Primary Extraskeletal Falcine Myxoid Chondrosarcoma-A Case Report and Review of Literature.

Intracranial chondrosarcomas are rare malignant lesions. Both skull base and dural-based extraosseous chondrosarcomas have been reported to occur intracranially. Dural-based chondrosarcomas arising from the falx cerebri are rare lesions with only 19 cases reported till date. Although conventional, mesenchymal, and myxoid variants of chondrosarcomas have been reported intracranially, myxoid variant are the rarest with only 17 cases reported till date, among which only 2 were falcine. We are reporting the third case of falcine myxoid chondrosarcoma in a 32-year-old man who presented with seizures and subtle lower limb weakness. Radiological findings were suggestive of an atypical meningioma in the falcine region. Macroscopically total resection of the tumor was done. Histopathological examination confirmed myxoid chondrosarcoma, grade 1. Postoperative period was uneventful, and the patient remains asymptomatic 34 months after the surgery without the application of any adjuvant therapy. Falcine myxoid chondrosarcomas are extremely rare lesions with variable aggressiveness as suggested by the three cases reported till now including the present case.

A Comparative Study of Intralesional Acyclovir vs Immunotherapy for Treatment of Viral Warts.

BACKGROUND: Viral warts are caused by human papillomavirus (HPV), are difficult to treat with conventional modalities, and are cosmetically disfiguring; hence, immunomodulators are being used. The viral origin of warts suggests the antiviral drug acyclovir as a potential therapeutic option. The current study compares the effect of intralesional acyclovir (nucleoside analogue) and intralesional purified protein derivative (PPD) (immunotherapy) in treating various viral warts. METHODOLOGY: Prospective observational comparative study was conducted to determine the efficacy of acyclovir, and PPD administered via the intralesional route in patients with viral warts. The study population was categorized into two groups. One group received intralesional acyclovir, and the other received intralesional PPD. Patients were followed-up with for three months. Outcomes considered in our study were recovery (complete, partial, and no recovery) and side effects like pain, burning sensation, and desquamation. Statistical analysis was carried out by coguide software. RESULTS: In our study total of 40 participants, 20 in each group were included. 25 and 15 were of age <30, and ≥ 30, respectively, while 20 were males, and 20 females. Our study reported 60%, and 30% of complete recovery with intralesional acyclovir treatment and intralesional PPD treatment, respectively, in the twelfth week. However, p-value > 0.05 represented no significance between groups. 90% in the acyclovir-treated group presented with pain, and 100% presented with burning sensation, while in the case of PPD-treated group, 60% presented no side effects and the rest 40% showed pain. CONCLUSIONS: Intralesional acyclovir is more effective in treating viral warts than PPD. The focus is to be laid on anticipated side effects.

Assessment of trace element accumulation in surface sediments off Chennai coast after a major flood event.

The present study was conducted to assess the trace element concentration in marine surface sediments after major flood event of Chennai metropolis, India. Thirty surface samples were collected from off Chennai coast. Trace elements, organic matter, CaCO3, sand-silt-clay and C/N ratios were studied to understand the accumulation dynamics on sediments. The elemental concentration, calcium carbonate and OM distribution suggest that they are derived from urban runoff and transported through Adyar and Cooum Rivers. The enrichment factor reveals that the sediments are enriched by Pb, Cu, Zn, Cr, Co, Ni followed by Fe. The observed Igeo value shows that the samples are contaminated by Pb, Cu and Zn. The elemental concentration of the surface sediments is low when compared to other coastal region except Pb. The elevated level of Pb in the surface sediments is probably due to migration of contaminated urban soil from industrial and transportation sectors into marine environment.

Effects of HCl pretreatment, drying, and storage on the stable isotope ratios of soil and sediment samples.

