Structures of substrate- and nucleotide-bound propionate kinase from Salmonella typhimurium: substrate specificity and phosphate-transfer mechanism

Kinases are ubiquitous enzymes that are pivotal to many biochemical processes. There are contrasting views on the phosphoryl-transfer mechanism in propionate kinase, an enzyme that reversibly transfers a phosphoryl group from propionyl phosphate to ADP in the final step of non-oxidative catabolism of l-threonine to propionate. Here, X-ray crystal structures of propionate- and nucleotide-bound Salmonella typhimurium propionate kinase are reported at 1.8-2.0 Å resolution. Although the mode of nucleotide binding is comparable to those of other members of the ASKHA superfamily, propionate is bound at a distinct site deeper in the hydrophobic pocket defining the active site. The propionate carboxyl is at a distance of ∼5 Å from the γ-phosphate of the nucleotide, supporting a direct in-line transfer mechanism. The phosphoryl-transfer reaction is likely to occur via an associative SN2-like transition state that involves a pentagonal bipyramidal structure with the axial positions occupied by the nucleophile of the substrate and the O atom between the β- and the γ-phosphates, respectively. The proximity of the strictly conserved His175 and Arg236 to the carboxyl group of the propionate and the γ-phosphate of ATP suggests their involvement in catalysis. Moreover, ligand binding does not induce global domain movement as reported in some other members of the ASKHA superfamily. Instead, residues Arg86, Asp143 and Pro116-Leu117-His118 that define the active-site pocket move towards the substrate and expel water molecules from the active site. The role of Ala88, previously proposed to be the residue determining substrate specificity, was examined by determining the crystal structures of the propionate-bound Ala88 mutants A88V and A88G. Kinetic analysis and structural data are consistent with a significant role of Ala88 in substrate-specificity determination. The active-site pocket-defining residues Arg86, Asp143 and the Pro116-Leu117-His118 segment are also likely to contribute to substrate specificity

Effect of Music Interventions on Sedation in Children Undergoing Magnetic Resonance Imaging: Clinical Trial

Background: Although parenteral sedation is often required in MRI studies in children, it is stressful and increases the cost of healthcare. Objectives: We evaluated the impact of music interventions in children receiving parenteral sedation for MRI studies on total number of doses of sedation medications, sedation time, levels of cortisol and cytokines, sedation success, adverse events, parental satisfaction, and cost savings. Methods: We conducted a prospective open unblinded four-arm clinical evaluation of interventions on 471 children 1-12 years of age undergoing MRI and receiving parenteral sedation. Children were assigned to active music therapy (AMT), facilitated music listening (FML), and as comparison another intervention (child life intervention or CLI), or no intervention (NI); measures included number of doses of sedation medications, time of sedation, sedation success, adverse events, parental satisfaction, and salivary levels of the stress hormone cortisol and pro-inflammatory cytokines, before and after intervention. Results: The total number of sedation doses, total sedation time, and levels of salivary cortisol and cytokines did not differ between the four groups. One FMLA choice, Wee Sing Animal Songs, resulted in significant decrease in total sedation time and reduction of associated costs. Conclusions: The use of one type of FML led to decreased total sedation time in children. This is an important finding since FML is an inexpensive non-invasive intervention which could be of significant time and cost saving benefits

Severe Gingival Enlargement with Coexisting Erosive Lichen Planus in Severe Chronic Periodontitis Patient

Plaque induced gingival enlargement is most commonly seen and when encountered simultaneously with erosive lichen planus poses a challenge to the treating dentist. Prognosis of one condition may influence the prognosis of another condition. The presented case highlights the significance of proper diagnosis and the management of simultaneously occurring gingival lesions. A 49-year-old hypertensive female presented with painful enlarged bleeding and suppurating gums with burning sensation on eating food along with long-term usage of antihypertensive drug amlodipine known for its gingival enlargement effect. All these multiple factors led to diagnostic dilemma. Effective management of the gingival enlargement was done by using electrocautery to rehabilitate the functions and esthetics of the patient. Gingival condition was also complicated by the presence of coexisting lichen planus which was predominantly erosive for which topical corticosteroid, antifungal, and antimicrobial agents were prescribed. Eight-month follow-up did not show recurrence of gingival enlargement. Electrocautery is an effective tool for the gingivectomy in severe inflammatory type of gingival enlargement because of rapid postoperative hemostasis. For the management of erosive lichen planus, long-term use of topical corticosteroids is an effective approach. Maintenance of oral hygiene and regular follow-ups are essential for these conditions

