Mammalian Esterase Activity: Implications for Peptide Prodrugs.

As a traceless, bioreversible modification, the esterification of carboxyl groups in peptides and proteins has the potential to increase their clinical utility. An impediment is the lack of strategies to quantify esterase-catalyzed hydrolysis rates for esters in esterified biologics. We have developed a continuous Förster resonance energy transfer (FRET) assay for esterase activity based on a peptidic substrate and a protease, Glu-C, that cleaves a glutamyl peptide bond only if the glutamyl side chain is a free acid. Using pig liver esterase (PLE) and human carboxylesterases, we validated the assay with substrates containing simple esters (e.g., ethyl) and esters designed to be released by self-immolation upon quinone methide elimination. We found that simple esters were not cleaved by esterases, likely for steric reasons. To account for the relatively low rate of quinone methide elimination, we extended the mathematics of the traditional Michaelis-Menten model to conclude with a first-order intermediate decay step. By exploring two regimes of our substrate → intermediate → product (SIP) model, we evaluated the rate constants for the PLE-catalyzed cleavage of an ester on a glutamyl side chain (kcat/KM = 1.63 × 103 M-1 s-1) and subsequent spontaneous quinone methide elimination to regenerate the unmodified peptide (kI = 0.00325 s-1; t1/2 = 3.55 min). The detection of esterase activity was also feasible in the human intestinal S9 fraction. Our assay and SIP model increase the understanding of the release kinetics of esterified biologics and facilitate the rational design of efficacious peptide prodrugs.

Association between preterm infant body composition in the first 3 months of life and preschool age: a cohort study.

Compared with full-term infants, preterm infants have fat-free mass deficit in the first months of life, which increases the risk of metabolic diseases in the future. In this cohort of children born under 32-week gestational age or less than 1500 g, we aimed to evaluate the associations of body composition at term equivalent age and in the first 3 months of life with fat-free mass and fat mass percentage at 4 to 7 years of life. Body composition assessments by air displacement plethysmography and anthropometry were performed at term, at 3 months of corrected age, and at 4 to 7 years of age. Multiple linear regression analysis was used to observe the associations between body composition at these ages. At term, fat mass percentage showed a negative association and fat-free mass a positive association with fat-free mass at 4 to 7 years. The fat-free mass at 3 months and the gain in fat-free mass between term and 3 months showed positive associations with fat-free mass at 4 to 7 years.   Conclusion: Body composition at preschool age is associated with fat-free mass in the first 3 months of life, a sensitive period for the risk of metabolic diseases. What is Known: • Preterm infants have a deficit in fat-free mass and high adiposity at term equivalent age compared to full-term infants. • Fat-free mass reflects metabolic capacity throughout life and therefore is considered a protective factor against the risk of metabolic syndrome. What is New: •Fat-free mass gain in the first 3 months of corrected age is associated with fat-free mass at preschool and school ages. •The first 3 months of life is a sensitive period to the risk of metabolic diseases.

Wildfire and cattle legacies on gradients of soil nitrogen underlie patterns of annual brome invasion.

Human activities are increasing wildfires and livestock activity in arid ecosystems with potential implications for the spread of invasive grasses. The objective of this study was to test whether fire history and cattle activity alter soil resource gradients, thereby affecting patterns of Bromus rubens L. (red brome) invasion. Six paired burned and unburned transect lines (1-km long) were established in the northeast Mojave Desert along the boundaries of four independent wildfire scars. At 100-m transect increment points, we measured the distance to the two nearest cowpats, and two random points and measured the density, height, biomass, and seed production of red brome, soil moisture and inorganic nitrogen (N). Cattle activity was 29% greater along burned transects compared to unburned transects (P < 0.05). Red brome height, density, and seed production were 11-34% greater along burned transects than unburned transects (P < 0.05). Red brome height, biomass, density, and seed production were twofold to tenfold greater next to cowpats compared to random points (P < 0.05). Soils along burned transects and beneath cowpats had greater soil inorganic N (P < 0.05), which was positively correlated with red brome density, height, biomass, and seed production (R2 = 0.60-0.85, P < 0.0001). Transgenerational effects were evident as seeds from red brome next to cowpats had 27% higher germination than seeds collected from random points. Positive responses of red brome to increased inorganic N related to fire and cattle activity may contribute fine fuel infill that drives invasive grass-fire cycles in deserts.

