Miracle-dz/UniFAR-FTUs huggingface dataset:
Diversity in plant hydraulic traits explains seasonal and inter-annual variations of vegetation dynamics in seasonally dry tropical forests.

We assessed whether diversity in plant hydraulic traits can explain the observed diversity in plant responses to water stress in seasonally dry tropical forests (SDTFs). The Ecosystem Demography model 2 (ED2) was updated with a trait-driven mechanistic plant hydraulic module, as well as novel drought-phenology and plant water stress schemes. Four plant functional types were parameterized on the basis of meta-analysis of plant hydraulic traits. Simulations from both the original and the updated ED2 were evaluated against 5 yr of field data from a Costa Rican SDTF site and remote-sensing data over Central America. The updated model generated realistic plant hydraulic dynamics, such as leaf water potential and stem sap flow. Compared with the original ED2, predictions from our novel trait-driven model matched better with observed growth, phenology and their variations among functional groups. Most notably, the original ED2 produced unrealistically small leaf area index (LAI) and underestimated cumulative leaf litter. Both of these biases were corrected by the updated model. The updated model was also better able to simulate spatial patterns of LAI dynamics in Central America. Plant hydraulic traits are intercorrelated in SDTFs. Mechanistic incorporation of plant hydraulic traits is necessary for the simulation of spatiotemporal patterns of vegetation dynamics in SDTFs in vegetation models.
Generation of slow waves in membrane potential is an intrinsic property of interstitial cells of Cajal.

To reveal the unique intrinsic properties of interstitial cells of Cajal (ICC), morphological and electrophysiological characteristics of isolated ICC from the adult mouse small intestine were investigated and compared with those of smooth muscle cells. All typical ultrastructural features of in situ ICC were evident in isolated ICC throughout the isolation procedure and short-term culture. With the use of the nystatin perforated patch-clamp technique, ICC demonstrated spontaneous voltage oscillations that were not abolished by hyperpolarization nor by L-type calcium channel blockers. This rhythmic activity occurred at room temperature at a frequency of 13.9 ± 11.2 cycles/min, with an amplitude of 13.4 ± 11.2 mV at membrane potentials from -20 to -70 mV. Smooth muscle cells from the same culture only generated voltage-sensitive action potentials above the threshold potential of -35 mV. Hyperpolarization as well as the addition of L-type calcium channel blockers abolished the action potentials. In whole cell voltage-clamp recordings from ICC, a large noninactivating outward current was observed to be activated (5% threshold) at -49.6 mV with a half-activation voltage of -18.7 mV and slope factor of 9.9 mV. In contrast, in smooth muscle cells, smaller outward currents with distinctive transient outward currents were present. In conclusion, the generation of L-type calcium channel blocker-insensitive slow waves in membrane potential is a unique intrinsic property of ICC.
Glutamatergic and dopaminergic contributions to rat bladder hyperactivity after cerebral artery occlusion.

The contribution of glutamatergic and dopaminergic mechanisms to bladder hyperactivity after left middle cerebral artery occlusion was evaluated by determining the effects of intravenous cumulative doses of an N-methyl-d-aspartate (NMDA) glutamatergic antagonist (MK-801) and D1-selective (Sch-23390), D2-selective (sulpiride), or nonselective (haloperidol) dopaminergic antagonists on bladder activity in sham-operated (SO) and cerebral-infarcted (CI) rats. MK-801 (1 and 10 mg/kg) or sulpiride (3-30 mg/kg) significantly increased bladder capacity (BC) in CI but decreased or had no effect, respectively, on BC in SO. Sch-23390 (0.1-3 mg/kg) decreased BC in both SO and CI. In both CI and SO, low doses of haloperidol (0.1-1 mg/kg) increased BC, but a higher dose (3 mg/kg) reversed this effect. Administration of haloperidol (0.3 mg/kg) or sulpiride (10 mg/kg) in combination with MK-801 (0.01-10 mg/kg) markedly increased BC in CI but produced small decreases or increases in BC depending on the dose of MK-801 in SO. These results indicate that the bladder hyperactivity induced by cerebral infarction is mediated in part by NMDA glutamatergic and D2dopaminergic excitatory mechanisms.
Human monocyte stimulus-coupled IL-1β posttranslational processing: modulation via monovalent cations.

