Next Issue
Previous Issue

Table of Contents

Genes, Volume 4, Issue 3 (September 2013), Pages 306-521

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Readerexternal link to open them.
View options order results:
result details:
Displaying articles 1-9
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle Notch1 Activation Up-Regulates Pancreatic and Duodenal Homeobox-1
Genes 2013, 4(3), 358-374; doi:10.3390/genes4030358
Received: 14 May 2013 / Revised: 2 July 2013 / Accepted: 11 July 2013 / Published: 19 July 2013
Cited by 1 | PDF Full-text (1396 KB) | HTML Full-text | XML Full-text
Abstract
Transcription factor pancreatic and duodenal homeobox-1 (PDX-1) plays an essential role in pancreatic development, β-cell differentiation, maintenance of normal β-cell function and tumorigenesis. PDX-1 expression is tightly controlled through a variety of mechanisms under different cellular contexts. We report here that overexpression [...] Read more.
Transcription factor pancreatic and duodenal homeobox-1 (PDX-1) plays an essential role in pancreatic development, β-cell differentiation, maintenance of normal β-cell function and tumorigenesis. PDX-1 expression is tightly controlled through a variety of mechanisms under different cellular contexts. We report here that overexpression of Notch1 intracellular domain (NICD), an activated form of Notch1, enhanced PDX-1 expression in both PDX-1 stable HEK293 cells and mouse insulinoma β-TC-6 cells, while NICD shRNA inhibited the enhancing effect. NICD-enhanced PDX-1 expression was accompanied by increased insulin expression/secretion and cell proliferation in β-TC-6 cells, which was reversed by NICD shRNA. Cre activation-induced specific expression of NICD in islet β cells of transgenic βNICD+/+ mice induced increased expression of PDX-1, insulin and proliferating cell nuclear antigen (PCNA) and decreased expression of p27 with accompanied fasting hyperinsulinemia and hypoglycemia and altered responses to intraperitoneal glucose tolerance test. Systemically delivered NICD shRNA suppressed islet expression of PDX-1 and reversed the hypoglycemia and hyperinsulinemia. Moreover, expression levels of NICD were correlated with those of PDX-1 in human pancreatic neuroendocrine tumor. Thus, Notch1 acts as a positive regulator for PDX-1 expression, cooperates with PDX-1 in the development of insulin overexpression and islet cell neoplasia and represents a potential therapeutic target for islet neoplasia. Full article
(This article belongs to the Special Issue Gene Silencing)
Open AccessArticle Polymorphisms in Fatty Acid Desaturase (FADS) Gene Cluster: Effects on Glycemic Controls Following an Omega-3 Polyunsaturated Fatty Acids (PUFA) Supplementation
Genes 2013, 4(3), 485-498; doi:10.3390/genes4030485
Received: 8 June 2013 / Revised: 22 August 2013 / Accepted: 2 September 2013 / Published: 10 September 2013
Cited by 6 | PDF Full-text (186 KB) | HTML Full-text | XML Full-text
Abstract
Changes in desaturase activity are associated with insulin sensitivity and may be associated with type 2 diabetes mellitus (T2DM). Polymorphisms (SNPs) in the fatty acid desaturase (FADS) gene cluster have been associated with the homeostasis model assessment of insulin sensitivity [...] Read more.
Changes in desaturase activity are associated with insulin sensitivity and may be associated with type 2 diabetes mellitus (T2DM). Polymorphisms (SNPs) in the fatty acid desaturase (FADS) gene cluster have been associated with the homeostasis model assessment of insulin sensitivity (HOMA-IS) and serum fatty acid composition. Objective: To investigate whether common genetic variations in the FADS gene cluster influence fasting glucose (FG) and fasting insulin (FI) responses following a 6-week n-3 polyunsaturated fatty acids (PUFA) supplementation. Methods: 210 subjects completed a 2-week run-in period followed by a 6-week supplementation with 5 g/d of fish oil (providing 1.9 g–2.2 g of EPA + 1.1 g of DHA). Genotyping of 18 SNPs of the FADS gene cluster covering 90% of all common genetic variations (minor allele frequency ≥ 0.03) was performed. Results: Carriers of the minor allele for rs482548 (FADS2) had increased plasma FG levels after the n-3 PUFA supplementation in a model adjusted for FG levels at baseline, age, sex, and BMI. A significant genotype*supplementation interaction effect on FG levels was observed for rs482548 (p = 0.008). For FI levels, a genotype effect was observed with one SNP (rs174456). For HOMA-IS, several genotype*supplementation interaction effects were observed for rs7394871, rs174602, rs174570, rs7482316 and rs482548 (p = 0.03, p = 0.01, p = 0.03, p = 0.05 and p = 0.07; respectively). Conclusion: Results suggest that SNPs in the FADS gene cluster may modulate plasma FG, FI and HOMA-IS levels in response to n-3 PUFA supplementation. Full article
(This article belongs to the Special Issue Genetics of Diabetes)

