In normal and cancer cells, successful cell division requires accurate duplication of chromosomal DNA. All cells require a multiprotein DNA duplication system (replisomes) for their existence. However, death of normal cells in our body occurs through the apoptotic process. During apoptotic process several crucial genes are downregulated with the upregulation of caspase pathways, leading to ultimate degradation of genomic DNA. In metastatic cancer cells (SKBR-3, MCF-7, and MDA-462), this process is inhibited to achieve immortality as well as overexpression of the enzymes for the synthesis of marker molecules. It is believed that the GSL of the lacto family such as Le(X), SA-Le(X), Le(Y), Le(a), and Le(b) are markers on the human colon and breast cancer cells. Recently, we have characterized that a few apoptotic chemicals (cis-platin, L-PPMP, D-PDMP, GD3 ganglioside, GD1b ganglioside, betulinic acid, tamoxifen, and melphalan) in low doses kill metastatic breast cancer cells. The apoptosis-inducing agent (e. g., cis-platin) showed inhibition of DNA polymerase/helicase (part of the replisomes) and also modulated (positively) a few glycolipid-glycosyltransferase (GSL-GLTs) transcriptions in the early stages (within 2 h after treatment) of apoptosis. These Lc-family GSLs are also present on the surfaces of human breast and colon carcinoma cells. It is advantageous to deliver these apoptotic chemicals through the metastatic cell surfaces containing high concentration of marker glycolipids (Lc-GSLs). Targeted application of apoptotic chemicals (in micro scale) to kill the cancer cells would be an ideal way to inhibit the metastatic growth of both breast and colon cancer cells. It was observed in three different breast cancer lines (SKBR-3, MDA-468, and MCF-7) that in 2 h very little apoptotic process had started, but predominant biochemical changes (including inactivation of replisomes) started between 6 and 24 h of the drug treatments. The contents of replisomes (replisomal complexes) during induction of apoptosis are not known. It is known that DNA helicase activities (major proteins catalyze the melting of dsDNA strands) change during apoptotic induction process. Previously DNA Helicase-III was characterized as a component of the replication complexes isolated from carcinoma cells and normal rapid growing embryonic chicken brain cells. Helicase activities were assayed by a novel method (combined immunoprecipitation-ROME assay), and DNA polymerase-alpha activities were determined by regular chain extension of nicked "ACT-DNA," by determining values obtained from +/- aphidicolin added to the incubation mixtures. Very little is known about the stability of the "replication complexes" (or replisomes) during the apoptotic process. DNA helicases are motor proteins that catalyze the melting of genomic DNA during replication, repair, and recombination processes. In all three breast carcinoma cell lines (SKBR-3, MCF-7, and MDA-468), a common trend, decrease of activities of DNA polymerase-alpha and Helicase-III (estimated and detected with a polyclonal antibody), was observed, after cisplatin- and L-PPMP-induced apoptosis. Previously our laboratory has documented downregulation (within 24-48 h) of several GSL-GLTs with these apoptotic reagents in breast and colon cancer cells also. Perhaps induced apoptosis would improve the prognosis in metastatic breast and colon cancer patients.
This paper reports on the classification of Hindi (language) words with respect to deep dyslexia phenomena as found during a linguistic investigation of specific errors as shown by children with dyslexia (CWD) during reading. The analysis is based on the data collected throughout an academic year from a total of forty-six children identified as dyslexic, having Hindi as a mother tongue or first language, and studying in class second to fifth. The findings are organised under four themes; first is similar meaning and the same language, second is similar meaning but different language, third is different orthography and different meaning but share a relationship, and fourth is different words but have some resemblance in orthography but differ in „matraa‟. One another possibility was also considered as fifth theme i.e. incoherent, but no details came under this out of the data collected. It was found that despite differences in the linguistic contexts of English and Hindi, deep dyslexia crosses language boundaries. The derived considerations are discussed which will perhaps work as a foundation, provide some reflections for further research, and hope to convey comprehension to some extent of how deep dyslexia reflects in words of Hindi language.
