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In this work, harvested mushroom substrate (HMS) has been explored for the first time through a comprehensive optimization study for the green synthesis of silver nanoparticles (AgNPs). A multiple response central composite design with three parameters: pH of the reaction mixture, temperature, and incubation period at three distinct levels was employed in the optimization study. The particle size of AgNPs, UV absorbance, and the percentage of Ag/Cl elemental ratio were considered as the response parameters. For each response variable examined the model used was found to be significant (P < 0.05). The ideal conditions were: pH 8.9, a temperature of 59.4 °C, and an incubation period of 48.5 h. The UV-visible spectra of AgNPs indicated that the absorption maxima for AgNP-3 were 414 nm, 420 for AgNPs-2, and 457 for AgNPs-1. The XRD analysis of AgNPs-3 and AgNPs-2 show a large diffraction peak at ∼38.2°, ∼44.2°, ∼64.4°, and ∼77.4°, respectively, which relate to the planes of polycrystalline face-centered cubic (fcc) silver. Additionally, the XRD result of AgNPs-1, reveals diffraction characteristics of AgCl planes (111, 200, 220, 311, 222, and 400). The TEM investigations indicated that the smallest particles were synthesized at pH 9 with average diameters of 35 ± 6 nm (AgNPs-3). The zeta potentials of the AgNPs are -36 (AgNPs-3), -28 (AgNPs-2), and -19 (AgNPs-1) mV, respectively. The distinct IR peak at 3400, 1634, and 1383 cm -1 indicated the typical vibration of phenols, proteins, and alkaloids, respectively. The AgNPs were further evaluated against gram (+) strain Bacillus subtilis (MTCC 736) and gram (-) strain Escherichia coli (MTCC 68). All of the NPs tested positive for antibacterial activity against both bacterial strains. The study makes a sustainable alternative to disposing of HMS to achieve the Sustainable Development Goals (SDGs)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Youth with intellectual and/or developmental disabilities (IDD) often struggle with depression and anxiety, which adversely impacts transition to adulthood. Integrated behavioral health care coordination, wherein care coordinators and behavioral health specialists collaborate to provide systematic, cost-effective, patient-centered care, is a promising strategy to improve access to behavioral health services and address factors that impact transition to adulthood, including depression/anxiety symptoms. Current care coordination models (e.g., Title V Maternal and Child Health Bureau [MCHB]) do not include behavioral health services. The CHECK (Coordinated HealthCarE for Complex Kids) mental health model, hereby refined and renamed BEhavioral Health Stratified Treatment (B.E.S.T.), is a behavioral health intervention delivery program designed for integration into care coordination programs. This study aims to determine whether an integrated behavioral health care coordination strategy (i.e., MCHB care coordination plus B.E.S.T.) would be more acceptable and lead to better youth health and transition outcomes, relative to standard care coordination (i.e., MCHB care coordination alone). Results would guide future investment in improving outcomes for youth with IDD. This study is a two-arm randomized clinical trial of 780 transition-aged youth with IDD (13-20 years) to evaluate the comparable efficacy of MCHB Care Coordination alone vs. MCHB Care Coordination plus B.E.S.T. on the following outcomes: 1) decreased symptoms and episodes of depression and anxiety over time; 2) improved health behaviors, adaptive functioning and health related quality of life; 3) increased health care transition (HCT) readiness; and 4) improved engagement and satisfaction with care coordination among stakeholders., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Resistance to apoptosis stands as a roadblock to the successful pharmacological execution of anticancer drug effect. A comprehensive insight into apoptotic signaling pathways and an understanding of the mechanisms of apoptosis resistance are crucial to unveil new drug targets. At this juncture, researchers are heading towards natural sources in particular, mushroom as their potential drugs leads to being the reliable source of potent bioactive compounds. Given the continuous increase in cancer cases, the potent anticancer efficacy of mushrooms has inevitably become a fascinating object to researchers due to their higher safety margin and multitarget. This review aimed to collect and summarize all the available scientific data on mushrooms from their extracts to bioactive molecules in order to suggest their anticancer attributes via a mitochondrion -mediated intrinsic signaling mechanism. Compiled data revealed that bioactive components of mushrooms including polysaccharides, sterols and terpenoids as well as extracts prepared using 15 different solvents from 53 species could be effective in the supportive treatment of 20 various cancers. The underlying therapeutic mechanisms of the studied mushrooms are explored in this review through diverse and complementary investigations: in vitro assays, pre-clinical studies and clinical randomized controlled trials. The processes mainly involved were ROS production, mitochondrial membrane dysfunction, and action of caspase 3, caspase 9, XIAP, cIAP, p53, Bax, and Bcl-2. In summary, the study provides facts pertaining to the potential beneficial effect of mushroom extracts and their active compounds against various types of cancer and is shedding light on the underlying targeted signaling pathways., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Research Question: What patient populations and outcomes are depicted on IVF videos on the short-form video-sharing application 'TikTok'?, Design: This cross-sectional study investigated the 100 most-viewed videos utilizing the #IVF hashtag on TikTok. Only videos in English or Spanish were included in the analysis. An automated web-scraping platform was used to extract information from these videos. Standardized video coding was used to evaluate the featured subject(s), phase of care and IVF outcomes from the videos., Results: Videos meeting the inclusion criteria (n=93) had 731 million views, 91 million likes and 893,000 shares. Patients' personal stories about IVF are over-represented relative to videos created by healthcare professionals. #IVF videos popular on TikTok disproportionately depict same-sex couples (38.1%), gestational carriers (14.0%), multiple gestations (60.0%) and live births (89.3%) relative to real-world data. Among the videos making scientific claims (n=16), nearly all were moderately to highly accurate (93.8%). Most videos had a positive (55.9%) or neutral (5.5%) tone towards IVF., Conclusions: Popular #IVF videos on TikTok contribute to public discourse about infertility, and highlight demographics that have traditionally been under-represented in health care. Videos rarely focused on health education or made informational claims, with low scores on measures of quality of information and actionability. This gap represents an opportunity for health providers and educators to create more engaging and educational content to reach patients considering IVF., (Copyright © 2023 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

