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Full-Text Articles in Microbiology

Prospective Evaluation Of Serum Procalcitonin In Critically Ill Patients With Suspected Sepsis- Experience From A Tertiary Care Hospital In Pakistan, Sibtain Ahmed, Imran Siddiqui, Lena Jafri, Madiha Hashmi, Aysha Habib, Farooq Ghani Oct 2018

Prospective Evaluation Of Serum Procalcitonin In Critically Ill Patients With Suspected Sepsis- Experience From A Tertiary Care Hospital In Pakistan, Sibtain Ahmed, Imran Siddiqui, Lena Jafri, Madiha Hashmi, Aysha Habib, Farooq Ghani

Department of Pathology and Laboratory Medicine

Background: Sepsis is the leading cause of mortality in critically ill patients. Procalcitonin (PCT) is a promising marker for identification of bacterial sepsis. The aim of this study was to determine the diagnostic accuracy of serum PCT concentration in patients with suspected sepsis admitted to mixed medical-surgical Intensive care unit (ICU).
Material and methods: A cross-sectional study conducted at section of Chemical Pathology, Department of Pathology and Laboratory Medicine and ICU. Patients with suspected sepsis were included, serum PCT cut off ≥0.5 ng/ml was taken for diagnosing sepsis. Diagnostic accuracy was measured in terms of sensitivity, specificity, positive predictive value …


Susceptibility Genes To Plant Viruses, Hernan Garcia-Ruiz Sep 2018

Susceptibility Genes To Plant Viruses, Hernan Garcia-Ruiz

Nebraska Center for Virology: Faculty Publications

Plant viruses use cellular factors and resources to replicate and move. Plants respond to viral infection by several mechanisms, including innate immunity, autophagy, and gene silencing, that viruses must evade or suppress. Thus, the establishment of infection is genetically determined by the availability of host factors necessary for virus replication and movement and by the balance between plant defense and viral suppression of defense responses. Host factors may have antiviral or proviral activities. Proviral factors condition susceptibility to viruses by participating in processes essential to the virus. Here, we review current advances in the identification and characterization of host factors …


Mechanisms Adopted By Dengue-2 Viruses To Induce Autophagy In Mammalian Cells, Sounak Ghosh Roy Sep 2018

Mechanisms Adopted By Dengue-2 Viruses To Induce Autophagy In Mammalian Cells, Sounak Ghosh Roy

Dissertations, Theses, and Capstone Projects

Dengue, the most rapidly spreading flavivirus, threatens to affect almost half of the human global population. We previously showed that dengue-2 protects canine kidney cells (MDCK) from cytotoxic chemicals. We showed, independently, that cell protection, as well as viral replication and maturation, are positively regulated by PI3K-dependent autophagy. However, we had not identified the specific pathway that induces autophagy in infected cells. The current study explores the role of a specific branch of the endoplasmic reticulum (ER) stress-mediated Unfolded Protein Response (UPR), the PERK/eIF2α/ATF4 pathway in the induction of autophagy by …


Microbiological And Clinical Profile Of Infective Endocarditis Patients: An Observational Study Experience From Tertiary Care Center Karachi Pakistan, Uzma Shahid, Hasanat Sharif, Joveria Farooqi, Bushra Jamil, E. Khan Sep 2018

Microbiological And Clinical Profile Of Infective Endocarditis Patients: An Observational Study Experience From Tertiary Care Center Karachi Pakistan, Uzma Shahid, Hasanat Sharif, Joveria Farooqi, Bushra Jamil, E. Khan

Department of Pathology and Laboratory Medicine

Background:
The study analyzed microbiological and antimicrobial susceptibility profile of organisms isolated from patients with infective endocarditis (2015–17) and compared disease outcomes in cohorts of endocarditis patient with history of prior invasive vascular intervention (high risk group) vs those without (native valve group). We hypothesized that high risk group would be more likely to have severe disease outcomes.
Methods:
This was a prospective cohort study (2015–17). All blood and cardiac tissue samples of enrolled patients suspected of endocarditis according to modified Duke’s criteria were followed for microbiological and antimicrobial susceptibility profile. The high risk group was compared with the native …


Congenital Zika Virus Infection In Immunocompetent Mice Causes Postnatal Growth Impediment And Neurobehavioral Deficits, Amber M. Paul, Dhiraj Acharya, Biswas Neupane, E. Ashley Thompson, Gabriel Gonzalez-Fernandez, Katherine M. Copeland Aug 2018

Congenital Zika Virus Infection In Immunocompetent Mice Causes Postnatal Growth Impediment And Neurobehavioral Deficits, Amber M. Paul, Dhiraj Acharya, Biswas Neupane, E. Ashley Thompson, Gabriel Gonzalez-Fernandez, Katherine M. Copeland

