scholarly journals Genome-wide transcriptional responses of marine nematode Litoditis marina to hyposaline and hypersaline stresses

2021 ◽  
Author(s):  
Yusu Xie ◽  
Pengchi Zhang ◽  
Liusuo Zhang
Keyword(s):  
Molecular Mechanisms ◽  
Unsaturated Fatty Acids ◽  
Biological Evolution ◽  
Intraflagellar Transport ◽  
Marine Nematode ◽  
Marine Animals ◽  
Transcriptional Responses ◽  
Genome Wide ◽  
Wide Range ◽  
Collagen Genes

AbstractMaintenance of osmotic homeostasis is essential for all organisms, especially for marine animals in the ocean with 30‰ salinity or higher. However, the underlying molecular mechanisms that how marine animals adapt to high salinity environment compared to their terrestrial relatives, remain elusive. Here, we investigated marine animal’s genome-wide transcriptional responses to salinity stresses using an emerging marine nematode model Litoditis marina. We found that the transthyretin-like family genes were significantly increased in both hyposaline and hypersaline conditions, while multiple neurotransmitter receptor and ion transporter genes were down-regulated in both conditions, suggesting the existence of conserved strategies for response to stressful salinity environments in L. marina. Unsaturated fatty acids biosynthesis related genes, neuronal related tubulins and intraflagellar transport genes were specifically up-regulated in hyposaline treated worms, while exhibited the opposite regulation in hypersaline condition. By contrast, cuticle related collagen genes were enriched and up-regulated for hypersaline response, interestingly, the expression of these collagen genes was significantly decreased in hyposaline condition. Given a wide range of salinity tolerance of the marine nematodes, this study and further genetic analysis of key gene(s) of osmoregulation in L. marina will likely provide important insights into biological evolution and environmental adaptation mechanisms in nematodes and other invertebrate animals in general.

scholarly journals Transcriptome signature of E. coli under a prolonged starvation environment

2020 ◽  
Author(s):  
Sotaro Takano ◽  
Hiromi Takahashi ◽  
Yoshie Yama ◽  
Ryo Miyazaki ◽  
Saburo Tsuru
Keyword(s):  
Stationary Phase ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Physiological State ◽  
Exponential Growth Phase ◽  
Transcriptional Responses ◽  
E Coli ◽  
Viable Cells ◽  
Genome Wide

ABSTRACTBackground“Non-growing” is a dominant life form of microorganisms in nature, where available nutrients and resources are extremely limited. However, the knowledge of the manner in which microorganisms resist nutrient deficiency is still rudimentary compared to those of the growing cells. In laboratory culture, Escherichia coli can survive for several years under starvation, denoted as long-term stationary phase (LSP), where a small fraction of the cells survive by recycling resources released from the starved nonviable cells and constitute a model system for understanding survival mechanisms under long-term starvation. Although the physiology by which viable cells in LSP adapt to long-term starvation is of great interest, their genome-wide response has not yet been fully understood.ResultsTo understand the physiological state of viable cells in the LSP environment, we analyzed the transcriptional profiles of cells exposed to the supernatant of LSP culture. We found that high expression of transporter genes and low expression of biosynthesis genes are the primary responses of the cells in the LSP supernatant compared to growing cells, which display similar responses to cells entering the stationary phase from the exponential growth phase. We also revealed some specific transcriptional responses in the LSP supernatant, such as higher expression of stress-response genes and lower expression of translation-related genes, compared to other non-growing conditions. This suggests that cells in LSP are highly efficient in terms of cellular survival and maintenance functions under starvation conditions. We also found population-density-dependent gene expression profiles in LSP, which are also informative to understand the survival mechanism of bacterial population.ConclusionOur current comprehensive analysis of the transcriptome of E. coli cells provides an overview of the genome-wide response to the long-term starvation environment. We detected both common and distinctive responses in the primary transcriptional changes between the short- and long-term stationary phase cultures, which could provide clues to understand the possible molecular mechanisms underlying survivability in the starved environment.

scholarly journals Genome-wide discovery and characterization of long noncoding RNAs in patients with multiple myeloma

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Minqiu Lu ◽  
Ying Hu ◽  
Yin Wu ◽  
Huixing Zhou ◽  
Yuan Jian ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Molecular Mechanisms ◽  
Malignant Tumors ◽  
Coiled Coil ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Aberrant Expression ◽  
Genome Wide ◽  
Wide Range ◽  
Whole Transcriptome

