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Articles 1 - 30 of 121

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Diversity, Structure And Sources Of Bacterial Communities In Earthworm Cocoons., Manuel Aira, Marcos Pérez-Losada, Jorge Domínguez Apr 2018

Diversity, Structure And Sources Of Bacterial Communities In Earthworm Cocoons., Manuel Aira, Marcos Pérez-Losada, Jorge Domínguez

Computational Biology Institute

Animals start interactions with the bacteria that will constitute their microbiomes at embryonic stage. After mating, earthworms produce cocoons externally which will be colonized with bacteria from their parents and the environment. Due to the key role bacterial symbionts play on earthworm fitness, it is important to study bacterial colonization during cocoon formation. Here we describe the cocoon microbiome of the earthworms Eisenia andrei and E. fetida, which included 275 and 176 bacterial species, respectively. They were dominated by three vertically-transmitted symbionts, Microbacteriaceae, Verminephrobacter and Ca. Nephrothrix, which accounted for 88% and 66% of the sequences respectively. Verminephrobacter and Ca ...


Glucocorticoids Modulate Gastrointestinal Microbiome In A Wild Bird., José C Noguera, Manuel Aira, Marcos Pérez-Losada, Jorge Domínguez, Alberto Velando Apr 2018

Glucocorticoids Modulate Gastrointestinal Microbiome In A Wild Bird., José C Noguera, Manuel Aira, Marcos Pérez-Losada, Jorge Domínguez, Alberto Velando

Computational Biology Institute

It has recently been hypothesized that stress exposure (e.g. via glucocorticoid secretion) may dysregulate the bacterial gut microbiome, a crucial 'organ' in animal health. However, whether stress exposure (e.g. via glucocorticoid secretion) affects the bacterial gut microbiome of natural populations is unknown. We have experimentally altered the basal glucocorticoid level (corticosterone implants) in a wild avian species, the yellow-legged gull


Evolution Of Echovirus 11 In A Chronically Infected Immunodeficient Patient., Majid Laassri, Tatiana Zagorodnyaya, Sharon Hassin-Baer, Rachel Handsher, Danit Sofer, Merav Weil, Konstantinos Karagiannis, Vahan Simonyan, Konstantin Chumakov, Lester Shulman Mar 2018

Evolution Of Echovirus 11 In A Chronically Infected Immunodeficient Patient., Majid Laassri, Tatiana Zagorodnyaya, Sharon Hassin-Baer, Rachel Handsher, Danit Sofer, Merav Weil, Konstantinos Karagiannis, Vahan Simonyan, Konstantin Chumakov, Lester Shulman

Biochemistry and Molecular Medicine Faculty Publications

Deep sequencing was used to determine complete nucleotide sequences of echovirus 11 (EV11) strains isolated from a chronically infected patient with CVID as well as from cases of acute enterovirus infection. Phylogenetic analysis showed that EV11 strains that circulated in Israel in 1980-90s could be divided into four clades. EV11 strains isolated from a chronically infected individual belonged to one of the four clades and over a period of 4 years accumulated mutations at a relatively constant rate. Extrapolation of mutations accumulation curve into the past suggested that the individual was infected with circulating EV11 in the first half of ...


Benchmark Evaluation Of True Single Molecular Sequencing To Determine Cystic Fibrosis Airway Microbiome Diversity, Andrea Hahn, Matthew L. Bendall, Keylie M. Gibson, Hollis Chaney, Iman Sami, Geovanny F. Perez, Anastassios C. Koumbourlis, Timothy A. Mccaffrey, Robert J. Freishtat, Keith A Crandall Jan 2018

Benchmark Evaluation Of True Single Molecular Sequencing To Determine Cystic Fibrosis Airway Microbiome Diversity, Andrea Hahn, Matthew L. Bendall, Keylie M. Gibson, Hollis Chaney, Iman Sami, Geovanny F. Perez, Anastassios C. Koumbourlis, Timothy A. Mccaffrey, Robert J. Freishtat, Keith A Crandall

Computational Biology Institute

Cystic fibrosis (CF) is an autosomal recessive disease associated with recurrent lung infections that can lead to morbidity and mortality. The impact of antibiotics for treatment of acute pulmonary exacerbations on the CF airway microbiome remains unclear with prior studies giving conflicting results and being limited by their use of 16S ribosomal RNA sequencing. Our primary objective was to validate the use of true single molecular sequencing (tSMS) and PathoScope in the analysis of the CF airway microbiome. Three control samples were created with differing amounts of Burkholderia cepacia, Pseudomonas aeruginosa, and Prevotella melaninogenica, three common bacteria found in cystic ...