Chemoselective Caging of Carboxyl Groups for On-Demand Protein Activation with Small Molecules.

Tools for on-demand protein activation enable impactful gain-of-function studies in biological settings. Thus far, however, proteins have been chemically caged at primarily Lys, Tyr, and Sec, typically through the genetic encoding of unnatural amino acids. Herein, we report that the preferential reactivity of diazo compounds with protonated acids can be used to expand this toolbox to solvent-accessible carboxyl groups with an elevated pKa value. As a model protein, we employed lysozyme (Lyz), which has an active-site Glu35 residue with a pKa value of 6.2. A diazo compound with a bioorthogonal self-immolative handle esterified Glu35 selectively, inactivating Lyz. The hydrolytic activity of the caged Lyz on bacterial cell walls was restored with two small-molecule triggers. The decaging was more efficient by small molecules than by esterases. This simple chemical strategy was also applied to a hemeprotein and an aspartyl protease, setting the stage for broad applicability.

Energy expenditure and body composition in infants with bronchopulmonary dysplasia at term age.

In this cross-sectional study, conducted in a cohort of infants with a gestational age of < 32 weeks, we aimed to evaluate and compare resting energy expenditure (REE) and body composition between infants who developed bronchopulmonary dysplasia (BPD) and those who did not. REE and body composition were assessed at term equivalent age using indirect calorimetry and air displacement plethysmography. Anthropometric measurements (weight, head circumference, and length) were obtained and transformed into Z-scores per the Fenton (2013) growth curve, at birth and at term equivalent age. Forty-two infants were included in this study, of which 26.2% developed BPD. Infants with BPD had significantly higher energy expenditure at term equivalent age, with no difference in body composition between the two groups. CONCLUSION: Despite expending more energy, infants with BPD maintained a similar body composition distribution to those without BPD, and this is likely due to the recommended nutritional approach. WHAT IS KNOWN: • Greater resting energy expenditure impairs growth of preterm infants with bronchopulmonary dysplasia. WHAT IS NEW: • Although preterm infants with bronchopulmonary dysplasia had a higher resting energy expenditure at the corrected term age, this did not affect their body composition and growth.

Assessment of early nutritional intake in preterm infants with bronchopulmonary dysplasia: a cohort study.

This cohort study evaluated the nutritional supply in 78 very preterm newborns, with 20.5% developing bronchopulmonary dysplasia (BPD). This work aimed to evaluate the nutritional intake and the calorie/protein ratio received in the first 4 weeks of life. Anthropometric measures at birth and term age, the weight at each of the first 4 weeks of life, and the feeding practices were registered. The mean gestational age and birth weight were lower in those who developed BPD. At term age, head circumference and length Z-scores were significantly lower in newborns with BPD, who started enteral feeding and reached full diet later, staying longer in parenteral nutrition. The protein rate received by all newborns was similar, whether developing BPD or not, but those who developed BPD received significantly lower fluid volume and calorie rates after the second week. The daily calorie/protein ratio (30 kcal/1-g protein) was reached by 88.7% of the newborns who did not develop BPD in the third week, with those who developed BPD receiving less than this ratio until the second week, persisting in 56.3% of them on the fourth week.Conclusion: A calorie/protein ratio below that recommended for growth was found in preterm newborns who developed BPD, and providing nutrition for these newborns remains a challenge. What is Known: • The importance of preterm newborn nutrition is well known. • Early nutritional support may avoid severe BPD. What is New: • Newborns who developed BPD received a calorie/protein ratio below that recommended for preterm newborns' growth during the first 2 weeks of life, lasting until the fourth week in most of these newborns.

Growth and body composition in preterm newborns with bronchopulmonary dysplasia: a cohort study.

Objective To compare growth and body composition of preterm infants (gestational age <32 weeks) with and without bronchopulmonary dysplasia (BPD). Methods A prospective cohort involving three neonatal units in the public health system of the Brazilian city of Rio de Janeiro. Inclusion: newborns with gestational age <32 weeks. EXPOSURE: BPD. Anthropometric measurements were performed at birth and at 1 month of infant corrected age. Body composition was measured using an air displacement plethysmography (ADP) (PEA POD®) at 1 month of infant corrected age. Results Ninety-five newborns were eligible, of which 67 were included, 32.8% of them with BPD. Newborns with BPD presented lower gestational age at birth, greater need for resuscitation in the delivery room, received parenteral nutrition (PN) for a longer period of time, achieved lower weights during hospital stay and required more time to reach a full enteral diet. No statistically significant differences were observed in relation to anthropometric measurements and body composition at 1 month of infant corrected age between the groups with and without BPD. Conclusion This study, unlike previous ones, has shown that children who developed BPD were able to regain growth, as measured by anthropometric measures, with no change in body composition at 1 month of infant corrected age.

