylogenetically related species, we have developed a novel phylogenetic negative binomial regression model that allows for overdispersion, a limitation present in the phylogenetic Poisson regression model in the literature. This model overcomes limitations of conventional GLMs, which overlook the inherent dependence arising from shared lineage. Instead, our proposed model acknowledges this factor and uses the generalized estimating equation (GEE) framework for precise parameter estimation. The effectiveness of the proposed model was corroborated by a rigorous simulation study, which, despite the need for careful convergence monitoring, demonstrated its reasonable efficacy. The empirical application of the model to lizard egg-laying count and mammalian litter size data further highlighted its practical relevance. In particular, our results identified negative correlations between increases in egg mass, litter size, ovulation rate, and gestation length with respective yearly counts, while a positive correlation was observed with species lifespan. This study underscores the importance of our proposed model in providing nuanced and accurate analyses of count-dependent variables in related species, highlighting the often overlooked impact of shared ancestry. The model represents a critical advance in research methodologies, opening new avenues for interpretation of related species data in the field. Full article

Bone formation is driven by many signaling molecules including bone morphogenetic protein 9 (BMP-9) and hypoxia-inducible factor 1-alpha (HIF-1α). We demonstrated that cell therapy using mesenchymal stem cells (MSCs) overexpressing BMP-9 (MSCs^+BMP-9) enhances bone formation in calvarial defects. Here, the effect of hypoxia on BMP components and targets of MSCs^+BMP-9 and of these hypoxia-primed cells on osteoblast differentiation and bone repair was evaluated. Hypoxia was induced with cobalt chloride (CoCl₂) in MSCs^+BMP-9, and the expression of BMP components and targets was evaluated. The paracrine effects of hypoxia-primed MSCs^+BMP-9 on cell viability and migration and osteoblast differentiation were evaluated using conditioned medium. The bone formation induced by hypoxia-primed MSCs^+BMP-9 directly injected into rat calvarial defects was also evaluated. The results demonstrated that hypoxia regulated BMP components and targets without affecting BMP-9 amount and that the conditioned medium generated under hypoxia favored cell migration and osteoblast differentiation. Hypoxia-primed MSCs^+BMP-9 did not increase bone repair compared with control MSCs^+BMP-9. Thus, despite the lack of effect of hypoxia on bone formation, the enhancement of cell migration and osteoblast differentiation opens windows for further investigations on approaches to modulate the BMP-9-HIF-1α circuit in the context of cell-based therapies to induce bone regeneration. Full article

Macrobenthos is widely used as an indicator of ecological health in marine monitoring and assessment. The present study aimed to characterize the interrelationships between the distribution of the macrobenthos community and environmental factors near Xiaoqing Estuary, Laizhou Bay. Responses of species richness to environmental factors were studied using the generalized additive model (GAM) and the Margalef diversity index (d_M) as indicators of species diversity instead of individual indicator species. Six factors were selected in the optimal model by stepwise regression: sediment factors (organic matter, phosphate, nitrate nitrogen, and ammonium nitrogen) and water factors (salinity, and ammonium nitrogen). The response curves generated by the GAM showed a unimodal relationship among taxa diversity, salinity in water, and sediment organic matter. d_M was positively correlated with ammonium nitrogen in water and was negatively correlated with phosphate in the sediment. The model optimized by forward stepwise optimization explained 92.6% of the Margalef diversity index with a small residual (2.67). The model showed good performance, with the measured d_M strongly correlated with the predicted d_M (Pearson R² = 0.845, p < 0.05). The current study examined the combined influence of multiple eco-factors on macrobenthos, and the Margalef diversity index of macrobenthos was predicted by the GAM model in a salinity-stressed estuary. Full article

