Down-conversion luminescence nanocomposites based on nitrogen-doped carbon quantum dots@bioplastic for applications in optical displays, LEDs and UVC tubes.

Carbon quantum dots (CQDs)-based composites as luminous down-conversion materials are becoming more popular due to several advantages such as steady fluorescence, ease of functionalization, tailoring of emission in the visible range, and so on. We report an inexpensive and environmentally sustainable synthesis of fluorescent nitrogen doped-CQDs produced from Cissus quadrangularis, a low-cost plant precursor with therapeutic value. The morphological, structural, and physicochemical features of the material were carefully investigated. Under UV stimulation (365 nm), almost spherical shaped N-CQDs with an average diameter of 5.1 nm were discovered to generate yellow-green fluorescence, have excellent photostability, and strong water solubility, with a quantum yield of up to 5 %. Furthermore, as a solid-phase dispersion matrix for CQDs, ecologically friendly and biodegradable bioplastic is appealing. The down-conversion of solid-state fluorescence of LEDs and UVC tubes was demonstrated by creating a nanocomposite by inserting N-CQDs into the solid matrix of a wheat starch-based bioplastic. Furthermore, employing constructed quantum dot-based optical displays, down-converted LEDs, and UVC tubes, the impacts of varied CQD concentrations and pH sensitivity were examined.

Development and application of reverse transcription-loop mediated isothermal amplification assay for sensitive detection of groundnut bud necrosis virus infecting potato.

Reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed for detection of groundnut bud necrosis virus (GBNV) causing potato stem necrosis disease. The isothermal temperatures, reaction periods and concentrations of reaction mixture were optimized where, the assay worked well at 65 °C for 50 min, 6 U of WarmStart Bst 2.0 DNA polymerase, 1.4 mM dNTPs and 2.0 mM MgSO4. The optimized assay proved to be specific to GBNV with no cross reactivity to other viruses infecting potato in India. The specificity of RT-LAMP assay was found to be 100 fold more sensitive than that of RT-PCR. The developed assay was applied for the detection of GBNV from 80 potato leaf samples where 24 samples were found infected which was confirmed by RT-PCR. It was concluded that the RT-LAMP assay developed for detection of GBNV was specific, sensitive and suitable for its use in virus indexing under potato seed production programme.

Spraying of dsRNA molecules derived from Phytophthora infestans, along with nanoclay carriers as a proof of concept for developing novel protection strategy for potato late blight.

BACKGROUND: Phytophthora infestans is a late blight-causing oomycetes pathogen. It rapidly evolves and adapts to the host background and new fungicide molecules within a few years of their release, most likely because of the predominance of transposable elements in its genome. Frequent applications of fungicides cause environmental concerns. Here, we developed target-specific RNA interference (RNAi)-based molecules, along with nanoclay carriers, that when sprayed on plants are capable of effectively reducing late blight infection. RESULTS: Targeted the genes unique to sporulation, early satge infection and the metabolism pathway stages based on in an our own microarray data. We used nanoclay as a carrier for sorbitol dehydrogenase, heat shock protein 90, translation elongation factor 1-α, phospholipase-D like 3 and glycosylphosphatidylinositol-anchored acidic serine-threonine-rich HAM34-like protein double-stranded (ds)RNAs, which were assessed by culture bioassay, detached leaf assay and spray methods, and revealed a reduction in growth, sporulation and symptom expression. Plants sprayed with multigene targeted dsRNA-nanoclay showed enhanced disease resistance (4% disease severity) and less sporulation (<1 × 103 ) compared with plants sprayed with dsRNA alone. CONCLUSION: The use of nanoclay with multigene targeted dsRNA was assumed to be involved in effective delivery, protection and boosting the action of RNAi as a spray-induced gene silencing approach (SIGS). A significant reduction in growth, sporulation, disease severity and decreased gene expression authenticates the effects of SIGS on late blight progression. This study demonstrated as a proof of concept the dsRNA-nanoclay SIGS approach, which could be used as an alternative to chemical fungicides and transgenic approaches to develop an environmentally friendly novel plant protection strategy for late blight. © 2022 Society of Chemical Industry.

Nanocomposite of functional silver metal containing curcumin biomolecule model systems: Protein BSA bioavailability.

