Digital Commons Network^™

High-Intensity Focused Ultrasound: Past, Present, And Future In Neurosurgery, Syed A. Quadri,, Muhammad Waqas, Inamullah Khan, Muhammad Adnan Khan, Sajid S. Suriya, Mudassir Farooqui, Brian Fiani

Section of Neurosurgery

Since Lynn and colleagues first described the use of focused ultrasound (FUS) waves for intracranial ablation in 1942, many strides have been made toward the treatment of several brain pathologies using this novel technology. In the modern era of minimal invasiveness, high-intensity focused ultrasound (HIFU) promises therapeutic utility for multiple neurosurgical applications, including treatment of tumors, stroke, epilepsy, and functional disorders. Although the use of HIFU as a potential therapeutic modality in the brain has been under study for several decades, relatively few neuroscientists, neurologists, or even neurosurgeons are familiar with it. In this extensive review, the authors intend to …

Self-Reported Academic Performance In Relation To Health Behaviours Among Bahria University Students, Rehana Rehman, Amara Zafar, Aleena Mohib, Mehwish Hussain, Rabiya Ali

Department of Biological & Biomedical Sciences

Objective: To find an association between self-reported academic performance with different socio-demographic factors, health behaviours and mental health amongst university students.
Methods: This cross-sectional study was conducted at Bahria University, Karachi, from January 2012 to December 2013, and comprised university students of different disciplines. An anonymous, self-reported questionnaire was distributed among the subjects. Convenient sampling technique was used. Demographic information, including age, gender and field of study, were obtained. Depresion was evaluated via Centre for Epidemiological Studies Depression Scale. SPSS 22 was used to analyse data.
Results: Of the 813 respondents, 334(41.1%) were males and 479(58.9%) females. The mean age …

Lack Of Association Of Statin Use With Vitamin D Levels In A Hospital Based Population Of Type 2 Diabetes Mellitus Patients, Khalida Iqbal, Najmul Islam, Iqbal Azam Syed, Naseema Mehboobali, Mohammad Perwaiz Iqbal

Department of Biological & Biomedical Sciences

Objective: To investigate the relationship of statins (drug given to reduce serum levels of LDL-cholesterol) on vitamin D levels of Pakistani type 2 diabetes mellitus (DM) patients in a hospital in Karachi.
Methods: In a cross-sectional survey, 312 consecutive patients with type 2 DM (219 males and 93 females, age 22-70 years) were recruited with informed consent. A questionnaire was administered to find out whether they were statin users or non-users. Serum was analyzed for concentrations of 25(OH) vitamin D [25(OH)D] and other related biomarkers such as serum cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, phosphate and calcium using kit methods. Multiple Linear …

Novel Combination Bmp7 And Hgf Gene Therapy Instigates Selective Myofibroblast Apoptosis And Reduces Corneal Haze In Vivo, Suneel Gupta, Michael K. Fink, Arkasubhra Ghosh, Ratnakar Tripathi, Prashant R. Sinha, Ajay Sharma, Nathan P. Hesemann, Shyam S. Chaurasia, Elizabeth A. Giuliano, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

PURPOSE. We tested the potential of bone morphogenic protein 7 (BMP7) and hepatocyte growth factor (HGF) combination gene therapy to treat preformed corneal fibrosis using established rabbit in vivo and human in vitro models.

METHODS. Eighteen New Zealand White rabbits were used. Corneal fibrosis was produced by alkali injury. Twenty-four hours after scar formation, cornea received topically either balanced salt solution (BSS; n ¼ 6), polyethylenimine-conjugated gold nanoparticle (PEI2-GNP)-naked plasmid (n ¼ 6) or PEI2-GNP plasmids expressing BMP7 and HGF genes (n ¼ 6). Donor human corneas were used to obtain primary human corneal fibroblasts and myofibroblasts for mechanistic studies. …

Treated Hypothyroidism Is Associated With Cerebrovascular Disease But Not Alzheimer's Disease Pathology In Older Adults, Willa D. Brenowitz, Fang Han, Walter A. Kukull, Peter T. Nelson

