Life Sciences Commons^™

Genetic Variants In Immune Related Genes As Predictors Of Responsiveness To Bcg Immunotherapy In Metastatic Melanoma Patients., Romela Irene Ramos, Misa A Shaw, Leland Foshag, Stacey L Stern, Negin Rahimzadeh, David Elashoff, Dave Hoon

Articles, Abstracts, and Reports

Adjuvant immunotherapy in melanoma patients improves clinical outcomes. However, success is unpredictable due to inherited heterogeneity of immune responses. Inherent immune genes associated with single nucleotide polymorphisms (SNPs) may influence anti-tumor immune responses. We assessed the predictive ability of 26 immune-gene SNPs genomic panels for a clinical response to adjuvant BCG (Bacillus Calmette-Guérin) immunotherapy, using melanoma patient cohorts derived from three phase III multicenter clinical trials: AJCC (American Joint Committee on Cancer) stage IV patients given adjuvant BCG (pilot cohort; n = 92), AJCC stage III patients given adjuvant BCG (verification cohort; n = 269), and …

December 23, 2020: Covid-19 Campus Update, Kettering University

Communication Updates

All residential and non-residential students, faculty and staff that will be on campus during Winter Term will be required to be tested on campus through Helix Diagnostics with a negative test result. The University will offer free, scheduled testing through Helix Diagnostics prior to the start of Winter Term at scheduled times during the first week of January.

The new Safe Campus 2021 Guidelines for Winter Term are now online on the University’s website. It includes: Testing & Health Services, Safety Measures, Academics & Co-op, Student Life, Facilities and Visiting Campus.

Beyond Low-Earth Orbit: Characterizing Immune And Microrna Differentials Following Simulated Deep Spaceflight Conditions In Mice, Amber M. Paul, Margareth Cheng-Campbell, Elizabeth A. Blaber, Sulekha Anand, Sharmila Bhattacharya

Publications

Spaceflight missions can cause immune system dysfunction in astronauts with little understanding of immune outcomes in deep space. This study assessed immune responses in mice following ground-based, simulated deep spaceflight conditions, compared with data from astronauts on International Space Station missions. For ground studies, we simulated microgravity using the hindlimb unloaded mouse model alone or in combination with acute simulated galactic cosmic rays or solar particle events irradiation. Immune profiling results revealed unique immune diversity following each experimental condition, suggesting each stressor results in distinct circulating immune responses, with clear consequences for deep spaceflight. Circulating plasma microRNA sequence analysis revealed …

Correction: Moxley, R.A., Et Al. Intimate Attachment Of Escherichia Coli O157:H7 To Urinary Bladder Epithelium In The Gnotobiotic Piglet Model. Microorganisms 2020, 8, 263, Rodney A. Moxley, Tom W. Bargar, Stephen D. Kachman, Diane R. Baker, David Francis

School of Veterinary and Biomedical Sciences: Faculty Publications

The authors wish to make the following corrections to this paper [1]: On page 2, the sentence that reads, “Hence, EHEC is a rare but established cause of HUS in children and adults.” should read, “Hence, EHEC is a rare but established cause of UTI-associated HUS in children and adults.” On page 4, the sentence that reads, “As noted previously, 14 of 126 (13.3%) piglets orally inoculated with EHEC O157:H7 strains developed mild to moderate purulent cystitis within 8 d PI [25] (Table 1).” should read, “As noted previously, 14 of 105 (13.3%) piglets orally inoculated with EHEC O157:H7 strains …

Dysregulated Interferon Response Underlying Severe Covid-19, Leann Lopez, Peter C. Sang, Yun Tian, Yongming Sang

Agricultural and Environmental Sciences Faculty Research

Innate immune interferons (IFNs), including type I and III IFNs, constitute critical antiviral mechanisms. Recent studies reveal that IFN dysregulation is key to determine COVID-19 pathogenesis. Effective IFN stimulation or prophylactic administration of IFNs at the early stage prior to severe COVID-19 may elicit an autonomous antiviral state, restrict the virus infection, and prevent COVID-19 progression. Inborn genetic flaws and autoreactive antibodies that block IFN response have been significantly associated with about 14% of patients with life-threatening COVID-19 pneumonia. In most severe COVID-19 patients without genetic errors in IFN-relevant gene loci, IFN dysregulation is progressively worsened and associated with the …

December 11, 2020: Letter From The President- Covid Update, Kettering University

Communication Updates

No abstract provided.