RATIONALE: Stable isotope (δ(13) C, δ(15) N, δ(34) S values) analysis has become increasingly important for tracing contaminant sources in environments. Pretreatment of environmental samples allows accurate analysis of stable isotope ratios. The pretreatment of a sample and its subsequent preservation could either contaminate or create experimental artifacts affecting the validity of the resulting C/N ratios and the elemental isotopic contents of a sample. METHODS: The effects of acid pretreatment (0.1, 0.5, 1, 2, 5, 13 M HCl) and exposure period (2, 6, 12, 24, and 48 h) on the stable isotopic ratios of marine sediment (MS), river sediment (RS) and terrestrial soil (TS) samples were evaluated. The effects of storage temperatures (-80, -20 and 2°C), storage duration (1 week, 1 to 12 months) and washing steps (1, 2, 3, 5, 7 or 12 times) on the stable isotopic ratios were also considered. The %C, %N and %S, as well as the δ(13) C, δ(15) N, and δ(34) S values, of each sample were measured using continuous flow Elemental Analyzer/Isotope Ratio Mass Spectrometry (EA/IRMS). RESULTS: The HCl treatment was applicable for δ(13) C analysis. However, the acid concentration and duration of exposure that brought about total removal of carbonate for the three sample types varied; e.g. the TS sample required stronger acid and a shorter exposure time. Storage time also had an effect: the δ(13) C values were lower and the δ(15) N and δ(34) S values higher after storage for 300 days. CONCLUSIONS: HCl pretreatment effectively eliminates carbonates and thereby helps δ(13) C analysis of the organic fraction. HCl pretreatment is not recommended for δ(15) N and δ(34) S analysis. Freeze-drying of samples is recommended rather than oven drying. A temperature-dependent change in the isotopic ratios of long-term stored samples was observed during this study; therefore, relatively short-term storage (-80°C) of freeze-dried samples is preferable. Copyright © 2016 John Wiley & Sons, Ltd.

Seasonal variation in nutritional composition of Kappaphycus alvarezii (Doty) Doty-an edible seaweed.

Seasonal variation in the proximate and mineral composition of Kappaphycus alvarezii were investigated in the present study, moreover, the relationship between the nutritive components of this seaweed and the environment were also established. Carbohydrates represented the major portion of the algae (i.e. average total carbohydrate content was 23.01 ± 1.64 g/100 g DW), while the lipid content was the lowest among the constituents investigated (0.39 ± 0.04 to 0.91 ± 0.51 g/100 g DW). The protein content of K. alvarezii varied from 12.69 ± 0.6 to 23.61 ± 0.02 g/100 g DW, and the fiber content varied between 9.68 ± 0.08 to 18.57 ± 0.15 g/100 g DW. Highest total mineral content (29939.61 ± 9340.38 mg/100 g DW) was observed in April 2005, while least values were recorded in January 2006 i.e. (10997.62 ± 1120.26 mg/100 g DW). The Na/K ratio during the study ranged from 0.34 to 0.87. All the samples showed remarkable semi-refined carrageenan (SRC) yield ranging from 42.70 ± 1.07 to 63.73 ± 1.73 % (average 53.90 ± 1.37 %), and, the samples collected during December 2004 and January 2006 demonstrated maximum gel strengths i.e. 743 ± 15.28 and 783.33 ± 15.28 g·cm(-2) respectively. Various environmental parameters influenced the chemical composition of K. alvarezii, and these parameters demonstrated seasonal fluctuations. Moreover, based on the nutritional composition obtained, it could be stated that this seaweed has great scope to be incorporated into several food products as an excellent nutritional supplement, or as a value additive in animal or pet food.

Applicability of stable C and N isotope analysis in inferring the geographical origin and authentication of commercial fish (Mackerel, Yellow Croaker and Pollock).

Globalisation of seafood and aquaculture products and their convenient marketing worldwide, increases the possibility for the distribution of mislabelled products; thereby, underlining the need to identify their origin. Stable isotope analysis is a promising approach to identify the authenticity and traceability of seafood and aquaculture products. In this investigation, we measured carbon and nitrogen stable isotope ratios (δ(13)C and δ(15)N) of three commercial fish, viz. Mackerel, Yellow Croaker and Pollock, originating from various countries. Apart from the species-dependent variation in the isotopic values, marked differences in the δ(13)C and δ(15)N ratios were also observed with respect to the country of origin. This suggests that C and N isotopic signatures could be reliable tools to identify and trace the origin of commercial fish.

