Glycome dynamics in T and B cell development: basic immunological mechanisms and clinical applications.

Glycans cover the surfaces of all mammalian cells through a process called glycosylation. Nearly all proteins and receptors that integrate the intricate series of co-stimulatory/inhibitory pathways of the immune system are glycosylated. Growing evidence indicates that the development of the immune system at the origins of T and B cell development is tightly regulated by glycosylation. In this opinion, we hypothesize that the glycome composition of developing T and B cells is developmentally regulated. We discuss how glycans play fundamental roles in lymphocyte development and how glycans early define T and B cell functionality in multiple aspects of adaptive immunity. These advances can provide opportunities for the discovery of novel disease factors and more effective candidate treatments for various conditions.

Glycans as shapers of tumour microenvironment: A sweet driver of T-cell-mediated anti-tumour immune response.

Essentially all cells are covered with a dense coat of different glycan structures/sugar chains, giving rise to the so-called glycocalyx. Changes in cellular glycosylation are a hallmark of cancer, affecting most of the pathophysiological processes associated with malignant transformation, including tumour immune responses. Glycans are chief macromolecules that define T-cell development, differentiation, fate, activation and signalling. Thus, the diversity of glycans expressed at the surface of T cells constitutes a fundamental molecular interface with the microenvironment by regulating the bilateral interactions between T-cells and cancer cells, fine-tuning the anti-tumour immune response. In this review, we will introduce the power of glycans as orchestrators of T-cell-mediated immune response in physiological conditions and in cancer. We discuss how glycans modulate the glyco-metabolic landscape in the tumour microenvironment, and whether glycans can synergize with immunotherapy as a way of rewiring T-cell effector functions against cancer cells.

Altered IgG glycosylation at COVID-19 diagnosis predicts disease severity.

The nature of the immune responses associated with COVID-19 pathogenesis and disease severity, as well as the breadth of vaccine coverage and duration of immunity, is still unclear. Given the unpredictability for developing a severe/complicated disease, there is an urgent need in the field for predictive biomarkers of COVID-19. We have analyzed IgG Fc N-glycan traits of 82 SARS-CoV-2+ unvaccinated patients, at diagnosis, by nano-LC-ESI-MS. We determined the impact of IgG Fc glyco-variations in the induction of NK cells activation, further evaluating the association between IgG Fc N-glycans and disease severity/prognosis. We found that SARS-CoV-2+ individuals display, at diagnosis, variations in the glycans composition of circulating IgGs. Importantly, levels of galactose and sialic acid structures on IgGs are able to predict the development of a poor COVID-19 disease. Mechanistically, we demonstrated that a deficiency on galactose structures on IgG Fc in COVID-19 patients appears to induce NK cells activation associated with increased release of IFN-γ and TNF-α, which indicates the presence of pro-inflammatory immunoglobulins and higher immune activation, associated with a poor disease course. This study brings to light a novel blood biomarker based on IgG Fc glycome composition with capacity to stratify patients at diagnosis.

SARS-CoV-2 Infection Drives a Glycan Switch of Peripheral T Cells at Diagnosis.

COVID-19 is a highly selective disease in which SARS-CoV-2 infection can result in different clinical manifestations ranging from asymptomatic/mild to severe disease that requires hospitalization. In this study, we demonstrated that SARS-CoV-2 infection results in a glycosylation reprogramming of circulating lymphocytes at diagnosis. We identified a specific glycosignature of T cells, defined upon SARS-CoV-2 infection and apparently triggered by a serological factor. This specific glycan switch of T cells is detected at diagnosis being more pronounced in asymptomatic patients. We further demonstrated that asymptomatic patients display an increased expression of a viral-sensing receptor through the upregulation of DC-SIGN in monocytes. We showed that higher levels of DC-SIGN in monocytes at diagnosis correlates with better COVID-19 prognosis. This new evidence pave the way to the identification of a novel glycan-based response in T cells that may confer protection against SARS-CoV-2 infection in asymptomatic patients, highlighting a novel prognostic biomarker and potential therapeutic target.

