Microbial assisted multifaceted amelioration processes of heavy-metal remediation: a clean perspective toward sustainable and greener future.

Rapidly increasing heavy metal waste has adversely affected the environment and the Earth's health. The lack of appropriate remediation technologies has worsened the issue globally, especially in developing countries. Heavy-metals contaminants have severely impacted the environment and led to devastating conditions owing to their abundance and reactivity. As they are nondegradable, the potential risk increases even at a low concentration. However, heavy-metal remediation has increased with the up-gradation of technologies and integration of new approaches. Also, of all the treatment methodologies, microbial-assisted multifaceted approach for ameliorating heavy metals is a promising strategy for propagating the idea of a green and sustainable environment with minimal waste aggregation. Microbial remediation combined with different biotechniques could aid in unraveling new methods for eradicating heavy metals. Thus, the present review focuses on various microbial remediation approaches and their affecting factors, enabling recapitulation of the interplay between heavy-metals ions and microorganisms. Additionally, heavy-metals remediation mechanisms adapted by microorganisms, the role of genetically modified (GM) microorganisms, life cycle assessment (LCA), techno-economic assessment (TEA) limitations, and prospects of microbial-assisted amelioration of heavy-metals have been elaborated in the current review with focus toward "sustainable and greener future."

Allergic sensitization impairs lung resident memory CD8 T-cell response and virus clearance.

BACKGROUND: Patients with asthma often suffer from frequent respiratory viral infections and reduced virus clearance. Lung resident memory T cells provide rapid protection against viral reinfections. OBJECTIVE: Because the development of resident memory T cells relies on the lung microenvironment, we investigated the impact of allergen sensitization on the development of virus-specific lung resident memory T cells and viral clearance. METHODS: Mice were sensitized with house dust mite extract followed by priming with X47 and a subsequent secondary influenza infection. Antiviral memory T-cell response and protection to viral infection was assessed before and after secondary influenza infection, respectively. Gene set variation analysis was performed on data sets from the U-BIOPRED asthma cohort using an IFN-γ-induced epithelial cell signature and a tissue resident memory T-cell signature. RESULTS: Viral loads were higher in lungs of sensitized compared with nonsensitized mice after secondary infection, indicating reduced virus clearance. X47 priming induced fewer antiviral lung resident memory CD8 T cells and resulted in lower pulmonary IFN-γ levels in the lungs of sensitized as compared with nonsensitized mice. Using data from the U-BIOPRED cohort, we found that patients with enrichment of epithelial IFN-γ-induced genes in nasal brushings and bronchial biopsies were also enriched in resident memory T-cell-associated genes, had more epithelial CD8 T cells, and reported significantly fewer exacerbations. CONCLUSIONS: The allergen-sensitized lung microenvironment interferes with the formation of antiviral resident memory CD8 T cells in lungs and virus clearance. Defective antiviral memory response might contribute to increased susceptibility of patients with asthma to viral exacerbations.

Microbial cell factories a new dimension in bio-nanotechnology: exploring the robustness of nature.

Bio-based nanotechnology has its existence in biological dimensions e.g. microbial cell factories (bacteria, fungi. algae, yeast, cyanobacteria) plants, and biopolymers. They provide multipurpose biological platforms to supply well-designed materials for diverse nano-biotechnological applications. The "green or bio-based synthesis of nanoparticles (NPs)" has witnessed a research outburst in the past decade. The bio-based synthesis of NPs using microbial cell factories is a benign process and requires mild conditions for the synthesis with end products being less/non-toxic. As a result, its application has extended in multitudinous industries including environment, cosmetics, and pharmaceutical. Thus, the present review summarizes all the significant aspects of nanotechnology and the reason to switch towards the bio-based synthesis of NPs using microbial cell factories. It consists of a detailed description of the bio-based methods employed for the synthesis and classification of NPs. Also, a comprehensive study on the application of bio-based NPs in the various industrial and biotechnological domains has been discussed. The limitation and its solution would help identify the applicability of NPs to "identified and unidentified" sectors.

Phycoremediation of nitrogen and phosphate from wastewater using Picochlorum sp.: A tenable approach.

