Making bioinformatics training FAIR: the EMBL-EBI training portal.

EMBL-EBI provides a broad range of training in data-driven life sciences. To improve awareness and access to training course listings and to make digital learning materials findable and simple to use, the EMBL-EBI Training website, www.ebi.ac.uk/training, was redesigned and restructured. To provide a framework for the redesign of the website, the FAIR (findable, accessible, interoperable, reusable) principles were applied to both the listings of live training courses and the presentation of on-demand training content. Each of the FAIR principles guided decisions on the choice of technology used to develop the website, including the details provided about training and the way in which training was presented. Since its release the openly accessible website has been accessed by an average of 58,492 users a month. There have also been over 12,000 unique users creating accounts since the functionality was added in March 2022, allowing these users to track their learning and record completion of training. Development of the website was completed using the Agile Scrum project management methodology and a focus on user experience. This framework continues to be used now that the website is live for the maintenance and improvement of the website, as feedback continues to be collected and further ways to make training FAIR are identified. Here, we describe the process of making EMBL-EBI's training FAIR through the development of a new website and our experience of implementing Agile Scrum.

Simultaneous Measurement of Muon Neutrino ν_{µ} Charged-Current Single π

Neutrino-induced charged-current single π^{+} production in the Δ(1232) resonance region is of considerable interest to accelerator-based neutrino oscillation experiments. In this Letter, high statistic differential cross sections are reported for the semiexclusive reaction ν_{µ}A→µ^{-}π^{+}+ nucleon(s) on scintillator, carbon, water, iron, and lead targets recorded by MINERvA using a wideband ν_{µ} beam with ⟨E_{ν}⟩≈6 GeV. Suppression of the cross section at low Q^{2} and enhancement of low T_{π} are observed in both light and heavy nuclear targets compared with phenomenological models used in current neutrino interaction generators. The cross sections per nucleon for iron and lead compared with CH across the kinematic variables probed are 0.8 and 0.5 respectively, a scaling which is also not predicted by current generators.

Tau filaments are tethered within brain extracellular vesicles in Alzheimer's disease.

The abnormal assembly of tau protein in neurons is the pathological hallmark of multiple neurodegenerative diseases, including Alzheimer's disease (AD). In addition, assembled tau associates with extracellular vesicles (EVs) in the central nervous system of patients with AD, which is linked to its clearance and prion-like propagation between neurons. However, the identities of the assembled tau species and the EVs, as well as how they associate, are not known. Here, we combined quantitative mass spectrometry, cryo-electron tomography and single-particle cryo-electron microscopy to study brain EVs from AD patients. We found filaments of truncated tau enclosed within EVs enriched in endo-lysosomal proteins. We observed multiple filament interactions, including with molecules that tethered filaments to the EV limiting membrane, suggesting selective packaging. Our findings will guide studies into the molecular mechanisms of EV-mediated secretion of assembled tau and inform the targeting of EV-associated tau as potential therapeutic and biomarker strategies for AD.

Evolution of the intracranial features of congenital cytomegalovirus on MRI.

AIM: To describe the evolution of the intracranial features of congenital cytomegalovirus (cCMV) on magnetic resonance imaging (MRI). MATERIALS AND METHODS: Sixteen infants with polymerase chain reaction (PCR)-confirmed cCMV who had undergone at least two MRI examinations of the brain were identified. Two paediatric neuroradiologists reviewed the baseline studies retrospectively for intracranial features of cCMV, including white matter signal abnormalities, subependymal cysts, malformations of cortical development, and intracranial calcification. The subsequent MRI studies were then reviewed and directly compared to the baseline examinations. RESULTS: White matter signal abnormalities were seen on all 16 baseline studies (100%); these persisted on all subsequent examinations but were patchier, more focal, and associated with an interval reduction in white matter volume. Subependymal cysts were present on 11 (69%) of the baseline scans; these almost universally regressed (in 10 of the 11 cases [91%]), with no new cysts appreciable on subsequent imaging. Malformations of cortical development, exclusively in the form of polymicrogyria, were seen in six (38%) patients and persisted, unchanged, on subsequent imaging. Intracranial calcification was seen in a minority of baseline studies (4 [25%]) and remained stable on subsequent scans. CONCLUSION: Children with cCMV who present later in life without an established or suspected underlying pathology can pose a challenge to the assessing radiologist. The radiological sequelae of cCMV can be non-specific; in some cases, white matter signal abnormalities and focal loss of white matter volume may be the only intracranial features. It is therefore important that radiologists are aware of cCMV as a potential differential for these findings.

