The mechanisms of boronate ester formation and fluorescent turn-on in ortho-aminomethylphenylboronic acids

ortho-Aminomethylphenylboronic acids are used in receptors for carbohydrates and various other compounds containing vicinal diols. The presence of the o-aminomethyl group enhances the affinity towards diols at neutral pH, and the manner in which this group plays this role has been a topic of debate. Further, the aminomethyl group is believed to be involved in the turn-on of the emission properties of appended fluorophores upon diol binding. In this treatise, a uniform picture emerges for the role of this group: it primarily acts as an electron-withdrawing group that lowers the pK(a) of the neighbouring boronic acid thereby facilitating diol binding at neutral pH. The amine appears to play no role in the modulation of the fluorescence of appended fluorophores in the protic-solvent-inserted form of the boronic acid/boronate ester. Instead, fluorescence turn-on can be consistently tied to vibrational-coupled excited-state relaxation (a loose-bolt effect). Overall, this Review unifies and discusses the existing data as of 2019 whilst also highlighting why o-aminomethyl groups are so widely used, and the role they play in carbohydrate sensing using phenylboronic acids

Potential virulence of Klebsiella sp. isolates from enteral diets

We aimed to evaluate the potential virulence of Klebsiella isolates from enteral diets in hospitals, to support nosocomial infection control measures, especially among critical-care patients. Phenotypic determination of virulence factors, such as capsular expression on the external membrane, production of aerobactin siderophore, synthesis of capsular polysaccharide, hemolytic and phospholipase activity, and resistance to antibiotics, which are used therapeutically, were investigated in strains of Klebsiella pneumoniae and K. oxytoca. Modular industrialized enteral diets (30 samples) as used in two public hospitals were analyzed, and Klebsiella isolates were obtained from six (20%) of them. The hypermucoviscous phenotype was observed in one of the K. pneumoniae isolates (6.7%). Capsular serotypes K1 to K6 were present, namely K5 and K4. Under the conditions of this study, no aerobactin production, hemolytic activity or lecithinase activity was observed in the isolates. All isolates were resistant to amoxicillin and ampicillin and sensitive to cefetamet, imipenem, chloramphenicol, gentamicin and sulfamethoxazole-trimethoprim. Most K. pneumoniae isolates (6/7, 85.7%) from hospital B presented with a higher frequency of resistance to the antibiotics tested in this study, and multiple resistance to at least four antibiotics (3/8; 37.5%) compared with isolates from Hospital A. The variations observed in the antibiotic resistance profiles allowed us to classify the Klebsiella isolates as eight antibiotypes. No production of broad-spectrum β-lactamases was observed among the isolates. Our data favor the hypothesis that Klebsiella isolates from enteral diets are potential pathogens for nosocomial infections

Bloodstream-To-Eye Infections Are Facilitated by Outer Blood-Retinal Barrier Dysfunction