The wastewater originates from different industrial, municipal, and agriculture processes and contains different nitrogen sources, for example, nitrate, ammonium, nitrite, and phosphate such as inorganic and organic sources. The discharge of high nitrate and phosphate to the ecosystem or nearby water bodies can cause eutrophication which disbalances the aquatic ecosystem. Furthermore, ingestion of these pollutants can cause severe toxicity and disease to humans and animals. Thus, from an environmental and social perspective, its treatment is essential with no negative impact on the ecosystem. Microalgae are fundamental, mixotrophic microorganisms that treat different wastewater and utilize nitrate and phosphate in the medium as a source of nutrients. Among them, Picochlorum sp., have the potential to remove nitrogen and phosphate from wastewater. The biomass produced by Picochlorum sp. can be a promising candidate as a sustainable feedstock for biofuel and bioproducts formation. Thus, the present review provides a brief knowledge and understanding about the concentration of nitrogen and phosphate in different wastewater, their negative impacts, and the uptake mechanism of microalgae. Furthermore, the review also provides an insight into Picochlorum sp., and the effects of different physiological and nutritional factors on their growth, wastewater treatment efficacy, and biomass for value-added products and biorefinery applications. In addition, the review is useful to understand the potential of Picochlorum sp. for a tenable wastewater treatment process.

Insight into multicopper oxidase laccase from Myrothecium verrucaria ITCC-8447: a case study using in silico and experimental analysis.

The oxidation activity of multicopper-oxidases overlaps with different substrates of laccases and bilirubin oxidases, thus in the present study an integrated approach of bioinformatics using homology modeling, docking, and experimental validation was used to confirm the type of multicopper-oxidase in Myrothecium verrucaria ITCC-8447. The result of peptide sequence of M. verrucaria ITCC-8447 enabled to predict the 3 D-structure of multicopper-oxidase. It was overlapped with the structure of laccase and root mean square deviation (RMSD) was 1.53 Å for 533 and, 171 residues. The low binding energy with azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) (-5.64) as compared to bilirubin (-4.39) suggested that M. verrucaria ITCC-8447 have laccase-like activity. The experimental analysis confirmed high activity with laccase specific substrates, phenol (18.3 U/L), ampyrone (172.4 U/L) and, ampyrone phenol coupling (50 U/L) as compared to bilirubin oxidase substrate bilirubin (16.6 U/L). In addition, lowest binding energy with ABTS (-5.64), syringaldazine SYZ (-4.83), guaiacol GCL (-4.42), and 2,6-dimethoxyphenol DMP (-4.41) confirmed the presence of laccase. Further, complete remediation of two hazardous model pollutants i.e., phenol and resorcinol (1.5 mM) after 12 h of incubation and low binding energy of -4.32 and, -4.85 respectively confirmed its removal by laccase. The results confirmed the presence of laccase in M. verrucaria ITCC-8447 and its effective bioremediation potential.

Protease activity of Per a 10 potentiates Th2 polarization by increasing IL-23 and OX40L.

Proteases are implicated in exacerbation of allergic diseases. In this study, the role of proteolytic activity of Per a 10 was evaluated on Th2 polarization. Intranasal administration of Per a 10 in mice led to allergic airway inflammation as seen by higher IgE levels, cellular infiltration, IL-17A, and Th2 cytokines, whereas, inactive (Δ)Per a 10 showed attenuated response. There was an increased OX40L expression on lung and lymph node dendritic cells in Per a 10 immunized group and on Per a 10 stimulated BMDCs. Reduction in CD40 expression without any change at transcript level in lungs of Per a 10 immunized mice suggested CD40 cleavage. BMDCs pulsed with Per a 10 showed reduced CD40 expression with lower IL-12p70 secretion as compared to heat inactivated Per a 10. IL-23, TNF-α, and IL-6 levels were significantly higher in Per a 10 stimulated BMDCs supernatant. In DC-T cell coculture studies, Per a 10 pulsed BMDCs showed higher levels of IL-4 and IL-13 that were reduced on blocking of either IL-23 or OX40L. In conclusion, the data suggests a critical role of protease activity of Per a 10 in promoting Th2 polarization by increasing IL-23 secretion and OX40L expression on dendritic cells.