Microalgae - A promising tool for heavy metal remediation.

Biotechnology of microalgae has gained popularity due to the growing need for novel environmental technologies and the development of innovative mass-production. Inexpensive growth requirements (solar light and CO2), and, the advantage of being utilized simultaneously for multiple technologies (e.g. carbon mitigation, biofuel production, and bioremediation) make microalgae suitable candidates for several ecofriendly technologies. Microalgae have developed an extensive spectrum of mechanisms (extracellular and intracellular) to cope with heavy metal toxicity. Their wide-spread occurrence along with their ability to grow and concentrate heavy metals, ascertains their suitability in practical applications of waste-water bioremediation. Heavy metal uptake by microalgae is affirmed to be superior to the prevalent physicochemical processes employed in the removal of toxic heavy metals. In order to evaluate their potential and to fill in the loopholes, it is essential to carry out a critical assessment of the existing microalgal technologies, and realize the need for development of commercially viable technologies involving strategic multidisciplinary approaches. This review summarizes several areas of heavy metal remediation from a microalgal perspective and provides an overview of various practical avenues of this technology. It particularly details heavy metals and microalgae which have been extensively studied, and provides a schematic representation of the mechanisms of heavy metal remediation in microalgae.

Studies on the functional properties of protein concentrate of Kappaphycus alvarezii (Doty) Doty - an edible seaweed.

Protein concentrate (PC) of Kappaphycus alvarezii (cultivated on the West coast of India), was extracted and its functional properties were evaluated. The K. alvarezii PC contained 62.3 ± 1.62% proteins. At pH 12, the nitrogen solubility of this PC was 58.72 ± 1.68% in the presence of 0.5M NaCl. The emulsifying and foaming properties of this PC varied with time and pH. However, it formed remarkably stable emulsions with Jatropha oil after 720 min (i.e. E720=53.67 ± 1.59). On the other hand, maximum foaming ability (53.33 ± 2.31%) of the PC was recorded at pH 4.0. This PC had high oil (1.29 ± 0.20 ml oil/g PC) and water absorption capacity (2.22 0.04 ml H2O/g PC). DSC analysis revealed thermal transitions at about 109.25°C at neutral pH. The results obtained in this investigation suggest the suitability of K. alvarezii PC as an inexpensive source of protein; thus this PC could be incorporated into several value-added food products.

Selective Dual Inhibitors of the Cancer-Related Deubiquitylating Proteases USP7 and USP47.

Inhibitors of the cancer-related cysteine isopeptidase human ubiquitin-specific proteases 7 (USP7) and 47 (USP47) are considered to have potential as cancer therapeutics, owing to their ability to stabilize the tumor suppressor p53 and to decrease DNA polymerase ß (Polß), both of which are potential anticancer effects. A new class of dual small molecule inhibitors of these enzymes has been discovered. Compound 1, a selective inhibitor of USP7 and USP47 with moderate potency, demonstrates inhibition of USP7 in cells and induces elevated p53 and apoptosis in cancer cell lines. Compound 1 has been shown to demonstrate modest activity in human xenograft multiple myeloma and B-cell leukemia in vivo models. This activity may be the result of dual inhibition of USP7 and USP47. To address issues regarding potency and developability, analogues of compound 1 have been synthesized and tested, leading to improvements in potency, solubility, and metabolic reactivity profile. Further optimization is expected to yield preclinical candidates and, ultimately, clinical candidates for the treatment of multiple myeloma, prostate cancer, and other cancers.

The multifaceted roles of USP7: new therapeutic opportunities.

The deubiquitylating enzyme USP7 (HAUSP) sits at a critical node regulating the activities of numerous proteins broadly characterized as tumor suppressors, DNA repair proteins, immune responders, viral proteins, and epigenetic modulators. Aberrant USP7 activity may promote oncogenesis and viral disease making it a compelling target for therapeutic intervention. Disclosed drug discovery programs have identified inhibitors of USP7 such as P005091 with cellular proof of concept and anti-proliferative activity in cancer models. Taken together, USP7 inhibitors hold promise as a new strategy for the treatment of disease.