Pathology and Laboratory Medicine Faculty Publications

Thyroid hormone (TH) disease is common among older adults and is associated with cognitive impairment. However, pathologic correlates are not well understood. We studied pathologic and clinical factors associated with hypothyroidism, the most common form of TH disease, in research subjects seen annually for clinical evaluations at U.S. Alzheimer’s Disease Centers. Thyroid disease and treatment status were assessed during clinician interviews. Among autopsied subjects, there were 555 participants with treated hypothyroidism and 2,146 with no known thyroid disease; hypothyroidism was associated with severe atherosclerosis (OR=1.35 95% CI: 1.02, 1.79) but not Alzheimer’s disease (AD) pathologies (amyloid plaques or neurofibrillary tangles). …

Association Between Environmental Tobacco Smoke And Dental Caries Amongst 5-14 Years Old Children In Karachi, Pakistan., Anna Ali Nayani, Romaina Iqbal, Syed Iqbal Azam, Farhan Raza Khan, Aysha Habib Khan, Naveed Janjua, Azmina Hussain

Community Health Sciences

Objective:To determine the association between environmental tobacco smoke and dental caries.
Methods:This cross-sectional study was conducted in peri-urban and urban areas of Karachi, from February to August 2014, and comprised children aged 5-14 years. A pre-coded questionnaire for environmental tobacco smoke and food frequency questionnaire for dietary habits were used. Dental examination of children was done to detect caries. Cox-proportional hazard algorithm was used to measure the association of environmental tobacco smoke with dental caries at multivariable level. STATA version 12.0 was used for statistical analysis.
Result:Of the 500 children, 250(50%) each were from peri-urban and urban …

Parp Pet Imaging Agents, Brandon Carney

Dissertations, Theses, and Capstone Projects

The poly (adenosine-diphosphate (ADP) ribose) polymerase (PARP) family of enzymes has been of interest to researchers and clinicians for over fifty years, especially the first member of the family, PARP1. This enzyme has become a target for cancer therapeutics due the reliance of highly proliferating cells on PARP1 for genomic maintenance. In the coming age of individualized medicine, however, highly specific therapeutic agents like PARP inhibitors are in need of similarly highly specific companion diagnostic agents. These kind of agents have been made possible with the quickly progressing field of molecular imaging. Specifically, positron emission tomography (PET) has enabled the …

Microrna 1207-3p In Prostate Cancer, Dibash Das

Dissertations, Theses, and Capstone Projects

Prostate cancer (PCa) is the most commonly diagnosed male cancer and the second leading cause of cancer-related death for men in the United States. Understanding the molecular mechanisms involved in progression from the asymptomatic androgen-dependent PCa to the lethal castration resistant prostate cancer (CRPC) is a major challenge. MicroRNAs (miRNAs), are known to be dysregulated in PCa. MicroRNA-1207-3p (miR-1207-3p) is encoded by the non-protein coding gene locus PVT1 on the 8q24 human chromosomal region, an established PCa susceptibility locus. However, the role of miR-1207-3p in PCa is unclear. We have discovered that miR-1207-3p is significantly underexpressed in PCa cell lines …

Genomic And Cellular Studies Establish The Pathogenesis And Cellular Mechanisms Of Disease-Causing Mutations In Families With Autosomal Recessive Disorders, Nesreen Khalid Ahmad Al Jezawi

Dissertations

The majority of the reported genetic disorders in the UAE population are of the autosomal recessive type, which is mainly due to high rates of consanguinity within the UAE national population, and within a significant proportion of other UAE expatriate communities; such as Arabs and Pakistanis. It is estimated that more than 50% of all marriages among Emiratis occur between biologically related couples, with first cousin marriages being the highest. That could be attributed to sociocultural values in the region. Successful management of genetic diseases can be achieved by the implementation of effective preventative programs that could help reduce the …