Differential proteomic expression of himalayan psychrotrophic diazotroph Pseudomonas palleroniana N26 under low temperature diazotrophic conditions.

BACKGROUND: In low temperature nitrogen-deficient ecosystems, native microorganisms must possess adaptive mechanisms to cope with environmental stress as well as nitrogen (N) starvation-like conditions. However, moderate information is available about the cold adapted diazotrophs and diazotrophy. OBJECTIVE: The aim of this study was to examine the proteomic response(s) of Himalayan psychrotrophic diazotroph under low temperature nitrogen fixing conditions. MATERIALS AND METHODS: Proteomic analysis of Pseudomonas palleroniana N26 was carried out using two dimensional electrophoresis technique. RESULTS: Altogether, fifty three protein spots were found to be differentially expressed revealing several mechanisms thought to be involved in low temperature adaptation and nitrogen fixation, including general stress adaptation, protein synthesis and modifications, and energy metabolism. Expression profiling of the spots revealed the up-regulation of low molecular weight acidic proteins; a majority of which were stress proteins. The largest group of down-regulated proteins were related to biosynthetic processes; thereby, providing the evidence for stress-associated metabolic adaptations. CONCLUSION: The present study, which provides an overview of the cold diazotrophy of a Himalayan psychrotrophic bacterium and its adaptive responses, can facilitate further studies of low temperature nitrogen fixing mechanisms, psychrophilic diazotrophic markers, and transgenic microorganism(s)/crop(s) development.

Acute liver failure histopathology: A 5-year retrospective study.

BACKGROUND: Acute liver failure (ALF) is a rare, life-threatening disease of diverse etiology. It is defined as severe acute liver injury for fewer than 26 weeks' duration with encephalopathy and impaired synthetic function (international normalized ratio [INR] of 1.5 or higher) in a patient without cirrhosis or pre-existing liver disease. The diagnosis rests mainly on the clinical ground with wide range of pathological features. The present study seeks to explore the diverse histological patterns observed in cases for ALF and assess their usefulness in determining the underlying causes for the condition. METHODOLOGY: A retrospective cross-sectional study was conducted among patients of ALF who underwent liver transplant and transjugular liver biopsy over a five-year period. From 1082 explant liver and 2446 liver biopsies, 22 cases of ALF (10 explants and 12 liver biopsies) were included in the study. Clinical and laboratory details were retrieved and histological findings were reviewed. RESULT: Age ranged from 10 to 72 years (mean age, 40 years). There was a female predominance with a male:female ratio of 1:1.7. The commonest cause for ALF was virus-induced hepatocellular damage in 36.3% (eight patients), followed by autoimmune hepatitis in 22.7% (five patients), drug-induced liver injury (DILI) in 18.1% (four patients), cryptogenic in 13.6% (three patients) and ischemic injury secondary to large vein thrombosis in 9.0% (two) patients. The histological patterns identified were categorized into six categories. A more comprehensive morphological evaluation was conducted specifically for cases of ALF associated with autoimmune hepatitis (AIH) and compared with other cases of ALF. CONCLUSION: In summary, our present study illustrates a morphological overlap in various patterns for the purpose of etiological assessment. In cases of AIH ALF, the presence of portal plasma cell infiltrate and central perivenulitis were identified as significant histological features to guide diagnosis.

A comparative study of blood cell count in four automated hematology analyzers: An evaluation of the impact of preanalytical factors.