Received: January 04, 2021 Revised: January 27, 2021 Accepted: January 29, 2021 Published Online: March 31, 2021 Parenting holds tremendous significance in today’s world as quality parenting facilitates the development of social and emotional competence in a child. The present study explores the dual role of domestic workers as workers and parents. Domestic Workers work from dawn to dusk to take care of their employees’ families. The obvious question arises: who takes care of their children, back home? As a parent, Domestic workers with their odd working hours and low or no literacy rate are nowadays trying to overcome the socio-economic challenges as well as handicaps of the profession by getting involved in their children’s academics. This paper investigates the effects of the length of working hours and education levels of domestic worker parents on their academic involvement with the children. The present study uses a descriptive survey research design to find out the relationship between academic involvement and work hours. The data was subjected to appropriate descriptive and inferential statistics. The results indicate a negative relationship between work hours and academic involvement. It is also revealed that higher education level to be associated with better academic involvement. The study thus calls for further intervention by schools and the government to motivate parents. Parent-teacher meetings may be of help in this respect along with workshops and governmentsponsored programs to educate the parents to support them to climb up the socio-economic ladder through their children.
Protocols for assay of 24 different Glycolipid-Glycosyltransferases (GSL-GLTs) of the eukaryotic systems are described. Problems of quantitating the activities in crude membranes are also described. Different separation methods (for separation of substrate, donors, and the product of the reaction) have been described based on the paper chromatography or high voltage paper electrophoresis in 1.0% Na2B4O7. Liquid Scintillation counting system was used for quantitation of the enzymatic product. In the assay of each GSL-GLT it is recommended to compare the selected method to be used with the exact conditions used by the authors published previously. As a test case for these assays the following kinetic parameters for Lactosylceramide Synthase, GalT-2 (UDP-Gal: Glc-Cer β1-4-galactosyltransferase), (Km of glucosylceramide = 1.65 × 10-4 M; Km for UDP-Gal = 0.5 × 10-4 M; V max is determined in the presence of optimum detergent concentrations (2-15 mg/ml of Cutscum-Triton X-100, 2:1); Mn++ and Mg++, 10-20 mM) has been reported. The importance of use of GalT-2 assay method (as a model system) in the purified Golgi-rich membranes from 13-day-old embryonic chicken brains (13-ECB) is described.
Spectrin-based proteinaceous membrane skeletal network has been found to be implicated in membrane disorders like hereditary spherocytosis (HS). HS greatly affects eryptosis via loss of membrane asymmetry which is seen to be the case in haemoglobin disorders like thalassemia and sickle cell disease as well. The biological implications of the status of membrane asymmetry are strongly correlated to spectrin interactions with aminophospholipids, e.g. PE and PS. Fluorescence and X-ray reflectivity (XRR) measurements of spectrin interactions with small unilamellar vesicles (SUVs) and cushioned bilayers of phospholipids, respectively, were studied. Both the XRR and fluorescence measurements led to the characterization of spectrin orientation on the surface of lipid bilayer of phosphatidylcholine (PC) and PC/aminophospholipid mixed membrane systems showing formation of a uniform layer of spectrin on top of the mixed phospholipid bilayer. Fluorescence studies show that spectrin interacts with PC and phosphatidylethanolamine (PE)/phosphatidylserine (PS) membranes with binding dissociation constants (Kd) in the nanomolar range indicating the role of spectrin in the maintenance of the overall membrane asymmetry of erythrocytes.
Background: The role of the teacher is of immense importance in early years schooling of any children. Dyslexia is one of the most common learning disability which causes difficulty in reading and distracts the progress of the children in various aspects including their academic achievements, and later on, introduces various other complications. To overcome these cumbersome problems teachers need to behave more responsible and prudent when the learners are children with dyslexia. Aims: The present study has explored the views and experiences of special educators towards academic performance and classroom difficulties faced by dyslexic children during the teaching-learning process, and also made an effort to know the need and nature of help provided to facilitate learning. Methods: The study was conducted with purposively selected special educators of selected schools situated in the Delhi region and, serving the children with special educational needs. The measure for the above domain was developed in the form of a questionnaire, to suit the background and the aim of the study, and administered to the selected special educators. In furtherance of the answered questionnaire, the experiences, and perceptions regarding schooling, learning, needs, and nature of dyslexic children were discussed in details, with the respective respondent. Results: The findings position special educators as strategic agents, who actively negotiate a range of obstacles, resolve and handle the problems of children with dyslexia to ensure their learning and continuity in school. They are having a system designed to support them, help each one at some point in their education. Conclusion: Particularly, the perceptions and perspectives of special educators forge a large difference in the learning and academic achievement of dyslexic children. There is potential waiting to be unlocked in dyslexic children, and teaching them, if done well, is the most fulfilling of tasks.
