Testing the Labeling Effect in Autistic Children.

PURPOSE: Our objective was to test the labeling effect in autistic children. The effect has been robustly tested in typically developing (TD) individuals. TD children expect that any two objects that receive the same linguistic label will have similar properties, which suggests that they generate concepts based on acts of labeling. The labeling effect has not been tested on autistic children, who may not be equally attuned to the relevance of linguistic clues or may not generalize as swiftly as TD children. METHODS: We reproduced Graham et al.,'s (Frontiers in Psychology 10.3389/fpsyg.2012.00586, 2013) design on 30 autistic children of different ages. Participants were divided into two groups depending on whether objects presented to them were named alike or differently (Same or Distinct Label between-individuals condition). The dependent variable was the number of target actions the child performed on an object, depending on whether that object made the same sound as a previously shown test object. RESULTS: We did not reproduce results similar to those reported in Graham et al., (Frontiers in Psychology 10.3389/fpsyg.2012.00586, 2013). Children in the Same Label group did not perform significantly more actions than children in the Distinct Label group when the objects that were handed to the children did not make the same sound as the test object. CONCLUSIONS: Autistic children do not seem to be sensitive to the labeling effect to the same extent as TD children. If these results are confirmed, intervention programs for autistic children should consider trainings on this way of generating concepts shared by their linguistic community.

That kid is a grasshopper! Metaphor development from 3 to 9 years of age.

Two major trends on children's skills to comprehend metaphors have governed the literature on the subject: the literal stage hypothesis vs. the early birds hypothesis (Falkum, 2022). We aim to contribute to this debate by testing children's capability to comprehend novel metaphors ('X is a Y') in Spanish with a child-friendly, picture selection task, while also tracking their gaze. Further, given recent findings on the development of metonymy comprehension suggesting a U-shaped developmental curve for this phenomenon (Köder & Falkum, 2020), we aimed to determine the shape of the developmental trajectory of novel metaphor comprehension, and to explore how both types of data (picture selection and gaze behavior) relate to each other. Our results suggest a linear developmental trajectory with 6-year-olds significantly succeeding in picture selection and consistently looking at the metaphorical target even after question onset.

Profiling Cell Heterogeneity and Fructose Transporter Expression in the Rat Nephron by Integrating Single-Cell and Microdissected Tubule Segment Transcriptomes.

Single-cell RNA sequencing (scRNAseq) is a crucial tool in kidney research. These technologies cluster cells based on transcriptome similarity, irrespective of the anatomical location and order within the nephron. Thus, a transcriptome cluster may obscure the heterogeneity of the cell population within a nephron segment. Elevated dietary fructose leads to salt-sensitive hypertension, in part, through fructose reabsorption in the proximal tubule (PT). However, the organization of the four known fructose transporters in apical PTs (SGLT4, SGLT5, GLUT5, and NaGLT1) remains poorly understood. We hypothesized that cells within each subsegment of the proximal tubule exhibit complex, heterogeneous fructose transporter expression patterns. To test this hypothesis, we analyzed rat kidney transcriptomes and proteomes from publicly available scRNAseq and tubule microdissection databases. We found that microdissected PT-S1 segments consist of 81% ± 12% cells with scRNAseq-derived transcriptional characteristics of S1, whereas PT-S2 express a mixture of 18% ± 9% S1, 58% ± 8% S2, and 19% ± 5% S3 transcripts, and PT-S3 consists of 75% ± 9% S3 transcripts. The expression of all four fructose transporters was detectable in all three PT segments, but key fructose transporters SGLT5 and GLUT5 progressively increased from S1 to S3, and both were significantly upregulated in S3 vs. S1/S2 (Slc5a10: 1.9 log2FC, p < 1 × 10-299; Scl2a5: 1.4 log2FC, p < 4 × 10-105). A similar distribution was found in human kidneys. These data suggest that S3 is the primary site of fructose reabsorption in both humans and rats. Finally, because of the multiple scRNAseq transcriptional phenotypes found in each segment, our findings also imply that anatomical labels applied to scRNAseq clusters may be misleading.