"I think it impacts all areas of his life": Perspectives on hearing from mothers of individuals with Down syndrome.

BACKGROUND: Individuals with Down syndrome are known to have high rates of hearing loss, but it is unclear how this impacts their ability to communicate and function in real-world environments. METHODS: Sixteen English-speaking and Spanish-speaking mothers of individuals with Down syndrome ages 6-40 years participated in individual, semi-structured interviews using a videoconferencing platform. Session transcripts were analysed using applied thematic analysis. RESULTS: Mothers described listening environments, the impact of hearing on daily life, barriers to successful listening, and strategies to overcome communication barriers for their children with Down syndrome. CONCLUSIONS: Hearing was largely discussed in terms of challenges and detriments, suggesting that hearing experiences are predominately considered to negatively impact the functional abilities of individuals with Down syndrome. Background noise and hearing loss were sources of communication difficulties. Parent-reported barriers and strategies can inform ecologically valid research priorities aimed at improving outcomes for individuals with Down syndrome.

Early calcium and cardiac contraction defects in a model of phospholamban R9C mutation in zebrafish.

The phospholamban mutation Arg 9 to Cys (R9C) has been found to cause a dilated cardiomyopathy in humans and in transgenic mice, with ventricular dilation and premature death. Emerging evidence suggests that phospholamban R9C is a loss-of-function mutation with dominant negative effect on SERCA2a activity. We imaged calcium and cardiac contraction simultaneously in 3 and 9 days-post-fertilization (dpf) zebrafish larvae expressing plnbR9C in the heart to unveil the early pathological pathway that triggers the disease. We generated transgenic zebrafish lines expressing phospholamban wild-type (Tg(myl7:plnbwt)) and phospholamban R9C (Tg(myl7:plnbR9C)) in the heart of zebrafish. To measure calcium and cardiac contraction in 3 and 9 dpf larvae, Tg(myl7:plnbwt) and Tg(myl7:plnbR9C) fish were outcrossed with a transgenic line expressing the ratiometric fluorescent calcium biosensor mCyRFP1-GCaMP6f. We found that PlnbR9C raised calcium transient amplitude, induced positive inotropy and lusitropy, and blunted the ß-adrenergic response to isoproterenol in 3 dpf larvae. These effects can be attributed to enhanced SERCA2a activity induced by the PlnbR9C mutation. In contrast, Tg(myl7:plnbR9C) larvae at 9 dpf exhibited ventricular dilation, systolic dysfunction and negative lusitropy, hallmarks of a dilated cardiomyopathy in humans. Importantly, N-acetyl-L-cysteine rescued this deleterious phenotype, suggesting that reactive oxygen species contribute to the pathological pathway. These results also imply that dysregulation of calcium homeostasis during embryo development contributes to the disease progression at later stages. Our in vivo model in zebrafish allows characterization of pathophysiological mechanisms leading to heart disease, and can be used for screening of potential therapeutical agents.

Risks and new challenges in the food chain: Viral contamination and decontamination from a global perspective, guidelines, and cleaning.

Even during the continuing world pandemic of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), consumers remain exposed to the risk of getting infected by existing, emerging, or re-emerging foodborne and waterborne viruses. SARS-CoV-2 is different in that it is transmitted directly via the airborne route (droplets and aerosols) or indirect contact (surfaces contaminated with SARS-CoV-2). International food and health organizations and national regulatory bodies have provided guidance to protect individuals active in food premises from potential occupational exposure to SARS-CoV-2, and have recommended chemicals effective in controlling the virus. Additionally, to exclude transmission of foodborne and waterborne viruses, hygiene practices to remove viral contaminants from surfaces are applied in different stages of the food chain (e.g., food plants, food distribution, storage, retail sector, etc.), while new and enhanced measures effective in the control of all types of viruses are under development. This comprehensive review aims to analyze and compare efficacies of existing cleaning practices currently used in the food industry to remove pathogenic viruses from air, nonfood, and food contact surfaces, as well as from food surfaces. In addition, the classification, modes of transmission, and survival of food and waterborne viruses, as well as SARS-CoV-2 will be presented. The international guidelines and national regulations are summarized in terms of virucidal chemical agents and their applications.