Publications

A small percentage of babies born to Zika virus (ZIKV)-infected mothers' manifest severe defects at birth, including microcephaly. Among those who appeared healthy at birth, there are increasing reports of postnatal growth or developmental defects. However, the impact of congenital ZIKV infection in postnatal development is poorly understood. Here, we report that a mild congenital ZIKV-infection in pups born to immunocompetent pregnant mice did not display apparent defects at birth, but manifested postnatal growth impediments and neurobehavioral deficits, which include reduced locomotor and cognitive deficits that persisted into adulthood. We found that the brains of these pups were smaller, had …


Low Grade Mullerian Adenosarcoma Of Pouch Of Douglas Recurring As Bilateral Ovarian High Grade Mullerian Adenosarcoma With Rhabdomyosarcomatous Overgrowth After 11 Years, Sandeep Kumar, Muhammad Raza, Muhammad Usman Tariq Aug 2018

Low Grade Mullerian Adenosarcoma Of Pouch Of Douglas Recurring As Bilateral Ovarian High Grade Mullerian Adenosarcoma With Rhabdomyosarcomatous Overgrowth After 11 Years, Sandeep Kumar, Muhammad Raza, Muhammad Usman Tariq

Department of Pathology and Laboratory Medicine

Mullerian adenosarcoma (MA) of ovary with sarcomatous (rhabdomyoblastic) overgrowth is an extremely rare malignant type of female genital tract neoplasm. These tumours are highly aggressive and presence of heterologous elements is associated with worse prognosis. A 44 year old female presented with lower abdominal pain and distension. She had history of removal of tumour from pouch of Douglas in 2006 for which she did not receive any additional treatment nor did she keep continuous follow up. Current preoperative radiological examination revealed bilateral ovarian masses. She underwent abdominal hysterectomy with bilateral oophorectomy. Microscopic examination revealed biphasic tumours exhibiting sarcomatous overgrowth with …


Dietary Inclusion Of Enriched Chicken Bone Broth Prevents Trigeminal Sensitization Meditated By Early Life Stress, Orion Peterson Aug 2018

Dietary Inclusion Of Enriched Chicken Bone Broth Prevents Trigeminal Sensitization Meditated By Early Life Stress, Orion Peterson

Graduate Theses/Dissertations

Early life stress is considered a risk factor for development of migraine, which is a prevalent painful neurological disorder involving sensitization and activation of trigeminal neurons, and irritable bowel syndrome, a condition often comorbid with chronic migraine. The focus of my study was to determine the effects of early life stress and dietary inclusion of enriched chicken bone broth on trigeminal nociceptor sensitization and the gut microbiota. Adult Sprague-Dawley male “sender” rats subjected to primary traumatic stress were placed next to breeding or pregnant female rats that served as “receiver” rats (secondary traumatic stress) and in proximity to the offspring …


Her2 Basolateral Versus Circumferential Ihc Expression Is Dependent On Polarity And Differentiation Of Epithelial Cells In Gastric/Ge Adenocarcinoma, Shahid Pervez, Sidra Arshad, Brooj Abro Jul 2018

Her2 Basolateral Versus Circumferential Ihc Expression Is Dependent On Polarity And Differentiation Of Epithelial Cells In Gastric/Ge Adenocarcinoma, Shahid Pervez, Sidra Arshad, Brooj Abro

Department of Pathology and Laboratory Medicine

Aim: Antigenic expression in epithelial cells can be heterogeneous which may pose a problem in immunohistochemical (IHC) analysis of tumor markers, in particular, predictive markers like HER2. Studies have shown that epithelial cells have distinct apical and basolateral domains which are separated by tight junctions. The cell membrane in these two domains has a different composition of macromolecules and hence can have variable antigen expression on immunohistochemistry. In our study, we aimed to investigate this phenomenon of basolateral versus circumferential IHC staining of HER2 in gastric/GE adenocarcinoma.
Methods: We selected 45 cases of gastric/GE adenocarcinoma and evaluated equal number of …


Type 2 Bovine Viral Diarrhea Virus NPro Suppresses Type I Interferon Pathway Signaling In Bovine Cells And Augments Bovine Respiratory Syncytial Virus Replication, Abdulrahman Abdulaziz A. Alkheraif Jul 2018

Type 2 Bovine Viral Diarrhea Virus NPro Suppresses Type I Interferon Pathway Signaling In Bovine Cells And Augments Bovine Respiratory Syncytial Virus Replication, Abdulrahman Abdulaziz A. Alkheraif