Pregnancy Outcomes Among Women With An Unintended Pregnancy: Findings From A Prospective Registry In Rural Pakistan, Sumera Aziz Ali, Shiyam Sunder Tikmani, Margo S. Harrison, Sarah Saleem, Robert L. Goldenberg, Elizabeth M. Mcclure, Omrana Pasha

Community Health Sciences

Background: Unintended pregnancies are an important public health issue in both developed and developing countries. An unintended pregnancy may affect maternal health seeking behavior during the antenatal and postpartum periods, which can adversely affect perinatal outcomes. Aim: The specific aim of our study was to measure antepartum, intrapartum, and postpartum pregnancy outcomes among women with unintended pregnancies in a rural Pakistani population.
Methods: Using a prospective maternal and newborn health registry in Thatta Pakistan, we evaluated temporal associations between unintended pregnancy and several dimensions of health seeking behavior including: antenatal care, preference for private versus government facility for antenatal care, …

Incidence Of Dementia In Elderly Latin Americans: Results Of The Maracaibo Aging Study, Gladys E. Maestre, Luis J. Mena, Jesus D. Melgarejo, Daniel C. Aguirre-Acevedo, Gloria Pino-Ramírez, Milady Urribarrí, Inara J. Chacon, Carlos A. Chavez, Luis Falque-Madrid, Ciro A. Gaona

School of Medicine Publications

Introduction—There are few longitudinal studies of dementia in developing countries. We used longitudinal data from the Maracaibo Aging Study (MAS) to accurately determine the age- and sex-specific incidence of dementia in elderly Latin Americans.

Methods—The DSM IV-R was used to diagnose dementia, which was classified as Alzheimer’s disease (AD), vascular dementia (VaD), or other. Age- and sex-specific incidence was estimated as the number of new cases of dementia divided by person-years of follow-up (p-y).

Results—The incidence of all dementia diagnoses was 9.10 per 1000 p-y (95% CI 7.13–11.44; 8026 total p-y), 5.18 for AD (95% CI 3.72–7.03; …

Impact Of Direct Acting Antivirals On Occurrence And Recurrence Of Hepatocellular Carcinoma: Biologically Plausible Or An Epiphenomenon?, Amna Subhan Butt, Fatima Sharif, Shahab Abid

Section of Gastroenterology

Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality worldwide. Chronic hepatitis C virus infection (HCV) is the most common cause of HCC in many European countries, Japan and Pakistan. Introduction of the new direct acting antivirals (DAAs) has revolutionized the management of HCV worldwide, with high rates of sustained virologic response in patients who could not have tolerated the previous interferon based treatments. However, recently there have been reports raising caution about the long term effects of DAAs, particularly a possible increased risk of HCC. Therefore this review explores the current molecular studies as well as clinical …

Frequency Of Macroprolactin In Hyperprolactinemia, Aysha Habib Khan, Noreen Abbas Sherazi, Mirza Zain Baig

Department of Pathology and Laboratory Medicine

Objective: To determine the frequency of Macroprolactin (MaPRL) in patients with increased total prolactin and its clinical and financial impact.
Study Design: Cross-sectional study.
Place and Duration of Study: Section of Clinical Chemistry, Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, from March to May 2015. Methodology: Patients with high total prolactin were screened by polyethylene glycol (PEG) precipitation for determination of MaPRL. Clinical history, imaging work-ups, and cost incurred in further investigations were collected by telephonic interview after verbal consent. Patients were stratified into true hyperprolactinemia and macroprolactinemia after PEG treatment, based on monomeric prolactin …

Comparison Of New Metrics For Assessment Of Risks Of Occupational Noise, Wisam Al-Dayyeni, Jun Qin

Journal of Applied Sciences and Arts

Noise induced hearing loss (NIHL) is one of the most common occupational related health problems worldwide. Exposure to excessive noise is the major avoidable cause of permanent hearing loss. The conventional metrics for noise evaluation cannot accurately assess the exposure risks to high-level complex noise, which commonly occurs in many industrial and military fields. Recently, we have developed two advanced models, an adaptive weighting (F-weighting) and a complex velocity level (CVL) auditory fatigue model, to evaluate the risks of occupational noise. In this study, we compared performances of five noise assessment metrics, including F-weighted sound pressure level (SPL) LFeq, CVL …