Lipopolysaccharide-activated human monocytes produce prointerleukin (pro-IL)-1β but release little of this inflammatory cytokine as the biologically active species. Efficient externalization of mature 17-kDa cytokine requires that the activated monocytes encounter a secondary stimulus such as ATP. To identify cation requirements of the ATP-induced process, lipopolysaccharide-activated monocytes were treated with ATP in media containing different Cl- salts or sucrose. Media devoid of Na+ did not support IL-1β processing. Titration of NaCl into choline chloride- or sucrose-based media restored 17-kDa IL-1β production. Na+ replacement, however, was not sufficient to support ATP-induced production of 17-kDa IL-1β in the presence of ≥37 mM extracellular K+ or Li+. Inhibition by K+ suggests that efflux of this cation is a necessary component of the stimulus-coupled response. The inhibitory effect achieved by Na+depletion is not due to inactivation of the ATP receptor and is distinct from a caspase-1 inhibitor. Stimulus-coupled IL-1β posttranslational processing, therefore, requires extracellular Na+ for a step downstream of the initiating stimulus but preceding caspase-1 activation.
H+ secretion is inhibited by clostridial toxins in an inner medullary collecting duct cell line.

Renal epithelial cell H+secretion is an exocytic-endocytic phenomenon. In the inner medullary collecting duct (IMCD) cell line, which we have utilized as a model of renal epithelial cell acid secretion, we found previously that acidification increased exocytosis and alkalinization increased endocytosis. It is likely, therefore, that the rate of proton secretion is regulated by the membrane insertion and retrieval of proton pumps. There is abundant evidence from studies in the nerve terminal and the chromaffin cell that vesicle docking, membrane fusion, and discharge of vesicular contents (exocytosis) involve a series of interactions among so-called trafficking proteins. The clostridial toxins, botulinum and tetanus, are proteases that specifically inactivate some of these proteins. In these experiments we demonstrated, by immunoblot and immunoprecipitation, the presence in this IMCD cell line of the specific protein targets of these toxins, synaptobrevin/vesicle-associated membrane proteins (VAMP), syntaxin, and synaptosomal-associated protein-25 (SNAP-25). Furthermore, we showed that these toxins markedly inhibit the capacity of these cells to realkalinize after an acid load. Thus these data provide new insight into the mechanism for H+ secretion in the IMCD.
Protein Biomarkers for Insulin Resistance and Type 2 Diabetes Risk in Two Large Community Cohorts

Insulin resistance (IR) is a precursor of type 2 diabetes (T2D), and improved risk prediction and understanding of the pathogenesis are needed. We used a novel high-throughput 92-protein assay to identify circulating biomarkers for HOMA of IR in two cohorts of community residents without diabetes (n = 1,367) (mean age 73 ± 3.6 years). Adjusted linear regression identified cathepsin D and confirmed six proteins (leptin, renin, interleukin-1 receptor antagonist [IL-1ra], hepatocyte growth factor, fatty acid–binding protein 4, and tissue plasminogen activator [t-PA]) as IR biomarkers. Mendelian randomization analysis indicated a positive causal effect of IR on t-PA concentrations. Two biomarkers, IL-1ra (hazard ratio [HR] 1.28, 95% CI 1.03–1.59) and t-PA (HR 1.30, 1.02–1.65) were associated with incident T2D, and t-PA predicted 5-year transition to hyperglycemia (odds ratio 1.30, 95% CI 1.02–1.65). Additional adjustment for fasting glucose rendered both coefficients insignificant and revealed an association between renin and T2D (HR 0.79, 0.62–0.99). LASSO regression suggested a risk model including IL-1ra, t-PA, and the Framingham Offspring Study T2D score, but prediction improvement was nonsignificant (difference in C-index 0.02, 95% CI −0.08 to 0.12) over the T2D score only. In conclusion, proteomic blood profiling indicated cathepsin D as a new IR biomarker and suggested a causal effect of IR on t-PA.
Arginine-induced insulin release is decreased and glucagon increased in parallel with islet NO production