The Uli Dataset: An Exercise in Experience Led Annotation of oGBV

Online gender based violence has grown concomitantly with adoption of the internet and social media. Its effects are worse in the Global majority where many users use social media in languages other than English. The scale and volume of conversations on the internet has necessitated the need for automated detection of hate speech, and more specifically gendered abuse. There is, however, a lack of language specific and contextual data to build such automated tools. In this paper we present a dataset on gendered abuse in three languages- Hindi, Tamil and Indian English. The dataset comprises of tweets annotated along three questions pertaining to the experience of gender abuse, by experts who identify as women or a member of the LGBTQIA community in South Asia. Through this dataset we demonstrate a participatory approach to creating datasets that drive AI systems

A cross-institutional analysis of the effects of broadening trainee professional development on research productivity

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Brandt, P. D., Sturzenegger Varvayanis, S., Baas, T., Bolgioni, A. F., Alder, J., Petrie, K. A., Dominguez, I., Brown, A. M., Stayart, C. A., Singh, H., Van Wart, A., Chow, C. S., Mathur, A., Schreiber, B. M., Fruman, D. A., Bowden, B., Wiesen, C. A., Golightly, Y. M., Holmquist, C. E., Arneman, D., Hall, J. D., Hyman, L. E., Gould, K. L., Chalkley, R., Brennwald, P. J., Layton, R. L. A cross-institutional analysis of the effects of broadening trainee professional development on research productivity. Plos Biology, 19(7), (2021): e3000956, https://doi.org/10.1371/journal.pbio.3000956.PhD-trained scientists are essential contributors to the workforce in diverse employment sectors that include academia, industry, government, and nonprofit organizations. Hence, best practices for training the future biomedical workforce are of national concern. Complementing coursework and laboratory research training, many institutions now offer professional training that enables career exploration and develops a broad set of skills critical to various career paths. The National Institutes of Health (NIH) funded academic institutions to design innovative programming to enable this professional development through a mechanism known as Broadening Experiences in Scientific Training (BEST). Programming at the NIH BEST awardee institutions included career panels, skill-building workshops, job search workshops, site visits, and internships. Because doctoral training is lengthy and requires focused attention on dissertation research, an initial concern was that students participating in additional complementary training activities might exhibit an increased time to degree or diminished research productivity. Metrics were analyzed from 10 NIH BEST awardee institutions to address this concern, using time to degree and publication records as measures of efficiency and productivity. Comparing doctoral students who participated to those who did not, results revealed that across these diverse academic institutions, there were no differences in time to degree or manuscript output. Our findings support the policy that doctoral students should participate in career and professional development opportunities that are intended to prepare them for a variety of diverse and important careers in the workforce.Funding sources included the Common Fund NIH Director’s Biomedical Research Workforce Innovation Broadening Experiences in Scientific Training (BEST) Award. The following institutional NIH BEST awards (alphabetical by institution) included: DP7OD020322 (Boston University; AFB, ID, BMS, LEH); DP7OD020316 (University of Chicago; CAS); DP7OD018425 (Cornell University; SSV); DP7OD018428 (Virginia Polytechnic Institute; AVW, BB); DP7OD020314 (Rutgers University; JA); DP7OD020315 (University of Rochester; TB); DP7OD018423 (Vanderbilt University; KAP, AMB, KLG, RC); DP7OD020321 (University of California, Irvine; HS, DAF); DP7OD020317 (University of North Carolina, Chapel Hill; PDB, PJB, RLL); DP7 OD018427 (Wayne State University; CSC, AM). National Institutes of Health (NIH) General Medical Sciences - Science of Science Policy Approach to Analyzing and Innovating the Biomedical Research Enterprise (SCISIPBIO) Award (GM-19-011) - 1R01GM140282-01 (University of North Carolina at Chapel Hill; RLL, PDB, PJB)

Severe Gingival Enlargement with Coexisting Erosive Lichen Planus in Severe Chronic Periodontitis Patient

Plaque induced gingival enlargement is most commonly seen and when encountered simultaneously with erosive lichen planus poses a challenge to the treating dentist. Prognosis of one condition may influence the prognosis of another condition. The presented case highlights the significance of proper diagnosis and the management of simultaneously occurring gingival lesions. A 49-year-old hypertensive female presented with painful enlarged bleeding and suppurating gums with burning sensation on eating food along with long-term usage of antihypertensive drug amlodipine known for its gingival enlargement effect. All these multiple factors led to diagnostic dilemma. Effective management of the gingival enlargement was done by using electrocautery to rehabilitate the functions and esthetics of the patient. Gingival condition was also complicated by the presence of coexisting lichen planus which was predominantly erosive for which topical corticosteroid, antifungal, and antimicrobial agents were prescribed. Eight-month follow-up did not show recurrence of gingival enlargement. Electrocautery is an effective tool for the gingivectomy in severe inflammatory type of gingival enlargement because of rapid postoperative hemostasis. For the management of erosive lichen planus, long-term use of topical corticosteroids is an effective approach. Maintenance of oral hygiene and regular follow-ups are essential for these conditions