This work was funded by National Institutes of Health (NIH; http://www.nih.gov) Grants R01EY024140 and R21EY022466 (to M.C.C.) and R01EY019494 (to M.H.E.). Our research is also funded in part by NIH Core Grant P30EY021725 (to Robert E. Anderson, OUHSC) and an unrestricted grant from Research to Prevent Blindness Inc. (http://www.rpbusa.org) to the Dean A. McGee Eye Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.We thank Bolanle Adebayo (Cameron University, Lawton OK), Craig Land (Oklahoma State University, Stillwater OK), Nathan Jia (Oklahoma Christian University, Edmond OK), Kobbe Wiafe (Oklahoma School of Science and Mathematics, Oklahoma City OK), and Amanda Roehrkasse and Madhu Parkunan (OUHSC) for intellectual discussions and technical assistance. The authors also acknowledge thank Nanette Wheatley, Dr. Feng Li, and Mark Dittmar (OUHSC Live Animal Imaging Core, P30EY021725) for their invaluable technical assistance.This work was presented in part at the 2014 Association for Research in Vision and Ophthalmology Annual Conference in Orlando FL.The blood-retinal barrier (BRB) functions to maintain the immune privilege of the eye, which is necessary for normal vision. The outer BRB is formed by tightly-associated retinal pigment epithelial (RPE) cells which limit transport within the retinal environment, maintaining retinal function and viability. Retinal microvascular complications and RPE dysfunction resulting from diabetes and diabetic retinopathy cause permeability changes in the BRB that compromise barrier function. Diabetes is the major predisposing condition underlying endogenous bacterial endophthalmitis (EBE), a blinding intraocular infection resulting from bacterial invasion of the eye from the bloodstream. However, significant numbers of EBE cases occur in non-diabetics. In this work, we hypothesized that dysfunction of the outer BRB may be associated with EBE development. To disrupt the RPE component of the outer BRB in vivo, sodium iodate (NaIO3) was administered to C57BL/6J mice. NaIO3-treated and untreated mice were intravenously injected with 108 colony forming units (cfu) of Staphylococcus aureus or Klebsiella pneumoniae. At 4 and 6 days postinfection, EBE was observed in NaIO3-treated mice after infection with K. pneumoniae and S. aureus, although the incidence was higher following S. aureus infection. Invasion of the eye was observed in control mice following S. aureus infection, but not in control mice following K. pneumoniae infection. Immunohistochemistry and FITC-dextran conjugate transmigration assays of human RPE barriers after infection with an exoprotein-deficient agr/sar mutant of S. aureus suggested that S. aureus exoproteins may be required for the loss of the tight junction protein, ZO-1, and for permeability of this in vitro barrier. Our results support the clinical findings that for both pathogens, complications which result in BRB permeability increase the likelihood of bacterial transmigration from the bloodstream into the eye. For S. aureus, however, BRB permeability is not required for the development of EBE, but toxin production may facilitate EBE pathogenesis.Yeshttp://www.plosone.org/static/editorial#pee

Synthesis and prospective study of the use of thiophene thiosemicarbazones as signalling scaffolding for the recognition of anions

A family of phenyl-thiosemicarbazone dyes have been prepared and their interactions with anions monitorized via UV-Vis, fluorescence and 1H NMR titrations. Additionally quantum chemical calculations and electrochemical studies completed the studies carried out. The phenyl-thiosemicarbazone dyes show a modulation of their hydrogen-bonding and electron-donating capabilities as a function of the chemical groups attached and display two different chromo-fluorogenic responses towards anions in acetonitrile solutions. The more basic anions fluoride and cyanide are able to induce the dual coordination-deprotonation processes for all the receptors studied, whereas acetate only interacts with receptors 2, 3, 6, 7, 8, 9 and dihydrogen phosphate displays sensing features only with the more acidic receptors 6. Coordinative hydrogen bonding interactions is indicated by a small bathochromic shift, whilst deprotonation results in the appearance of a new band at ca. 400-450 nm corresponding to a colour change from colourless-yellow to yellow-red depending on the receptor. In the emission fluorescence, hydrogen bonding interaction is visible through the enhancement of the emission band, whereas deprotonation induced the growth of a new red-shifted emission. The chromo-fluorogenic behaviour could be explained on the basis of the deprotonation tendency of the binding sites and the proton affinity of the anions. PM3 and 1H NMR calculations are in agreement with the existence of the dual complexation-deprotonation process, whereas both studies are in discrepancy in relation to which is the proton involved in the deprotonation. Electrochemical studies carried with receptor 3 showed a quite complex redox behaviour and anodic shifts of the reduction peaks in the presence of the basic anions fluoride, cyanide and acetate.Fundação para a Ciência e a Tecnologia (FCT

Bacterial endophthalmitis: Therapeutic challenges and host–pathogen interactions

Endophthalmitis is an infection of the posterior segment of the eye that frequently results in loss of vision. This devastating result occurs despite prompt and often aggressive therapeutic and surgical intervention. Over the past decade, research has centered on determining the bacterial and host factors involved in this potentially blinding disease. The initial focus on the bacterial factors responsible for intraocular virulence has recently expanded into analysis the inflammatory response to infection, including the molecular and cellular interactions between the pathogen and host. This review discusses the epidemiology and therapeutic challenges posed by endophthalmitis, as well as recent findings from the analysis of interactions between the host and pathogen. Based on these findings, a model for the pathogenesis of endophthalmitis is presented. A more comprehensive understanding of the molecular and cellular interactions taking place between pathogen and host during endophthalmitis will expose possible therapeutic targets designed to arrest the infection and prevent vision loss