Composition of the immunoglobulin G glycome associates with the severity of COVID-19.

A large variation in the severity of disease symptoms is one of the key open questions in coronavirus disease 2019 (COVID-19) pandemics. The fact that only a small subset of people infected with severe acute respiratory syndrome coronavirus 2 develops severe disease suggests that there have to be some predisposing factors, but biomarkers that reliably predict disease severity have not been found so far. Since overactivation of the immune system is implicated in a severe form of COVID-19 and the immunoglobulin G (IgG) glycosylation is known to be involved in the regulation of different immune processes, we evaluated the association of interindividual variation in IgG N-glycome composition with the severity of COVID-19. The analysis of 166 severe and 167 mild cases from hospitals in Spain, Italy and Portugal revealed statistically significant differences in the composition of the IgG N-glycome. The most notable difference was the decrease in bisecting N-acetylglucosamine in severe patients from all three cohorts. IgG galactosylation was also lower in severe cases in all cohorts, but the difference in galactosylation was not statistically significant after correction for multiple testing.

Soil erosion modelling: A bibliometric analysis.

Soil erosion can present a major threat to agriculture due to loss of soil, nutrients, and organic carbon. Therefore, soil erosion modelling is one of the steps used to plan suitable soil protection measures and detect erosion hotspots. A bibliometric analysis of this topic can reveal research patterns and soil erosion modelling characteristics that can help identify steps needed to enhance the research conducted in this field. Therefore, a detailed bibliometric analysis, including investigation of collaboration networks and citation patterns, should be conducted. The updated version of the Global Applications of Soil Erosion Modelling Tracker (GASEMT) database contains information about citation characteristics and publication type. Here, we investigated the impact of the number of authors, the publication type and the selected journal on the number of citations. Generalized boosted regression tree (BRT) modelling was used to evaluate the most relevant variables related to soil erosion modelling. Additionally, bibliometric networks were analysed and visualized. This study revealed that the selection of the soil erosion model has the largest impact on the number of publication citations, followed by the modelling scale and the publication's CiteScore. Some of the other GASEMT database attributes such as model calibration and validation have negligible influence on the number of citations according to the BRT model. Although it is true that studies that conduct calibration, on average, received around 30% more citations, than studies where calibration was not performed. Moreover, the bibliographic coupling and citation networks show a clear continental pattern, although the co-authorship network does not show the same characteristics. Therefore, soil erosion modellers should conduct even more comprehensive review of past studies and focus not just on the research conducted in the same country or continent. Moreover, when evaluating soil erosion models, an additional focus should be given to field measurements, model calibration, performance assessment and uncertainty of modelling results. The results of this study indicate that these GASEMT database attributes had smaller impact on the number of citations, according to the BRT model, than anticipated, which could suggest that these attributes should be given additional attention by the soil erosion modelling community. This study provides a kind of bibliographic benchmark for soil erosion modelling research papers as modellers can estimate the influence of their paper.

The Role of Glycosylation in Inflammatory Diseases.

The diversity of glycan presentation in a cell, tissue and organism is enormous, which reflects the huge amount of important biological information encoded by the glycome which has not been fully understood. A compelling body of evidence has been highlighting the fundamental role of glycans in immunity, such as in development, and in major inflammatory processes such as inflammatory bowel disease, systemic lupus erythematosus and other autoimmune disorders. Glycans play an instrumental role in the immune response, integrating the canonical circuits that regulate innate and adaptive immune responses. The relevance of glycosylation in immunity is demonstrated by the role of glycans as important danger-associated molecular patterns and pathogen-associated molecular patterns associated with the discrimination between self and non-self; also as important regulators of the threshold of T cell activation, modulating receptors signalling and the activity of both T and other immune cells. In addition, glycans are important determinants that regulate the dynamic crosstalk between the microbiome and immune response. In this chapter, the essential role of glycans in the immunopathogenesis of inflammatory disorders will be presented and its potential clinical applications (diagnosis, prognosis and therapeutics) will be highlighted.