Amine Containing Analogs Of Sulindac For Cancer Prevention, Bini Mathew, Judith V. Hobrath, Michele C. Connelly, R. Kiplin Guy, Robert C. Reynolds

Pharmaceutical Sciences Faculty Publications

Background:

Sulindac belongs to the chemically diverse family of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) that effectively prevent adenomatous colorectal polyps and colon cancer, especially in patients with familial adenomatous polyposis. Sulindac sulfide amide (SSA), an amide analog of sulindac sulfide, shows insignificant COX-related activity and toxicity while enhancing anticancer activity in vitro and demonstrating in vivo xenograft activity.

Objective:

Develop structure-activity relationships in the sulindac amine series and identify analogs with promising anticancer activities.

Method:

A series of sulindac amine analogs were designed and synthesized and then further modified in a “libraries from libraries” approach to produce amide, sulfonamide and N,N-disubstituted …

Ependymomas Overexpress Chemoresistance And Dna Repair-Related Proteins., Sherise D Ferguson, Shouhao Zhou, Joanne Xiu, Yuuri Hashimoto, Nader Sanai, Lyndon Kim, Santosh Kesari, John De Groot, David Spetzler, Amy B Heimberger

Articles, Abstracts, and Reports

Background: After surgery and radiation, treatment options for ependymoma are few making recurrence a challenging issue. Specifically, the efficacy of chemotherapy at recurrence is limited. We performed molecular profiling on a cohort of ependymoma cases in order to uncover therapeutic targets and to elucidate the molecular mechanisms contributing to treatment resistance.

Results: This ependymoma cohort showed minimal alterations in gene amplifications and mutations but had high expression rates of DNA synthesis and repair enzymes such as RRM1 (47%), ERCC1 (48%), TOPO1 (62%) and class III β-tublin (TUBB3) (57%), which are also all associated with chemoresistance. This cohort also had high …

Amyloid-Beta Solubility In The Treatment Of Alzheimer's Disease, Michael Paul Murphy

Molecular and Cellular Biochemistry Faculty Publications

No abstract provided.

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 …

Partnerships For Child Health: Capitalising On Links Between The Sustainable Development Goals, Yulia Blomstedt, Zulfiqar Ahmed Bhutta, Johan Dahlstrand, Peter Friberg, Lawrence O. Gostin, Måns Nilsson, Nelson K. Sewankambo, Göran Tomson, Tobias Alfvén

Department of Paediatrics and Child Health

No abstract provided.

Specific Relationship Between The Shape Of The Readiness Potential, Subjective Decision Time, And Waiting Time Predicted By An Accumulator Model With Temporally Autocorrelated Input Noise, Aaron Schurger

Psychology Faculty Articles and Research

Self-initiated movements are reliably preceded by a gradual buildup of neuronal activity known as the readiness potential (RP). Recent evidence suggests that the RP may reflect subthreshold stochastic fluctuations in neural activity that can be modeled as a process of accumulation to bound. One element of accumulator models that has been largely overlooked in the literature is the stochastic term, which is traditionally modeled as Gaussian white noise. While there may be practical reasons for this choice, we have long known that noise in neural systems is not white – it is long-term correlated with spectral density of the form …

Management Of Aortic Insufficiency In Patients With Left Ventricular Assist Device ̶ A Retrospective Analysis, Hartmuth B. Bittner

The VAD Journal

Background: Aortic insufficiency is increasingly recognized as a complication of left ventricular assist device (LVAD) support and may lead to clinical decompensation requiring correction. This article describes experiences in managing patients presenting with concomitant aortic insufficiency and with de novo aortic insufficiency following left ventricular assist device implantations.

Methods: All patients undergoing LVAD implantation between 2012 and 2014 were included in this retrospective analysis if aortic valve insufficiency was present on implantation or newly developed (de novo) after implantation. Moderate to severe aortic valve insufficiency was corrected at implantation.