Linguistic, concept and symbolic composition in adults with minimal receptive vocabulary.

In this paper, we examine some basic linguistic abilities in a small sample of adults with minimal receptive vocabulary, whose receptive mental verbal age ranges from 1;2 to 3;10. In particular, we examine whether the participants in our study understand noun phrases consisting of a noun modified by an adjective. We use stimuli that they can recognise by name. Except for one participant, we find that, while all of them understand the noun and adjective in isolation, none seems to understand these noun phrases, which means that they seem to not do linguistic composition. In order to test whether the difficulty is linguistic or conceptual, we ran two other studies, one on concept composition, and the other on iconic symbolic composition (composition of pictograms). Results suggest that linguistic composition is particularly difficult in this population, and that vocabulary breadth may not predict compositional abilities.

Knocking Out Sodium Glucose-Linked Transporter 5 Prevents Fructose-Induced Renal Oxidative Stress and Salt-Sensitive Hypertension.

BACKGROUND: A fructose high-salt (FHS) diet increases systolic blood pressure and Ang II (angiotensin II)-stimulated proximal tubule (PT) superoxide (O2-) production. These increases are prevented by scavenging O2- or an Ang II type 1 receptor antagonist. SGLT4 (sodium glucose-linked cotransporters 4) and SGLT5 are implicated in PT fructose reabsorption, but their roles in fructose-induced hypertension are unclear. We hypothesized that PT fructose reabsorption by SGLT5 initiates a genetic program enhancing Ang II-stimulated oxidative stress in males and females, thereby causing fructose-induced salt-sensitive hypertension. METHODS: We measured systolic blood pressure in male and female Sprague-Dawley (wild type [WT]), SGLT4 knockout (-/-), and SGLT5-/- rats. Then, we measured basal and Ang II-stimulated (37 nmol/L) O2- production by PTs and conducted gene coexpression network analysis. RESULTS: In male WT and female WT rats, FHS increased systolic blood pressure by 15±3 (n=7; P<0.0027) and 17±4 mm Hg (n=9; P<0.0037), respectively. Male and female SGLT4-/- had similar increases. Systolic blood pressure was unchanged by FHS in male and female SGLT5-/-. In male WT and female WT fed FHS, Ang II stimulated O2- production by 14±5 (n=6; P<0.0493) and 8±3 relative light units/µg protein/s (n=7; P<0.0218), respectively. The responses of SGTL4-/- were similar. Ang II did not stimulate O2- production in tubules from SGLT5-/-. Five gene coexpression modules were correlated with FHS. These correlations were completely blunted in SGLT5-/- and partially blunted by chronically scavenging O2- with tempol. CONCLUSIONS: SGLT5-mediated PT fructose reabsorption is required for FHS to augment Ang II-stimulated proximal nephron O2- production, and increases in PT oxidative stress likely contribute to FHS-induced hypertension.

Association of mental health-related patient reported outcomes with blood pressure in adults and children with primary proteinuric glomerulopathies.

INTRODUCTION: The prevalence of mental health disorders including anxiety and depression is increasing and is linked to hypertension in healthy individuals. However, the relationship of psychosocial patient-reported outcomes on blood pressure (BP) in primary proteinuric glomerulopathies is not well characterized. This study explored longitudinal relationships between psychosocial patient-reported outcomes and BP status among individuals with proteinuric glomerulopathies. METHODS: An observational cohort study was performed using data from 745 adults and children enrolled in the Nephrotic Syndrome Study Network (NEPTUNE). General Estimating Equations for linear regression and binary logistic analysis for odds ratios were performed to analyze relationships between the exposures, longitudinal Patient-Reported Outcome Measurement Information System (PROMIS) measures and BP and hypertension status as outcomes. RESULTS: In adults, more anxiety was longitudinally associated with higher systolic and hypertensive BP. In children, fatigue was longitudinally associated with increased odds of hypertensive BP regardless of the PROMIS report method. More stress, anxiety, and depression were longitudinally associated with higher systolic BP index, higher diastolic BP index, and increased odds of hypertensive BP index in children with parent-proxy patient-reported outcomes. DISCUSSION/CONCLUSION: Chronically poor psychosocial patient-reported outcomes may be significantly associated with higher BP and hypertension in adults and children with primary proteinuric glomerulopathies. This interaction appears strong in children but should be interpreted with caution, as multiple confounders related to glomerular disease may influence both mental health and BP independently. That said, access to mental health resources may help control BP, and proper disease and BP management may improve overall mental health.