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

Bovine viral diarrhea virus (BVDV) and bovine respiratory syncytial virus (BRSV) infections contribute to the bovine respiratory disease complex (BRDC), which is a multi-factorial disorder involving co-infections of viruses and bacteria including mycoplasma. BRDC causes great economic losses to the United States feedlot industry. BVDV infection induces immunosuppression in infected animals. BVDV Npro binds and degrades the transcription factor interferon regulatory factor-3 (IRF-3) and effectively blocks type I interferon (type I IFN) expression in host cells. BRSV nonstructural proteins, NS1 and NS2, block activation of IRF-3. In calves, concurrent infection with BVDV and BRSV resulted in more severe clinical …


Clinicopathologic Features Of Invasive Metaplastic And Micropapillary Breast Carcinoma: Comparison With Invasive Ductal Carcinoma Of Breast, Atif Ali Hashmi, Saher Aijaz, Raeesa Mahboob, Saadia Mehmood Khan, Muhammad Irfan, Narisa Iftikhar, Mariam Nisar, Maham Siddiqui, Muhammad Muzzammil Edhi, Naveen Faridi, Amir Khan Jul 2018

Clinicopathologic Features Of Invasive Metaplastic And Micropapillary Breast Carcinoma: Comparison With Invasive Ductal Carcinoma Of Breast, Atif Ali Hashmi, Saher Aijaz, Raeesa Mahboob, Saadia Mehmood Khan, Muhammad Irfan, Narisa Iftikhar, Mariam Nisar, Maham Siddiqui, Muhammad Muzzammil Edhi, Naveen Faridi, Amir Khan

Department of Pathology and Laboratory Medicine

Objective: The aim of this study was to determine the frequency of metaplastic breast carcinoma and invasive micropapillary carcinoma in our population and also to compare the clinico-pathologic features of metaplastic breast carcinoma and invasive micropapillary carcinoma with invasive ductal carcinoma, not otherwise specified (IDC, NOS).
Result: 86.9% of the cases were identified as ductal carcinoma, NOS, while 2.2% were metaplastic and 0.76% cases were micropapillary carcinoma. Metaplastic carcinomas were found to be of higher grade as compared to IDC, NOS as 81% of metaplastic carcinoma were grade III compared to 35% IDC, NOS. 79% of metaplastic carcinoma were ER …


Global Distribution Of Invasive Serotype 35d Streptococcus Pneumoniae Isolates Following Introduction Of 13-Valent Pneumococcal Conjugate Vaccine, Stephanie W. Lo, Rebecca A. Gladstone, Andries J. Van Tonder, Paulina A. Hawkins, Brenda Kwambana Adams, Jennifer E. Cornick, Shabir A. Madhi, Susan A. Nzenze, Mignon Du Plessis, Rama Kandasamy, Philip E. Carter, Sadia Shakoor Jun 2018

Global Distribution Of Invasive Serotype 35d Streptococcus Pneumoniae Isolates Following Introduction Of 13-Valent Pneumococcal Conjugate Vaccine, Stephanie W. Lo, Rebecca A. Gladstone, Andries J. Van Tonder, Paulina A. Hawkins, Brenda Kwambana Adams, Jennifer E. Cornick, Shabir A. Madhi, Susan A. Nzenze, Mignon Du Plessis, Rama Kandasamy, Philip E. Carter, Sadia Shakoor

Department of Pathology and Laboratory Medicine

A newly recognized pneumococcal serotype 35D, which differs from the 35B polysaccharide in structure and serology by not binding to factor serum 35a, was recently reported. The genetic basis for this distinctive serology is due to the presence of an inactivating mutation in wciG, which encodes an O-acetyltransferase responsible for O-acetylation of a galactofuranose. Here, we assessed the genomic data of a worldwide pneumococcal collection to identify serotype 35D isolates and understand their geographical distribution, genetic background and invasiveness potential. Of 21,980 pneumococcal isolates, 444 were originally typed as serotype 35B by PneumoCaT. Analysis of wciGrevealed 23 isolates …


Role Of Tnf Α, Il-6 And Cxcl10 In Dengue Disease Severity, Kiran I. Masood, Bushra Jamil, Maryam Rahim, Muniba Islam, Muhammad Farhan, Zahra Hasan Jun 2018

Role Of Tnf Α, Il-6 And Cxcl10 In Dengue Disease Severity, Kiran I. Masood, Bushra Jamil, Maryam Rahim, Muniba Islam, Muhammad Farhan, Zahra Hasan

Department of Pathology and Laboratory Medicine

Background and objective: Dengue virus infections (Dengue) have become increasingly common in Pakistan and can result in case fatalities if not managed appropriately. Patients with Dengue virus infection may be asymptomatic or present with Dengue fever (DF), Dengue with warning signs (DWS) or severe Dengue (SD). Severity in Dengue is coincident with an exacerbated production of lymphocyte-induced cytokines and chemokines which are associated with plasma leakage. We investigated the association of circulating levels of cytokines such as Interleukin (IL)-6, tumor necrosis factor (TNF)-alpha and CXCL-10 in Dengue patients with differing severity of disease.
Material and methods: Dengue infection was confirmed …