Differential white blood cell counts are frequently used in diagnosis, patient stratification, and treatment selection to optimize therapy responses. Referral laboratories are often used but challenged with use of different hematology platforms, variable blood shipping times and storage conditions, and the different sensitivities of specific cell types. To extend the scientific literature and knowledge on the temporal commutability of blood samples between hematology analyzers, we performed a comparative ex-vivo study using four of the most utilized commercial platforms, focusing on the assessment of eosinophils given its importance in asthma management. Whole blood from healthy volunteers with and without atopy (n = 6+6) and participants with eosinophilic asthma (n = 6) were stored under different conditions (at 4, 20, 30, and 37°C, with or without agitation) and analyzed at different time points (3, 6, 24, 48 and 72h post-sampling) in parallel on the Abbott CELL-DYN Sapphire, Beckman Coulter DxH900, Siemens ADVIA 2120i and Sysmex XN-1000V. In the same blood samples, eosinophil-derived neurotoxin (EDN), eosinophil activation and death markers were analyzed. All platforms gave comparable measurements of cell differentials on fresh blood within the same day of sampling. However, by 24 hours, significant temporal and temperature-dependent differences were observed, most markedly for eosinophils. None of the platforms performed perfectly across all temperatures tested during the 72 hours, showing that handling conditions should be optimized depending on the cell type of interest and the hematology analyzer. Neither disease status (healthy vs. asthma) nor agitation of the sample affected the cell quantification result or EDN release. The eosinophil activation markers measured by flow cytometry increased with time, were influenced by temperature, and were higher in those with asthma versus healthy participants. In conclusion, hematology analyzer, time window from sampling until analysis, and temperature conditions must be considered when analyzing blood cell differentials, particularly for eosinophils, via central labs to obtain counts comparable to the values obtained in freshly sampled blood.

Organosolv pretreatment: an in-depth purview of mechanics of the system.

The concept of biorefinery has been advancing globally and organosolv pretreatment strategy has seen an upsurge in research due to its efficiency in removing the recalcitrant lignin and dissolution of cellulose. The high-performance organosolv system uses green solvents and its reusability contributes concurrently to the biorefinery sector and sustainability. The major advantage of the current system involves the continuous removal of lignin to enhance cellulose accessibility, thereby easing the later biorefinery steps, which were immensely restricted due to the recalcitrant lignin. The current system process can be further explored and enhanced via the amalgamation of new technologies, which is still a work in progress. Thus, the current review summarizes organosolv pretreatment and the range of solvents used, along with a detailed mechanistic approach that results in efficient pretreatment of LCB. The latest developments for designing high-performance pretreatment systems, their pitfalls, and advanced assessments such as Life Cycle Assessment along with Techno-Economic Assessment have also been deliberated to allow an insight into its diverse potential applicability towards a sustainable future.

Development of economical and sustainable cultivation system for biomass production and simultaneous treatment of municipal wastewater using Tetraselmis indica BDUG001.

Microalgal-based bioprocess offers several advantages including wastewater reclamations, therefore present study assessed the usability of the combination of untreated municipal sewage wastewater (UTMSWW) and secondary treated municipal sewage wastewater (STSWW) for nutrient removal and recovery by Tetraselmis indica (T. indica) BDUG001. The present study optimized the additional nutrient supplementations (e.g. ASN-III) percentage and day-night cycle, pH and pH with aeration for monitoring high-rate biomass production and nutrient recovery. The study results showed that the combination of 75% UTMSWW + 25% ASN-III supported maximum biomass production (2.65 ± 0.07 g/L). In the optimized day-night cycle (12:12 h), T. indica BDUG001 showed improved biomass production (2.75 ± 0.07 g/L), biomass productivity (165.63 ± 4.42 mg/L/d), and photosynthetic pigments production. Under optimized pH∼ 7.0 with aeration, maximum total nitrate (TN) removal efficiency (87.67 ± 3.08-91.55 ± 1.92%) was observed, while COD and TP removal was maximum at pH ∼ 9.0. The maximum biomass production (2.35 ± 0.07-2.77 ± 0.04 g/L) with biomass productivity (93.75 ± 167.19 ± 2.21 mg/L/d) and lipid content (42.98 ± 1.86-47.85 ± 0.21% DCW) were also at pH 7.0. with aeration. The present study verified the utilization of UTMSWW with the combination of conventional medium, optimized day-night cycle, pH with aeration along with designing low-cost PBR. It was the ideal system for the cultivation of T. indica BDUG001 for the recovery of nutrients from wastewater, production of biofuels and value-added feedstock.