A novel image database for social concepts reveals preference biases in autistic spectrum in adults and children.

Human beings display the extraordinary ability of grasping and communicating abstract concepts. Yet, no standardized instruments exist to assess this ability. Developing these tools is paramount for understanding abstract representations such as social concepts, with ramifications in educational and clinical settings. Here, we developed an image database depicting abstract social concepts varying in social desirability. We first validated the image database in a sample of neurotypical participants. Then, we applied the database to test different hypotheses regarding how social concepts are represented across samples of adults and children with autism spectrum condition (ASC). Relative to the neurotypicals, we did not observe differences related to ASC in identification performance of the social desirability of the concepts, nor differences in metacognitive ability. However, we observed a preference bias away from prosocial concepts that was linked to individual autistic traits in the neurotypicals, and higher in ASC relative to the neurotypicals both in adults and children. These results indicate that abstract representations such as social concepts are dependent on individual neurodevelopmental traits. The image database thus provides a standardized assessment tool for investigating the representation of abstract social concepts in the fields of psycholinguistics, neuropsychology, neuropsychiatry, and cognitive neuroscience, across different cultures and languages.

Angiotensin II-stimulated proximal nephron superoxide production and fructose-induced salt-sensitive hypertension.

Angiotensin II (ANG II) increases proximal tubule superoxide (O2-) production more in rats fed a 20% fructose normal-salt diet compared with rats fed a 20% glucose normal-salt diet. A 20% fructose high-salt diet (FHS) increases systolic blood pressure (SBP), whereas a 20% glucose high-salt diet (GHS) does not. However, it is unclear whether FHS enhances ANG II-induced oxidative stress in proximal tubules and whether this contributes to increases in blood pressure in this model. We hypothesized that FHS augments the ability of ANG II to stimulate O2- production by proximal tubules, and this contributes to fructose-induced salt-sensitive hypertension. We measured SBP in male Sprague-Dawley rats fed FHS and GHS and determined the effects of 3 mM tempol and 50 mg/kg losartan for 7 days. We then measured basal and ANG II-stimulated (3.7 × 10-8 M) O2- production by proximal tubule suspensions and the role of protein kinase C. FHS increased SBP by 27 ± 5 mmHg (n = 6, P < 0.006) but GHS did not. Rats fed FHS + tempol and GHS + tempol showed no significant increases in SBP. ANG II increased O2- production by 11 ± 1 relative light units/µg protein/s in proximal tubules from FHS-fed rats (n = 6, P < 0.05) but not in tubules from rats fed GHS. ANG II did not significantly stimulate O2- production by proximal tubules from rats fed FHS + tempol or FHS + losartan. The protein kinase C inhibitor Gö6976 blunted ANG II-stimulated O2- production. In conclusion, FHS enhances the sensitivity of proximal tubule O2- production to ANG II, and this contributes to fructose-induced salt-sensitive hypertension.NEW & NOTEWORTHY A diet containing amounts of fructose consumed by 17 million Americans causes salt-sensitive hypertension. Oxidative stress is an initiating cause of this model of fructose-induced salt-sensitive hypertension increasing blood pressure. This salt-sensitive hypertension is prevented by losartan and thus is angiotensin II (ANG II) dependent. Fructose-induced salt-sensitive hypertension depends on ANG II stimulating oxidative stress in the proximal tubule. A fructose/high-salt diet augments the ability of ANG II to stimulate proximal tubule O2- via protein kinase C.