Sitetack: A Deep Learning Model that Improves PTM Prediction by Using Known PTMs.

Post-translational modifications (PTMs) increase the diversity of the proteome and are vital to organismal life and therapeutic strategies. Deep learning has been used to predict PTM locations. Still, limitations in datasets and their analyses compromise success. Here we evaluate the use of known PTM sites in prediction via sequence-based deep learning algorithms. Specifically, PTM locations were encoded as a separate amino acid before sequences were encoded via word embedding and passed into a convolutional neural network that predicts the probability of a modification at a given site. Without labeling known PTMs, our model is on par with others. With labeling, however, we improved significantly upon extant models. Moreover, knowing PTM locations can increase the predictability of a different PTM. Our findings highlight the importance of PTMs for the installation of additional PTMs. We anticipate that including known PTM locations will enhance the performance of other proteomic machine learning algorithms.

Colonic torsion and volvulus in dogs is associated with a low mortality rate and good long-term outcome.

OBJECTIVE: To describe clinical findings, complications, and short- and long-term outcomes associated with colonic torsion and volvulus in dogs. ANIMALS: 28 client-owned dogs. CLINICAL PRESENTATION: Multi-institutional, retrospective study. Medical records were searched for dogs of any age, body weight, sex, and breed that underwent surgery for colonic torsion and volvulus. Collected data included signalment, previous history, preoperative findings, time until surgery, intraoperative findings, postoperative complications, length of hospitalization, survival to discharge, and outcomes. RESULTS: 28 dogs were included. Thirteen of 28 dogs (46.4%) had preexisting gastrointestinal conditions. Nine of 28 dogs (32.1%) had a gastropexy performed prior to presentation. Ten dogs (35.7%) were found to have a resolution of colonic torsion and volvulus at the time of the surgery. All but 1 dog (27 of 28 [96.4%]) survived to discharge. Two dogs died during the postoperative period, yielding a mortality rate of 7.1%. Postoperative complications were noted in 9 dogs (9 of 28 [32.1%]). Long-term follow-up information was available in 16 of 28 dogs (57%). Among 16 dogs with at least 6 months' follow-up, all dogs (16 of 16 [100%]) were alive at 6 months postoperatively. Two dogs developed mesenteric torsion after the initial surgery. CLINICAL RELEVANCE: Dogs with colonic torsion and volvulus undergoing surgery can have an excellent survival-to-discharge ratio with a low mortality rate. Surgeons should not be prompted to euthanize or assume a guarded prognosis solely on the basis of the intraoperative appearance of the bowel and should consider all factors prior to making decisions. Owners should be informed of the risk of developing further torsional diseases after surgery.

Duodenal activation of cAMP-dependent protein kinase induces vagal afferent firing and lowers glucose production in rats.

BACKGROUND & AIMS: The duodenum senses nutrients to maintain energy and glucose homeostasis, but little is known about the signaling and neuronal mechanisms involved. We tested whether duodenal activation of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase A (PKA) is sufficient and necessary for cholecystokinin (CCK) signaling to trigger vagal afferent firing and regulate glucose production. METHODS: In rats, we selectively activated duodenal PKA and evaluated changes in glucose kinetics during the pancreatic (basal insulin) pancreatic clamps and vagal afferent firing. The requirement of duodenal PKA signaling in glucose regulation was evaluated by inhibiting duodenal activation of PKA in the presence of infusion of the intraduodenal PKA agonist (Sp-cAMPS) or CCK1 receptor agonist (CCK-8). We also assessed the involvement of a neuronal network and the metabolic impact of duodenal PKA activation in rats placed on high-fat diets. RESULTS: Intraduodenal infusion of Sp-cAMPS activated duodenal PKA and lowered glucose production, in association with increased vagal afferent firing in control rats. The metabolic and neuronal effects of duodenal Sp-cAMPS were negated by coinfusion with either the PKA inhibitor H89 or Rp-CAMPS. The metabolic effect was also negated by coinfusion with tetracaine, molecular and pharmacologic inhibition of NR1-containing N-methyl-d-aspartate (NMDA) receptors within the dorsal vagal complex, or hepatic vagotomy in rats. Inhibition of duodenal PKA blocked the ability of duodenal CCK-8 to reduce glucose production in control rats, whereas duodenal Sp-cAMPS bypassed duodenal CCK resistance and activated duodenal PKA and lowered glucose production in rats on high-fat diets. CONCLUSIONS: We identified a neural glucoregulatory function of duodenal PKA signaling.

