Organisms Commons^™

Nanosecond Pulsed Electric Fields Increase Antibiotic Susceptibility In Methicillin-Resistant Staphylococcus Aureus, Alexandra E. Chittams-Miles, Areej Malik, Erin B. Purcell, Claudia Muratori

Bioelectrics Publications

Staphylococcus aureus is the leading cause of skin and soft-tissue infections (SSTIs). SSTIs caused by bacteria resistant to antimicrobials, such as methicillin-resistant S. aureus (MRSA), are increasing in incidence and have led to higher rates of hospitalization. In this study, we measured MRSA inactivation by nanosecond pulsed electric fields (nsPEF), a promising new cell ablation technology. Our results show that treatment with 120 pulses of 600 ns duration (28 kV/cm, 1 Hz), caused modest inactivation, indicating cellular damage. We anticipated that the perturbation created by nsPEF could increase antibiotic efficacy if nsPEF were applied as a co-treatment. To test this …

Additive Effects Of Cyclic Peptide [R4w4] When Added Alongside Azithromycin And Rifampicin Against Mycobacterium Avium Infection, Melissa Kelley, Kayvan Sasaninia, Arbi Abnousian, Ali Badaoui, James Owens, Abrianna Beever, Nala Kachour, Rakesh Kumar Tiwari, Vishwanath Venketaraman

Pharmacy Faculty Articles and Research

Mycobacterium avium (M. avium), a type of nontuberculous mycobacteria (NTM), poses a risk for pulmonary infections and disseminated infections in immunocompromised individuals. Conventional treatment consists of a 12-month regimen of the first-line antibiotics rifampicin and azithromycin. However, the treatment duration and low antibiotic tolerability present challenges in the treatment of M. avium infection. Furthermore, the emergence of multidrug-resistant mycobacterium strains prompts a need for novel treatments against M. avium infection. This study aims to test the efficacy of a novel antimicrobial peptide, cyclic [R4W4], alongside the first-line antibiotics azithromycin and rifampicin in reducing M. avium survival. Colony-forming unit (CFU) …

Outpatient Sexually Transmitted Infection Testing And Treatment Patterns In The United States: A Real-World Database Study, Rebecca Lillis, Louis Kuritzky, Zune Huynh, Rodney Arcenas, Avneet Hansra, Roma Shah, Baiyu Yang, Stephanie N. Taylor

School of Medicine Faculty Publications

Background: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the most common notifiable sexually transmitted infections (STIs) in the United States. Because symptoms of these infections often overlap with other urogenital infections, misdiagnosis and incorrect treatment can occur unless appropriate STI diagnostic testing is performed in clinical settings. The objective of this study was to describe STI diagnostic testing and antimicrobial treatment patterns and trends among adolescent and adult men and women with lower genitourinary tract symptoms (LGUTS). Methods: We analyzed insurance claims data from the IBM® MarketScan® Research Databases. Patients included were between 14 and 64 years old with …

Time Is Ticking For Cervical Cancer, Vijay Kumar, Caitlin Bauer, John H. Stewart

School of Medicine Faculty Publications

Cervical cancer (CC) is a major health problem among reproductive-age females and comprises a leading cause of cancer-related deaths. Human papillomavirus (HPV) is the major risk factor associated with CC incidence. However, lifestyle is also a critical factor in CC pathogenesis. Despite HPV vaccination introduction, the incidence of CC is increasing worldwide. Therefore, it becomes critical to understand the CC tumor immune microenvironment (TIME) to develop immune cell-based vaccination and immunotherapeutic approaches. The current article discusses the immune environment in the normal cervix of adult females and its role in HPV infection. The subsequent sections discuss the alteration of different …

Mirnas Signature As Potential Biomarkers For Cervical Precancerous Lesions In Human Papillomavirus Positive Women, Martha I. González-Ramírez, Yurley T. Cardona, María C. Agudelo, Carolina López, Juan J. Florez-Acosta, Samuel Agudelo-Gamboa, Jone Garai, Li Li, Carlos A. Orozco-Castaño, Jovanny Zabaleta, Gloria I. Sánchez

School of Medicine Faculty Publications

Biomarkers to identify women at risk of cervical cancer among those with high-risk HPV infection (hrHPV+) are needed. Deregulated expression of microRNAs (miRNAs) contributes to hrHPV-induced cervical carcinogenesis. We aimed at identifying miRNAs with the capacity to distinguish high (CIN2+) and low (≤ CIN1) grade cervical lesions. We sequenced miRNA libraries from Formalin-Fixed Paraffin-Embedded (FFPE) tissues from women with CIN2+ (n = 10) and age-matched women with ≤ CIN1 (n = 10), randomly and retrospectively selected from a trial that followed women for 24 months after a hrHPV+ test at the screening visit. Five miRNAs differentially expressed were validated by …