Review

Jump to: Research

Open AccessReview Signaling Pathways from the Endoplasmic Reticulum and Their Roles in Disease
Genes 2013, 4(3), 306-333; doi:10.3390/genes4030306
Received: 28 March 2013 / Revised: 1 May 2013 / Accepted: 14 May 2013 / Published: 1 July 2013
Cited by 13 | PDF Full-text (860 KB) | HTML Full-text | XML Full-text
Abstract
The endoplasmic reticulum (ER) is an organelle in which newly synthesized secretory and transmembrane proteins are assembled and folded into their correct tertiary structures. However, many of these ER proteins are misfolded as a result of various stimuli and gene mutations. The [...] Read more.
The endoplasmic reticulum (ER) is an organelle in which newly synthesized secretory and transmembrane proteins are assembled and folded into their correct tertiary structures. However, many of these ER proteins are misfolded as a result of various stimuli and gene mutations. The accumulation of misfolded proteins disrupts the function of the ER and induces ER stress. Eukaryotic cells possess a highly conserved signaling pathway, termed the unfolded protein response (UPR), to adapt and respond to ER stress conditions, thereby promoting cell survival. However, in the case of prolonged ER stress or UPR malfunction, apoptosis signaling is activated. Dysfunction of the UPR causes numerous conformational diseases, including neurodegenerative disease, metabolic disease, inflammatory disease, diabetes mellitus, cancer, and cardiovascular disease. Thus, ER stress-induced signaling pathways may serve as potent therapeutic targets of ER stress-related diseases. In this review, we will discuss the molecular mechanisms of the UPR and ER stress-induced apoptosis, as well as the possible roles of ER stress in several diseases. Full article
(This article belongs to the Special Issue Signal Transduction)
Open AccessReview Roles of EphA2 in Development and Disease
Genes 2013, 4(3), 334-357; doi:10.3390/genes4030334
Received: 23 April 2013 / Revised: 22 May 2013 / Accepted: 23 May 2013 / Published: 1 July 2013
Cited by 9 | PDF Full-text (250 KB) | HTML Full-text | XML Full-text
Abstract
The Eph family of receptor tyrosine kinases (RTKs) has been implicated in the regulation of many aspects of mammalian development. Recent analyses have revealed that the EphA2 receptor is a key modulator for a wide variety of cellular functions. This review focuses [...] Read more.
The Eph family of receptor tyrosine kinases (RTKs) has been implicated in the regulation of many aspects of mammalian development. Recent analyses have revealed that the EphA2 receptor is a key modulator for a wide variety of cellular functions. This review focuses on the roles of EphA2 in both development and disease. Full article
(This article belongs to the Special Issue Signal Transduction)
Open AccessReview Abnormal Base Excision Repair at Trinucleotide Repeats Associated with Diseases: A Tissue-Selective Mechanism
Genes 2013, 4(3), 375-387; doi:10.3390/genes4030375
Received: 2 May 2013 / Revised: 25 June 2013 / Accepted: 26 June 2013 / Published: 25 July 2013
Cited by 2 | PDF Full-text (324 KB) | HTML Full-text | XML Full-text
Abstract
More than fifteen genetic diseases, including Huntington’s disease, myotonic dystrophy 1, fragile X syndrome and Friedreich ataxia, are caused by the aberrant expansion of a trinucleotide repeat. The mutation is unstable and further expands in specific cells or tissues with time, which [...] Read more.
More than fifteen genetic diseases, including Huntington’s disease, myotonic dystrophy 1, fragile X syndrome and Friedreich ataxia, are caused by the aberrant expansion of a trinucleotide repeat. The mutation is unstable and further expands in specific cells or tissues with time, which can accelerate disease progression. DNA damage and base excision repair (BER) are involved in repeat instability and might contribute to the tissue selectivity of the process. In this review, we will discuss the mechanisms of trinucleotide repeat instability, focusing more specifically on the role of BER. Full article
(This article belongs to the Special Issue Microsatellite Instability)
Open AccessReview Replication Checkpoint: Tuning and Coordination of Replication Forks in S Phase
Genes 2013, 4(3), 388-434; doi:10.3390/genes4030388
Received: 7 May 2013 / Revised: 30 July 2013 / Accepted: 2 August 2013 / Published: 19 August 2013
Cited by 12 | PDF Full-text (2237 KB) | HTML Full-text | XML Full-text
Abstract
Checkpoints monitor critical cell cycle events such as chromosome duplication and segregation. They are highly conserved mechanisms that prevent progression into the next phase of the cell cycle when cells are unable to accomplish the previous event properly. During S phase, cells [...] Read more.
Checkpoints monitor critical cell cycle events such as chromosome duplication and segregation. They are highly conserved mechanisms that prevent progression into the next phase of the cell cycle when cells are unable to accomplish the previous event properly. During S phase, cells also provide a surveillance mechanism called the DNA replication checkpoint, which consists of a conserved kinase cascade that is provoked by insults that block or slow down replication forks. The DNA replication checkpoint is crucial for maintaining genome stability, because replication forks become vulnerable to collapse when they encounter obstacles such as nucleotide adducts, nicks, RNA-DNA hybrids, or stable protein-DNA complexes. These can be exogenously induced or can arise from endogenous cellular activity. Here, we summarize the initiation and transduction of the replication checkpoint as well as its targets, which coordinate cell cycle events and DNA replication fork stability. Full article