There is no reference of microbiological water quality in the European Union's Water Framework Directive, adapted into English law, and consequently microbial water quality is not routinely monitored in English rivers, except for two recently designated bathing water sites. To address this knowledge gap, we developed an innovative monitoring approach for quantitative assessment of combined sewer overflow (CSO) impacts on the bacteriology of receiving rivers. Our approach combines conventional and environmental DNA (eDNA) based methods to generate multiple lines of evidence for assessing risks to public health. We demonstrated this approach by investigating spatiotemporal variation in the bacteriology of the Ouseburn in northeast England for different weather conditions in the summer and early autumn of the year 2021 across eight sampling locations that comprised rural, urban, and recreational land use settings. We characterized pollution source attributes by collecting sewage from treatment works and CSO discharge at the peak of a storm event. CSO discharge was characterized by log 10 values per 100 mL (average ± stdev) of 5.12 ± 0.03 and 4.90 ± 0.03 for faecal coliforms and faecal streptococci, and 6.00 ± 0.11 and 7.78 ± 0.04 for rodA and HF183 genetic markers, for E. coli and human host associated Bacteroides, respectively, indicating about 5 % sewage content. SourceTracker analysis of sequencing data attributed 72-77 % of bacteria in the downstream section of the river during a storm event to CSO discharge sources, versus only 4-6 % to rural upstream sources. Data from sixteen summer sampling events in a public park exceeded various guideline values for recreational water quality. Quantitative microbial risk assessment (QMRA) predicted a median and 95th percentile risk of 0.03 and 0.39, respectively, of contracting a bacterial gastrointestinal disease when wading and splashing around in the Ouseburn. We show clearly why microbial water quality should be monitored where rivers flow through public parks, irrespective of their bathing water designation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Development of biofilm is a protective strategy for invading bacterial pathogens against host immune response and administered antimicrobials. Quorum sensing (QS) mediated alteration of gene expression profile have been identified as the key modulator of biofilm dynamics. In the context of rapid and prompt emergence of antimicrobial resistance and tolerance, there is an urgent demand to develop alternatives to available interventions to control biofilm associated infections. Exploring phytochemicals products remains a viable approach to find new hits. Various plant extracts and purified phyto-compounds have been explored against model biofilm formers and clinical isolates for QS-inhibition and prospective anti-biofilm action. Triterpeniods, with the potential to perturb QS and impairing biofilm formation and stability against a number of bacterial pathogens, have been explored and profiled systemically in recent years. Along with the identification of bioactive derivatives and scaffolds, mechanistic insights have also been revealed for antibiofilm action of several triterpenoids. This review offers a comprehensive account of recent studies on QS inhibition and biofilm impairment by triterpenoids and their derivatives., Competing Interests: Declaration of competing interest The authors declare no conflict of interest. None of the authors were paid from the funding of the project., (Copyright © 2023 Elsevier B.V. All rights reserved.)

We report a case series of patients presenting with undiagnosed pulmonary fibrosis as a primary manifestation. On evaluation, after excluding other causes, the fibrosis was attributed to asymptomatic or mild COVID illness in the past. This case series serves to highlight the difficulties posed to clinicians while evaluating pulmonary fibrosis in the post-COVID era, more so in mild to asymptomatic COVID-19. The intriguing possibility of fibrosis setting even in mild to asymptomatic COVID is discussed., (Copyright © 2022 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Background: The main protease is an important structural protein of SARS-CoV-2, essential for its survivability inside a human host. Considering current vaccines' limitations and the absence of approved therapeutic targets, M pro may be regarded as the potential candidate drug target. Novel fungal phytocompound Astrakurkurone may be studied as the potential M pro inhibitor, considering its medicinal properties reported elsewhere., Methods: In silico molecular docking was performed with Astrakurkurone and its twenty pharmacophore-based analogues against the native M pro protein. A hypothetical M pro was also constructed with seven mutations and targeted by Astrakurkurone and its analogues. Furthermore, multiple parameters such as statistical analysis (Principal Component Analysis), pharmacophore alignment, and drug likeness evaluation were performed to understand the mechanism of protein-ligand molecular interaction. Finally, molecular dynamic simulation was done for the top-ranking ligands to validate the result., Result: We identified twenty Astrakurkurone analogues through pharmacophore screening methodology. Among these twenty compounds, two analogues namely, ZINC89341287 and ZINC12128321 showed the highest inhibitory potentials against native and our hypothetical mutant M pro , respectively (-7.7 and -7.3 kcal mol -1 ) when compared with the control drug Telaprevir (-5.9 and -6.0 kcal mol -1 ). Finally, we observed that functional groups of ligands namely two aromatic and one acceptor groups were responsible for the residual interaction with the target proteins. The molecular dynamic simulation further revealed that these compounds could make a stable complex with their respective protein targets in the near-native physiological condition., Conclusion: To conclude, Astrakurkurone analogues ZINC89341287 and ZINC12128321 can be potential therapeutic agents against the highly infectious SARS-CoV-2 virus., Competing Interests: Declaration of competing interest Financial segment: This research was not funded by any government or private organisation. Authors are from three respective universities that are not going to get/loss financially from the publication. No patent or patent applications were filed, either by the authors or from the respective institutions. Non-Financial segment: Authors are not associated with any organisation that has a stake in this research publication. Declaration: Authors declare that, they have no competing interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In Addis Ababa and its environs, most urban wastewater is discharged into rivers without treatment. This study related urban wastewater characteristics to the prevalence of faecal, antibiotic resistant, and potentially pathogenic bacteria in rivers of the Akaki catchment across six locations, for the dry and wet season. Spatiotemporal variation in bacterial hazards across the catchment was up to 6 log 10 units. Cooccurrence of sewage pollution marker gene HF183 in all river samples testing positive for the Vibrio cholerae marker gene ompW, and high levels of these two genes in untreated wastewater, identified human sewage as the likely source of Vibrio cholerae hazards in the catchment. Levels of the marker genes rodA for E. coli, HF183 for human host associated Bacteroides, ciaB for Arcobacter, and ompW for Vibrio cholerae were all higher in the dry season than in the wet season. Marker gene gyrB for Pseudomonas aeruginosa was not detected in the samples. From the sequencing data, notable bacterial genera in the dry season included wastewater pollution indicators Arcobacter and Aeromonas, whereas soil erosion may explain the greater prominence of Legionella, Vicinamibacter, and Sphingomonas during the wet season. Except for the most upstream location, all faecal coliform (FC) counts exceeded WHO standards of 1000 CFU/100 mL for unrestricted irrigation. Concerningly, 0.6-20% of FC had ESBL producing antimicrobial resistance traits. In conclusion, multiple bacterial hazards were of concern for river water users in the Akaki catchment, and elevated in the dry season, when the river water is being used for irrigation of vegetable fields that supply the markets of Addis Ababa. This reflects inadequate treatment and limited dilution of urban wastewater by the natural river flows during periods of low rainfall., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Relatively little is known about the factors associated with child, early, and forced marriage (CEFM) for boys. This brief explores potential economic, social, and demographic drivers of CEFM for boys, highlighting the role of gendered social norms., Methods: Forty-two indicators related to CEFM were drawn from a combination of Demographic and Health Survey and publicly available national-level data and associations with CEFM presented in scatterplots with a linear regression line., Results: CEFM for boys is consistently associated with economic factors related to "readiness to marry," including overall labor force participation, the proportion of boys who are not in school, and youth unemployment., Conclusions: Patriarchal norms regulating sexual and reproductive behavior influence CEFM for boys through pressures to marry as soon as economic independence is achieved. This perpetuates cycles of poverty and locks boys into unfavorable life course pathways., (Copyright © 2022 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Boosting or suppressing our immune system represents an attractive adjunct in the treatment of infections including SARS-CoV-2, cancer, AIDS, malnutrition, age related problems and some inflammatory disorders. Thus, there has been a growing interest in exploring and developing novel drugs, natural or synthetic, that can manipulate our defence mechanism. Many of such studies, reported till date, have been designed to explore effect of the therapeutic on function of macrophages, being a key component in innate immune system. Indeed, RAW264.7, J774A.1, THP-1 and U937 cell lines act as ideal model systems for preliminary investigation and selection of dose for in vivo studies. Several bioassays have been standardized so far where many techniques require high throughput instruments, cost effective reagents and technical assistance that may hinder many scholars to perform a method demanding compilation of available protocols. In this review, we have taken an attempt for the first time to congregate commonly used in vitro immune-modulating techniques explaining their principles. The study detected that among about 40 different assays and more than 150 sets of primers, the methods of cell proliferation by MTT, phagocytosis by neutral red, NO detection by Griess reaction and estimation of expression of TLRs, COX-2, iNOS, TNF-α, IL-6 and IL-1β by PCR have been the most widely used to screen the therapeutics under investigation., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