Curcumin, a constituent of Curcuma longa L-Zingiberaceae is used in traditional Indian and worldwide medicine and shows anticancer and antioxidant properties. Curcumin has numerous biological and pharmacological activities but due to its hydrophobic nature, the major drawback is poor absorption and rapid elimination, rendering curcumin with the tag of a poor biomaterial. Hence, there is a need to develop functional metal containing curcumin model systems (FMCCMS) as a metallo-biomolecule to enhance the bioavailability of curcumin. We designed the interaction of silver metal ion with curcumin to form curcumin-silver nanocomposite (CURC-AgNCP) via ultrasonic synthetic route. Formations of FMCCMS were characterized by spectroscopic techniques. The crystalline face-centered cubic pattern and particle size of the nanocomposite was evaluated using X-ray diffraction and high-resolution transmission electron microscopy. The bonding of silver metal to curcumin was confirmed by X-ray photon spectroscopy. Interaction of the nanocomposite with bovine serum albumin (BSA) protein was performed using excitation, emission, and circular dichroism spectroscopy. In binding interaction of BSA, the negative value of ∆S° (-358.04 J mol-1 K-1) and ∆H° (-129.42 KJ mol-1) demonstrates the hydrophilic nature of the nanocomposite. The binding distance r evaluated according to the Forster resonance energy transfer theory and was 4.69 nm for CURC-AgNCP, which suggested non-radiative transfer of energy between CURC-AgNCP and BSA. The role of FMCCMS metallo-biomolecule CURC-AgNCP in medicine for cancer activity can have immense importance and hence we performed Sulphorhodamine B based in-vitro cytotoxicity assay on human breast cancer Michigan Cancer Foundation-7 cell line.

Genetic diversity studies based on morpho-pathological and molecular variability of the Sclerotinia sclerotiorum population infecting potato (Solanum tuberosum L.).

White mould or stem rot, caused by Sclerotinia sclerotiorum (Lib.) de Bary, is a devastating fungal disease found in major potato cultivation areas worldwide. The aim of this study was to characterize genetic diversity in the S. sclerotiorum population from the main potato producing regions of India by means of morphological (mycelial growth, colony colour, number and distribution pattern of sclerotia) and molecular characteristics, as well as to evaluate the virulence of S. sclerotiorum isolates in potato for the first time. Among the S. sclerotiorum population analyzed, high phenotypic and genotypic diversity were observed. Using all the morphological characteristics, a dendrogram was constructed based on Gower's similarity coefficient that distributed all the isolates into three clusters at the 0.62 similarity coefficient. Carpogenic germination of apothecia revealed that larger sclerotia produced a greater number of apothecia while smaller sclerotia produced fewer apothecia. Pathogenicity test results revealed that out of 25 isolates, seven were highly aggressive, 14 were moderate and four had low aggressiveness, whilst isolates from Punjab were more pathogenic than those of Uttar Pradesh. Phylogenetic analysis of universal rice primer polymorphism showed high genetic variability within the isolates that grouped all the isolates in three evolutionary lineages in the resulting dendrogram and showed partial relationship with geographical locations of the isolates. Further, the findings suggest the occurrence of higher heterogeneity and genetic diversity among the S. sclerotiorum isolates that indicates the existence of both clonal and sexual reproduction in the pathogen population of potato producing areas in India.

Development of a visual detection method for Potato virus S by reverse transcription loop-mediated isothermal amplification.

A reverse transcription-loop mediated isothermal amplification (RT-LAMP) assay was developed to detect the Potato virus S (PVS) in potato. Two sets of six novel primers that recognize the coat protein gene sequence of the PVS were designed and RT-LAMP assay was optimized for the parameters such as different concentrations of primers, MgSO4, betaine, dNTPs, Bst DNA polymerase, temperature and duration. The RT-LAMP was carried out under isothermal conditions without the thermal cycler using PVS infected leaf and tuber samples, LAMP specific primers with amplification at 65 °C for 60 min, and 80 °C for 5 min. The results were assessed by gel electrophoresis and visual observation of colour change using SYBR Green I dye. The detection limit of the developed RT-LAMP assay was determined and compared with a conventional reverse transcription-polymerase chain reaction (RT-PCR). RT-LAMP was found 100 times more sensitive than RT-PCR. The optimized RT-LAMP assay is robust, reliable, sensitive and convenient for the detection of the PVS in infected potato tubers including asymptomatic plants. No cross-reactions were observed with healthy plants and other potato viruses. The assay is economical and can be employed in large scale testing of potato plants against PVS under healthy seed potato production programme.