Developmental Networks Among Mentors and Mentees Involved in a Mentoring Intervention

The growing application of social network-based theories and methods (Burt et al., 2013) in scholarship on mentoring illustrates that mentoring goes beyond dyadic relationships comprising a senior mentor and a junior protégé (Higgins & Kram, 2001). However, limited data exist on the state of developmental networks of university faculty. This study examines developmental network characteristics among mentors and mentees participating in an ongoing intervention that aims to enhance career success through improved mentoring. Cross-sectional data come from 81 faculty mentors and mentees at three universities in the Southwestern United States. Using the online Modified Mentoring Network Questionnaire (MNQ), participants provided information on relationships with developers, who are people that have taken concerted action, and provided professional and/or personal guidance to help participants advance in their careers. An individual’s developmental network comprises relationships with developers. We conducted exploratory analyses examining key characteristics of mentors’ and mentees’ developmental networks. Participants received psychosocial and career support from an average of 4.9 developers (4.8 and 5.1 for mentors and mentees respectively) from 2.3 arenas (2.2 and 2.4 arenas for mentors and mentees, respectively). While the most common arena was the respondents’ current job/position (62%, 64% and 59% for all participants, mentors, and mentees respectively), developers were from graduate school (11%, 6% and 17%); prior jobs/positions (13%, 16% and 9%) and family (8%, 5% and 11%). Our preliminary findings suggest that developers are important for university faculty and that methods and insights from social network analysis can be applied to examine their support networks. As our study is part of an ongoing longitudinal intervention, these findings will inform future analyses that will examine changes in developmental network characteristics and its impact on participants’ careers.This study was supported by NIH/NIGMS U01GM132175 (Sood, PI); and 2U54GM104944 (Sy, PI).https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258986

Mentoring Network Questionnaire Support Scales Reliable and Valid with University Faculty

The Developmental Network Questionnaire (DNQ) is used in business to self-assess relationships with developers, or people who support one’s career. The Mentoring Network Questionnaire (MNQ) is an online modification of the DNQ and includes two scales that rate developer’s contributions to career or psychosocial help. The psychometrics of these scales for different populations are unreported. This study analyzed the construct validity and reliability of the two scales measuring support provided by developers of university faculty. Mentors and mentees (G=156) from multiple Southwestern and Mountain West universities rated 741 developers on the MNQ’s five-item career- and psychosocial-support scales. Participants responded on a seven-point scale ranging from “never, not at all” to “to the maximum extent possible.” Multilevel confirmatory factor analysis (MCFA) using Mplus and the multi-level reliability coefficient omega assessed construct validity and internal consistency reliability, respectively. Results supported the validity of two latent constructs of career- and psychosocial support, each measured by the established five-item scale: Comparative fit index (CFI)=.93, Tucker-Lewis Index (TLI)=.91, root mean square error of approximation (RMSEA)=.06, standardized root mean square residual (SRMR): W=.09, B=.10. The measurement model was improved when the “removes barriers” item was removed from the career-support scale (CFI=.96, TLI=.95, RMSEA=.05, SRMR: W=.06 B=.09. Factor loadings at both the within- and between-levels were strong and statistically significant. Reliability omegas ranged from .85 to .92. Career and psychosocial support provided to university faculty by developers in their networks may be validly and reliably measured at both the within- and between-levels by a modified four-item career support scale and the original five-item psychosocial support scale from the DNQ and the modified MNQ. Limitations include reduced statistical power due to small sample size and lack of testing at the university level. Future work will assess the responsiveness of these scales to measuring change over time in the amount of support provided.Funded by the NIH/NIGMS U01GM132175 (Sood, PI) and 2U54GM104944 (Sy, PI); HRSA grant 1 D34HP45723-01-00 (PI Romero-Leggott); and NIH/NCATS UL1 TR001449 (Pandhi, N/Campen, M)https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10768921