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Sunil Kumar

Publications and source records attributed to Sunil Kumar.

At least 19 recordsLinked to original sources

Spatial transcriptomics of primary and metastatic ALK-rearranged NSCLC reveals site-specific adaptations.

INTRODUCTION: Genetic alterations and the tumor microenvironment (TME) influence treatment response in anaplastic lymphoma kinase-rearranged non-small cell lung cancer (ALK+ NSCLC). This study maps site-specific TME adaptations and exploratory risk-associated signatures in lymph node metastases (LNT) to investigate metastatic evolution. METHOD: We applied spatial transcriptomics to profile tumor (PanCK+) and stromal (PanCK-) compartments in a pilot cohort of 16 cases: primary lung tumors (LT, n = 3), LNT (n = 10), and brain metastases (BT, n = 3), with three site-matched non-tumor controls. LNT-derived prognostic signatures were evaluated using The Cancer Genome Atlas-Lung Adenocarcinoma (TCGA LUAD) cohorts. RESULTS: Distinct, site-specific TME features were observed. LNT stroma was enriched in fibroblasts and macrophages, while tumor segments showed increased neutrophils. BT exhibited a macrophage-associated immunosuppressive TME. Tumor cells evolved divergently: LT retained pulmonary identity and showed trend towards translation-associated programs, LNT cells shifted toward senescence and epigenetic remodeling, and BT cells showed activation of Class A/1 (Rhodopsin-like) receptor, GPCR and drug metabolism pathways. In LNT, exploratory risk-associated differences were observed. Low-risk cases (n = 6) showed adaptive immune signatures, whereas high-risk cases (n = 4) showed enrichment for stromal MET signaling and stress-response pathways. Because treatment exposure differed markedly between the risk groups, these observations should be interpreted as hypothesis-generating. TCGA LUAD analysis suggested the broader biological relevance of immune-associated markers, but reflected general LUAD rather than ALK+ specific biology. Discordant associations for GCLC and TIMP1 underscored the importance of spatial context. CONCLUSION: Site-specific microenvironments may influence tumor adaptation across metastatic niches in ALK+ NSCLC. The exploratory risk-associated findings require validation in larger, uniformly treated cohorts.

Humans↗

On the state of protein function prediction: a report on the fourth CAFA challenge.

BACKGROUND: The Critical Assessment of Functional Annotation (CAFA) is a community effort held to understand the field of computational protein function prediction. Every three years, since 2010, the organizers initiate an experiment to collect function predictions on a large set of proteins and then evaluate the performance of predicting methods on a subset of proteins that have accumulated experimental annotations between the submission deadline and the evaluation time. CAFA provides an independent and rigorous assessment of the current state of the art, thus leveling the playing field, highlighting successes, revealing bottlenecks, and offering a forum for the exchange of ideas in protein science. Here, we report the results of the fourth CAFA experiment (CAFA4). RESULTS: CAFA4 featured the participation of 148 methods from 70 research groups on a total of 46,205 unique proteins over a 5-year annotation accumulation phase, the longest in any CAFA. In a comparison across CAFA2-CAFA4 methods, the prediction of Gene Ontology (GO) terms has clearly improved across all three GO aspects and traditional evaluation settings. While not achieving the first rank, several CAFA2 and CAFA3 methods featured in the top ten methods in many evaluations, suggesting that earlier methods still hold relevance. The performance is weaker in the newly introduced "partial knowledge" evaluation category (proteins with experimental annotations before submission deadline that gained additional annotations in the same GO aspect during the annotation accumulation phase), highlighting the need for a new class of methods. The rankings of the methods were stable over the years in traditional evaluation settings, but less so in the new partial knowledge evaluation. Overall, the field continues to progress with some influx of new participants. Sustained efforts will be necessary to substantially advance it.

Journal Article↗

Biosorption of Cr(III) from aqueous solution using algal biomass spirogyra spp.