Non-vitamin K antagonist oral anticoagulants (NOACs) for thromboembolic prevention, are they safe in congenital heart disease? Results of a worldwide study.

BACKGROUND: Current guidelines consider vitamin K antagonists (VKA) the oral anticoagulant agents of choice in adults with atrial arrhythmias (AA) and moderate or complex forms of congenital heart disease, significant valvular lesions, or bioprosthetic valves, pending safety data on non-VKA oral anticoagulants (NOACs). Therefore, the international NOTE registry was initiated to assess safety, change in adherence and quality of life (QoL) associated with NOACs in adults with congenital heart disease (ACHD). METHODS: An international multicenter prospective study of NOACs in ACHD was established. Follow-up occurred at 6 months and yearly thereafter. Primary endpoints were thromboembolism and major bleeding. Secondary endpoints included minor bleeding, change in therapy adherence (≥80% medication refill rate, ≥6 out of 8 on Morisky-8 questionnaire) and QoL (SF-36 questionnaire). RESULTS: In total, 530 ACHD patients (mean age 47 SD 15 years; 55% male) with predominantly moderate or complex defects (85%), significant valvular lesions (46%) and/or bioprosthetic valves (11%) using NOACs (rivaroxaban 43%; apixaban 39%; dabigatran 12%; edoxaban 7%) were enrolled. The most common indication was AA (91%). Over a median follow-up of 1.0 [IQR 0.0-2.0] year, thromboembolic event rate was 1.0% [95%CI 0.4-2.0] (n = 6) per year, with 1.1% [95%CI 0.5-2.2] (n = 7) annualized rate of major bleeding and 6.3% [95%CI 4.5-8.5] (n = 37) annualized rate of minor bleeding. Adherence was sufficient during 2 years follow-up in 80-93% of patients. At 1-year follow-up, among the subset of previous VKA-users who completed the survey (n = 33), QoL improved in 6 out of 8 domains (p ≪ 0.05). CONCLUSIONS: Initial results from our worldwide prospective study suggest that NOACs are safe and may be effective for thromboembolic prevention in adults with heterogeneous forms of congenital heart disease.

Endothelin-1 regulation is entangled in a complex web of epigenetic mechanisms in diabetes.

Endothelial cells (ECs) are primary targets of glucose-induced tissue damage. As a result of hyperglycemia, endothelin-1 (ET-1) is upregulated in organs affected by chronic diabetic complications. The objective of the present study was to identify novel transcriptional mechanisms that influence ET-1 regulation in diabetes. We carried out the investigation in microvascular ECs using multiple approaches. ECs were incubated with 5 mM glucose (NG) or 25 mM glucose (HG) and analyses for DNA methylation, histone methylation, or long non-coding RNA- mediated regulation of ET-1 mRNA were then performed. DNA methylation array analyses demonstrated the presence of hypomethylation in the proximal promoter and 5' UTR/first exon regions of EDN1 following HG culture. Further, globally blocking DNA methylation or histone methylation significantly increased ET-1 mRNA expressions in both NG and HG-treated HRECs. While, knocking down the pathogenetic lncRNAs ANRIL, MALAT1, and ZFAS1 subsequently prevented the glucose-induced upregulation of ET-1 transcripts. Based on our past and present findings, we present a novel paradigm that reveals a complex web of epigenetic mechanisms regulating glucose-induced transcription of ET-1. Improving our understanding of such processes may lead to better targeted therapies.

Chronic kidney damage in the adult Fontan population.