Simultaneous Measurement of Proton and Lepton Kinematics in Quasielasticlike ν_{µ}-Hydrocarbon Interactions from 2 to 20 GeV.

Neutrino charged-current quasielastic-like scattering, a reaction category extensively used in neutrino oscillation measurements, probes nuclear effects that govern neutrino-nucleus interactions. This Letter reports the first measurement of the triple-differential cross section for ν_{µ} quasielastic-like reactions using the hydrocarbon medium of the MINERvA detector exposed to a wideband beam spanning 2≤E_{ν}≤20 GeV. The measurement maps the correlations among transverse and longitudinal muon momenta and summed proton kinetic energies, and compares them to predictions from a state-of-art simulation. Discrepancies are observed that likely reflect shortfalls with modeling of pion and nucleon intranuclear scattering and/or spectator nucleon ejection from struck nuclei. The separate determination of leptonic and hadronic variables can inform experimental approaches to neutrino-energy estimation.

Diagnostic analysis of baseline brain MRI features in infants with congenital cytomegalovirus infection: a simplified scoring system.

AIM: To characterise the magnetic resonance imaging (MRI) features of infants with congenital cytomegalovirus (CMV) and categorise those into a simplified MRI scoring system. MATERIALS AND METHODS: Three neuroradiologists reviewed the examinations of 71 infants retrospectively and scored for the presence of a white matter signal abnormality and structural lesion and each MRI was given a score of 0, 1, 2, or 3 for normal, structural abnormality alone, white matter abnormality alone, white matter abnormality plus structural lesion, respectively. Imaging features were outlines according to symptomatology. Chi-square and Spearman's rho were used to test relationships between MRI features and viral loads and MRI score/symptomatic disease respectively. Cohen's Kappa coefficient was used to assess interobserver agreement. RESULTS: Of the 49 abnormal studies, 40% (n=20) were seen in asymptomatic infants. The commonest finding was white matter signal abnormality, followed by cyst formation and polymicrogyria (86%, n=42; 71%, n=35; and 33%, n=16, respectively). Cysts were significantly positively correlated with white matter abnormalities and polymicrogyria. On the MRI score, 31%, 10%, 15%, and 44% obtained a score of 0, 1, 2, and 3, respectively; the MRI score was positively correlated with log-transformed viral loads. Interobserver agreement for the presence of white matter signal abnormality, cyst formation, malformations of cortical development (MCD), and global MRI score was excellent (k = 0.82, 0.94, 0.96, and 0.86, respectively). CONCLUSION: Baseline MRI provides information valuable for treatment decisions, especially in "asymptomatic" infants. The simplified scoring system is easier to use, incorporating solely the imaging findings that are anticipated to have an effect on clinical outcome.

Toxicological analysis of aerosols derived from three electronic nicotine delivery systems using normal human bronchial epithelial cells.

Electronic nicotine delivery systems (ENDS) are a rapidly growing global market advertised as a safer alternative to combustible cigarettes. However, comprehensive investigations of END aerosol physicochemical and toxicological properties have not been fully explored across brands to assess relative safety. In this study, we evaluated aerosols collected from three ENDS - Juul Fruit Medley (5% nicotine), Logic Power (2.4% nicotine), and Mistic (1.8% nicotine). ENDS aerosols were generated using standard machine puffing regimen and collected with a novel fluoropolymer condensation trap. Triple quadrupole-inductively coupled plasma-mass determined the presence of heavy metals in collected aerosols. The toxicological effects of ENDS aerosols on normal human bronchial epithelial cells (NHBE) were investigated using cellular viability, reactive oxygen species, oxidative stress assays, along with DNA damage assessments using the CometChip©. Results indicated the total metal concentrations within collected ENDS aerosols were higher for Mistic and Logic compared to Juul. Logic Power aerosols elicited higher reactive oxygen species levels than Mistic and Juul in NHBE after 24-h exposure. Similar dose-dependent reductions of cellular viability and total glutathione were found for each exposure. However, Logic and Juul aerosols caused greater single stranded DNA damage compared to Mistic. Our study indicates that regardless of brand, ENDS aerosols are toxic to upper airway epithelial cells and may pose a potential respiratory hazard to occasional and frequent users.