Targeting the ubiquitin E3 ligase MuRF1 to inhibit muscle atrophy.

Progressive muscle wasting, also known as myopathy or muscle atrophy is a debilitating and life-threatening disorder. Myopathy is a pathological condition of many diseases including cancer, diabetes, COPD, and AIDS and is a natural consequence of inactivity and aging (sarcopenia). Muscle atrophy occurs when there is a net loss of muscle mass resulting in a change in the balance between protein synthesis and protein degradation. The ubiquitin pathway and specific ubiquitin pathway enzymes have been directly implicated in the progression of atrophy. The ubiquitin E3 ligase Muscle-specific RING Finger E3 ligase (MuRF1) is upregulated and increases protein degradation and muscle wasting in numerous muscle atrophy models. The inhibition of MuRF1 could be a novel mechanism to prevent or reverse muscle wasting associated with various pathologies. We screened a small molecule library for inhibitors to MuRF1 activity and identified P013222, an inhibitor of MuRF1 autoubiquitylation. Further, P013222 was shown to inhibit MuRF1-dependent substrate ubiquitylation, and was active in inhibiting MuRF1 in a cellular atrophy model. Thus MuRF1 can be targeted in a specific manner and produce positive results in cellular atrophy models.

Novel approach for characterizing ubiquitin E3 ligase function.

The ubiquitin-proteasome system is central to the regulation of numerous cellular events, and dysregulation may lead to disease pathogenesis. E3 ubiquitin ligases typically function in concert with E1 and E2 enzymes to recruit specific substrates, thereby coordinating their ubiquitylation and subsequent proteasomal degradation or cellular activity. E3 ligases have been implicated in a wide range of pathologies, and monitoring their activity in a rapid and cost-effective manner would be advantageous in drug discovery. The relative lack of high-throughput screening (HTS)-compliant E3 ligase assays has significantly hindered the discovery of E3 inhibitors. Herein, the authors describe a novel HTS-compliant E3 ligase assay platform that takes advantage of a ubiquitin binding domain's inherent affinity for polyubiquitin chains, permitting the analysis of ubiquitin chain formation in an E3 ligase-dependent manner. This assay has been used successfully with members of both the RING and HECT families, demonstrating the platform's broad utility for analyzing a wide range of E3 ligases. The utility of the assay platform is demonstrated by the identification of inhibitors of the E3 ligase CARP2. As the number of E3 ligases associated with various disease states increases, the ability to quantitate the activity of these enzymes in an expeditious manner becomes imperative in drug discovery.

Microchip gel electrophoresis with programmed field strength gradients for ultra-fast detection of canine T-cell lymphoma in dogs.

This paper describes the applicability of microchip gel electrophoresis using a programmed field strength gradients (MGE-PFSG) method coupled with a polymerase chain reaction (PCR) for the ultra-fast diagnosis of canine T-cell lymphoma. The variable region in the T-cell receptor gamma (TCRgamma) gene from a T-cell lymphoma was used in PCR amplification. The contributions of the various parameters, including the effects of the molecular weight, concentration of the sieving matrix and field strength in MGE, were examined. 0.5% poly (ethyleneoxide) (PEO, M(r) 8000000) was used as the sieving matrix for the ultra-rapid separation of the amplified-PCR products (90 and 130-bp DNA fragments) from the PFSG at an effective length of 20mm in a glass microchip. The PCR products (90 and 130-bp DNA) of the T-cell lymphoma were analyzed within 41.7+/-0.1s, 15.5+/-0.2s and only 7.0+/-0.1s using a low-constant field strength, high-constant field strength and the PFSG, respectively. When 11 clinical samples were analyzed using the MGE-PFSG method, there was a 100% correlation with those obtained using conventional slab gel electrophoresis. The ultra-fast detection and rapid separation capabilities of MGE-PFSG make it an efficient tool for diagnosing T-cell lymphoma in clinical samples with high sensitivity.

Ligand-independent pathway that controls stability of interferon alpha receptor.