Hirame novirhabdovirus (HIRRV) is one of most serious viral pathogens causing significant economic losses to the flounder (Paralichthys olivaceus)-farming industry. Previous studies have shown that the outbreak of HIRRV is highly temperature-dependent, and revealed the viral replication was significantly affected by the antiviral response of flounders under different temperatures. In the present study, the proteome and phosphoproteome was used to analyze the different antiviral responses in the HIRRV-infected flounder under 10 °C and 20 °C. Post viral infection, 472 differentially expressed proteins (DEPs) were identified in the spleen of flounder under 10 °C, which related to NOD-like receptor signaling pathway, RIG-I-like receptor signaling pathway, RNA transport and so on. Under 20 °C, 652 DEPs were identified and involved in focal adhesion, regulation of actin cytoskeleton, phagosome, NOD-like receptor signaling pathway and RIG-I-like receptor signaling pathway. Phosphoproteome analysis showed that 675 differentially expressed phosphoproteins (DEPPs) were identified in the viral infected spleen under 10 °C and significantly enriched in Spliceosome, signaling pathway, necroptosis and RNA transport. Under 20 °C, 1304 DEPPs were identified and significantly enriched to Proteasome, VEGF signaling pathway, apoptosis, Spliceosome, mTOR signaling pathway, mRNA surveillance pathway, and RNA transport. To be noted, the proteins and phosphoproteins involved in interferon production and signaling showed significant upregulations in the viral infected flounder under 20 °C compared with that under 10 °C. Furthermore, the temporal expression profiles of eight selected antiviral-related mRNA including IRF3, IRF7, IKKβ, TBK1, IFIT1, IFI44, MX1 and ISG15 were detected by qRT-PCR, which showed a significantly stronger response at early infection under 20 °C. These results provided fundamental resources for subsequent in-depth research on the HIRRV infection mechanism and the antiviral immunity of flounder, and also gives evidences for the high mortality of HIRRV-infected flounder under low temperature. Full article

The aim of this study was to investigate the effects of acute high-intensity interval training (HIIT) on immune function and oxidative stress in male canoe/kayak athletes who were well trained. A total of 22 participants were voluntarily recruited with an age range of 15.9 ± 2.3 years, height of 172.2 ± 5.5 cm, body mass of 63.30 ± 6.95 kg, and body fat of 13.77 ± 3.76%. The modified Wingate kayaking test on a kayak ergometer was performed by all participants. Blood samples were collected at three different time points: before the test (Pre-T), immediately after (Post-T), and 3 h post-test (Post-3 h). Saliva samples were collected at two different time points: before the test (Pre-T) and 3 h after the test (Post-3 h). Results indicated that acute canoe/kayak ergometry HIIT had significant effects on the percentages and counts of leukocytes, neutrophils, lymphocytes, and lymphocyte subsets. Additionally, it resulted in increased total LPS-stimulated neutrophil elastase release and alterations in plasma concentrations of superoxide dismutase, catalase, and TBARS. These findings suggest that conventional kayak HIIT regimens can have short-term effects on immune function and induce oxidative stress in athletes. Full article

Biological modularity refers to the organization of living systems into separate functional units that interact in different combinations to promote individual well-being and species survival. Modularity provides a framework for generating and selecting variations that can lead to adaptive evolution. While the exact mechanisms underlying the evolution of modularity are still being explored, it is believed that the pressure of conflicting demands on limited resources is a primary selection force. One prominent example of conflicting demands is the trade-off between survival and reproduction. In this review, we explore the available evidence regarding the modularity of plant hormones within the context of the survival-reproduction trade-off. Our findings reveal that the cytokinin module is dedicated to maximizing reproduction, while the remaining hormone modules function to ensure reproduction. The signaling mechanisms of these hormone modules reflect their roles in this survival-reproduction trade-off. While the cytokinin response pathway exhibits a sequence of activation events that aligns with the developmental robustness expected from a hormone focused on reproduction, the remaining hormone modules employ double-negative signaling mechanisms, which reflects the necessity to prevent the excessive allocation of resources to survival. Full article

