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Articles 181 - 210 of 584

Full-Text Articles in Medical Microbiology

Association Between Sulfur-Metabolizing Bacterial Communities In Stool And Risk Of Distal Colorectal Cancer In Men, Long H. Nguyen, Wenjie Ma, Dong D. Wang, Yin Cao, Himel Mallick, Teklu K. Gerbaba, Jason Lloyd-Price, Galeb Abu-Ali, A. Brantley Hall, Daniel Sikavi, David A. Drew, Raaj S. Mehta, Cesar Arze, Amit D. Joshi, Yan Yan, Tobyn Branck, Casey Dulong, Kerry L. Ivey, Shuji Ogino, Eric B. Rimm, Mingyang Song, Wendy S. Garrett, Jacques Izard, Cutis Huttenhower, Andrew T. Chan Apr 2020

Association Between Sulfur-Metabolizing Bacterial Communities In Stool And Risk Of Distal Colorectal Cancer In Men, Long H. Nguyen, Wenjie Ma, Dong D. Wang, Yin Cao, Himel Mallick, Teklu K. Gerbaba, Jason Lloyd-Price, Galeb Abu-Ali, A. Brantley Hall, Daniel Sikavi, David A. Drew, Raaj S. Mehta, Cesar Arze, Amit D. Joshi, Yan Yan, Tobyn Branck, Casey Dulong, Kerry L. Ivey, Shuji Ogino, Eric B. Rimm, Mingyang Song, Wendy S. Garrett, Jacques Izard, Cutis Huttenhower, Andrew T. Chan

Department of Food Science and Technology: Faculty Publications

Background and aims: Sulfur-metabolizing microbes, which convert dietary sources of sulfur into genotoxic hydrogen sulfide (H2S), have been associated with development of colorectal cancer (CRC). We identified a dietary pattern associated with sulfur-metabolizing bacteria in stool and then investigated its association with risk of incident CRC using data from a large prospective study of men.

Methods: We collected data from 51,529 men enrolled in the Health Professionals Follow-up Study since 1986 to determine the association between sulfur-metabolizing bacteria in stool and risk of CRC over 26 years of follow-up. First, in a subcohort of 307 healthy men, we …


Assessing Embalmer Exposure To Bioaerosols And The Associated Health Risk, Geneviève Marchand, Loïc Wingert, Stéphane Hallé, Maximilien Debia Jan 2020

Assessing Embalmer Exposure To Bioaerosols And The Associated Health Risk, Geneviève Marchand, Loïc Wingert, Stéphane Hallé, Maximilien Debia

Rapports de recherche scientifique

Plusieurs manipulations réalisées sur les corps des défunts par les thanatopracteurs produisent des bioaérosols qui peuvent contenir des agents pathogènes infectieux. La ventilation générale est souvent le seul moyen utilisé dans les laboratoires de thanatopraxie pour maîtriser les bioaérosols. Toutefois, il n’y a pas de recommandations précises pour sa mise en application. De plus, peu d'études abordent les expositions professionnelles aux bioaérosols dans le domaine de la thanatopraxie tant quantitativement (niveau d’exposition) que qualitativement (identification et classification selon les groupes de risque). L’objectif de cette étude était d’évaluer l’exposition des thanatopracteurs aux bioaérosols afin d’apprécier les risques potentiels sur leur …


Aging Induces B Cell Defects And Decreased Antibody Responses To Influenza Infection And Vaccination, Daniela Frasca, Bonnie B. Blomberg Jan 2020

Aging Induces B Cell Defects And Decreased Antibody Responses To Influenza Infection And Vaccination, Daniela Frasca, Bonnie B. Blomberg

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Background: Aging is characterized by a progressive decline in the capacity of the immune system to fight influenza virus infection and to respond to vaccination. Among the several factors involved, in addition to increased frailty and high-risk conditions, the age-associated decrease in cellular and humoral immune responses plays a relevant role. This is in large part due to inflammaging, the chronic low-grade inflammatory status of the elderly, associated with intrinsic inflammation of the immune cells and decreased immune function.