What does it take to be rigid? Reflections on the notion of rigidity in autism.

Characterizations of autism include multiple references to rigid or inflexible features, but the notion of rigidity itself has received little systematic discussion. In this paper we shed some light on the notion of rigidity in autism by identifying different facets of this phenomenon as discussed in the literature, such as fixed interests, insistence on sameness, inflexible adherence to routines, black-and-white mentality, intolerance of uncertainty, ritualized patterns of verbal and non-verbal behavior, literalism, and discomfort with change. Rigidity is typically approached in a disjointed fashion (i.e., facet by facet), although there are recent attempts at providing unifying explanations. Some of these attempts assume that the rigidity facets mainly relate to executive functioning: although such an approach is intuitively persuasive, we argue that there are equally plausible alternative explanations. We conclude by calling for more research on the different facets of rigidity and on how they cluster together in the autistic population, while suggesting some ways in which intervention could benefit from a finer-grained view of rigidity.

Language in autism: domains, profiles and co-occurring conditions.

This article reviews the current knowledge state on pragmatic and structural language abilities in autism and their potential relation to extralinguistic abilities and autistic traits. The focus is on questions regarding autism language profiles with varying degrees of (selective) impairment and with respect to potential comorbidity of autism and language impairment: Is language impairment in autism the co-occurrence of two distinct conditions (comorbidity), a consequence of autism itself (no comorbidity), or one possible combination from a series of neurodevelopmental properties (dimensional approach)? As for language profiles in autism, three main groups are identified, namely, (i) verbal autistic individuals without structural language impairment, (ii) verbal autistic individuals with structural language impairment, and (iii) minimally verbal autistic individuals. However, this tripartite distinction hides enormous linguistic heterogeneity. Regarding the nature of language impairment in autism, there is currently no model of how language difficulties may interact with autism characteristics and with various extralinguistic cognitive abilities. Building such a model requires carefully designed explorations that address specific aspects of language and extralinguistic cognition. This should lead to a fundamental increase in our understanding of language impairment in autism, thereby paving the way for a substantial contribution to the question of how to best characterize neurodevelopmental disorders.

T-cell receptor diversity in minimal change disease in the NEPTUNE study.

BACKGROUND: Minimal change disease (MCD) is the major cause of childhood idiopathic nephrotic syndrome, which is characterized by massive proteinuria and debilitating edema. Proteinuria in MCD is typically rapidly reversible with corticosteroid therapy, but relapses are common, and children often have many adverse events from the repeated courses of immunosuppressive therapy. The pathobiology of MCD remains poorly understood. Prior clinical observations suggest that abnormal T-cell function may play a central role in MCD pathogenesis. Based on these observations, we hypothesized that T-cell responses to specific exposures or antigens lead to a clonal expansion of T-cell subsets, a restriction in the T-cell repertoire, and an elaboration of specific circulating factors that trigger disease onset and relapses. METHODS: To test these hypotheses, we sequenced T-cell receptors in fourteen MCD, four focal segmental glomerulosclerosis (FSGS), and four membranous nephropathy (MN) patients with clinical data and blood samples drawn during active disease and during remission collected by the Nephrotic Syndrome Study Network (NEPTUNE). We calculated several T-cell receptor diversity metrics to assess possible differences between active disease and remission states in paired samples. RESULTS: Median productive clonality did not differ between MCD active disease (0.0083; range: 0.0042, 0.0397) and remission (0.0088; range: 0.0038, 0.0369). We did not identify dominant clonotypes in MCD active disease, and few clonotypes were shared with FSGS and MN patients. CONCLUSIONS: While these data do not support an obvious role of the adaptive immune system T-cells in MCD pathogenesis, further study is warranted given the limited sample size. A higher resolution version of the Graphical abstract is available as Supplementary information.

