Genes

12 pages, 1662 KiB

Open AccessBrief Report

Environmental Temperature Controls Accumulation of Transacting siRNAs Involved in Heterochromatin Formation

by Marcello Pirritano^1,‡, Ulrike Götz^1,‡, Sivarajan Karunanithi², Karl Nordström³, Marcel H. Schulz² and Martin Simon^1,*,†

¹ Molecular Cell Dynamics, Centre for Human and Molecular Biology, Saarland University, 66123 Saarbrücken, Germany

² Cluster of Excellence, Multimodal Computing and Interaction, Saarland University and Department for Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Saarland Informatics Campus, 66123 Saarbrücken, Germany

³ Genetics/Epigenetics, Centre for Human and Molecular Biology, Saarland University, 66123 Saarbrücken, Germany

^† Current address: Molecular Cell Biology and Microbiology, Wuppertal University, Gausstraße 20, V.12.070, 42097 Wuppertal, Germany

^‡ These authors contributed equally to this work.

Genes 2018, 9(2), 117; https://doi.org/10.3390/genes9020117 - 21 Feb 2018

Cited by 5 | Viewed by 3837

Abstract

Genes or alleles can interact by small RNAs in a homology dependent manner meaning that short interfering (siRNAs) can act in trans at the chromatin level producing stable and heritable silencing phenotypes. Because of the puzzling data on endogenous paramutations, their impact contributing [...] Read more.

Genes or alleles can interact by small RNAs in a homology dependent manner meaning that short interfering (siRNAs) can act in trans at the chromatin level producing stable and heritable silencing phenotypes. Because of the puzzling data on endogenous paramutations, their impact contributing to adaptive evolution in a Lamarckian manner remains unknown. An increasing number of studies characterizes the underlying siRNA accumulation pathways using transgene experiments. Also in the ciliate Paramecium tetraurelia, we induce trans silencing on the chromatin level by injection of truncated transgenes. Here, we characterize the efficiency of this mechanism at different temperatures showing that silencing of the endogenous genes is temperature dependent. Analyzing different transgene constructs at different copy numbers, we dissected whether silencing efficiency is due to varying precursor RNAs or siRNA accumulation. Our data shows that silencing efficiency correlates with more efficient accumulation of primary siRNAs at higher temperatures rather than higher expression of precursor RNAs. Due to higher primary levels, secondary siRNAs also show temperature dependency and interestingly increase their relative proportion to primary siRNAs. Our data shows that efficient trans silencing on the chromatin level in P. tetraurelia depends on environmental parameters, thus being an important epigenetic factor limiting regulatory effects of siRNAs. Full article

(This article belongs to the Section Population and Evolutionary Genetics and Genomics)

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28 pages, 6500 KiB

Open AccessReview

In a quest for engineering acidophiles for biomining applications: challenges and opportunities

by Yosephine Gumulya^1,*, Naomi J. Boxall¹

, Himel N. Khaleque¹, Ville Santala², Ross P. Carlson³ and Anna H. Kaksonen^1,4

¹ Commonwealth Scientific and Industrial Research Organisation (CSIRO), Floreat WA 6014, Australia

² Laboratory of Chemistry and Bioengineering, Tampere University of Technology (TUT), 33101 Tampere, Finland

³ Department of Chemical and Biological Engineering, Montana State University (MSU), Bozeman, MT 59717, USA

⁴ School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, WA 6009, Australia

Genes 2018, 9(2), 116; https://doi.org/10.3390/genes9020116 - 21 Feb 2018

Cited by 88 | Viewed by 14062

Abstract

Biomining with acidophilic microorganisms has been used at commercial scale for the extraction of metals from various sulfide ores. With metal demand and energy prices on the rise and the concurrent decline in quality and availability of mineral resources, there is an increasing [...] Read more.

Biomining with acidophilic microorganisms has been used at commercial scale for the extraction of metals from various sulfide ores. With metal demand and energy prices on the rise and the concurrent decline in quality and availability of mineral resources, there is an increasing interest in applying biomining technology, in particular for leaching metals from low grade minerals and wastes. However, bioprocessing is often hampered by the presence of inhibitory compounds that originate from complex ores. Synthetic biology could provide tools to improve the tolerance of biomining microbes to various stress factors that are present in biomining environments, which would ultimately increase bioleaching efficiency. This paper reviews the state-of-the-art tools to genetically modify acidophilic biomining microorganisms and the limitations of these tools. The first part of this review discusses resilience pathways that can be engineered in acidophiles to enhance their robustness and tolerance in harsh environments that prevail in bioleaching. The second part of the paper reviews the efforts that have been carried out towards engineering robust microorganisms and developing metabolic modelling tools. Novel synthetic biology tools have the potential to transform the biomining industry and facilitate the extraction of value from ores and wastes that cannot be processed with existing biomining microorganisms. Full article

(This article belongs to the Special Issue Genetics and Genomics of Extremophiles)

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20 pages, 1149 KiB

Open AccessReview

Dynamin-Related Protein 1 at the Crossroads of Cancer

by Ana Rita Lima³

, Liliana Santos^1,2,4

, Marcelo Correia^1,2

, Paula Soares^1,2,5

, Manuel Sobrinho-Simões^1,2,5,6

, Miguel Melo^1,2,7,8 and Valdemar Máximo^1,2,5,*

¹ Cancer Signaling & Metabolism Group, Instituto de Investigação e Inovação em Saúde (Institute for Research and Innovation in Health Sciences) (I3S), University of Porto, Porto 4200-135, Portugal

² Cancer Signaling & Metabolism Group, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto 4200-135, Portugal

³ Medical Faculty of University of Porto—FMUP, Porto 4200-135, Portugal

⁴ Abel Salazar Biomedical Sciences Institute (ICBAS), University of Porto, Porto 4200-135, Portugal

⁵ Department of Pathology, Medical Faculty of University of Porto (FMUP), Porto 4200-135, Portugal

⁶ Department of Pathology and Oncology, Centro Hospitalar São João, Porto 4200-135, Portugal

⁷ Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar e Universitário de Coimbra (Coimbra University Hospital Centre), Coimbra 3000-075, Portugal

⁸ Faculty of Medicine, University of Coimbra, Coimbra 3000-548, Portugal

Genes 2018, 9(2), 115; https://doi.org/10.3390/genes9020115 - 21 Feb 2018

Cited by 73 | Viewed by 9657

Abstract

Mitochondrial dynamics are known to have an important role in so-called age-related diseases, including cancer. Mitochondria is an organelle involved in many key cellular functions and responds to physiologic or stress stimuli by adapting its structure and function. Perhaps the most important structural [...] Read more.

Mitochondrial dynamics are known to have an important role in so-called age-related diseases, including cancer. Mitochondria is an organelle involved in many key cellular functions and responds to physiologic or stress stimuli by adapting its structure and function. Perhaps the most important structural changes involve mitochondrial dynamics (fission and fusion), which occur in normal cells as well as in cells under dysregulation, such as cancer cells. Dynamin-related protein 1 (DRP1), a member of the dynamin family of guanosine triphosphatases (GTPases), is the key component of mitochondrial fission machinery. Dynamin-related protein 1 is associated with different cell processes such as apoptosis, mitochondrial biogenesis, mitophagy, metabolism, and cell proliferation, differentiation, and transformation. The role of DRP1 in tumorigenesis may seem to be paradoxical, since mitochondrial fission is a key mediator of two very different processes, cellular apoptosis and cell mitosis. Dynamin-related protein 1 has been associated with the development of distinct human cancers, including changes in mitochondrial energetics and cellular metabolism, cell proliferation, and stem cell maintenance, invasion, and promotion of metastases. However, the underlying mechanism for this association is still being explored. Herein, we review the published knowledge on the role of DRP1 in cancer, exploring its interaction with different biological processes in the tumorigenesis context. Full article

(This article belongs to the Special Issue The Double-Edged Role of Noncanonical Oncogenes and Tumor Suppressor Genes in Cancer Progression; An Oncojanus Function)

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10 pages, 2042 KiB

Open AccessArticle

Skin-on-a-Chip: Transepithelial Electrical Resistance and Extracellular Acidification Measurements through an Automated Air-Liquid Interface

by Frank A. Alexander, Jr.¹, Sebastian Eggert^1,2,3 and Joachim Wiest^1,*

¹ cellasys GmbH, 87758 Kronburg, Germany

² Department of Mechanical Engineering, Technical University of Munich, 80333 Munich, Germany

³ Centre in Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology, 4059 Kelvin Grove, Australia

Genes 2018, 9(2), 114; https://doi.org/10.3390/genes9020114 - 21 Feb 2018

Cited by 66 | Viewed by 11017

Abstract

Skin is a critical organ that plays a crucial role in defending the internal organs of the body. For this reason, extensive work has gone into creating artificial models of the epidermis for in vitro skin toxicity tests. These tissue models, called reconstructed [...] Read more.