Results: Aging is usually associated with reduced influenza virus-specific and influenza vaccine-specific antibody responses but some elderly individuals with higher pre-exposure …


Mucosa-Associated Microbiota In Barrett’S Esophagus, Dysplasia, And Esophageal Adenocarcinoma Differ Similarly Compared With Healthy Controls, Shajan Peter, Amanda Pendergraft,, William Vanderpol, Mel Wilcox, Kondal R. Kyanam Kabir Baig, Casey Morrow, Jacques Izard, Peter J. Mannon Jan 2020

Mucosa-Associated Microbiota In Barrett’S Esophagus, Dysplasia, And Esophageal Adenocarcinoma Differ Similarly Compared With Healthy Controls, Shajan Peter, Amanda Pendergraft,, William Vanderpol, Mel Wilcox, Kondal R. Kyanam Kabir Baig, Casey Morrow, Jacques Izard, Peter J. Mannon

Department of Food Science and Technology: Faculty Publications

Introduction: Alterations in the composition of the human gut microbiome and its metabolites have been linked to gut epithelial neoplasia. We hypothesized that differences in mucosa-adherent Barrett’s microbiota could link to risk factors, providing risk of progression to neoplasia.

Methods: Paired biopsies from both diseased and nonaffected esophagus (as well as gastric cardia and gastric juice for comparison) from patients with intestinal metaplasia (n = 10), low grade dysplasia (n = 10), high grade dysplasia (n = 10), esophageal adenocarcinoma (n = 12), and controls (n = 10) were processed for mucosa-associated bacteria …


Tick-Borne Infections In New Hampshire: An Evaluation Of The Diagnostic Process In A Local Patient Population, Katherine Anderson Jan 2020

Tick-Borne Infections In New Hampshire: An Evaluation Of The Diagnostic Process In A Local Patient Population, Katherine Anderson

Honors Theses and Capstones

Overall, approximately 95 percent of reported cases of vector-borne disease were associated with ticks, making these the most medically important group of arthropods in the United States.1 Despite the prevalence of tick-borne infections, the process for the diagnosis of this condition is not well studied. This study aims to analyze data from a pool of 100 patients who underwent testing for tick-borne disease in the same institution in Dover, New Hampshire during the most recent peak tick season of 2019. Information utilized in this study included: patient age, sex, location of testing (inpatient versus outpatient), diagnostic testing methods used …


Nlrp6 In Gram-Positive Pneumonia And Sepsis, Laxman Ghimire Oct 2019

Nlrp6 In Gram-Positive Pneumonia And Sepsis, Laxman Ghimire

LSU Doctoral Dissertations

Acute lower respiratory infections (pneumonia) and pneumonia-derived sepsis are among the leading causes of death in the world causing 7.8 million deaths annually. In this regard, Methicillin-resistant Staphylococcus aureus (MRSA) is endemic in the US and implicated for causing high mortality-associated necrotizing pneumonia and aggravating viral pneumonia with superinfection. Additionally, sepsis is the 7th leading cause of death among newborns in the US and is responsible for more than 750,000 hospitalization cases every year. Although there is a plethora of research in both pneumonia and sepsis, the detailed pathophysiology still remains elusive. Understanding the host defense mechanism will help …


Role Of Dietary Flavonoid Compounds In Driving Patterns Of Microbial Community Assembly, Kerry L. Ivey, Andrew T. Chan, Jacques Izard, Aedin Cassidy, Geraint B. Rogers, Eric B. Rimm Sep 2019

Role Of Dietary Flavonoid Compounds In Driving Patterns Of Microbial Community Assembly, Kerry L. Ivey, Andrew T. Chan, Jacques Izard, Aedin Cassidy, Geraint B. Rogers, Eric B. Rimm

Department of Food Science and Technology: Faculty Publications

Flavonoids are a group of polyphenolic dietary compounds found in many different plant-based foods. There is increasing evidence that higher flavonoid intake may be causally linked to a reduced risk of cardiovascular disease and other chronic diseases. The bioactivity and bioavailability of many dietary flavonoids can be influenced by gastrointestinal microbiome metabolism. However, the role that habitual flavonoid intake plays in shaping the human gut microbiome is poorly understood. We describe an application of an ecosystem-based analytic approach to nutritional, microbiome, and questionnaire data from a cohort of more than 240 generally healthy adult males to assess the role of …


Elucidating Immune Signaling Of Influenza A Virus And Aspergillus Fumigatus Co-Infections Through Pioneered Model Development, Meagan Danyelle Rippee-Brooks Aug 2019

Elucidating Immune Signaling Of Influenza A Virus And Aspergillus Fumigatus Co-Infections Through Pioneered Model Development, Meagan Danyelle Rippee-Brooks

Graduate Theses/Dissertations

Bacterial co-infections with influenza A virus (IAV) are extremely serious and life-threatening. However, there exists limited understanding about the importance of fungal infections with IAV. Clinical case reports indicate that fungal co-infections do occur and suggest the IAV pandemic of 2009 had a propensity to predispose patients to secondary fungal infections more than previous IAV strains. IAV-fungal co-infections are marked by high mortality rates of 47 to 61% in previously healthy individuals between the ages of 20 and 60. Yet, the variables involved in this co-infection remain undetermined. I achieved effective recapitulation of this co-infection using a C57Bl/6 murine (mouse) …