In the present investigation, a fresh water green algae spirogyra spp. was used as an inexpensive and efficient biosorbent for Cr(III) removal from aqueous solution. The algal biomass was treated with 0.1M NaOH, 0.2M CaCl(2) and 5% HCHO. The biosorption efficiency was compared with untreated biomass. The effects of various physico-chemical parameters were studied, e.g. pH 3.0-6.0, initial metal ions concentration 20-150mgL(-1), algal dose 1.0-3.0gL(-1), and contact time 15-180min, respectively. Biosorption of Cr(III) is highly pH dependent. Maximum 81.02% adsorption of Cr(III) was observed with 0.2M CaCl(2) treated biomass at pH 5.0. Removal of Cr(III) was more than 70% in 45min of contact time with different treated and untreated algal biomass at concentration 30mgL(-1). Maximum metal uptake (Q(max)) was observed as 30.21mgg(-1) with 0.2M CaCl(2) treated algal biomass indicate good biosorbents than other treated and untreated biomass. The high values of correlation coefficient (r(2)<0.90) indicate equilibrium data of treated and untreated form of algal biomass well fitted in Freundlich than Langmuir isotherms model equations.

Adsorption↗

Preliminary study of physico-chemical treatment options for hospital wastewater.

Hospital effluents are loaded with pathogenic microorganisms, partially metabolized pharmaceutical substances, radioactive elements, and other toxic substances. Such effluents if not treated properly can damage the natural environment and create a biological imbalance. This paper points out the areas of concern for hospital wastewater disposal and reports the findings of a limited physico-chemical study of treatment options for hospital effluents conducted at Christian Medical College and Hospital, Vellore, Tamil Nadu. The effluent collected was checked for conventional parameters and subjected to coagulation experiments. The raw and settled effluents were coagulated with FeCl(3), filtered and disinfected. Physico-chemical treatment seems to be an attractive option for the cost-effective disposal of hospital effluents. The results of this study call for further detailed study in this area.

Biodegradation, Environmental↗

Microclusters of inhibitory killer immunoglobulin-like receptor signaling at natural killer cell immunological synapses.

We report the supramolecular organization of killer Ig-like receptor (KIR) phosphorylation using a technique applicable to imaging phosphorylation of any green fluorescent protein-tagged receptor at an intercellular contact or immune synapse. Specifically, we use fluorescence lifetime imaging (FLIM) to report Förster resonance energy transfer (FRET) between GFP-tagged KIR2DL1 and a Cy3-tagged generic anti-phosphotyrosine monoclonal antibody. Visualization of KIR phosphorylation in natural killer (NK) cells contacting target cells expressing cognate major histocompatibility complex class I proteins revealed that inhibitory signaling is spatially restricted to the immune synapse. This explains how NK cells respond appropriately when simultaneously surveying susceptible and resistant target cells. More surprising, phosphorylated KIR was confined to microclusters within the aggregate of KIR, contrary to an expected homogeneous distribution of KIR signaling across the immune synapse. Also, yellow fluorescent protein-tagged Lck, a kinase important for KIR phosphorylation, accumulated in a multifocal distribution at inhibitory synapses. Spatial confinement of receptor phosphorylation within the immune synapse may be critical to how activating and inhibitory signals are integrated in NK cells.

Cell Line↗

Bilateral ankle edema with bilateral iritis.

I report two patient presented to me with bilateral symmetrical ankle edema and bilateral acute iritis. A 42-year-old female of Indian origin and 30-year-old female from Somalia both presented with bilateral acute iritis. In the first patient, bilateral ankle edema preceded the onset of bilateral acute iritis. Bilateral ankle edema developed during the course of disease after onset of ocular symptoms in the second patient. Both patients did not suffer any significant ocular problem in the past, and on systemic examination, all clinical parameters were within normal limit. Lacrimal gland and conjunctival nodule biopsy established the final diagnosis of sarcoidosis in both cases, although the chest x-rays were normal.

Adult↗

Topological alterations in human spermatozoa associated with the polyelectrolytic effect of RISUG.

