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Reconciling intrinsic and ecosystem water-use efficiency reveals physiological mechanisms underlying carbon-water coupling across biological scales

Understanding how carbon-water coupling scales from leaves to ecosystems remains a major challenge because water-use efficiency (WUE) metrics integrate physiological, hydrological, and ecological processes. We integrated tree-ring width, triple stable isotopes ({delta}13C, {delta}18O and {delta}2H), eddy covariance (EC) observations, and a process-based model to investigate the drivers of intrinsic (iWUE) and ecosystem water-use efficiency (WUEeco) across biological scales in a mature Fagus sylvatica forest between 2004 and 2023. Modelled and isotope-derived iWUE were strongly correlated (r = 0.61, p < 0.05) and both indicated an approximately 20% long-term increase, consistent with increasing gross primary productivity. In contrast, WUEeco derived from EC was lower than model estimates and exhibited a positive trend not reproduced by the model. This divergence primarily reflected differences in biological representation and hydrological integration, as the single-species model underestimated ecosystem evapotranspiration by excluding co-occurring deciduous and evergreen species together with understory vegetation. Triple-isotope analyses showed that the long-term increase in iWUE was driven by enhanced photosynthetic assimilation rather than sustained stomatal closure, whereas {delta}18O and {delta}2H variability was mainly controlled by source-water dynamics. These findings provide a mechanistic framework for reconciling leaf- and ecosystem-scale WUE and improving predictions of forest carbon-water coupling under climate change.

ecology↗

Genomic and physiological characterization of Neobacillus ammoniipjilus sp. nov. reveals versatile inorganic nitrogen utilization and ammonia-mitigation potential

A novel bacterial strain (KR4-4T), was isolated from soil in the Republic of Korea and subjected to polyphasic taxonomic and functional characterization. Phylogenetic analysis based on the 16S rRNA gene sequence placed strain KR4-4T within the genus Neobacillus. Phylogenomic analysis based on 92 bacterial core genes further supported its distinct taxonomic position. Average nucleotide identity and digital DNA-DNA hybridization values between KR4-4T and related Neobacillus type strains were 69.76-82.31% and 18.3-25.9%, respectively, supporting its recognition as a distinct species. Cells were Gram-stain-positive, non-motile, facultatively anaerobic rods, with growth occurring at 15-45 {degrees}C, pH 6.0-8.0, and 0-2.0% (w/v) NaCl. The major cellular fatty acids were iso-C15:0 and anteiso-C15:0, while the major polar lipids included diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylethanolamine. Genome analysis revealed genes associated with inorganic nitrogen transport, nitrate and nitrite reduction, and ammonium assimilation. In liquid culture, KR4-4T removed NH4+-N under aerobic conditions and was able to utilize ammonium, nitrate, and nitrite as individual nitrogen sources, with removal efficiencies of 86.5%, 69.35%, and 62.9%, respectively. The strain also contributed to the reduction of gaseous NH3 in a closed-flask assay. Together, these physiological and genomic characteristics indicate a versatile capacity for inorganic nitrogen utilization and transformation and suggest potential for further evaluation in biological ammonia-mitigation applications. Based on phylogenetic, genomic, phenotypic, and chemotaxonomic evidence, strain KR4-4T represents a novel species of the genus Neobacillus, for which the name Neobacillus ammoniiphilus sp. nov. is proposed. The type strain is KR4-4T (= KACC 24003T = CCTCC AB 2025077T).

microbiology↗

Diverse stresses converge on bacterial periplasmic expansion through distinct physiological mechanisms

Diverse environmental and antibiotic stresses induce localized periplasmic expansion, the separation of the inner membrane from the cell wall and outer membrane, in Gram-negative bacteria, yet whether these morphologically similar responses arise through a common mechanism remains unclear. Here, we compare periplasmic expansion induced by sudden starvation, ciprofloxacin, mitomycin C, and globomycin in Escherichia coli. We find that these perturbations produce similar morphologies through distinct physiological and mechanical routes. Ciprofloxacin- and mitomycin C-induced periplasmic expansion coincides with loss of turgor, whereas starvation requires water efflux, and globomycin leads to unequal expansion of the inner and outer membrane as a result of aberrant inner membrane-cell wall crosslinking. Outer membrane stiffness modulates expansion during ciprofloxacin treatment. Despite these distinct mechanisms, robust periplasmic expansion during starvation and treatment with ciprofloxacin or globomycin requires UDP-glucose synthesis. Together, these findings establish periplasmic expansion as a convergent physical outcome of diverse stresses and reveal the remarkable plasticity of the Gram-negative cell envelope.