COVID-19-Associated Cytotoxic Lesions of the Corpus Callosum.

There are very limited published data on the neurologic complications associated with coronavirus disease 2019 (COVID-19) in the pediatric population. Here we present the first 2 pediatric cases of presumed COVID-19 related cytotoxic lesions of the corpus callosum. Similar to reports in adults, these cases suggest that the COVID-19 infection in children may rarely mediate a hyperinflammatory response that can cause CNS pathology. As the pandemic continues further, the presentation of cytotoxic lesions of the corpus callosum should prompt radiologists to consider COVID-19, among other known causes.

Correction: Therapeutic targeting of Id2 reduces growth of human colorectal carcinoma in the murine liver.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Is it not time for international guidelines to combat congenital cytomegalovirus infection? A review of central nervous system manifestations.

Cytomegalovirus (CMV) is the most commonly transmitted virus in utero with a prevalence of up to 1.5%. The infection has potentially debilitating and devastating consequences for the infected fetus, being a leading cause for neurological disability worldwide. Once acquired, it often goes undetected with only an assumed 10% of infected neonates displaying the classic clinical or imaging features. Viral DNA polymerase chain reaction (PCR) of saliva or urine obtained within the first 21 days of life is required to make the diagnosis. As the majority of infected neonates are initially asymptomatic, diagnosis is often delayed. An abnormal routine neonatal hearing test and characteristic antenatal cranial ultrasound imaging findings may raise the suspicion of congenital CMV (cCMV) in the asymptomatic group. Ultimately, the aim is to facilitate early diagnosis and timely treatment. In this article, we highlight diagnostic and treatment challenges of the commonest congenital infection, we present the current available central nervous system imaging severity grading systems, and highlight the need for an internationally agreed diagnostic grading system that can aid treatment decision-making.

AML1 protein interacts with influenza A virus neuraminidase and upregulates IFN-ß response in infected mammalian cells.

Neuraminidase (NA) is an integral membrane protein of influenza A virus (IAV) and primarily aids in the release of progeny virions, following the intracellular viral replication cycle. In an attempt to discover new functions of NA, we conducted a classical yeast two-hybrid screen and found acute myeloid leukaemia marker 1 (AML1) as a novel interacting partner of IAV-NA. The interaction was further validated by co-immunoprecipitation in IAV-infected cells and in an in vitro coupled transcription/translation system. Interestingly, we found an increase in the expression of AML1 upon IAV infection in a dose-dependent manner. As expected, we also observed an increase in the IFN-ß levels, the first line of defence against viral infections. Subsequently, when AML1 was downregulated using siRNA, the IFN-ß levels were found to be remarkably reduced. Our study also shows that AML1 is induced upon IAV infection and results in the induction of IFN-ß. Thus, AML1 is proposed to be an important player in IFN induction and has a role in an antiviral response against IAV infection. SIGNIFICANCE AND IMPACT OF THE STUDY: Influenza epidemics and pandemics are constant threats to human health. Development of antiviral therapeutics has focused on important and major IAV proteins as targets. However, the rate at which this virus mutates makes the task challenging. Thus, next-generation approaches aim at host cellular proteins that aid the virus in its replication. This study reports a new host-virus interaction, of acute myeloid leukaemia marker 1 (AML1) with influenza A neuraminidase (IAV-NA). We have found that this interaction has a direct effect on the upregulation of host IFN-ß response. Further studies may lead to a greater understanding of this new innate defence pathway in infected cells.