The Effect Of Cellular Dehydration On Glucose Regulation In Lean And Obese Females, Chunbo Yang May 2018

The Effect Of Cellular Dehydration On Glucose Regulation In Lean And Obese Females, Chunbo Yang

Graduate Theses and Dissertations

A chronically elevated vasopressin level has been associated with an impaired glucose regulation system in humans. A recent study in patients with diabetes suggested that low water intake is associated with impaired glucose regulation. The aim of this study was to examine the effect of hypertonic saline infusion on glucose regulation in healthy females. Thirty healthy, non-diabetic females performed a 2-h infusion followed by a 4-h oral glucose tolerance test (OGTT). Every subject participated in two trials separated by one month, in a counterbalanced order. Two trials were identical in the procedure, differing in the concentration of saline infusion, with …


Non O1, Non O139 Vibrio Cholerae Bacteraemia In An Infant; Case Report And Literature Review, Mirza Zain Baig, Umme Hani Abdullah, Yusra Shafquat, Khadija Nuzhat Humayun, Afia Zafar Apr 2018

Non O1, Non O139 Vibrio Cholerae Bacteraemia In An Infant; Case Report And Literature Review, Mirza Zain Baig, Umme Hani Abdullah, Yusra Shafquat, Khadija Nuzhat Humayun, Afia Zafar

Medical College Documents

Non 01, Non O139 Vibrio cholerae bacteraemia is a rare but potentially fatal occurrence. There have been very few incidents of this infection from around the world. The treatment regimen of antibiotics also varies in literature. We present a case of bacteraemia caused by Non O1, Non O139 Vibrio cholerae along with associated risk factors, disease manifestations, laboratory diagnosis and treatment regimen. This serves to add additional information regarding symptoms and signs of this infection along with management of patient. Knowledge regarding this topic shall be highly useful to professionals if further cases are detected. In the discussion section, a …


In Vitro Assay Development As An Alternative To The Use Of Laboratory Animals For Measuring Clostridium Perfingens Type C Toxoid, Lauren M. Wilmes Apr 2018

In Vitro Assay Development As An Alternative To The Use Of Laboratory Animals For Measuring Clostridium Perfingens Type C Toxoid, Lauren M. Wilmes

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

Clostridium perfringens type C produces beta toxin, which is a primary virulence determinate that can cause necrotic enteritis in neonatal animals. Vaccines directed against C. perfringens toxins have shown to be efficacious in preventing disease. However, the production of a commercial vaccine requires not only an efficacious antigen, but also testing methods for quantifying antigens and potency on final product. This research was undertaken to fulfill a need for the reduction in small animal usage to produce and deliver vaccines. The current testing methods are performed in vivo according to the Code of Federal Regulations number 9 (9CFR) United …


A Comparison Of Oral And Intravenous Mouse Models Of Listeriosis, Michelle G. Pitts, Sarah E. F. D'Orazio Mar 2018

A Comparison Of Oral And Intravenous Mouse Models Of Listeriosis, Michelle G. Pitts, Sarah E. F. D'Orazio

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Listeria monocytogenes is one of several enteric microbes that is acquired orally, invades the gastric mucosa, and then disseminates to peripheral tissues to cause systemic disease in humans. Intravenous (i.v.) inoculation of mice with L. monocytogenes has been the most widely-used small animal model of listeriosis over the past few decades. The infection is highly reproducible and has been invaluable in deciphering mechanisms of adaptive immunity in vivo, particularly CD8+ T cell responses to intracellular pathogens. However, the i.v. model completely bypasses the gut phase of the infection. Recent advances in generating both humanized mice and murinized bacteria, as well …


Integrating Tuberculosis And Antimicrobial Resistance Control Programmes, Rumina Hasan, Sadia Shakoor, Johanna Hanefeld, Mishal Khan Mar 2018

Integrating Tuberculosis And Antimicrobial Resistance Control Programmes, Rumina Hasan, Sadia Shakoor, Johanna Hanefeld, Mishal Khan

Department of Pathology and Laboratory Medicine

Many low- and middle-income countries facing high levels of antimicrobial resistance, and the associated morbidity from ineffective treatment, also have a high burden of tuberculosis. Over recent decades many countries have developed effective laboratory and information systems for tuberculosis control. In this paper we describe how existing tuberculosis laboratory systems can be expanded to accommodate antimicrobial resistance functions. We show how such expansion in services may benefit tuberculosis case-finding and laboratory capacity through integration of laboratory services. We further summarize the synergies between high-level strategies on tuberculosis and antimicrobial resistance control. These provide a potential platform for the integration of …