An Artificial Intelligence-Based, Personalized Smartphone App To Improve Childhood Immunization Coverage And Timelines Among Children In Pakistan: Protocol For A Randomized Controlled Trial, Abdul Momin Kazi, Saad Ahmed Qazi, Sadori Khawaja, Nazia Ahsan, Rao Moueed Ahmed, Muhammad Ayub Khan Mughal, Hussain Kalimuddin, Yasir Rauf, Mehreen Raza, Saima Jamal

Department of Paediatrics and Child Health

Background: The immunization uptake rates in Pakistan are much lower than desired. Major reasons include lack of awareness, parental forgetfulness regarding schedules, and misinformation regarding vaccines. In light of the COVID-19 pandemic and distancing measures, routine childhood immunization (RCI) coverage has been adversely affected, as caregivers avoid tertiary care hospitals or primary health centers. Innovative and cost-effective measures must be taken to understand and deal with the issue of low immunization rates. However, only a few smartphone-based interventions have been carried out in low- and middle-income countries (LMICs) to improve RCI.
Objective: The primary objectives of this study are to …

November 20, 2020: Covid-19 Campus Update, Kettering University

Communication Updates

As we approach the Thanksgiving holiday, we want to encourage everyone to be very cautious so as to safely celebrate with loved ones. Stay safe and informed not just for the well-being of your friends and families, but also for our campus community upon your return. This means all of us continuing to practice social distancing, properly wearing a face mask and washing our hands often.

Immunogenetic Association Underlying Severe Covid-19, Kendall Mccoy, Autumn Peterson, Yun Tian, Yongming Sang

Agricultural and Environmental Sciences Faculty Research

SARS-CoV2 has caused the current pandemic of new coronavirus disease 2019 (COVID-19) worldwide. Clinical outcomes of COVID-19 illness range broadly from asymptotic and mild to a life-threatening situation. This casts uncertainties for defining host determinants underlying the disease severity. Recent genetic analyses based on extensive clinical sample cohorts using genome-wide association studies (GWAS) and high throughput sequencing curation revealed genetic errors and gene loci associated with about 20% of life-threatening COVID-19 cases. Significantly, most of these critical genetic loci are enriched in two immune signaling pathways, i.e., interferon-mediated antiviral signaling and chemokine-mediated/inflammatory signaling. In line with these genetic profiling studies, …

Strategies To Improve Coverage Of Typhoid Conjugate Vaccine (Tcv) Immunization Campaign In Karachi, Pakistan, Farah Qamar Naz, Rabab Batool, Sonia Qureshi, Miqdad Ali, Tahira Sadaf, Junaid Mehmood, Khalid Iqbal, Akram Sultan, Noah Duff, Mohammad Tahir Yousafzai

Department of Paediatrics and Child Health

The emergence and spread of extensively drug-resistant (XDR) typhoid in Karachi, Pakistan led to an outbreak response in Lyari Town, Karachi utilizing a mass immunization campaign with typhoid conjugate vaccine (TCV), Typbar TCV®. The mass immunization campaign, targeted Lyari Town, Karachi, one of the worst affected towns during the XDR typhoid outbreak. Here we describe the strategies used to improve acceptance and coverage of Typbar TCV in Lyari Town, Karachi. The mass immunization campaign with Typbar TCV was started as a school- and hospital-based vaccination campaign targeting children between the age of 6 months to 15 years old. A dose …