Infection Potential Of Rickettsia Felis Via Ingestion, Matthew M. Schexnayder Jul 2019

Infection Potential Of Rickettsia Felis Via Ingestion, Matthew M. Schexnayder

LSU Master's Theses

Rickettsia felis is the etiologic agent of flea-borne spotted fever (FBSF) in humans and a poorly described cause of fever in animals. It is transmitted by its primary arthropod vector and reservoir host, the cat flea Ctenocephalides felis. Known routes of Rickettsia felis transmission between Rickettsia felis-infected cat fleas and vertebrate hosts include cutaneous bites and contamination of cutaneous wounds with infective flea feces. The bulk of FBSF infections occur in young children in Africa, though infections of people at all ages all over the world have been confirmed. As mammals and young children frequently come into contact …


Identification Of Anaerobes In Clinical Specimens Comparison Between The Rapid Ana Ii System And The Bruker Maldi-Tof Ms System Utilized In The Clinical Laboratory, Raymond Chow May 2019

Identification Of Anaerobes In Clinical Specimens Comparison Between The Rapid Ana Ii System And The Bruker Maldi-Tof Ms System Utilized In The Clinical Laboratory, Raymond Chow

Natural Sciences and Mathematics | Clinical Laboratory Sciences

Matrix-Assisted Laser Desorption and Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) has been revealed as an invaluable platform for identifying anaerobic bacteria in the clinical laboratory over traditional methods such as the RapID ANA II System.

A qualitative comparison is made, through the analysis of methodologies and specifications, to determine whether the RapID ANA II system or Bruker MALDI-TOF MS is more suitable for identifying anaerobic organism in the clinical laboratory. Based on the data reviewed, the MALDI-TOF MS is a more intuitive platform within the clinical laboratory due to its increased specificity, cost-effectiveness, and shorten turnaround time for the identification …


Long-Term Use Of Antibiotics And Risk Of Colorectal Adenoma, Yin Cao, Kana Wu, Raaj Mehta, David A. Drew, Mingyang Song, Paul Lochhead, Long H. Nguyen, Jacques Izard, Charles S. Fuchs, Wendy S. Garrett, Curtis Huttenhower, Shuji Ogino, Edward L. Giovannucci, Andrew T. Chan Apr 2019

Long-Term Use Of Antibiotics And Risk Of Colorectal Adenoma, Yin Cao, Kana Wu, Raaj Mehta, David A. Drew, Mingyang Song, Paul Lochhead, Long H. Nguyen, Jacques Izard, Charles S. Fuchs, Wendy S. Garrett, Curtis Huttenhower, Shuji Ogino, Edward L. Giovannucci, Andrew T. Chan

Department of Food Science and Technology: Faculty Publications

Objective: Recent evidence suggests that antibiotic use, which alters the gut microbiome, is associated with an increased risk of colorectal cancer. However, the association between antibiotic use and risk of colorectal adenoma, the precursor for the majority of colorectal cancers, has not been investigated.

Design: We prospectively evaluated the association between antibiotic use at age 20–39 and 40–59 (assessed in 2004) and recent antibiotic use (assessed in 2008) with risk of subsequent colorectal adenoma among 16,642 women aged ≥ 60 enrolled in the Nurses’ Health Study who underwent at least one colonoscopy through 2010. We used multivariate logistic …


The Microbiomes Of Pancreatic And Duodenum Tissue Overlap And Are Highly Subject Specific But Differ Between Pancreatic Cancer And Non-Cancer Subjects, Erika Del Castillo, Richard Meier, Mei Chung, Devin C. Koestler, Tsute Chen, Bruce J. Paster, Kevin P. Charpentier, Karl T. Kelsey, Jacques Izard, Dominique S. Michaud Jan 2019

The Microbiomes Of Pancreatic And Duodenum Tissue Overlap And Are Highly Subject Specific But Differ Between Pancreatic Cancer And Non-Cancer Subjects, Erika Del Castillo, Richard Meier, Mei Chung, Devin C. Koestler, Tsute Chen, Bruce J. Paster, Kevin P. Charpentier, Karl T. Kelsey, Jacques Izard, Dominique S. Michaud

Department of Food Science and Technology: Faculty Publications

Background: In mice, bacteria from the mouth can translocate to the pancreas and impact pancreatic cancer progression. In humans, oral bacteria associated with periodontal disease have been linked to pancreatic cancer risk. It is not known if DNA bacterial profiles in the pancreas and duodenum are similar within individuals.