Background: Socio-economic status of a family is a key factor in parenting and nurturing as well as schooling and education of children. Due to socio- economic disadvantage, they suffer from inferiority and marginalisation from the mainstream of this society. These marginalised populations become incompetence and have difficulty in coping with the educational system, resulted in lower academic achievement and further higher level of behavioral problems and emotional problems. Aim: To compare academic achievement, behavioural and emotional problem in marginalised children living at the hostel and living with parents. Sample: The sample size consisted of sixty children, aged between 8-13 years, studying in class 3rd to 5th, out of which thirty were living in the hostel and another thirty were living with parents. Methods: The children were examined for behavioural and emotional problems by using DPCL, and progress report used for academic achievement. Results: The statistical findings showed that the children living with parents had the lesser severity of emotional problems than children living at the hostel, but both had no significantly differ in terms of behavioural problems and academic achievements. The children with less behavioural and emotional problems found better in academic achievement than the children having more behavioural and emotional problems.
The normal cells in their life cycle die through apoptosis (programmed cell death or degradation of genomic DNA). On the other hand, metastatic cancer cells die mostly by Necrosis where toxic gene products come out through the holes on the cancer cell surface to induce necrotic death‐effect on normal cells. In cancer cells, the following chemical could inhibit blocked steps for apoptosis: cis‐platin (commonly used drug for testicular cancer treatment), Betulinic acid (a naturally occurring triterpene), L‐PPMP, D‐PDMP (inhibitor of GlcT [ceramide: glucosyltransferase]), Tamoxifen (commonly used drug for breast cancer treatment), and Melphalan (Golgi bodies scrambler). When three clones of metastatic breast cancer cells (SKBR‐3, MCF‐7 and MDA468) were treated with these apoptotic reagents separately, they induced apoptosis [activated Caspases (‐3, ‐8, or ‐9)] and down‐regulated the genes for cancer markers like sialo‐LeX (determined by DNA‐microarray studies). Targeted application of apoptotic chemicals to kill the cancer cells would be an ideal way for breast cancer therapy. Support or Funding Information Supported by NIH‐CA‐14764 and NIH‐NS‐18005
Bikunin (Bik) and uristatin (Uri) impacted cellular signaling of kidney proximal tubular, kidney gluomerlar, muscle, and carcinoma cells. Cell cultures were induced with Bik and Uri at 12-40 mg/L and compared to unexposed cell cultures. The balance in serine protease trypsin activity was shifted to complete trypsin inhibition. Cell proliferation was slowed to 50 %. Cell death by apoptosis signaling though caspases, was not activated by the presence of Bik or Uri. Proliferation signaling though the mitogen-activated protein kinases (MAPK) was active. Phosphatidylinositol 3-kinase (PIK3) and protein kinase B (Akt) signaling were activated. Cell death occurs through a non-programmed cell death. Exposed cells showed increased release of a membrane-bound protein, dipeptidyl peptidase 4 (DPP-4). Membrane disruption was also evidenced by phosphatidylserine (PS) externalization measured by binding a fluorescence dye (PSS-380). Exposed cells were depleted of intercellular calcium as shown by using calcium-binding fluorescence dye (Fluo-4). Blockage of the Ca2+ sensitive potassium (K-Ca) channels (or calcium-activated potassium (BK) channels) is thought to lower the intracellular Ca2+. All of the information was supported by a kidney cell model, of Bik/Uri being protective of immune mediated apoptosis and proliferation during the inflammatory process, but causing cell loss by decreased renal regeneration by Akt-PIK3 signaling.