microbiology↗

Ascorbate is a physiological tumor suppressor metabolite in leukemia

Accumulation of oncometabolites promotes tumorigenesis, but it is not known if there are naturally occurring tumor suppressor metabolites whose deficiency within cancer-initiating cells causes cancer. Many leukemia patients are ascorbate deficient. Here we show that hematopoietic-specific ascorbate depletion in mice is sufficient to cause or promote leukemogenesis. Hematopoietic-specific ascorbate depletion promoted leukemogenesis by acting within leukemia initiating cells. Ascorbate depletion in myeloid leukemia expanded plasmacytoid dendritic cells, an effect mediated by the ascorbate molecular targets TET2 and TET3. Leukemia cells accumulated ascorbate as part of a tumor suppressor response to neoplastic proliferation that limited progression but depleted circulating ascorbate. Ascorbate restoration in mice with established leukemias extended survival. Hematopoietic-specific ascorbate depletion caused leukemia in collaboration with TET2 loss and was sufficient to cause leukemia with high penetrance even in the absence of other engineered mutations. These results identify ascorbate as a physiological tumor suppressor metabolite in blood cancers.

cancer biology↗

Cisplatin Exposure Alters the Effects of Honokiol on Genes Involved in Outer Hair Cell Physiological Function

Outer hair cell (OHC) loss occurs in cisplatin-induced hearing loss (CIHL). We previously reported that honokiol protects against CIHL and mitigates cisplatin-induced transcriptomic changes in OHCs. Here, we re-analyzed OHC RNA-seq to determine whether honokiol differentially affects genes involved in OHC physiological function depending on cisplatin exposure. Twenty-two genes involved in mechanotransduction and hair bundle function, membrane potential and ion homeostasis, electromotility, and efferent regulation were selected. Among 20 genes with available interaction statistics, 16 showed significant Honokiol x Cisplatin interactions, of which 15 were negative. Notably, in the presence of cisplatin, honokiol downregulated several genes associated with mechanotransduction (MET) machinery, including Lhfpl5, Tmc1, Cib2, and Tomt. Because MET channels have been implicated in cisplatin entry into hair cells, these changes raise the possibility that altered MET machinery may contribute to honokiol-mediated protection against CIHL. However, whether these changes decrease cisplatin uptake remains to be determined.

neuroscience↗

Dietary fructose promotes anxiety through impairment of microglia physiology

Excessive dietary fructose has been linked to metabolic and mood disorders but the underlying brain mechanisms remain unclear. In this study, we tested whether microglia, the brain resident immune cells, mediate fructose-induced anxiety. Adult C57BL/6J mice and mice knock-down for the fructose transporter Glut5 selectively in microglia (Slc2a5flox/flox:Tmem119-Cre-positive mice) were exposed to 25% fructose in drinking water for 8 weeks. We assessed metabolic parameters, anxiety- and depression-like behaviors using a battery of behavioral tests. We then performed RNA sequencing in several brain regions, including the hippocampus to characterize fructose-induced transcriptional changes. Microglial responsiveness to lipopolysaccharide (LPS) treatment was assessed in vitro and in vivo using immunohistochemistry (microglia morphology) and RT-qPCR (cytokine gene expression). Fructose feeding induced marked metabolic alterations and robust anxiety-like behavior in male mice, together with memory deficits, whereas females showed milder metabolic changes and memory impairment without clear emotional disturbances. RNA sequencing revealed that fructose alters microglial gene-expression profiles in the hippocampus. Microglial Glut5 knockdown prevented fructose-induced anxiety-like behavior in the novelty-suppressed feeding test, indicating that microglial fructose uptake is required for this effect. At the molecular level, physiological fructose exposure did not markedly increase microglial cytokine expression but blunted the cytokine response to lipopolysaccharide, consistent with a hypo-reactive microglial state. Overall, these findings identify microglia as a critical mediator of fructose-induced anxiety and suggest that chronic fructose exposure promotes a maladaptive microglial phenotype that disrupts brain circuit function, with potential implications for diet-related mental health risk.