Henningsson, Ragnar, and Ingmar Lundquist. Arginine-induced insulin release is decreased and glucagon increased in parallel with islet NO production. Am. J. Physiol. 275 (Endocrinol. Metab. 38): E500–E506, 1998. —Nitric oxide (NO) produced by islet constitutive NO synthase (cNOS) is a putative modulator of islet hormone secretion. We show here for the first time that the release of insulin induced by L-arginine or L-homoarginine is inhibited and that of glucagon stimulated in parallel with the rate of islet NO production. It was found that L-homoarginine was <25–30% less potent than L-arginine as an insulin secretagogue but equally potent as a glucagon secretagogue. Biochemical determination of islet cNOS activity revealed that the NO production with L-homoarginine as substrate was only <40% of that of L-arginine. Selective inhibition of islet cNOS potentiated insulin release during amino acid stimulation. Moreover, inhibition of cNOS suppressed glucagon release, more so with L-arginine than with L-homoarginine as secretagogue, reflecting the relative rates of their NO production. In K1depolarized islets, inhibition of cNOS enhanced the insulin response to L-arginine by 50% and that to L-homoarginine by 23%, largely corresponding to their relative NO production. The intracellular NO donor hydroxylamine dose dependently inhibited insulin but increased glucagon secretion in K1depolarized and amino acid-stimulated islets. We conclude that both amino acids have a dual action on insulin release, since their stimulatory effects are reduced in parallel with the rates of their NO production. Furthermore, the greater NO production induced by L-arginine relative to L-homoarginine corresponds to NO-mediated increases in glucagon release. These NO effects are mainly exerted independently of membrane depolarization events.
Role of circulating endotoxin and interleukin-6 in the ACTH and corticosterone response to intraperitoneal LPS.

Peripheral administration of lipopolysaccharide (LPS) may activate the hypothalamus-pituitary-adrenal (HPA) axis by way of both neural and humoral mechanisms. We have investigated whether biologically active endotoxin appears in the general circulation after intraperitoneal administration of LPS (5 or 100 μg/kg) to rats and whether this is a prerequisite for activation of this HPA axis. Within 15 min, endotoxin appeared in the general circulation, whereas elevations of plasma adrenocorticotropic hormone (ACTH), corticosterone, and interleukin (IL)-6 concentrations were not detected until 90 min after LPS injection. At this time, a marked interindividual variation was observed in plasma concentrations of endotoxin, ACTH, corticosterone, and IL-6. Elevated levels of plasma endotoxin were associated with elevated levels of ACTH, corticosterone, and IL-6. Intravenous administration of the LPS antagonist cationic antimicrobial protein 18 (5 mg/kg), which did not affect cytokine production in the peritoneal cavity, markedly reduced plasma ACTH, corticosterone, and IL-6 levels after 5 μg/kg LPS. Our results suggest that circulating endotoxin is required for the activation of the HPA axis. They also favor a role for circulating IL-6 in this response.
Drosophila melanogaster Models of Metal-Related Human Diseases and Metal Toxicity

Iron, copper and zinc are transition metals essential for life because they are required in a multitude of biological processes. Organisms have evolved to acquire metals from nutrition and to maintain adequate levels of each metal to avoid damaging effects associated with its deficiency, excess or misplacement. Interestingly, the main components of metal homeostatic pathways are conserved, with many orthologues of the human metal-related genes having been identified and characterized in Drosophila melanogaster. Drosophila has gained appreciation as a useful model for studying human diseases, including those caused by mutations in pathways controlling cellular metal homeostasis. Flies have many advantages in the laboratory, such as a short life cycle, easy handling and inexpensive maintenance. Furthermore, they can be raised in a large number. In addition, flies are greatly appreciated because they offer a considerable number of genetic tools to address some of the unresolved questions concerning disease pathology, which in turn could contribute to our understanding of the metal metabolism and homeostasis. This review recapitulates the metabolism of the principal transition metals, namely iron, zinc and copper, in Drosophila and the utility of this organism as an experimental model to explore the role of metal dyshomeostasis in different human diseases. Finally, a summary of the contribution of Drosophila as a model for testing metal toxicity is provided.
Conserving relics from ancient underground worlds: assessing the influence of cave and landscape features on obligate iron cave dwellers from the Eastern Amazon