Microalgae are well known for their metal sorption capacities, but their potential in the remediation of hydrophobic organic compounds has received little attention in polar regions. We evaluated in the laboratory the ability of an Antarctic microalga to remediate diesel hydrocarbons and also investigated physiological changes consequent upon diesel exposure. Using a polyphasic taxonomic approach, the microalgal isolate, WCY_AQ5_1, originally sampled from Greenwich Island (South Shetland Islands, maritime Antarctica) was identified as Tritostichococcus sp. (OQ225631), a recently erected lineage within the redefined Stichococcus clade. Over a nine-day experimental incubation, 57.6% of diesel (~3.47 g/L) was removed via biosorption and biodegradation, demonstrating the strain’s potential for phytoremediation. Fourier transform infrared spectroscopy confirmed the adsorption of oil in accordance with its hydrophobic characteristics. Overall, degradation predominated over sorption of diesel. Chromatographic analysis confirmed that the strain efficiently metabolised medium-chain length n-alkanes (C-7 to C-21), particularly n-heneicosane. Mixotrophic cultivation using diesel as the organic carbon source under a constant light regime altered the car/chl-a ratio and triggered vacuolar activities. A small number of intracellular lipid droplets were observed on the seventh day of cultivation in transmission electron microscopic imaging. This is the first confirmation of diesel remediation ability in an Antarctic green microalga. Full article

(1) Background: Since 2013, the pathogenic bacterium Xylella fastidiosa has been severely affecting olive production in Apulia, Italy, with consequences for the economy, local culture, landscape and biodiversity. The production of a phenolic extract from fresh olive leaves was employed for endotherapeutic injection into naturally infected olive trees by Xylella fastidiosa in Apulia region, Italy. (2) Methods: The effectiveness of the extract was tested in vitro and in planta in comparison with analogous treatments based on garlic powder and potassium phosphite. (3) Results: The uptake of phenolic compounds from olive leaves through a trunk injection system device resulted in a statistically significant increase in leaf area index and leaf area density, as well as in the growth of newly formed healthy shoots. Plant growth-promoting effects were also observed for potassium phosphite. Moreover, the bacteriostatic activities of the phenolic extract and of the garlic-powder-based solution have been demonstrated in in vitro tests. (4) Conclusions: The results obtained and the contained costs of extraction make the endotherapeutic treatment with phenolic compounds a promising strategy for controlling X fastidiosa to be tested on a larger scale, although the experiments conducted in this study proved not to be suitable for centenary trees. Full article

Karyotype diversity reflects genome integrity and stability. A strong correlation between karyotype diversity and species richness, meaning the number of species in a phylogenetic clade, was first reported in mammals over forty years ago: in mammalian phylogenetic clades, the standard deviation of karyotype diversity (KD) closely corresponded to species richness (SR) at the order level. These initial studies, however, did not control for phylogenetic signal, raising the possibility that the correlation was due to phylogenetic relatedness among species in a clade. Accordingly, karyotype diversity trivially reflects species richness simply as a passive consequence of adaptive radiation. A more recent study in mammals controlled for phylogenetic signals and established the correlation as phylogenetically independent, suggesting that species richness cannot, in itself, explain the observed corresponding karyotype diversity. The correlation is, therefore, remarkable because the molecular mechanisms contributing to karyotype diversity are evolutionarily independent of the ecological mechanisms contributing to species richness. Recently, it was shown in salamanders that the two processes generating genome size diversity and species richness were indeed independent and operate in parallel, suggesting a potential non-adaptive, non-causal but biologically meaningful relationship. KD depends on mutational input generating genetic diversity and reflects genome stability, whereas species richness depends on ecological factors and reflects natural selection acting on phenotypic diversity. As mutation and selection operate independently and involve separate and unrelated evolutionary mechanisms—there is no reason a priori to expect such a strong, let alone any, correlation between KD and SR. That such a correlation exists is more consistent with Kimura’s theory of non-adaptive radiation than with ecologically based adaptive theories of macro-evolution, which are not excluded in Kimura’s non-adaptive theory. The following reviews recent evidence in support of Kimura’s proposal, and other findings that contribute to a wider understanding of the molecular mechanisms underlying the process of non-adaptive radiation. Full article