neuroscience↗

Concurrent cognitive, behavioral and systemic physiological features mark preclinical Alzheimer's disease

Alzheimer's disease (AD) pathology accumulates years before overt cognitive impairment, yet its multidomain phenotype remains poorly defined. To limit confounding by uncontrolled comorbidities, we assembled a cohort of 644 older adults self-reporting intact cognition, free of systemic or neurological diseases and managed medically for risk factors. Plasma p-tau217 was elevated in 20%, and 93 of these were cognitively unimpaired. This biomarker-defined, risk factor -controlled preclinical AD subgroup showed subtle, concurrent cognitive and behavioral differences, accompanied by modest differences in physiological measures within clinical reference ranges, and alongside higher biomarkers of astrogliosis (GFAP) and neurodegeneration (NfL). Reported modifiable risk factor histories were not associated with p-tau217 when effectively managed. A proof-of-concept AI classifier integrating routine multidomain clinical data improved identification of p-tau217-high individuals relative to cognitive screening alone. These findings indicate preclinical AD is not phenotypically silent at the group level and support multidomain-based screening for biomarker testing and early-detection.

neuroscience↗

Volatile organic compounds of L. enzymogenes LEC suppress the growth of fungal and oomycete pathogens and modify the cell physiology of Rhizoctonia solani

Lysobacter enzymogenes LEC is a plant disease-suppressive bacterium. To obtain a more comprehensive understanding of its biocontrol activity and to identify further potential application methods, we investigated the function of its volatile organic compounds (VOCs). VOC activity was assessed in vitro using split-plate assays with eight different fungal and oomycete isolates and in planta against Pseudoperonospora cubensis on cucumber plants. The volatilomes of LEC and the less active L. enzymogenes DSM2043 were analysed by GC-MS analyses. Further, the effects of VOCs on cell physiology of Rhizoctonia solani were analyzed by fluorescence and transmission electron microscopy. The strongest inhibition of LEC VOCs was observed for Phytophthora infestans (94%) and Phoma lingam (83%), while inhibitions were lower for Rhizoctonia solani (42%) and Alternaria spp. (24% and 29%) and not detectable for two Fusarium isolates. VOC exposure also significantly reduced downy mildew caused by P. cubensis on cucumber plants (39%), although this effect was locally restricted to the leaf directly above the VOC source. In R. solani, VOC exposure reduced nuclei abundance and increased lipid accumulation. GC MS analyses revealed distinct volatile profiles between LEC and L. enzymogenes DSM2043 and identified ketones, such as 2-dodecanone and undecanone as candidate bioactive compounds, which is in agreement with previous findings. Our results demonstrate broad-spectrum VOC-mediated biocontrol activity, and thereby provide a more comprehensive understanding of its biocontrol activity and highlight new ways for potential applications of LEC.

microbiology↗

Physiological mapping and prediction reveal stress-responsive translation initiation landscapes

Translation initiation defines the protein output of the transcriptome, but its physiological dynamics in cells and tissues remain incompletely characterized. Here we develop TISCA2, an inhibitor-free method that captures eIF5B-associated initiating ribosomes to map translation initiation sites genome-wide. By directly identifying start sites rather than inferring translation from elongating-ribosome periodicity, TISCA2 improves the detection of short and overlapping translons. Translation of a subset of TISCA2-identified translons is supported by N-terminal proteomics and HLA-I immunopeptidomics. The arsenite-induced integrated stress response broadly redistributes start-site usage, reducing upstream initiation in favor of downstream initiation. TISCA2 further reveals tissue-specific initiation landscapes in vivo, with increased detection of downstream candidate start sites in the testis. Finally, we develop IncepTIS, a sequence-based deep learning model that predicts position-resolved and condition-dependent initiation landscapes. IncepTIS-guided optimization generates de novo mRNA 5' leaders with stress-responsive initiation patterns. Together, TISCA2 and IncepTIS provide an experimental and computational framework for mapping, predicting and engineering translation initiation in mammalian cells and tissues.

molecular biology↗

Hyper-variability in Circulating Insulin and Physiological Outcomes in Male High Fat-fed Ins1-/-:Ins2+/- Mice in a Conventional Facility