Effectiveness of soil erosion barriers to reduce sediment connectivity at small basin scale in a fire-affected forest.

Forest fires and post-fire management practices (PFMP) cause changes in the hydrological response of a hillslope. This study evaluates the effect of log erosion barriers (LB) and Easy-Barriers® (EB) on the spatial patterns and values of structural sediment connectivity (SC) in a Mediterranean mountainous pine forest affected by an arson fire in August 2017. A drone flight was done in July 2019 (23 months after the fire and 11 months after the PFMP) to obtain a high-resolution orthomosaic and DEM (at 0.05 m). Two contrasted areas, with and without PFMP, were selected along the same hillslope and 26 small basins were identified: 16 in the treated area (mean area, slope and vegetation recovery of 916 m2, 60% and 25%; with 94 LB and 39 EB) and 10 in the untreated area (1952 m2, 75% and 20%). The aggregated index of sediment connectivity (AIC) was chosen to compute SC in three temporal scenarios: Before and just after the fire and when all PFMP were implemented including the incipient vegetation recovery. Output normalization allowed the comparison of the non-nested basins among them. After accounting the intrinsic differences among the basins and areas, and the temporal changes of SC between the three scenarios, the contribution of the barriers was estimated in 27% from the total decrease of SC in the treated area (-8.5%). The remaining 73% was explained by the vegetation recovery. The effectiveness of the LB (11.3% on average) and EB (13.4%) did not diminish with increasing slope gradients. These percentages become relevant considering the small area affected by the LB (2.8%) and EB (1.3%). Independent metrics (convergence index, flow width, flat areas and LS factor) also reported clear differences between the two areas -higher soil erosive intensity in the untreated area- and in accordance with the AIC results.

Mapping Calcium Dynamics in the Heart of Zebrafish Embryos with Ratiometric Genetically Encoded Calcium Indicators.

Zebrafish embryos have been proposed as a cost-effective vertebrate model to study heart function. Many fluorescent genetically encoded Ca2+ indicators (GECIs) have been developed, but those with ratiometric readout seem more appropriate to image a moving organ such as the heart. Four ratiometric GECIs based on troponin C, TN-XXL, Twitch-1, Twitch-2B, and Twitch-4 were expressed transiently in the heart of zebrafish embryos. Their emission ratio reported the Ca2+ levels in both the atrium and the ventricle. We measured several kinetic parameters of the Ca2+ transients: systolic and diastolic ratio, the amplitude of the systolic Ca2+ rise, the heart rate, as well as the rise and decay times and slopes. The systolic ratio change decreased in cells expressing high biosensor concentration, possibly caused by Ca2+ buffering. The GECIs were able to report the effect of nifedipine and propranolol on the heart, which resulted in changes in heart rate, diastolic and systolic Ca2+ levels, and Ca2+ kinetics. As a result, Twitch-1 and Twitch-4 (Kd 0.25 and 2.8 µM, respectively) seem the most promising GECIs for generating transgenic zebrafish lines, which could be used for modeling heart disorders, for drug screening, and for cardiotoxicity assessment during drug development.

Visualization of Mitochondrial Ca2+ Signals in Skeletal Muscle of Zebrafish Embryos with Bioluminescent Indicators.

