• Title/Summary/Keyword: Human genetics

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Tyrosine 1045 Codon Mutations in Exon 27 of EGFR are Infrequent in Oral Squamous Cell Carcinomas

  • Tushar, Mehta Dhaval;Ramanathan, Arvind
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.7
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    • pp.4279-4282
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    • 2013
  • Background: The activation and inactivation of receptor tyrosine kinases are tightly regulated to ensure faithful replication of cells. After having transduced extracellular growth activating signals, activated EGFR is subjected to downregulation either by clathrin mediated endocytosis or c-Cbl mediated proteasome degradation depending on the ligand concentration. c-Cbl is an ubiquitin ligase which requires a phosphorylated tyrosine residue at position 1045 in the cytoplasmic domain of EGFR to interact and add ubiquitin molecules. While activating mutations in exons 19 and 21 have been associated with the development of several cancers, the status of mutations at tyrosine 1045 coding exon 27 of EGFR remain to be investigated. Consistently, defective phosphorylation at 1045 has been associated with sustained phosphorylation of EGFR in non-small lung carcinomas. Hence in the present study we investigated the genetic status of the tyrosine 1045 coding site within exon 27 of EGFR gene to explore for possible occurrence of mutations in this region, especially since no studies have addressed this issue so far. Materials and Methods: Tumor chromosomal DNA isolated from thirty five surgically excised oral squamous cell carcinoma tissues was subjected to PCR amplification with intronic primers flanking the tyrosine 1045 coding exon 27 of EGFR gene. The PCR amplicons were subsequently subjected to direct sequencing to elucidate the mutation status. Results: Sequence analysis identified no mutations in the tyrosine 1045 codon of EGFR in any of the thirty five samples that were analyzed. Conclusions: The lack of identification of mutation in the tyrosine 1045 codon of EGFR suggests that mutations in this region may be relatively rare in oral squamous cell carcinomas. To the best of our knowledge, this study is the first to have explored the genetic status of exon 27 of EGFR in oral squamous cell carcinoma tissue samples.

Leu432Val Polymorphism of CYP1B1 is Not Associated with Squamous Cell Carcinoma of Esophagus - a Case-Control Study from Kashmir, India

  • Shah, Idrees Ayoub;Mehta, Promila;Lone, Mohd Maqbool;Dar, Nazir Ahmad
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.13
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    • pp.5337-5341
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    • 2015
  • Background: Individual susceptibility to cancer has been attributed to polymorphisms in xenobiotic metabolizing genes. To evaluate the association of the Leu432Val polymorphism of cytochrome P4501B1 (CYP1B1) with esophageal squamous cell carcinoma (ESCC), we conducted a case control study in Kashmir, India, an area with a relatively high incidence of ESCC. Materials and Methods: We recruited 404 histopathologically confirmed ESCC cases, and an equal number of controls, individually matched for sex, age and district of residence to respective cases. Information was obtained on various dietary, lifestyle and environmental factors in face to face interviews, using a structured questionnaire, from each subject. Genotypes were analysed by polymerase chain reaction, restriction fragment length polymorphism and sequencing of randomly selected samples. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). Results: Among the three possible variants, we did not find any Leu432Leu genotype of CYP1B1 in the study population and the genotypic distribution of Val432Val and Leu432Val carriers was nearly equal in both cases (89.6% and 10.4%) and controls (88.9% and 11.1%) respectively. We did not find any risk associated with this polymorphism in the current study (OR = 0.64; 95% CI: 0.55 - 1.64). Conclusions: The study indicates that (Leu432Val) polymorphism of CYP1B1, is not associated with ESCC risk. However, replicative studies with larger sample size are needed to substantiate the findings.