Profiling cellular heterogeneity and fructose transporter expression in the rat nephron by integrating single-cell and microdissected tubule segment transcriptomes.

Single-cell RNA sequencing (scRNAseq) is a crucial tool in kidney research. These technologies cluster cells according to transcriptome similarity, irrespective of the anatomical location and ordering within the nephron. Thus, a cluster transcriptome may obscure heterogeneity of the cell population within a nephron segment. Elevated dietary fructose leads to salt-sensitive hypertension, in part by fructose reabsorption in the proximal tubule (PT). However, organization of the four known fructose transporters in apical PTs (SGLT4, SGLT5, GLUT5 and NaGLT1) remains poorly understood. We hypothesized that cells within each subsegment of the proximal tubule exhibit complex, heterogenous fructose transporter expression patterns. To test this hypothesis we analyzed rat and kidney transcriptomes and proteomes from publicly available scRNAseq and tubule microdissection databases. We found that microdissected PT-S1 segments consist of 81±12% cells with scRNAseq-derived transcriptional characteristics of S1, whereas PT-S2 express a mixture of 18±9% S1, 58±8% S2, and 19±5% S3 transcripts, and PT-S3 consists of 75±9% S3 transcripts. The expression of all four fructose transporters was detectable in all three PT segments, but key fructose transporters SGLT5 and GLUT5 progressively increased from S1 to S3, and both were significantly upregulated in S3 vs. S1/S2 (Slc5a10: 1.9 log 2 FC, p<1×10 -299 ; Scl2a5: 1.4 log 2 FC, p<4×10 -105 ). A similar distribution was found in human kidneys. These data suggest that S3 is the primary site of fructose reabsorption in both humans and rats. Finally, because of the multiple scRNAseq transcriptional phenotypes found in each segment our findings also imply that anatomic labels applied to scRNAseq clusters may be misleading.

Independent effects of sex and stress on fructose-induced salt-sensitive hypertension.

Proximal tubule fructose metabolism is key to fructose-induced hypertension, but the roles of sex and stress are unclear. We hypothesized that females are resistant to the salt-sensitive hypertension caused by low amounts of dietary fructose compared to males and that the magnitude of the increase in blood pressure (BP) depends, in part, on amplification of the stress response of renal sympathetic nerves. We measured systolic BP (SBP) in rats fed high salt with either no sugar (HS), 20% glucose (GHS) or 20% fructose (FHS) in the drinking water for 7-8 days. FHS increased SBP in both males (Δ22 ± 9 mmHg; p < 0.046) and females (Δ16 ± 3 mmHg; p < 0.0007), while neither GHS nor HS alone induced changes in SBP in either sex. The FHS-induced increase in SBP as measured by telemetry in the absence of added stress (8 ± 2 mmHg) was significantly lower than that measured by plethysmography (24 ± 5 mmHg) (p < 0.014). However, when BP was measured by telemetry simulating the stress of plethysmography, the increase in SBP was significantly greater (15 ± 3 mmHg) than under low stress (8 ± 1 mmHg) (p < 0.014). Moderate-stress also increased telemetric diastolic (p < 0.006) and mean BP (p < 0.006) compared to low-stress in FHS-fed animals. Norepinephrine excretion was greater in FHS-fed rats than HS-fed animals (Male: 6.4 ± 1.7 vs.1.8 ± 0.4 nmole/kg/day; p < 0.02. Female 54 ± 18 vs. 1.2 ± 0.6; p < 0.02). We conclude that fructose-induced salt-sensitive hypertension is similar in males and females unlike other forms of hypertension, and the increase in blood pressure depends in part on an augmented response of the sympathetic nervous system to stress.

Mechanisms of decreased tubular flow-induced nitric oxide in Dahl salt-sensitive rat thick ascending limbs.