OBJECTIVES: 1) To determine the accuracy of estimated GFR (eGFR) as compared to directly measured GFR (mGFR) in the adult Fontan population; 2) to determine the true prevalence of chronic kidney damage (CKD) as determined by uACR AND eGFR. METHODS: Prospective study of 81 patients Fontan patients (≥18years) followed at St. Paul's Hospital, University of British Columbia. CKD-EPI and MDRD equations used to calculate eGFR, mGFR determined by 99mTc-DTPA renal dynamic imaging and urine albumin to creatinine ratios were calculated. RESULTS: The mGFR was 93±27ml/min/1.73m2: 28 (53%) had an mGFR<90ml/min/1.73m2 and 1 (2%) had an mGFR <60ml/min/1.73m2. There was a modest correlation between mGFR and eGFR (EPI/MDRD) (r=0.50, p<0.0001 and r=0.54, p<0.0001 respectively). Both eGFR (EPI) (bias 27.0; 95% CI 18.0-27.7ml/min/m2, p<0.0001) and eGFR (MDRD) (bias 15.5; 95% CI 7.6-17.4ml/min/m2, p<0.0001) overestimated GFR as compared to mGFR. Among patients with an eGFR (EPI)/(MDRD) >90ml/min/1.73m2, 50% and 46% respectively had an mGFR <90ml/min/1.73m2. Significant albuminuria (>3mg/mmol) was present in 33% and upwards of 32% of patients with a normal eGFR (MDRD/EPI) had evidence of CKD with uACR >3mg/mmol. Using combined criteria of eGFR <90ml/min/1.73m2 and/or uACR >3mg/mmol, 46% of patients had evidence of CKD. CONCLUSIONS: This study draws attention to the need for stringent CKD screening as an important proportion of CKD is currently not being detected. Mild undetected CKD, an early marker of end organ damage, may also be an early sign of Fontan failure that requires warrants further research.

Positive Aspects of Caregiving and Its Correlates among Caregivers of Bipolar Affective Disorder.

OBJECTIVE: To evaluate the positive aspects of caregiving and its correlates (socio-demographic and clinical variables, caregiver burden, coping, quality of life, psychological morbidity) in the primary caregivers of patients with bipolar affective disorder (BPAD). METHODS: A total of 60 primary caregivers of patients with a diagnosis of BPAD were evaluated on the Scale for Positive Aspects of Caregiving Experience (SPACE) and the Hindi version of Involvement Evaluation Questionnaire, Family Burden Interview Schedule (FBIS), modified Hindi version of Coping Checklist, shorter Hindi version of the World Health Organization Quality of Life (WHOQOL-BREF), and Hindi translated version of 12-item General Health Questionnaire (GHQ-12). RESULTS: Caregivers of patients with BPAD had the highest mean score in the SPACE domain of Motivation for caregiving role (2.45), followed by Caregiver satisfaction (2.38) and Caregiving personal gains (2.20). The mean score was the lowest for the domain of Self-esteem and social aspect of caring (2.01). In terms of correlations, age of onset of BPAD had a negative correlation with various domains of SPACE. The mean number of total lifetime affective and depressive episodes correlated positively with Self-esteem and social aspect of caring. Caregiver satisfaction correlated negatively with FBIS domains of Disruption of routine family activities, Effect on mental health of others, and subjective burden. Coercion as a coping mechanism correlated positively with domains of Caregiving personal gains, Caregiver satisfaction, and the total score on SPACE. Three (Physical health, Psychological health, Environment) out of 5 domains of the WHOQOL-BREF correlated positively with the total SPACE score. No association was noted between GHQ-12 and SPACE scores. CONCLUSION: Positive caregiving experience in primary caregivers of patients with BPAD is associated with better quality of life of the caregivers.

Longitudinal sequential biventricular assessment in adults with transposition of the great arteries and relationship with adverse outcomes.

BACKGROUND: In a cohort of congenitally corrected transposition of the great arteries (cc-TGA) and transposition of the great arteries after atrial switch procedure (d-TGA) the study objectives were: 1) to assess the change of quantitative systemic right ventricle (sRV) parameters over time and; 2) to examine the relationship of quantitative sRV parameters with adverse clinical outcomes. METHODS AND RESULTS: Single-center cohort study that included 49 (39%) cc-TGA and 76 (61%) d-TGA patients >18years who had at least one MUGA sRV assessment, 18/39 had more than one respectively. The primary clinical endpoint was all-cause mortality, heart transplantation and/or heart failure hospitalization. At a median clinical follow-up of 7years following the first MUGA, the primary endpoint occurred more often in cc-TGA versus d-TGA patients (18 (36.7%) vs. 9 (11.8%), p=0.03). Median time between the MUGA assessments was 5.8 (cc-TGA) and 4.9years (d-TGA). At last MUGA follow-up: 6 (33%) cc-TGA/14 (36%) d-TGA patients showed a significant decline in sRVEF (>5%); 6 (33%) cc-TGA/17 (44%) d-TGA patients had a significant increase in sRVEDVi; and 7 (39%) cc-TGA/19 (49%) PA-TGA patients had a significant increase in sRVESVi. Baseline sRV parameters were not associated with the primary end point or sRV changes over time. CONCLUSIONS: An important proportion of both patient cohorts demonstrated a significant change in sRV parameters over time and these are likely related to multiple factors that vary between individuals given population heterogeneity. The TGA patients have distinct clinical trajectories with increased adverse heart failure outcomes in the cc-TGA population and sRV parameters were not related to adverse heart failure events in either group.