Carbapenemase Screening In An Irish Tertiary Referral Hospital: Best Practice, Or Can We Do Better?, Sinéad Fahy, J. A. O'Connor, D. O'Brien, L. Fitzpatrick, M. O'Connor, J. Crowley, M. Bernard, Roy D. Sleator, Brigid Lucey

Department of Biological Sciences Publications

Initially, United States Centre of Disease Control (CDC) recommended culture-based CPE screens; using broth enrichment in tryptone soy broth (TSB), followed by culture onto MacConkey agar with a carbapenem disc. However, this protocol is both time consuming (approx. 48hrs) and labour intensive, making it impractical for routine screening, particularly in a busy hospital laboratory [10]. Some improvements have been observed using commercially available culture plates, particularly in terms of decreased turnaround times (approx. 24hrs) and increased sensitivity/specificity for CPE producers; mSuperCarba (CHROMagar) media, for example has shown an increased sensitivity rate of 83% compared to 69% for MacConkey culture with …

November 16, 2020: Letter From The President- Covid-19 Update, Kettering University

Communication Updates

No abstract provided.

Interleukin-17a Facilitates Chikungunya Virus Infection By Inhibiting Ifn-Α2 Expression, Biswas Neupane, Dhiraj Acharya, Farzana Nazneen, Gabriel Gonzalez-Fernandez, Alex Sutton Flynt, Fengwei Bai

Faculty Publications

Interferons (IFNs) are the key components of innate immunity and are crucial for host defense against viral infections. Here, we report a novel role of interleukin-17A (IL-17A) in inhibiting IFN-α2 expression thus promoting chikungunya virus (CHIKV) infection. CHIKV infected IL-17A deficient (Il17a^−/−) mice expressed a higher level of IFN-α2 and developed diminished viremia and milder footpad swelling in comparison to wild-type (WT) control mice, which was also recapitulated in IL-17A receptor-deficient (Il17ra^−/−) mice. Interestingly, IL-17A selectively blocked IFN-α2 production during CHIKV, but not West Nile virus (WNV) or Zika virus (ZIKV), infections. Recombinant IL-17A …

November 15, 2020: Covid-19 Campus Update, Kettering University

Communication Updates

We are currently evaluating the full extent and impact on our campus community of the announcement by the Michigan Governor on Sunday evening. This announcement includes limitations to be imposed statewide effective this Wednesday.

Actions to be taken by the University to be in compliance with local and state directives will be determined and communicated promptly to the campus community.

Impact Of Porcine Arterivirus, Influenza B, And Their Coinfection On Antiviral Response In The Porcine Lung, Damarius S. Fleming, Laura C. Miller, Yun Tian, Yonghai Li, Wenjun Ma, Yongming Sang

Agricultural and Environmental Sciences Faculty Research

Interferon (IFN) cytokines induce an autonomous antiviral state in cells of the infected site to restrict virus spreading and critically regulate overall antiviral response. The antiviral state leads to host protection through expression of hundreds of IFN-stimulated genes that restrict viral infection through multiple mechanisms, for example, directly in viral genome degradation and indirectly through cellular metabolic inhibition. Young pigs were split into four treatment groups: control, porcine reproductive and respiratory syndrome virus (PRRSV, also known as porcine arterivirus) infected, influenza B virus (IBV) infected, and IBV/PRRSV coinfection. Lung tissue was collected at 3, 5, and 7 days post infection …

November 11, 2020: Letter From The President- Covid-19 Town Hall Meeeting, Kettering University

Communication Updates

All students, faculty and staff are invited to join members of the Kettering University’s COVID-19 Response Team for a virtual Town Hall to discuss COVID-19 and the safety measures put in place on campus.

November 3, 2020: Covid-19 Campus Update, Kettering University

Communication Updates

No abstract provided.

November 2, 2020: Covid-19 Campus Update, Kettering University

Communication Updates

No abstract provided.