Emergence Of An Extensively Drug-Resistant Salmonella Enterica Serovar Typhi Clone Harboring A Promiscuous Plasmid Encoding Resistance To Fluoroquinolones And Third-Generation Cephalosporins, Rumina Hasan, Sadia Shakoor, Farah Naz Qamar, Dania Khalid Saeed, Ghazala Shaheen, Shahida Qureshi, Mohammad Tahir Yousafzai, Muhammad Khalid Salim, Zahra Hasan, Elizabeth J. Klemma, Andrew J. Page, Kim Judge, Vanessa K. Wong, Timothy J. Dallman, Satheesh Nair, Stephen Baker, Gordon Dougan Feb 2018

Emergence Of An Extensively Drug-Resistant Salmonella Enterica Serovar Typhi Clone Harboring A Promiscuous Plasmid Encoding Resistance To Fluoroquinolones And Third-Generation Cephalosporins, Rumina Hasan, Sadia Shakoor, Farah Naz Qamar, Dania Khalid Saeed, Ghazala Shaheen, Shahida Qureshi, Mohammad Tahir Yousafzai, Muhammad Khalid Salim, Zahra Hasan, Elizabeth J. Klemma, Andrew J. Page, Kim Judge, Vanessa K. Wong, Timothy J. Dallman, Satheesh Nair, Stephen Baker, Gordon Dougan

Department of Pathology and Laboratory Medicine

Antibiotic resistance is a major problem in Salmonella enterica serovar Typhi, the causative agent of typhoid. Multidrug-resistant (MDR) isolates are prevalent in parts of Asia and Africa and are often associated with the dominant H58 haplotype. Reduced susceptibility to fluoroquinolones is also widespread, and sporadic cases of resistance to third-generation cephalosporins or azithromycin have also been reported. Here, we report the first large-scale emergence and spread of a novel S. Typhi clone harboring resistance to three first-line drugs (chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) as well as fluoroquinolones and third-generation cephalosporins in Sindh, Pakistan, which we classify as extensively drug resistant …


Infection Of A Ventricular Septal Defect Patch With Acremonium Species, Nosheen Nasir, Kauser Jabeen, Joveria Farooqi, Binish Arif Sultan, Afia Zafar, Aamir Hameed Khan, Muneer Amanullah, Farheen Ali Jan 2018

Infection Of A Ventricular Septal Defect Patch With Acremonium Species, Nosheen Nasir, Kauser Jabeen, Joveria Farooqi, Binish Arif Sultan, Afia Zafar, Aamir Hameed Khan, Muneer Amanullah, Farheen Ali

Section of Internal Medicine

A ventricular septal defect (VSD) patch infection with Acremonium species isolated from vegetation and blood culture is described. Antifungal treatment was discontinued after 3 months and patient developed relapse. Surgery with prolonged oral voriconazole was instituted with recovery. We emphasize importance of surgery and prolonged therapy to treat such infections.


Direct Detection Of Shigella In Stool Specimens By Use Of A Metagenomic Approach, Jie Liu, Mathieu Almeida, Furqan Kabir, Sadia Shakoor, Shahida Qureshi, Anita K. M. Zaidi, Shan Li, Boubou Tamboura, Samba O. Sow, Inacio Mandomando Jan 2018

Direct Detection Of Shigella In Stool Specimens By Use Of A Metagenomic Approach, Jie Liu, Mathieu Almeida, Furqan Kabir, Sadia Shakoor, Shahida Qureshi, Anita K. M. Zaidi, Shan Li, Boubou Tamboura, Samba O. Sow, Inacio Mandomando

Department of Paediatrics and Child Health

The underestimation of Shigella species as a cause of childhood diarrhea disease has become increasingly apparent with quantitative PCR (qPCR)-based diagnostic methods versus culture. We sought to confirm qPCR-based detection of Shigella via a metagenomics approach. Three groups of samples were selected from diarrheal cases from the Global Enteric Multicenter Study: nine Shigella culture-positive and qPCR-positive (culture+ qPCR+) samples, nine culture-negative but qPCR-positive (culture- qPCR+) samples, and nine culture-negative and qPCR-negative (culture- qPCR-) samples. Fecal DNA was sequenced using paired-end Illumina HiSeq, whereby 3.26 × 108 ± 5.6 × 10 …


Lipoblastoma: A Clinicopathologic Review Of 23 Cases From A Major Tertiary Care Center Plus Detailed Review Of Literature, Jamshid Abdul Ghafar, Zubair Ahmad, Muhammad Usman Tariq, Naila Kayani Naila Kayani, Nasir Ud Din Jan 2018

Lipoblastoma: A Clinicopathologic Review Of 23 Cases From A Major Tertiary Care Center Plus Detailed Review Of Literature, Jamshid Abdul Ghafar, Zubair Ahmad, Muhammad Usman Tariq, Naila Kayani Naila Kayani, Nasir Ud Din