Insulin is an ancient, multi-functional hormone with essential roles in glucose homeostasis and energy storage. Recently, our group has taken advantage of the ability to limit insulin secretion in vivo by reducing insulin gene dosage to demonstrate that insulin hypersecretion is a requirement for diet-induced obesity. Our previous studies employed male Ins1+/-:Ins2-/- mice that exhibit a complete inhibition of diet-induced hyperinsulinemia relative to Ins1+/+:Ins2-/- littermate controls, as well as female Ins1-/-:Ins2+/- mice with transient, partial reduction in circulating insulin relative to Ins1-/-:Ins2+/+ littermates. In the present study, we sought to extend these studies to male Ins1-/-:Ins2+/- mice on the same chow and high fat diets. Surprisingly, while reduced Ins2 gene dosage appeared capable of reducing Ins2 mRNA, insulin protein levels in these mice were not significantly reduced. Moreover, there was a marked hyper-variability in circulating insulin levels within and between two independent cohorts of mice that persisted over at least the first year of life. In Cohort 1, we observed a paradoxical increase in body weight in some high fat-fed male Ins1-/-:Ins2+/- mice relative to Ins1-/-:Ins2+/+ littermate controls. This phenomenon is consistent with the known satiety effects of insulin and our previous observations with Ins2 can be expressed in the brain. Collectively, our data reveal unexpected complexity associated with the Ins2 gene in male mice, and establish the Ins2 gene as a candidate for studying the effects of modifier genes and/or environmental influences on gene-to-phenotype variability. Further studies are required to define the molecular mechanisms of this phenotypic hyper-variability and to define the role of reduced Ins2 gene dosage in the brain.

Physiology↗

Measuring physiological responses to stressors using a novel Hmox1 reporter mouse

Hmox1 protein holds great promise as a biomarker of organismal health as it is highly expressed in stressed or damaged cells. However, documenting Hmox1 expression patterns has thus far only been feasible in simple model organisms with limited relevance to humans. We now report a new Hmox1 reporter line that makes it possible to access this information in mice, the premiere model system for studying human disease and toxicology. Using a state-of-the-art strategy, we express multiple complementary reporter molecules from the murine Hmox1 locus, including firefly luciferase to allow long-term, non-invasive imaging of Hmox1 expression, and {beta}-galactosidase for high-resolution mapping of expression patterns post-mortem. We validate the model by confirming the absence of haplo-insufficiency effects, the fidelity of reporter expression, and its responsiveness to oxidative and inflammatory stimuli. In addition to providing blueprints for Hmox1 expression in mice that provide novel biological insights for follow-up, this work paves the way for the broad application of this model to regulatory toxicology studies and, also, pre-clinical investigations into human degenerative diseases.

physiology↗

Parametric Imaging Of FDG-PET Data Using Physiology And Iterative Regularization: Application To The Hepatic And Renal Systems

I. AIMS I. AIMS II. METHODS III. RESULTS IV. CONCLUSIONS REFERENCES Positron Emission Tomography (PET) [1] is a nuclear medicine imaging technique capable of detecting the time dependent spatial distribution of pico-molar quantities of a labelled tracer, which is diffused into a living body. FDG-PET is a PET modality in which the radiopharmaceutical [18F]Fluoro-2-deoxy-D-glucose (FDG) is used as a tracer to observe metabolic processes related to glucose consumption. In order to overcome the limits of spatial resolution in PET and to improve the quality of information achievable from PET images, one approach is to develop parametric imaging methods able of showing the tracer metabolism at a local level. Starting from the design of compartmental models appropriate to describe the tracer kinetics in a predefined physiol ...