Neutrophil-To-Lymphocyte Ratio: A Biomarker To Monitor The Immune Status Of Astronauts, Amber M. Paul, Siddhita D. Mhatre, Egle Cekanaviciute, Ann-Sofie Schreurs, Candice G.T. Tahimic, Ruth K. Globus, Sulekha Anand, Brian E. Crucian, Sharmila Bhattacharya

Publications

A comprehensive understanding of spaceflight factors involved in immune dysfunction and the evaluation of biomarkers to assess in-flight astronaut health are essential goals for NASA. An elevated neutrophil-to-lymphocyte ratio (NLR) is a potential biomarker candidate, as leukocyte differentials are altered during spaceflight. In the reduced gravity environment of space, rodents and astronauts displayed elevated NLR and granulocyte-to-lymphocyte ratios (GLR), respectively. To simulate microgravity using two well-established ground-based models, we cultured human whole blood-leukocytes in high-aspect rotating wall vessels (HARV-RWV) and used hindlimb unloaded (HU) mice. Both HARV-RWV simulation of leukocytes and HU-exposed mice showed elevated NLR profiles comparable to spaceflight …

Varroa Destructor Mites Vector And Transmit Pathogenic Honey Bee Viruses Acquired From An Artificial Diet, Francisco Posada-Florez, Eugene V. Ryabov, Matthew C. Heerman, Yanping Chen, Jay D. Evans, Daniel E. Sonenshine, Steven C. Cook

Biological Sciences Faculty Publications

The ectoparasitic mite Varroa destructoris one of the most destructive pests of the honey bee (Apis mellifera) and the primary biotic cause of colony collapse in many regions of the world. These mites inflict physical injury on their honey bee hosts from feeding on host hemolymph and fat body cells/cellular components, and serve as the vector for deadly honey bee viruses, including Deformed wing virus (DWV) and the related Varroa destructor virus-1 (VDV-1) (i.e., DWV-like viruses). Studies focused on elucidating the dynamics of Varroa-mediated vectoring and transmission of DWV-like viruses may be confounded by viruses present in …

A Statistical Learning Regression Model Utilized To Determine Predictive Factors Of Social Distancing During Covid-19 Pandemic, Timothy A. Smith, Albert J. Boquet, Matthew V. Chin

Publications

In an application of the mathematical theory of statistics, predictive regression modelling can be used to determine if there is a trend to predict the response variable of social distancing in terms of multiple predictor input “predictor” variables. In this study the social distancing is measured as the percentage reduction in average mobility by GPS records, and the mathematical results obtained are interpreted to determine what factors drive that response. This study was done on county level data from the state of Florida during the COVID-19 pandemic, and it is found that the most deterministic predictors are county population density …

Investigating Microbial And Host Factors That Modulate Severity Of Clostridioides Difficile Associated Disease, Armando Lerma

Department of Food Science and Technology: Dissertations, Theses, and Student Research

Clostridioides difficile is recognized as one of the most important pathogens in hospital and community healthcare settings. The clinical outcome of infection of toxigenic C. difficile infection (CDI) ranges from asymptomatic colonization to fulminant pseudomembranous colitis and death. In recent studies, it has been suggested that a high proportion of nosocomial CDI cases are transmitted from asymptomatic carriers which might be acting as infection reservoirs. Understanding what causes the different responses to infection could lead to the development of novel prevention and treatment strategies. Although several explanations have been proposed to explain variations in susceptibility, understanding of the exact mechanisms …

October 29, 2020: Covid-19 Campus Update, Kettering University

Communication Updates

The COVID-19 Response Team continues to work with the Genesee County Public Health Department and with the Of ice of the President to adapt to the situation as it evolves and provide our community with the most current information regarding the COVID-19 pandemic. The University is fully committed to the health and safety of its entire community, and will continue to closely monitor this situation and any others that impact our campus. In addition to providing updates on a regular basis, the team meets regularly to review, evaluate and address immediate and future issues related to the pandemic. Members of …

October 29, 2020: Letter From The President- Covid-19 Update, Kettering University

Communication Updates

No abstract provided.