Traumatic brain injury (TBI) is one of the leading causes of long-lasting morbidity and mortality worldwide, being a devastating condition related to the impairment of the nervous system after an external traumatic event resulting in transitory or permanent functional disability, with a significant burden to the healthcare system. Harmful events underlying TBI can be classified into two sequential stages, primary and secondary, which are both associated with breakdown of the tissue homeostasis due to impairment of the blood–brain barrier, osmotic imbalance, inflammatory processes, oxidative stress, excitotoxicity, and apoptotic cell death, ultimately resulting in a loss of tissue functionality. The present study provides an updated review concerning the roles of brain edema, inflammation, excitotoxicity, and oxidative stress on brain changes resulting from a TBI. The proper characterization of the phenomena resulting from TBI can contribute to the improvement of care, rehabilitation and quality of life of the affected people. Full article

Extracellular vesicles (EVs) include exosomes, microvesicles, and apoptotic bodies. EVs are released by all cell types and are found in biological fluids including plasma and urine. Urinary extracellular vesicles (uEVs) are a mixed population of EVs that comprise small EVs that are filtered and excreted, EVs secreted by tubular epithelial cells, and EVs released from the bladder, urethra, and prostate. The packaged cargo within uEVs includes bioactive molecules such as metabolites, lipids, proteins, mRNAs, and miRNAs. These molecules are involved in intercellular communication, elicit changes in intracellular signaling pathways, and play a role in the pathogenesis of various diseases including diabetes-associated hypertension and diabetic nephropathy. uEVs represent a rich source of biomarkers, prognosis markers, and can be loaded with small-molecule drugs as a vehicle for delivery. Full article

This study aimed to analyze the hematological parameters, blood viscosity, and cytokines of dogs infected by Ehrlichia canis untreated and treated with doxycycline. Initially, 47 dogs were examined, and 36 were suspected to have canine monocytic ehrlichiosis, which was confirmed through molecular polymerase chain reaction tests. This study consisted of 25 dogs, with 11 being healthy and 14 testing positive for E. canis. The dogs were divided into experimental groups based on their test results, including a control group of healthy dogs (N = 11), a group of infected dogs without treatment (N = 7), and a group of infected dogs treated with doxycycline (N = 7) at a 10 mg/kg dose every 12 h for 28 days. Blood samples were taken to determine hematological parameters, viscosity, and cytokine levels. It was observed that, regardless of doxycycline treatment, there was a reduction in total leukocytes and lymphocytes in infected dogs with Ehrlichia canis. The eosinophils and platelets decreased in dogs with Ehrlichia canis infections without treatment. Monocytes, eosinophils, and platelets increased when the dogs were treated with doxycycline. Regardless of treatment, infected dogs’ blood viscosity was lower than uninfected dogs. Infected dogs showed lower TNF-α and increased IL-1β. There was a correlation between the blood viscosity with the cytokines IL-10 and IL-12 in the infected dogs. The eosinophil count correlated with TNF-α in the group of infected and untreated dogs. In conclusion, treating dogs with monocytic ehrlichiosis using doxycycline can increase platelet and eosinophil levels but may also increase IL-1β and monocyte levels, exacerbating inflammation. Therefore, evaluating viscosity and cytokine levels is important when treating dogs with this condition. Full article