Department of Pathology and Laboratory Medicine

Objective: Lipoblastoma is a rare neoplasm that occurs mostly in infants and children. Although benign, it has a tendency for local recurrence.
Results: Clinical and pathological features of 23 cases of lipoblastoma described. Patients’ age ranged from 8 months to 18 years with mean and median age 4.1 and 2.5 years, respectively. Male:female ratio was 2.8:1. Most common sites were lower extremities (9 cases), followed by abdominal cavity and retroperitoneum (4 cases), and scrotum/groin (3 cases). Grossly, 22 tumors were well circumscribed and multi nodular. All cases showed lobules composed of adi‑ pocytes and lipoblasts with intervening fbrous septa and …


Methylation In Mycobacterium Tuberculosis Is Lineage Specific With Associated Mutations Present Globally, Jody Phelan, Paola Florez De Sessions, Leopold Tientcheu, Joao Perdigao, Diana Machado, Rumina Hasan, Zahra Hasan, Indra L. Bergval, Richard Anthony, Ruth Mcnerney Jan 2018

Methylation In Mycobacterium Tuberculosis Is Lineage Specific With Associated Mutations Present Globally, Jody Phelan, Paola Florez De Sessions, Leopold Tientcheu, Joao Perdigao, Diana Machado, Rumina Hasan, Zahra Hasan, Indra L. Bergval, Richard Anthony, Ruth Mcnerney

Department of Pathology and Laboratory Medicine

DNA methylation is an epigenetic modification of the genome involved in regulating crucial cellular processes, including transcription and chromosome stability. Advances in PacBio sequencing technologies can be used to robustly reveal methylation sites. The methylome of the Mycobacterium tuberculosis complex is poorly understood but may be involved in virulence, hypoxic survival and the emergence of drug resistance. In the most extensive study to date, we characterise the methylome across the 4 major lineages of M. tuberculosis and 2 lineages of M. africanum, the leading causes of tuberculosis disease in humans. We reveal lineage-specific methylated motifs and strain-specific mutations that are …


Wdr5 Supports Colon Cancer Cells By Promoting Methylation Of H3k4 And Suppressing Dna Damage, Beth K. Neilsen, Binita Chakraborty, Jamie L. Mccall, Danielle E. Frodyma, Richard L. Sleightholm, Kurt W. Fisher, Robert E. Lewis Jan 2018

Wdr5 Supports Colon Cancer Cells By Promoting Methylation Of H3k4 And Suppressing Dna Damage, Beth K. Neilsen, Binita Chakraborty, Jamie L. Mccall, Danielle E. Frodyma, Richard L. Sleightholm, Kurt W. Fisher, Robert E. Lewis

Faculty & Staff Scholarship

Background: KMT2/MLL proteins are commonly overexpressed or mutated in cancer and have been shown to support cancer maintenance. These proteins are responsible for methylating histone 3 at lysine 4 and promoting transcription and DNA synthesis; however, they are inactive outside of a multi-protein complex that requires WDR5. WDR5 has been implicated in cancer for its role in the COMPASS complex and its interaction with Myc; however, the role of WDR5 in colon cancer has not yet been elucidated.

Methods: WDR5 expression was evaluated using RT-qPCR and western blot analysis. Cell viability and colony forming assays were utilized to evaluate the …


Spontaneous Dna Damage To The Nuclear Genome Promotes Senescence, T Redox Imbalance And Aging, Andria R. Robinson, Matthew J. Yousefzadeh, Tania A. Rozgaja, Jin Wang, Xuesen Li, Jeremy S. Tilstra, Chelsea H. Feldman, Siobhan Q. Gregg, Caroline H. Johnson, Erin M. Skoda, Marie-Celine Frantz, Harris Bell-Temin, Hannah Pope-Varsalona, Aditi U. Gurkar, Luigi A. Nasto, Rena A.S. Robinson, Heike Fuhrmann-Stroissnigg, Jolanta Czerwinska, Sara J. Mcgowan, Nadiezhda Cantu-Madellin, Jamie B. Harris, Salony Maniar, Mark A. Ross, Christy E. Trussoni, Nicholas F. Larusso, Eugenia Cifuentes-Pagano, Patrick J. Pagano, Barbara Tudek, Nam V. Vo, Lora H. Rigatti, Patricia L. Opresko, Donna B. Stolz, Simon C. Watkins, Christin E. Burd, Claudette M. St, Croix, Gary Siuzdak, Nathan A. Yates, Paul D. Robbins, Yinsheng Wang, Peter Wipf, Eric E. Kelley, Laura J. Neidernhofer Jan 2018