Skin is a critical organ that plays a crucial role in defending the internal organs of the body. For this reason, extensive work has gone into creating artificial models of the epidermis for in vitro skin toxicity tests. These tissue models, called reconstructed human epidermis (RhE), are used by researchers in the pharmaceutical, cosmetic, and environmental arenas to evaluate skin toxicity upon exposure to xenobiotics. Here, we present a label-free solution that leverages the use of the intelligent mobile lab for in vitro diagnostics (IMOLA-IVD), a noninvasive, sensor-based platform, to monitor the transepithelial electrical resistance (TEER) of RhE models and adherent cells cultured on porous membrane inserts. Murine fibroblasts cultured on polycarbonate membranes were first used as a test model to optimize procedures using a custom BioChip encapsulation design, as well as dual fluidic configurations, for continuous and automated perfusion of membrane-bound cultures. Extracellular acidification rate (EAR) and TEER of membrane-bound L929 cells were monitored. The developed protocol was then used to monitor the TEER of MatTek EpiDerm^TM RhE models over a period of 48 h. TEER and EAR measurements demonstrated that the designed system is capable of maintaining stable cultures on the chip, monitoring metabolic parameters, and revealing tissue breakdown over time. Full article

(This article belongs to the Special Issue From the Lab-on-a-Chip to the Organ-on-a-Chip)

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15 pages, 1993 KiB

Open AccessArticle

Biofilm Formation by the Acidophile Bacterium Acidithiobacillus thiooxidans Involves c-di-GMP Pathway and Pel exopolysaccharide

by Mauricio Díaz¹, Matias Castro¹, Sylvia Copaja² and Nicolas Guiliani^1,*

¹ Bacterial Communication Laboratory, Biology Department, Faculty of Sciences, Universidad de Chile, Ñuñoa 7800003, Santiago, Chile

² Organic and Environmental Chemistry Laboratory, Faculty of Sciences, Universidad de Chile, Ñuñoa 7800003, Santiago, Chile

Genes 2018, 9(2), 113; https://doi.org/10.3390/genes9020113 - 21 Feb 2018

Cited by 42 | Viewed by 7913

Abstract

Acidophile bacteria belonging to the Acidithiobacillus genus are pivotal players for the bioleaching of metallic values such as copper. Cell adherence to ores and biofilm formation, mediated by the production of extracellular polymeric substances, strongly favors bioleaching activity. In recent years, the second [...] Read more.

Acidophile bacteria belonging to the Acidithiobacillus genus are pivotal players for the bioleaching of metallic values such as copper. Cell adherence to ores and biofilm formation, mediated by the production of extracellular polymeric substances, strongly favors bioleaching activity. In recent years, the second messenger cyclic diguanylate (c-di-GMP) has emerged as a central regulator for biofilm formation in bacteria. C-di-GMP pathways have been reported in different Acidithiobacillus species; however, c-di-GMP effectors and signal transduction networks are still largely uncharacterized in these extremophile species. Here we investigated Pel exopolysaccharide and its role in biofilm formation by sulfur-oxidizing species Acidithiobacillus thiooxidans. We identified 39 open reading frames (ORFs) encoding proteins involved in c-di-GMP metabolism and signal transduction, including the c-di-GMP effector protein PelD, a structural component of the biosynthesis apparatus for Pel exopolysaccharide production. We found that intracellular c-di-GMP concentrations and transcription levels of pel genes were higher in At. thiooxidans biofilm cells compared to planktonic ones. By developing an At. thiooxidans ΔpelD null-mutant strain we revealed that Pel exopolysaccharide is involved in biofilm structure and development. Further studies are still necessary to understand how Pel biosynthesis is regulated in Acidithiobacillus species, nevertheless these results represent the first characterization of a c-di-GMP effector protein involved in biofilm formation by acidophile species. Full article

(This article belongs to the Special Issue Genetics and Genomics of Extremophiles)

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10 pages, 3457 KiB

Open AccessArticle

Delineation of Novel Autosomal Recessive Mutation in GJA3 and Autosomal Dominant Mutations in GJA8 in Pakistani Congenital Cataract Families

by Shazia Micheal¹, Ilse Therésia Gabriëla Niewold¹, Sorath Noorani Siddiqui², Saemah Nuzhat Zafar², Muhammad Imran Khan³ and Arthur A. B. Bergen^1,4,5,*

¹ Department of Clinical Genetics, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

² Department of Pediatric Ophthalmology and Strabismus, Al-Shifa Eye Trust Hospital Jhelum Road, Rawalpindi 46000, Pakistan

³ Department of Human Genetics, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands

⁴ Department of Ophthalmology, Academic Medical Centre, 1105 AZ Amsterdam, The Netherlands

⁵ Netherlands Institute for Neuroscience, (NIN-KNAW), 1105 AZ Amsterdam, The Netherlands

Genes 2018, 9(2), 112; https://doi.org/10.3390/genes9020112 - 20 Feb 2018

Cited by 19 | Viewed by 5386

Abstract

Congenital cataract is a clinically and genetically heterogeneous disease. The present study was undertaken to find the genetic cause of congenital cataract families. DNA samples of a large consanguineous Pakistani family were genotyped with a high resolution single nucleotide polymorphism Illumina microarray. Homozygosity [...] Read more.

Congenital cataract is a clinically and genetically heterogeneous disease. The present study was undertaken to find the genetic cause of congenital cataract families. DNA samples of a large consanguineous Pakistani family were genotyped with a high resolution single nucleotide polymorphism Illumina microarray. Homozygosity mapping identified a homozygous region of 4.4 Mb encompassing the gene GJA3. Sanger sequence analysis of the GJA3 gene revealed a novel homozygous variant c.950dup p.(His318ProfsX8) segregating in an autosomal recessive (AR) manner. The previously known mode of inheritance for GJA3 gene mutations in cataract was autosomal dominant (AD) only. The screening of additional probands (n = 41) of cataract families revealed a previously known mutation c.56C>T p.(Thr19Met) in GJA3 gene. In addition, sequencing of the exon-intron boundaries of the GJA8 gene in 41 cataract probands revealed two additional mutations: a novel c.53C>T p.(Ser18Phe) and a known c.175C>G p.(Pro59Ala) mutation, both co-segregating with the disease phenotype in an AD manner. All these mutations are predicted to be pathogenic by in silico analysis and were absent in the control databases. In conclusion, results of the current study enhance our understanding of the genetic basis of cataract, and identified the involvement of the GJA3 in the disease etiology in both AR and AD manners. Full article

(This article belongs to the Section Human Genomics and Genetic Diseases)

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12 pages, 1675 KiB

Open AccessArticle

Genetic Variation and Hybridisation among Eight Species of kōwhai (Sophora: Fabaceae) from New Zealand Revealed by Microsatellite Markers

by Peter Heenan^1,*, Caroline Mitchell² and Gary Houliston²

¹ Research Associate, Allan Herbarium, Landcare Research, PO Box 40, Lincoln 7640, New Zealand

² Landcare Research, PO Box 40, Lincoln 7640, New Zealand

Genes 2018, 9(2), 111; https://doi.org/10.3390/genes9020111 - 20 Feb 2018

Cited by 12 | Viewed by 4510

Abstract

We analysed nine microsatellite markers for 626 individuals representing the geographic range of eight closely related endemic New Zealand species of Sophora. Structure analysis identified the optimal K value as seven, with samples identified as Sophora chathamica, Sophora fulvida [...] Read more.

We analysed nine microsatellite markers for 626 individuals representing the geographic range of eight closely related endemic New Zealand species of Sophora. Structure analysis identified the optimal K value as seven, with samples identified as Sophora chathamica, Sophora fulvida, Sophora longicarinata, and Sophora prostrata retrieved as well-defined groups. The remaining samples formed less resolved groups referable to Sophora tetraptera and Sophora godleyi, with Sophora microphylla and Sophora molloyi forming the seventh group. Our data suggest that considerable admixture occurs and this is most likely the result of hybridisation or introgression. S. fulvida shows admixture with the sympatric S. chathamica, and the widespread S. microphylla exhibits admixture with the sympatric S. godleyi, S. molloyi, and S. tetraptera. Full article

(This article belongs to the Special Issue Genetics and Genomics of the Rhizobium-Legume Symbiosis)

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15 pages, 6614 KiB

Open AccessArticle

Genome-Wide Analysis of the GRF Family Reveals Their Involvement in Abiotic Stress Response in Cassava

by Sang Shang^1,†, Chunlai Wu^2,†, Chao Huang^3,†, Weiwei Tie², Yan Yan², Zehong Ding², Zhiqiang Xia², Wenquan Wang², Ming Peng², Libo Tian^1,* and Wei Hu^2,*

¹ Tropical Agriculture and Foresty Institute, Hainan University, Haikou, Hainan, 570228, China

² Key Laboratory of Biology and Genetic Resources of Tropical Crops, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou, Hainan, 571101, China

³ College of Life Science and Technology, Huazhong University of Science and Technology (HUST), Wuhan, Hubei, 430074, China

^† These authors contributed equally to this work.