New biosimilar apoptotic agents identified during our recent studies can be employed as a new generation of anti-cancer drugs after being properly delivered to the patients by a proper drug delivery system. These agents regulate at gene level as evidenced by both translational and transcriptional studies. In order to study glyco-gene regulation, we used four clonal metastatic cancer cells of colon and breast cancer-tissue origin (Colo-205, SKBR-3, MDA-468, and MCF-7). The glyco-genes for synthesis of SA-Lex and SA-Lea (which contain N-acetylglucosamine, sialic acid, and fucose) in these cells was modulated differentially at various phases induced by l-PPMP, d-PDMP (inhibitor of glucosylceramide biosynthesis), Betulinic Acid (a triterpinoid isolated from the bark of certain trees and used for cancer treatment in China), Tamoxifen (a drug in use in the west for treatment of early stages of the disease in breast cancer patients), and cis-platin (an inhibitor of DNA biosynthesis used for testicular cancer patients) when used for induction of apoptosis in the above mentioned cell lines. Biosimilarities of these chemicals reside in their killing abilities of these highly metastatic cells by apoptosis. Within 2–6 h, transcriptional modulation of a number of glyco-genes was observed by DNA micro-array (containing over 340 glyco-genes attached to the glass cover slips) studies. Under a long incubation time (24–48 h) almost all of the glyco-gene products, glycolipid: glycosyltransferases (GLTs) were downregulated. The cause of these glyco-gene regulations during apoptotic induction in metastatic carcinoma cells is unknown and needs future investigations for further explanations. At least two GSL-GLT activities (GLTs) of Basu-Roseman pathway2 catalyzing the biosynthesis of GD1a and GD3 gangliosides and more than five GSL: GLTs in the SA-LeX pathway2 have been regulated. Most of these glyco-genes are expressed in the early stages (7–17 days) of embryonic chicken-brain development and lowered in the adult stage. However, the mechanism of regulation of the enzymatic activities of these GLTs in the synthesis of SA-LeX (human cancer cell marker) is unknown. Our recent attempt of in vitro Glyco-gene regulation in apoptotic metastatic cells may lead us to explain the in vivo Glyco-gene regulation in normal or diseased animal organs.
The present study was conducted with the objective of finding out the perceptions of teachers towards child with dyslexia. This study was conducted at schools in Delhi region. Many misperceptions were also identified based on how long teachers had taught, whether teachers had specialist certificate or training to teach child with dyslexia, the school from which teachers earned their teaching degree, and overall beliefs’ about child with dyslexia. Significance of the findings in relation to the wider inclusive educational ideology is discussed and suggestions are made about the child with dyslexia.
The study was conducted with the objective of finding out the classroom process and provisions related to children with dyslexia from teachers’ perspective. This study was conducted at schools of Delhi region. Significance of the findings in relation to the wider inclusive educational ideology is discussed and suggestions are made by the investigator on the basis of the findings of the study.
Evidence indicates that blood group-related Lewis (Le) antigens (glycosphingolipids: GSLs and Glycoproteins: GPs) are tumor-associated cell surface molecules. The Lea, Leb, LeX, LeY, and their sialosyl-derivatives, all N-acetylglucosaminyl-containing glycoconjugate antigens, are overexpressed on the surfaces of breast, colon, and ovarian cancer cells during metastasis. A few inhibitors of GSLs (l-/d-PPMP) and DNA (cisplatin) biosynthesis, betulinic acid (a herbal origin of a triterpenoid used for cancer treatment in China), melphalan, and disialosylgangliosides (GD3 and GD1b) induced apoptosis (intrinsic mitochondrial or extrinsic receptor-mediated pathways) in human breast (SKBR-3, MCF-7, and MDA-468) and colon (Colo-205) cells. These chemicals are suggested to be potential anticancer drugs. In this review, we try to compare our recent observations with reported observations from many other laboratories. We discuss the induction of apoptosis in breast and other cancer cells by various new chemicals. We also discuss the biosynthesis and regulation of GSLs in nonapoptotic and apoptotic cancer cells.