Results: The data of 39 patients were included. At the time …

Mammographic Breast Density And Breast Cancer Molecular Subtypes: The Kenyan-African Aspect, Asim Jamal, Maeve Mullooly, Shahin Sayed, Rose Ndumia, Innocent Abayo, James Orwa, Ronald Wasike, Zahir Moloo, Gretchen L. Gierach

Internal Medicine, East Africa

Introduction: Data examiningmammographic breast density (MBD) among patients in Sub-Saharan Africa are sparse.We evaluated how MBD relates to breast cancer characteristics in Kenyan women undergoing diagnostic mammography.

Methods: This crosssectional study included women with pathologically confirmed breast cancers (𝑛 = 123). Pretreatment mammograms of the unaffectedbreast were assessed to estimate absolute dense area (cm2), nondense area (cm2), and percent density (PD). Relationships between density measurements and clinical characteristics were evaluated using analysis of covariance.

Results: Median PD and dense area were 24.9% and 85.3 cm2. Higher PD and dense area were observed in younger women (𝑃 < 0.01). Higher dense and nondense areas were observed in obese women (𝑃-trend < 0.01). Estrogen receptor (ER) positive patients (73%) had higher PD and dense area than ER-negative patients (𝑃 ≤ 0.02). Triple negative breast cancer (TNBC) patients (17%) had lower PD and dense area (𝑃 ≤ 0.01) compared with non-TNBCs. No associations were observed between MBD and tumor size and grade.

Conclusions: Our findings show …

Emotion Regulation And Positive Affect In The Context Of Salivary Alpha-Amylase Response To Pain In Children With Cancer, Brooke N. Jenkins, Douglas A. Granger, Ryan J. Roemer, Ariana Martinez, Tara K. Torres, Michelle A. Fortier

Psychology Faculty Articles and Research

Background

Children with cancer routinely undergo painful medical procedures invoking strong physiological stress responses. Resilience to this pain may be conferred through resources such as emotion regulation strategies and positive affect.

Procedure

This study measured dispositional positive affect in children with cancer (N = 73) and randomly assigned participants to one of three emotion regulation strategy conditions (distraction, reappraisal, or reassurance). Children applied their assigned strategy during an experimental pain procedure (the cold pressor task [CPT]) and provided saliva samples before, immediately after, and 15 min after the CPT. Saliva samples were later assayed for salivary alpha amylase (sAA)—a surrogate …

Resting Hormone Alterations And Injuries: Block Vs. Dup Weight-Training Among D-1 Track And Field Athletes, Keith B. Painter, G. Gregory Haff, N. Travis Triplett, Charles Stuart, Guy Hornsby, Mike W. Ramsey, Caleb D. Bazyler, Michael H. Stone

ETSU Faculty Works

Daily undulating periodization (DUP), using daily alterations in repetitions, has been advocated as a superior method of resistance training, while traditional forms of programming for periodization (Block) have been questioned. Nineteen Division I track and field athletes were assigned to either a 10-week Block or DUP training group. Year and event were controlled. Over the course of the study, there were four testing sessions, which were used to evaluate a variety of strength characteristics, including maximum isometric strength, rate of force development, and one repetition maximum (1RM). Although, performance trends favored the Block group for strength and rate of force …

Beta-Catenin Cleavage Enhances Transcriptional Activation, Tatiana Goretsky, Emily M. Bradford, Qing Ye, Olivia F. Lamping, Tomas Vanagunas, Mary Pat Moyer, Patrick C. Keller, Preetika Sinh, Josep M. Llovet, Tianyan Gao, Qing-Bai She, Linheng Li, Terrence A. Barrett