Attitudes of South Asian Women to Breast Health and Breast Cancer Screening: Findings from a Community Based Sample in the United States

  • Poonawalla, Insiya B.;Goyal, Sharad;Mehrotra, Naveen;Allicock, Marlyn;Balasubramanian, Bijal A.
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.20
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    • pp.8719-8724
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    • 2014
  • Background: Breast cancer incidence is increasing among South Asian migrants to the United States (US). However, their utilization of cancer screening services is poor. This study characterizes attitudes of South Asians towards breast health and screening in a community sample. Materials and Methods: A cross-sectional survey based on the Health Belief Model (HBM) was conducted among South Asians (n=124) in New Jersey and Chicago. The following beliefs and attitudes towards breast cancer screening were assessed-health motivation, breast self-examination confidence, breast cancer susceptibility and fear, and mammogram benefits and barriers. Descriptive statistics and Spearman rank correlation coefficients were computed for HBM subscales. Findings: Mean age of participants was 36 years with an average 10 years stay in the US. Most women strived to care for their health ($3.82{\pm}1.18$) and perceived high benefits of screening mammography ($3.94{\pm}0.95$). However, they perceived lower susceptibility to breast cancer in the future ($2.30{\pm}0.94$). Conclusions: Increasing awareness of breast cancer risk for South Asian women may have a beneficial effect on cancer incidence because of their positive attitudes towards health and breast cancer screening. This is especially relevant because South Asians now constitute one of the largest minority populations in the US and their incidence of breast cancer is steadily increasing.

Effects of Regular Endurance Exercise or Acute-exercise and Rest on the Levels of Lipids, Carnitines and Carnitine Palmitoyltransferase-I in rats

  • Cha, Youn-Soo;Kim, Hyoung-Yon;Soh, Ju-Ryoun;oh, Suk-Heung
    • BMB Reports
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    • v.34 no.5
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    • pp.434-439
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    • 2001
  • The effects of regular endurance exercise, or acute-exercise and rest on the levels of lipids, carnitines and carnitine palmitoyltransferase-I (CPT-I) were investigated in male Sprague-Dawley rats. The rats were exercise trained on a treadmill for 60 min per day for 60 days (long-term trained, LT), or non-trained for 59 days (NT) and exercised for 60 min on the 60th day. In NT rats, the levels of serum nonesterified carnitine (NEC), acidsoluble acylcarnitine (ASAC), and total carnitine (TONE) increased significantly during the post-exercise recovery period (PERP). In LT rats, ASAC, and TCNE, which increased right after the 60 min running session decreased to the levels of pre-exercise during the PERP. The levels of skeletal muscle ASAC in NT rats, which increased significantly by the acute-exercise, decreased to the pre-exercise levels during the PERP. However, the ASAC level in LT rats reached its peak at 4 h after running for 60 min. Liver triglyceride (TG) and total lipids (TL), which increased by the acute-exercise, decreased to the pre-exercise levels during the PERP in both NT and LT rats. CPT-I activity in NT rats increased significantly after 1 h of a 60-min exercise and slowly decreased to pre-exercise levels during the PERP. However, the CPT-I activity in LT rats, which increased significantly by the 60 min exercise, decreased slowly and reached its pre-exercise level within 8 h of the PERP. Northern blot analysis showed that the changes of CPT-I activities during the PERP coincided with changes in CPT-I mRNA levels. This study shows that both regular endurance exercise, and acute-exercise and rest, can influence differently the levels of carnitines, lipids and CPT-I in rats. The results suggest that regular endurance exercise, rather than the acute-exercise, can change effectively the distributions of carnitines, lipids and CPT-I in rats during exercise and rest.

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COVID-19: an update on diagnostic and therapeutic approaches

  • Iyer, Mahalaxmi;Jayaramayya, Kaavya;Subramaniam, Mohana Devi;Lee, Soo Bin;Dayem, Ahmed Abdal;Cho, Ssang-Goo;Vellingiri, Balachandar
    • BMB Reports
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    • v.53 no.4
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    • pp.191-205
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    • 2020
  • The unexpected pandemic set off by the novel coronavirus 2019 (COVID-19) has caused severe panic among people worldwide. COVID-19 has created havoc, and scientists and physicians are urged to test the efficiency and safety of drugs used to treat this disease. In such a pandemic situation, various steps have been taken by the government to control and prevent the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). This pandemic situation has forced scientists to rework strategies to combat infectious diseases through drugs, treatment, and control measures. COVID-19 treatment requires both limiting viral multiplication and neutralizing tissue damage induced by an inappropriate immune reaction. Currently, various diagnostic kits to test for COVID-19 are available, and repurposing therapeutics for COVID-19 has shown to be clinically effective. As the global demand for diagnostics and therapeutics continues to rise, it is essential to rapidly develop various algorithms to successfully identify and contain the virus. This review discusses the updates on specimens/samples, recent efficient diagnostics, and therapeutic approaches to control the disease and repurposed drugs mainly focusing on chloroquine/hydroxychloroquine and convalescent plasma (CP). More research is required for further understanding of the influence of diagnostics and therapeutic approaches to develop vaccines and drugs for COVID-19.