Structural and functional changes to the retina and optic nerve following panretinal photocoagulation over a 2-year time period.

PurposeTo evaluate long-term structural and functional changes to the retina and optic nerve following panretinal photocoagulation (PRP) in diabetic retinopathy (DR) patients.MethodsParticipants were patients with DR requiring PRP and control patients with DR not requiring PRP. The Heidelberg retinal tomography (HRT) and optical coherence tomography (OCT) were performed to analyze the optic nerve and macula. Best-corrected visual acuity (BCVA) and visual field (VF) testing were done to measure central and peripheral vision. Wide-field fluorescein angiogram was performed to monitor the progression of diabetic ischemia. The primary outcome measure was to determine the degree of retinal and optic nerve changes before and after PRP.ResultsThere was a non-significant thickening of the macula and retinal nerve fiber layer at 6 months post laser that recovered by 24 months. Mean perfused ratio was significantly increased (P=0.02) at 12 and 24 months post laser. Independently grading patient stereophotographs, grader 1 indicated there was a non-significant increase in cup to disk ratio post laser, while grader 2 indicated a significant increase at 6 (P=0.04), 12 (P=0.02), and 24 months (P=0.005). There was a significant VF decrease (P≤0.02) at 12 and 24 months post laser with BCVA showing a non-significant trend of deteriorating results.ConclusionDespite an improvement in peripheral perfusion, there was a significant progressive decline of peripheral VF over the study period. Clinical grading of the optic nerve was more unreliable following PRP, despite the absence of significant morphological changes as detected by the OCT and HRT.

Complete mitogenome mapping of potato late blight pathogen, Phytophthora infestans A2 mating type.

Complete mitochondrial genome of Phytophthora infestans, A2 mating type (MT) with a size of ≅37,767 bp was sequenced. A total of 53 protein-coding genes are predicted on both strands, including 25 tRNA, 2 rRNA, and 18 respiratory proteins. Gene order of A2MT was consistent with that established in A1, despite high level of polymorphism in both coding and non-coding regions. The mtDNA of A2MT was found to have 99.5% and 99.4% homology with Ia and Ib, whereas 94.7% and 94.3% with IIa and IIb, respectively. Study of repeats revealed a dinucleotide (AT)9 specific to A1 and homology of cox1 gene sequence revealed the relationship among 50 Phytophthora species.

Voice outcomes after thyroidectomy without superior and recurrent laryngeal nerve injury: VoiSS questionnaire and GRBAS tool assessment.

Voice symptoms are frequently reported early after thyroidectomy, even in the absence of laryngeal nerves injury. We evaluated the short-term outcomes of these functional alterations. Thirty-nine patients were enrolled in a prospective observational trial, evaluating voice function before and 3 months after uncomplicated thyroidectomy, using VoiSS as assessed using a validated patient rated questionnaire; and perceptual voice analysis using GRBAS scale (Grade, Roughness, Breathiness, Asthenia, Strain). Impact of dysphonia on patient's life using VoiSS questionnaire revealed differences between pre- and postoperative assessment. There was statistically significant worsening in the impairment subgroup of VoiSS (p = 0.027). GRBAS evaluation was consistent between the three independent raters but showed differences between pre- and postoperative voice assessment. Age, TSH and a preoperative finding of laryngopharyngeal reflux significantly predicted quality of voice after thyroid surgery (all p < 0.004), as identified by the GRBAS assessment tool, but not type of surgery, gender or smoking status; although prediction of total variance in changes of voice was modest (r 2 = 0.07). Voice changes may occur after thyroidectomy without evident laryngeal nerve injury. Patients should be made aware of possible mild changes in voice even after uncomplicated thyroid surgery and this might be considered to be part of the informed consent.