The study represents in vitro chemometric approach for assessing the heavy metal pollution in Indian Sundarbans. Physio-chemical and elemental characterisation of the sediment samples of Indian Sundarbans had shown high enrichments of toxic metal ions. It was characterised by elevated enrichment factors (2.16-10.12), geo-accumulation indices (0.03 -1.21), contamination factors (0.7-3.43) and pollution load indices (1.0-1.25) which showed progressive sediment quality deterioration and ecotoxicological risk due to metal ions contamination. The physio-chemical parameters of the sediments were replicated and computational chemometric modeling was utilized to assess fungal metabolic growth. All the fungi isolates had shown maximum metabolic activity in high temperature, alkaline pH, and high salinity. Further, the fungal metabolic activity was assessed in different gradient of heavy metal concentration. The significant deterioration of biochemical marker with increasing concentration of heavy metal indicates the status of the microbial health due to toxic metal pollution in the mangrove habitat., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

We assessed antimicrobial resistance (AMR) potential to seven major classes of antibiotics in Central Thailand's coastal aquaculture region using high-throughput qPCR targeting 295 antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs). In parallel, we used MinION next generation sequencing (NGS) of 16S rRNA gene amplicons, qPCR of faecal pollution makers, and conventional plate count methods for the comprehensive characterization of environmental microbiomes. We tested the hypothesis that aquaculture increases environmental AMR by comparing ARGs and MGEs in water and sediment samples from five aquaculture sites and their associated canals. There was no evidence from the ARG and MGE data that aquaculture is a major driver of environmental AMR in Central Thailand. Instead, the highest relative prevalence of resistance traits was found in Hua Krabue canal water influenced by urban pollution from Bangkok at the inland edge of the coastal aquaculture region. The sum of ARGs and MGEs, relative to 16S rRNA genes used as markers for overall bacterial abundance, was between 0.495 ± 0.011 and 0.498 ± 0.013 in Hua Krabue canal water, compared with at most 0.132 ± 0.005 in all the other environmental samples. Corresponding patterns were observed for most faecal pollution markers, which were also elevated in Hua Krabue canal water., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

River systems in developing and emerging countries are often fragmented relative to land and waste management in their catchment. The impact of inconsistent waste management and releases is a major challenge in water quality management. To examine how anthropogenic activities and estuarine effects impact water quality, we characterised water conditions, in-situ microbiomes, profiles of faecal pollution indicator, pathogenic and antibiotic resistant bacteria in the River Melayu, Southern Malaysia. Overall, upstream sampling locations were distinguished from those closer to the coastline by physicochemical parameters and bacterial communities. The abundances of bacterial DNA, total E. coli marker genes, culturable bacteria as well as antibiotic resistance ESBL-producing bacteria were elevated at upstream sampling locations especially near discharge of a wastewater oxidation pond. Furthermore, 85.7% of E. faecalis was multidrug-resistant (MDR), whereas 100% of E. cloacae, E. coli, K. pneumoniae were MDR. Overall, this work demonstrates how pollution in river estuaries does not monotonically change from inland towards the coast but varies according to local waste releases and tidal mixing. We also show that surrogate markers, such dissolved oxygen, Bacteroides and Prevotella abundances, and the rodA qPCR assay for total E. coli, can identify locations on a river that deserve immediate attention to mitigate AMR spread through improved waste management., (Copyright © 2020. Published by Elsevier B.V.)