Gangliosides, the acidic glycosphingolipids (GSLs) containing N-acetylgalactosamine and sialic acid are ubiquitous in the central nervous system. At least six DSL-glycosyltransferase activities (GLTs Gangliosides, the acidic glycosphingolipids (GSLs) containing N-acetylgalactosamine and sialic acid (or NAc-Neuraminic acid) are ubiquitous in the central nervous system. At least six GSL-glycosyltransferase activities (GLTs) of Basu-Roseman pathway catalyzing the biosynthesis of these gangliosides have been characterized in developing chicken brains. Most of these glyco-genes are expressed in the early stages (7-17 days) of brain development and lowered in the adult stage, but the cause of reduction of enzymatic activities of these GLTs in the adult stages is not known. In order to study glyco-gene regulation we used four clonal metastatic cancer cells of colon and breast cancer tissue origin (Colo-205, SKBR-3, MDA-468, and MCF-3). The glyco-genes for synthesis of SA-LeX and SA-LeA (which contain N-acetylglucosamine, sialic acid and fucose) in these cells were modulated differently at different phases (between 2 and 48 h) of apoptotic inductions. L-PPMP, D-PDMP (inhibitor of glucosylceramide biosynthesis), Betulinic Acid (a triterpinoid isolated from bark of certain trees and used for cancer treatment in China), Tamoxifen a drug in use in the west for treatment of early stages of the disease in breast cancer patients), and cis-platin (an inhibitor of DNA biosynthesis used for testicular cancer patients) were used for induction of apoptosis in the above-mentioned cell lines. Within 2-6 h, transcriptional modulation of a number of glyco-genes was observed by DNA-micro-array (containing over 300 glyco genes attached to the glass cover slips) studies. Under long incubation time (24-48 h) almost all of the glyco-genes were downregulated. The cause of these glyco-gene regulations during apoptotic induction in metastatic carcinoma cells is unknown and needs future investigations for further explanations. These apoptotic agents could be employed as a new generation of anti-cancer drugs after properly delivered to the patients.
The process of apoptosis is usually triggered by various signals that may have originated extracellularly or intracellularly [1] (Fig. 33.1). The apoptotic signaling initiating from an extracellular source is called an “extrinsic pathway” [2]. The extrinsic apoptotic inducers could be small molecules, such as nitric oxide, hormones such as estrogen [3], or cytokines such as a tumor necrosis factor (TNF-alpha) [4–7]. The death receptor (DR) family plays the most crucial role in transducing the extracellular apoptotic signal to the cytosol apoptotic machinery [8]. The DR family is part of the TNF-receptor superfamily and is usually activated by several cytokines called death ligands. Eight members of the DR family have been identified to date. Although the names of the DRs have varied since the initial discovery of each member, the most common names for each have now been accepted. These are DR1-TNFR1, DR2-CD95, DR3-TRAMP, DR4-TRAILR1, DR5-TRAILR2, DR-6, EDAR, and NGF-R.
The functions of glycosphingolipids on the eukaryotic cell membranes during the onset of oncogenic processes and cell death are not well understood. Inhibitors of glycosphingolipid biosynthesis (L‐PPMP and D‐PDMP) and DNA‐biosynthesis inhibitor (cis‐platin) were recently found to trigger apoptosis in human breast carcinoma cells (SKBR‐3, MCF‐7, and MDA‐468) through either intrinsic or extrinsic apoptotic pathways. These anti‐cancer inhibitors increase ceramide concentration. Apoptotic effects in these cells were determined by activationof caspases (‐3, ‐8, and ‐9) and fluorescent studies using PS‐binding PSS‐380 dye, and intracellular membrane‐binding AKS‐O dye. A time‐dependent scrambling of intracellular membranes was observed after treatment with D‐PDMP upto 6‐ hours. The neolacto‐series glycolipid (SA‐LeX) is distributed mostly on the outer lamella of plasma membranes of human metastatic breast cancer cells. The direct analyses of these glyco‐molecules suggest they alter their structures during the onset of oncogenic processes. Regulation of glycosyltransferase (GLTs) activities involved in the biosynthesis of SA‐LeX is reported in cells treated with L‐PPMP. DNA‐microarrays designed for screening over 340 Glyco‐related genes, transcriptional up‐regulation of several GLTs (in the biosyntheses of Sialo‐LeX and Sialo‐Lea ) was observed with L‐PPMP. GLT‐ activities and gene expressions will be compared with the cells treated with D‐PDMP. Down‐regulation of GLT activities and up‐regulation of some GLT mRNA suggest a tight regulation of these enzymes by signal transduction pathways. 11