Genes 2018, 9(2), 110; https://doi.org/10.3390/genes9020110 - 20 Feb 2018

Cited by 25 | Viewed by 5666

Abstract

GENERAL REGULATORY FACTOR (GRF) proteins play vital roles in the regulation of plant growth, development, and response to abiotic stress. However, little information is known for this gene family in cassava (Manihot esculenta). In this study, 15 MeGRFs were identified from [...] Read more.

GENERAL REGULATORY FACTOR (GRF) proteins play vital roles in the regulation of plant growth, development, and response to abiotic stress. However, little information is known for this gene family in cassava (Manihot esculenta). In this study, 15 MeGRFs were identified from the cassava genome and were clustered into the ε and the non-ε groups according to phylogenetic, conserved motif, and gene structure analyses. Transcriptomic analyses showed eleven MeGRFs with constitutively high expression in stems, leaves, and storage roots of two cassava genotypes. Expression analyses revealed that the majority of GRFs showed transcriptional changes under cold, osmotic, salt, abscisic acid (ABA), and H₂O₂ treatments. Six MeGRFs were found to be commonly upregulated by abiotic stress, ABA, and H₂O₂ treatments, which may be the converging points of multiple signaling pathways. Interaction network analysis identified 18 possible interactors of MeGRFs. Taken together, this study elucidates the transcriptional control of MeGRFs in tissue development and the responses of abiotic stress and related signaling in cassava. Some constitutively expressed, tissue-specific, and abiotic stress-responsive candidate MeGRF genes were identified for the further genetic improvement of crops. Full article

(This article belongs to the Section Plant Genetics and Genomics)

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24 pages, 1958 KiB

Open AccessReview

Wnt Signaling and Its Impact on Mitochondrial and Cell Cycle Dynamics in Pluripotent Stem Cells

by Megan L. Rasmussen¹, Natalya A. Ortolano¹

, Alejandra I. Romero-Morales¹ and Vivian Gama^1,2,3,*

¹ Department of Cell and Developmental Biology; Vanderbilt University, Nashville, TN 37232, USA

² Vanderbilt Center for Stem Cell Biology; Vanderbilt University, Nashville, TN 37232, USA

³ Vanderbilt Ingram Cancer Center; Vanderbilt University, Nashville, TN 37232, USA

Genes 2018, 9(2), 109; https://doi.org/10.3390/genes9020109 - 19 Feb 2018

Cited by 38 | Viewed by 13458

Abstract

The core transcriptional network regulating stem cell self-renewal and pluripotency remains an intense area of research. Increasing evidence indicates that modified regulation of basic cellular processes such as mitochondrial dynamics, apoptosis, and cell cycle are also essential for pluripotent stem cell identity and [...] Read more.

The core transcriptional network regulating stem cell self-renewal and pluripotency remains an intense area of research. Increasing evidence indicates that modified regulation of basic cellular processes such as mitochondrial dynamics, apoptosis, and cell cycle are also essential for pluripotent stem cell identity and fate decisions. Here, we review evidence for Wnt regulation of pluripotency and self-renewal, and its connections to emerging features of pluripotent stem cells, including (1) increased mitochondrial fragmentation, (2) increased sensitivity to cell death, and (3) shortened cell cycle. We provide a general overview of the stem cell–specific mechanisms involved in the maintenance of these uncharacterized hallmarks of pluripotency and highlight potential links to the Wnt signaling pathway. Given the physiological importance of stem cells and their enormous potential for regenerative medicine, understanding fundamental mechanisms mediating the crosstalk between Wnt, organelle-dynamics, apoptosis, and cell cycle will be crucial to gain insight into the regulation of stemness. Full article

(This article belongs to the Special Issue Wnt Signaling in Stem Cells)

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14 pages, 769 KiB

Open AccessReview

Glutamine Synthetase: Localization Dictates Outcome

by Alessandra Castegna^1,2,* and Alessio Menga²

¹ Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari 70125, Italy

² Hematology Unit, National Cancer Research Center, Istituto Tumori 'Giovanni Paolo II', Bari 70124, Italy

Genes 2018, 9(2), 108; https://doi.org/10.3390/genes9020108 - 19 Feb 2018

Cited by 45 | Viewed by 9859

Abstract

Glutamine synthetase (GS) is the adenosine triphosphate (ATP)-dependent enzyme that catalyses the synthesis of glutamine by condensing ammonium to glutamate. In the circulatory system, glutamine carries ammonia from muscle and brain to the kidney and liver. In brain reduction of GS activity has [...] Read more.

Glutamine synthetase (GS) is the adenosine triphosphate (ATP)-dependent enzyme that catalyses the synthesis of glutamine by condensing ammonium to glutamate. In the circulatory system, glutamine carries ammonia from muscle and brain to the kidney and liver. In brain reduction of GS activity has been suggested as a mechanism mediating neurotoxicity in neurodegenerative disorders. In cancer, the delicate balance between glutamine synthesis and catabolism is a critical event. In vitro evidence, confirmed in vivo in some cases, suggests that reduced GS activity in cancer cells associates with a more invasive and aggressive phenotype. However, GS is known to be highly expressed in cells of the tumor microenvironment, such as fibroblasts, adipocytes and immune cells, and their ability to synthesize glutamine is responsible for the acquisition of protumoral phenotypes. This has opened a new window into the complex scenario of the tumor microenvironment, in which the balance of glutamine consumption versus glutamine synthesis influences cellular function. Since GS expression responds to glutamine starvation, a lower glutamine synthesizing power due to the absence of GS in cancer cells might apply a metabolic pressure on stromal cells. This event might push stroma towards a GS-high/protumoral phenotype. When referred to stromal cells, GS expression might acquire a ‘bad’ significance to the point that GS inhibition might be considered a conceivable strategy against cancer metastasis. Full article

(This article belongs to the Special Issue The Double-Edged Role of Noncanonical Oncogenes and Tumor Suppressor Genes in Cancer Progression; An Oncojanus Function)

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31 pages, 1314 KiB

Open AccessReview

Alternative Splicing of Transcription Factors Genes in Muscle Physiology and Pathology

by Carol Imbriano

and Susanna Molinari^*

University of Modena and Reggio Emilia, Department of Life Sciences, Modena, Italy

Genes 2018, 9(2), 107; https://doi.org/10.3390/genes9020107 - 19 Feb 2018

Cited by 24 | Viewed by 9619

Abstract

Skeletal muscle formation is a multi-step process that is governed by complex networks of transcription factors. The regulation of their functions is in turn multifaceted, including several mechanisms, among them alternative splicing (AS) plays a primary role. On the other hand, altered AS [...] Read more.

Skeletal muscle formation is a multi-step process that is governed by complex networks of transcription factors. The regulation of their functions is in turn multifaceted, including several mechanisms, among them alternative splicing (AS) plays a primary role. On the other hand, altered AS has a role in the pathogenesis of numerous muscular pathologies. Despite these premises, the causal role played by the altered splicing pattern of transcripts encoding myogenic transcription factors in neuromuscular diseases has been neglected so far. In this review, we systematically investigate what has been described about the AS patterns of transcription factors both in the physiology of the skeletal muscle formation process and in neuromuscular diseases, in the hope that this may be useful in re-evaluating the potential role of altered splicing of transcription factors in such diseases. Full article

(This article belongs to the Special Issue Aberrant Pre-mRNA Splicing in Disease)

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11 pages, 910 KiB

Open AccessCommunication

Antibiotic Resistance Genetic Markers and Integrons in White Soft Cheese: Aspects of Clinical Resistome and Potentiality of Horizontal Gene Transfer

by Ana Caroline L. De Paula, Julliane D. Medeiros, Analice C. De Azevedo, Jéssica M. De Assis Chagas, Vânia L. Da Silva and Cláudio G. Diniz^*

Department of Parasitology, Microbiology and Immunology, Institute of Biological Sciences, Federal University of Juiz de Fora, 36036-900 Juiz de Fora, MG, Brazil

Genes 2018, 9(2), 106; https://doi.org/10.3390/genes9020106 - 19 Feb 2018

Cited by 15 | Viewed by 6238

Abstract

Antibiotic resistance poses an important threat to global public health and has become a challenge to modern medicine. The occurrence of antibiotic-resistant bacteria in a broad range of foods has led to a growing concern about the impact that food may have as [...] Read more.