Mitochondria are believed to play an important role in shaping the intracellular Ca2+ transients during skeletal muscle contraction. There is discussion about whether mitochondrial matrix Ca2+ dynamics always mirror the cytoplasmic changes and whether this happens in vivo in whole organisms. In this study, we characterized cytosolic and mitochondrial Ca2+ signals during spontaneous skeletal muscle contractions in zebrafish embryos expressing bioluminescent GFP-aequorin (GA, cytoplasm) and mitoGFP-aequorin (mitoGA, trapped in the mitochondrial matrix). The Ca2+ transients measured with GA and mitoGA reflected contractions of the trunk observed by transmitted light. The mitochondrial uncoupler FCCP and the inhibitor of the mitochondrial calcium uniporter (MCU), DS16570511, abolished mitochondrial Ca2+ transients whereas they increased the frequency of cytosolic Ca2+ transients and muscle contractions, confirming the subcellular localization of mitoGA. Mitochondrial Ca2+ dynamics were also determined with mitoGA and were found to follow closely cytoplasmic changes, with a slower decay. Cytoplasmic Ca2+ kinetics and propagation along the trunk and tail were characterized with GA and with the genetically encoded fluorescent Ca2+ indicator, Twitch-4. Although fluorescence provided a better spatio-temporal resolution, GA was able to resolve the same kinetic parameters while allowing continuous measurements for hours.

Suppression of Contraction Raises Calcium Ion Levels in the Heart of Zebrafish Larvae.

Zebrafish larvae have emerged as a valuable model for studying heart physiology and pathophysiology, as well as for drug discovery, in part thanks to its transparency, which simplifies microscopy. However, in fluorescence-based optical mapping, the beating of the heart results in motion artifacts. Two approaches have been employed to eliminate heart motion during calcium or voltage mapping in zebrafish larvae: the knockdown of cardiac troponin T2A and the use of myosin inhibitors. However, these methods disrupt the mechano-electric and mechano-mechanic coupling mechanisms. We have used ratiometric genetically encoded biosensors to image calcium in the beating heart of intact zebrafish larvae because ratiometric quantification corrects for motion artifacts. In this study, we found that halting heart motion by genetic means (injection of tnnt2a morpholino) or chemical tools (incubation with para-aminoblebbistatin) leads to bradycardia, and increases calcium levels and the size of the calcium transients, likely by abolishing a feedback mechanism that connects contraction with calcium regulation. These outcomes were not influenced by the calcium-binding domain of the gene-encoded biosensors employed, as biosensors with a modified troponin C (Twitch-4), calmodulin (mCyRFP1-GCaMP6f), or the photoprotein aequorin (GFP-aequorin) all yielded similar results. Cardiac contraction appears to be an important regulator of systolic and diastolic Ca2+ levels, and of the heart rate.

ERG potassium channels and T-type calcium channels contribute to the pacemaker and atrioventricular conduction in zebrafish larvae.

AIM: Bradyarrhythmias result from inhibition of automaticity, prolonged repolarization, or slow conduction in the heart. The ERG channels mediate the repolarizing current IKr in the cardiac action potential, whereas T-type calcium channels (TTCC) are involved in the sinoatrial pacemaker and atrioventricular conduction in mammals. Zebrafish have become a valuable research model for human cardiac electrophysiology and disease. Here, we investigate the contribution of ERG channels and TTCCs to the pacemaker and atrioventricular conduction in zebrafish larvae and determine the mechanisms causing atrioventricular block. METHODS: Zebrafish larvae expressing ratiometric fluorescent Ca2+ biosensors in the heart were used to measure Ca2+ levels and rhythm in beating hearts in vivo, concurrently with contraction and hemodynamics. The atrioventricular delay (the time between the start of atrial and ventricular Ca2+ transients) was used to measure impulse conduction velocity and distinguished between slow conduction and prolonged refractoriness as the cause of the conduction block. RESULTS: ERG blockers caused bradycardia and atrioventricular block by prolonging the refractory period in the atrioventricular canal and in working ventricular myocytes. In contrast, inhibition of TTCCs caused bradycardia and second-degree block (Mobitz type I) by slowing atrioventricular conduction. TTCC block did not affect ventricular contractility, despite being highly expressed in cardiomyocytes. Concomitant measurement of Ca2+ levels and ventricular size showed mechano-mechanical coupling: increased preload resulted in a stronger heart contraction in vivo. CONCLUSION: ERG channels and TTCCs influence the heart rate and atrioventricular conduction in zebrafish larvae. The zebrafish lines expressing Ca2+ biosensors in the heart allow us to investigate physiological feedback mechanisms and complex arrhythmias.