The Igf2/Igf1r/Nanog Signaling Pathway Regulates The Proliferation Of Acute Myeloid Leukemia Stem Cells., Dan-Dan Xu, Ying Wang, Peng-Jun Zhou, Shu-Rong Qin, Rong Zhang, Yi Zhang, +Several Additional Authors Jan 2018

The Igf2/Igf1r/Nanog Signaling Pathway Regulates The Proliferation Of Acute Myeloid Leukemia Stem Cells., Dan-Dan Xu, Ying Wang, Peng-Jun Zhou, Shu-Rong Qin, Rong Zhang, Yi Zhang, +Several Additional Authors

Biochemistry and Molecular Medicine Faculty Publications

Acute myeloid leukemia is an aggressive disease characterized by clonal proliferation and differentiation into immature hematopoietic cells of dysfunctional myeloid precursors. Accumulating evidence shows that CD34+CD38- leukemia stem cells (LSCs) are responsible for drug resistance, metastasis, and relapse of leukemia. In this study, we found that Nanog, a transcription factor in stem cells, is significantly overexpressed in CD34+ populations from patients with acute myeloid leukemia and in LSCs from leukemia cell lines. Our data demonstrate that the knockdown of Nanog inhibited proliferation and induced cell cycle arrest and cell apoptosis. Moreover, Nanog silencing suppressed the leukemogenesis of LSCs in ...


Association Of Two Foxp3 Polymorphisms With Breast Cancer In Chinese Han Women, Wenge Zhu, +Several Additional Authors Jan 2018

Association Of Two Foxp3 Polymorphisms With Breast Cancer In Chinese Han Women, Wenge Zhu, +Several Additional Authors

Biochemistry and Molecular Medicine Faculty Publications

Background

Forkhead box P3 (FOXP3) is a key gene in the immune system which also plays a role in tumor development. This study aims to explore the association of two FOXP3 polymorphisms (rs3761548 and rs3761549) with susceptibility to breast cancer (BC).

Method

A case–control study was conducted, involving 560 patients and 583 healthy individuals from the Chinese Han population. The genotypes of FOXP3 polymorphisms were detected using the Sequenom MassARRAY method. The association between FOXP3 polymorphisms and BC risk was evaluated using a χ2 test with an odds ratio (OR) and 95% confidence intervals (95% CIs) under six genetic ...


Robust Expression Of Tumor Suppressor Mirna's Let-7 And Mir-195 Detected In Plasma Of Saudi Female Breast Cancer Patients., Amal Qattan, Haya Intabli, Wafa Alkhayal, Chafica Eltabache, Taher Tweigieri, Suad Bin Amer Nov 2017

Robust Expression Of Tumor Suppressor Mirna's Let-7 And Mir-195 Detected In Plasma Of Saudi Female Breast Cancer Patients., Amal Qattan, Haya Intabli, Wafa Alkhayal, Chafica Eltabache, Taher Tweigieri, Suad Bin Amer

Biochemistry and Molecular Medicine Faculty Publications

Background

Female breast cancer is frequently diagnosed at a later stage and the leading cause of cancer deaths world-wide. Levels of cell-free circulating microRNAs (miRNAs) can potentially be used as biomarkers to measure disease progression in breast cancer patients in a non-invasive way and are therefore of high clinical value.

Methods

Using quantitative RT-PCR, circulating miRNAs were measured in blood samples collected from disease-free individuals (n = 34), triple-negative breast tumours (TNBC) (n = 36) and luminal tumours (n = 57). In addition to intergroup comparisons, plasma miRNA expression levels of all groups were analyzed against RNASeq data from cancerous breast tissue via ...


An Organismal Model For Gene Regulatory Networks In The Gut-Associated Immune Response, Katherine M. Buckley, J P. Rast Oct 2017

An Organismal Model For Gene Regulatory Networks In The Gut-Associated Immune Response, Katherine M. Buckley, J P. Rast

Biochemistry and Molecular Medicine Faculty Publications

The gut epithelium is an ancient site of complex communication between the animal immune system and the microbial world. While elements of self-non-self receptors and effector mechanisms differ greatly among animal phyla, some aspects of recognition, regulation, and response are broadly conserved. A gene regulatory network (GRN) approach provides a means to investigate the nature of this conservation and divergence even as more peripheral functional details remain incompletely understood. The sea urchin embryo is an unparalleled experimental model for detangling the GRNs that govern embryonic development. By applying this theoretical framework to the free swimming, feeding larval stage of the ...