A new water soluble galactoglucan with apparent molecular weight ~1.61 × 10 5  Da, was isolated from the edible mushroom Pleurotus djamor by hot water extraction followed by purification through dialysis tubing cellulose membrane and sepharose 6B column chromatography. The sugar analysis showed the presence of glucose and galactose in a molar ratio of nearly 3:1 respectively. The structure of the repeating unit in the polysaccharide was determined through chemical and NMR experiments as: In vitro antioxidant studies showed that the PDPS exhibited hydroxyl radical scavenging activity (EC 50  = 1.681 ± 0.034 mg/mL), DPPH radical scavenging activity (EC 50  = 3.83 ± 0.427 mg/mL), reducing power (EC 50  = 4.258 ± 0.095 mg/mL), and ABTS radical quenching activity (EC 50  = 0.816 ± 0.077 mg/mL). So, PDPS should be explored as a natural antioxidant., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Compared to non-Hispanic white individuals, assistive technology (AT) utilization is lower among Hispanic individuals. 1-7 In the US, Spanish is the 2nd most frequently spoken language. Greater than one-fifth of Spanish-speaking households are limited English proficiencty (LEP) households (i.e., all individuals over age 14 in the household speak English less than "very well"). 8 Availability of AT materials in Spanish is one factor influencing knowledge about and utilization of AT among Spanish-speakers., Objective: To examine the availability of Spanish-language AT information on state AT program websites and to assess the relationship between availability and state demographic and linguistic characteristics., Methods: In 2018, we evaluated 56 state and territory AT program websites for the availability of AT information in Spanish. We calculated 4 measures (US Hispanic population in the state/territory; Hispanic individuals as a proportion of state population; overall Spanish-speaking households, and Spanish-speaking, limited English proficient households) from the 2016 American Community Survey and created ranked lists for each measure. Point biserial (r pb ) correlations were calculated to test associations between each measure and availability of AT information in Spanish on each program's website., Results: Sixteen program websites (15 states, 1 territory) provided access to Spanish-language AT information. None of the 4 measures were strongly associated with this outcome (r pb ranged from 0.30 to 0.42). For any of the 4 measures, no more than half of states in the top 10 ranks offered online access to AT information in Spanish., Conclusions: Improving the online availability of AT information in Spanish is necessary to increase equity in AT utilization among Spanish-speaking people with disabilities., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The impact on the hydrologic cycle of permafrost degradation under the influence of climate change has caused an inestimable threat to sustainable regulation of the ecosystem. This study quantified the responses of main hydrological elements, including soil moisture, groundwater, runoff components and discharge to totally degraded permafrost in eastern High Asia by establishing cases with and without thermodynamics using a cold region model combining hydrological processes and thermodynamics. The results showed that the model successfully simulated discharge in cold region basins. Totally degraded permafrost decreased soil moisture in the vadose zone (SMV) and increased the absolute depth to ground water (ADGW). In the daily scale, total permafrost degradation decreased the direct flow in autumn, slightly increased direct flow in spring and decreased interflow in summer. Total permafrost degradation also increased daily baseflow all year round and by >50% in spring, decreased daily discharge during autumn and increased daily discharge during spring. In the annual scale, total permafrost degradation increased direct flow, baseflow, and discharge, and decreased interflow. The magnitudes of these changes were positively related to the ratios of permafrost to the subbasin area. The responses of daily runoff components and discharge to totally degraded permafrost were significantly larger than the annual value. The groundwater level, direct flow and baseflow were far more sensitive to permafrost degradation than SMV, interflow and discharge. The responses of annual individual hydrological elements were more obvious than the annual discharge. These quantified results can be extensively used in lumped hydrology simulations, water resource assessments and eco-system management for partial permafrost degradation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Wind-induced sediment resuspension frequently occurs in Lake Taihu, a typical large shallow lake in China. Internal nutrients release accompanied by sediment resuspension is supposed to sustain the eutrophic status and algal boom persistence. In this study, high-frequency and synchronous in situ observation of the wind field, currents, waves, suspended sediments, and nutrients were collected to understand the dynamic behaviors of sediment and nutrients under multiple natural disturbances in Meiliang Bay, Lake Taihu. Results suggest that both wind speed and wind fetch length could effectively activate the sediment layer and trigger particles entrainment into the overlying water. Wind speed of 4 m/s with long wind fetch (between east and southeast wind direction) was the critical value for sediment resuspension. Furthermore, wind-induced wave shear stress and stochastic nature of turbulence at the water-sediment interface were the driving force for sediment resuspension. Specifically, incipient motion of sediment occurred when shear stress was ranging from 0.02 to 0.07 N/m 2 . Wind-induced sediment resuspension had significantly contributed to nutrients release of particulate N and P, whereas dissolved nutrients concentration was less affected. Internal nutrients release by wind could maintain a significant potential for obstinate eutrophication and algal bloom. This study has revealed the dynamic response of nutrients release to sediment resuspension and wind-induced hydrodynamics. Therefore, a better understanding of the mechanism of internal nutrients release will benefit the effective and sustainable management of the shallow and wind-exposed lakes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Peri-urban aquacultures produce nutritious food in proximity to markets, but poor surface water quality in rapidly expanding megacities threatens their success in emerging economies. Our study compared, for a wide range of parameters, water quality downstream of Bangkok with aquaculture regulations and standards. For parameters not meeting those requirements, we sought to establish whether aquaculture practice or external factors were responsible. We applied conventional and advanced methods, including micropollutant analysis, genetic markers, and 16S rRNA amplicon sequencing, to investigate three family-owned aquacultures spanning extensive, semi-intensive and intensive practices. Canals draining the city of Bangkok did not meet quality standards for water to be used in aquaculture, and were sources for faecal coliforms, Bacteriodes, Prevotella, Human E. coli, tetracycline resistance genes, and nitrogen into the aquaculture ponds. Because of these inputs, aquacultures suffered algae blooms, with and without fertilizer and feed addition to the ponds. The aquacultures were sources of salinity and the herbicide diuron into the canals. Diuron was detectable in shrimp, but not at a level of concern to human health. Given the extent and nature of pollution, peri-urban water policy should prioritize charging for urban wastewater treatment over water fees for small-scale agricultural users. The extensive aquaculture attenuated per year an estimated twenty population equivalents of nitrogen pollution and trillions of faecal coliform bacteria inputs from the canal. Extensive aquacultures could thus contribute to peri-urban blue-green infrastructures providing ecosystem services to the urban population such as flood risk management, food production and water pollution attenuation., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Till date, only three techniques namely Zinc Finger Nuclease (ZFN), Transcription-Activator Like Effector Nucleases (TALEN) and Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-Associated 9 (CRISPR-Cas9) are available for targeted genome editing. CRISPR-Cas system is very efficient, fast, easy and cheap technique for achieving knock-out gene in the cell. CRISPR-Cas9 system refurbishes the targeted genome editing approach into a more expedient and competent way, thus facilitating proficient genome editing through embattled double-strand breaks in approximately any organism and cell type. The off-target effects of CRISPR Cas system has been circumnavigated by using paired nickases. Moreover, CRISPR-Cas9 has been used effectively for numerous purposes, like knock-out of a gene, regulation of endogenous gene expression, live-cell labelling of chromosomal loci, edition of single-stranded RNA and high-throughput gene screening. The execution of the CRISPR-Cas9 system has amplified the number of accessible scientific substitutes for studying gene function, thus enabling generation of CRISPR-based disease models. Even though many mechanistic questions are left behind to be answered and the system is not yet fool-proof i.e., a number of challenges are yet to be addressed, the employment of CRISPR-Cas9-based genome engineering technologies will increase our understanding to disease processes and their treatment in the near future. In this review we have discussed the history of CRISPR-Cas9, its mechanism for genome editing and its application in animal, plant and protozoan parasites. Additionally, the pros and cons of CRISPR-Cas9 and its potential in therapeutic application have also been detailed here., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A green, efficient synthesis of cadmium oxide decorated reduced graphene oxide nanocomposites (RGO/CdO) was prepared by one-step co-precipitation and hydrothermal method. Crystalline nature of the nanocomposites was characterized by X-ray diffraction analysis. To evaluate the structural morphology and particle size, high resolution transmission electron microscopy were used. X-ray photoelectron spectroscopy, Raman spectroscopy and Fourier transform infrared spectroscopy techniques were employed to establish chemical structure of the nanocomposites and Atomic Force Microscopy was done to measure the thickness. The optical properties were evaluated by UV-visible absorption spectroscopy. Thermo-gravimetric analysis, BET surface area and zeta potential measurements were carried out to study the thermal and surface characteristics. The CdO nano-particles (NPs) decorated on RGO sheets exhibit better electrical conductivity compared to RGO. The antibacterial activity of the nanocomposites has also been monitored in different culture media imparting good potentiality than RGO., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A water-soluble heteroglycan (PS-I) isolated from the aqueous extract of a wild edible mushroom Lentinus sajor-caju showed average molecular weight ∼1.79×10 5 Da. The structure of the polysaccharide was determined using chemical and 1D/2D NMR experiments. Acid hydrolysis indicated the presence of d-glucose, d-galactose, d-mannose, and l-fucose in a molar ratio of nearly 4:4:1:1 respectively. The presence of terminal Fucp, terminal Galp, (1→3)-Glcp, (1→6)-Galp, (1→6)-Glcp, (1→4,6)-Galp, and (1→2,4)-Manp moieties were established from methylation analysis. The chemical and NMR analyses indicated that the PS-I was a heteroglycan composed of a repeating unit with backbone chain of three (1→6)-α-d-galactopyranosyl residues, two (1→6)-β-d-glucopyranosyl residues, one (1→4)-α-d-mannopyranosyl residue, and two (1→3)-β-d-glucopyranosyl residues where one (1→6)-α-d-galactopyranosyl residue was branched at O-4 position with terminal α-l-fucopyranosyl residue and (1→4)-α-d-mannopyranosyl residue was branched at O-2 position with terminal α-d-galactopyranosyl residue and the structure was proposed as; The PS-I is a moderate antioxidant compound which showed DPPH radical scavenging activity, hydroxyl radical scavenging activity, ABTS radical scavenging property, reducing power, and ferrous ion chelating ability., (Copyright © 2017 Elsevier B.V. All rights reserved.)

