Skin Diseases and Non-Syndromic Hearing Loss Linked to Cx30 Mutations Arise Through Several Distinct Mechanisms

Connexin 30 (Cx30), a member of the large gap junction protein family, plays a role in the homeostasis of the epidermis and inner ear through gap junctional intercellular communication (GJIC). Here, we investigated four autosomal dominant Cx30 gene mutations linked to hearing loss and/or various skin diseases. First, the T5M mutant linked to non-syndromic hearing loss formed functional gap junction channels and hemichannels, similar to wild-type Cx30. The V37E mutant associated with keratitis-ichthyosis-deafness (KID) syndrome was retained in the endoplasmic reticulum (ER) and significantly induced unfolded protein response (UPR)-mediated apoptosis. The loss-of-function G59R mutant linked to Vohwinkel and Bart-Pumphrey syndromes was retained primarily in the Golgi apparatus. Lastly, the Clouston syndrome-linked A88V mutant significantly induced apoptosis, primarily through an UPR-independent mechanism. Collectively, we discovered that four unique Cx30 mutants cause disease through different mechanisms, highlighting the overall complexity of connexin-linked diseases and the importance of GJIC in disease prevention

Views of student engagement among students and faculty in online courses

As part of an effort to learn more about the technologies currently available to students, three executives in the online division of a private, not-for-profit four-year university requested a survey of students and faculty to learn more about the technologies to which they currently have access. Additionally, each of three executives wanted to better understand student and faculty views of student engagement in the division\u27s online courses. To that end, research-based questions about student engagement levels were added to a survey about access to technology. This mixed-method non-experimental study collected data from students and faculty about which definition of student engagement taken from the literature they primarily relate to, as well as their views of current levels of student engagement in online courses offered by the university. Interestingly, student and faculty responses regarding the definition of student engagement to which they related, whether they felt the only courses are engaging based on that definition and the course activities they found most engaging were nearly identical. Given that the responses between the subject groups were so similar, survey bias may be a valid consideration. Recommendations include editing of survey questions, surveying faculty and students in individual courses and more research on the role gender differences may play in student engagement in online learning environments

Ethical Challenges and Solutions Involved in Reviewing a Protocol with Sex Offenders as Participants: The Concerns and Solutions Identified for Protecting a Highly Controversial Population

In reviewing research, the three basic tenets IRBs are expected to abide by are beneficence, justice and respect for persons. The IRB was challenged in meeting these tenets during the course of a recent review. Given the highly controversial participant population of sex offenders and the methodology initially proposed, there were a multitude of ethical challenges uncovered that required unique solutions. The protocol presented to the IRB was developed to investigate the use of networked technologies and communications for the purpose of human trafficking. To do so the researchers proposed recruiting “Johns” or individuals convicted of soliciting sex and interviewing them to discover how they use the internet and networked technologies to find victims online. Ultimately, the research intends to provide technology-based tools for combatting trafficking of minors. So the question for the IRB was how to go about protecting “Johns” while protecting the potential victims and meet the criteria for approval

Creating a Culture of Compliance with Integrity: It Takes More Than Solid Procedures and a Snazzy Submission System

Creating a Culture of Compliance with Integrity: It Takes More Than Solid Policies and a Snazzy Submission System (1) Problem Statement IRB Offices can often have contentious relationships with researchers, and building a culture of compliance with integrity as well as a level of mutual trust and respect, can often be a very overwhelming task. Solid policies and procedures and a user-friendly electronic submission system are now best practices for streamlining IRB operations. However, our ongoing goal is to find novel approaches to outreach and education, subsequently allowing us to build that mutual understanding of purpose and collaboration. (2) Program Description We have implemented multiple modalities. Some of the outreach examples below are novel while others are modified best practices. Creating unique infographics to communicate our policies. Our office uses an infographic software to elevate lackluster emails with copious text into visually pleasing, eye-catching educational material. For example: https://www.montclair.edu/provost/institutional-review-board/cayuse/submission/submissionflow/ Offering your community IRB swag in a cost effective way. Our office creates magnets in-house that have become ubiquitous on filing cabinets. They simply state “I Support Research at University X.” They are extremely popular and several hundred have been distributed at events. Attending students’ research events and making them feel appreciated. We set up a table and create a large poster congratulating students and their faculty mentors for obtaining IRB approval. Many of our student researchers are new researchers and that extra appreciation is well received. Attending all New Faculty Orientations with a smile. This is where you capture the new faculty at a time when they are most willing to learn about how to best go about their research. Many new faculty contact us immediately after the event. Offering workshops (N=19 for FY16) and guest lecturing as often as possible. Post workshop surveys show 92% of participants felt better prepared to submit to the IRB afterwards. When we guest lecture (N=18 for FY16) not only do our students learn about compliance but our faculty can be reminded of existing and new policies. Offering online learning modules that can be integrated into a faculty member’s course. Nearly every discipline at our University offers a Research Methods course. We built recorded lectures, materials, and a quiz that can be imported into our Learning Management System. (3) Future program usage These program activities can be brought into effect at any IRB or HRP. There is no doubt that resources are slim here and elsewhere; however we know these approaches have built rapport and reputation over the last few years