Abstract Background Long noncoding RNAs (lncRNAs) are involved in a wide range of biological processes in tumorigenesis. However, the role of lncRNA expression in the biology, prognosis, and molecular classification of human multiple myeloma (MM) remains unclear, especially the biological functions of the vast majority of lncRNAs. Recently, lncRNAs have been identified in neoplastic hematologic disorders. Evidence has accumulated on the molecular mechanisms of action of lncRNAs, providing insight into their functional roles in tumorigenesis. This study aimed to characterize potential lncRNAs in patients with MM. Methods In this study, the whole-transcriptome strand-specific RNA sequencing of samples from three newly diagnosed patients with MM was performed. The whole transcriptome, including lncRNAs, microRNAs, and mRNAs, was analyzed. Using these data, MM lncRNAs were systematically analyzed, and the lncRNAs involved in the occurrence of MM were identified. Results The results revealed that MM lncRNAs had distinctive characteristics different from those of other malignant tumors. Further, the functions of a set of lncRNAs preferentially expressed in MM were verified, and several lncRNAs were identified as competing endogenous RNAs. More importantly, the aberrant expression of certain lncRNAs, including maternally expressed gene3, colon cancer–associated transcript1, and coiled-coil domain-containing 26, as well as some novel lncRNAs involved in the occurrence of MM was established. Further, lncRNAs were related to some microRNAs, regulated each other, and participated in MM development. Conclusions Genome-wide screening and functional analysis enabled the identification of a set of lncRNAs involved in the occurrence of MM. The interaction exists among microRNAs and lncRNAs.

Genome-wide alterations in gene expression of prostate cancer (PC) cells surviving neoadjuvant androgen deprivation therapy (ADT).

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 88-88
Author(s):  
Anna C. Ferrari ◽  
Ying Chen ◽  
Hatem E. Sabaawy ◽  
Mark N. Stein ◽  
David Foran ◽  
...  
Keyword(s):  
Gene Expression ◽  
Androgen Deprivation Therapy ◽  
Unsaturated Fatty Acids ◽  
R Package ◽  
Tumor Burden ◽  
Androgen Deprivation ◽  
Rna Seq ◽  
Genome Wide ◽  
Wide Range ◽  
Castrate Resistant

88 Background: Although androgen deprivation therapy initially decreases PC tumor burden, resistance to further androgen receptor (AR)-directed treatments or chemotherapy is inevitable once CRPC is established. We postulated that the stress of ADT triggers widespread alterations in expression that renders a metastable physiologic state conditioned by epigenetic changes that might be initially reversible by targeting non-androgen pathways. We conducted a pilot study to explore genome-wide expression alterations in PC foci surviving 3 months ADT (eADT). Methods: mRNA from 7 frozen microdissected PC foci and normal counterparts (NC) were processed for RNA-seq. RNA-seq changes in eADT specimens were compared first with NC and the untreated PC in the TCGA PRAD (TCGA) database to castrate resistant (mCRPC) specimens in the dbGAP study phs000915.v1.p1database. The raw data (fastq files) was quantified using kallisto, normalized by TMM using R package edgeR, batch effects corrected using R package SVA. Analysis of differential gene expression by R package sleuth. Pathway and gene set by GSEA, GAGE/pathview packages for Gene Ontology (GO) and KEGG. Results: TMPRSS2-ERG+, 5/7. Highest DEG in eADT vs. TCGA vs mCRPC were non-coding RNA’s. Among 17431 differentially regulated paths; GSEA of eADT vs TCGA or mCRPC: 341 (1.95%) and 1366 (7.84%) up- vs 46 (0.26%) and 59 (0.34%) down-regulated. KEGG paths, eADT vs. TCGA or mCRPC, 11 and 53 up vs. 2 and 3 down- respectively. Highly down- path in eADT vs TCGA (log q < 10-17) was ribosomal vs. cell cycle and DNA replication in mCRPC. Six paths significantly up- in eADT vs TCGA or mCRPC: Wnt, adherence junction, steroid biosynthesis, unsaturated fatty acids, citrate cycle, ErbB. Calcium, MAPK, insulin, GnRH and Hedgehog were also up- in eADT vs mCRPC. AR full-length was marginally higher in eADT than TCGA and lower than mCRPC, no differences in gene targets. Conclusions: This pilot data shows that ADT triggers a wide range of gene expression alterations that support PC cell survival and may be vulnerable to therapeutic targeting in addition to the androgen pathway. Validation of these findings is planned in a larger set of samples from the same bank.