This study sought to detect the presence of sucrose as an adulterant in selected honey varieties from different floral origins by employing Electrical Impedance Spectroscopy (EIS) technique which has been simultaneously supported by Fourier Transform-Mid Infrared Spectroscopy (FT-MIR) measurements to provide a rapid, robust yet simple platform for honey quality evaluation. Variation of electrical parameters such as impedance, capacitance and conductance for 10%, 20%, 30%, 40%, 50%, 60% and 70% (w/w) sucrose syrup (SS) adulterated honey samples are analyzed and their respective current-voltage (I-V) characteristics are studied. Capacitance, conductance and net current flowing through the system are observed to decrease linearly whereas system impedance has been found to increase similarly with the increase in adulterant content. Also, FT-MIR measurements in the spectral region between 1800cm -1 and 650cm -1 reveal the increment of absorbance values due to the addition of SS. Full-Width-at-Half-Maximum (FWHM) is estimated from the spectral peak 1056cm -1 for all pure and adulterated honey samples and is observed to be linearly increasing with increase in adulterant content. Finally, the coefficient of sensitivity has been extracted for all varieties of honey considered in terms of the measured conductance values., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: Medial collateral ligament (MCL) is a prime valgus stabilizer of the knee, and MCL tears are currently managed conservatively. However, posteromedial corner (PMC) injury along with MCL tear is not same as isolated MCL tear and the former is more serious injury and requires operative attention. However, literature is scarce about the management and outcome of PMC-MCL tear alongside anterior cruciate ligament (ACL) tear. The purpose of this study is to report the clinical outcome of primary repair of MCL and PMC with or without staged ACL reconstruction., Methods: A retrospective evaluation was performed on patients with MCL-PMC complex injury with ACL tear who underwent primary repair of MCL-PMC tear followed by rehabilitation. Further, several of them chose to undergo ACL reconstruction whereas rest opted conservative treatment for the ACL tear. A total of 35 patients of two groups [Group 1 (n=15): MCL-PMC repaired and ACL conserved; Group 2 (n=20): MCL-PMC repaired and ACL reconstructed] met the inclusion criteria with a minimum follow-up of two years. Clinical outcome measures included grade of valgus medial opening (0° extension and 30° flexion), Lysholm and International knee documentation committee (IKDC) scores, KT-1000 measurement, subjective feeling of instability, range of motion (ROM) assessment and complications., Results: While comparing group 2 versus group 1, mean Lysholm (94.6 vs. 91.06; p=0.017) and IKDC scores (86.3 vs. 77.6; p=0.011) of group 2 were significantly higher than group 1. 60% patients of group 1 complained of instability against none in the group 2 (p<0.0001). All the knees of both the groups were valgus stable with none requiring late reconstruction. The mean loss of flexion ROM in group 1 and 2 was 12° and 9° respectively which was not statistically different (p=0.41). However while considering the loss of motion, two groups did not show any significant difference in clinical scores., Conclusions: Primary MCL-PMC repair renders the knee stable in coronal plane in both the groups and further ACL reconstruction adds on to the stability of the knee providing a superior clinical outcome. Minor knee stiffness remains a concern after primary MCL-PMC repair but without any unfavorable clinical effect., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The persistence and fate of pharmaceutical and personal care products (PPCPs) in the Lake Mead ecosystem are particularly important considering the potential ecological risks and human health impacts. This study evaluated the removal of five common PPCPs (i.e., trimethoprim, sulfamethoxazole, carbamazepine, ciprofloxacin, and triclosan) from Lake Mead water mediated by the green alga Nannochloris sp. The results from the incubation studies showed that trimethoprim and carbamazepine were highly resistant to uptake in the algal cultural medium and were measured at approximately 90%-100% of the applied dose after 14days of incubation. Sulfamethoxazole was found relatively persistent, with >60% of the applied dose remaining in the water after 14days, and its removal was mainly caused by algae-mediated photolysis. However, ciprofloxacin and triclosan dissipated significantly and nearly 100% of the compounds were removed from the water after 7days of incubation under 24h of light. Ciprofloxacin and triclosan were highly susceptible to light, and their estimated half-lives were 12.7hours for ciprofloxacin and 31.2hours for triclosan. Algae-mediated sorption contributed to 11% of the removal of trimethoprim and sulfamethoxazole, 13% of the removal of carbamazepine, and 27% of the removal of triclosan from the lake water. This research showed that 1) trimethoprim, sulfamethoxazole, and carbamazepine are quite persistent in aquatic environments and may potentially affect human health via drinking water intake; 2) photolysis is the dominant pathway to remove ciprofloxacin from aquatic ecosystems, which indicates that ciprofloxacin may have lower ecological risks compared with other PPCPs; and 3) triclosan can undergo photolysis as well as algae-mediated uptake and it may potentially affect the food web because of its high toxicity to aquatic species., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A water soluble heteroglycan (PCPS) was isolated from the aqueous extract of an edible mushroom Pleurotus cystidiosus. Structural characterization of the heteroglycan was carried out using total hydrolysis, methylation analysis, periodate oxidation, Smith degradation, and 1D/2D NMR experiments. Sugar analysis indicated the presence of glucose, galactose, and mannose in a molar ratio of nearly 6:2:1 respectively. The chemical and NMR analysis of the PCPS indicated the presence of a repeating unit with a backbone consisting of one unit of (1→6)-β-d-glucopyranosyl, two (1→3)-β-d-glucopyranosyl, one (1→3)-α-d-glucopyranosyl, one (1→6)-α-d-glucopyranosyl, and two (1→6)-α-d-galactopyranosyl moieties respectively, out of which one (1→3)-β-d-glucopyranosyl residue was branched at O-6 with terminal β-d-glucopyranosyl and another (1→6)-α-d-galactopyranosyl residue was branched at O-2 with terminal β-d-mannopyranosyl moiety. The polysaccharide was found to exhibit cellular activities at different concentrations (10, 25, 50, 100, 200, 400μg/mL) and maintained the redox balance as well as reduced lipid per oxidation which protect the cell destruction., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Trimethoprim (TMP), sulfamethoxazole (SMX), and triclosan (TCS) are widely used and continuously released into aquatic environments. Freshwater algae can be responsible for the uptake and transfer of the contaminants because they are a major food source for most aquatic organisms. This research applied incubation studies to evaluate the removal efficiency of TMP, SMX, and TCS by the green alga Nannochloris sp. The results showed that the hydrophilic antibiotics TMP and SMX remained in the algal culture at 100% and 68%, respectively, after 14days of incubation, and therefore were not significantly removed from the medium. However, the lipophilic antimicrobial TCS was significantly removed from the medium. Immediately after incubation began, 74% of TCS dissipated and 100% of TCS was removed after 7days of incubation. Additionally, over 42% of TCS was found associated with the algal cells throughout the incubation. The results demonstrate that the presence of Nannochloris sp. eliminated TCS in the aquatic system, but could not significantly remove the antibiotics TMP and SMX. The removal mechanisms of SMX and TCS were found to be different in the algal culture. Algae-promoted photolysis was the primary process for removing SMX and algae-mediated uptake played a major role in removing TCS., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A water-soluble heteroglycan (PS) of an average molecular weight ∼1.98 ×10(5) Da was isolated from the aqueous extract of an edible mushroom Termitomyces clypeatus (R. Heim). The structure of the polysaccharide (PS) was established using total hydrolysis, methylation analysis, Smith degradation, and 1D/2D NMR experiments. Total hydrolysis indicated the presence of d-glucose, d-galactose, d-mannose, and l-fucose in a molar ratio of 4.10:1.95:1.0:0.95, respectively. The chemical and NMR analysis indicated the presence of a repeating unit with a backbone consisting of one each of the residues (1→3)-α-d-galactopyranosyl, (1→3)-α-d-mannopyranosyl, (1→3)-α-d-glucopyranosyl, (1→3)-β-d-glucopyranosyl, (1→6)-β-d-glucopyranosyl, and (1→6)-α-d-galactopyranosyl, respectively. The (1→3)-α-d-mannopyranosyl residue was found branched at O-2 with terminal α-l-fucopyranosyl moiety and (1→3)-β-d-glucopyranosyl residue was branched at O-6 with terminal α-d-glucopyranosyl residue. The PS exhibited antioxidant properties., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