Elucidating The Impact Of Sos-Response Timing In On Escherichia Coli Survival Following Treatment With Fluoroquinolone Topoisomerase Inhibitors, Stephanie Schofield

Honors Scholar Theses

Antibiotic treatment failure is a public health crisis, with a 2019 report stating that roughly 35,000 deaths occur in the United States yearly due to bacterial infections that are unresponsive to antibiotics (1). One complication in the treatment of bacterial infection is antibiotic persistence which further compromises our battle to effectively treat infection. Bacterial persisters can exist in clonal bacterial cultures and can tolerate antibiotic treatment by undergoing reversible phenotypic changes. They can survive drug concentrations that their genetically identical kin cannot. Some persisters remain in a slow growing state and are difficult to target with current antibiotics. A specific …

Echinomycin As A Promising Therapeutic Agent Against Kshv-Related Malignancies, Jungang Chen, Zhen Lin, Jiao Song, Karlie Plaisance-Bonstaff, Jennifer James, Shengyu Mu, Steven R. Post, Lu Dai, Zhiqiang Qin

School of Medicine Faculty Publications

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent of several human cancers, including Kaposi’s sarcoma (KS) and primary effusion lymphoma (PEL), which preferentially arise in immunocompromised patients while lack of effective therapeutic options. Oncoproteins Myc and hypoxia-inducible factor-1α (HIF1α) have been found closely related to KSHV infection, replication and oncogenesis. However, the strategies of dual targeting these two oncoproteins have never been developed and tested for treatments of KSHV-related malignancies. In the current study, we report that treatment of echinomycin dramatically regresses cell growth both in vitro-cultured KSHV + tumor cells and in vivo KS or PEL xenograft mice models, …

Independent Effects Of Hiv And Antiretroviral Therapy On The Oral Microbiome Identified By Multivariate Analyses, Clifford J. Beall, Elizabeth A. Lilly, Carolina Granada, Kelly Treas, Kenneth R. Dubois, Shahr B. Hashmi, Jose A. Vazquez, Michael E. Hagensee, Ann L. Griffen, Eugene J. Leys, Paul L. Fidel

School of Dentistry Faculty Publications

The oral microbiome is an important predictor of health and disease. We recently reported significant yet modest effects of HIV under highly active antiretroviral therapy (ART) on the oral microbiome (bacterial and fungal) in a large cohort of HIV-positive (HIV+) and matched HIV-negative (HIV-) individuals. As it was unclear whether ART added to or masked further effects of HIV on the oral microbiome, the present study aimed to analyze the effects of HIV and ART independently, which also included HIV- subjects on preexposure prophylaxis (PrEP) therapy. Cross-sectional analyses of the effect of HIV devoid of ART (HIV+ ART- versus matched …

Topical Anesthetic Gel Interferes With Antibacterial Efficacy Of Povidone-Iodine Both In Vitro And In Vivo, Cecilly Kelleher Bs, Jacob Im Md, Linda Kang Bs, Aleksey Mishulin Md, Sukhvinder Singh Phd, Ashok Kumar Phd

Medical Student Research Symposium

Purpose: To evaluate the effects of viscous lidocaine gel on the antimicrobial efficacy of povidone-iodine (PI) and their order of application in both in vitro and in vivo models.

Methods: In vitro antibacterial effects were tested against Staphylococcus aureus (S. aureus) with disc diffusion methods for application of lidocaine alone, PI alone, PI before lidocaine, and lidocaine before PI. Zones of inhibition were measured after incubation at 37°C overnight. Mouse eyes were colonized with S. aureus for in vivo study to which PI and/or lidocaine were applied in various combinations. Eyes were then rinsed with saline, and …