October 27, 2020: Covid-19 Campus Update, Kettering University

Communication Updates

The COVID-19 Response Team continues to work with the Genesee County Public Health Department and with the Of ice of the President to adapt to the situation as it evolves and provide our community with the most current information regarding the COVID-19 pandemic. The University is fully committed to the health and safety of its entire community, and will continue to closely monitor this situation and any others that impact our campus. In addition to providing updates on a regular basis, the team meets regularly to review, evaluate and address immediate and future issues related to the pandemic. Members of …

October 25, 2020: Covid-19 Campus Update, Kettering University

Communication Updates

The COVID-19 Response Team continues to work with the Genesee County Public Health Department and with the Of ice of the President to adapt to the situation as it evolves and provide our community with the most current information regarding the COVID-19 pandemic. The University is fully committed to the health and safety of its entire community, and will continue to closely monitor this situation and any others that impact our campus. In addition to providing updates on a regular basis, the team meets regularly to review, evaluate and address immediate and future issues related to the pandemic. Members of …

Chain-Selective Isotopic Labeling Of The Heterodimeric Type Iii Secretion Chaperone, Scc4:Scc1, Reveals The Total Structural Rearrangement Of The Chlamydia Trachomatis Bi-Functional Protein, Scc4, Thilini O. Ukwaththage, Samantha M. Keane, Li Shen, Megan A. Macnaughtan

School of Medicine Faculty Publications

Scc4 is an unusual bi-functional protein from Chlamydia trachomatis (CT) that functions as a type III secretion system (T3SS) chaperone and an RNA polymerase (RNAP)-binding protein. Both functions require interactions with protein partners during specific stages of the CT developmental cycle. As a T3SS chaperone, Scc4 binds Scc1 during the late stage of development to form a heterodimer complex, which chaperones the essential virulence effector, CopN. During the early-middle stage of development, Scc4 regulates T3SS gene expression by binding the σ66-containing RNAP holoenzyme. In order to study the structure and association mechanism of the Scc4:Scc1 T3SS chaperone complex using nuclear …

October 23, 2020: Covid-19 Campus Update, Kettering University

Communication Updates

The COVID-19 Response Team continues to work with the Genesee County Public Health Department and with the Of ice of the President to adapt to the situation as it evolves and provide our community with the most current information regarding the COVID-19 pandemic. The University is fully committed to the health and safety of its entire community, and will continue to closely monitor this situation and any others that impact our campus. In addition to providing updates on a regular basis, the team meets regularly to review, evaluate and address immediate and future issues related to the pandemic. Members of …

October 16, 2020: Covid-19 Campus Update, Kettering University

Communication Updates

The COVID-19 Response Team continues to work with the Genesee County Public Health Department and with the Of ice of the President to adapt to the situation as it evolves and to provide our community with the most current information regarding the COVID-19 pandemic. The University is fully committed to the health and safety of its entire community, and will continue to closely monitor this situation and any others that impact our campus.

Field Evaluation Of Recombinant Antigen Elisa In Detecting Zoonotic Schistosome Infection Among Water Buffaloes In Endemic Municipalities In The Philippines, Jose Ma. M. Angeles, Yasuyuki Goto, Masahi Kirinoki, Elena A. Villacorte, Kharleezelle J. Moendeg, Pilarita T. Rivera, Yuichi Chigusa, Shin-Ichiro Kawazu

Biology Faculty Publications

In this study, we investigated the use of recombinant antigens thioredoxin peroxidase-1 (rSjTPx-1) and tandem repeat rSj1TR in evaluating the antibody positivity rates of Schistosoma japonicum infection among water buffaloes from four endemic areas in the Philippines, two municipalities with high endemicity (Calatrava, Negros Occidental and Catarman, Northern Samar) and two municipalities nearing elimination with no cases of human schistosomiasis (Talibon and Trinidad, Bohol). These recombinant antigen ELISA assays were compared with other diagnostic tests including SEA-ELISA, FECT, and fecal-based PCR. Results showed that rSj1TR-ELISA has the highest agreement with PCR in all study areas. Furthermore, significant positivity rates among …