Antibiotic resistance poses an important threat to global public health and has become a challenge to modern medicine. The occurrence of antibiotic-resistant bacteria in a broad range of foods has led to a growing concern about the impact that food may have as a reservoir of antibiotic resistance genes. Considering Minas Frescal Cheese (MFC)—a typical Brazilian white soft cheese—and its economic and cultural values, in this study, medically relevant antimicrobial-resistance genetic markers (AR genes) were screened, and the occurrence of integrons were evaluated in manufactured MFC using culture-independent approaches. Through a fingerprinting analysis, the tested MFCs were brand-clustered, indicating reproducibility along the production chain. A common core of resistance markers in all brands evaluated and related antimicrobials such as β-lactams, tetracyclines, quinolones, and sulfonamide was detected. Several other markers, including efflux pumps and aminoglycosides-resistance were distributed among brands. Class 1 and 2 integrons were observed, respectively, in 77% and 97% of the samples. The presence of AR genes is of special interest due to their clinical relevance. Taken together, the data may suggest that the production chain of MFC might contribute to the spread of putative drug-resistant bacteria, which could greatly impact human health. Furthermore, detection of class 1 and class 2 integrons in MFC has led to discussions about resistance gene spread in this traditional cheese, providing evidence of potential horizontal transfer of AR genes to human gut microbiota. Full article

(This article belongs to the Special Issue Genetics and Genomics of Foodborne Pathogens)

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21 pages, 690 KiB

Open AccessReview

The Role of Wnt Signal in Glioblastoma Development and Progression: A Possible New Pharmacological Target for the Therapy of This Tumor

by Mariachiara Zuccarini^1,2,†, Patricia Giuliani^1,2,†, Sihana Ziberi^1,2,3, Marzia Carluccio^1,2,3, Patrizia Di Iorio^1,2, Francesco Caciagli^1,2 and Renata Ciccarelli^1,2,3,*

¹ Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, via dei Vestini 29, 66100 Chieti, Italy

² Aging Research Center and Translational Medicine (CeSI-MeT), via L. Polacchi 11, 66100 Chieti, Italy

³ StemTeCh Group, via L. Polacchi 11, 66100 Chieti, Italy

^† These authors contribute equally to this work.

Genes 2018, 9(2), 105; https://doi.org/10.3390/genes9020105 - 17 Feb 2018

Cited by 98 | Viewed by 7603

Abstract

Wnt is a complex signaling pathway involved in the regulation of crucial biological functions such as development, proliferation, differentiation and migration of cells, mainly stem cells, which are virtually present in all embryonic and adult tissues. Conversely, dysregulation of Wnt signal is implicated [...] Read more.

Wnt is a complex signaling pathway involved in the regulation of crucial biological functions such as development, proliferation, differentiation and migration of cells, mainly stem cells, which are virtually present in all embryonic and adult tissues. Conversely, dysregulation of Wnt signal is implicated in development/progression/invasiveness of different kinds of tumors, wherein a certain number of multipotent cells, namely “cancer stem cells”, are characterized by high self-renewal and aggressiveness. Hence, the pharmacological modulation of Wnt pathway could be of particular interest, especially in tumors for which the current standard therapy results to be unsuccessful. This might be the case of glioblastoma multiforme (GBM), one of the most lethal, aggressive and recurrent brain cancers, probably due to the presence of highly malignant GBM stem cells (GSCs) as well as to a dysregulation of Wnt system. By examining the most recent literature, here we point out several factors in the Wnt pathway that are altered in human GBM and derived GSCs, as well as new molecular strategies or experimental drugs able to modulate/inhibit aberrant Wnt signal. Altogether, these aspects serve to emphasize the existence of alternative pharmacological targets that may be useful to develop novel therapies for GBM. Full article

(This article belongs to the Special Issue Wnt Signaling in Stem Cells)

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13 pages, 812 KiB

Open AccessArticle

Microbiome Data Accurately Predicts the Postmortem Interval Using Random Forest Regression Models

by Aeriel Belk^1,†, Zhenjiang Zech Xu^2,†, David O. Carter³, Aaron Lynne⁴, Sibyl Bucheli⁴

, Rob Knight^2,5,6,* and Jessica L. Metcalf^1,*

¹ Department of Animal Sciences, Colorado State University, Fort Collins, CO 80525, USA

² Department of Pediatrics, University of California, La Jolla, San Diego, CA 92093, USA

³ Laboratory of Forensic Taphonomy, Forensic Sciences Unit, Division of Natural Sciences and Mathematics, Chaminade University of Honolulu, Honolulu, HI 96816, USA

⁴ Department of Biological Sciences, Sam Houston State University, Huntsville, TX 77340, USA

⁵ Department of Computer Science and Engineering, University of California, San Diego, CA 92037, USA

⁶ Microbiome Innovation Center, University of California, San Diego, CA 92037, USA

^† Contributed equally.

Genes 2018, 9(2), 104; https://doi.org/10.3390/genes9020104 - 16 Feb 2018

Cited by 85 | Viewed by 12651

Abstract

Death investigations often include an effort to establish the postmortem interval (PMI) in cases in which the time of death is uncertain. The postmortem interval can lead to the identification of the deceased and the validation of witness statements and suspect alibis. Recent [...] Read more.

Death investigations often include an effort to establish the postmortem interval (PMI) in cases in which the time of death is uncertain. The postmortem interval can lead to the identification of the deceased and the validation of witness statements and suspect alibis. Recent research has demonstrated that microbes provide an accurate clock that starts at death and relies on ecological change in the microbial communities that normally inhabit a body and its surrounding environment. Here, we explore how to build the most robust Random Forest regression models for prediction of PMI by testing models built on different sample types (gravesoil, skin of the torso, skin of the head), gene markers (16S ribosomal RNA (rRNA), 18S rRNA, internal transcribed spacer regions (ITS)), and taxonomic levels (sequence variants, species, genus, etc.). We also tested whether particular suites of indicator microbes were informative across different datasets. Generally, results indicate that the most accurate models for predicting PMI were built using gravesoil and skin data using the 16S rRNA genetic marker at the taxonomic level of phyla. Additionally, several phyla consistently contributed highly to model accuracy and may be candidate indicators of PMI. Full article

(This article belongs to the Special Issue Forensic Genomics)

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24 pages, 2566 KiB

Open AccessReview

Microfluidic Devices for Drug Delivery Systems and Drug Screening

by Samar Damiati^1,*

, Uday B. Kompella², Safa A. Damiati³ and Rimantas Kodzius^4,5,6,7,*

¹ Department of Biochemistry, Faculty of Science, King Abdulaziz University (KAU), Jeddah 21589, Saudi Arabia

² Department of Pharmaceutical Sciences, Ophthalmology, and Bioengineering, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA

³ Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University (KAU), Jeddah 21589, Saudi Arabia

⁴ Mathematics and Natural Sciences Department, The American University of Iraq, Sulaimani, Sulaymaniyah 46001, Iraq

⁵ Materials Genome Institute, Shanghai University, Shanghai 200444, China

⁶ Faculty of Medicine, Ludwig Maximilian University of Munich (LMU), 80539 Munich, Germany

⁷ Faculty of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany

Genes 2018, 9(2), 103; https://doi.org/10.3390/genes9020103 - 16 Feb 2018

Cited by 315 | Viewed by 24050

Abstract

Microfluidic devices present unique advantages for the development of efficient drug carrier particles, cell-free protein synthesis systems, and rapid techniques for direct drug screening. Compared to bulk methods, by efficiently controlling the geometries of the fabricated chip and the flow rates of multiphase [...] Read more.

Microfluidic devices present unique advantages for the development of efficient drug carrier particles, cell-free protein synthesis systems, and rapid techniques for direct drug screening. Compared to bulk methods, by efficiently controlling the geometries of the fabricated chip and the flow rates of multiphase fluids, microfluidic technology enables the generation of highly stable, uniform, monodispersed particles with higher encapsulation efficiency. Since the existing preclinical models are inefficient drug screens for predicting clinical outcomes, microfluidic platforms might offer a more rapid and cost-effective alternative. Compared to 2D cell culture systems and in vivo animal models, microfluidic 3D platforms mimic the in vivo cell systems in a simple, inexpensive manner, which allows high throughput and multiplexed drug screening at the cell, organ, and whole-body levels. In this review, the generation of appropriate drug or gene carriers including different particle types using different configurations of microfluidic devices is highlighted. Additionally, this paper discusses the emergence of fabricated microfluidic cell-free protein synthesis systems for potential use at point of care as well as cell-, organ-, and human-on-a-chip models as smart, sensitive, and reproducible platforms, allowing the investigation of the effects of drugs under conditions imitating the biological system. Full article

(This article belongs to the Special Issue From the Lab-on-a-Chip to the Organ-on-a-Chip)

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17 pages, 1784 KiB

Open AccessArticle

Dietary Fiber Treatment Corrects the Composition of Gut Microbiota, Promotes SCFA Production, and Suppresses Colon Carcinogenesis

by Faraz Bishehsari^1,*, Phillip A. Engen¹, Nailliw Z. Preite¹

, Yunus E. Tuncil^2,†

, Ankur Naqib³, Maliha Shaikh¹, Marco Rossi¹, Sherry Wilber¹, Stefan J. Green^3,4

, Bruce R. Hamaker², Khashayarsha Khazaie⁵, Robin M. Voigt¹, Christopher B. Forsyth¹ and Ali Keshavarzian^1,6,7,8

¹ Department of Internal Medicine, Division of Gastroenterology, Rush University Medical Center, Chicago, IL 60612, USA

² Whistler Center for Carbohydrate Research, Department of Food Science, Purdue University, West Lafayette, IN 47907-2009, USA

³ DNA Services Facility, Research Resources Center, University of Illinois at Chicago, Chicago, IL 60612, USA

⁴ Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA

⁵ Department of Immunology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN 55905, USA

⁶ Department of Physiology, Rush University Medical Center, Chicago, IL 60612, USA

⁷ Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands

⁸ Department of Pharmacology, Rush University Medical Center, Chicago, IL 60612, USA

^† Present address: Department of Food Engineering, Ordu University, Ordu, Turkey.