A water soluble fucogalactan (PS-II) of an average molecular weight ∼1.2×10(5) Da was isolated from the aqueous extract of an edible mushroom Macrolepiota dolichaula. It was composed of fucose, galactose and 3-O-methyl galactose in a molar ratio of nearly 1:4:1. Structural characterization of PS-II was carried out using total hydrolysis, methylation analysis, Smith degradation, and 1D/2D NMR experiments. These results indicated that the proposed repeating unit of the PS-II had a backbone chain consisting of four (1→6)- linked α-d-Galp residues, one residue methylated at O-3, and another one substituted at O-2 by (1→2)-α-d-Galp residue, which is terminated with a α-l-Fucp moiety. The PS-II exhibited the antioxidant properties in different in vitro test systems, and also showed in vitro macrophage activation in RAW 264.7 cell line as well as splenocyte and thymocyte activation in mouse cell culture medium., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

A water soluble pectic polysaccharide (PS) isolated from the aqueous extract of the green fruits of Momordica charantia contains D-galactose and D-methyl galacturonate in a molar ratio of nearly 1:4. It showed splenocyte, thymocyte as well as macrophage activations. Moreover, it exhibited potent antioxidant activities. On the basis of total acid hydrolysis, methylation analysis, periodate oxidation, and 1D and 2D NMR studies, the structure of the repeating unit of the pectic polysaccharide was established as: [Formula: see text]., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Fish diseases caused by Pseudomonas aeruginosa, a known pathogenic organism, is responsible for considerable economic losses in the commercial cultivation of Oreochromis mossambicus (Tilapia). The bacteria were injected into healthy fish through intramuscular injection, oral and immersion challenge. Infection was confirmed by histopathological investigation of the infected organs. Lime nanoemulsion was prepared and the effectiveness of the nanoemulsion was studied both in vitro and in vivo by well diffusion assay and in vivo in the artificially infected fish. Results showed that the lime nanoemulsion was effective against the P. aeruginosa infection in O. mossambicus both in vitro and in vivo., (Copyright © 2014 Elsevier B.V. All rights reserved.)