scholarly journals Genome-Wide Association Study (GWAS) Analysis of Camelina Seedling Germination under Salt Stress Condition

Agronomy ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1444
Author(s):  
Zinan Luo ◽  
Aaron Szczepanek ◽  
Hussein Abdel-Haleem
Keyword(s):  
Molecular Mechanisms ◽  
Unsaturated Fatty Acids ◽  
Germination Rate ◽  
Genome Wide Association ◽  
Oilseed Crop ◽  
Salt Stress Condition ◽  
Genome Wide ◽  
Nacl Concentration ◽  
Seedling Germination ◽  
Two Stages

Camelina sativa is an important renewable oilseed crop for biofuel and feedstock that can relieve the reliance on petroleum-derived oils and reduce greenhouse gases and waste solids resulting from petroleum-derived oils consumption. C. sativa has recently seen revived attention due to its high oil content, high omega-3 unsaturated fatty acids, short life cycle, broader regional adaptation, and low-input agronomic requirements. However, abiotic stress such as salinity stress has imposed threatens on plant photosynthesis and growth by reducing water availability or osmotic stress, ion (Na+ and Cl−) toxicity, nutritional disorders and oxidative stress yield. There still remains much to know for the molecular mechanisms underlying these effects. In this study, a preliminary study applying 10 C. sativa cultivars to be treated under a gradient NaCl concentrations ranging from 0–250 mM and found that 100 mM was the optimal NaCl concentration to effectively differentiate phenotypic performance among different genotypes. Then, a spring panel consisting of 211 C. sativa accessions were germinated under 100 mM NaCl concentration. Six seedling germination traits, including germination rate at two stages (5-day and 9-day seedling stages), germination index, dry and fresh weight, and dry/fresh ratio, were measured. Significant correlations were found between the germination rate at two stages as well as plant biomass traits. Combining the phenotypic data and previously obtained genotypic data, a total of 17 significant trait-associated single nucleotide polymorphisms (SNPs) for the germination rate at the two stages and dry weight were identified from genome-wide association analysis (GWAS). These SNPs are located on putative candidate genes controlling plant root development by synergistically mediating phosphate metabolism, signal transduction and cell membrane activities. These identified SNPs could provide a foundation for future molecular breeding efforts aimed at improved salt tolerance in C. sativa.

scholarly journals Genome-Wide Analysis of Protein Family Diversity Provides Insights into Species-Specific Protein Family Expansions in Insects

2021 ◽  
Author(s):  
Mehmet DAYI
Keyword(s):  
Copy Number ◽  
Molecular Mechanisms ◽  
Specific Protein ◽  
Protein Family ◽  
Insect Species ◽  
Protein Families ◽  
Family Diversity ◽  
Genome Wide ◽  
Wide Range ◽  
Species Specific

Abstract Insects are one of the earliest land animals with more than 400 million years old history on Earth, and they compose more than 80% of species. Insects invade a wide range of ecosystems and are considered one of the most evolutionary successful organism groups. Today, many insect species’ genomes have been sequenced to encode molecular mechanisms behind this magnificent evolutionary plasticity. However, only limited genome-wide studies have been carried out to compare protein family diversity in insects. A total of 20 insect species belonging to seven insect orders and two morphogenesis groups were investigated for evolutionary relationships and to uncover protein family diversity in the present study. The phylogenetic analysis inferred from a total of 530 one-to-one single-copy ortholog genes were separated insects into two evolutionary clades based on morphogenesis. Protein family analyses showed that insects share core protein families that perform essential tasks in development and metabolic processes, such as Pkinase and Zinc Finger, cellular signaling and odorant perception (7tm), digestion of food molecules (Trypsin), and detoxification (p450) with copy number expansion compared to other protein families. Additionally, species-specific protein family expansion was observed in various protein families. This study provided insights into protein family diversity and variation among insects and highlights high copy number variation in protein families species-wide.