Sustainable Low-Cost Phosphorus Recovery Using Nanostructured Materials with Reusability Potential.

A new low-cost material with a polymeric base formed from sodium silicate was developed. The material presents a nanostructured, highly rich iron surface with a large phosphorus retention capacity and potential reuse as a crop fertilizer. In the present study, we demonstrate that iron is the element that acts as an adsorbent for phosphate, while the polymeric base functions exclusively as a support for iron. The iron is uniformly adsorbed on the surface of the material, forming nanostructures, which ensure that iron works similarly to nanoparticles in solution but avoid other problems, such as particle agglomeration or the difficulty of separating them after the removal process. Materials were characterised by SEM, EDS, N2 sorption, and image processing, and the effect of pH, ionic strength, and temperature was studied. Sorption kinetics were analysed using Boyd's diffusion model, and adsorption equilibria were studied using several adsorption models. A maximum iron adsorption on the polymeric base of 23.9 ± 0.3 mg Fe∙g-1 was found, while maximum phosphorus adsorption was 366 ± 21 mg P∙g-1 Fe. Thus, phosphorus is recovered from the aqueous medium with an inexpensive material that has the potential to be used directly as a fertilizer.

Predicting Behavioral Threshold at 6 and 8 kHz for Children and Adults Based on the Auditory Brainstem Response.

PURPOSE: Common clinical application of auditory brainstem response (ABR) testing is limited to 0.25-4 kHz. Prior research has demonstrated associations between ABR and behavioral thresholds for tone burst stimuli > 4 kHz in adults, but there are no comparable data for children. The ability to predict behavioral thresholds > 4 kHz clinically based on the ABR would provide valuable audiologic information for individuals who are unable to provide behavioral thresholds. This study included children with hearing loss and children with normal hearing to determine the association between ABR and behavioral thresholds at 6 and 8 kHz. METHOD: ABR and behavioral thresholds were obtained for children ages 4.7-16.7 years (M = 10.5, SD = 3.4) with sensorineural hearing loss (n = 24) or normal hearing sensitivity (n = 16) and for adults ages 18.4-54.4 years (M = 32.7, SD = 10.4) with sensorineural hearing loss (n = 13) or normal hearing sensitivity (n = 11). Thresholds obtained for 6 and 8 kHz using ABR and conventional audiometry were compared. RESULTS: Differences between ABR and behavioral thresholds averaged 5-6 dB for both children and adults for both test frequencies, with differences of ≤ 20 dB in all instances. Linear mixed modeling for data from participants with hearing loss suggested that ABR threshold is a good predictor of behavioral threshold at 6 and 8 kHz for both children and adults. Test specificity was 100%; no participants with behavioral thresholds ≤ 20 dB HL had ABR thresholds > 25 dB nHL. CONCLUSIONS: Initial evidence suggests that ABR testing at 6 and 8 kHz is reliable for estimating behavioral threshold in listeners with hearing loss and accurately identifies normal hearing sensitivity. The results of this study contribute to efforts to improve outcomes for vulnerable populations by reducing barriers to clinical implementation of ABR testing at > 4 kHz.

Combined use of UAV-SfM surveys, soil particle tracking with RFID tags and a sediment connectivity index to study plot-scale sediment transport.