Internal Medicine Faculty Publications

Nuclear activation of Wnt/β-catenin signaling is required for cell proliferation in inflammation and cancer. Studies from our group indicate that β-catenin activation in colitis and colorectal cancer (CRC) correlates with increased nuclear levels of β-catenin phosphorylated at serine 552 (pβ-Cat⁵⁵²). Biochemical analysis of nuclear extracts from cancer biopsies revealed the existence of low molecular weight (LMW) pβ-Cat⁵⁵², increased to the exclusion of full size (FS) forms of β-catenin. LMW β-catenin lacks both termini, leaving residues in the armadillo repeat intact. Further experiments showed that TCF4 predominantly binds LMW pβ-Cat⁵⁵² in the nucleus of inflamed and …

Inhibition Of Dihydrotestosterone Synthesis In Prostate Cancer By Combined Frontdoor And Backdoor Pathway Blockade, Michael V. Fiandalo, John J. Stocking, Elena A. Pop, John H. Wilton, Krystin M. Mantione, Yun Li, Kristopher M. Attwood, Gissou Azabdaftari, Yue Wu, David S. Watt, Elizabeth M. Wilson, James L. Mohler

Center for Pharmaceutical Research and Innovation Faculty Publications

Androgen deprivation therapy (ADT) is palliative and prostate cancer (CaP) recurs as lethal castration-recurrent/resistant CaP (CRPC). One mechanism that provides CaP resistance to ADT is primary backdoor androgen metabolism, which uses up to four 3α-oxidoreductases to convert 5α-androstane-3α,17β-diol (DIOL) to dihydrotestosterone (DHT). The goal was to determine whether inhibition of 3α-oxidoreductase activity decreased conversion of DIOL to DHT. Protein sequence analysis showed that the four 3α-oxidoreductases have identical catalytic amino acid residues. Mass spectrometry data showed combined treatment using catalytically inactive 3α-oxidoreductase mutants and the 5α-reductase inhibitor, dutasteride, decreased DHT levels in CaP cells better than dutasteride alone. Combined blockade …

Childhood Interpersonal Violence And Adult Alcohol, Cannabis, And Tobacco Use Disorders: Variation By Race/Ethnicity?, Jacquelyn Meyers, Carolyn Sartor, Kimberly Werner, Karestan Koenen, Bridget Grant, Deborah Hasin

Nursing Faculty Works

No abstract provided.

Surgical Interventions For Advanced Parameningeal Rhabdomyosarcoma Of Children And Adolescents., Paul J Choi, Joe Iwanaga, R Shane Tubbs, Emre Yilmaz

Articles, Abstracts, and Reports

Owing to its rarity, rhabdomyosarcoma of the head and neck (HNRMS) has seldom been discussed in the literature. As most of the data is based only on the retrospective experiences of tertiary healthcare centers, there are difficulties in formulating a standard treatment protocol. Moreover, the disease is poorly understood at its pathological, genetic, and molecular levels. For instance, 20% of all histological assessment is inaccurate; even an experienced pathologist can confuse rhabdomyosarcoma (RMS) with neuroblastoma, Ewing's sarcoma, and lymphoma. RMS can occur sporadically or in association with genetic syndromes associated with predisposition to other cancers such as Li-Fraumeni syndrome and …

A Plasma Telomeric Cell-Free Dna Level In Unaffected Women With Brca1 Or/And Brca2 Mutations: A Pilot Study, Shatovisha Dey, Natascia Marino, Kanokwan Bishop, Paige N. Dahlgren, Aditi Shendre, Anna Maria Storniolo, Chunyan He, Hiromi Tanaka

Internal Medicine Faculty Publications

Plasma cell-free DNA (cfDNA) is a small DNA fragment circulating in the bloodstream originating from both non-tumor- and tumor-derived cells. A previous study showed that a plasma telomeric cfDNA level decreases in sporadic breast cancer patients compared to controls. Tumor suppressor gene products including BRCA1 and BRCA2 (BRCA1&2) play an important role in telomere maintenance. In this study, we hypothesized that the plasma telomeric cfDNA level is associated with the mutation status of BRCA1&2 genes. To test this hypothesis, we performed plasma telomeric cfDNA quantitative PCR (qPCR)-based assays to compare 28 women carriers of the BRCA1&2 mutation with age-matched controls …

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 …