Speech evaluation in children with missing anterior teeth and after prosthetic rehabilitation with fixed functional space maintainer

Introduction: Speech and language development in children is a dynamic process. Development of vocal sound into meaningful speech was one of the major discoveries which have made the human beings to reach the pinnacle of the animal kingdom. The ability to speak is determined by the flow of air into the mouth which affects pronunciation of various words and phrases. Aim: This study aimed to evaluate speech changes before and after prosthetic rehabilitation with fixed functional space maintainer in children with missing maxillary anterior teeth. Materials and Methods: The study sample comprised of 25 children in the age range of 3–6 years having at least two maxillary anterior teeth indicated for extraction or had already got extracted. Speech therapist evaluated articulation of [v], [ph], [n], [d], [dh], [th], [t], [s.],[s], and [l] speech sounds of patients preoperatively (T0), postoperatively after the appliance insertion (T1), and postoperatively after 7 days (T2) using Weiss Comprehensive Articulation Test. The data obtained were analyzed using Chi-square and Mcnemar's test. Results: There was statistically significant (P < 0.05) correction in [v], [ph], [d], [dh], [th], [t], [s.], and [s] speech sounds immediately after prosthetic rehabilitation (T1). While, the assessment of speech sounds after 7 days of appliance insertion (T2) showed statistically nonsignificant differences. Conclusions: The results suggested that treatment of a patient with missing anterior teeth should not be restricted to esthetic and functional oral rehabilitation, but also comprehend with the speech, as premature loss of the primary maxillary incisor appears to have long-term effect on the speech development

A research-based inter-institutional collaboration to diversify the biomedical workforce: ReBUILDetroit

Abstract Background and purpose Faced with decades of severe economic decline, the city of Detroit, Michigan (USA) is on the cusp or reinventing itself. A Consortium was formed of three higher education institutions that have an established mission to serve an urban population and a vested interest in the revitalization of the health, welfare, and economic opportunity in the Detroit metro region that is synergistic with national goals to diversify the biomedical workforce. The purpose of this article is to describe the rationale, approach, and model of the Research Enhancement for BUILDing Detroit (ReBUILDetroit) Consortium, as a cross-campus collaborative for students, faculty, and institutional development. The ReBUILDetroit program is designed to transform the culture of higher education in Detroit, Michigan by educating and training students from diverse and socio-economically disadvantaged backgrounds to become the next generation of biomedical researchers. Key program highlights Marygrove College, University of Detroit Mercy, and Wayne State University established a Consortium to create and implement innovative, evidence-based and cutting-edge programming. Specific elements include: (1) a pre-college summer enrichment experience; (2) an inter-institutional curricular re-design of target foundational courses in biology, chemistry and social science using the Research Coordination Network (RCN) model; and (3) cross-institutional summer faculty-mentored research projects for ReBUILDetroit Scholars starting as rising sophomores. Student success support includes intentional and intrusive mentoring, financial support, close faculty engagement, ongoing workshops to overcome academic and non-academic barriers, and cohort building activities across the Consortium. Institutional supports, integral to program creation and sustainability, include creating faculty learning communities grounded in professional development opportunities in pedagogy, research and mentorship, and developing novel partnerships and accelerated pipeline programming across the Consortium. This article highlights the development, implementation and evolution of high-impact practices critical for student learning, research-based course development, and the creation of inter-institutional learning communities as a direct result of ReBUILDetroit. Implications Our cross-institutional collaboration and leveraging of resources in a difficult economic environment, drawing students from high schools with a myriad of strengths and challenges, serves as a model for higher education institutions in large, urban centers who are seeking to diversify their workforces and provide additional opportunities for upward mobility among diverse populations

Research ethics in inter- and multi-disciplinary teams: Differences in disciplinary interpretations.

As research teams are increasingly comprised of members from multiple disciplines, ranging from the physical sciences, life sciences, social and behavioral sciences to the arts and humanities, it is important to revisit how research is conducted at several levels. Coupled with the national concern over rigor and reproducibility in research, it is therefore crucial to ensure that all members of such multidisciplinary teams view the need for ethics in the conduct of research in similar ways. Towards this end, Wayne State University developed a course in the Responsible Conduct of Research (RCR) which was mandatory for all its 1500 doctoral students across all disciplines in its 75 PhD programs. We found that student perceptions of the validity, applicability and usefulness of the course varied by discipline. This was in spite of iterative changes made to the course by faculty in those disciplines to make the content palatable to all. The findings show that more work needs to be done to fully incorporate the needs of social sciences and humanities disciplines in a comprehensive university course. This is especially important as these students become members of large multidisciplinary research teams in order to uphold the highest levels of rigor, reproducibility and ethics