Developing Future Biologists: Developmental Biology for Undergraduates from Underserved Communities

Developing Future Biologists (DFB) is an inclusive, trainee-run organization that strives to excite and engage the next generation of biologists, regardless of race, gender or socioeconomic status, in the field of developmental biology. DFB offers a week-long course consisting of active lectures, hands-on laboratory sessions, and professional development opportunities through interactions with scientists from a variety of backgrounds and careers. A major goal of DFB is to propel undergraduate students from underserved communities to pursue biomedical research opportunities and advanced degrees in science. To achieve this goal, we provide DFB participants with continuing access to a diverse network of scientists that students can utilize to secure opportunities and foster success throughout multiple stages of their research careers. Here, we describe the flourishing DFB program at the University of Michigan to encourage other institutions to create their own DFB programs

Synthesis and Biological Evaluation of Novobiocin Core Analogues as Hsp90 Inhibitors

Development of heat shock protein 90 (Hsp90) C‐terminal inhibitors has emerged as an exciting strategy for the treatment of cancer. Previous efforts have focused on modifications to the natural products novobiocin and coumermycin. Moreover, variations in both the sugar and amide moieties have been extensively studied, whereas replacements for the coumarin core have received less attention. Herein, 24 cores were synthesized with varying distances and angles between the sugar and amide moieties. Compounds that exhibited good anti‐proliferative activity against multiple cancer cell lines and Hsp90 inhibitory activity, were those that placed the sugar and amide moieties between 7.7 and 12.1 Å apart along with angles of 180°.Angle of attack: The distance and angle between the N‐methylpiperidine and the biaryl side chain was analyzed in an effort to develop more potent Hsp90 C‐terminal inhibitors. Compounds that exhibited good anti‐proliferative activity against multiple cancer cell lines and Hsp90 inhibitory activity were those that placed the sugar and amide moieties between 7.7 and 12.1 Å apart along with angles of 180°.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136281/1/chem201504955_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136281/2/chem201504955.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136281/3/chem201504955-sup-0001-misc_information.pd

Subjective cues to deception/honesty in a high stakes situation: An exploratory approach

This is an Accepted Manuscript of an article published by Taylor & Francis in The Journal of Psychology: Interdisciplinary and Applied on 7/5/2014 available online: http://wwww.tandfonline.com/10.1080/00223980.2014.911140The low ecological validity of much of the research on deception detection is a limitation recognised by researchers in the field. Consequently, the present studies investigated subjective cues to deception using the real life, high stakes situation of people making public appeals for help with missing or murdered relatives. It was expected that cues related to affect would be particularly salient in this context. Study 1 was a qualitative investigation identifying cues to deception reportedly used by people accurate at detecting deception. Studies 2 and 3 were then empirical investigations which mainly employed the cues reported in Study 1. A number of subjective cues were found to discriminate between honest and deceptive appeals, including some previously unidentified cues, and cues likely to be context-specific. Most could be categorised under the themes of authenticity of emotion, and negative and positive affective reactions to the appealer. It is concluded that some cues to deception may emerge only in real life, high stakes situations; however, it is argued that some of these may be influenced by observers’ perceptions of the characteristics of offenders, rather than acts of deception per se.ESRC grant number ES/I90316X/

Prevalence of Polycystic Ovary Syndrome in Women from Opposite-Sex Twin Pairs

Introduction: Intrauterine androgens of a male fetus may influence the female fetus in opposite-sex twin pairs. Because female intrauterine overexposure to androgens could lead to polycystic ovary syndrome (PCOS), the prevalence of PCOS should be higher in women from opposite-sex twin pairs. Therefore, the aim of the current study was to evaluate the prevalence of PCOS in women from opposite-sex twin pairs compared to women from same-sex twin pairs, sisters, and female spouses of twins. Subjects and Methods: Data from 1325 monozygotic twins, 1191 dizygotic twins (711 women from same-sex twin pairs and 480 women from opposite-sex twin pairs), 745 sisters of twins, and 218 spouses of male twins were evaluated. PCOS was defined as less than nine natural menstrual cycles a year combined with either hirsutism or acne. The prevalence of PCOS was compared using a ±2 test. Binary logistic regression analyses were conducted to test for confounding effects of smoking, age, and body mass index. Results: No significant differences in PCOS prevalence were found between women from same-sex twin pairs (either monozygotic or dizygotic), opposite-sex twin pairs, sisters, and spouses. Conclusion: The prevalence of PCOS is not different in women from opposite-sex and same-sex twin pairs, singleton sisters, or spouses. This indicates that possible androgen exposure of the female fetus, caused by a shared intrauterine environment with a male fetus, does not result in PCOS-like traits. Copyright © 2009 by The Endocrine Society