Ligand-specific negative regulation of cytokine-induced signaling relies on down regulation of the cytokine receptors. Down regulation of the IFNAR1 sub-unit of the Type I interferon (IFN) receptor proceeds via lysosomal receptor proteolysis, which is triggered by ubiquitination that depends on IFNAR1 serine phosphorylation. While IFN-inducible phosphorylation, ubiquitination, and degradation requires the catalytic activity of the Tyk2 Janus kinase, here we found the ligand- and Tyk2-independent pathway that promotes IFNAR1 phosphorylation, ubiquitination, and degradation when IFNAR1 is expressed at high levels. A major cellular kinase activity that is responsible for IFNAR1 phosphorylation in vitro does not depend on either ligand or Tyk2 activity. Inhibition of ligand-independent IFNAR1 degradation suppresses cell proliferation. We discuss the signaling events that might lead to ubiquitination and degradation of IFNAR1 via ligand-dependent and independent pathways and their potential physiologic significance.

A case study of real-world tailpipe emissions for school buses using a 20% biodiesel blend.

Numerous laboratory studies report carbon monoxide, hydrocarbon, and particulate matter emission reductions with a slight nitrogen oxides emission increase from engines operating with biodiesel and biodiesel blends as compared to using petroleum diesel. We conducted a field study on a fleet of school buses to evaluate the effects of biodiesel use on gaseous and particulate matter fuel-based emission factors under real-world conditions. The field experiment was carried out in two phases during winter 2004. In January (phase I), emissions from approximately 200 school buses operating on petroleum diesel were measured. Immediately after the end of the first phase measurement period, the buses were switched to a 20% biodiesel blend. Emission factors were measured again in March 2004 (phase II) and compared with the January emission factors. To measure gaseous emission factors we used a commercial gaseous remote sensor. Particulate matter emission factors were determined with a combination of the gaseous remote sensor, a Lidar (light detection and ranging), and transmissometer system developed at the Desert Research Institute of Reno, NV, U.S.A. Particulate matter emissions from school buses significantly increased (up to a factor of 1.8) after the switch from petroleum diesel to a 20% biodiesel blend. The fuel used during this campaign was provided by a local distributor and was independently analyzed at the end of the on-road experiment. The analysis found high concentrations of free glycerin and reduced flash points in the B 100 parent fuel. Both measures indicate improper separation and processing of the biodiesel product during production. The biodiesel fuels used in the school buses were not in compliance with the U.S.A. ASTM D6751 biodiesel standard that was finalized in December of 2001. The U.S.A. National Biodiesel Board has formed a voluntary National Biodiesel Accreditation Program for producers and marketers of biodiesel to ensure product quality and compliance with the ASTM standard. The results of our study underline the importance of the program since potential emission benefits from biodiesel may be reduced or even reversed without appropriate fuel quality control on real-world fuels.

Preconcentration and solid phase extraction method for the determination of Co, Cu, Ni, Zn and Cd in environmental and biological samples using activated carbon by FAAS.

2-{[1-(2-Hydroxynaphthyl) methylidene] amino} benzoic acid (HNMABA) was synthesized for solid phase extraction (SPE) to the determination of Co, Cu, Ni, Zn and Cd in environmental and biological samples by flame atomic absorption spectrophotometry (FAAS). These metals were sorbed as HNMABA complexes on activated carbon (AC) at the pH range of 5.0+/-0.2 and eluted with 6 ml of 1M HNO3 in acetone. The effects of sample volume, eluent volume and recovery have been investigated to enhance the sensitivity and selectivity of proposed method. The effect of interferences on the sorption of metal ions was studied. The concentration of the metal ions detected after preconcentration was in agreement with the added amount. The detection limits for the metals studied were in the range of 0.75-3.82 microg ml(-1). The proposed system produced satisfactory results for the determination of Co, Cu, Ni, Zn and Cd metals in environmental and biological samples.

Oncogenic BRAF regulates beta-Trcp expression and NF-kappaB activity in human melanoma cells.