Phylogenetic Evidence From Freshwater Crayfishes That Cave Adaptation Is Not An Evolutionary Dead-End., David B Stern, Jesse Breinholt, Carlos Pedraza-Lara, Marilú López-Mejía, Christopher L Owen, Heather Bracken-Grissom, James W Fetzner, Keith A Crandall Oct 2017

Phylogenetic Evidence From Freshwater Crayfishes That Cave Adaptation Is Not An Evolutionary Dead-End., David B Stern, Jesse Breinholt, Carlos Pedraza-Lara, Marilú López-Mejía, Christopher L Owen, Heather Bracken-Grissom, James W Fetzner, Keith A Crandall

Computational Biology Institute

Caves are perceived as isolated, extreme habitats with a uniquely specialized biota, which long ago led to the idea that caves are "evolutionary dead-ends." This implies that cave-adapted taxa may be doomed for extinction before they can diversify or transition to a more stable state. However, this hypothesis has not been explicitly tested in a phylogenetic framework with multiple independently evolved cave-dwelling groups. Here, we use the freshwater crayfish, a group with dozens of cave-dwelling species in multiple lineages, as a system to test this hypothesis. We consider historical patterns of lineage diversification and habitat transition as well as current ...


Engaging Medical Students In Problem-Based Search And Study Of The Biomedical Literature., Zhiyong Han, Samantha L Margulies, Divya Kurian, Joshua M Jabaut, Akshita Mehta, Ramzi Dudum, Huberta Koudoro, Ria S Roberts, Jay Lee, Jonathan Li, Hieu T Nguyen, Mark Elliott Aug 2017

Engaging Medical Students In Problem-Based Search And Study Of The Biomedical Literature., Zhiyong Han, Samantha L Margulies, Divya Kurian, Joshua M Jabaut, Akshita Mehta, Ramzi Dudum, Huberta Koudoro, Ria S Roberts, Jay Lee, Jonathan Li, Hieu T Nguyen, Mark Elliott

Biochemistry and Molecular Medicine Faculty Publications

No abstract provided.


Metastasis-Associated Protein 1 Deficiency Results In Compromised Pulmonary Alveolar Capillary Angiogenesis In Mice., Jun-Hui Qin, Zhen-Yu Ke, Qiang Zhou, Li Wang, Yuan Liang, Ying-Mei Wang, Tong Yang, Xing Gao, Jing Ye, Rekesh Kumar, Rui-An Wang Aug 2017

Metastasis-Associated Protein 1 Deficiency Results In Compromised Pulmonary Alveolar Capillary Angiogenesis In Mice., Jun-Hui Qin, Zhen-Yu Ke, Qiang Zhou, Li Wang, Yuan Liang, Ying-Mei Wang, Tong Yang, Xing Gao, Jing Ye, Rekesh Kumar, Rui-An Wang

Biochemistry and Molecular Medicine Faculty Publications

Background

The aim of this study was to investigate the effects of metastasis-associated protein 1 (MTA1) deficiency during angiogenesis of pulmonary alveolar capillaries in mice and to determine the molecular mechanisms involved.

Material/Methods

The expressions of MTA1, CD34, vascular endothelial growth factor (VEGF), alpha smooth muscle actin (α-SMA), and HIF-1α were analyzed in the lungs of MTA1-knockout (KO) and wild-type mice at embryonic day 18.5 and 2 months by quantitative PCR, immunoblotting, and immunohistochemistry. The morphological changes were investigated during pulmonary alveolar capillary formation. The heart weight/body weight (HW/BW) ratio and the size of the ...