Early growth and body composition assessed by air displacement plethysmography in infants born with simple gastroschisis.

BACKGROUND: Gastroschisis is an abdominal wall malformation usually associated with impaired growth. OBJECTIVE: To evaluate the growth and body composition of infants born with simple gastroschisis in a referral center. METHODS: This was a single-center, prospective case series of infants with simple gastroschisis who were measured at birth, at discharge, and at 3 months. Body composition was assessed via air-displacement plethysmography at discharge and at 3 months. The results were compared with those reported for healthy infants at an equivalent gestational age. RESULTS: Simple gastroschisis infants were lighter and smaller at birth and remained similar at 3 months. All anthropometric z scores decreased from birth to discharge, followed by an increase but not a full recovery toward 3 months. Overall, gastroschisis infants had a similar FM percentage, FM% (11.1 ± 4.7), but a lower FFM, FFM (2481 ± 478 g), at discharge. FM% (18.5 ± 5.3) decreased at 3 months, and FFM remained lower (3788 ± 722 g) but improved between the two exams. Boys had significantly more FFM than girls at both evaluations. The multiple regression analysis showed that male sex, prematurity, total parenteral nutrition duration, and exclusive breast milk diets were associated with differences in body composition. CONCLUSIONS: Infants with simple gastroschisis cared for in a referral center experienced growth failure at discharge and showed a similar FM% but lower FFM than healthy infants. At 3 months, they exhibited smaller FM% and FFM, but FFM improved after the first exam, representing a better protein accretion. TYPE OF STUDY: Prognostic. LEVEL OF EVIDENCE: IV.

Physical and social activities constraint and its effects on Body Mass Index of former Neonatal Intensive Care children.

OBJECTIVE: It is reported weight gain in children due to the confinement measures during the Covid-19 pandemic. We aimed to describe the effect of these measures on the nutritional status of former Neonatal Intensive Care Unit children. METHODS: Cross-sectional study, including former Neonatal Intensive Care Unit children. The outcome was the Body mass index (BMI). RESULTS: We enrolled 126 children (74.6 % preterm; 31 % small-for-gestational-age). Weight excess was greater in the youngest group (≤5 years: 33.8 %; >5 years: 15.2 %). Prematurity was associated with weight excess in both groups (≤5 years: p value 0.006; >5 years: p value 0.046; Pearson test). Mealtime changes, lack of physical activity, socioeconomic factors and the perinatal morbidities significantly influenced the mean BMI. Birth length Z score less than -1.28 was negatively associated with BMI, while gestational age at birth presented a positive association with BMI (linear regression model). CONCLUSIONS: The BMI increase due to the confinement measures associated with the gestational age at birth and in those born with intrauterine growth restriction is a matter of concern, as it might indicate a risk for future obesity.

High-risk children and social isolation: the importance of family functioning.

High-risk newborns are exposed to neonatal conditions such as prematurity, very low birth weight, and congenital malformations that can affect development and behavior. Coronavirus disease 2019 (COVID-19) restraint and control measures have been identified as important stressor events and cumulative risk factors for behavioral changes in these children. This study examined social isolation-related factors that contribute to internalizing and externalizing behavior problems in children already at risk for neurodevelopmental disorders. This cross-sectional, multicenter study included 113 children (18 months to 9 years) who were followed in reference services for neonatal follow-up in tertiary units of the public health system in the city of Rio de Janeiro, Brazil. Behavior was assessed using the child behavior checklist, and a structured questionnaire was used to assess sociodemographic aspects. In the bivariate analysis, prematurity was associated with externalizing problems and change in eating habits with internalizing problems. The logistic model indicated that both parents having completed high school and both sharing care of the child were protective factors for behavioral problems; however, reports of sleep problems and living with another child were risk factors. In conclusion, the study identified internalizing and externalizing behavior problems related to prematurity and aspects of family structure and routine in children at risk. The findings confirm the importance of family functioning for child health and family-centered interventions.