Genes 2018, 9(2), 102; https://doi.org/10.3390/genes9020102 - 16 Feb 2018

Cited by 175 | Viewed by 16107

Abstract

Epidemiological studies propose a protective role for dietary fiber in colon cancer (CRC). One possible mechanism of fiber is its fermentation property in the gut and ability to change microbiota composition and function. Here, we investigate the role of a dietary fiber mixture [...] Read more.

Epidemiological studies propose a protective role for dietary fiber in colon cancer (CRC). One possible mechanism of fiber is its fermentation property in the gut and ability to change microbiota composition and function. Here, we investigate the role of a dietary fiber mixture in polyposis and elucidate potential mechanisms using TS4Cre × cAPC^l°^x468 mice. Stool microbiota profiling was performed, while functional prediction was done using PICRUSt. Stool short-chain fatty acid (SCFA) metabolites were measured. Histone acetylation and expression of SCFA butyrate receptor were assessed. We found that SCFA-producing bacteria were lower in the polyposis mice, suggesting a decline in the fermentation product of dietary fibers with polyposis. Next, a high fiber diet was given to polyposis mice, which significantly increased SCFA-producing bacteria as well as SCFA levels. This was associated with an increase in SCFA butyrate receptor and a significant decrease in polyposis. In conclusion, we found polyposis to be associated with dysbiotic microbiota characterized by a decline in SCFA-producing bacteria, which was targetable by high fiber treatment, leading to an increase in SCFA levels and amelioration of polyposis. The prebiotic activity of fiber, promoting beneficial bacteria, could be the key mechanism for the protective effects of fiber on colon carcinogenesis. SCFA-promoting fermentable fibers are a promising dietary intervention to prevent CRC. Full article

(This article belongs to the Special Issue Intestinal Microbes and Cancer)

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11 pages, 2698 KiB

Open AccessOpinion

Modeling the Role of Wnt Signaling in Human and Drosophila Stem Cells

by Prameet Kaur^1,†, Helen Jingshu Jin^1,†, Jay B Lusk^1,†

and Nicholas S. Tolwinski^1,2,*

¹ Yale-NUS College Research Labs, Singapore 117608, Singapore

² Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore

^† Authors contributed equally to this work.

Genes 2018, 9(2), 101; https://doi.org/10.3390/genes9020101 - 16 Feb 2018

Cited by 15 | Viewed by 6758

Abstract

The discovery of induced pluripotent stem (iPS) cells, barely more than a decade ago, dramatically transformed the study of stem cells and introduced a completely new way to approach many human health concerns. Although advances have pushed the field forward, human application remains [...] Read more.

The discovery of induced pluripotent stem (iPS) cells, barely more than a decade ago, dramatically transformed the study of stem cells and introduced a completely new way to approach many human health concerns. Although advances have pushed the field forward, human application remains some years away, in part due to the need for an in-depth mechanistic understanding. The role of Wnts in stem cells predates the discovery of iPS cells with Wnts established as major pluripotency promoting factors. Most work to date has been done using mouse and tissue culture models and few attempts have been made in other model organisms, but the recent combination of clustered regularly interspaced short palindromic repeats (CRISPR) gene editing with iPS cell technology provides a perfect avenue for exploring iPS cells in model organisms. Drosophila is an ideal organism for such studies, but fly iPS cells have not yet been made. In this opinion article, we draw parallels between Wnt signaling in human and Drosophila stem cell systems, propose ways to obtain Drosophila iPS cells, and suggest ways to exploit the versatility of the Drosophila system for future stem cell studies. Full article

(This article belongs to the Special Issue Wnt Signaling in Stem Cells)

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20 pages, 1238 KiB

Open AccessArticle

High Prevalence of Quorum-Sensing and Quorum-Quenching Activity among Cultivable Bacteria and Metagenomic Sequences in the Mediterranean Sea

by Andrea Muras¹

, Mario López-Pérez², Celia Mayer¹, Ana Parga¹

, Jaime Amaro-Blanco¹ and Ana Otero^1,*

¹ Departamento de Microbioloxía e Parasitoloxía, Facultade de Bioloxía-CIBUS, Universidade de Santiago de Compostela, Santiago de Compostela 15782, Spain

² Evolutionary Genomics Group, División de Microbiología, Universidad Miguel Hernández, San Juan de Alicante 03202, Spain

Genes 2018, 9(2), 100; https://doi.org/10.3390/genes9020100 - 16 Feb 2018

Cited by 38 | Viewed by 6294

Abstract

There is increasing evidence being accumulated regarding the importance of N-acyl homoserine lactones (AHL)-mediated quorum-sensing (QS) and quorum-quenching (QQ) processes in the marine environment, but in most cases, data has been obtained from specific microhabitats, and subsequently little is known regarding these [...] Read more.

There is increasing evidence being accumulated regarding the importance of N-acyl homoserine lactones (AHL)-mediated quorum-sensing (QS) and quorum-quenching (QQ) processes in the marine environment, but in most cases, data has been obtained from specific microhabitats, and subsequently little is known regarding these activities in free-living marine bacteria. The QS and QQ activities among 605 bacterial isolates obtained at 90 and 2000 m depths in the Mediterranean Sea were analyzed. Additionally, putative QS and QQ sequences were searched in metagenomic data obtained at different depths (15–2000 m) at the same sampling site. The number of AHL producers was higher in the 90 m sample (37.66%) than in the 2000 m sample (4.01%). However, the presence of QQ enzymatic activity was 1.63-fold higher in the 2000 m sample. The analysis of putative QQ enzymes in the metagenomes supports the relevance of QQ processes in the deepest samples, found in cultivable bacteria. Despite the unavoidable biases in the cultivation methods and biosensor assays and the possible promiscuous activity of the QQ enzymes retrieved in the metagenomic analysis, the results indicate that AHL-related QS and QQ processes could be common activity in the marine environment. Full article

(This article belongs to the Special Issue Genetic Networks and Gene Regulation Mechanisms for Quorum Sensing and Quorum Quenching in Bacteria)

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15 pages, 3482 KiB

Open AccessArticle

Characterization of the Symbiotic Nitrogen-Fixing Common Bean Low Phytic Acid (lpa1) Mutant Response to Water Stress

by Remo Chiozzotto¹, Mario Ramírez¹, Chouhra Talbi¹, Eleonora Cominelli², Lourdes Girard¹, Francesca Sparvoli² and Georgina Hernández^1,*

¹ Center for Genomic Sciences, National Autonomous University of Mexico, Av, Universidad 1001, Cuernavaca 62210, Mor., Mexico

² Institute of Agricultural Biology and Biotechnology, National Research Council, IBBA-CNR, Via Edoardo Bassini 15, 20133 Milano, Italy

Genes 2018, 9(2), 99; https://doi.org/10.3390/genes9020099 - 15 Feb 2018

Cited by 8 | Viewed by 4907

Abstract

The common bean (Phaseolus vulgaris L.) low phytic acid (lpa1) biofortified genotype produces seeds with improved nutritional characteristics and does not display negative pleiotropic effects. Here we demonstrated that lpa1 plants establish an efficient nitrogen-fixing symbiosis with Rhizobium etli CE3. [...] Read more.