Effect of Water Extract of Germinated Brown Rice on Adiposity and Obesity Indices in Mice Fed a High Fat Diet

  • Oh, Suk-Heung;Moon, Yeon-Jeong;Soh, Ju-Ryoun;Cha, Youn-Soo
    • Preventive Nutrition and Food Science
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    • v.10 no.3
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    • pp.251-256
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    • 2005
  • An extract obtained from germinated brown rice was evaluated for protective effects against the adverse effects of a chronic high fat diet. C57BL6/J mice were divided into three groups; normal diet + water group (ND), high fat diet + water group (HD), high fat diet + brown rice water extract group (HD + BE) and fed for 8 weeks (6 day/week). The ND group diet was 11 kcal fat $\%$. The HD group and HD + BE group diet were 42 kcal fat $\%$. Weight gains were not significantly different between groups. However, abdominal fat $\%$ was 1.6-fold higher in the HD group than HD + BE group. Feed consumption was significantly higher in the ND group than HD group. Serum triglyceride, total cholesterol and LDL-cholesterol increased with a high fat diet, but decreased by brown rice water extract administration to the high fat diet group. Serum HDL-cholesterol decreased by the high fat diet, but increased by the brown rice wate extract administration. Also, serum HDL-cholesterol/total cholesterol ratio was 2.3-fold higher in the HD + BE than the HD. Liver triglyceride and total cholesterol were not significantly different among groups. These data suggest that brown rice water extract administration improves the serum lipid profiles of C57BL/6J mice.

Potential mechanism of anti-diabetic activity of Picrorhiza kurroa

  • Husain, Gulam Mohammed;Rai, Richa;Rai, Geeta;Singh, Harikesh Bahadur;Thakur, Ajit Kumar;Kumar, Vikas
    • CELLMED
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    • v.4 no.4
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    • pp.27.1-27.5
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    • 2014
  • Picrorhiza kurroa Royle ex Benth. (Scrophulariaceae) is a traditional Ayurvedic herb known as Kutki. It is used as a remedy for diabetes by tribes of North Eastern Himalayan region of India. Present study was conducted to explore the mechanism of antidiabetic activity of standardized aqueous extract of Picrorhiza kurroa (PkE). PkE (100 and 200 mg/kg/day) was orally administered to streptozotocin induced diabetic rats, for 14 consecutive days. Plasma insulin levels were measured and pancreas of rat was subjected to histopathological investigations. Glucose transporter type 4 (GLUT-4) protein content in the total membrane fractions of soleus muscle was estimated by Western blot analysis. Plasma insulin level was significantly increased along with concomitant increase in GLUT-4 content of total membrane fractions of soleus muscle of diabetic rats treated with extract. There was evidence of regeneration of ${\beta}$-cells of pancreatic islets of PkE treated group in histopathological examinations. PkE increased the insulin-mediated translocation of GLUT-4 from cytosol to plasma membrane or increased GLUT-4 expression, which in turn facilitated glucose uptake by skeletal muscles in diabetic rats.

The parental origin correlates with the karyotype of human embryos developing from tripronuclear zygotes

  • Joergensen, Mette Warming;Labouriau, Rodrigo;Hindkjaer, Johnny;Stougaard, Magnus;Kolevraa, Steen;Bolund, Lars;Agerholm, Inge Errebo;Sunde, Lone
    • Clinical and Experimental Reproductive Medicine
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    • v.42 no.1
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    • pp.14-21
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    • 2015
  • Objective: It has previously been suggested that embryos developing from intracytoplasmic sperm-injected (ICSI) zygotes with three pronuclei (3PN) are endowed with a mechanism for self-correction of triploidy to diploidy. 3PN are also observed in zygotes after conventional in vitro fertilization (IVF). The parental origin, however, differs between the two fertilization methods. Whereas the vast majority of 3PN IVF zygotes are of dispermic origin and thus more likely to have two centrioles, the 3PN ICSI zygotes are digynic in origin and therefore, more likely to have one centriole. In the present study, we examine whether the parental origin of 3PN embryos correlates with the karyotype. Methods: The karyotype of each nucleus was estimated using four sequential fluorescence in situ hybridizations-each with two probes-resulting in quantitative information of 8 different chromosomes. The karyotypes were then compared and correlated to the parental origin. Results: 3PN ICSI embryos displayed a significantly larger and more coordinated reduction from the assumed initial 3 sets of chromosomes than 3PN IVF embryos. Conclusion: The differences in the parental origin-and hence the number of centrioles-between the 3PN IVF and the 3PN ICSI zygotes are likely to be the cause of the differences in karyotypes.