Spontaneous Dna Damage To The Nuclear Genome Promotes Senescence, T Redox Imbalance And Aging, Andria R. Robinson, Matthew J. Yousefzadeh, Tania A. Rozgaja, Jin Wang, Xuesen Li, Jeremy S. Tilstra, Chelsea H. Feldman, Siobhan Q. Gregg, Caroline H. Johnson, Erin M. Skoda, Marie-Celine Frantz, Harris Bell-Temin, Hannah Pope-Varsalona, Aditi U. Gurkar, Luigi A. Nasto, Rena A.S. Robinson, Heike Fuhrmann-Stroissnigg, Jolanta Czerwinska, Sara J. Mcgowan, Nadiezhda Cantu-Madellin, Jamie B. Harris, Salony Maniar, Mark A. Ross, Christy E. Trussoni, Nicholas F. Larusso, Eugenia Cifuentes-Pagano, Patrick J. Pagano, Barbara Tudek, Nam V. Vo, Lora H. Rigatti, Patricia L. Opresko, Donna B. Stolz, Simon C. Watkins, Christin E. Burd, Claudette M. St, Croix, Gary Siuzdak, Nathan A. Yates, Paul D. Robbins, Yinsheng Wang, Peter Wipf, Eric E. Kelley, Laura J. Neidernhofer

Faculty & Staff Scholarship

Accumulation of senescent cells over time contributes to aging and age-related diseases. However, what drives senescence in vivo is not clear. Here we used a genetic approach to determine if spontaneous nuclear DNA damage is sufficient to initiate senescence in mammals. Ercc1-/Δ mice with reduced expression of ERCC1-XPF endonuclease have impaired capacity to repair the nuclear genome. Ercc1-/Δ mice accumulated spontaneous, oxidative DNA damage more rapidly than wild-type (WT) mice. As a consequence, senescent cells accumulated more rapidly in Ercc1-/Δ mice compared to repair-competent animals. However, the levels of DNA damage and senescent cells in Ercc1-/Δ mice never exceeded that …


Altered Ratio Of T Follicular Helper Cells To T Follicular Regulatory Cells Correlates With Autoreactive Antibody Response In Simian Immunodeficiency Virus–Infected Rhesus Macaques, Wenjin Fan, Andrew James Demers, Yanmin Wan, Qingsheng Li Jan 2018

Altered Ratio Of T Follicular Helper Cells To T Follicular Regulatory Cells Correlates With Autoreactive Antibody Response In Simian Immunodeficiency Virus–Infected Rhesus Macaques, Wenjin Fan, Andrew James Demers, Yanmin Wan, Qingsheng Li

Nebraska Center for Virology: Faculty Publications

Individuals with chronic HIV-1 infection have an increased prevalence of autoreactive Abs. Many of the isolated HIV broadly neutralizing Abs from these individuals are also autoreactive. However, the underlying mechanism(s) that produce these autoreactive broadly neutralizing Abs remains largely unknown. The highly regulated coordination among B cells, T follicular helper (TFH) cells, and T follicular regulatory (TFR) cells in germinal centers (GCs) of peripheral lymphatic tissues (LTs) is essential for defense against pathogens while also restricting autoreactive responses. We hypothesized that an altered ratio of TFH/TFR cells in the GC contributes to the …


Mucosal Antibody Responses To Vaccines Targeting Siv Protease Cleavage Sites Or Fulllength Gag And Env Proteins In Mauritian Cynomolgus Macaques, Hongzhao Li, Yan Hai, So-Yon Lim, Nikki Toledo, Jose Crecente-Campo, Dane Schalk, Lin Li, Robert W. Omange, Tamara G. Dacoba, Lewis R. Liu, Mohammad Abul Kashem, Yanmin Wan, Binhua Liang, Qingsheng Li, Eva Rakasz, Nancy Schultz-Darken, Maria J. Alonso, Francis A. Plummer, James B. Whitney, Ma Luo Jan 2018

Mucosal Antibody Responses To Vaccines Targeting Siv Protease Cleavage Sites Or Fulllength Gag And Env Proteins In Mauritian Cynomolgus Macaques, Hongzhao Li, Yan Hai, So-Yon Lim, Nikki Toledo, Jose Crecente-Campo, Dane Schalk, Lin Li, Robert W. Omange, Tamara G. Dacoba, Lewis R. Liu, Mohammad Abul Kashem, Yanmin Wan, Binhua Liang, Qingsheng Li, Eva Rakasz, Nancy Schultz-Darken, Maria J. Alonso, Francis A. Plummer, James B. Whitney, Ma Luo