A new method of male contraception has been developed which results in long-term infertility and has the potential advantage of being reversible. The contraceptive, given the name RISUG (an acronym for Reversible Inhibition of Sperm Under Guidance) is a polyelectrolytic compound and when injected into the lumen of the vas deferens, induces a surface charge imbalance on the sperm membrane system leading to its destabilization. In the present study, morphological and topological alterations in human spermatozoa induced by RISUG have been investigated using atomic force microscopy (AFM). Complete disintegration of the plasma membrane with subsequent rupture and dispersion of the acrosomal contents is observed on treatment with RISUG in vitro. Considerable damage to the midpiece region with significant clustering of the mitochondria and its fusion with the head region is also observed. These observations are in agreement with the significant increase in the volume of RISUG-treated sperm-head region. Topological alterations in the flagellar and midpiece region of RISUG-treated spermatozoa have also been studied.

Acrosome↗

Diagnosis of isolated tuberculous orchitis by fine-needle aspiration cytology.

An isolated tuberculous Orchitis without epididymal involvement is rare. This case report describes an extra pulmonary tuberculosis with exclusively testicular presentation. The confirmatory diagnosis of which was made on FNAC of the testis. A 22-year-old adult presented with unilateral testicular enlargement and scrotal ulcer on the same side. FNAC was performed and subsequent smear examination revealed epitheloid granuloma in a necrotic background. This was suggestive of tubercular orchitis, which was further confirmed by demonstration of very occasional acid fast bacilli in the smear. Isolated tuberculous orchitis is a rare entity; FNAC is a useful first choice of investigation. It provides a successful diagnosis thereby preventing unnecessary orchidectomy.

Adult↗

Thin calcium phosphate coatings on titanium by electrochemical deposition in modified simulated body fluid.

Adherent and optically semitransparent thin calcium phosphate (CaP) films were electrochemically deposited on titanium substrates in a modified simulated body fluid at 37 degrees C. Coatings deposited by using periodic pulsed potentials showed better adhesion and better mechanical properties than coatings deposited with use of a constant potential. Scanning electron microscopy was used to study the morphology of the coatings. The coatings displayed a polydispersed porous structure with pores in the range of a few nanometers to 1 mum. Furthermore, X-ray diffractometry and the O(1s) satellite peaks in X-ray photoelectron spectroscopy indicated that the coatings possessed a similar surface chemistry to that of natural bone minerals. These results were confirmed by inductively coupled plasma optical emission spectrometry, which yielded a Ca:P ratio of 1.65, close to that of hydroxyapatite. Contact mode atomic force microscopy (AFM) showed the average thickness of the coatings was in the order of 200 nm. Root-mean-square (RMS) roughness values, also derived by AFM, were shown to be much higher on the titanium-CaP surfaces in comparison with untreated titanium substrates, with RMS values of about 300 and 110 nm, respectively. Cell culture experiments showed that the CaP surfaces are nontoxic to MG63 osteoblastic cells in vitro and were able to support cell growth for up to 4 days, outperforming the untreated titanium surface in a direct comparison. These easily prepared coatings show promise for hard-tissue biomaterials.

Adhesiveness↗

Adsorption of bisphosphonate onto hydroxyapatite using a novel co-precipitation technique for bone growth enhancement.

Premature bone resorption and remodeling by osteoclasts can limit the longevity of implant fixation and recovery time. Orally administered bisphosphonates (BPs) have been used to inhibit osteoclast action at the implant/bone interface. Ideally, these should be delivered at the interface with the osteoblast-active hydroxyapatite (HA) for maximum effect. This investigation introduces a novel BP loading technique to achieve improved BP release from a simulated body fluid-grown HA (SBF-HA) with the aim of improving implant fixation. A solution co-precipitation technique incorporates the BP (pamidronate) into a thin SBF-HA coating. Surface analysis, using X-ray photoelectron spectroscopy (XPS), of the resultant coating was employed to confirm the presence of the adsorbed BP on the surface of SBF-HA. XPS analysis was also used to determine the optimal adsorption process. Osteoclast cell culture experiments confirmed the biological effectiveness of BP adsorption and proved that the pamidronate was biologically active, causing both decreased osteoclast numbers and decreased resorption.