The degradation of subterranean habitats is believed to represent a serious threat for the conservation of obligate subterranean dwellers (troglobites), many of which are short-range endemics. However, while the factors influencing cave biodiversity remain largely unknown, the influence of the surrounding landscape and patterns of subterranean connectivity of terrestrial troglobitic communities have never been systematically assessed. Using spatial statistics to analyze the most comprehensive speleological database yet available for tropical caves, we first assess the influence of iron cave characteristics and the surrounding landscape on troglobitic communities from the Eastern Amazon. We then determine the spatial pattern of troglobitic community composition, species richness, phylogenetic diversity, and the occurrence of frequent troglobitic species, and finally quantify how different landscape features influence the connectivity between caves. Our results reveal the key importance of habitat amount, guano, water, lithology, geomorphology, and elevation in shaping iron cave troglobitic communities. While mining within 250 m from the caves influenced species composition, increasing agricultural land cover within 50 m from the caves reduced species richness and phylogenetic diversity. Troglobitic species composition, species richness, phylogenetic diversity, and the occurrence of frequent troglobites showed spatial autocorrelation for up to 40 km. Finally, our results suggest that the conservation of cave clusters should be prioritized, as geographic distance was the main factor determining connectivity between troglobitic communities. Overall, our work sheds important light onto one of the most overlooked terrestrial ecosystems, and highlights the need to shift conservation efforts from individual caves to subterranean habitats as a whole.
Adaptive upregulation of DNA repair genes following benzo(a)pyrene diol epoxide protects against cell death at the expense of mutations

A coordinated and faithful DNA damage response is of central importance for maintaining genomic integrity and survival. Here, we show that exposure of human cells to benzo(a)pyrene 9,10-diol-7,8-epoxide (BPDE), the active metabolite of benzo(a)pyrene (B(a)P), which represents a most important carcinogen formed during food preparation at high temperature, smoking and by incomplete combustion processes, causes a prompt and sustained upregulation of the DNA repair genes DDB2, XPC, XPF, XPG and POLH. Induction of these repair factors on RNA and protein level enhanced the removal of BPDE adducts from DNA and protected cells against subsequent BPDE exposure. However, through the induction of POLH the mutation frequency in the surviving cells was enhanced. Activation of these adaptive DNA repair genes was also observed upon B(a)P treatment of MCF7 cells and in buccal cells of human volunteers after cigarette smoking. Our data provide a rational basis for an adaptive response to polycyclic aromatic hydrocarbons, which occurs however at the expense of mutations that may drive cancer formation.
Osteogenic Potential of Pre-Osteoblastic Cells on a Chitosan-graft-Polycaprolactone Copolymer

A chitosan-graft-polycaprolactone (CS-g-PCL) copolymer synthesized via a multi-step process was evaluated as a potential biomaterial for the adhesion and growth of MC3T3-E1 pre-osteoblastic cells. A strong adhesion of the MC3T3-E1 cells with a characteristic spindle-shaped morphology was observed from the first days of cell culture onto the copolymer surfaces. The viability and proliferation of the cells on the CS-g-PCL surfaces, after 3 and 7 days in culture, were significantly higher compared to the cells cultured on the tissue culture treated polystyrene (TCPS) control. The osteogenic potential of the pre-osteoblastic cells cultured on CS-g-PCL surfaces was evaluated by determining various osteogenic differentiation markers and was compared to the TCPS control surface. Specifically, alkaline phosphatase activity levels show significantly higher values at both time points compared to TCPS, while secreted collagen into the extracellular matrix was found to be higher on day 7. Calcium biomineralization deposited into the matrix is significantly higher for the CS-g-PCL copolymer after 14 days in culture, while the levels of intracellular osteopontin were significantly higher on the CS-g-PCL surfaces compared to TCPS. The enhanced osteogenic response of the MC3T3-E1 pre-osteoblasts cultured on CS-g-PCL reveals that the copolymer underpins the cell functions towards bone tissue formation and is thus an attractive candidate for use in bone tissue engineering.
Development and application of a novel recombinant Aleuria aurantia lectin with enhanced core fucose binding for identification of glycoprotein biomarkers of hepatocellular carcinoma