The common bean (Phaseolus vulgaris L.) low phytic acid (lpa1) biofortified genotype produces seeds with improved nutritional characteristics and does not display negative pleiotropic effects. Here we demonstrated that lpa1 plants establish an efficient nitrogen-fixing symbiosis with Rhizobium etli CE3. The lpa1 nodules showed a higher expression of nodule-function related genes than the nodules of the parental wild type genotype (BAT 93). We analyzed the response to water stress of lpa1 vs. BAT 93 plants grown under fertilized or under symbiotic N₂-fixation conditions. Water stress was induced by water withholding (up to 14% soil moisture) to fertilized or R. etli nodulated plants previously grown with normal irrigation. The fertilized lpa1 plants showed milder water stress symptoms during the water deployment period and after the rehydration recovery period when lpa1 plants showed less biomass reduction. The symbiotic water-stressed lpa1 plants showed decreased nitrogenase activity that coincides with decreased sucrose synthase gene expression in nodules; lower turgor weight to dry weight (DW) ratio, which has been associated with higher drought resistance index; downregulation of carbon/nitrogen (C/N)-related and upregulation of stress-related genes. Higher expression of stress-related genes was also observed in bacteroids of stressed lpa1 plants that also displayed very high expression of the symbiotic cbb₃ oxidase (fixNd). Full article

(This article belongs to the Special Issue Genetics and Genomics of the Rhizobium-Legume Symbiosis)

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10 pages, 1010 KiB

Open AccessReview

Modulation of VEGF-A Alternative Splicing as a Novel Treatment in Chronic Kidney Disease

by Megan Stevens^* and Sebastian Oltean^*

Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Exeter, EX1 2LU, UK

Genes 2018, 9(2), 98; https://doi.org/10.3390/genes9020098 - 15 Feb 2018

Cited by 17 | Viewed by 7410

Abstract

Vascular endothelial growth factor A (VEGF-A) is a prominent pro-angiogenic and pro-permeability factor in the kidney. Alternative splicing of the terminal exon of VEGF-A through the use of an alternative 3′ splice site gives rise to a functionally different family of isoforms, termed [...] Read more.

Vascular endothelial growth factor A (VEGF-A) is a prominent pro-angiogenic and pro-permeability factor in the kidney. Alternative splicing of the terminal exon of VEGF-A through the use of an alternative 3′ splice site gives rise to a functionally different family of isoforms, termed VEGF-A_xxxb, known to have anti-angiogenic and anti-permeability properties. Dysregulation of the VEGF-A_xxx/VEGF-A_xxxb isoform balance has recently been reported in several kidney pathologies, including diabetic nephropathy (DN) and Denys–Drash syndrome. Using mouse models of kidney disease where the VEGF-A isoform balance is disrupted, several reports have shown that VEGF-A₁₆₅b treatment/over-expression in the kidney is therapeutically beneficial. Furthermore, inhibition of certain splice factor kinases involved in the regulation of VEGF-A terminal exon splicing has provided some mechanistic insight into how VEGF-A splicing could be regulated in the kidney. This review highlights the importance of further investigation into the novel area of VEGF-A splicing in chronic kidney disease pathogenesis and how future studies may allow for the development of splicing-modifying therapeutic drugs. Full article

(This article belongs to the Special Issue Aberrant Pre-mRNA Splicing in Disease)

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14 pages, 1654 KiB

Open AccessArticle

Exploration and Exploitation of Novel SSR Markers for Candidate Transcription Factor Genes in Lilium Species

by Manosh Kumar Biswas¹

, Ujjal Kumar Nath^1,2, Jewel Howlader¹, Mita Bagchi¹, Sathishkumar Natarajan¹

, Md Abdul Kayum¹, Hoy-Taek Kim^1,3, Jong-In Park¹, Jong-Goo Kang¹ and Ill-Sup Nou^1,*

¹ Department of Horticulture, Sunchon National University, 255 Jungang-ro, Suncheon, Jeonnam 57922, Korea

² University-Industry Cooperation Foundation, Sunchon National University, 255 Jungang-ro, Suncheon, Jeonnam 57922, Korea

³ University-Industry Cooperation Foundation, Sunchon National University, 255 Jungang-ro, Suncheon, Jeonnam 57922, Korea

Genes 2018, 9(2), 97; https://doi.org/10.3390/genes9020097 - 14 Feb 2018

Cited by 19 | Viewed by 5130

Abstract

Lilies (Lilium sp.) are commercially important horticultural crops widely cultivated for their flowers and bulbs. Here, we conducted large-scale data mining of the lily transcriptome to develop transcription factor (TF)-associated microsatellite markers (TFSSRs). Among 216,768 unigenes extracted from our sequence data, 6966 [...] Read more.

Lilies (Lilium sp.) are commercially important horticultural crops widely cultivated for their flowers and bulbs. Here, we conducted large-scale data mining of the lily transcriptome to develop transcription factor (TF)-associated microsatellite markers (TFSSRs). Among 216,768 unigenes extracted from our sequence data, 6966 unigenes harbored simple sequence repeats (SSRs). Seventy-one SSRs were associated with TF genes, and these were used to design primers and validate their potential as markers. These 71 SSRs were accomplished with 31 transcription factor families; including bHLH, MYB, C2H2, ERF, C3H, NAC, bZIP, and so on. Fourteen highly polymorphic SSRs were selected based on Polymorphic Information Content (PIC) values and used to study genetic diversity and population structure in lily accessions. Higher genetic diversity was observed in Longiflorum compared to Oriental and Asiatic populations. Lily accessions were divided into three sub-populations based in our structure analysis, and an un-rooted neighbor-joining tree effectively separated the accessions according to Asiatic, Oriental, and Longiflorum subgroups. Finally, we showed that 46 of the SSR-associated genes were differentially expressed in response to Botrytis elliptica infection. Thus, our newly developed TFSSR markers represent a powerful tool for large-scale genotyping, high-density and comparative mapping, marker-aided backcrossing, and molecular diversity analysis of Lilium sp. Full article

(This article belongs to the Section Plant Genetics and Genomics)

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27 pages, 6121 KiB

Open AccessReview

Vertebrate Genome Evolution in the Light of Fish Cytogenomics and rDNAomics

by Radka Symonová^1,*

and W. Mike Howell²

¹ Faculty of Science, Department of Biology, University of Hradec Králové, 500 03 Hradec Králové, Czech Republic

² Department of Biological and Environmental Sciences, Samford University, Birmingham, AL 35229, USA

Genes 2018, 9(2), 96; https://doi.org/10.3390/genes9020096 - 14 Feb 2018

Cited by 29 | Viewed by 7189

Abstract

To understand the cytogenomic evolution of vertebrates, we must first unravel the complex genomes of fishes, which were the first vertebrates to evolve and were ancestors to all other vertebrates. We must not forget the immense time span during which the fish genomes [...] Read more.

To understand the cytogenomic evolution of vertebrates, we must first unravel the complex genomes of fishes, which were the first vertebrates to evolve and were ancestors to all other vertebrates. We must not forget the immense time span during which the fish genomes had to evolve. Fish cytogenomics is endowed with unique features which offer irreplaceable insights into the evolution of the vertebrate genome. Due to the general DNA base compositional homogeneity of fish genomes, fish cytogenomics is largely based on mapping DNA repeats that still represent serious obstacles in genome sequencing and assembling, even in model species. Localization of repeats on chromosomes of hundreds of fish species and populations originating from diversified environments have revealed the biological importance of this genomic fraction. Ribosomal genes (rDNA) belong to the most informative repeats and in fish, they are subject to a more relaxed regulation than in higher vertebrates. This can result in formation of a literal ‘rDNAome’ consisting of more than 20,000 copies with their high proportion employed in extra-coding functions. Because rDNA has high rates of transcription and recombination, it contributes to genome diversification and can form reproductive barrier. Our overall knowledge of fish cytogenomics grows rapidly by a continuously increasing number of fish genomes sequenced and by use of novel sequencing methods improving genome assembly. The recently revealed exceptional compositional heterogeneity in an ancient fish lineage (gars) sheds new light on the compositional genome evolution in vertebrates generally. We highlight the power of synergy of cytogenetics and genomics in fish cytogenomics, its potential to understand the complexity of genome evolution in vertebrates, which is also linked to clinical applications and the chromosomal backgrounds of speciation. We also summarize the current knowledge on fish cytogenomics and outline its main future avenues. Full article

(This article belongs to the Special Issue Chromosomal Evolution)

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14 pages, 3973 KiB

Open AccessArticle

Differential Expression of Six Rnase2 and Three Rnase3 Paralogs Identified in Blunt Snout Bream in Response to Aeromonas hydrophila Infection

by Ruijing Geng¹, Han Liu^1,2,* and Weimin Wang^1,3,*

¹ Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education/Key Lab of Freshwater Animal Breeding, College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China

² Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Chinese Academy of Fishery Sciences, Wuxi 214081, China

³ Collaborative Innovation Center for Efficient and Health Production of Fisheries in Hunan Province, Changde 415000, China

Genes 2018, 9(2), 95; https://doi.org/10.3390/genes9020095 - 14 Feb 2018

Cited by 11 | Viewed by 4066

Abstract

Ribonucleases (Rnases)2 and Rnase3 belong to the ribonuclease A (RnaseA) superfamily. Apart from their role in molecular evolutionary and functional biological studies, these genes have also been studied in the context of defense against pathogen infection in mammals. However, expression [...] Read more.