physiology↗

Physiological factors of importance for load carriage

The energy expenditure during carrying no load, 20, 35 and 50 kg at two walking speeds, 3 and 5 km h-1, was studied in 36 healthy participants, 19 men (30 {+/-} 6 yrs, 82.5 {+/-} 7.0 kg) and 17 women (29 {+/-} 6 yrs, 66.1 {+/-} 8.9 kg). Anthropometric data, leg muscle strength as well as trunk muscle endurance and muscle fibre distribution of the thigh were also obtained. To load the participant a standard backpack filled with extra weight according to the carrying weight tested was used. Extra Load Index (ELI), the oxygen uptake (VO2) during total load over no-load-exercise, was used as a proxy for load carrying ability. In addition to analyzing factors of importance for the ELI values, we also conducted mediator analyzes using sex and long term carrying experience as causal variables for ELI as the outcome value.\n\nFor the lowest load (20 kg), ELI20, was correlated with body mass but no other factors. Walking at 5 km h-1 body mass, body height, leg muscle strength and absolute VO2max were correlated to ELI35 and ELI50, but relative VO2max, trunk muscle endurance and leg muscle fibre distribution were not.\n\nSex as causal factor was evaluated in a mediator analyses with ELI50 as outcome. ELI50 at 5 km h-1 differed between the sexes. The limit for acceptable body load, 40 % of VO2max (according to [A]strand, 1967), was nearly reached for women carrying 35 kg (39%) and surpassed at 50 kg at 3 km h-1, and for men carrying 50 kg at 5 km h-1. This difference was only mediated by difference in body mass. Neither muscle fibre distribution, leg muscle strength, trunk muscle endurance and body height nor did absolute or relative VO2max explain the difference.\n\nParticipants with long term experience of heavy load carrying had significant lower ELI20 and ELI50 values than those with minor or non-experience, but none of the above studied factors could explain this difference.\n\nThe study showed that body mass and experience of carrying heavy loads are important factors for the ability to carry heavy loads.\n\nFundingThis study was founded by the Swedish Military Forces{acute} Research Authority and The Research Funds of The Swedish School of Sport and Health Sciences.\n\nAbbreviations

physiology↗

Serum biochemistry suggests grey squirrels (Sciurus carolinensis) have poorer physiological condition in urban settings

Human food waste in cities presents urban wildlife with predictable, easily accessible high-calorie food sources, but this can be both beneficial and harmful for individual health. We analyzed body condition and serum chemistry (electrolyte levels, markers of kidney and liver function, protein, glucose, and cholesterol) in an urban and rural population of eastern grey squirrels (Sciurus carolinensis) to assess whether proximity to the human food waste that is associated with urban habitats had ill effects on health. We found no differences in body condition between habitats and no evidence of malnutrition at either site. However, urban squirrels had higher blood glucose, lower potassium, phosphorus, chloride, and albumin:globulin ratios. These results align with previous findings of increased dietary sugar in cities, and suggest that urban populations of grey squirrels are under greater environmental stress than rural populations.

physiology↗

Area per player in small-sided games to replicate the external load and estimated physiological match demands in elite soccer players

The current study determined the area-per-player during small- or large-sided games with or without goalkeeper that replicates the relative (m{middle dot}min-1) total distance, high-intensity running distance, sprint distance and metabolic power covered during official matches. Time-motion analysis was performed on twenty-five elite soccer-players during 26 home-matches. A total of 2565 individual samples for SSGs using different pitch sizes and different number of players were collected and classified as SSGs with (SSG-G) or without goalkeeper (SSG-P). A between-position comparison was also performed. The area-per-player needed to replicate the official match demands was largely greater in SSG-G vs SSG-P for total distance [187{+/-}53 vs 115{+/-}35 m2, effect size (ES): 1.60 95%CI 0.94/2.21], high-intensity running distance [262{+/-}72 vs 166{+/-}39 m2, ES: 1.66(0.99/2.27)] and metabolic power [177{+/-}42 vs 94{+/-}40, ES: 1.99(1.31/2.67)], but similar for sprint distance [(316{+/-}75 vs 295{+/-}99 m2, ES: 0.24(-0.32/0.79)] with direction of larger area-per-player for sprint distance > high-intensity running > total distance {cong} metabolic power for both SSG-G and SSG-P. In SSG-G, forwards required greater area-per-player than central-defenders [ES: 2.96(1.07/4.35)], wide-midfielders [ES: 2.45(0.64/3.78)] and wide-defenders [ES: 3.45(1.13/4.99)]. Central-midfielders required greater area-per-player than central-defenders [ES: 1.69(0.20/2.90)] and wide-midfielders [ES: 1.35(-0.13/2.57)]. In SSG-P, central defenders need smaller area-per-player (ES: -6.01/-0.92) to overall replicate the match demands compared to all other positions. The current results highlight that soccer players need a specific area-per-player during the small-side games with or without goalkeeper to replicate the overall match demands, especially to perform high-intensity running or sprint distance. Additionally, central defenders, central midfielders and forwards need to be trained with tailored area-per-player or specific rules/additional exercises.