Transcriptomic Differentiation Underlying Marine‐To‐Freshwater Transitions In The South American Silversides Odontesthes Argentinensis And O. Bonariensis (Atheriniformes), Lily Hughes, Gustavo Somoza, Bryan Nguyen, James Bernot, Mariano Gonzalez-Castro, Juan Martin Diaz De Astarloa, Guillermo Orti Jul 2017

Transcriptomic Differentiation Underlying Marine‐To‐Freshwater Transitions In The South American Silversides Odontesthes Argentinensis And O. Bonariensis (Atheriniformes), Lily Hughes, Gustavo Somoza, Bryan Nguyen, James Bernot, Mariano Gonzalez-Castro, Juan Martin Diaz De Astarloa, Guillermo Orti

Computational Biology Institute

Salinity gradients are critical habitat determinants for freshwater organisms. Silverside fishes in the genus Odontesthes have recently and repeatedly transitioned from marine to freshwater habitats, overcoming a strong ecological barrier. Genomic and transcriptomic changes involved in this kind of transition are only known for a few model species. We present new data and analyses of gene expression and microbiome composition in the gills of two closely related silverside species, marine O. argentinensis and freshwater O. bonariensis and find more than three thousand transcripts differentially expressed, with osmoregulatory/ion transport genes and immune genes showing very different expression patterns across species ...


Safety And Potential Efficacy Of Gemfibrozil As A Supportive Treatment For Children With Late Infantile Neuronal Ceroid Lipofuscinosis And Other Lipid Storage Disorders., Kyeongsoon Kim, Hynda K Kleinman, Hahn-Jun Lee, Kalipada Pahan Jun 2017

Safety And Potential Efficacy Of Gemfibrozil As A Supportive Treatment For Children With Late Infantile Neuronal Ceroid Lipofuscinosis And Other Lipid Storage Disorders., Kyeongsoon Kim, Hynda K Kleinman, Hahn-Jun Lee, Kalipada Pahan

Biochemistry and Molecular Medicine Faculty Publications

Neuronal Ceroid Lipofuscinosis (NCL), also known as Batten disease, is a group of genetically distinct lysosomal disorders that mainly affect the central nervous system, resulting in progressive motor and cognitive decline primarily in children. Multiple distinct genes involved in the metabolism of lipids have been identified to date with various mutations in this family of diseases. There is no cure for these diseases but some new therapeutic approaches have been tested that offer more hope than the standard palliative care. Many of the therapeutic advances require invasive procedures but some progress in slowing the disease has been found and more ...


Il-18 Polymorphisms Contribute To Hepatitis B Virus-Related Cirrhosis And Hepatocellular Carcinoma Susceptibility In Chinese Population: A Case-Control Study., Zhi-Jun Dai, Xing-Han Liu, Meng Wang, Yan Guo, Wenge Zhu, Xiao Li, Shuai Lin, Tian Tian, Kang Liu, Yi Zheng, Peng Xu, Tianbo Jin, Xiaopeng Li Jun 2017

Il-18 Polymorphisms Contribute To Hepatitis B Virus-Related Cirrhosis And Hepatocellular Carcinoma Susceptibility In Chinese Population: A Case-Control Study., Zhi-Jun Dai, Xing-Han Liu, Meng Wang, Yan Guo, Wenge Zhu, Xiao Li, Shuai Lin, Tian Tian, Kang Liu, Yi Zheng, Peng Xu, Tianbo Jin, Xiaopeng Li

Biochemistry and Molecular Medicine Faculty Publications

IL-18 polymorphisms influence the transcriptional activity of the IL-18 gene and associated with various diseases. However, their relationships with hepatitis B virus-related liver diseases had not reached a consensus. So we conducted this case-control study with a view to clarifying the association. We included four groups: healthy controls, chronic hepatitis B virus (CHB) carriers, liver cirrhosis (LC) and hepatocellular carcinoma (HCC) groups with each group of 250 persons. Odd ratios (ORs) and 95% confidence intervals (95%CIs) with or without adjustment were calculated. Haplotype analysis was also performed. The results showed people carrying rs187238 CG genotype had a lower risk ...


Rnaseq Analysis Of The Drosophila Response To The Entomopathogenic Nematode Steinernema., Shruti Yadav, Sean Daugherty, Amol Carl Shetty, Ioannis Eleftherianos Jun 2017

Rnaseq Analysis Of The Drosophila Response To The Entomopathogenic Nematode Steinernema., Shruti Yadav, Sean Daugherty, Amol Carl Shetty, Ioannis Eleftherianos

Computational Biology Institute

Drosophila melanogaster is an outstanding model to study the molecular and functional basis of host-pathogen interactions. Currently, our knowledge of microbial infections in D. melanogaster is well understood; however, the response of flies to nematode infections is still in its infancy. Here, we have used the potent parasitic nematode Steinernema carpocapsae, which lives in mutualism with its endosymbiotic bacteria Xenorhabdus nematophila, to examine the transcriptomic basis of the interaction between D. melanogaster and entomopathogenic nematodes. We have employed next-generation RNA sequencing (RNAseq) to investigate the transcriptomic profile of D. melanogaster larvae in response to infection by S. carpocapsae symbiotic (carrying ...