Ribonucleases (Rnases)2 and Rnase3 belong to the ribonuclease A (RnaseA) superfamily. Apart from their role in molecular evolutionary and functional biological studies, these genes have also been studied in the context of defense against pathogen infection in mammals. However, expression patterns, structures and response to bacterial infection of the two genes in blunt snout bream (Megalobrama amblycephala) remain unknown. In this study, we identified multiple copies of Rnase2 (six) and Rnase3 (three) in the M. amblycephala genome. The nine genes all possess characteristics typical of the RnaseA superfamily. No expression was detected in the early developmental stages, while a weak expression was observed at 120 and 140 h post-fertilization (hpf) for Rnase2b, Rnase2c, Rnase2e and Rnase3a, suggesting that only three copies of Rnase2 and one of Rnase3 are expressed. Interestingly, only Rnase2e was up-regulated in the kidney of M. amblycephala after Aeromonas hydrophila infection, while Rnase3a was significantly up-regulated in liver, gut and blood after the infection. We conclude that the paralogs of Rnase3 are more susceptible to A. hydrophila infection than Rnase2. These results indicate that different Rnase2 and Rnase3 paralogs suggest a role in the innate immune response of M. amblycephala to bacterial infection. Full article

(This article belongs to the Section Animal Genetics and Genomics)

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1 pages, 124 KiB

Open AccessAddendum

Addendum: Iwaszko et al., Influence of NKG2D Genetic Variants on Response to Anti-TNF Agents in Patients with Rheumatoid Arthritis. Genes 2018, 9, 64

by Milena Iwaszko^1,*, Jerzy Świerkot², Katarzyna Kolossa³, Sławomir Jeka³, Piotr Wiland² and Katarzyna Bogunia-Kubik^1,4

¹ Laboratory of Clinical Immunogenetics and Pharmacogenetics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland

² Department of Rheumatology and Internal Medicine, Wrocław Medical University, Borowska 213, 50-556 Wrocław, Poland

³ Clinical Department of Rheumatology and Connective Tissue Diseases, Hospital University Number 2 Jana Biziela, Ujejskiego 75, 85-168 Bydgoszcz, Poland

⁴ Department of Internal, Occupational Diseases, Hypertension and Clinical Oncology, Wrocław Medical University, Borowska 213, 50-556 Wrocław, Poland

Genes 2018, 9(2), 94; https://doi.org/10.3390/genes9020094 - 14 Feb 2018

Viewed by 2777

Abstract

It has been brought to our attention that the funding of the National Center of Science (Poland) was missing in the acknowledgements section of our published paper [1], and therefore we would like to add this and report the acknowledgements as follows:[...] Full article

(This article belongs to the Special Issue DNA Variations in Evolution and Human Diseases)

23 pages, 4884 KiB

Open AccessReview

The Pleiotropic Effects of the Canonical Wnt Pathway in Early Development and Pluripotency

by Anchel De Jaime-Soguero^†, Willy Antoni Abreu de Oliveira^† and Frederic Lluis^*

¹ Stem Cell Signalling Laboratory, Department of Development and Regeneration, KU Leuven Stem Cell Institute, Herestraat 49, Onderwijs en Navorsing 4, Box 804, 3000 Leuven, Belgium

^† These authors contributed equally to this work.

Genes 2018, 9(2), 93; https://doi.org/10.3390/genes9020093 - 14 Feb 2018

Cited by 49 | Viewed by 15937

Abstract

The technology to derive embryonic and induced pluripotent stem cells from early embryonic stages and adult somatic cells, respectively, emerged as a powerful resource to enable the establishment of new in vitro models, which recapitulate early developmental processes and disease. Additionally, pluripotent stem [...] Read more.

The technology to derive embryonic and induced pluripotent stem cells from early embryonic stages and adult somatic cells, respectively, emerged as a powerful resource to enable the establishment of new in vitro models, which recapitulate early developmental processes and disease. Additionally, pluripotent stem cells (PSCs) represent an invaluable source of relevant differentiated cell types with immense potential for regenerative medicine and cell replacement therapies. Pluripotent stem cells support self-renewal, potency and proliferation for extensive periods of culture in vitro. However, the core pathways that rule each of these cellular features specific to PSCs only recently began to be clarified. The Wnt signaling pathway is pivotal during early embryogenesis and is central for the induction and maintenance of the pluripotency of PSCs. Signaling by the Wnt family of ligands is conveyed intracellularly by the stabilization of β-catenin in the cytoplasm and in the nucleus, where it elicits the transcriptional activity of T-cell factor (TCF)/lymphoid enhancer factor (LEF) family of transcription factors. Interestingly, in PSCs, the Wnt/β-catenin–TCF/LEF axis has several unrelated and sometimes opposite cellular functions such as self-renewal, stemness, lineage commitment and cell cycle regulation. In addition, tight control of the Wnt signaling pathway enhances reprogramming of somatic cells to induced pluripotency. Several recent research efforts emphasize the pleiotropic functions of the Wnt signaling pathway in the pluripotent state. Nonetheless, conflicting results and unanswered questions still linger. In this review, we will focus on the diverse functions of the canonical Wnt signaling pathway on the developmental processes preceding embryo implantation, as well as on its roles in pluripotent stem cell biology such as self-renewal and cell cycle regulation and somatic cell reprogramming. Full article

(This article belongs to the Special Issue Wnt Signaling in Stem Cells)

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16 pages, 2681 KiB

Open AccessArticle

Identification of Key Pathways and Genes in the Dynamic Progression of HCC Based on WGCNA

by Li Yin^1,2,3,*, Zhihui Cai³, Baoan Zhu³ and Cunshuan Xu^1,2,*

¹ College of Life Science, Henan Normal University, Xinxiang 453007, Henan, China

² State Key Laboratory Cultivation Base for Cell Differentiation Regulation and Henan Engineering Laboratory for Bioengineering and Drug Development, Henan Normal University, Xinxiang 453007, Henan, China

³ Luohe Medical College, Luohe 462002, Henan, China

Genes 2018, 9(2), 92; https://doi.org/10.3390/genes9020092 - 14 Feb 2018

Cited by 128 | Viewed by 13732

Abstract

Hepatocellular carcinoma (HCC) is a devastating disease worldwide. Though many efforts have been made to elucidate the process of HCC, its molecular mechanisms of development remain elusive due to its complexity. To explore the stepwise carcinogenic process from pre-neoplastic lesions to the end [...] Read more.

Hepatocellular carcinoma (HCC) is a devastating disease worldwide. Though many efforts have been made to elucidate the process of HCC, its molecular mechanisms of development remain elusive due to its complexity. To explore the stepwise carcinogenic process from pre-neoplastic lesions to the end stage of HCC, we employed weighted gene co-expression network analysis (WGCNA) which has been proved to be an effective method in many diseases to detect co-expressed modules and hub genes using eight pathological stages including normal, cirrhosis without HCC, cirrhosis, low-grade dysplastic, high-grade dysplastic, very early and early, advanced HCC and very advanced HCC. Among the eight consecutive pathological stages, five representative modules are selected to perform canonical pathway enrichment and upstream regulator analysis by using ingenuity pathway analysis (IPA) software. We found that cell cycle related biological processes were activated at four neoplastic stages, and the degree of activation of the cell cycle corresponded to the deterioration degree of HCC. The orange and yellow modules enriched in energy metabolism, especially oxidative metabolism, and the expression value of the genes decreased only at four neoplastic stages. The brown module, enriched in protein ubiquitination and ephrin receptor signaling pathways, correlated mainly with the very early stage of HCC. The darkred module, enriched in hepatic fibrosis/hepatic stellate cell activation, correlated with the cirrhotic stage only. The high degree hub genes were identified based on the protein-protein interaction (PPI) network and were verified by Kaplan-Meier survival analysis. The novel five high degree hub genes signature that was identified in our study may shed light on future prognostic and therapeutic approaches. Our study brings a new perspective to the understanding of the key pathways and genes in the dynamic changes of HCC progression. These findings shed light on further investigations Full article

(This article belongs to the Special Issue Computational Approaches for Disease Gene Identification)

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11 pages, 741 KiB

Open AccessArticle

PClass: Protein Quaternary Structure Classification by Using Bootstrapping Strategy as Model Selection

by Chi-Chou Huang^1,2, Chi-Chang Chang^3,4

, Chi-Wei Chen^5,6, Shao-yu Ho⁵, Hsung-Pin Chang⁶ and Yen-Wei Chu^5,7,*

¹ School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan

² Division of Colon & Rectal Surgery, Department of Surgery, Chung Shan Medical University Hospital, Taichung 40201, Taiwan

³ School of Medical Informatics, Chung-Shan Medical University, Taichung 40201, Taiwan

⁴ IT Office, Chung Shan Medical University Hospital, Taichung 40201, Taiwan

⁵ Institute of Genomics and Bioinformatics, National Chung Hsing University, Kuo Kuang Rd., Taichung 402, Taiwan

⁶ Department of Computer Science and Engineering, National Chung-Hsing University, Kuo Kuang Rd., Taichung 402, Taiwan

⁷ Biotechnology Center, Agricultural Biotechnology Center, Institute of Molecular Biology, Graduate Institute of Biotechnology, National Chung Hsing University, Kuo Kuang Rd., Taichung 402, Taiwan

Genes 2018, 9(2), 91; https://doi.org/10.3390/genes9020091 - 14 Feb 2018

Cited by 5 | Viewed by 4725

Abstract

Protein quaternary structure complex is also known as a multimer, which plays an important role in a cell. The dimer structure of transcription factors is involved in gene regulation, but the trimer structure of virus-infection-associated glycoproteins is related to the human immunodeficiency virus. [...] Read more.