The suprachiasmatic nuclei (SCN) of the hypothalamus contain the circadian pacemaker that coordinates mammalian rhythms in tune with the day-night cycle. Understanding the determinants of the intrinsic rhythmicity of this biological clock, its outputs, and resetting by environmental cues, has been a longstanding goal of the field. Integrated techniques of neurophysiology, including lesion studies and in vivo multi-unit electrophysiology, have been key to characterizing the rhythmic nature and outputs of the SCN in animal models. In parallel, reduced ex vivo and in vitro approaches have permitted us to unravel molecular, cellular, and multicellular mechanisms underlying the pacemaker properties of the SCN. New questions have emerged in recent years that will require combining investigation at a cell resolution within the physiological context of the living animal: What is the role of specific cell subpopulations in the SCN neural network? How do they integrate various external and internal inputs? What are the circuits involved in controlling other body rhythms? Here, we review what we have already learned about the SCN from in vivo studies, and how the recent development of new genetically encoded tools and cutting-edge imaging technology in neuroscience offers chronobiologists the opportunity to meet these challenges. Full article

Fish aquaculture is a rapidly expanding global industry, set to support growing demands for sources of marine protein. Enhancing feed efficiency (FE) in farmed fish is required to reduce production costs and improve sector sustainability. Recognising that organisms are complex systems whose emerging phenotypes are the product of multiple interacting molecular processes, systems-based approaches are expected to deliver new biological insights into FE and growth performance. Here, we establish 14 diverse layers of multi-omics and clinical covariates to assess their capacities to predict FE and associated performance traits in a fish model (Oncorhynchus tshawytscha) and uncover the influential variables. Inter-omic relatedness between the different layers revealed several significant concordances, particularly between datasets originating from similar material/tissue and between blood indicators and some of the proteomic (liver), metabolomic (liver), and microbiomic layers. Single- and multi-layer random forest (RF) regression models showed that integration of all data layers provide greater FE prediction power than any single-layer model alone. Although FE was among the most challenging of the traits we attempted to predict, the mean accuracy of 40 different FE models in terms of root-mean square errors normalized to percentage was 30.4%, supporting RF as a feature selection tool and approach for complex trait prediction. Major contributions to the integrated FE models were derived from layers of proteomic and metabolomic data, with substantial influence also provided by the lipid composition layer. A correlation matrix of the top 27 variables in the models highlighted FE trait-associations with faecal bacteria (Serratia spp.), palmitic and nervonic acid moieties in whole body lipids, levels of free glycerol in muscle, and N-acetylglutamic acid content in liver. In summary, we identified subsets of molecular characteristics for the assessment of commercially relevant performance-based metrics in farmed Chinook salmon. Full article

Human neuroblastoma (NB) is the most common childhood extracranial tumor arising from the sympathetic nervous system. It is also a clinically heterogeneous disease that ranges from spontaneous regression to high-risk stage 4 disease. The cause of this disease remains elusive. However, the amplification of NMYC oncogene occurred in roughly 30% of NB patients, which strongly correlated with the advanced stage of disease subtype and the worse prognosis status. We discovered that N-Myc oncoprotein binds and activates INSM1, a zinc-finger transcription factor of neuroendocrine tumors. We also found that INSM1 modulates N-Myc stability mediated through PI3K/AKT/GSK3β signaling pathway. Therefore, INSM1 emerges as a critical co-player with N-Myc in facilitating NB tumor cell growth and sustaining the advanced stage of malignancy. Using an INSM1-promoter driven luciferase screening-platform, we have recently identified fifteen small molecules that negatively regulate INSM1 expression. Interestingly, the identified small molecules can be divided into four large groups of compounds such as cell signaling inhibitor, DNA/RNA inhibitor, HDAC inhibitor, and cardiac glycoside. These findings support the presence of a unique mechanism associated with INSM1 and N-Myc interplay, which is critical in regulating NB tumor cell growth. We discuss the feasibility of identifying novel or repurposing small molecules targeting INSM1 as a potential treatment option for high-risk NB. Full article

