Genomic interactions of the transcription factor VEZF1

VEZF1 is a highly conserved vertebrate transcription factor. VEZF1 binding sites have been reported to function in gene promoter activation, insulator barrier activity and protection from de novo DNA methylation. This study aims to identify VEZF1 binding sites across the human genome and to develop a better understanding of the gene regulatory processes mediated by VEZF1

The SNARE Protein Syntaxin 3 Confers Specificity for Polarized Axonal Trafficking in Neurons.

Cell polarity and precise subcellular protein localization are pivotal to neuronal function. The SNARE machinery underlies intracellular membrane fusion events, but its role in neuronal polarity and selective protein targeting remain unclear. Here we report that syntaxin 3 is involved in orchestrating polarized trafficking in cultured rat hippocampal neurons. We show that syntaxin 3 localizes to the axonal plasma membrane, particularly to axonal tips, whereas syntaxin 4 localizes to the somatodendritic plasma membrane. Disruption of a conserved N-terminal targeting motif, which causes mislocalization of syntaxin 3, results in coincident mistargeting of the axonal cargos neuron-glia cell adhesion molecule (NgCAM) and neurexin, but not transferrin receptor, a somatodendritic cargo. Similarly, RNAi-mediated knockdown of endogenous syntaxin 3 leads to partial mistargeting of NgCAM, demonstrating that syntaxin 3 plays an important role in its targeting. Additionally, overexpression of syntaxin 3 results in increased axonal growth. Our findings suggest an important role for syntaxin 3 in maintaining neuronal polarity and in the critical task of selective trafficking of membrane protein to axons

Randomized Trial of 3 Techniques of Perineal Skin Closure During Second‐Degree Perineal Laceration Repair

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151863/1/jmwh13020.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151863/2/jmwh13020_am.pd

Moving Toward Patient‐Centered Care: Women's Decisions, Perceptions, and Experiences of the Induction of Labor Process

Background Patient preferences and clinician practices are possible causative factors to explain the increase in induction of labor, but scientific studies that demonstrate this link are limited. The purpose of this study is to identify factors that influence inductions from the perspective of women. Methods A qualitative investigation using grounded theory methodology was conducted. Women were interviewed preinduction and postinduction. Analysis of the interviews was conducted using constant comparison to identify codes, categories, and themes. Through this process the complex intersection between women, their clinician, and the application of evidence‐based care in clinical practice was explored. Results Five major themes from the preinduction interview were identified; safety of baby, women's trust in their clinician, relief of discomfort and/or anxiety, diminish potential or actual risk, and lack of informed decision making. Five major themes were identified from the postinduction interview; lack of informed decision making, induction as part of a checklist, women's trust in their clinician, happy with induction, and opportunities to improve the experience. Conclusions Lack of informed decision making was cited as a barrier to optimal care. This study has important implications for patient‐centered research and clinical care, requiring the inclusion of women and the salient concepts of care that they identify.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/107354/1/birt12080.pd

Novel genetic mutations in genes AGBL5 and TULP1 for presumed unilateral retinitis pigmentosa managed with low vision rehabilitation: A case report and review

Background: Retinitis pigmentosa is a group of hereditary retinal diseases characterized by the degeneration of rod and cone photoreceptors. It commonly results in night blindness followed by tunnel vision and central vision reduction. The classic triad of clinical signs includes pigmented bone spicules, waxy disc pallor, and arterial attenuation. Unilateral retinitis pigmentosa is rare and can be supported with ancillary testing including genetic and laboratory studies to rule out differential diagnoses. Case Report: A 68-year-old Hispanic female was referred to the low vision rehabilitation clinic due to progressive vision loss in the left eye (OS) that began 15 years ago. The vision was normal in the right eye (OD). Additionally, she suffered from hearing loss in the right ear since age 3. Examination revealed abnormal visual acuity, visual field, fundus appearance, optical coherence tomography, and electrodiagnostic test results in the OS only. Laboratory studies ruled out various infectious, autoimmune, traumatic, and toxic drug etiologies. Genetic testing revealed novel mutations in genes associated with retinitis pigmentosa. Conclusion: The genetic testing results along with the clinical examination and electrodiagnostic evaluation supports the diagnosis of unilateral retinitis pigmentosa

Application of pharmacogenomics and bioinformatics to exemplify the utility of human <i>ex vivo</i> organoculture models in the field of precision medicine