physiology↗

Differential TAM receptor regulation of hepatic physiology and injury

The TAM receptor tyrosine kinases (RTK) Mer and Axl have been implicated in liver disease, yet our understanding of their roles in liver homeostasis and injury is limited. We therefore examined the performance of Mer and Axl mutant mice during aging, and in four models of liver injury. We find that Mer and Axl are most prominently expressed in Kupffer and hepatic endothelial cells, and that as Axl-/-Mertk-/- mice normally age, they develop profound liver disease. We further find that Mer signaling is critical to the phagocytosis of apoptotic hepatocytes that are generated during acute hepatic injury, and that Mer and Axl act in concert to inhibit injury-triggered cytokine production. TAM expression in Kupffer cells is crucial for these effects. In contrast, we show that Axl is uniquely important in mitigating liver damage during acute acetaminophen intoxication. Finally, we demonstrate that Axl exacerbates the fibrosis that develops in a model of chronic hepatic injury. These divergent effects have important implications for the design and implementation of TAM-directed therapeutics that target these RTKs in the liver.

physiology↗

Changing color and intensity of LED lighting across the day impacts on human circadian physiology, sleep, visual comfort and cognitive performance

We examined whether dynamic light across a scheduled 16-h waking day influences cognitive performance, visual comfort, melatonin secretion, sleepiness and sleep under strictly controlled laboratory conditions of 49-h duration. Participants spent the first 5-h in the evening under standard lighting, followed by an 8-h nocturnal sleep episode at habitual bedtimes. Thereafter volunteers either woke up with static daylight LED (100 lux and 4000 Kelvin) or with a dynamic daylight LED that changed color (2700 - 5000 Kelvin) and intensity (0 - 100 lux) across the scheduled 16-h waking day. This was followed by an 8-h nocturnal treatment sleep episode at habitual bedtimes. Thereafter, volunteers spent another 12-h either under static or dynamic light during scheduled wakefulness. Under dynamic light, evening melatonin levels were less suppressed 1.5hours prior to usual bedtime, and participants felt less vigilant in the evening compared to static light. Sleep latency was significantly shorter in both the baseline and treatment night compared to the static light condition while sleep structure, sleep quality, cognitive performance and visual comfort did not significantly change. Our results support the recommendation of using blue-depleted light and low illuminances in the late evening, which can be achieved by a dynamically changing daylight LED solution.

physiology↗

Salt transport by the gill Na+-K+-2Cl- symporter in palaemonid shrimps: exploring physiological, molecular and evolutionary landscapes

Palaemonid shrimps include species from distinct osmotic niches that hyper-regulate hemolymph osmolality and ionic concentrations in dilute media but hypo-regulate in saline media. Their gill epithelia express ion transporters like the Na+-K+-2Cl- symporter (NKCC) thought to play a role in salt secretion. Using a palaemonid series from niches including marine tide pools through estuaries (Palaemon) to coastal and continental fresh waters (Macrobrachium), we established their critical upper salinity limits (UL50) and examined their short-(24 h) and long-term (120 h) hypo-regulatory abilities at salinities corresponding to 80% of the UL50s (80%UL50). We tested for phylogenetic correlations between gill NKCC gene and protein expression and hemolymph Cl- hypo-regulatory capability, and evaluated whether niche salinity might have driven gill NKCC expression. The Palaemon species from saline habitats showed the highest UL50s and greatest hypo-regulatory capabilities compared to the Macrobrachium species among which UL50s were higher in the diadromous than in the hololimnetic species. While basal gill NKCC mRNA transcription rates differed among species, expressions were unaffected by exposure time or salinity, suggesting post-transcriptional regulation of protein synthesis. Unexpectedly, hemolymph Cl- hyper-regulatory capability correlated with gill NKCC gene expression, while gill NKCC protein synthesis was associated with hyper-regulation of hemolymph osmolality at the 80%UL50s of almost all Macrobrachium species, suggesting a role for the gill NKCC symporter in salt uptake. The evolutionary history of osmoregulation in these palaemonid shrimps suggests that, while some molecular and systemic mechanisms have accompanied cladogenetic events during radiation into different osmotic niches, others may be driven by salinity.

physiology↗