Cardiovascular disease (CVD) is the leading cause of death globally. The underlying pathological driver of CVD is atherosclerosis. The primary risk factor for atherosclerosis is elevated low-density lipoprotein cholesterol (LDL-C). Dysregulation of cholesterol metabolism is synonymous with a rise in LDL-C. Due to the complexity of cholesterol metabolism and atherosclerosis mathematical models are routinely used to explore their non-trivial dynamics. Mathematical modelling has generated a wealth of useful biological insights, which have deepened our understanding of these processes. To date however, no model has been developed which fully captures how whole-body cholesterol metabolism intersects with atherosclerosis. The main reason for this is one of scale. Whole body cholesterol metabolism is defined by macroscale physiological processes, while atherosclerosis operates mainly at a microscale. This work describes how a model of cholesterol metabolism was combined with a model of atherosclerotic plaque formation. This new model is capable of reproducing the output from its parent models. Using the new model, we demonstrate how this system can be utilized to identify interventions that lower LDL-C and abrogate plaque formation. Full article

The variability observed in the annual seed production of perennial plants can be seen as an indication of changes in the allocation of resources between growth and reproduction, which can be attributed to fluctuations in the environment. However, a significant knowledge gap exists concerning the impacts of nitrogen addition on the interannual seed production patterns of perennial plants. We hypothesized that the addition of nitrogen would impact the annual variations in the seed production of perennial plants, ultimately affecting their overall reproductive efficiency. A multiyear field experiment was conducted to investigate the effects of varying nitrogen supply levels (e.g., 0, 4, and 8 kg N ha⁻¹ yr⁻¹ of N0, N4, and N8) on vegetative and floral traits, pollinator visitation rates, and seed traits over a period of four consecutive years. The results showed that the N0 treatment exhibited the highest levels of seed production and reproductive efficiency within the initial two years. In contrast, the N4 treatment displayed its highest level of performance in these metrics in the second and third years, whereas the N8 treatment showcased its most favorable outcomes in the third and fourth years. Similar patterns were found in the number of flowers per capitulum and the number of capitula per plant. There exists a positive correlation between aboveground biomass and several factors, including the number of flowers per capitulum, the number of capitula per plant, the volume of nectar per capitulum, and the seed production per plant. A positive correlation was found between pollinator visitation and the number of flowers per capitulum or the number of capitula per plant. This implies that the addition of N affected the maintenance of plant aboveground biomass, flower trait stability, pollinator visitation, and, subsequently, the frequency of seed production and reproductive efficiency. Our results suggest that augmenting the nitrogen content in the soil may have the capacity to modify the inherent variability in seed production that is observed across various years and enhance the effectiveness of reproductive processes. These findings have the potential to enhance our comprehension of the impact of nitrogen addition on the reproductive performance of perennial herbaceous plants and the underlying mechanisms of biodiversity in the context of global environmental changes. Full article

Many cancers utilize l-glutamine as a major energy source. Often cited in the literature as “l-glutamine addiction”, this well-characterized pathway involves hydrolysis of l-glutamine by a glutaminase to l-glutamate, followed by oxidative deamination, or transamination, to α-ketoglutarate, which enters the tricarboxylic acid cycle. However, mammalian tissues/cancers possess a rarely mentioned, alternative pathway (the glutaminase II pathway): l-glutamine is transaminated to α-ketoglutaramate (KGM), followed by ω-amidase (ωA)-catalyzed hydrolysis of KGM to α-ketoglutarate. The name glutaminase II may be confused with the glutaminase 2 (GLS2) isozyme. Thus, we recently renamed the glutaminase II pathway the “glutamine transaminase—ω-amidase (GTωA)” pathway. Herein, we summarize the metabolic importance of the GTωA pathway, including its role in closing the methionine salvage pathway, and as a source of anaplerotic α-ketoglutarate. An advantage of the GTωA pathway is that there is no net change in redox status, permitting α-ketoglutarate production during hypoxia, diminishing cellular energy demands. We suggest that the ability to coordinate control of both pathways bestows a metabolic advantage to cancer cells. Finally, we discuss possible benefits of GTωA pathway inhibitors, not only as aids to studying the normal biological roles of the pathway but also as possible useful anticancer agents. Full article