Longitudinal Ultrasound Imaging And Network Modeling In Rats Reveal Sex-Dependent Suppression Of Liver Regeneration After Resection In Alcoholic Liver Disease, Benjamin K. Barnhart, Toshiki Kan, Ankita Srivastava, Corinne E. Wessner, John Waters, Manju Ambelil, John R. Eisenbrey, Jan B. Hoek, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Liver resection is an important surgical technique in the treatment of cancers and transplantation. We used ultrasound imaging to study the dynamics of liver regeneration following two-thirds partial hepatectomy (PHx) in male and female rats fed via Lieber-deCarli liquid diet protocol of ethanol or isocaloric control or chow for 5–7 weeks. Ethanol-fed male rats did not recover liver volume to the pre-surgery levels over the course of 2 weeks after surgery. By contrast, ethanol-fed female rats as well as controls of both sexes showed normal volume recovery. Contrary to expectations, transient increases in both portal and hepatic artery blood flow …

Endogenous Mirna-Based Innate-Immunity Against Sars-Cov-2 Invasion Of The Brain, Walter J. Lukiw, Aileen I. Pogue

School of Medicine Faculty Publications

The severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, possesses an unusually large positive-sense, single-stranded viral RNA (ssvRNA) genome of about ~29,903 nucleotides (nt). In many respects, this ssvRNA resembles a very large, polycistronic messenger RNA (mRNA) possessing a 5′-methyl cap (m7GpppN), a 3′- and 5′-untranslated region (3′-UTR, 5′-UTR), and a poly-adenylated (poly-A+) tail. As such, the SARS-CoV-2 ssvRNA is susceptible to targeting by small non-coding RNA (sncRNA) and/or microRNA (miRNA), as well as neutralization and/or inhibition of its infectivity via the human body’s natural complement of about ~2650 miRNA species. Depending on host cell and tissue …

Implementation Of Mrsa Nasal Swabs As An Antimicrobial Stewardship Intervention To Decrease Anti-Mrsa Therapy In Covid-19 Infection, Alaina Dekerlegand, Emily Johnston, Britney Mellor, Melanie Rae Schrack, Catherine O’Neal

School of Medicine Faculty Publications

In the early stages of treating patients with SARS-CoV-2, limited information was available to guide antimicrobial stewardship interventions. The COVID-19 Task Force and Antimicrobial Stewardship Committee, at a 988-bed academic medical center, implemented the use of methicillin-resistant Staphylococcus aureus (MRSA) nasal swab polymerase chain reaction (PCR) testing to assist with the de-escalation of anti-MRSA therapy in patients with suspected superimposed bacterial pneumonia in COVID-19. A retrospective study was conducted to evaluate the impact of MRSA nasal swab PCR testing on the rate of anti-MRSA therapy between 13 April 2020 and 26 July 2020. A total of 122 patients were included …

Characterizing The Cutaneous Microbiome Of Eurycea Lucifuga As A Potential Defense Against Chytridiomycosis, Madeline Key

Senior Honors Theses

Chytridiomycosis is an emerging infectious disease that is significantly reducing global amphibian populations. The disease is caused by Batrachochytrium dendrobatidis (Bd), a fungus that lethally modifies amphibian skin. Recent research has suggested that the cutaneous microbiome of individual amphibians may play a role in susceptibility to the pathogen. In this study, twelve cave salamanders (Eurycea lucifuga) were collected. Cutaneous bacteria from each salamander were isolated and identified using Sanger Sequencing. Additionally, a Bd-challenge assay was performed to determine each isolate’s antifungal activity. Results indicated many microbial isolates possessed inhibitory capabilities against Bd, which may …

Impact Of Alcohol On Bone Health In People Living With Hiv: Integrating Clinical Data From Serum Bone Markers With Morphometric Analysis In A Non-Human Primate Model, Alexandra Denys, Allison Norman, Daniel S. Perrien, Larry J. Suva, Liz Simon, Lee S. Mcdaniel, Tekeda Ferguson, Kim Pedersen, David Welsh, Patricia E. Molina, Martin J.J. Ronis

School of Medicine Faculty Publications

People living with HIV (PLWH) represent a vulnerable population to adverse musculoskeletal outcomes due to HIV infection, antiretroviral therapy (ART), and at-risk alcohol use. Developing measures to prevent skeletal degeneration in this group requires a grasp of the relationship between alcohol use and low bone mass in both the PLWH population and its constituents as defined by sex, age, and race. We examined the association of alcohol use with serum biochemical markers of bone health in a diverse cohort of PLWH enrolled in the New Orleans Alcohol Use in HIV (NOAH) study. To explore the effects of alcohol on bone …

Emergence Of A Multidrug-Resistant And Virulent Streptococcus Pneumoniae Lineage Mediates Serotype Replacement After Pcv13: An International Whole-Genome Sequencing Study, Stephanie W. Lo, Kate Mellor, Robert Cohen, Alba Redin Alonso, Sophie Belman, Narender Kumar, Paulina A. Hawkins, Rebecca A. Gladstone, Sadia Shakoor, Muhammad Imran Nisar