Characteristics of posterior zone I retinopathy of prematurity.

OBJECTIVE: To report the demographic profile and clinical characteristics of retinopathy of prematurity (ROP) in posterior Zone I. METHODS: In a partly retrospective (ten years) and partly prospective (one year) study, we analysed the demographic profile and clinical characteristics of babies with ROP in posterior Zone I. RESULTS: The study included 130 eyes of 67 infants with a mean gestational age and birth weight of 29.3 (±2.2) weeks and 1217.3 (±381.9) grams, respectively. All babies had received unblended oxygen. In 47 of 51 (91.1%) babies, the weekly weight gain was <100 g (details were not available in 16 babies). The ROP subtypes included aggressive, threshold, hybrid, stage 4, and atypical types in 78 (60%), 20 (15.4%), 11 (8.5%), 15 (11.5%), and 6 (4.6%) eyes, respectively. Fibrovascular proliferation, when present, was prominent nasally, occasionally overriding the disc margin. Extensive arteriovenous tortuosity was more prominent than vascular dilatation. Atypical observations included bleb-like detachment (6 eyes; 4.6%) and candle wax-like preretinal deposits (23 eyes; 17.7%). CONCLUSIONS: Retinopathy of Prematurity in posterior Zone I in this cohort was strongly associated with 100% unblended oxygen supplementation, poor weight gain, and multiple systemic co-morbidities. ROP in posterior zone 1 has a distinct profile with several atypical characteristics different from ROP in other zones.

An insight into the principles of lignocellulosic biomass-based zero-waste biorefineries: a green leap towards imperishable energy-based future.

Lignocellulosic biomass (LCB) is an energy source that has a huge impact in today's world. The depletion of fossil fuels, increased pollution, climatic changes, etc. have led the public and private sectors to move towards sustainability i.e. using LCB for the production of biofuels and value-added compounds. A major bottleneck of the process is the recalcitrant nature of LCB. This can be overcome by using various pretreatment strategies like physical, chemical, biological, physicochemical, etc. Further, the pretreated biomass is made to undergo various steps like hydrolysis, saccharification, etc. for the conversion of value-added products and the remaining waste residues can be further utilized for the synthesis of secondary products thus favouring the zero-waste biorefinery concept. Currently, microorganisms are being explored for their use in biorefinery but the unavailability of commercial strains is a major limitation. Thus, the use of metagenomics can be used to overcome the limitation which is both cost-effective and environmentally friendly. The review deliberates the composition of LCBs, and their recalcitrance nature, followed by the structural changes caused by various pretreatment methods. The further steps in biorefineries, strategies for the development of zero-waste refineries, bottlenecks, and suggestions are also discussed. Special emphasis is given to the use of metagenomics for the discovery of microorganisms efficient for zero-waste biorefineries.

Current perspective on wastewater treatment using photobioreactor for Tetraselmis sp.: an emerging and foreseeable sustainable approach.

Urbanization is a revolutionary and necessary step for the development of nations. However, with development emanates its drawback i.e., generation of a huge amount of wastewater. The existence of diverse types of nutrient loads and toxic compounds in wastewater can reduce the pristine nature of the ecosystem and adversely affects human and animal health. The conventional treatment system reduces most of the chemical contaminants but their removal efficiency is low. Thus, microalgae-based biological wastewater treatment is a sustainable approach for the removal of nutrient loads from wastewater. Among various microalgae, Tetraselmis sp. is a robust strain that can remediate industrial, municipal, and animal-based wastewater and reduce significant amounts of nutrient loads and heavy metals. The produced biomass contains lipids, carbohydrates, and pigments. Among them, carbohydrates and lipids can be used as feedstock for the production of bioenergy products. Moreover, the usage of a photobioreactor (PBR) system improves biomass production and nutrient removal efficiency. Thus, the present review comprehensively discusses the latest studies on Tetraselmis sp. based wastewater treatment processes, focusing on the use of different bioreactor systems to improve pollutant removal efficiency. Moreover, the applications of Tetraselmis sp. biomass, advancement and research gap such as immobilized and co-cultivation have also been discussed. Furthermore, an insight into the harvesting of Tetraselmis biomass, effects of physiological, and nutritional parameters for their growth has also been provided. Thus, the present review will broaden the outlook and help to develop a sustainable and feasible approach for the restoration of the environment.