Nebraska Center for Virology: Faculty Publications

HIV mutates rapidly and infects CD4+ T cells, especially when they are activated. A vaccine targeting conserved, essential viral elements while limiting CD4+ T cell activation could be effective. Learning from natural immunity observed in a group of highly HIV-1 exposed seronegative Kenyan female sex workers, we are testing a novel candidate HIV vaccine targeting the 12 viral protease cleavage sites (PCSs) (the PCS vaccine), in comparison with a vaccine targeting full-length Gag and Env (the Gag/Env vaccine) in a Mauritian cynomolgus macaque/SIV model. In this study we evaluated these vaccines for induction of mucosal antibodies to SIV …


Adherence Mechanism Analysis: The Role Of Prsa Gene In Lactobacillus Acidophilus And Other Infectious Microorganisms, Nujuma Moussa Jan 2018

Adherence Mechanism Analysis: The Role Of Prsa Gene In Lactobacillus Acidophilus And Other Infectious Microorganisms, Nujuma Moussa

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

No abstract provided.


Sivcpz Closely Related To The Ancestral Hiv-1 Is Less Or Non-Pathogenic To Humans In A Hu-Blt Mouse Model, Zhe Yuan, Guobin Kang, Lance Daharsh, Wenjin Fan, Qingsheng Li Jan 2018

Sivcpz Closely Related To The Ancestral Hiv-1 Is Less Or Non-Pathogenic To Humans In A Hu-Blt Mouse Model, Zhe Yuan, Guobin Kang, Lance Daharsh, Wenjin Fan, Qingsheng Li

Nebraska Center for Virology: Faculty Publications

The HIV-1 pandemic is a consequence of the cross-species transmission of simian immunodeficiency virus in wild chimpanzees (SIVcpz) to humans. Our previous study demonstrated SIVcpz strains that are closely related to the ancestral viruses of HIV-1 groups M (SIVcpzMB897) and N (SIVcpzEK505) and two SIVcpz lineages that are not associated with any known HIV-1 infections in humans (SIVcpzMT145 and SIVcpzBF1167), all can readily infect and robustly replicate in the humanized-BLT mouse model of humans. However, the comparative pathogenicity of different SIVcpz strains remains unknown. Herein, we compared the pathogenicity of the above four SIVcpz strains with HIV-1 using humanized-BLT mice. …


Identification Of Unequally Represented Founder Viruses Among Tissues In Very Early Siv Rectal Transmission, Jian Chen, Yanqin Ren, Lance Daharsh, Lu Liu, Guobin Kang, Qingsheng Li, Qiang Wei, Yanmin Wu, Jianqing Xu Jan 2018

Identification Of Unequally Represented Founder Viruses Among Tissues In Very Early Siv Rectal Transmission, Jian Chen, Yanqin Ren, Lance Daharsh, Lu Liu, Guobin Kang, Qingsheng Li, Qiang Wei, Yanmin Wu, Jianqing Xu

Nebraska Center for Virology: Faculty Publications

Characterizing the transmitted/founder (T/F) viruses of multi-variant SIV infection may shed new light on the understanding of mucosal transmission.We intrarectally inoculated six Chinese rhesus macaques with a single high dose of SIVmac251 (3.1 × 104 TCID50) and obtained 985 full-length env sequences from multiple tissues at 6 and 10 days post-infection by single genome amplification (SGA). All 6 monkeys were infected with a range of 2 to 8 T/F viruses and the dominant variants from the inoculum were still dominant in different tissues from each monkey. Interestingly, our data showed that a cluster of rare T/F viruses …


Analytical Performance Of A Low‐Cost Multiplex Polymerase Chain Reaction Human Papillomavirus Genotyping Assay For Use In Sub‐Saharan Africa, Kandali Samwel, Crispin Kahesa, Julius Mwaiselage, Daniela Gonzalez, John T. West, Charles Wood, Joel Palefsky, Peter C. Angeletti Jan 2018

Analytical Performance Of A Low‐Cost Multiplex Polymerase Chain Reaction Human Papillomavirus Genotyping Assay For Use In Sub‐Saharan Africa, Kandali Samwel, Crispin Kahesa, Julius Mwaiselage, Daniela Gonzalez, John T. West, Charles Wood, Joel Palefsky, Peter C. Angeletti

Nebraska Center for Virology: Faculty Publications

We have tested a multiplex polymerase chain reaction (PCR) human papillomavirus (HPV) genotyping assay to fill the need for rapid and low‐cost HPV detection in Sub‐ Saharan Africa. This method allows high throughput genotyping and simultaneous detection of 14 high‐risk and two low‐risk HPV types, by PCR amplification of HPV DNAs in a single reaction tube. In this study, we describe stepwise experiments to validate the multiplex HPV PCR assay for determination of HPV genotypes from 104 cervical brush samples from Tanzanian women. Assay performance was evaluated by determination of intra‐laboratory reproducibility, sensitivity, and specificity. Further performance was assessed by …