Methods: Tissue samples were obtained from 50 subjects with pancreatic cancer or other conditions requiring foregut surgery at the Rhode Island Hospital (RIH), and from thirty-four organs obtained from the National Disease Research Interchange. 16S rRNA gene sequencing was performed on 189 tissue samples (pancreatic duct, duodenum, pancreas), 57 …


Dna Methylation By Restriction Modification Systems Affects The Global Transcriptome Profile In Borrelia Burgdorferi, Timothey Casselli, Yvonne Tourand, Adam Scheidegger, William K. Arnold, Anna Proulx, Brian Stevenson, Catherine A. Brissette Dec 2018

Dna Methylation By Restriction Modification Systems Affects The Global Transcriptome Profile In Borrelia Burgdorferi, Timothey Casselli, Yvonne Tourand, Adam Scheidegger, William K. Arnold, Anna Proulx, Brian Stevenson, Catherine A. Brissette

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Prokaryote restriction modification (RM) systems serve to protect bacteria from potentially detrimental foreign DNA. Recent evidence suggests that DNA methylation by the methyltransferase (MTase) components of RM systems can also have effects on transcriptome profiles. The type strain of the causative agent of Lyme disease, Borrelia burgdorferi B31, possesses two RM systems with N6-methyladenosine (m6A) MTase activity, which are encoded by the bbe02 gene located on linear plasmid lp25 and bbq67 on lp56. The specific recognition and/or methylation sequences had not been identified for either of these B. burgdorferi MTases, and it was not previously known whether these RM …


Floxed-Cassette Allelic Exchange Mutagenesis Enables Markerless Gene Deletion In Chlamydia Trachomatis And Can Reverse Cassette-Induced Polar Effects, Gabrielle Keb, Robert Hayman, Kenneth A. Fields Dec 2018

Floxed-Cassette Allelic Exchange Mutagenesis Enables Markerless Gene Deletion In Chlamydia Trachomatis And Can Reverse Cassette-Induced Polar Effects, Gabrielle Keb, Robert Hayman, Kenneth A. Fields

Microbiology, Immunology, and Molecular Genetics Faculty Publications

As obligate intracellular bacteria, Chlamydia spp. have evolved numerous, likely intricate, mechanisms to create and maintain a privileged intracellular niche. Recent progress in elucidating and characterizing these processes has been bolstered by the development of techniques enabling basic genetic tractability. Florescence-reported allelic exchange mutagenesis (FRAEM) couples chromosomal gene deletion with the insertion of a selection cassette encoding antibiotic resistance and green fluorescent protein (GFP). Similar to other bacteria, many chlamydial genes exist within polycistronic operons, raising the possibility of polar effects mediated by insertion cassettes. Indeed, FRAEM-mediated deletion of Chlamydia trachomatis tmeA negatively impacts the expression of tmeB. We …


Virulence Regulation In Pseudomonas Aeruginosa Via The Alginate Regulators, Algu And Algr, The Posttranscriptional Regulator, Rsma, And The Two-Component System, Algz/R, Sean Stacey Dec 2018

Virulence Regulation In Pseudomonas Aeruginosa Via The Alginate Regulators, Algu And Algr, The Posttranscriptional Regulator, Rsma, And The Two-Component System, Algz/R, Sean Stacey

Electronic Theses and Dissertations

Pseudomonas aeruginosa is a Gram-negative bacillus able to colonize a wide variety of environments. In the human host, P. aeruginosa can establish an acute infection or persist and create a chronic infection. P. aeruginosa is able to establish a niche and persist in human hosts by using a wide array of virulence factors used for: movement, killing host cells, and evading immune cells and antibiotics. Understanding virulence factors and their regulation has proved to be an important means of combating the morbidity and mortality of P. aeruginosa as well as the ever-increasing threat of drug resistance. By targeting virulence factors …


Antibody Epitope Specificity For Dsdna Phosphate Backbone Is An Intrinsic Property Of The Heavy Chain Variable Germline Gene Segment Used, Tatjana Srdic-Rajic, Heinz Kohler, Vladimir Jurisic, Radmila Metlas Oct 2018

Antibody Epitope Specificity For Dsdna Phosphate Backbone Is An Intrinsic Property Of The Heavy Chain Variable Germline Gene Segment Used, Tatjana Srdic-Rajic, Heinz Kohler, Vladimir Jurisic, Radmila Metlas