A surface enhanced Raman spectroscopy study of aminothiophenol and aminothiophenol-C60 self-assembled monolayers: evolution of Raman modes with experimental parameters.

P-aminothiophenol (PATP) is a well-known molecule for the preparation of self-assembled monolayers on gold via its thiol functional group. After adsorption, it has been demonstrated that this molecule is anchored to gold through its thiol group, and standing nearly upright at the surface with the amino functional group on top. This molecule has been extensively studied by surface enhanced Raman spectroscopy but its exact SERS spectrum remains unclear. Here, we demonstrate that it can be strongly affected by at least two experimental parameters: laser power and layer density. Those features are discussed in terms of a dimerization of the PATP molecules. The free amino group affords the adsorption of other molecules such as C(60). In this case, a complex multilayer system is formed and the question of its precise characterisation remains a key point. In this article, we demonstrate that surface enhanced Raman spectroscopy combined with x ray photoelectron spectroscopy can bring very important information about the organization of such a self-assembled multilayer on gold. In our study, the strong evolution of Raman modes after C(60) adsorption suggests a change in the organization of aminothiophenol molecules during C(60) adsorption. These changes, also observed when the aminothiophenol layer is annealed in toluene, do not prevent the adsorption of C(60) molecules.

Resting energy expenditure in preterm newborns with bronchopulmonary dysplasia.

BACKGROUND & AIMS: Greater energy expenditure is reported in newborns with bronchopulmonary dysplasia (BPD). This study assessed resting energy expenditure (REE) in newborns with BPD. METHODS: BPD was classified as mild and moderate/severe. REE was assessed using indirect calorimetry between the time points of the discontinuation of oxygen (O2) (T1) and at term-equivalent age (T2) in preterm newborns with BPD. RESULTS: The moderate group (10 newborns) presented with higher REE (kcal/kg/day) after discontinuation of mechanical ventilation and a decrease of 18% between the two time points; 72.7 and 59.6 kcal/kg/day at T1 and T2 respectively (p value 0.08). No differences were observed in REE in the mild BPD group between timepoints; 50.9-56.4 kcal/kg/day at T1 and T2 respectively (p value 0.73). CONCLUSION: Newborns with BPD presented different metabolic behaviors depending on the classification criteria: those classified as having moderate BPD showed a decrease in REE toward term-equivalent age.

Activation of N-methyl-D-aspartate (NMDA) receptors in the dorsal vagal complex lowers glucose production.

Diabetes is characterized by hyperglycemia due partly to increased hepatic glucose production. The hypothalamus regulates hepatic glucose production in rodents. However, it is currently unknown whether other regions of the brain are sufficient in glucose production regulation. The N-methyl-D-aspartate (NMDA) receptor is composed of NR1 and NR2 subunits, which are activated by co-agonist glycine and glutamate or aspartate, respectively. Here we report that direct administration of either co-agonist glycine or NMDA into the dorsal vagal complex (DVC), targeting the nucleus of the solitary tract, lowered glucose production in vivo. Direct infusion of the NMDA receptor blocker MK-801 into the DVC negated the metabolic effect of glycine. To evaluate whether NR1 subunit of the NMDA receptor mediates the effect of glycine, NR1 in the DVC was inhibited by DVC NR1 antagonist 7-chlorokynurenic acid or DVC shRNA-NR1. Pharmacological and molecular inhibition of DVC NR1 negated the metabolic effect of glycine. To evaluate whether the NMDA receptors mediate the effects of NR2 agonist NMDA, DVC NMDA receptors were inhibited by antagonist D-2-amino-5-phosphonovaleric acid (D-APV). DVC D-APV fully negated the ability of DVC NMDA to lower glucose production. Finally, hepatic vagotomy negated the DVC glycine ability to lower glucose production. These findings demonstrate that activation of NR1 and NR2 subunits of the NMDA receptors in the DVC is sufficient to trigger a brain-liver axis to lower glucose production, and suggest that DVC NMDA receptors serve as a therapeutic target for diabetes and obesity.

Gut-brain signalling: how lipids can trigger the gut.