Department of Pathology and Laboratory Medicine

Background: Serotype 24F is one of the emerging pneumococcal serotypes after the introduction of pneumococcal conjugate vaccine (PCV). We aimed to identify lineages driving the increase of serotype 24F in France and place these findings into a global context.
Methods: Whole-genome sequencing was performed on a collection of serotype 24F pneumococci from asymptomatic colonisation (n=229) and invasive disease (n=190) isolates among individuals younger than 18 years in France, from 2003 to 2018. To provide a global context, we included an additional collection of 24F isolates in the Global Pneumococcal Sequencing (GPS) project database for analysis. A Global Pneumococcal Sequence Cluster …

The Impact Of The Covid-19 Pandemic On The Career Choice Of Medicine: A Cross-Sectional Study Amongst Pre-Medical Students In Pakistan, Raisa Saleh, Russell Seth Martins, Muhammad Saad, Asad Saulat Fatimi, Manzar Abbas, Inaara Akbar, Hamzah Jehanzeb, Shamila Ladak, Shamama Kaleem, Sarah Nadeem

Medical College Documents

Background: The COVID-19 pandemic has significantly affected the lives of healthcare workers due to the frontline nature of their work. Their hard work and sacrifice have forged new perceptions of healthcare workers. These changes may potentially influence students' interest in medicine. This study explores how the COVID-19 pandemic has affected premedical students' decisions to pursue medicine as a career.
Methods: A cross-sectional study using a self-designed online questionnaire was carried out amongst pre-medical students across Pakistan.
Results: A total of 1695 students from 93 public and private schools filled in the survey. After the onset of the COVID-19 pandemic, significantly …

Microplastics In Freshly Fallen Snow: How May It Adversely Impact Human Health And Exacerbate The Covid-19 Crisis?, Ayesha Liaquat, Aleena Kashif, Sushma Rathi, Alishba Raza

Medical College Documents

No abstract provided.

Impact Of Biosecurity Measures, Social Pressure And Bullying On Attitudes, Perceptions, And Job Satisfaction Levels Among Healthcare Workers During The Covid-19 Pandemic: A Cross-Sectional Survey, Azza Sarfraz, Zouina Sarfraz, Genesis Camacho-Leon, Geovanny Efraín Alvarado-Villa, Derly Madeleiny Andrade-Molina, Juan Carlos Fernandez-Cadena, Arjola Agolli, Zeynep Yukselen, Miguel Felix, Juan Carlos Gallardo Bastidas

Department of Paediatrics and Child Health

Introduction: The extent and nature of social pressure and bullying towards healthcare workers (HCWs) during the COVID-19 remains unclear. The following study identifies the effect of social pressure and bullying directed towards HCWs when using biosecurity measures during the COVID-19 pandemic; further, the impact on perceptions, attitudes and job satisfaction level is also explored.
Methodology: We conducted a cross-sectional survey-based study among 684 Ecuadorian HCWs. The survey consisted of 38 questions related to the frequency, attitudes, and perceptions of biosecurity measures during the COVID-19 pandemic. Exploratory factor analysis was performed to assess the validity of the questionnaire. Associations between variables …

Incidence Of Typhoid And Paratyphoid Fever In Bangladesh, Nepal, And Pakistan: Results Of The Surveillance For Enteric Fever In Asia Project, Mohammad Tahir Yousafzai, Sadia Shakoor, Irum Fatima Dehraj, Junaid Mehmood, Rozina Thobani, Aneeta Hotwani, Najeeb Rehman, Seema Irfan, Abdul Momin Kazi, Mohammed J. Hunzai

Department of Paediatrics and Child Health

Background: Precise enteric fever disease burden data are needed to inform prevention and control measures, including the use of newly available typhoid vaccines. We established the Surveillance for Enteric Fever in Asia Project (SEAP) to inform these strategies.
Methods: From September, 2016, to September, 2019, we conducted prospective clinical surveillance for Salmonella enterica serotype Typhi (S Typhi) and Paratyphi (S Paratyphi) A, B, and C at health facilities in predetermined catchment areas in Dhaka, Bangladesh; Kathmandu and Kavrepalanchok, Nepal; and Karachi, Pakistan. Patients eligible for inclusion were outpatients with 3 or more consecutive days of fever in the last 7 …