Outcomes of Primary Arteriovenous Fistula for Hemodialysis in Elderly Patients (>65 Years) with End Stage Renal Disease: A Study on Indian Population.

INTRODUCTION: The outcome of arteriovenous fistula (AVF) for hemodialysis (HD) in elderly population remains an issue. The aim of our study was to evaluate the outcomes of arteriovenous fistulas created at our institute in patients older than 65 years. METHODS: All chronic HD patients with age >65 years who had an AVF created between January 1, 2010 and January 1, 2017 were included retrospectively. Baseline demographic information including age, gender, etiology of renal failure and comorbidities were recorded. Access characteristics including access type and anatomic location were recorded. The end point of study was primary and secondary patency. Minimum follow up period of study was 1 year. RESULTS: A total of 422 AVF were created within the study period. The mean age was 69.3 years. The anatomical site of AVF creation was radiocephalic (RCF) in 74.8% (n = 316), brachiocephalic (BCF) in 18.9% (n = 80) and brachiobasilic (BBF) in 6.1% (n = 26). At one year after creation, cumulative survival of the AVF was 64.7%. At 36 months the primary and secondary patency of RCF, BCF and BBF was 43.6%, 58.6%, 42.6% and 47.3%, 62.5%, 56.9% respectively. The overall median survival did not differ between RCF and BBF fistulas. However, when both were compared with BCF (median survival 1034 days), BBF (median survival 741 days) and RCF (median survival 592 days) had significantly poorer survival (P = 0.004). The most common reason for access failure was thrombosis (28.4%) followed by failure to mature (9%) and aneurysm related complications (9%). CONCLUSIONS: Age should not be a limiting factor when choosing AVF as the preferred HD access. Brachiocephalic AVF has better primary and secondary patency with higher overall median survival. However RCF also provides reasonably good survival rates with acceptable complications in elderly population. Thrombosis and fistulas that fail to mature present as a primary concern to patients in elderly population, and demand further study.

Intermediate monocytes are increased in enthesitis-related arthritis, a category of juvenile idiopathic arthritis.

Microarray of peripheral blood (PB) and synovial fluid mononuclear cells (PBMC, SFMC) of patients with juvenile idiopathic arthritis-enthesitis-related arthritis (JIA-ERA) has shown the involvement of monocytes. On the basis of CD14 and CD16 expression, monocytes are classified as classical, intermediate and non-classical. In response to Toll-like receptor (TLR) stimulation, intermediate monocytes produce proinflammatory cytokines and play a role in inflammatory diseases. Therefore, we have studied the microarray profile of monocytes, the frequency of their subsets and cytokine production. Monocyte-specific microarray analysis was performed in six healthy controls' PBMC and six patients' PBMC and SFMC using Illumina chips WG12. Monocyte subsets were assessed in 46 patients with JIA-ERA and 17 healthy controls and 17 disease controls by flow cytometry. Interleukin (IL)-23 and tumour necrosis factor (TNF) levels were measured in culture supernatants of eight controls and seven patients' PBMC/SFMC with/without lipopolysaccharide (LPS) stimulation. Cytokine-producing intermediate monocytes were assessed by flow cytometry. Genes related to antigen presentation, cytokine signalling and TLR pathway were regulated differentially in PB and synovial monocytes of patients with JIA-ERA. Key genes of intermediate monocytes, such as CLEC10A and MARCO, were expressed three- to fourfold more in JIA-ERA. In PB, the frequency of intermediate monocytes was significantly higher in JIA-ERA (4·90% ± 3·5) compared to controls (1·8% ± 1·06; P < 0·001). Patients' synovial cells also had more intermediate monocytes compared to PB (11·25% ± 11·32, 5·9% ± 4·8; P = 0.004). Intermediate monocytes are the major producers of IL-23. Thus, intermediate monocytes may play an important role in JIA-ERA, possibly by producing cytokines, and contribute to joint inflammation.

Gut microbiome in children with enthesitis-related arthritis in a developing country and the effect of probiotic administration.