The gut plays a unique role in the metabolic defence against energy excess and glucose imbalance. Nutrients, such as lipids, enter the small intestine and activate sensing mechanisms to maintain energy and glucose homeostasis. It is clear that a lipid-induced gut-brain axis exists and that cholecystokinin and a neuronal network are involved, yet the underlying mechanisms in gut lipid sensing that regulate homeostasis remain largely unknown. In parallel, studies underscore the importance of enzymes involved in lipid metabolism within the brain, such as adenosine monophosphate -activated protein kinase, to maintain homeostasis. In this review, we will first examine what is known regarding the mechanisms involved in this lipid-induced gut-brain neuronal axis that regulate food intake and hepatic glucose production. We will also discuss how enzymes that govern brain lipid metabolism could potentially reveal how lipids trigger the gut, and that both the gut and brain may share common biochemical pathways to sense lipids.

[Know-how and techniques of Family Health Strategy managers and professionals in the prevention of violence against adolescents]. / Conhecimentos e práticas de gerentes e profissionais da ESF na prevenção das violências com adolescentes.

The scope of this study was to identify empowering factors for the actions of the Family Health Strategy (FHS) in coping with violence among adolescents. The sample was random from 61 teams of the Family Health Strategy of three municipalities. Questionnaires tabulated by EpiINFO 7.0, with bivariate analyses were used. Chi-square, Fisher and the "classification tree" were then used to analyze the experiences in this theme and the following issues: bonding, time since training completed, qualification, knowledge of public policies among others. There is acknowledgement of adolescents' vulnerability to violence, however, only two teams have ongoing prevention experiences. The prevailing opinion is that such activities are not the responsibility of the FHS. The study identifies interdependent variables that increase the likelihood of preventing violence and the promoting of a culture of peace among adolescents.

Este estudo objetivou identificar fatores potencializadores das ações da Estratégia Saúde da Família (ESF) no enfrentamento das violências contra adolescentes. A amostra foi aleatória de 61 equipes da ESF de três municípios. Utilizou-se questionários tabulados pelo programa EpiINFO 7.0, com análises bivariadas: qui-quadrado, Fisher e "árvore de classificação", para análise das experiências nessa temática e das seguintes questões - vínculo, tempo de formado, capacitação, conhecimento de políticas públicas, entre outras. Há o reconhecimento da vulnerabilidade dos adolescentes às violências, porém apenas duas equipes possuem experiências de prevenção com continuidade. Predomina a opinião de que tais atividades não competem à ESF. O estudo identifica variáveis interdependentes que aumentam a probabilidade da prevenção das violências e a promoção de cultura de paz entre adolescentes.

Megafire affects stream sediment flux and dissolved organic matter reactivity, but land use dominates nutrient dynamics in semiarid watersheds.

Climate change is causing larger wildfires and more extreme precipitation events in many regions. As these ecological disturbances increasingly coincide, they alter lateral fluxes of sediment, organic matter, and nutrients. Here, we report the stream chemistry response of watersheds in a semiarid region of Utah (USA) that were affected by a megafire followed by an extreme precipitation event in October 2018. We analyzed daily to hourly water samples at 10 stream locations from before the storm event until three weeks after its conclusion for suspended sediment, solute and nutrient concentrations, water isotopes, and dissolved organic matter concentration, optical properties, and reactivity. The megafire caused a ~2,000-fold increase in sediment flux and a ~6,000-fold increase in particulate carbon and nitrogen flux over the course of the storm. Unexpectedly, dissolved organic carbon (DOC) concentration was 2.1-fold higher in burned watersheds, despite the decreased organic matter from the fire. DOC from burned watersheds was 1.3-fold more biodegradable and 2.0-fold more photodegradable than in unburned watersheds based on 28-day dark and light incubations. Regardless of burn status, nutrient concentrations were higher in watersheds with greater urban and agricultural land use. Likewise, human land use had a greater effect than megafire on apparent hydrological residence time, with rapid stormwater signals in urban and agricultural areas but a gradual stormwater pulse in areas without direct human influence. These findings highlight how megafires and intense rainfall increase short-term particulate flux and alter organic matter concentration and characteristics. However, in contrast with previous research, which has largely focused on burned-unburned comparisons in pristine watersheds, we found that direct human influence exerted a primary control on nutrient status. Reducing anthropogenic nutrient sources could therefore increase socioecological resilience of surface water networks to changing wildfire regimes.