A water soluble branched β-D-glucan (PS-I) with an average molecular weight ~2.1×10(5) Da was isolated from alkaline extract of the fruit bodies of the edible mushroom Entoloma lividoalbum (Kühner & Romagn) Kubička which consists of terminal β-D-glucopyranosyl, (1→3)-β-D-glucopyranosyl, (1→6)-β-D-glucopyranosyl, and (1→3,6)-β-D-glucopyranosyl moieties in a molar ratio of nearly 1:3:2:1. The structure of PS-I was elucidated using acid hydrolysis, methylation analysis, periodate oxidation study, partial hydrolysis, and 1D/2D NMR experiments. The repeating unit of the polysaccharide (PS-I) contains a backbone chain of three (1→6)-β-D-glucopyranosyl residues, one of which was branched at O-3 position with the side chain consisting of three (1→3)-β-D-glucopyranosyl and a terminal β-D-glucopyranosyl residues. Total antioxidant capacity of 1mg PS-I was measured and found equivalent to 70±15 μg of ascorbic acid. The PS-I was found to possess hydroxyl and superoxide radical-scavenging activities with EC50 values of 480 and 150 μg/mL, respectively. The reducing power of PS-I was determined 0.5 at 480 μg/mL., (Copyright © 2013 Elsevier B.V. All rights reserved.)

A heteroglycan (PS) isolated from the mycelia of Pleurotus ostreatus was found to consist of l-fucose, d-mannose, and d-glucose in a molar ratio of nearly 1:2:3. On the basis of acid hydrolysis, methylation analysis, periodate oxidation, and NMR studies (1H, 13C, TOCSY, DQF-COSY, NOESY, ROESY, HSQC, HMBC, and DEPT), the structure of the repeating unit of the PS was determined. The repeating unit had a branched backbone composed of (1→6)-linked α and βd-glucose and (1→2)-linked α-l-fucose. Branching occurred at C-4 position of (1→6)-linked α-d-glucopyranosyl residue with terminal β-d-mannose and C-3 position of (1→6)-linked β-d-glucopyranosyl residue with (1→6)-α-d-mannopyranosyl moiety terminated by α-d-glucose. The structure of the repeating unit of the PS was proposed as: [formula: see text]. The antioxidant properties of the PS were studied. The scavenging activity of hydroxyl free radicals whose EC50 value of PS at 943 μg/mL was determined. Further, EC50 value of the PS at 53 μg/mL was observed for scavenging activity of superoxide free radicals. Chelating effects (54.82%) of ferrous ions were observed at 1mg/mL of the PS., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: A pilot study to determine whether prenatal and neonatal sickle cell tests conform to the guidelines established by the American Congress of Obstetricians and Gynecologists and the American Academy of Pediatrics., Methods: The project was initially structured as a pair of in-person interviews of postpartum women at the University of Chicago, the first collecting medical information and the second surveying the ethical, social, and legal implications (ELSI) of sickle cell trait (SCT). Due to inadequate enrollment, we elected to focus only on the second survey. Descriptive statistics and bivariate analyses were performed., Results: A convenience sample was established from 205 women who had completed surveys of whom 12 (6%) received no prenatal care. Of the 60 women who completed both surveys, 15 (25%) were unsure of their hemoglobinopathy status. Of the 50 results we could verify, 2 women (4%) incorrectly recalled their hemoglobinopathy status. Of the 193 women who received prenatal care and completed the ELSI survey, 47 knew their hemoglobinopathy status from a previous pregnancy and 1 had sickle cell disease. Of the remaining 145 women, 53 (37%) recalled hemoglobinopathy testing during this pregnancy and 44 (30%) were unsure. Only 56 (39%) recalled being told they could refuse testing. Of the 115 women whose infants had newborn screening done prior to the interview, only 51 (44%) recalled discussions with a pediatric provider., Conclusion: Despite professional guidelines that stress the importance of education, counseling, and consent for prenatal and neonatal testing, postpartum women do not recall these conversations.

A water soluble glucan of average molecular weight ∼1.74×10(5)Da was isolated from hot aqueous extract of the fruiting bodies of an ectomycorrhizal edible mushroom Tricholoma crassum (Berk.) Sacc. The structure of this glucan was elucidated on the basis of total hydrolysis, methylation analysis, Smith degradation, and 1D/2D NMR studies. Based on the above experiments the repeating unit of the glucan was established as: [formula see text]. This glucan showed macrophage activation in vitro by NO production in a dose dependent manner and strong splenocyte and thymocyte immunostimulation in mouse cell culture medium. It also exhibited good inhibition activity toward lipid peroxidation., (Copyright © 2012. Published by Elsevier Ltd.)

A water soluble glucan (PS-I) was isolated from the hot aqueous extract of the fruit bodies of an ectomycorrhizal edible mushroom, Russula albonigra (Krombh.) Fr. The total hydrolysis, methylation analysis, periodate oxidation, and NMR ((1)H, (13)C, DEPT-135, TOCSY, DQF-COSY, NOESY, ROESY, HSQC, and HMBC) studies revealed the presence of the following repeating unit in the polysaccharide: This glucan showed excellent activation of macrophages as well as splenocytes and thymocytes in vitro., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

An immunoenhancing water-soluble hetero polysaccharide was isolated from an alkaline extract of the fruit bodies of an ectomycorrhizal edible mushroom, Tricholoma crassum (Berk.) Sacc. The structure of the molecule was investigated using acid hydrolysis, methylation analysis; periodate oxidation study, and NMR spectroscopy techniques ((1)H, (13)C, DEPT-135, DQF-COSY, TOCSY, NOESY, ROESY, HSQC, and HMBC). On the basis of the above-mentioned experiments the structure of the repeating unit of the polysaccharide was established as: This polysaccharide exhibited splenocyte, thymocyte as well as macrophage activations., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: The US Head Start program serves low-income preschoolers and their caregivers and provides an opportunity for assessment and intervention on obesity. We sought to determine the prevalence of obesity among children and their caregivers and to identify variables that are associated with child body mass index (BMI) z scores and caregiver BMI., Design/setting: Cross-sectional data on diet and BMI from 770 caregiver-child dyads recruited from 57 Head Start centers in Alabama and Texas., Methods: Height and weight of each caregiver and child were measured using standardized protocols. Dietary intakes of caregiver-child dyads were collected using three 24-hour dietary recalls and Block food frequency questionnaires. Data were collected between September 2004 and November 2005. The larger Food Pyramid categories were divided into 17 food consumption groups and tested for their association with child BMI z scores. Analysis of variance was used to test if food groups were significantly associated with child BMI z score., Results: The prevalence of obesity among children was 18.4%, 24.3%, and 37.3% among black, Hispanic, and white children, respectively (P<0.0001), whereas it was 58.3%, 41.4%, and 41.6% among black, Hispanic, and white caregivers, respectively (P<0.0001). Child BMI z scores and caregiver BMIs were correlated (r=0.16, P<0.0001). In multivariable models, children were 1.90 (95% confidence interval 1.31-2.74) times more likely to have BMI ≥95th percentile if their caregiver was obese. Five variables (fruits, unsweetened beverages, low-fat dairy, race, and caregiver's BMI) were significantly associated with child BMI z scores. Fruits were inversely related, whereas unsweetened beverages, low-fat dairy, and caregiver's BMI were positively associated with child BMI z score (P<0.03). Compared to whites, black and Hispanic children had lower BMI z scores (P<0.05)., Conclusions: The high prevalence of obesity in this population together with the observed inverse association between fruit consumption and BMI, if replicated in other studies, suggests that interventions that promote fruit consumption could have beneficial effects on child BMI., (Copyright © 2011 American Dietetic Association. Published by Elsevier Inc. All rights reserved.)