(This article belongs to the Special Issue DNA Replication)
Open AccessReview siRNA Treatment: “A Sword-in-the-Stone” for Acute Brain Injuries
Genes 2013, 4(3), 435-456; doi:10.3390/genes4030435
Received: 15 May 2013 / Revised: 17 August 2013 / Accepted: 22 August 2013 / Published: 5 September 2013
Cited by 5 | PDF Full-text (576 KB) | HTML Full-text | XML Full-text
Abstract
Ever since the discovery of small interfering ribonucleic acid (siRNA) a little over a decade ago, it has been highly sought after for its potential as a therapeutic agent for many diseases. In this review, we discuss the promising possibility of siRNA [...] Read more.
Ever since the discovery of small interfering ribonucleic acid (siRNA) a little over a decade ago, it has been highly sought after for its potential as a therapeutic agent for many diseases. In this review, we discuss the promising possibility of siRNA to be used as a drug to treat acute brain injuries such as stroke and traumatic brain injury. First, we will give a brief and basic overview of the principle of RNA interference as an effective mechanism to decrease specific protein expression. Then, we will review recent in vivo studies describing siRNA research experiments/treatment options for acute brain diseases. Lastly, we will discuss the future of siRNA as a clinical therapeutic strategy against brain diseases and injuries, while addressing the current obstacles to effective brain delivery. Full article
(This article belongs to the Special Issue Gene Silencing)
Open AccessReview Antisense Gene Silencing: Therapy for Neurodegenerative Disorders?
Genes 2013, 4(3), 457-484; doi:10.3390/genes4030457
Received: 20 May 2013 / Revised: 11 July 2013 / Accepted: 13 August 2013 / Published: 10 September 2013
Cited by 4 | PDF Full-text (942 KB) | HTML Full-text | XML Full-text
Abstract
Since the first reports that double-stranded RNAs can efficiently silence gene expression in C. elegans, the technology of RNA interference (RNAi) has been intensively exploited as an experimental tool to study gene function. With the subsequent discovery that RNAi could [...] Read more.
Since the first reports that double-stranded RNAs can efficiently silence gene expression in C. elegans, the technology of RNA interference (RNAi) has been intensively exploited as an experimental tool to study gene function. With the subsequent discovery that RNAi could also be applied to mammalian cells, the technology of RNAi expanded from being a valuable experimental tool to being an applicable method for gene-specific therapeutic regulation, and much effort has been put into further refinement of the technique. This review will focus on how RNAi has developed over the years and how the technique is exploited in a pre-clinical and clinical perspective in relation to neurodegenerative disorders. Full article
(This article belongs to the Special Issue Gene Silencing)
Open AccessReview Genes Involved in Type 1 Diabetes: An Update
Genes 2013, 4(3), 499-521; doi:10.3390/genes4030499
Received: 31 July 2013 / Revised: 26 August 2013 / Accepted: 5 September 2013 / Published: 16 September 2013
Cited by 7 | PDF Full-text (1195 KB) | HTML Full-text | XML Full-text
Abstract
Type 1 Diabetes (T1D) is a chronic multifactorial disease with a strong genetic component, which, through interactions with specific environmental factors, triggers disease onset. T1D typically manifests in early to mid childhood through the autoimmune destruction of pancreatic β cells resulting in [...] Read more.
Type 1 Diabetes (T1D) is a chronic multifactorial disease with a strong genetic component, which, through interactions with specific environmental factors, triggers disease onset. T1D typically manifests in early to mid childhood through the autoimmune destruction of pancreatic β cells resulting in a lack of insulin production. Historically, prior to genome-wide association studies (GWAS), six loci in the genome were fully established to be associated with T1D. With the advent of high-throughput single nucleotide polymorphism (SNP) genotyping array technologies, enabling investigators to perform high-density GWAS, many additional T1D susceptibility genes have been discovered. Indeed, recent meta-analyses of multiple datasets from independent investigators have brought the tally of well-validated T1D disease genes to almost 60. In this mini-review, we address recent advances in the genetics of T1D and provide an update on the latest susceptibility loci added to the list of genes involved in the pathogenesis of T1D. Full article
(This article belongs to the Special Issue Genetics of Diabetes)

Journal Contact

MDPI AG
Genes Editorial Office
St. Alban-Anlage 66, 4052 Basel, Switzerland
genes@mdpi.com
Tel. +41 61 683 77 34
Fax: +41 61 302 89 18
Editorial Board
Contact Details Submit to Genes
Back to Top