Association of p53 codon72 Arg>Pro polymorphism with susceptibility to nasopharyngeal carcinoma: evidence from a case-control study and meta-analysis.

Tumor suppressor p53 is a critical player in the fight against cancer as it controls the cell cycle check point, apoptotic pathways and genomic stability. It is known to be the most frequently mutated gene in a wide variety of human cancers. Single-nucleotide polymorphism of p53 at codon72 leading to substitution of proline (Pro) in place of arginine (Arg) has been identified as a risk factor for development of many cancers, including nasopharyngeal carcinoma (NPC). However, the association of this polymorphism with NPC across the published literature has shown conflicting results. We aimed to conduct a case-control study for a possible relation of p53 codon72 Arg>Pro polymorphism with NPC risk in underdeveloped states of India, combine the result with previously available records from different databases and perform a meta-analysis to draw a more definitive conclusion. A total of 70 NPC patients and 70 healthy controls were enrolled from different hospitals of north-eastern India. The p53 codon72 Arg>Pro polymorphism was typed by polymerase chain reaction, which showed an association with NPC risk. In the meta-analysis consisting of 1842 cases and 2330 controls, it was found that individuals carrying the Pro allele and the ProPro genotype were at a significantly higher risk for NPC as compared with those with the Arg allele and the ArgArg genotype, respectively. Individuals with a ProPro genotype and a combined Pro genotype (ProPro+ArgPro) also showed a significantly higher risk for NPC over a wild homozygote ArgArg genotype. Additionally, the strength of each study was tested by power analysis and genotype distribution by Hardy-Weinberg equilibrium. The outcome of the study indicated that both allele frequency and genotype distribution of p53 codon72 Arg>Pro polymorphism were significantly associated with NPC risk. Stratified analyses based on ethnicity and source of samples supported the above result.

Consequence of neo-adjuvant chemotherapy on morphology of breast carcinoma: A systematic evaluation.

BACKGROUND: Neo-adjuvant chemotherapy (NAC) in locally advanced breast cancer is the present trend. Following NAC, a considerable alteration of morphology occurs in the tumor. AIMS: To study effects of NAC on morphology of breast carcinoma and to evaluate the pathologic response (PR). MATERIALS AND METHODS: A total of 39 surgically resected mastectomy specimens of patients of invasive locally advanced breast carcinoma who received NAC were evaluated for macroscopic and microscopic (by routine stains and immunohistochemistry) alteration of morphology. RESULTS: Macroscopically well-defined tumor noted in 25 cases (64.1%) and in the rest (14 cases, 35.9%), only fibrotic areas identified. Microscopic examination identified malignant cells in 29 (74.4%), significant chronic inflammation in 24 (61.5%), hyalinized fibrosed stroma in 25 (64.1%) and necrosis in 11 (28.2%) cases. Immunohistochemistry assisted in differentiating malignant cells from histiocytes. In 15 cases (38.5%), axillary lymph nodes isolated where fibrosis seen in 12 (30.8%) and malignant cell in 8 (20.5%) cases. In 34 cases where the pre-treatment biopsy were available, complete pathologic response (pCR) and partial pathologic response (pPR) were achieved in 7 (20.6%) and 23 (67.4%) cases respectively. DISCUSSION: Protocol of systematic evaluation of morphological changes is different in cases of a patient treated by NAC. Nature of malignancy was difficult to categorize as morphology of typical breast carcinomas were altered. Sometimes, immunohistochemistry is advantageous as routine H and E stains are not sufficient to isolate malignant cells in fibrotic and necrotic areas. Appropriate morphological evaluation of the mastectomy specimen is absolutely crucial for assessment of PR and subsequent management.

DNA damage-induced ephrin-B2 reverse signaling promotes chemoresistance and drives EMT in colorectal carcinoma harboring mutant p53.