Current perspective on production and applications of microbial cellulases: a review.

The potential of cellulolytic enzymes has been widely studied and explored for bioconversion processes and plays a key role in various industrial applications. Cellulase, a key enzyme for cellulose-rich waste feedstock-based biorefinery, has increasing demand in various industries, e.g., paper and pulp, juice clarification, etc. Also, there has been constant progress in developing new strategies to enhance its production, such as the application of waste feedstock as the substrate for the production of individual or enzyme cocktails, process parameters control, and genetic manipulations for enzyme production with enhanced yield, efficiency, and specificity. Further, an insight into immobilization techniques has also been presented for improved reusability of cellulase, a critical factor that controls the cost of the enzyme at an industrial scale. In addition, the review also gives an insight into the status of the significant application of cellulase in the industrial sector, with its techno-economic analysis for future applications. The present review gives a complete overview of current perspectives on the production of microbial cellulases as a promising tool to develop a sustainable and greener concept for industrial applications.

Multicopper oxidase laccases with distinguished spectral properties: A new outlook.

Multicopper oxidases (MCOs) has a unique feature of having the presence of four Cu atoms arranged into three (Type I, II and III) spectral classification. MCOs laccase due to its broad range of substrate specificity has numerous biotechnological applications. The two types of laccases include the typical blue and the atypical white, yellow laccases which have been isolated from diverse geographical locations globally. In the present study laccases were identified using Liquid Chromatograph Mass Spectrometer Studies (LCMS) study where blue laccase exhibited homology with Trametes villosa Q99044 and Q99046 and white, yellow laccase exhibited homology with Myrothecium verrucaria OX = 1859699; Q12737 and Trametes versicolor Q12717 respectively. The spectral comparison between laccases were determined via spectroscopic analysis where UV-spectra of blue laccase from Trametes versicolor had a peak at 605 nm (Type I Cu atom) whereas in case of white and yellow laccases the peak was absent and in addition had an absorption peak at 400nm. It was followed by X-Ray Diffraction (XRD) analysis of proteins where α-helix (10°) and ß-sheet (22°) structure were observed in case of all the three laccases. However, the intensity of α-helix in white and yellow laccase was stronger as compared to the blue laccase whereas the intensity of ß-sheet was stronger in case of blue laccase as compared to other two laccases. Further, Fourier-transform infrared spectroscopy (FTIR) analysis was performed which enabled the analysis of proteins where α-helix (1650-1658 cm-1), ß-sheets (1620-1640 cm-1), amide I (1700-1600 cm-1) amide II (bands at under 1400 cm-1) and amide A, B (bands above 3000 cm-1).

Multicopper oxidase (MCO) laccase from Stropharia sp. ITCC-8422: an apparent authentication using integrated experimental and in silico analysis.

In the present study, specificity of laccase from Stropharia sp. ITCC-8422 against various substrates, i.e. 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,6-dimethoxyphenol (DMP), guaiacol (GCL) and syringaldazine (SYZ) was determined. It exhibited maximum affinity against ABTS, followed by DMP and negligible activity for GCL and SYZ. As the concentration of substrate increased from 0.5 to 1.5 mM (ABTS) and 1 to 5 mM (DMP), the activity increased from 301.1 to 567.8 U/L and 254.4 to 436.2 U/L. Further, quadrupole time-of-flight liquid chromatography mass spectrometry (QTOF-LCMS) analysis of the extracellular proteome of Stropharia sp. ITCC-8422 identified eighty-four (84) extracellular proteins. The peptide sequence for the enzyme of interest exhibited sequence similarity with laccase-5 of Trametes pubescens. Using high molecular mass sequence of laccase-5, the protein structure of laccase was modelled and binding energy of laccase with four substrates, i.e. ABTS (- 5.65), DMP (- 4.65), GCL (- 4.66) and SYZ (- 5.5) was determined using autodock tool. The experimental and in silico analyses revealed maximum activity of laccase and lowest binding energy with ABTS. Besides, laccase was purified and it exhibited 2.1-fold purification with purification yield of 20.4% and had stability of 70% at pH 5-9 and 30-40 â„ƒ. In addition, the bioremediation potential of laccase was explored by in silico analysis, where the binding energy of laccase with alizarin cyanine green was - 6.37 and both in silico work and experimental work were in agreement.