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Analysis of protein sequences by the informational spectrum method (ISM) enables characterization of their specificity according to encoded information represented with defined frequency (F). Our previous data showed that F(0.367) is characteristic for variable heavy chain (VH) domains (a combination of variable (V), diversity (D) and joining (J) gene segments) of the anti-phosphocholine (PC) T15 antibodies and mostly dependent on the CDR2 region, a site for PC phosphate group binding. Because the T15 dsDNA-reactive U4 mutant also encodes F(0.367), we hypothesized that the same frequency may also be characteristic for anti-DNA antibodies. Data obtained from an analysis of 60 spontaneously …


Vancomycin Delays Clindamycin-Induced Fatality In The Hamster Model Of Clostridioides [Clostridium] Difficile Infection, Amelia E. Fox-King, Chrisabelle Mefferd, Jacqueline R. Phan, Nancy O. Nou, Ernesto Abel-Santos, Brian P. Hedlund Oct 2018

Vancomycin Delays Clindamycin-Induced Fatality In The Hamster Model Of Clostridioides [Clostridium] Difficile Infection, Amelia E. Fox-King, Chrisabelle Mefferd, Jacqueline R. Phan, Nancy O. Nou, Ernesto Abel-Santos, Brian P. Hedlund

LSAMP Poster Presentations

Antibiotics can leave the host gut microbiome susceptible to Clostridioides [Clostridium] difficile colonization and lethal toxin production. For instance, clindamycin-induced susceptibility to C. difficile infection (CDI) results in rapid fatality in hamster models, yet vancomycin has been shown to offer increased survival in hamsters challenged with C. difficile. We aim to develop an antibiotic treatment that will facilitate CDI susceptibility without prompt fatality in hamster models. An antibiotic regimen starting with a continuous vancomycin treatment along with a single clindamycin dosage is thought to reduce the major disruption in the indigenous gut microbiome and prevent clindamycin-induced death. …


Experimental Evaluation Of The Importance Of Colonization History In Early-Life Gut Microbiota Assembly, Inés Martínez, Maria X. Maldonado-Gomez, João Carlos Gomes-Neto, Hatem Kittana, Hua Ding, Robert J. Schmaltz, Payal Joglekar, Roberto Jiménez Cardona, Nathan L Marsteller, Steven W. Kembel, Andrew K. Benson, Daniel A. Peterson, Amanda Ramer-Tait, Jens C. Walter Sep 2018

Experimental Evaluation Of The Importance Of Colonization History In Early-Life Gut Microbiota Assembly, Inés Martínez, Maria X. Maldonado-Gomez, João Carlos Gomes-Neto, Hatem Kittana, Hua Ding, Robert J. Schmaltz, Payal Joglekar, Roberto Jiménez Cardona, Nathan L Marsteller, Steven W. Kembel, Andrew K. Benson, Daniel A. Peterson, Amanda Ramer-Tait, Jens C. Walter

Department of Food Science and Technology: Faculty Publications

The factors that govern assembly of the gut microbiota are insufficiently understood. Here, we test the hypothesis that inter-individual microbiota variation can arise solely from differences in the order and timing by which the gut is colonized early in life. Experiments in which mice were inoculated in sequence either with two complex seed communities or a cocktail of four bacterial strains and a seed community revealed that colonization order influenced both the outcome of community assembly and the ecological success of individual colonizers. Historical contingency and priority effects also occurred in Rag1-/- mice, suggesting that the adaptive immune system …


Alterations In Platelet Secretion Differentially Affect Thrombosis And Hemostasis, Smita Joshi, Meenakshi Banerjee, Jinchao Zhang, Akhil Kesaraju, Irina D. Pokrovskaya, Brian Storrie, Sidney W. Whiteheart Sep 2018

Alterations In Platelet Secretion Differentially Affect Thrombosis And Hemostasis, Smita Joshi, Meenakshi Banerjee, Jinchao Zhang, Akhil Kesaraju, Irina D. Pokrovskaya, Brian Storrie, Sidney W. Whiteheart

Molecular and Cellular Biochemistry Faculty Publications

We genetically manipulated the major platelet vesicle-associated membrane proteins (VAMP2, VAMP3, and VAMP8) to create mice with varying degrees of disrupted platelet secretion. As previously shown, loss of VAMP8 reduced granule secretion, and this defect was exacerbated by further deletion of VAMP2 and VAMP3. VAMP2Δ3Δ8−/− platelets also had reduced VAMP7. Loss of VAMP2 and VAMP3 (VAMP2Δ3Δ) had a minimal impact on secretion when VAMP7 and VAMP8 were present. Integrin αIIbβ3 activation and aggregation were not affected, although spreading was reduced in VAMP2Δ3Δ8−/− platelets. Using these mice …