Dahl salt-sensitive (SS) rat kidneys produce less nitric oxide (NO) than those of salt-resistant (SR) rats. Thick ascending limb (TAL) NO synthase 3 (NOS3) is a major source of renal NO, and luminal flow enhances its activity. We hypothesized that flow-induced NO is reduced in TALs from SS rats primarily due to NOS uncoupling and diminished NOS3 expression rather than scavenging. Rats were fed normal-salt (NS) or high-salt (HS) diets. We measured flow-induced NO and superoxide in perfused TALs and performed Western blots of renal outer medullas. For rats on NS, flow-induced NO was 35 ± 6 arbitrary units (AU)/min in TALs from SR rats but only 11 ± 2 AU/min in TALs from SS (P < 0.008). The superoxide scavenger tempol decreased the difference in flow-induced NO between strains by about 36% (P < 0.020). The NOS inhibitor N-nitro-l-arginine methyl ester (l-NAME) decreased flow-induced superoxide by 36 ± 8% in TALs from SS rats (P < 0.02) but had no effect in TALs from SR rats. NOS3 expression was not different between strains on NS. For rats on HS, the difference in flow-induced NO between strains was enhanced (SR rats: 44 ± 10 vs. SS: 9 ± 2 AU/min, P < 0.005). Tempol decreased the difference in flow-induced NO between strains by about 37% (P < 0.012). l-NAME did not significantly reduce flow-induced superoxide in either strain. HS increased NOS3 expression in TALs from SR rats but not in TALs from SS rats (P < 0.003). We conclude that 1) on NS, flow-induced NO is diminished in TALs from SS rats mainly due to NOS3 uncoupling such that it produces superoxide and 2) on HS, the difference is enhanced due to failure of TALs from SS rats to increase NOS3 expression.NEW & NOTEWORTHY The Dahl rat has been used extensively to study the causes and effects of salt-sensitive hypertension. Our study suggests that more complex processes other than simple scavenging of nitric oxide (NO) by superoxide lead to less NO production in thick ascending limbs of the Dahl salt-sensitive rat. The predominant mechanism involved depends on dietary salt. Impaired flow-induced NO production in thick ascending limbs most likely contributes to the Na+ retention associated with salt-sensitive hypertension.

Relations between language, non-verbal cognition, and conceptualization in non- or minimally verbal individuals with ASD across the lifespan.

Background & aims: Individuals with non- or minimally verbal autism (nvASD) are primarily characterized by a severe speech production deficit, with speech limited to no or only a few words by school age. Significant unclarity remains over variability in language profiles across the lifespan, the nature of the language impairment seen, and (dis-) associations between linguistic and nonverbal cognitive measures. Methods: To address these questions, we recruited both a school-age and an adult group with nvASD (total N = 49) and investigated relations between expressive and receptive language, and between these and nonverbal intelligence quotient (NVIQ) and sense-making capacities (the ComFor test). Results: Results revealed limited variation across this sample in receptive language, which in turn predicted expressive language levels. Importantly, an upward trend in verbal mental age (VMA) across increasing chronological age was seen in the youngsters (only). A radical dissociation between NVIQ and both expressive and receptive language transpired as well, and a subset of individuals with normal NVIQ were comparable in terms of any other cognitive aspect. Sense-making reached symbolic levels in 62.2% of the sample and loaded on both verbal and nonverbal factors. Conclusions: These patterns inform theories of nvASD by revealing an impairment that is not conceptualizable as one of expressive language only, sharply limits learning opportunities across the lifespan, and cannot be compensated for by nonverbal cognition. Implications: These findings stress the need to seize developmental opportunities that may disappear when youngsters turn into adults, via therapies that specifically target language as a central cognitive system comprising both production and comprehension.

The Role of Inner Speech in Executive Functioning Tasks: Schizophrenia With Auditory Verbal Hallucinations and Autistic Spectrum Conditions as Case Studies.