Telomere Length and Autism Spectrum Disorder Within the Family: Relationships With Cognition and Sensory Symptoms.

Telomeres are repetitive noncoding deoxynucleotide sequences that cap chromosomes to protect DNA. Telomere length (TL) is affected by both genetic and environmental factors, and shortening of telomeres is associated with multiple neuropsychiatric disorders, early life stress, and age-related cognitive dysfunction. Two previous studies associated shorter TL with autism spectrum disorder (ASD). We aimed to replicate this finding, describe TL in unaffected siblings, and explore novel relationships with symptoms and cognitive function in families with ASD. Participants were 212 male children and adolescents ages 1-17 years (86 with ASD, 57 unaffected siblings, and 69 typically developing [TD]) and 64 parents. TL was measured from blood leukocytes with quantitative real-time polymerase chain reaction and results are expressed by relative ratios with a single copy gene. We replicated that children and adolescents with ASD have shorter TL, compared to TD, and show that unaffected siblings have TL in between those of TD and ASD. We present novel associations between TL and sensory symptoms in ASD. Finally, we demonstrate cognitive functions, but not autistic traits, are related to TL in parents of children with ASD. Cognitive function and TL were not related in children and adolescents. As the third replication, our results elicit confidence in the finding that ASD is associated with shorter TL. Our novel sensory investigation suggests that shortened TL may be a biological mechanism of sensory symptoms in ASD. Furthermore, results highlight the need to better understand relationships between cognition, aging, and TL in families with ASD. Autism Res 2020, 13: 1094-1101. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Telomeres cap chromosomes to protect DNA. They progressively shorten as people age and are related to health outcomes. We replicated previous findings that children and adolescents with autism spectrum disorder (ASD) have shorter telomeres, compared to typically developing (TD), and show that unaffected siblings have telomere length (TL) in between those of TD and ASD. We find shortened TL is related to more severe sensory symptoms. This may mean families with ASD, especially those with elevated sensory symptoms, are at risk for worse age-related health outcomes.

Extracellular microRNAs in blood differentiate between ischaemic and haemorrhagic stroke subtypes.

Rapid identification of patients suffering from cerebral ischaemia, while excluding intracerebral haemorrhage, can assist with patient triage and expand patient access to chemical and mechanical revascularization. We sought to identify blood-based, extracellular microRNAs 15 (ex-miRNAs) derived from extracellular vesicles associated with major stroke subtypes using clinical samples from subjects with spontaneous intraparenchymal haemorrhage (IPH), aneurysmal subarachnoid haemorrhage (SAH) and ischaemic stroke due to cerebral vessel occlusion. We collected blood from patients presenting with IPH (n = 19), SAH (n = 17) and ischaemic stroke (n = 21). We isolated extracellular vesicles from plasma, extracted RNA cargo, 20 sequenced the small RNAs and performed bioinformatic analyses to identify ex-miRNA biomarkers predictive of the stroke subtypes. Sixty-seven miRNAs were significantly variant across the stroke subtypes. A subset of exmiRNAs differed between haemorrhagic and ischaemic strokes, and LASSO analysis could distinguish SAH from the other subtypes with an accuracy of 0.972 ± 0.002. Further analyses predicted 25 miRNA classifiers that stratify IPH from ischaemic stroke with an accuracy of 0.811 ± 0.004 and distinguish haemorrhagic from ischaemic stroke with an accuracy of 0.813 ± 0.003. Blood-based, ex-miRNAs have predictive value, and could be capable of distinguishing between major stroke subtypes with refinement and validation. Such a biomarker could one day aid in the triage of patients to expand the pool eligible for effective treatment.