Mutational activation of BRAF is a frequent event in human malignant melanomas suggesting that BRAF-dependent signaling is conducive to melanoma cell growth and survival. Previously published work reported that melanoma cells exhibit constitutive anti-apoptotic nuclear factor kappaB (NF-kappaB) transcription factor activation triggered by proteolysis of its inhibitor IkappaB. IkappaB degradation is dependent upon its phosphorylation by the IkappaB kinase (IKK) complex and subsequent ubiquitination facilitated by beta-Trcp E3 ubiquitin ligase. Here, we report that melanocytes expressing a conditionally oncogenic form of BRAF(V600E) exhibit enhanced beta-Trcp expression, increased IKK activity and a concomitant increase in the rate of IkappaBalpha degradation. Conversely, inhibition of BRAF signaling using either a broad-spectrum Raf inhibitor (BAY 43-9006) or by selective knock-down of BRAF(V600E) expression by RNA interference in human melanoma cells leads to decreased IKK activity and beta-Trcp expression, stabilization of IkappaB, inhibition of NF-kappaB transcriptional activity and sensitization of these cells to apoptosis. Taken together, these data support a model in which mutational activation of BRAF in human melanomas contributes to constitutive induction of NF-kappaB activity and to increased survival of melanoma cells.

Phycoremediation of heavy metals by the three-color forms of Kappaphycus alvarezii.

In the present investigation, three living color forms (brown, green and pale yellow) of Kappaphycus alvarezii were examined for their biosorption ability in the laboratory. The brown color form proved to be an excellent metal biosorbent, i.e. it could adsorb good amount of cadmium 3.064 mg/100 gf.wt. and cobalt 3.365 mg/100 gf.wt. It also removed 2.799 mg/100 gf.wt. of chromium. The green color form absorbed 2.684, 3.43 and 2.692 mg/100 gf.wt. of cadmium, cobalt and chromium, respectively. In contrast, the pale yellow form removed almost equal proportion of cadmium 0.961 mg/100 gf.wt. and chromium 0.942 mg/100 gf.wt. It also removed 1.403 mg/100 gf.wt. cobalt. Thus, the living color forms of this seaweed could form an effective biosorbent material for removal of heavy metals.

Facile and sensitive spectrophotometric determination of vanadium in various samples.

Novel reactions were developed for facile, sensitive and selective rapid spectrophotometric determination of trace amounts of vanadium(V) in various samples. The methods were based on the interactions of 3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH) with N-(1-naphthyl)ethylenediamine dihydrochloride (NEDA) in the presence of vanadium to give blue colored derivative or on oxidation of dopamine hydrochloride (DPH) by vanadium in acidic medium and coupling with MBTH to yield pink color derivative. The blue color derivative having an absorbance maximum at 595nm was stable for 9 days and the pink color derivative with λ(max) 526nm for 5 days. Beer's law is obeyed for vanadium in the concentration range 0.05-6.0µgml(-1) (blue color derivative) and 0.06-7.0µgml(-1) (pink color derivative), respectively. The optimum reaction conditions and other important analytical parameters were established. Interference due to various non-target ions was also investigated. The proposed methods were applied to the analysis of vanadium(V) in environmental, biological, pharmaceutical and steel samples. The performance of proposed method was evaluated in terms of Student's t-test and variance ratio F-test that indicates the significance of proposed method over reported method.

Studies of selenium in environmental samples and synthetic mixtures by spectrophotometry.

A rapid, highly sensitive and selective spectrophotometric method for the determination of traces of selenium(IV) is described. The method is based on oxidation of p-nitroaniline by selenium(IV) followed by coupling reaction with N-(1-naphthalene-1-yl)ethane-1,2-diamine dihydrochloride (NEDA) in neutral medium to give red colored derivative with lambda(max) 515 nm and is stable for more than 10 days at 35 degrees C. Beer's law is obeyed for selenium(IV) in the concentration range of 0.02-3.2 microg ml(-1) at the wavelength of maximum absorption. The optimum reaction conditions and other analytical parameters were investigated to enhance the sensitivity of the present method. The detailed study of various interferences made the method more selective. The proposed method was successfully applied to the analysis of selenium in polluted water, natural water samples, plant material, soil samples, and synthetic mixtures. The results obtained were agreed with the reported methods at the 95% confidence level. The performance of proposed method was evaluated in terms of Student's t-test and Variance ratio f-test which indicates the significance of proposed method over reported method.