In Asia, enthesitis-related arthritis (ERA) is the most frequent category of juvenile idiopathic arthritis. ERA has a strong association with human leucocyte antigen (HLA)-B27 and subclinical gut inflammation. In an HLA-B27 transgenic rat model, the presence of Bacteroides bacteria in the gut appears to cause spondyloarthropathy (SpA). Thus, we studied gut microbiota in children with ERA. Stool specimens from 33 patients with ERA and 14 age-matched healthy controls were studied; none had any gastrointestinal symptom, or had received a drug known to affect gut motility or microbiota in the preceding 6 weeks. From each specimen, a cDNA library for the V3 region of bacterial 16S rRNA was subjected to high-throughput, massively parallel sequencing. Relationship of the specimens was studied using principal co-ordinate analysis (PCoA), and abundances of various bacterial taxa and alpha diversity were compared between groups. In eight patients, a repeat faecal specimen was studied after 12 weeks of probiotic therapy. The 55 specimens yielded a median (range) of 397 315 (102 093-1 502 380) high-quality reads each. In PCoA, gut microbiota from ERA showed a wider dispersion than those from controls. In patients, families Bacteroidaceae and Enterobacteriaceae were more abundant and Prevotellaceae were less abundant than in controls. Also, genera Bacteroides, Entercoccus and Klebsiella were over-represented and genus Prevotella was under-represented in ERA patients. Probiotic therapy led to a non-significant increase in Prevotellaceae. Patients with ERA have a dysbiosis in the gut, with increased abundance of Bacteroides and reduction of Prevotella. Probiotic supplementation in a subset of patients did not reverse these changes significantly.

Effect of probiotics on clinical and immune parameters in enthesitis-related arthritis category of juvenile idiopathic arthritis.

Gut microflora and dysbiosis as an environmental factor has been linked to the pathogenesis of enthesitis-related arthritis (JIA-ERA); thus, we performed a proof-of-concept study of probiotics to modulate the gut-flora and study the effects on immune and clinical parameters of children having JIA-ERA. Forty-six children with active JIA-ERA were randomized to placebo or probiotic therapy along with non-steroidal anti-inflammatory drugs (NSAIDs) for 12 weeks. Patients were assessed using a six-point composite disease activity index (mJSpADA) based on morning stiffness, joint count, enthesitis count, sacroiliitis/inflammatory back pain, uveitis and erythrocyte sedimentation rate/C-reactive protein (ESR/CRP). Frequencies of T helper type 1 (Th1), Th2, Th17 and regulatory T cells in blood were measured using flow cytometry. Serum cytokines interferon (IFN)-γ, interleukin (IL)-4, IL-17, IL-10, tumour necrosis factor (TNF)-α and IL-6 were measured by cytokine bead array using flow cytometer. The average age of 46 children (44 boys) was 15 ± 2.5 years and duration of disease was 3.5 ± 3 years. There was no significant difference in improvement in mJSpADA between the two groups (P = 0·16). Serum IL-6 levels showed a decrease (P < 0·05) in the probiotic-group. Th2 cell frequency (P < 0·05) and serum IL-10 levels (P < 0·01) showed an increase in the placebo group, but again the probiotic use did not show a significant change in immune parameters when compared to the placebo. Adverse effects among the probiotic and placebo groups were diarrhea (36 versus 45%), abdominal pain (9 versus 20%), minor infections (4·5 versus 20%) and flatulence (23 versus 15%), respectively. Thus, we can conclude that probiotic therapy in JIA-ERA children is well tolerated, but failed to show any significant immune or clinical effects over NSAID therapy.

Cadaveric feasibility study on the use of ultrasound contrast to assess spread of injectate in the serratus anterior muscle plane.