Resolving The Repression Pathway Of Virulence Gene Hila In Salmonella, Alexandra King, Lon Chubiz Phd, Brenda Pratte, Lauren Daugherty

Undergraduate Research Symposium

Salmonella is a relatively abundant, virulent species of bacteria that is most known for spreading gastrointestinal diseases through food. These illnesses result in approximately 1.35 million infections, including over 25,000 hospitalizations each year, in the U.S. alone (CDC.gov). As antibiotic resistance becomes an increasingly urgent public health problem, the importance of developing alternative treatment methods is only becoming more crucial. One of the genes responsible for this virulence is known as hilA. HilA is the main transcriptional regulator of Salmonella Pathogenicity Island-1 gene (UniProt). SPI-1 plays an important role in the invasion of Salmonella into epithelial cells. The proteins encoded …

Full- Versus Sub-Regional Quantification Of Amyloid-Beta Load On Mouse Brain Sections, Yuu Ohno, Riley Murphy, Matthew Choi, Weijun Ou, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Extracellular accumulation of amyloid-beta (Aβ) plaques is one of the major pathological hallmarks of Alzheimer's disease (AD), and is the target of the only FDA-approved disease-modifying treatment for AD. Accordingly, the use of transgenic mouse models that overexpress the amyloid precursor protein and thereby accumulate cerebral Aβ plaques are widely used to model human AD in mice. Therefore, immunoassays, including enzyme-linked immunosorbent assay (ELISA) and immunostaining, commonly measure the Aβ load in brain tissues derived from AD transgenic mice. Though the methods for Aβ detection and quantification have been well established and documented, the impact of the size of the …

Author Correction: Short Amylin Receptor Antagonist Peptides Improve Memory Deficits In Alzheimer’S Disease Mouse Model, Rania Soudy, Ryoichi Kimura, Aarti Patel, Wen Fu, Kamaljit Kaur, David Westaway, Jing Yang, Jack Jhamandas

Pharmacy Faculty Articles and Research

Correction to: Scientific Reports https://doi.org/10.1038/s41598-019-47255-9, published online 29 July 2019

The original Article contained an error in Figure 1A where the control trace for both the HEK-AMY3 and HEKWT cells was duplicated...

The original Article has been corrected.

Predominantly Methicillin-Susceptible S. Aureus Bacteria Found In Csp Students’ S. Aureus Strains, Roma Ambo

Research and Scholarship Symposium Posters

Positive Staphylococcus aureus strains from CSP students were tested for methicillin resistance (MRSA) using the Kirby-bauer assay. Kirby-bauer assay technique was used to determine the sensitivity of staphylococcus aureus bacteria against oxacillin. MRSA infection is the result of a bacteria that has built resistance against the antibiotics used to treat staph infections. The results of this experiment concludes that majority of the strains tested are methicillin-susceptible S. aureus (MSSA).

Development Of Evidence-Based Covid-19 Management Guidelines For Local Context: The Methodological Challenges, Sarah Nadeem, Salima Saleem Aamdani, Bushra Ayub, Nashia Ali Rizvi, Fatima Safi Arslan, Russell Seth Martins, Maria Khan, Syed Faisal Mahmood

Section of Diabetes, Endocrinology and Metabolism

Background: The coronavirus disease 2019 (COVID-19) pandemic has presented as a therapeutic challenge for clinicians worldwide due to its rapid spread along with evolving evidence and understanding of the disease. Internationally, recommendations to guide the management of COVID-19 have been created and updated continuously by the WHO and CDC, which have been locally adapted by different countries. Similarly, Pakistan's National Command Operation Center (NCOC), in its national COVID-19 management strategy, generated guidelines for national implementation. Keeping the guidelines updated has proved challenging globally and locally. Here, we present a summary of the process to assess the evidence, including a time-restricted …

Etiology, Clinical Characteristics, And Outcome Of Infective Endocarditis: 10-Year Experience From A Tertiary Care Center In Pakistan, Sara Salim Ali, Imran Ahmed Qureshi, Ahmed Ayaz, Ainan Arshad, Awais Farhad, Bushra Jamil, Muhammad Rizwan Sohail

Medical College Documents

This study was conducted to assess the clinical characteristics, causative agents, complications, and outcomes of infective endocarditis (IE) among patients presenting to our tertiary care center over the last decade. This retrospective cohort study included all adult patients admitted to the Aga Khan University Hospital with the diagnosis of IE over a ten-year period from 2010 to 2020. Outcomes variables included complications during hospitalization, surgical intervention, mortality, and length of stay. We identified a total of 305 cases out of which 176 (58%) were males and 129 (42%) were females. The mean age of the patients was 46.9±18.8 years. 95 …