Several theories propose that one of the core functions of inner speech (IS) is to support subjects in the completion of cognitively effortful tasks, especially those involving executive functions (EF). In this paper we focus on two populations who notoriously encounter difficulties in performing EF tasks, namely, people diagnosed with schizophrenia who experience auditory verbal hallucinations (Sz-AVH) and people with autism spectrum conditions (ASC). We focus on these two populations because they represent two different ways in which IS can fail to help in EF tasks, which can be illustrative for other mental conditions. First, we review the main components of EF (see section "Executive Functions"). Then we explain the functions that IS is taken to perform in the domain of EF (see section "Inner Speech and Executive Functions") and review the evidence concerning problems about EF in the two populations of our study: Sz-AVH (see section "Executive Functions and Inner Speech in Sz-AVH") and ASC (see section "Executive Function and Inner Speech in ASC"). After this we further detail our account about what a properly functioning IS can do for both populations and how different IS profiles may impact EF performance: in the case of Sz-AVH, the uncontrolled and intrusive character of IS negatively affects EF performance, whereas in ASC, EF is not sufficiently supported by IS, given the tendency in this population to present a diminished use of IS (see section "IS in ASC and Sz-AVH: How It Relates to EF"). We finally briefly discuss Attention Deficit/Hyperactivity Disorder (ADHD) and Developmental Language Disorders (DLD) (see section "Further Considerations").

Angiotensin II-induced superoxide and decreased glutathione in proximal tubules: effect of dietary fructose.

Angiotensin II exacerbates oxidative stress in part by increasing superoxide (O2-) production by many renal tissues. However, whether it does so in proximal tubules and the source of O2- in this segment are unknown. Dietary fructose enhances the stimulatory effect of angiotensin II on proximal tubule Na+ reabsorption, but whether this is true for oxidative stress is unknown. We hypothesized that angiotensin II causes proximal nephron oxidative stress in part by stimulating NADPH oxidase (NOX)4-dependent O2- production and decreasing the amount of the antioxidant glutathione, and this is exacerbated by dietary fructose. We measured basal and angiotensin II-stimulated O2- production with and without inhibitors, NOX1 and NOX4 expression, and total and reduced glutathione (GSH) in proximal tubules from rats drinking either tap water (control) or 20% fructose. Angiotensin II (10 nM) increased O2- production by 113 ± 42 relative light units·mg protein-1·s-1 in controls and 401 ± 74 relative light units·mg protein-1·s-1 with 20% fructose (n = 11 for each group, P < 0.05 vs. control). Apocynin and the Nox1/4 inhibitor GKT136901 prevented angiotensin II-induced increases in both groups. NOX4 expression was not different between groups. NOX1 expression was undetectable. Angiotensin II decreased GSH by 1.8 ± 0.8 nmol/mg protein in controls and by 4.2 ± 0.9 nmol/mg protein with 20% fructose (n = 18 for each group, P < 0.047 vs. control). We conclude that 1) angiotensin II causes oxidative stress in proximal tubules by increasing O2- production by NOX4 and decreasing GSH and 2) dietary fructose enhances the ability of angiotensin II to stimulate O2- and diminish GSH, thereby exacerbating oxidative stress in this segment.

Effects of reactive oxygen species on renal tubular transport.

Reactive oxygen species (ROS) play a critical role in regulating nephron transport both via transcellular and paracellular pathways under physiological and pathological circumstances. Here, we review the progress made in the past ~10 yr in understanding how ROS regulate solute and water transport in individual nephron segments. Our knowledge in this field is still rudimentary, with basic information lacking. This is most obvious when looking at the reported disparate effects of superoxide ([Formula: see text]) and H2O2 on proximal nephron transport, where there are no easy explanations as to how to reconcile the data. Similarly, we know almost nothing about the regulation of transport in thin descending and ascending limbs, information that is likely critical to understanding the urine concentrating mechanism. In the thick ascending limb, there is general agreement that ROS enhance transcellular reabsorption of NaCl, but we know very little about their effects on the paracellular pathway and therefore Ca2+ and Mg2+ transport. In the distal convoluted tubule, precious little is known. In the collecting duct, there is general agreement that ROS stimulate the epithelial Na+ channel.