Long-term overfertilization increases soil salinity and disease occurrence and reduces crop yield. Integrated application of microbial agents with low fertigation input might be a sustainable and cost-effective strategy. Herein, the promoting effects of Bacillus velezensis B006 on the growth of Chinese cabbage under different fertigation conditions in field trials were studied and the underlying mechanisms were revealed. In comparison with normal fertigation (water potential of −30 kPa and soluble N, P, K of 29.75, 8.26, 21.48 Kg hm⁻²) without B006 application, the combination of B. velezensis B006 and reduced fertigation input (−50 kPa and N, P, K of 11.75, 3.26, 6.48 Kg hm⁻²) promoted cabbage growth and root development, restrained the occurrence of soft rot disease, and improved the yield. High-performance liquid chromatography (HPLC) analyses indicated that B006 application promoted the production of indole-3-acetic acid and salicylic acid in cabbage roots, which are closely related to plant growth. Rhizosphere microbiota analyses indicated that the combination of low fertigation input and B006 application promoted the enrichment of Streptomyces, Lechevalieria, Promicromonospora, and Aeromicrobium and the abundance of Lechevalieria was positively correlated with the root length and vitality. This suggested that the integrated application of reduced fertigation and Bacillus is highly efficient to improve soil ecology and productivity and will benefit the sustainable development of crop cultivation in a cost-effective way. Full article

Metabolic dysregulation has been reported involving in the clinical outcomes of multiple cancers. However, systematical identification of the impact of metabolic pathways on cancer prognosis is still lacking. Here, we performed a pan-cancer analysis of popular metabolic checkpoint genes and pathways with cancer prognosis by integrating information of clinical survival with gene expression and pathway activity in multiple cancer patients. By discarding the effects of age and sex, we revealed extensive and significant associations between the survival of cancer patients and the expression of metabolic checkpoint genes, as well as the activities of three primary metabolic pathways: amino acid metabolism, carbohydrate metabolism, lipid metabolism, and eight nonprimary metabolic pathways. Among multiple cancers, we found the survival of kidney renal clear cell carcinoma and low-grade glioma exhibit high metabolic dependence. Our work systematically assesses the impact of metabolic checkpoint genes and pathways on cancer prognosis, providing clues for further study of cancer diagnosis and therapy. Full article

Due to the limited biological research on the blue shark in the Indian Ocean, such as the lack of a clear understanding of its reproductive biology and distribution, our study analyzed and evaluated the fork length distribution, sexual maturity length, reproductive capacity, and spatiotemporal distribution of blue sharks based on biological data and capture location information collected in the western Indian Ocean from 2010 to 2020. The objective of this study is to provide reliable biological information important in performing future stock assessments vital for species conservation in this region. A total of 791 male (33–249.5 cm FL) and 803 female (12–349.6 cm FL) blue sharks were collected in the West Indian Ocean. We used the morphology of the sexual organs to ascertain their sexual maturity. Results show that the observed size at 50% sexual maturity of male blue sharks in the West Indian Ocean was 161.4cm FL (192.4 cm TL) for males and 179.3 cm FL (213.9 cm TL) for females based on logistic curve analysis. The average litter size of pregnant blue sharks was 33.7 pups. There were significant differences in the distribution of blue shark individuals with different sexual maturity levels in different quarters (p < 0.05). This study suggests that the area near the equator in the Indian Ocean from October to March of the following year may be the mating ground for blue sharks, while the temperate waters in the Indian Ocean are the nursery ground and parturition ground for pregnant and juvenile throughout the whole year. Therefore, it is recommended to adopt a more scientific and reasonable operational method in these areas. Full article