Covid-19 In Cns And Pns: Basic And Clinical Focus On The Mechanisms Of Infection And New Tools For The Therapeutic Approach, Jorge Matias-Guiu, Jordi A. Matias-Guiu, Carmen Garrido, Genaro Pimienta, Patricio F. Reyes, Abdul Mannan Baig, Ulises Gomez-Pinedo

Department of Biological & Biomedical Sciences

No abstract provided.

Catheter-Associated Urinary Tract Infections: Patient Characteristics, Treatment, And Clinical Outcomes In One South Texas Acute Care Hospital, Kimberly A. Ambrosini, Jose Campo Maldonado

MEDI 9331 Scholarly Activities Clinical Years

Background: Catheter-associated urinary tract infections (CA-UTIs) account for 40 percent of nosocomial infections worldwide. Their elimination is at the forefront of quality improvement in one South Texas acute care hospital.

Methods: Over a period of 6 months, five CA-UTIs occurred in one South Texas acute care hospital. These cases were identified via regular surveillance by Infection Prevention staff and the Laboratory Department of the hospital. This research reviews patient age, sex, length of stay, bacteria contracted, appropriate antibiotic use, patient characteristics, and overall outcomes.

Results: Between the months of July and December 2021, 5 CAUTIs were contracted. Patients …

Arrhythmogenic Hearts In Pkd2 Mutant Mice Are Characterized By Cardiac Fibrosis, Systolic, And Diastolic Dysfunctions, Farideh Amirrad, Rajasekharreddy Pala, Kiumars Shamloo, Brian S. Muntean, Surya M. Nauli

Pharmacy Faculty Articles and Research

Autosomal dominant polycystic kidney disease (PKD) is a hereditary disorder affecting multiple organs, including the heart. PKD has been associated with many cardiac abnormalities including the arrhythmogenic remodeling in clinical evaluations. In our current study, we hypothesized that Pkd2 gene mutation results in structural and functional defects in the myocardium. The structural and functional changes of Pkd2 mutant hearts were analyzed in the myocardial-specific Pkd2 knockout (KO) mouse. We further assessed a potential role of TGF-b₁ signaling in the pathology of Pkd2-KO hearts. Hearts from age-matched 6-month-old MyH6•Pkd2^wt/wt (control or wild-type) and MyH6 …

Micronutrient Supplements Can Promote Disruptive Protozoan And Fungal Communities In The Developing Infant Gut, Ana Popovic, Celine Bourdon, Pauline W. Wang, David S. Guttman, Sajid Bashir Soofi, Zulfiqar Ahmed Bhutta, Robert H J. Bandsma, John Parkinson, Lisa G. Pell

Centre of Excellence in Women and Child Health

Supplementation with micronutrients, including vitamins, iron and zinc, is a key strategy to alleviate child malnutrition. However, association of gastrointestinal disorders with iron has led to ongoing debate over their administration. To better understand their impact on gut microbiota, we analyse the bacterial, protozoal, fungal and helminth communities of stool samples collected from a subset of 80 children at 12 and 24 months of age, previously enrolled into a large cluster randomized controlled trial of micronutrient supplementation in Pakistan (ClinicalTrials.gov identifier NCT00705445). We show that while bacterial diversity is reduced in supplemented children, vitamins and iron (as well as …

The Temperature-Dependent Conformational Ensemble Of Sars-Cov-2 Main Protease (Mpro), Ali Ebrahim, Blake T. Riley, Desigan Kumaran, Babak Andi, Martin R. Fuchs, Sean Mcsweeney, Daniel A. Keedy

Publications and Research

The COVID-19 pandemic, instigated by the SARS-CoV-2 coronavirus, continues to plague the globe. The SARS-CoV-2 main protease, or M^pro, is a promising target for development of novel antiviral therapeutics. Previous X-ray crystal structures of M^pro were obtained at cryogenic temperature or room temperature only. Here we report a series of high-resolution crystal structures of unliganded M^pro across multiple temperatures from cryogenic to physiological, and another at high humidity. We interrogate these datasets with parsimonious multiconformer models, multi-copy ensemble models, and isomorphous difference density maps. Our analysis reveals a temperature-dependent conformational landscape for M^pro, including …