Estimation Of The True Evolutionary Distance Under The Fragile Breakage Model., Nikita Alexeev, Max A Alekseyev May 2017

Estimation Of The True Evolutionary Distance Under The Fragile Breakage Model., Nikita Alexeev, Max A Alekseyev

Computational Biology Institute

BACKGROUND: The ability to estimate the evolutionary distance between extant genomes plays a crucial role in many phylogenomic studies. Often such estimation is based on the parsimony assumption, implying that the distance between two genomes can be estimated as the rearrangement distance equal the minimal number of genome rearrangements required to transform one genome into the other. However, in reality the parsimony assumption may not always hold, emphasizing the need for estimation that does not rely on the rearrangement distance. The distance that accounts for the actual (rather than minimal) number of rearrangements between two genomes is often referred to ...


Long Non-Coding Rna Profile In Mantle Cell Lymphoma Identifies A Functional Lncrna Ror1-As1 Associated With Ezh2/Prc2 Complex., Guangzhen Hu, Shiv K Gupta, Tammy P Troska, Asha Nair, Mamta Gupta May 2017

Long Non-Coding Rna Profile In Mantle Cell Lymphoma Identifies A Functional Lncrna Ror1-As1 Associated With Ezh2/Prc2 Complex., Guangzhen Hu, Shiv K Gupta, Tammy P Troska, Asha Nair, Mamta Gupta

Biochemistry and Molecular Medicine Faculty Publications

Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by rapid disease progression. The needs for new therapeutic strategies for MCL patients call for further understanding on the molecular mechanisms of pathogenesis of MCL. Recently, long noncoding RNAs (lncRNAs) have been recognized as key regulators of gene expression and disease development, however, the role of lncRNAs in non-Hodgkin lymphoma and specifically in MCL is still unknown. Next generation RNA-sequencing was carried out on MCL patient samples along with normal controls and data was analyzed. As a result, several novel lncRNAs were found significantly overexpressed in the MCL samples with ...


Transcriptomic Effects Of Dispersed Oil In A Non-Model Decapod Crustacean, Hernan Vazquez-Miranda, Brent Thoma, Juliet Wong, Darryl Felder, Keith A. Crandall, Heather Bracken-Grissom May 2017

Transcriptomic Effects Of Dispersed Oil In A Non-Model Decapod Crustacean, Hernan Vazquez-Miranda, Brent Thoma, Juliet Wong, Darryl Felder, Keith A. Crandall, Heather Bracken-Grissom

Computational Biology Institute

Background. Oil spills are major environmental disasters. Dispersants help control spills, as they emulsify oil into droplets to speed bioremediation. Although dispersant toxicity is controversial, the genetic consequences and damages of dispersed oil exposure are poorly understood. We used RNA-seq to measure gene expression of flatback mudcrabs (Eurypanopeus depressus, Decapoda, Brachyura, Panopeidae) exposed to dispersed oil.

Methods. Our experimental design included two control types, oil-only, and oil-dispersant treatments with three replicates each. We prepared 100 base pair-ended libraries from total RNA and sequenced them in one Illumina HiSeq2000 lane. We assembled a reference transcriptome with all replicates per treatment, assessed ...


Metastasis-Associated Protein 1 Is An Upstream Regulator Of Dnmt3a And Stimulator Of Insulin-Growth Factor Binding Protein-3 In Breast Cancer., S Deivendran, Hezlin Marzook, T R Santhoshkumar, Rakesh Kumar, M Radhakrishna Pillai Apr 2017

Metastasis-Associated Protein 1 Is An Upstream Regulator Of Dnmt3a And Stimulator Of Insulin-Growth Factor Binding Protein-3 In Breast Cancer., S Deivendran, Hezlin Marzook, T R Santhoshkumar, Rakesh Kumar, M Radhakrishna Pillai

Biochemistry and Molecular Medicine Faculty Publications

Despite a recognized role of DNA methyltransferase 3a (DNMT3a) in human cancer, the nature of its upstream regulator(s) and relationship with the master chromatin remodeling factor MTA1, continues to be poorly understood. Here, we found an inverse relationship between the levels of MTA1 and DNMT3a in human cancer and that high levels of MTA1 in combination of low DNMT3a status correlates well with poor survival of breast cancer patients. We discovered that MTA1 represses DNMT3a expression via HDAC1/YY1 transcription factor complex. Because IGFBP3 is an established target of DNMT3a, we investigated the effect of MTA1 upon IGFBP3 expression ...