Creating Subnetworks from Transcriptomic Data on Central Nervous System Diseases Informed by a Massive Transcriptomic Network

  • Feng, Yaping;Syrkin-Nikolau, Judith A.;Wurtele, Eve S.
    • Interdisciplinary Bio Central
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    • v.5 no.1
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    • pp.1.1-1.8
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    • 2013
  • High quality publicly-available transcriptomic data representing relationships in gene expression across a diverse set of biological conditions is used as a context network to explore transcriptomics of the CNS. The context network, 18367Hu-matrix, contains pairwise Pearson correlations for 22,215 human genes across18,637 human tissue samples1. To do this, we compute a network derived from biological samples from CNS cells and tissues, calculate clusters of co-expressed genes from this network, and compare the significance of these to clusters derived from the larger 18367Hu-matrix network. Sorting and visualization uses the publicly available software, MetaOmGraph (http://www.metnetdb.org/MetNet_MetaOm-Graph.htm). This identifies genes that characterize particular disease conditions. Specifically, differences in gene expression within and between two designations of glial cancer, astrocytoma and glioblastoma, are evaluated in the context of the broader network. Such gene groups, which we term outlier-networks, tease out abnormally expressed genes and the samples in which this expression occurs. This approach distinguishes 48 subnetworks of outlier genes associated with astrocytoma and glioblastoma. As a case study, we investigate the relationships among the genes of a small astrocytoma-only subnetwork. This astrocytoma-only subnetwork consists of SVEP1, IGF1, CHRNA3, and SPAG6. All of these genes are highly coexpressed in a single sample of anaplastic astrocytoma tumor (grade III) and a sample of juvenile pilocytic astrocytoma. Three of these genes are also associated with nicotine. This data lead us to formulate a testable hypothesis that this astrocytoma outlier-network provides a link between some gliomas/astrocytomas and nicotine.

Distribution of the 9-bp Deletion in Coll/$tRNA^{Lys}$ Intergenic Region of Mitochondrial DNA is Relatively Homogeneous in East Asian Populations

  • Hong, Seong-Su;Horai, Satoshi;Lee, Chung-Choo
    • Animal cells and systems
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    • v.2 no.2
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    • pp.259-267
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    • 1998
  • A deletion of one out of the two copies of 9-bp repeat sequence (CCCCCTCTA), between the cytochrome oxidase II and Iysine tranfer RNA (COII/$tRNA^{Lys}$) genes in human mitochondrial DNA (mtDNA) has been used as a polymorphic anthropological marker for people of east Asian origin, and to lesser extent, Pacific and African populations. We searched for the 9-bp deletion of the intergenic COII/$tRNA^{Lys}$ Lys region in two Korean populations (175 from Seoul and 38 from Cheju) and examine the distibution of this deletion in world populations. The 9-bp deletion was detected directly by electrophoresis of the polymerase chain reaction (PCR)-amplified nucleotide(nt) 8211-8310 mtDNA fragment. The frequencies of the 9-bp deletion were significantly different between the Seoul (16%) and Cheju (8%) populations. Examination of data from the world populations suggests a geographic gradient. The frequency reaches its highest values in some Pacific island populations and decreases along the southeast Asia-Siberia transect. In spite of this geographic gradient, Mongoloid populations including Korean, Chinese, Japanese, and Mongolian populations were relatively homo-geneous with regard to the 9-bp deletion type of the intergenic COII/$tRNA^{Lys}$ region. These results indicate Koreans are genetically related to northeast Asian populations, and have a maternal mongoloid ancestry. Therefore, the 9-bp deletion of the intergenic COII/$tRNA^{Lys}$ region will provide significant information to elucidate the historical patterns of migration of the Mongoloids.

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