Transcriptomic Insights On The Virulence-Controlling Csra, Badr, Rpon, And Rpos Regulatory Networks In The Lyme Disease Spirochete, William K. Arnold, Christina R. Savage, Kathryn G. Lethbridge, Trever C. Smith, Catherine A. Brisette, Janakiram Seshu, Brian Stevenson Aug 2018

Transcriptomic Insights On The Virulence-Controlling Csra, Badr, Rpon, And Rpos Regulatory Networks In The Lyme Disease Spirochete, William K. Arnold, Christina R. Savage, Kathryn G. Lethbridge, Trever C. Smith, Catherine A. Brisette, Janakiram Seshu, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Borrelia burgdorferi, the causative agent of Lyme disease, survives in nature through a cycle that alternates between ticks and vertebrates. To facilitate this defined lifestyle, B. burgdorferi has evolved a gene regulatory network that ensures transmission between those hosts, along with specific adaptations to niches within each host. Several regulatory proteins are known to be essential for the bacterium to complete these critical tasks, but interactions between regulators had not previously been investigated in detail, due to experimental uses of different strain backgrounds and growth conditions. To address that deficit in knowledge, the transcriptomic impacts of four critical …


N-Terminal Domain Of Human Uracil Dna Glycosylase (Hung2) Promotes Targeting To Uracil Sites Adjacent To Ssdna-Dsdna Junctions, Brian P Weiser, Gaddiel Rodriguez, Philip A Cole, James T Stivers Aug 2018

N-Terminal Domain Of Human Uracil Dna Glycosylase (Hung2) Promotes Targeting To Uracil Sites Adjacent To Ssdna-Dsdna Junctions, Brian P Weiser, Gaddiel Rodriguez, Philip A Cole, James T Stivers

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The N-terminal domain (NTD) of nuclear human uracil DNA glycosylase (hUNG2) assists in targeting hUNG2 to replication forks through specific interactions with replication protein A (RPA). Here, we explored hUNG2 activity in the presence and absence of RPA using substrates with ssDNA-dsDNA junctions that mimic structural features of the replication fork and transcriptional R-loops. We find that when RPA is tightly bound to the ssDNA overhang of junction DNA substrates, base excision by hUNG2 is strongly biased toward uracils located 21 bp or less from the ssDNA-dsDNA junction. In the absence of RPA, hUNG2 still showed an 8-fold excision bias …


Rna-Seq Reveals Transcriptomic Program Associated With Stemness In Taxane Resistant Prostate Cancer, Christina K. Cajigas-Du Ross Aug 2018

Rna-Seq Reveals Transcriptomic Program Associated With Stemness In Taxane Resistant Prostate Cancer, Christina K. Cajigas-Du Ross

Loma Linda University Electronic Theses, Dissertations & Projects

There is no cure for advanced prostate cancer (PCa), and taxane chemotherapy is the only treatment option once other therapies have failed. However, this is problematic since all patients eventually develop chemoresistance. Emerging treatments for advanced PCa have shown promise at the benchside, but clinical trials have not resulted in newly approved drugs due in part to redundant survival pathways utilized by prostate tumor cells to maintain therapy-resistance. Using RNAsequencing—an innovative approach for quantifying gene expression changes—this dissertation sought to elucidate chemoresistance-associated molecular pathways as a catalyst to develop new therapeutic targets. Results revealed a differential upregulation of stemness-associated genes …


Novel Role Of Prostate Apoptosis Response-4 Tumor Suppressor In B-Cell Chronic Lymphocytic Leukemia, Mary Kathryn Mckenna, Sunil K. Noothi, Sara S. Alhakeem, Karine Z. Oben, Joseph T. Greene, Rajeswaran Mani, Kathryn L. Perry, James P. Collard, Jacqueline R. Rivas, Gerhard C. Hildebrandt, Roger A. Fleischman, Eric B. Durbin, John C. Byrd, Chi Wang, Natarajan Muthusamy, Vivek M. Rangnekar, Subbarao Bondada Jun 2018