Artificial Intelligence for epigenetics: towards personalized medicine

2020 ◽  
Vol 27 ◽  
Author(s):  
Giulia De Riso ◽  
Sergio Cocozza
Keyword(s):  
Biological Sciences ◽  
Artificial Intelligence ◽  
Personalized Medicine ◽  
Molecular Mechanisms ◽  
Genomic Sequence ◽  
Health Care Interventions ◽  
Genome Wide ◽  
Genetic And Environmental Factors ◽  
Opening Up ◽  
Omic Data

: Epigenetics is a field of biological sciences focused on the study of reversible, heritable changes in gene function not due to modifications of the genomic sequence. These changes are the result of a complex cross-talk between several molecular mechanisms, that is in turn orchestrated by genetic and environmental factors. The epigenetic profile captures the unique regulatory landscape and the exposure to environmental stimuli of an individual. It thus constitutes a valuable reservoir of information for personalized medicine, which is aimed at customizing health-care interventions based on the unique characteristics of each individual. Nowadays, the complex milieu of epigenomic marks can be studied at the genome-wide level thanks to massive, highthroughput technologies. This new experimental approach is opening up new and interesting knowledge perspectives. However, the analysis of these complex omic data requires to face important analytic issues. Artificial Intelligence, and in particular Machine Learning, are emerging as powerful resources to decipher epigenomic data. In this review, we will first describe the most used ML approaches in epigenomics. We then will recapitulate some of the recent applications of ML to epigenomic analysis. Finally, we will provide some examples of how the ML approach to epigenetic data can be useful for personalized medicine.

High Altitude hypoxia

2020 ◽  
Vol 17 ◽  
Author(s):  
Asma Babar ◽  
Kifayatullah Mengal ◽  
Abdul Hanan Babar ◽  
Shixin Wu ◽  
Mujahid Ali Shah ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
High Altitude ◽  
Molecular Mechanisms ◽  
Strong Association ◽  
Haemoglobin Concentration ◽  
Metabolic Reprogramming ◽  
Molecular Networks ◽  
Whole Genome ◽  
Gene Expressions ◽  
Transcriptional Responses

: The world highest and largest altitude area is called the Qinghai-Tibetan plateau (QTB), which harbors unique animal and plant species. Mammals that inhabit the higher altitude regions have adapted well to the hypoxic conditions. One of the main stressors at high altitude is hypoxia. Metabolic responses to hypoxia play important roles in cell survival strategies and some diseases. However, the homeostatic alterations that equilibrate variations in the demand and supply of energy to maintain organismal function in a prolonged low O2 environment persist partly understood, making it problematic to differentiate adaptive from maladaptive responses in hypoxia. Tibetans and yaks are two perfect examples innate to the plateau for high altitude adaptation. By the scan of the whole-genome, EPAS1 and EGLN1 were identified as key genes associated with sustained haemoglobin concentration in high altitude mammals for adaptation. The yak is a much more ancient mammal which has existed on QTB longer than humans, it is, therefore, possible that natural selection represented a diverse group of genes/pathways in yaks. Physiological characteristics are extremely informative in revealing molecular networks associated with inherited adaptation, in addition to the whole-genome adaptive changes at the DNA sequence level. Gene-expression can be changed by a variety of signals originating from the environment, and hypoxia is the main factor amongst them. The hypoxia-inducible factors (HIF-1α and EPAS1/HIF-2α) are the main regulators of oxygen in homeostasis which play a role as maestro regulators of adaptation in hypoxic reaction of molecular mechanisms. (Vague) The basis of this review is to present recent information regarding the molecular mechanism involved in hypoxia that regulates candidate genes and proteins. Many transcriptional responses toward hypoxia are facilitated by HIFs that change the number of gene expressions and help in angiogenesis, erythropoiesis, metabolic reprogramming and metastasis. HIFs also activate several signals highlighting a strong association between hypoxia, the misfolded proteins’ accumulation in the endoplasmic reticulum in stress and activation of unfolded protein response (UPR). It was observed that at high-altitude, pregnancies yield a low birth weight ∼100 g per1000 m of the climb. (Vague) It may involve variation in the events of energy-demanding, like protein synthesis. Prolonged hypobaric hypoxia causes placental ER stress, which in turn, moderates protein synthesis and reduces proliferation. Further, Cardiac hypertrophy by cytosolic Ca2+ raises and Ca2+/calmodulin, calcineurin stimulation, NF-AT3 pathway might be caused by an imbalance in Sarcoplasmic reticulum ER Ca2, might be adaptive in beginning but severe later.

scholarly journals SARS-CoV-2 and the Nervous System: From Clinical Features to Molecular Mechanisms

2020 ◽  
Vol 21 (15) ◽  
pp. 5475 ◽  
Author(s):  
Manuela Pennisi ◽  
Giuseppe Lanza ◽  
Luca Falzone ◽  
Francesco Fisicaro ◽  
Raffaele Ferri ◽  
...  
Keyword(s):  
Nervous System ◽  
Molecular Mechanisms ◽  
Neuronal Damage ◽  
Neurological Complications ◽  
Neurological Manifestations ◽  
Wide Range ◽  
Inflammatory State ◽  
Acute Polyneuropathy ◽  
The Central Nervous System ◽  
The Impact