Here we describe a collaboration between industry, the National Health Service (NHS) and academia that sought to demonstrate how early understanding of both pharmacology and genomics can improve strategies for the development of precision medicines. Diseased tissue ethically acquired from patients suffering from chronic obstructive pulmonary disease (COPD), was used to investigate inter-patient variability in drug efficacy using ex vivo organocultures of fresh lung tissue as the test system. The reduction in inflammatory cytokines in the presence of various test drugs was used as the measure of drug efficacy and the individual patient responses were then matched against genotype and microRNA profiles in an attempt to identify unique predictors of drug responsiveness. Our findings suggest that genetic variation in CYP2E1 and SMAD3 genes may partly explain the observed variation in drug response

Ending AIDS as a public health threat by 2030: Time to reset targets for 2025.

Paul De Lay and co-authors introduce a Collection on the design of targets for ending the AIDS epidemic

Analysis of genetic copy number changes in cervical disease progression

<p>Abstract</p> <p>Background</p> <p>Cervical dysplasia and tumorigenesis have been linked with numerous chromosomal aberrations. The goal of this study was to evaluate 35 genomic regions associated with cervical disease and to select those which were found to have the highest frequency of aberration for use as probes in fluorescent in-situ hybridization.</p> <p>Methods</p> <p>The frequency of gains and losses using fluorescence in-situ hybridization were assessed in these 35 regions on 30 paraffin-embedded cervical biopsy specimens. Based on this assessment, 6 candidate fluorescently labeled probes (8q24, Xp22, 20q13, 3p14, 3q26, CEP15) were selected for additional testing on a set of 106 cervical biopsy specimens diagnosed as Normal, CIN1, CIN2, CIN3, and SCC. The data were analyzed on the basis of signal mean, % change of signal mean between histological categories, and % positivity.</p> <p>Results</p> <p>The study revealed that the chromosomal regions with the highest frequency of copy number gains and highest combined sensitivity and specificity in high-grade cervical disease were 8q24 and 3q26. The cytological application of these two probes was then evaluated on 118 ThinPrep™ samples diagnosed as Normal, ASCUS, LSIL, HSIL and Cancer to determine utility as a tool for less invasive screening. Using gains of either 8q24 or 3q26 as a positivity criterion yielded specificity (Normal +LSIL+ASCUS) of 81.0% and sensitivity (HSIL+Cancer) of 92.3% based on a threshold of 4 positive cells.</p> <p>Conclusions</p> <p>The application of a FISH assay comprised of chromosomal probes 8q24 and 3q26 to cervical cytology specimens confirms the positive correlation between increasing dysplasia and copy gains and shows promise as a marker in cervical disease progression.</p

Gonococcal vaccines: Public health value and preferred product characteristics; report of a WHO global stakeholder consultation, January 2019.

Renewed interest in developing vaccines against Neisseria gonorrhoeae has been sparked by the increasing threat of gonococcal antimicrobial resistance (AMR) and growing optimism that gonococcal vaccines are biologically feasible. Evidence suggests serogroup B Neisseria meningitidis vaccines might provide some cross-protection against N. gonorrhoeae, and new gonococcal vaccine candidates based on several approaches are currently in preclinical development. To further stimulate investment and accelerate development of gonococcal vaccines, greater understanding is needed regarding the overall value that gonococcal vaccines might have in addressing public health and societal goals in low-, middle-, and high-income country contexts and how future gonococcal vaccines might be accepted and used, if available. In January 2019, the World Health Organization (WHO) convened a multidisciplinary international group of experts to lay the groundwork for understanding the potential health, economic, and societal value of gonococcal vaccines and their likely acceptance and use, and for developing gonococcal vaccine preferred product characteristics (PPCs). WHO PPCs describe preferences for vaccine attributes that would help optimize vaccine value and use in meeting the global public health need. This paper describes the main discussion points and conclusions from the January 2019 meeting of experts. Participants emphasized the need for vaccines to control N. gonorrhoeae infections with the ultimate goals of preventing adverse sexual and reproductive health outcomes (e.g., infertility) and reducing the impact of gonococcal AMR. Meeting participants also discussed important PPC considerations (e.g., vaccine indications, target populations, and potential immunization strategies) and highlighted crucial research and data needs for guiding the value assessment and PPCs for gonococcal vaccines and advancing gonococcal vaccine development