Novel Role Of Prostate Apoptosis Response-4 Tumor Suppressor In B-Cell Chronic Lymphocytic Leukemia, Mary Kathryn Mckenna, Sunil K. Noothi, Sara S. Alhakeem, Karine Z. Oben, Joseph T. Greene, Rajeswaran Mani, Kathryn L. Perry, James P. Collard, Jacqueline R. Rivas, Gerhard C. Hildebrandt, Roger A. Fleischman, Eric B. Durbin, John C. Byrd, Chi Wang, Natarajan Muthusamy, Vivek M. Rangnekar, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Prostate apoptosis response-4 (Par-4), a proapoptotic tumor suppressor protein, is downregulated in many cancers including renal cell carcinoma, glioblastoma, endometrial, and breast cancer. Par-4 induces apoptosis selectively in various types of cancer cells but not normal cells. We found that chronic lymphocytic leukemia (CLL) cells from human patients and from Eµ-Tcl1 mice constitutively express Par-4 in greater amounts than normal B-1 or B-2 cells. Interestingly, knockdown of Par-4 in human CLL-derived Mec-1 cells results in a robust increase in p21/WAF1 expression and decreased growth due to delayed G1-to-S cell-cycle transition. Lack of Par-4 also increased the expression of p21 and …


Chronic Lymphocytic Leukemia-Derived Il-10 Suppresses Antitumor Immunity., Sara S Alhakeem, Mary K Mckenna, Karine Z Oben, Sunil K Noothi, Jacqueline R Rivas, Gerhard C Hildebrandt, Roger A Fleischman, Vivek M Rangnekar, Natarajan Muthusamy, Subbarao Bondada Jun 2018

Chronic Lymphocytic Leukemia-Derived Il-10 Suppresses Antitumor Immunity., Sara S Alhakeem, Mary K Mckenna, Karine Z Oben, Sunil K Noothi, Jacqueline R Rivas, Gerhard C Hildebrandt, Roger A Fleischman, Vivek M Rangnekar, Natarajan Muthusamy, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Chronic lymphocytic leukemia (CLL) patients progressively develop an immunosuppressive state. CLL patients have more plasma IL-10, an anti-inflammatory cytokine, than healthy controls. In vitro human CLL cells produce IL-10 in response to BCR cross-linking. We used the transgenic Eμ-T cell leukemia oncogene-1 (


Borrelia Burgdorferi Spovg Dna- And Rna-Binding Protein Modulates The Physiology Of The Lyme Disease Spirochete, Christina R. Savage, Brandon L. Jutras, Aaron Bestor, Kit Tilly, Patricia A. Rosa, Yvonne Tourand, Philip E. Stewart, Catherine A. Brissette, Brian Stevenson Jun 2018

Borrelia Burgdorferi Spovg Dna- And Rna-Binding Protein Modulates The Physiology Of The Lyme Disease Spirochete, Christina R. Savage, Brandon L. Jutras, Aaron Bestor, Kit Tilly, Patricia A. Rosa, Yvonne Tourand, Philip E. Stewart, Catherine A. Brissette, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The SpoVG protein of Borrelia burgdorferi, the Lyme disease spirochete, binds to specific sites of DNA and RNA. The bacterium regulates transcription of spoVG during the natural tick-mammal infectious cycle and in response to some changes in culture conditions. Bacterial levels of spoVG mRNA and SpoVG protein did not necessarily correlate, suggesting that posttranscriptional mechanisms also control protein levels. Consistent with this, SpoVG binds to its own mRNA, adjacent to the ribosome-binding site. SpoVG also binds to two DNA sites in the glpFKD operon and to two RNA sites in glpFKD mRNA; that operon encodes genes necessary for glycerol catabolism …


Stability Of The Human Faecal Microbiome In A Cohort Of Adult Men, Raaj S. Mehta, David A. Drew, Jason Lloyd-Price, Ayshwarya Subramaian, Paul Lochhead, Amit D. Joshi, Kerry L. Ivey, Hamed Khalili, Gordon T. Brown, Casey Dulong, Mingyang Song, Long H. Nguyen, Himel Mallick, Eric B. Rimm, Jacques Izard, Curtis Huttenhower, Andrew T. Chan, Galeb S. Abu-Ali Jun 2018

Stability Of The Human Faecal Microbiome In A Cohort Of Adult Men, Raaj S. Mehta, David A. Drew, Jason Lloyd-Price, Ayshwarya Subramaian, Paul Lochhead, Amit D. Joshi, Kerry L. Ivey, Hamed Khalili, Gordon T. Brown, Casey Dulong, Mingyang Song, Long H. Nguyen, Himel Mallick, Eric B. Rimm, Jacques Izard, Curtis Huttenhower, Andrew T. Chan, Galeb S. Abu-Ali

Department of Food Science and Technology: Faculty Publications

Characterizing the stability of the gut microbiome is important to exploit it as a therapeutic target and diagnostic biomarker. We metagenomically and metatranscriptomically sequenced the faecal microbiomes of 308 participants in the Health Professionals Follow-Up Study. Participants provided four stool samples—one pair collected 24–72 h apart and a second pair ~6 months later. Within-person taxonomic and functional variation was consistently lower than between-person variation over time. In contrast, metatranscriptomic profiles were comparably variable within and between subjects due to higher within-subject longitudinal variation. Metagenomic instability accounted for ~74% of corresponding metatranscriptomic instability. The rest was probably attributable to sources such …