Human Pathogens Abundant in the Bacterial Metagenome of Cigarettes

International audienceBACKGROUND: Many studies have evaluated chemical, heavy metal, and other abiotic substances present in cigarettes and their roles in the development of lung cancer and other diseases, yet no studies have comprehensively evaluated bacterial diversity of cigarettes and the possible impacts of these microbes on respiratory illnesses in smokers and exposed nonsmokers. OBJECTIVES: The goal of this study was to explore the bacterial metagenomes of commercially available cigarettes. METHODS: A 16S rRNA-based taxonomic microarray and cloning and sequencing were used to evaluate total bacterial diversity of four brands of cigarettes. Normalized microarray data were compared using principal component analysis and hierarchical cluster analysis to evaluate potential differences in microbial diversity across cigarette brands. RESULTS: Fifteen different classes of bacteria and a broad range of potentially pathogenic organisms were detected in all cigarette samples. Most notably, we detected Acinetobacter, Bacillus, Burkholderia, Clostridium, Klebsiella, Pseudomonas aeruginosa, and Serratia in >= 90% of all cigarette samples. Other pathogenic bacteria detected included Campylobacter, Enterococcus, Proteus, and Staphylococcus. No significant variability in bacterial diversity was observed across the four different cigarette brands. CONCLUSIONS: Previous studies have shown that smoking is associated with colonization by pathogenic bacteria and an increased risk of lung infections. However, this is the first study to show that cigarettes themselves could be the direct source of exposure to a wide array of potentially pathogenic microbes among smokers and other people exposed to secondhand smoke. The overall public health implications of these findings are unclear at this time, and future studies arc necessary to determine whether bacteria in cigarettes could play important roles in the development of both infectious and chronic respiratory diseases

Racial Justice and Black Lives in Research: Consider these areas of inquiry

Developed by the Black Matter in Research Working Group 2021 -- Researchers, Ethics & IRB Professionals

Multicoil2: predicting coiled coils and their oligomerization States from sequence in the twilight zone

The alpha-helical coiled coil can adopt a variety of topologies, among the most common of which are parallel and antiparallel dimers and trimers. We present Multicoil2, an algorithm that predicts both the location and oligomerization state (two versus three helices) of coiled coils in protein sequences. Multicoil2 combines the pairwise correlations of the previous Multicoil method with the flexibility of Hidden Markov Models (HMMs) in a Markov Random Field (MRF). The resulting algorithm integrates sequence features, including pairwise interactions, through multinomial logistic regression to devise an optimized scoring function for distinguishing dimer, trimer and non-coiled-coil oligomerization states; this scoring function is used to produce Markov Random Field potentials that incorporate pairwise correlations localized in sequence. Multicoil2 significantly improves both coiled-coil detection and dimer versus trimer state prediction over the original Multicoil algorithm retrained on a newly-constructed database of coiled-coil sequences. The new database, comprised of 2,105 sequences containing 124,088 residues, includes reliable structural annotations based on experimental data in the literature. Notably, the enhanced performance of Multicoil2 is evident when tested in stringent leave-family-out cross-validation on the new database, reflecting expected performance on challenging new prediction targets that have minimal sequence similarity to known coiled-coil families. The Multicoil2 program and training database are available for download from http://multicoil2.csail.mit.edu.National Institutes of Health (U.S.) (Grant 1R01GM081871)National Science Foundation (U.S.) (Grant MCB-0347203)National Science Foundation (U.S.) (Grant 0821391

Skin disease and non-syndromic hearing loss-linked Cx30 mutations exhibit several distinct cellular pathologies

Connexin 30 (Cx30), a member of the large gap junction protein family, plays a role in the homeostasis of the epidermis and inner ear through gap junctional intercellular communication (GJIC). Here, we investigated the underlying mechanisms of four autosomal dominant Cx30 gene mutations linked to hearing loss and/or various skin diseases. First, the T5M mutant linked to non-syndromic hearing loss formed functional gap junction channels and hemichannels, similar to wild type Cx30. The loss-of-function V37E mutant associated with Clouston syndrome or keratitis-ichthyosis-deafness syndrome was retained in the endoplasmic reticulum and significantly induced apoptosis. The G59R mutant linked to Vohwinkel and Bart-Pumphrey syndromes was retained primarily in the Golgi apparatus and exhibited loss of gap junction channel and hemichannel function, but did not cause cell death. Lastly, the A88V mutant related to Clouston syndrome also significantly induced apoptosis, although through an endoplasmic reticulum-independent mechanism. Collectively, we discovered that four unique Cx30 mutants may cause disease through different mechanisms that also likely include their selective transdominant effects on co-expressed connexins, highlighting the overall complexity of connexin-linked diseases and the importance of GJIC in disease prevention