BACKGROUND: The Serratus anterior muscle plane (SAP) block has recently been described for the purpose of perioperative pain management following cases of trauma and breast surgery. It might prove a safer alternative to the other regional thoracic paravertebral and central neuraxial blockade techniques. There are no descriptive cadaveric studies in the pre-existing literature to delineate the anatomical plane for this novel technique. The main objectives for our study were to examine the location of the Serratus anterior muscle belly, assess the efficacy of achieving adequate delineation of the muscle plane utilising ultrasound imaging with agitated water as the contrast agent, and finally, to observe the extent of the cepahlo-caudal spread of the injectate in the SAP. MATERIALS AND METHODS: Seven cadavers were studied. 20 mls of saline was injected into posterior axillary line (PAL) at the level of the 4-5(th) rib under ultrasound guidance. This was followed by injection of 10 mls of water with air (8 mls water and 2 mls of air). The presence of hyperechoic air bubbles in the fluid distended SAP (hypoechoic) area demonstrated the spread of water and air. RESULTS: In 36% of cadavers, fully formed Serratus Anterior muscle belly was identified at the midaxillary line (MAL), 14% in PAL, and remaining 50% between PAL and MAL. The lower most limit of air-water spread was identified at the subcostal margin. Cephalad spread of contrast was noted in 2(nd) intercostal space ICS (7%), 3(rd) ICS (71%), and 4(th) ICS (22%). CONCLUSION: This study describes that the serratus anterior muscle is well-formed near the PAL and the injectate spread can be determined with the help of agitated water contrast on ultrasound. Furthermore, there was variability in the cephalad spread of the injectate.

Urinary osteoprotegerin: a potential biomarker of lupus nephritis disease activity.

OBJECTIVES: Urinary biomarkers may help in identification, treatment and assessment of response in patients with lupus nephritis (LN). Osteoprotegerin (OPG) is produced by the kidneys and lymphoid cells and may reflect renal disease activity better. The data on its utility are sparse. METHODS: Fifty-eight patients with active LN (AN), 24 with active non-renal disease (ANR) and 39 with inactive disease (ID) were included. Median disease duration was 32 (1-204) months and median age was 27 (12-50) years. AN patients were followed up every three months for one year. Urine and serum samples were collected for OPG measurement by ELISA (pg/ml) and urinary values were normalised for creatinine excretion (pg/mg). Urine samples from 24 healthy individuals (HCs) and 20 patients each of rheumatoid arthritis (RA) and diabetic nephropathy (DM) served as controls. Variables were expressed as median (range). RESULTS: At baseline, normalised urinary OPG (uOPG) was significantly higher (p < 0.001) in AN (1229 (0-8577)) than ANR (236 (0-14713)), ID (463 (7-4253)), HCs (366 (120-2849)) and DM (350 (127-1577)) but it was not different from RA (1511 (122-8849)). uOPG correlated modestly with rSLEDAI (r = 0.4, p < 0.001) and SLEDAI (r = 0.31, p < 0.001) but not with serum OPG (sOPG). uOPG but not sOPG could differentiate between AN and ANR groups. In the longitudinal study, uOPG and sOPG decreased significantly with treatment at all follow-up visits but the trend of fall in sOPG was erratic. uOPG values at baseline, 3, 6, 9 and 12 months were 1229 (0-8577), 466 (3-4874), 104 (0-1598), 325 (0-4025) and 555 (6-6771) pg/mg, respectively. uOPG but not sOPG rose before conventional markers in three patients who had a relapse of LN. In two patients who developed chronic kidney disease, uOPG remained persistently high. For differentiating AN from ANR patients, uOPG performed the best on receiver operator characteristics analysis (AUC = 0.72) when compared with anti-dsDNA antibodies, C3, C4 and sOPG. CONCLUSION: uOPG is derived from kidneys and helps differentiate active SLE patients with and without LN. It shows modest correlation with disease activity and has a potential to predict poor response to therapy and relapse of LN.

Proliferation Index Predicts Survival after Second Craniotomy within 6 Months of Adjuvant Radiotherapy for High-grade Glioma.