The Small Rna Complement Of Adult Schistosoma Haematobium., Andreas J Stroehlein, Neil D Young, Pasi K Korhonen, Ross S Hall, Aaron R Jex, Bonnie L Webster, David Rollinson, Paul J Brindley, Robin B Gasser May 2018

The Small Rna Complement Of Adult Schistosoma Haematobium., Andreas J Stroehlein, Neil D Young, Pasi K Korhonen, Ross S Hall, Aaron R Jex, Bonnie L Webster, David Rollinson, Paul J Brindley, Robin B Gasser

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: Blood flukes of the genus Schistosoma cause schistosomiasis-a neglected tropical disease (NTD) that affects more than 200 million people worldwide. Studies of schistosome genomes have improved our understanding of the molecular biology of flatworms, but most of them have focused largely on protein-coding genes. Small non-coding RNAs (sncRNAs) have been explored in selected schistosome species and are suggested to play essential roles in the post-transcriptional regulation of genes, and in modulating flatworm-host interactions. However, genome-wide small RNA data are currently lacking for key schistosomes including Schistosoma haematobium-the causative agent of urogenital schistosomiasis of humans.

METHODOLOGY: MicroRNAs (miRNAs) and other …


Nutritional Virulence Of Legionella Pneumophila., Ashley M. Best May 2018

Nutritional Virulence Of Legionella Pneumophila., Ashley M. Best

Electronic Theses and Dissertations

Legionella pneumophila is an environment organism that parasitizes a wide range of protozoa. Growth within the environmental host primes L. pneumophila for infection of human alveolar macrophages when contaminated aerosols are inhaled. Intracellular replication within either host requires the establishment a replicative niche, known as the Legionella-containing vacuole (LCV). Biogenesis of the LCV depends on the type IVb translocation system, the Dot/Icm, to translocation >320 effectors into the host cytosol. Effectors are responsible for preventing lysosome fusion to the LCV, recruitment of ER-derived vesicles to the LCV, and modulation of a plethora of host processes to promote the intracellular …


Bioprospecting Deep-Sea Actinobacteria For Novel Anti-Infective Natural Products, Dongbo Xu, Linna Han, Chunhui Li, Qi Cao, Duolong Zhu, Nolan H. Barrett, Dedra Harmody, Jing Chen, Haining Zhu, Peter J. Mccarthy, Xingmin Sun, Guojun Wang Apr 2018

Bioprospecting Deep-Sea Actinobacteria For Novel Anti-Infective Natural Products, Dongbo Xu, Linna Han, Chunhui Li, Qi Cao, Duolong Zhu, Nolan H. Barrett, Dedra Harmody, Jing Chen, Haining Zhu, Peter J. Mccarthy, Xingmin Sun, Guojun Wang

Molecular and Cellular Biochemistry Faculty Publications

The global prevalence of drug resistance has created an urgent need for the discovery of novel anti-infective drugs. The major source of antibiotics in current clinical practice is terrestrial actinobacteria; the less-exploited deep-sea actinobacteria may serve as an unprecedented source of novel natural products. In this study, we evaluated 50 actinobacteria strains derived from diverse deep water sponges and environmental niches for their anti-microbial activities against a panel of pathogens including Candida albicans, Clostridium difficile, Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA), and Pseudomonas aeruginosa. More than half of the tested strains (27) were identified as …


Neutrophils From Both Susceptible And Resistant Mice Efficiently Kill Opsonized Listeria Monocytogenes, Michelle G. Pitts, Travis A. Combs, Sarah E. F. D'Orazio Apr 2018

Neutrophils From Both Susceptible And Resistant Mice Efficiently Kill Opsonized Listeria Monocytogenes, Michelle G. Pitts, Travis A. Combs, Sarah E. F. D'Orazio

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Inbred mouse strains differ in their susceptibility to infection with the facultative intracellular bacterium Listeria monocytogenes, largely due to delayed or deficient innate immune responses. Previous antibody depletion studies suggested that neutrophils (polymorphonuclear leukocytes [PMN]) were particularly important for clearance in the liver, but the ability of PMN from susceptible and resistant mice to directly kill L. monocytogenes has not been examined. In this study, we showed that PMN infiltrated the livers of BALB/c/By/J (BALB/c) and C57BL/6 (B6) mice in similar numbers and that both cell types readily migrated toward leukotriene B4 in an in vitro chemotaxis assay. However, …