Panorama sobre la bioética infantil en Iberoamérica / Panorama of Children's Bioethics in Ibero-America / Panorama da Bioética infantil na América Latina

Resumen Este trabajo tiene como objetivo ofrecer un acercamiento a la bioética infantil en el mundo iberoamericano. Partimos del estatus diferenciado del menor respecto de otros estadios evolutivos así como del desarrollo histórico de la bioética en el espacio iberoamericano. Primero, se presenta una propuesta para clasificar los principales asuntos susceptibles de ser considerados por la bioética infantil iberoamericana. A continuación, se discuten los principales problemas y conflictos de la bioética infantil en función de las normas bioéticas, biomorales o biopolíticas implicadas. Esta cuestión se ejemplifica con el debate sobre el trabajo infantil y con el debate entre una bioética autonomista o paternalista. Así mismo, se proponen dos criterios generales de actuación que comprometen a las políticas públicas en favor de la infancia. Se finaliza destacando que la bioética infantil merece un espacio destacado y diferenciado dentro de la bioética llevada a cabo desde Iberoamérica.

Abstract This work aims to offer an approach to children's bioethics in the Ibero-American world. We start from the differentiated status of the minor with respect to other stages of life as well as the historical development of bioethics in the Ibero-American space. First, a proposal is presented to classify the main topics that could be considered by Ibero-American children's bioethics. Next, the main problems and conflicts of child bioethics are discussed according to the bioethical, biomoral or biopolitical norms involved. This matter is exemplified by the debate on child labour and the debate between an autonomist or paternalistic bioethics. Likewise, two general criteria for action that commit public policies in favour of children are proposed. It is finalised emphasising that children's bioethics deserves a prominent and differentiated space within the bioethics in Ibero-America.

Resumo Este trabalho tem como objectivo oferecer uma aproximação à bioética infantil no mundo iberoamericano. Começamos a partir do estado diferenciado do menor em comparação com outros estágios evolutivos assim como do desenvolvimento histórico da bioética na América Latina. Primeiro, apresenta-se uma proposta para classificar os principais assuntos que poderiam ser considerados pela Bioética da criança na América Latina. Logo, discutem-se os principais problemas e conflitos da bioética infantil de acordo com os padrões bioéticos, bio-morais ou biopolíticos envolvidos. Esta questão é exemplificada com o debate sobre o trabalho infantil e com o debate entre uma bioética autonomista ou paternalista. Assim mesmo, são propostos dois critérios gerais de ação que comprometem políticas públicas a favor das crianças. Finaliza-se enfatizando que a Bioética da criança merece um espaço excepcional e diferenciado dentro da bioética realizada da América Latina.

Thick Ascending Limb Sodium Transport in the Pathogenesis of Hypertension.

The thick ascending limb plays a key role in maintaining water and electrolyte balance. The importance of this segment in regulating blood pressure is evidenced by the effect of loop diuretics or local genetic defects on this parameter. Hormones and factors produced by thick ascending limbs have both autocrine and paracrine effects, which can extend prohypertensive signaling to other structures of the nephron. In this review, we discuss the role of the thick ascending limb in the development of hypertension, not as a sole participant, but one that works within the rich biological context of the renal medulla. We first provide an overview of the basic physiology of the segment and the anatomical considerations necessary to understand its relationship with other renal structures. We explore the physiopathological changes in thick ascending limbs occurring in both genetic and induced animal models of hypertension. We then discuss the racial differences and genetic defects that affect blood pressure in humans through changes in thick ascending limb transport rates. Throughout the text, we scrutinize methodologies and discuss the limitations of research techniques that, when overlooked, can lead investigators to make erroneous conclusions. Thus, in addition to advancing an understanding of the basic mechanisms of physiology, the ultimate goal of this work is to understand our research tools, to make better use of them, and to contextualize research data. Future advances in renal hypertension research will require not only collection of new experimental data, but also integration of our current knowledge.