Adsorption↗

Comparison of the magnetization transfer ratio and fluid-attenuated inversion recovery imaging signal intensity in differentiation of various cystic intracranial mass lesions and its correlation with biological parameters.

PURPOSE: To compare the signal intensity on the fluid attenuated inversion recovery (FLAIR) sequence and magnetization transfer ratios (MTRs) for the differentiation of abscesses from non-abscess cystic brain lesions, and to correlate these MR parameters with the viscosity, viable cell density and total protein concentration of the cystic fluid. MATERIALS AND METHODS: Signal intensity on FLAIR and MTRs from the cystic cavity of lesions were calculated from 33 patients (brain abscess (N = 12) and non-abscess (N = 21)). The fluid from the lesion was aspirated at the time of surgery, and the viscosity, viable cell density, and total protein concentration were measured. RESULTS: Signal intensity on FLAIR correlated significantly with the total protein concentration in abscess (r = 0.60, P < 0.05) and non-abscess lesions (r = 0.41, P < 0.05). However, there was no significant difference (P > 0.05) in the FLAIR signal intensity of the abscess (318.8 +/- 75) and non-abscess group (258 +/- 47). The MTR of the brain abscesses (13 +/- 0.95) was significantly higher (P < 0.05) than that of the non-abscess group (3.5 +/- 0.3). A significant correlation was observed between MTR and viscosity (r = 0.75, P < 0.05), total protein concentration (r = 0.60, P < 0.05), and cell density (r = 0.70, P < 0.05) in brain abscess, and viscosity (r = 0.81, P < 0.05) and total protein concentration (r = 0.41, P < 0.05) in non-abscess lesions. CONCLUSION: It is possible to differentiate brain abscesses from non-abscess cystic lesions using MT imaging. The MTR correlates significantly with the viscosity, viable cell density, and total protein concentration in brain abscess, and with viscosity and total protein concentration in non-abscess lesions. FLAIR signal intensity correlates significantly only with the total protein concentration in abscess and non-abscess lesions.

Adolescent↗

Seminal plasma zinc concentration and alpha-glucosidase activity with respect to semen quality.

This study was conducted to examine the relationship between the concentration of zinc and neutral alpha-glucosidase (NAG) with semen quality. Semen samples from 75 male partners of couples who were attending the Obstetrics and Gynecology Department were analyzed for semen quality. Based on sperm count, the subjects were divided into three groups. Zinc and neutral alpha-glucosidase activity were estimated in seminal plasma. Results showed that mean the alpha-glucosidase activity was lowest among the azoospermic group with respect to oligozoospermic and normozoospermic groups. Mean zinc levels were also lower among azoospermics compared to oligozoospermic and normospermic groups. The difference was statistically significant (p < 0.05). A significant positive correlation was observed between zinc levels and sperm count (r = 0.29, p < 0.05) and zinc and alpha-glucosidase activity (r = 0.31, p < 0.05) in seminal plasma. These results suggest that zinc and neutral alpha-glucosidase seem to play an important role in human reproduction.

Humans↗

A study for evaluation of contaminant transport characteristics through fine-grained soil.

Transport of soluble toxic substances through porous media lead to some significant geoenvironmental problems, for example, leachate migration from municipal and industrial solid waste resulting from unregulated disposal. Advection, dispersion, diffusion, and decay are reported to be the principal mechanisms in such phenomena. Geotechnical properties of the soil also play a significant role in this deterioration. In the present study, laboratory tests were conducted to formulate an appropriate method for assessment of migration of metal ions, such as nickel, through the soil. Relevant kinetic and process parameters, such as aquifer data, surface area, dielectric constant, pH of zero point charge (pHzpc), and permeability were also studied. One-dimensional mathematical modeling was used to describe the dynamics of the process. The present investigation was carried out at an ash pond site of a thermal power plant situated in West Bengal, India.