The Aleuria aurantia lectin (AAL) derived from orange peel fungus contains five fucose‐binding sites that recognizes fucose bound in α‐1,2, α‐1,3, α‐1,4, and α‐1,6 linkages to N‐acetylglucosamine and galactose. Recently, we have created several recombinant AAL (rAAL) proteins that had altered binding affinity to fucose linkages. In this report, we further characterize the binding specificity of one of the mutated lectins, N224Q lectin. This lectin was characterized by lectin Western blotting, surface plasmon resonance, and glycan microarray and shown to have increased binding to fucosylated glycan. Subsequently, we used this lectin to identify secreted fucosylated glycoproteins from a fetal hepatic cell line. Proteomic analysis revealed several glycoproteins secreted by the fetal cell line that were bound by N224Q lectin. These findings were confirmed by subsequent proteomic analysis of human serum from control patients or patients with hepatocellular carcinoma. These represent candidate oncofetal markers for liver cancer.
Sex‐Ratio Selection in Species with Helpers at the Nest: The Repayment Model Revisited

We reexamine the theoretical and empirical basis for the “repayment model” of Emlen, Emlen, and Levin, which predicts that the overall sex ratio of offspring in cooperative‐breeding species with helpers at the nest should be biased toward the more helpful sex. We conclude that in theory the model may yield a biased sex ratio but only under restricted conditions that are unlikely to be met in most populations. In those cases where the model is potentially applicable, estimates of both direct and indirect fitness of sons and daughters are necessary in order to avoid double accounting. As a result, extensive demographic data are required to determine the expected sex‐ratio bias. Empirically, none of the three examples originally suggested as supporting the repayment model withstand critical scrutiny. Using long‐term demographic data from two populations of one of these species, the red‐cockaded woodpecker (Picoides borealis), we determine that the model predicts a biased sex ratio not observed in the data. This suggests that confounding factors may counter the sex‐ratio bias predicted by the model, that the extensive empirical data available for this species may be insufficient to test the model, or that there are as yet unknown theoretical difficulties with the model. Finally, we discuss the recently reported case of the Seychelles warbler (Acrocephalus sechellensis). The extraordinarily biased sex ratios reported in this species are in accord with those predicted by the model when applied at the scale of individual groups but not at the population level. Additional empirical work is necessary to determine what, if any, the generality and usefulness of the repayment model may be.
Contribution of carotid chemoreceptors to mesenteric venoconstriction during acute hypercapnia in rabbits.

The contribution of carotid chemoreceptors to hypercapnia-induced mesenteric venoconstriction was examined in 12 α-chloralose-anesthetized rabbits (1.0-1.6 kg). Surgical preparation consisted of a tracheotomy, femoral arterial and venous cannulation, and a midline laparotomy through which a 13-cm loop of ileum was exteriorized and superfused with physiological salt solution. Mesenteric vein diameter and intravenous pressure (using a servo-null measurement system) were measured in 500- to 1,000-μm mesenteric veins during 40-s periods of 15%, 20%, and 25% CO2 inhalation. Measurements were then repeated following bilateral ablation of the carotid chemoreceptors. Before denervation, mesenteric vein diameter constricted 6.5 ± 1.1%, 11.9 ± 1.1%, and 17.9 ± 2.2% during the 15%, 20%, and 25% CO2 inhalation, respectively. After denervation, these values were reduced to 5.0 ± 0.9%, 6.9 ± 1.2%, and 8.4 ± 1.3%, respectively. We conclude that activation of the carotid chemoreceptors by hypercapnia induces active mesenteric venoconstriction. After denervation of the carotid baroreceptors and chemoreceptors, there was also a small decrease in venule diameter proportional to the level of inspired CO2. We further conclude that noncarotid body chemoreceptor activation contributes to mesenteric venular constriction.