AIMS: To determine pathological features that predict survival in patients having repeat craniotomy within 6 months of radiotherapy for high-grade glioma (HGG). MATERIALS AND METHODS: HGG patients (World Health Organization grade 3/4) managed with repeat craniotomy within 6 months of completing radiotherapy between 2008 and 2012 were included. Based on the presence of residual tumour cells, the pathology was reported as pathological progression or pathological pseudoprogression. The proliferation index (Ki67) was reported and compared with initial pathology as a percentage change. Tumour necrosis was estimated as a percentage of the specimen. Overall survival was calculated in months. RESULTS: Of 327 patients managed with HGG, 27 patients underwent repeat craniotomy within 6 months of radiotherapy. The median survival after reoperation was 11 months (95% confidence interval 1-22). Ki67 at reoperation of 0%, 1-9% and >10% was associated with survival with a median survival of 13, 13 and 3 months, respectively (P = 0.007). Change in Ki67 was also associated with median survival, with <50% reduction median survival 3 months, 50-80% median survival 7 months and >80% reduction median survival 13 months, P = 0.02. Widespread treatment-related necrosis improved outcome, with >80% necrosis having a median survival of 13 months versus 3 months in those with <80% necrosis (P = 0.003). CONCLUSION: The presence of residual tumour at repeat craniotomy within 6 months of radiotherapy is not an independent indicator of prognosis. Patients with residual tumour that had a low Ki67 had a similar median survival as those with only treatment necrosis. Reduced proliferation of residual tumour cells and widespread necrosis may be more important indicators for future outcome.

Differential dendritic cell-mediated activation and functions of invariant NKT-cell subsets in oral cancer.

OBJECTIVES: Invariant natural killer T (iNKT) cells are unique subset of glycolipid-reactive T lymphocytes with potent antitumour characteristics. This study was planned to understand Th-like cytokine profiles of iNKT-cell subsets and modulation of their functions in response to glycolipid ligand and tumour cell lysate (TL). SUBJECTS AND METHODS: Cytokine profile of iNKT-cell subsets was evaluated from the peripheral blood of eight oral squamous cell carcinoma (OSCC) patients by flow cytometry and enzyme-linked immunosorbent assay (ELISA), while antitumour activity of iNKT cells was measured by methyl tetrazolium salt assay. RESULTS: CD4(+) (CD4(+) CD8(-)) iNKT subset from OSCC patients showed significant (P < 0.01) expansion and higher IL-4 production following activation with α-GalCer-pulsed DCs, while CD4(-) CD8(-) double negative (DN) and CD8(+) (CD4(-) CD8(+) iNKT subsets produced IFN-γ predominantly. iNKT cells showed significantly (P = 0.02) increased secretion of IFN-γ and enhanced cytotoxicity to KB and SCC-4 tumour cells in response to α-GalCer and TL-pulsed DCs. CONCLUSION: It appears that mutual balance/ratio of iNKT subsets may be important for their effector functions. Selectively expanded DN and CD8(+) iNKT cells with α-GalCer and TL may be a better candidate vaccine for iNKT-cell-based adoptive cancer immunotherapy.

Biodegradation of pyrene and phenanthrene by bacterial consortium and evaluation of role of surfactant.

High molecular weight poly aromatic hydrocarbons (HMW PAHs) are well known for their hydrophobicity and they get strongly adsorbed onto the soil particles. Generally, surfactants facilitate the biodegradation of PAH by enhancing their solubility and desorption of hydrophobic compounds from soil particles. To investigate the role of synthetic surfactant in biodegradation of PAHs, two bacterial strains BP10 and P2 were incubated in soil spiked with pyrene and phenantherene (100 µg g-1of soil each) in isolation and in combination with/without Tween 80. After 14 days of incubation, pyrene and phenantherene were degraded by a combination of BP10 and P2 to the extent of 98% and 99%, respectively. Addition of tween 80 reduced the degradation of pyrene and phenantherene by 35 and 10%, respectively. Biosurfactant produced by selected strains i.e. BP10 and P2 could enhance desorption of pyrene (100 µg g-1of soil) by about 27% and 12%, respectively. However, desorption activity was relatively higher (32 and 29%, respectively) in case of phenanthrene (100 µg g-1of soil) from the spiked soil. Present study showed that in spite of additional chemical surfactant, bioaugmentation of highly petroleum hydrocarbon degrading bacterial combination was very effective in boosting the bioremediation of PAHs- contaminated sites.