Metastasis-Associated Protein 1 Is An Upstream Regulator Of Dnmt3Α And Stimulator Of Insulin-Growth Factor Binding Protein-3 In Breast Cancer, S Deivendran Apr 2017

Metastasis-Associated Protein 1 Is An Upstream Regulator Of Dnmt3Α And Stimulator Of Insulin-Growth Factor Binding Protein-3 In Breast Cancer, S Deivendran

Biochemistry and Molecular Medicine Faculty Publications

Despite a recognized role of DNA methyltransferase 3a (DNMT3a) in human cancer, the nature of its upstream regulator(s) and relationship with the master chromatin remodeling factor MTA1, continues to be poorly understood. Here, we found an inverse relationship between the levels of MTA1 and DNMT3a in human cancer and that high levels of MTA1 in combination of low DNMT3a status correlates well with poor survival of breast cancer patients. We discovered that MTA1 represses DNMT3a expression via HDAC1/YY1 transcription factor complex. Because IGFBP3 is an established target of DNMT3a, we investigated the effect of MTA1 upon IGFBP3 expression ...


Analysis Of Hiv-1 Quasispecies Sequences Generated By High Throughput Sequencing (Hts) Using Hive, Naila Gulzar, Bhavna Hora, Konstantinos Karagiannis, Krista Smith, Feng Gao, Raja Mazumder Apr 2017

Analysis Of Hiv-1 Quasispecies Sequences Generated By High Throughput Sequencing (Hts) Using Hive, Naila Gulzar, Bhavna Hora, Konstantinos Karagiannis, Krista Smith, Feng Gao, Raja Mazumder

GW Research Days 2016 - Present

The high level of genetic variability of Human Immunodeficiency Virus type 1 (HIV-1) is caused by the low fidelity of its replication machinery. This leads to evolution of swarm-like viral populations often described as quasispecies. High throughput sequencing (HTS) technology provides higher resolution over Sanger sequencing, enabling detection of low frequency variant genomes. However, quasispecies analysis is still a challenge due to the systematic noise, introduced by HTS technology. This leads to the increase in type I errors (also known as false positives) and the underlying genetic diversity, which can lead to mathematically insolvable type II errors (also known as ...


The Temporal Dynamics Of The Tracheal Microbiome In Tracheostomised Patients With And Without Lower Respiratory Infections., Marcos Pérez-Losada, Robert J Graham, Madeline Coquillette, Amenah Jafarey, Eduardo Castro-Nallar, Manuel Aira, Robert J Freishtat, Jonathan M Mansbach Jan 2017

The Temporal Dynamics Of The Tracheal Microbiome In Tracheostomised Patients With And Without Lower Respiratory Infections., Marcos Pérez-Losada, Robert J Graham, Madeline Coquillette, Amenah Jafarey, Eduardo Castro-Nallar, Manuel Aira, Robert J Freishtat, Jonathan M Mansbach

Computational Biology Institute

Background: Airway microbiota dynamics during lower respiratory infection (LRI) are still poorly understood due, in part, to insufficient longitudinal studies and lack of uncontaminated lower airways samples. Furthermore, the similarity between upper and lower airway microbiomes is still under debate. Here we compare the diversity and temporal dynamics of microbiotas directly sampled from the trachea via tracheostomy in patients with (YLRI) and without (NLRI) lower respiratory infections. Methods: We prospectively collected 127 tracheal aspirates across four consecutive meteorological seasons (quarters) from 40 patients, of whom 20 developed LRIs and 20 remained healthy. All aspirates were collected when patients had no ...