Protein quaternary structure complex is also known as a multimer, which plays an important role in a cell. The dimer structure of transcription factors is involved in gene regulation, but the trimer structure of virus-infection-associated glycoproteins is related to the human immunodeficiency virus. The classification of the protein quaternary structure complex for the post-genome era of proteomics research will be of great help. Classification systems among protein quaternary structures have not been widely developed. Therefore, we designed the architecture of a two-layer machine learning technique in this study, and developed the classification system PClass. The protein quaternary structure of the complex is divided into five categories, namely, monomer, dimer, trimer, tetramer, and other subunit classes. In the framework of the bootstrap method with a support vector machine, we propose a new model selection method. Each type of complex is classified based on sequences, entropy, and accessible surface area, thereby generating a plurality of feature modules. Subsequently, the optimal model of effectiveness is selected as each kind of complex feature module. In this stage, the optimal performance can reach as high as 70% of Matthews correlation coefficient (MCC). The second layer of construction combines the first-layer module to integrate mechanisms and the use of six machine learning methods to improve the prediction performance. This system can be improved over 10% in MCC. Finally, we analyzed the performance of our classification system using transcription factors in dimer structure and virus-infection-associated glycoprotein in trimer structure. PClass is available via a web interface at http://predictor.nchu.edu.tw/PClass/. Full article

(This article belongs to the Special Issue Selected Papers from the Bioinformatics and Intelligent Information Processing Conference (BIIP2018))

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2 pages, 172 KiB

Open AccessCorrection

Correction: Shelly Y. Shih; et al.; Applications of Probe Capture Enrichment Next Generation Sequencing for Whole Mitochondrial Genome and 426 Nuclear SNPs for Forensically Challenging Samples. Genes 2018, 9, 49

by Shelly Y. Shih¹

, Nikhil Bose^1,2, Anna Beatriz R. Gonçalves^1,3, Henry A. Erlich¹ and Cassandra D. Calloway^1,2,*

¹ Children’s Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, USA

² Forensic Science Graduate Program, University of California, Davis, 1909 Galileo Ct. Ste. B, Davis, CA 95618, USA

³ Laboratório de Diagnósticos por DNA (LDD), Universidade do Estado do Rio de Janeiro (UERJ), Instituto de Biologia Roberto Alcantara Gomes (IBRAG), Rua São Francisco Xavier, number 524, Pavilhão Haroldo Lisboa da Cunha, Rio de Janeiro 20550-900, RJ, Brazil

Genes 2018, 9(2), 90; https://doi.org/10.3390/genes9020090 - 14 Feb 2018

Cited by 3 | Viewed by 3918

Abstract

The authors wish to make the following change to their paper [1][...] Full article

(This article belongs to the Special Issue Forensic Genomics)

11 pages, 2792 KiB

Open AccessArticle

Embedded Disposable Functionalized Electrochemical Biosensor with a 3D-Printed Flow Cell for Detection of Hepatic Oval Cells (HOCs)

by Samar Damiati^1,2,*

, Martin Peacock³, Stefan Leonhardt⁴, Laila Damiati^5,6, Mohammed A. Baghdadi⁷

, Holger Becker⁸

, Rimantas Kodzius^9,10,11,12

and Bernhard Schuster²

¹ Department of Biochemistry, Faculty of Science, King Abdulaziz University (KAU), Jeddah 21589, Saudi Arabia

² Institute for Synthetic Bioarchitecture, Department of Nanobiotechnology, University of Natural Resources and Life Sciences, 1190 Vienna, Austria

³ Zimmer and Peacock Ltd., Royston SG8 9JL, UK

⁴ Institute of Medical and Polymer Engineering, Technical University of Munich (TUM), 85748 Garching, Germany

⁵ Centre for Cell Engineering, University of Glasgow, Glasgow G12 8QQ, UK

⁶ Department of Biology, Jeddah University, Jeddah 23218, Saudi Arabia

⁷ Research Centre, King Faisal Specialist Hospital & Research Centre, Jeddah 21499, Saudi Arabia

⁸ Microfluidic ChipShop Gmbh, 07747 Jena, Germany

⁹ Mathematics and Natural Sciences Department, The American University of Iraq, Sulaimani, Sulaymaniyah 46001, Iraq

¹⁰ Materials Genome Institute, Shanghai University, Shanghai 200444, China

¹¹ Faculty of Medicine, Ludwig Maximilian University of Munich (LMU), 80539 Munich, Germany

¹² Faculty of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany

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Genes 2018, 9(2), 89; https://doi.org/10.3390/genes9020089 - 14 Feb 2018

Cited by 36 | Viewed by 6587

Abstract

Hepatic oval cells (HOCs) are considered the progeny of the intrahepatic stem cells that are found in a small population in the liver after hepatocyte proliferation is inhibited. Due to their small number, isolation and capture of these cells constitute a challenging task [...] Read more.

Hepatic oval cells (HOCs) are considered the progeny of the intrahepatic stem cells that are found in a small population in the liver after hepatocyte proliferation is inhibited. Due to their small number, isolation and capture of these cells constitute a challenging task for immunosensor technology. This work describes the development of a 3D-printed continuous flow system and exploits disposable screen-printed electrodes for the rapid detection of HOCs that over-express the OV6 marker on their membrane. Multiwall carbon nanotube (MWCNT) electrodes have a chitosan film that serves as a scaffold for the immobilization of oval cell marker antibodies (anti-OV6-Ab), which enhance the sensitivity of the biomarker and makes the designed sensor specific for oval cells. The developed sensor can be easily embedded into the 3D-printed flow cell to allow cells to be exposed continuously to the functionalized surface. The continuous flow is intended to increase capture of most of the target cells in the specimen. Contact angle measurements were performed to characterize the nature and quality of the modified sensor surface, and electrochemical measurements (cyclic voltammetry (CV) and square wave voltammetry (SWV)) were performed to confirm the efficiency and selectivity of the fabricated sensor to detect HOCs. The proposed method is valuable for capturing rare cells and could provide an effective tool for cancer diagnosis and detection. Full article

(This article belongs to the Special Issue From the Lab-on-a-Chip to the Organ-on-a-Chip)

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14 pages, 1879 KiB

Open AccessReview

Genome Size Diversity and Its Impact on the Evolution of Land Plants

by Jaume Pellicer^*

, Oriane Hidalgo, Steven Dodsworth and Ilia J. Leitch

Department of Comparative Plant and Fungal Biology, Royal Botanic Gardens, Kew TW9 3DS, UK

Genes 2018, 9(2), 88; https://doi.org/10.3390/genes9020088 - 14 Feb 2018

Cited by 268 | Viewed by 17833

Abstract

Genome size is a biodiversity trait that shows staggering diversity across eukaryotes, varying over 64,000-fold. Of all major taxonomic groups, land plants stand out due to their staggering genome size diversity, ranging ca. 2400-fold. As our understanding of the implications and significance of [...] Read more.

Genome size is a biodiversity trait that shows staggering diversity across eukaryotes, varying over 64,000-fold. Of all major taxonomic groups, land plants stand out due to their staggering genome size diversity, ranging ca. 2400-fold. As our understanding of the implications and significance of this remarkable genome size diversity in land plants grows, it is becoming increasingly evident that this trait plays not only an important role in shaping the evolution of plant genomes, but also in influencing plant community assemblages at the ecosystem level. Recent advances and improvements in novel sequencing technologies, as well as analytical tools, make it possible to gain critical insights into the genomic and epigenetic mechanisms underpinning genome size changes. In this review we provide an overview of our current understanding of genome size diversity across the different land plant groups, its implications on the biology of the genome and what future directions need to be addressed to fill key knowledge gaps. Full article

(This article belongs to the Special Issue Evolution and Biodiversity of the Plant Genome Architecture)

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Genes, Volume 9, Issue 2 (February 2018) – 63 articles

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