To explore the processes of soil erosion at the plot scale, Digital surface model of Differences (DoD) maps (Unmanned Aerial Vehicle - Structure from Motion (UAV-SfM) method) and data from Radio Frequency Identification (RFID) tags were analysed. The comparison of differences in accuracy of UAV-SfM and 3D terrestrial laser scanner (TLS) measurements, and the integration of the UAV-SfM method and soil particle tracing with RFID tag locations were conducted to assess sediment transport in a plot in Fukushima prefecture, Japan. The Universal Soil Loss Equation (USLE) plot was installed and kept with no vegetation and no cultivation. Water and sediment discharges were measured at the outlet of the plot, and the topographic index of runoff and sediment connectivity (IC) -focused on surface roughness- was also estimated. Based on field surveys, four periods were defined. Locations of RFID tags were firstly determined by using orthoimages derived from the UAV-SfM method and then compared with those locations measured with a laser total station. The mean and standard deviation of difference amounts of UAV-SfM were of 1 and 3.3 mm, respectively. On average, the RFID tags were located with an accuracy of 3.1 cm (RMSE). Although data of tags tracing showed short transport distances with rill erosion, the results of the UAV-SfM surveys showed an increase of sediment connectivity (SC) over the study period that may explain the largest sediment discharge, especially of fine soil particles. The concurrence of higher values of SC as well as the development of new and longer rills demonstrated the important activity of net soil loss in our study site. The combination of distinct methods and techniques, all providing accurate measurements, shed light on the sediment transport process at short distances, which affects the net water and sediment discharge at larger scales.

Mannosylated glycans impair normal T-cell development by reprogramming commitment and repertoire diversity.

T-cell development ensures the formation of diverse repertoires of T-cell receptors (TCRs) that recognize a variety of antigens. Glycosylation is a major posttranslational modification present in virtually all cells, including T-lymphocytes, that regulates activity/functions. Although these structures are known to be involved in TCR-selection in DP thymocytes, it is unclear how glycans regulate other thymic development processes and how they influence susceptibility to disease. Here, we discovered stage-specific glycome compositions during T-cell development in human and murine thymocytes, as well as dynamic alterations. After restricting the N-glycosylation profile of thymocytes to high-mannose structures, using specific glycoengineered mice (Rag1CreMgat1fl/fl), we showed remarkable defects in key developmental checkpoints, including ß-selection, regulatory T-cell generation and γδT-cell development, associated with increased susceptibility to colon and kidney inflammation and infection. We further demonstrated that a single N-glycan antenna (modeled in Rag1CreMgat2fl/fl mice) is the sine-qua-non condition to ensure normal development. In conclusion, we revealed that mannosylated thymocytes lead to a dysregulation in T-cell development that is associated with inflammation susceptibility.

Auditory Brainstem Responses at 6 and 8 kHz in Infants With Normal Hearing.

PURPOSE: Normative auditory brainstem response (ABR) data for infants and young children are available for 0.25-4 kHz, limiting clinical assessment to this range. As such, the high-frequency hearing sensitivity of infants and young children remains unknown until behavioral testing can be completed, often not until late preschool or early school ages. The purpose of this study was to obtain normative ABR data at 6 and 8 kHz in young infants. METHOD: Participants were 173 full-term infants seen clinically for ABR testing at 0.4-6.7 months chronological age (M = 1.4 months, SD = 1.0), 97% of whom were ≤ 12 weeks chronological age. Stimuli included 6 and 8 kHz tone bursts presented at a rate of 27.7/s or 30.7/s using Blackman window gating with six cycles (6 kHz) or eight cycles (8 kHz) rise/fall time and no plateau. Presentation levels included 20, 40, and 60 dB nHL. The ABR threshold was estimated in 5- to 10-dB steps. RESULTS: As previously observed with lower frequency stimuli, ABR waveforms obtained in response to 6 and 8 kHz tone bursts decreased in latency with increasing intensity and increasing age. Latency was shorter for 8-kHz tone bursts than 6-kHz tone bursts. Data tables are presented for clinical reference for infants ≤ 4 weeks, 4.1-8 weeks, and 8.1-12 weeks chronological age including median ABR latency for Waves I, III, and V and the upper and lower boundaries of the 90% prediction interval. Interpeak Latencies I-III, III-V, and I-V are also reported. CONCLUSION: The results from this study demonstrate that ABR assessment at 6 and 8 kHz is feasible for young infants within a standard clinical appointment and provide reference data for clinical interpretation of ABR waveforms for frequencies above 4 kHz.