Ptpro Represses Erbb2-Driven Breast Oncogenesis By Dephosphorylation And Endosomal Internalization Of Erbb2., H Dong, L Ma, J Gan, W Lin, Rakesh Kumar, +9 Additional Authors Jan 2017

Ptpro Represses Erbb2-Driven Breast Oncogenesis By Dephosphorylation And Endosomal Internalization Of Erbb2., H Dong, L Ma, J Gan, W Lin, Rakesh Kumar, +9 Additional Authors

Biochemistry and Molecular Medicine Faculty Publications

The plasma membrane-associated tyrosine phosphatase PTPRO is frequently transcriptionally repressed in cancers and signifies poor prognosis of breast cancer patients. In this study, deletion of Ptpro inMMTV-Erbb2 transgenic mice dramatically shortened the mammary tumor latency and accelerated tumor growth due to loss of Ptpro within the breast cancer cells but not in surrounding tissue as confirmed by hetero-transplantation studies. Both in vitro and in vivo data demonstrated that the phosphatase activity was required for the inactivation of ERBB2 and its downstream signaling. PTPRO regulated the phosphorylation status of ERBB2 at Y1248. Co-immunoprecipitation and proximity ligation assay (Duolink) indicated that ...


Distribution Bias Analysis Of Germline And Somatic Single-Nucleotide Variations That Impact Protein Functional Site And Neighboring Amino Acids, Y Pan, C Yan, Y Hu, Y Fan, Qing Pan, Q Wan, J Torcivia-Rodriguez, Raja Mazumder Jan 2017

Distribution Bias Analysis Of Germline And Somatic Single-Nucleotide Variations That Impact Protein Functional Site And Neighboring Amino Acids, Y Pan, C Yan, Y Hu, Y Fan, Qing Pan, Q Wan, J Torcivia-Rodriguez, Raja Mazumder

Biochemistry and Molecular Medicine Faculty Publications

Single nucleotide variations (SNVs) can result in loss or gain of protein functional sites. We analyzed the effects of SNVs on enzyme active sites, ligand binding sites, and various types of post translational modification (PTM) sites. We found that, for most types of protein functional sites, the SNV pattern differs between germline and somatic mutations as well as between synonymous and non-synonymous mutations. From a total of 51,138 protein functional site affecting SNVs (pfsSNVs), a pan-cancer analysis revealed 142 somatic pfsSNVs in five or more cancer types. By leveraging patient information for somatic pfsSNVs, we identified 17 loss of ...


Biomuta And Bioxpress: Mutation And Expression Knowledgebases For Cancer Biomarker Discovery, Hayley Dingerdissen, John Torcivia-Rodriguez, Yu Hu, Ting-Chia Chang, Raja Mazumder, Robel Kashay Jan 2017

Biomuta And Bioxpress: Mutation And Expression Knowledgebases For Cancer Biomarker Discovery, Hayley Dingerdissen, John Torcivia-Rodriguez, Yu Hu, Ting-Chia Chang, Raja Mazumder, Robel Kashay

Biochemistry and Molecular Medicine Faculty Publications

Single-nucleotide variation and gene expression of disease samples represent important resources for biomarker discovery. Many databases have been built to host and make available such data to the community, but these databases are frequently limited in scope and/or content. BioMuta, a database of cancer-associated single-nucleotide variations, and BioXpress, a database of cancer-associated differentially expressed genes and microRNAs, differ from other disease-associated variation and expression databases primarily through the aggregation of data across many studies into a single source with a unified representation and annotation of functional attributes. Early versions of these resources were initiated by pilot funding for specific ...


Genetic Polymorphisms In Caveolin-1 Associate With Breast Cancer Risk In Chinese Han Population, M Wang, T Tian, X Ma, W Zhu, Y Guo, Z Duan, J Fan, S Lin, K Liu, Y Zheng, Q Sheng, Z J. Dai, H Peng Jan 2017

Genetic Polymorphisms In Caveolin-1 Associate With Breast Cancer Risk In Chinese Han Population, M Wang, T Tian, X Ma, W Zhu, Y Guo, Z Duan, J Fan, S Lin, K Liu, Y Zheng, Q Sheng, Z J. Dai, H Peng

Biochemistry and Molecular Medicine Faculty Publications

Caveolin-1(CAV-1) was demonstrated to be a tumor suppressor gene and be implicated in the development of breast cancer (BC). Numerous potentially functional polymorphisms in CAV-1 have been identified, but their effects on BC were not clear. This case-control study aims to evaluate the relationship between CAV-1 polymorphisms and BC risk. 560 BC patients and 583 healthy controls were enrolled in the present study, all from Chinese Han population. We detected 3 single nucleotide polymorphisms (rs3807987, rs1997623, and rs7804372) in CAV-1 using the Sequenom MassARRAY method. The association between CAV-1genotypes and BC risk was assessed in six genetic models ...