Environmental Monitoring↗

Removal of aqueous nickel (II) using laterite as a low-cost adsorbent.

The present paper describes the laboratory study of laterite as a low-cost adsorbent for removal of aqueous nickel (II). At pH 7 and a temperature of 30 degrees C, a sorbent dose of 15 mg/L resulted in approximately 90% removal of nickel (II) from its initial concentration of 10 mg/L. A maximum removal of 98% of the adsorbate was observed with an adsorbent particle size of 210 micro with the above conditions. Batch kinetics results were described by fitting in a Langmuir isotherm. Helffrich's half-time equation (Helffrich, 1962) has been applied to evaluate the adsorption process. It appears that film diffusion would be the rate-limiting step. The effect of pH on the sorption process was carried out to a value of 8.0. The removal rate of nickel was found to be the function of pH of the reaction mixture. The rate of nickel uptake by laterite with the decrease in pH value has been explained on the basis of aqueous-complex formation and the subsequent acid-base dissociation at the solid-solution interface.

Adsorption↗

Neurobehavioral effects and hormones profile among spray painters.

A cross-sectional study was conducted in 25 spray painters and 35 control subjects to evaluate neurobehavioral function, and thyroid and reproductive hormones profile. This study indicated higher prevalence of psychological and neurological symptoms, and clinical findings among spray painters when compared with controls. Levels of TSH were significantly (p<0.01) elevated in spray painters over the control group (3.04 +/- 1.53 vs 1.88 +/- 1.07 microIU/ml, mean +/- SD), respectively. Two of the 25 spray painters acquired sub-clinical hypothyroidism, and one subject was detected with overt hypothyroidism. T4 levels were significantly (p<0.05) suppressed in spray painters while T3 was not changed significantly in both the groups. Reproductive hormones (LH, FSH, and testosterone) showed no significant changes in control and spray-painting group. However, two spray painters had abnormally high level of LH (26.43 and 12.22 IU/l; normal range 0.5-10 IU/l). These subjects were also found to have abnormally higher level of FSH (38.63 and 14.11 IU/l; normal range 1.3-11.5 IU/l). An isolated higher level of FSH (39.94 IU/l) was also observed in one spray painter. No abnormality in the level of LH was observed in control group while 3 subjects from this group had abnormally high level of FSH. Testosterone levels were under the normal range (3-12 ng/ ml) in both the groups. This study might suggest that spray painters are at risk of developing neurobehavioral, thyroid and reproductive problems.

Adult↗

Dose adjustment of allopurinol according to creatinine clearance does not provide adequate control of hyperuricemia in patients with gout.

OBJECTIVE: Published guidelines state that allopurinol doses should be adjusted according to creatinine clearance. We investigated whether such dosing provides adequate control of hyperuricemia. METHODS: We studied 250 patients with gout attending rheumatology clinics in South Auckland from 2001 to 2004. Allopurinol dose, creatinine clearance, and serum uric acid (SUA) level were recorded. We analyzed the relationship between recommended allopurinol dose and SUA lowering to <or= 0.36 mmol/l. RESULTS: For patients taking allopurinol, 70.9% were taking recommended doses, based on published allopurinol dosing guidelines. There were 4 (1.6%) patients with cutaneous hypersensitivity reactions to allopurinol, but none of these patients were taking higher than recommended allopurinol doses. The proportion of patients achieving SUA <or= 0.36 mmol/l was lower in those taking recommended doses, compared with those taking higher than recommended doses (19% vs 38.1%; p < 0.01). CONCLUSION: Adherence to published allopurinol dosing guidelines led to suboptimal control of hyperuricemia in this population of patients with gout. Further work is required to clarify the safety and efficacy of allopurinol dose escalation, particularly in patients with renal impairment.

Adult↗