Increasing evidence suggests that Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) can also invade the central nervous system (CNS). However, findings available on its neurological manifestations and their pathogenic mechanisms have not yet been systematically addressed. A literature search on neurological complications reported in patients with COVID-19 until June 2020 produced a total of 23 studies. Overall, these papers report that patients may exhibit a wide range of neurological manifestations, including encephalopathy, encephalitis, seizures, cerebrovascular events, acute polyneuropathy, headache, hypogeusia, and hyposmia, as well as some non-specific symptoms. Whether these features can be an indirect and unspecific consequence of the pulmonary disease or a generalized inflammatory state on the CNS remains to be determined; also, they may rather reflect direct SARS-CoV-2-related neuronal damage. Hematogenous versus transsynaptic propagation, the role of the angiotensin II converting enzyme receptor-2, the spread across the blood-brain barrier, the impact of the hyperimmune response (the so-called “cytokine storm”), and the possibility of virus persistence within some CNS resident cells are still debated. The different levels and severity of neurotropism and neurovirulence in patients with COVID-19 might be explained by a combination of viral and host factors and by their interaction.

scholarly journals Genetic analysis of amyotrophic lateral sclerosis identifies contributing pathways and cell types

2021 ◽  
Vol 7 (3) ◽  
pp. eabd9036
Author(s):  
Sara Saez-Atienzar ◽  
Sara Bandres-Ciga ◽  
Rebekah G. Langston ◽  
Jonggeol J. Kim ◽  
Shing Wan Choi ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Membrane Trafficking ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Polygenic Risk Score ◽  
Genome Wide ◽  
Genome Wide Data ◽  
Data Driven Approach ◽  
Single Nucleus ◽  
Lateral Sclerosis

Despite the considerable progress in unraveling the genetic causes of amyotrophic lateral sclerosis (ALS), we do not fully understand the molecular mechanisms underlying the disease. We analyzed genome-wide data involving 78,500 individuals using a polygenic risk score approach to identify the biological pathways and cell types involved in ALS. This data-driven approach identified multiple aspects of the biology underlying the disease that resolved into broader themes, namely, neuron projection morphogenesis, membrane trafficking, and signal transduction mediated by ribonucleotides. We also found that genomic risk in ALS maps consistently to GABAergic interneurons and oligodendrocytes, as confirmed in human single-nucleus RNA-seq data. Using two-sample Mendelian randomization, we nominated six differentially expressed genes (ATG16L2, ACSL5, MAP1LC3A, MAPKAPK3, PLXNB2, and SCFD1) within the significant pathways as relevant to ALS. We conclude that the disparate genetic etiologies of this fatal neurological disease converge on a smaller number of final common pathways and cell types.

scholarly journals Targeting AURKA in Cancer: molecular mechanisms and opportunities for Cancer therapy

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Ruijuan Du ◽  
Chuntian Huang ◽  
Kangdong Liu ◽  
Xiang Li ◽  
Zigang Dong
Keyword(s):  
Cancer Therapy ◽  
Molecular Mechanisms ◽  
Aurora Kinase ◽  
Interacting Proteins ◽  
Multiple Tumor ◽  
Oncogenic Pathways ◽  
Wide Range ◽  
The Family ◽  
Tumor Types ◽  
Cancer Tissues

AbstractAurora kinase A (AURKA) belongs to the family of serine/threonine kinases, whose activation is necessary for cell division processes via regulation of mitosis. AURKA shows significantly higher expression in cancer tissues than in normal control tissues for multiple tumor types according to the TCGA database. Activation of AURKA has been demonstrated to play an important role in a wide range of cancers, and numerous AURKA substrates have been identified. AURKA-mediated phosphorylation can regulate the functions of AURKA substrates, some of which are mitosis regulators, tumor suppressors or oncogenes. In addition, enrichment of AURKA-interacting proteins with KEGG pathway and GO analysis have demonstrated that these proteins are involved in classic oncogenic pathways. All of this evidence favors the idea of AURKA as a target for cancer therapy, and some small molecules targeting AURKA have been discovered. These AURKA inhibitors (AKIs) have been tested in preclinical studies, and some of them have been subjected to clinical trials as monotherapies or in combination with classic chemotherapy or other targeted therapies.

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