Metabolic Reprogramming Of Triple-Negative Breast Cancer: The Role Of Mirnas, Amal Qattan Jan 2017

Metabolic Reprogramming Of Triple-Negative Breast Cancer: The Role Of Mirnas, Amal Qattan

Biochemistry and Molecular Medicine Faculty Publications

MicroRNAs (miRNAs) are well known to influence the expression of the genes that regulate critical cellular functions. Various reports have suggested that they play critical roles in breast cancer metabolism through the regulation of various metabolic pathways, including the metabolism of glucose, lipids, glycolysis and the mitochondrial tricarboxylic acid cycle (TCA). miRNAs regulate the metabolic process by targeting key molecules (enzymes, kinases transporters) or by modifying the expression of key transcription molecules. In addition, miRNAs can indirectly regulate mRNA translation by targeting chromatin-remodeling enzymes. Furthermore, miRNAs influence the expression of both oncogenes and tumor suppressors and have a major impact ...


Oxidative Stress And Inflammation In Hepatic Diseases: Current And Future Therapy., Karina Reyes-Gordillo, Ruchi Shah, Pablo Muriel Jan 2017

Oxidative Stress And Inflammation In Hepatic Diseases: Current And Future Therapy., Karina Reyes-Gordillo, Ruchi Shah, Pablo Muriel

Biochemistry and Molecular Medicine Faculty Publications

Liver disease is a highly prevalent disease that is one of the leading causes of death worldwide. The continuous exposure of the liver to some factors such as viruses, alcohol, fat, and biotransformed metabolites can cause hepatic injury, which can lead to inflammation and liver degeneration. When the injury is sustained for long time, it can cause chronic liver diseases (CLDs), which include a spectrum of disease states ranging from simple steatosis and steatohepatitis (steatosis with inflammation and hepatocyte injury and death) to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Multiple evidences indicate that oxidative stress and inflammation are the most ...


The Vasodilatory Effects Of Anti-Inflammatory Herb Medications: A Comparison Study Of Four Botanical Extracts., Hong Ping Zhang, Dan-Dan Zhang, Yan Ke, Ka Bian Jan 2017

The Vasodilatory Effects Of Anti-Inflammatory Herb Medications: A Comparison Study Of Four Botanical Extracts., Hong Ping Zhang, Dan-Dan Zhang, Yan Ke, Ka Bian

Biochemistry and Molecular Medicine Faculty Publications

Inflammation plays a pivotal role in the development and progression of cardiovascular diseases, in which, the endothelium dysfunction has been a key element. The current study was designed to explore the vasodilatory effect of anti-inflammatory herbs which have been traditionally used in different clinical applications. The total saponins from Actinidia arguta radix (SAA), total flavonoids from Glycyrrhizae radix et rhizoma (FGR), total coumarins from Peucedani radix (CPR), and total flavonoids from Spatholobi caulis (FSC) were extracted. The isometric measurement of vasoactivity was used to observe the effects of herbal elements on the isolated aortic rings with or without endothelium. To ...


Presence Of A Prophage Determines Temperature-Dependent Capsule Production In Streptococcus Pyogenes., Leslie Brown, Jeong-Ho Kim, Kyu Hong Cho Sep 2016

Presence Of A Prophage Determines Temperature-Dependent Capsule Production In Streptococcus Pyogenes., Leslie Brown, Jeong-Ho Kim, Kyu Hong Cho

Biochemistry and Molecular Medicine Faculty Publications

A hyaluronic acid capsule is a major virulence factor in the pathogenesis of Streptococcus pyogenes. It acts as an anti-phagocytic agent and adhesin to keratinocytes. The expression of the capsule is primarily regulated at the transcriptional level by the two-component regulatory system CovRS, in which CovR acts as a transcriptional repressor. The covRS genes are frequently mutated in many invasive strains, and a subset of the invasive CovRS mutants does not produce a detectable level of the capsule at 37 °C, but produces a significant amount of the capsule at sub-body temperatures. Here, we report that a prophage has a ...