Gene and genome comparison represent an invaluable tool to identify evolutionarily conserved sequences with possible functional significance. In this work, we have analyzed orthologous genes encoding subunits and assembly factors of the V-ATPase complex, an important enzymatic complex of the vacuolar and lysosomal compartments of the eukaryotic cell with storage and recycling functions, respectively, as well as the main pump in the plasma membrane that energizes the epithelial transport in insects. This study involves 70 insect species belonging to eight insect orders. We highlighted the conservation of a short sequence in the genes encoding subunits of the V-ATPase complex and their assembly factors analyzed with respect to their exon-intron organization of those genes. This study offers the possibility to study ultra-conserved regulatory elements under an evolutionary perspective, with the aim of expanding our knowledge on the regulation of complex gene networks at the basis of organellar biogenesis and cellular organization. Full article

Background: Bladder cancer (BCa) in patients suffering from neurogenic lower urinary tract dysfunction (NLUTD) is a significant concern due to its advanced stage at diagnosis and high mortality rate. Currently, there is a scarcity of specific guidelines for BCa screening in these patients. The development of urine biomarkers for BCa seems to be an attractive non-invasive method of screening or risk stratification in this patient population. DNA methylation is an epigenetic modification, resulting in the transcriptional silencing of tumor suppression genes, that is frequently detected in the urine of BCa patients. Objectives: We aimed to investigate DNA hypermethylation in five gene promoters, previously associated with BCa, in the urine of NLUTD patients, and in comparison with healthy controls. Design, setting and participants: This was a prospective case–control study that recruited neurourology outpatients from a public teaching hospital who had suffered from NLUTD for at least 5 years. They all underwent cystoscopy combined with biopsy for BCa screening following written informed consent. DNA was extracted and DNA methylation was assessed for the RASSF1, RARβ, DAPK, TERT and APC gene promoters via quantitative methylation-specific PCR in urine specimens from the patients and controls. Results: Forty-one patients of mixed NLUTD etiology and 35 controls were enrolled. DNA was detected in 36 patients’ urine specimens and in those of 22 controls. In the urine specimens, DNA was hypermethylated in at least one of five gene promoters in 17/36 patients and in 3/22 controls (47.22% vs. 13.64%, respectively, p = 0.009). RASSF1 was hypermethylated in 10/17 (58.82%) specimens with detected methylation, APC in 7/17 (41.18%), DAPK in 4/17 (23.53%), RAR-β2 in 3/17 (17.56%) and TERT in none. According to a multivariate logistic regression analysis, NLUTD and male gender were significantly associated with hypermethylation (OR = 7.43, p = 0.007 and OR = 4.21; p = 0.04, respectively). In the tissue specimens, histology revealed TaLG BCa in two patients and urothelial squamous metaplasia in five patients. Chronic bladder inflammation was present in 35/41 bladder biopsies. Conclusions: DNA hypermethylation in a panel of five BCa-associated genes in the urine was significantly more frequent in NLUTD patients than in the controls. Our results warrant further evaluation in longitudinal studies assessing the clinical implications and possible associations between DNA hypermethylation, chronic inflammation and BCa in the NLUTD population. Full article

Long human ultra-conserved non-coding elements (UCNEs) do not have any sequence similarity to each other or other characteristics that make them unalterable during vertebrate evolution. We hypothesized that UCNEs have unique dinucleotide (DN) composition and arrangements compared to the rest of the genome. A total of 4272 human UCNE sequences were analyzed computationally and compared with the whole genomes of human, chicken, zebrafish, and fly. Statistical analysis was performed to assess the non-randomness in DN spacing arrangements within the entire human genome and within UCNEs. Significant non-randomness in DN spacing arrangements was observed in the entire human genome. Additionally, UCNEs exhibited distinct patterns in DN arrangements compared to the rest of the genome. Approximately 83% of all DN pairs within UCNEs showed significant (>10%) non-random genomic arrangements at short distances (2–6 nucleotides) relative to each other. At the extremes, non-randomness in DN spacing distances deviated up to 40% from expected values and were frequently associated with GpC, CpG, ApT, and GpG/CpC dinucleotides. The described peculiarities in DN arrangements have persisted for hundreds of millions of years in vertebrates. These distinctive patterns may suggest that UCNEs have specific DNA conformations. Full article