The CCN proteins are extracellular matrix associated proteins involved in critical cell activities and several aggressive forms of cancer. The proteins share a modular structure of four discrete domains and 38 conserved cysteine residues. The absence of any structural information of these proteins has resulted in a need for the ability to produce substantial amounts of pure CCN protein. Through bacterial expression and inclusion body based purification, pure recombinant CCN proteins have been produced for use in structural and biochemical experiments., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The tumor necrosis factor (TNF)-family cytokine TL1A (TNFSF15) costimulates T cells through its receptor DR3 (TNFRSF25) and is required for autoimmune pathology driven by diverse T-cell subsets. TL1A has been linked to human inflammatory bowel disease (IBD), but its pathogenic role is not known. We generated transgenic mice that constitutively express TL1A in T cells or dendritic cells. These mice spontaneously develop IL-13-dependent inflammatory small bowel pathology that strikingly resembles the intestinal response to nematode infections. These changes were dependent on the presence of a polyclonal T-cell receptor (TCR) repertoire, suggesting that they are driven by components in the intestinal flora. Forkhead box P3 (FoxP3)-positive regulatory T cells (Tregs) were present in increased numbers despite the fact that TL1A suppresses the generation of inducible Tregs. Finally, blocking TL1A-DR3 interactions abrogates 2,4,6 trinitrobenzenesulfonic acid (TNBS) colitis, indicating that these interactions influence other causes of intestinal inflammation as well. These results establish a novel link between TL1A and interleukin 13 (IL-13) responses that results in small intestinal inflammation, and also establish that TL1A-DR3 interactions are necessary and sufficient for T cell-dependent IBD.

Angiotensin I-converting enzyme (ACE) plays a key role in the renin-angiotesin aldosterone cascade. We analysed the secondary structure and structural organization of a purified 65kDa N-domain ACE (nACE) from Wistar rat mesangial cells, a 90 kDa nACE from spontaneously hypertensive rats and a 130 kDa somatic ACE. The C-terminal alignment of the 65 kDa nACE with rat ACE revealed that the former was truncated at Ser(482), and the sequence of the 90 kDa nACE ended at Pro(629). Protein's secondary structure consisted predominantly of alpha-helices. The 90 and 65 kDa isoforms were the most stable in guanidine and at low pH, respectively. Enzymatic activity decreased with loss in secondary structure, except in the case of guanidine HCl where the 90 kDa fragment loses its secondary structure faster than its enzymatic activity. We identified and characterized the activity and stability of these isoforms and these findings would be helpful on the understanding of the role of nACE isoforms in hypertension., (Copyright 2010 Elsevier B.V. All rights reserved.)

Angiotensin-I converting enzyme (ACE, a zinc dependent dipeptidyl carboxypeptidase) is a major target of drugs due to its role in the modulation of blood pressure and cardiovascular disorders. Here we present a crystal structure of AnCE (an ACE homologue from Drosophila melanogaster with a single enzymatic domain) in complex with a natural product-phosphonotripeptide, K-26 at 1.96A resolution. The inhibitor binds exclusively in the S(1) and S(2) binding pockets of AnCE (coordinating the zinc ion) through ionic and hydrogen bond interactions. A detailed structural comparison of AnCE.K-26 complex with individual domains of human somatic ACE provides useful information for further exploration of ACE inhibitor pharmacophores involving phosphonic acids., (Copyright 2010 Elsevier Inc. All rights reserved.)

Angiotensin I-converting enzyme (ACE), one of the central components of the renin-angiotensin system, is a key therapeutic target for the treatment of hypertension and cardiovascular disorders. Human somatic ACE (sACE) has two homologous domains (N and C). The N- and C-domain catalytic sites have different activities toward various substrates. Moreover, some of the undesirable side effects of the currently available and widely used ACE inhibitors may arise from their targeting both domains leading to defects in other pathways. In addition, structural studies have shown that although both these domains have much in common at the inhibitor binding site, there are significant differences and these are greater at the peptide binding sites than regions distal to the active site. As a model system, we have used an ACE homologue from Drosophila melanogaster (AnCE, a single domain protein with ACE activity) to study ACE inhibitor binding. In an extensive study, we present high-resolution structures for native AnCE and in complex with six known antihypertensive drugs, a novel C-domain sACE specific inhibitor, lisW-S, and two sACE domain-specific phosphinic peptidyl inhibitors, RXPA380 and RXP407 (i.e., nine structures). These structures show detailed binding features of the inhibitors and highlight subtle changes in the orientation of side chains at different binding pockets in the active site in comparison with the active site of N- and C-domains of sACE. This study provides information about the structure-activity relationships that could be utilized for designing new inhibitors with improved domain selectivity for sACE., (2010 Elsevier Ltd. All rights reserved.)

Introduction: In the United States, newborn screening programs universally identify newborns with sickle cell disease (SCD) and heterozygote carriers (sickle cell trait [SCT]). Although there is a consensus to disclose SCT to parents, there are limited empirical data about whether and how this information is transmitted to the carrier children., Methods: In-person questionnaires were administered to parents with SCT and parents of a child with either SCD or SCT to examine the knowledge, attitudes, beliefs, and disclosure patterns about SCT of parents., Results: Fifty-three adults were interviewed, half (27) of whom had a child with SCD. There was significant misunderstanding about sickle cell inheritance (mean score, 68%), but parents who have a child with SCD have better knowledge compared to those without a child with SCD (78% vs 58%, p = .002). Respondents perceive minimal stigma associated with SCT. Unless there is an affected proband, individuals with SCT rarely receive counseling or education outside of the family., Conclusions: There is significant misinformation about what it means to be a carrier and its health and reproductive implications. Formal professional counseling is rare, especially for those families without an affected proband. Strategies to increase the utilization of counseling and improve genetic literacy are necessary.