Mutation in the TP53 gene positively correlates with increased incidence of chemoresistance in different cancers. In this study, we investigated the mechanism of chemoresistance and epithelial-to-mesenchymal transition (EMT) in colorectal cancer involving the gain-of-function (GOF) mutant p53/ephrin-B2 signaling axis. Bioinformatic analysis of the NCI-60 data set and subsequent hub prediction identified EFNB2 as a possible GOF mutant p53 target gene, responsible for chemoresistance. We show that the mutant p53-NF-Y complex transcriptionally upregulates EFNB2 expression in response to DNA damage. Moreover, the acetylated form of mutant p53 protein is recruited on the EFNB2 promoter and positively regulates its expression in conjunction with coactivator p300. In vitro cell line and in vivo nude mice data show that EFNB2 silencing restores chemosensitivity in mutant p53-harboring tumors. In addition, we observed high expression of EFNB2 in patients having neoadjuvant non-responder colorectal carcinoma compared with those having responder version of the disease. In the course of deciphering the drug resistance mechanism, we also show that ephrin-B2 reverse signaling induces ABCG2 expression after drug treatment that involves JNK-c-Jun signaling in mutant p53 cells. Moreover, 5-fluorouracil-induced ephrin-B2 reverse signaling promotes tumorigenesis through the Src-ERK pathway, and drives EMT via the Src-FAK pathway. We thus conclude that targeting ephrin-B2 might enhance the therapeutic potential of DNA-damaging chemotherapeutic agents in mutant p53-bearing human tumors.

Squamous cell carcinoma of the upper aerodigestive tract in exclusive smokers, chewers, and those with no habits.

BACKGROUND: Tobacco consumption is the major risk factor for developing head and neck squamous cell cancer (SCC). The site of development of HNSCC may depend on the way the tobacco is consumed. While laryngeal cancers are more common among smokers, oral cancers are more common among tobacco chewers. Since the use of smokeless tobacco is increasing, it is important to know whether this difference is restricted only to site wise distribution or it has other clinical and pathological implications. PATIENTS AND METHODS: We analyzed a prospectively collected dataset of HNSCC patients other than nasopharyngeal cancers attending our outpatient department at a single unit of the head and neck services at Tata Memorial Hospital, Mumbai, India, between January 2010 and September 2011. There were 747 eligible patients and were divided into three groups: Those with chewing as the only habit (chewers), those with smoking as the only habit (smokers), and those with no habits. Patients with regular use of alcohol were excluded from the study. The clinical and pathological parameters were analyzed. RESULTS: Of the 747 patients, the tobacco chewers formed 69.3% followed by smokers (19.5%) and patients with no habits (11.1%). Majority of smokers were men (98%). Site distribution revealed patients with chewing as the only habit had oral cancers (most commonly gingivobuccal complex cancers) as the most common site and those with smoking as the only habit had larynx as the most common site. In patients with no habits, oral tongue was found to be the most common site. No statistically significant pathological differences were observed in between these groups in patients who underwent surgery (n = 366) at the initial modality of treatment. CONCLUSIONS: There is a direct relationship between the form of tobacco use and site of appearance of HNSCC. However, there are no differences in clinical or pathological parameters between HNSCC caused by tobacco chewing or tobacco smoking.

Two Dimensional Effective Electron Mass at the Fermi Level in Quantum Wells of III-V, Ternary and Quaternary Semiconductors.

In this paper we study the influence of strong electric field on the two dimensional (2D)effective electron mass (EEM) at the Fermi level in quantum wells of III-V, ternary and quaternary semiconductors within the framework of k x p formalism by formulating a new 2D electron energy spectrum. It appears taking quantum wells of InSb, InAs, Hg(1-x)Cd(x)Te and In(1-x)Ga(x)As(1-y)P(y) lattice matched to InP as examples that the EEM increases with decreasing film thickness, increasing electric field and increases with increasing surface electron concentration exhibiting spikey oscillations because of the crossing over of the Fermi level by the quantized level in quantum wells and the quantized oscillation occurs when the Fermi energy touches the sub-band energy. The electric field makes the mass quantum number dependent and the oscillatory mass introduces quantum number dependent mass anisotropy in addition to energy. The EEM increases with decreasing alloy composition where the variations are totally band structure dependent. Under certain limiting conditions all the results for all the cases get simplified into the well-known parabolic energy bands and thus confirming the compatibility test. The content of this paper finds three applications in the fields of nano-science and technology.