Effect of a Motivational Interviewing–Based Intervention on Initiation of Mental Health Treatment and Mental Health After an Emergency Department Visit Among Suicidal Adolescents

Abstract IMPORTANCE Emergency department (ED) visits present opportunities to identify and refer suicidal youth for outpatient mental health care, although this practice is not routine. OBJECTIVE To examine whether a motivational interviewing–based intervention increases linkage of adolescents to outpatient mental health services and reduces depression symptoms and suicidal ideation in adolescents seeking emergency care for non–mental health–related concerns who screen positive for suicide risk. DESIGN, SETTING, AND PARTICIPANTS In this randomized clinical trial, adolescents aged 12 to 17 years who screened positive on the Ask Suicide Screening Questions (ASQ) during a nonpsychiatric ED visit at 2 academic pediatric EDs in Ohio were recruited from April 2013 to July 2015. Intention-totreat analyses were performed from September 2018 to October 2019. INTERVENTIONS The Suicidal Teens Accessing Treatment After an Emergency Department Visit (STAT-ED) intervention included motivational interviewing to target family engagement, problem solving, referral assistance, and limited case management. The enhanced usual care (EUC) intervention consisted of brief mental health care consultation and referral. MAIN OUTCOMES AND MEASURES Primary outcomes were mental health treatment initiation and attendance within 2 months of ED discharge and suicidal ideation (assessed by the Suicidal Ideation Questionnaire JR) and depression symptoms (assessed by the Center for Epidemiologic Studies– Depression scale) at 2 and 6 months. Exploratory outcomes included treatment initiation and attendance and suicide attempts at 6 months. RESULTS A total of 168 participants were randomized and 159 included in the intention-to-treat analyses (mean [SD] age, 15.0 [1.5] years; 126 [79.2%] female; and 80 [50.3%] white). Seventy-nine participants were randomized to receive the STAT-ED intervention and 80 to receive EUC. At 2 months, youth in the STAT-ED group had similar rates of mental health treatment initiation compared with youth in the EUC group as assessed by parent report (29 [50.9%] vs 22 [34.9%]; adjusted odds ratio [OR], 2.08; 95% CI, 0.97-4.45) and administrative data from mental health care agencies (19 [29.7%] vs 11 [19.3%]; adjusted OR, 1.77; 95% CI, 0.76-4.15). At 2 months, youth in the STAT-ED group and the EUC group had similar rates of treatment attendance (1 appointment: 6 [9.7%] vs 2 [3.6%]; adjusted OR, 2.97; 95% CI, 0.56-15.73; 2 appointments: 10 [16.1%] vs 7 [12.7%]; adjusted OR, 1.43; 95% CI, 0.50-4.11). There were no significant group × time differences in suicidal ideation (F = 0.28; P = .72) and depression symptoms (F = 0.49; P = .60) during the 6-month follow-up period. In exploratory analyses, at 6 months, STAT-ED participants had significantly higher rates of agencyreported mental health treatment initiation (adjusted OR, 2.48; 95% CI, 1.16-5.28) and more completed appointments (t99.7 = 2.58; P = .01). CONCLUSIONS AND RELEVANCE This study’s findings indicate that no differences were found on any primary outcome by study condition. However, STAT-ED was more efficacious than EUC at increasing mental health treatment initiation and attendance at 6 months. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01779414 JAMA Network Open. 2019;2(12):e1917941. doi:10.1001/jamanetworkopen.2019.1794

Adenovirus vector expressing Stx1/Stx2-neutralizing agent protects piglets infected with Escherichia coli O157: H7 against fatal systemic intoxication

Hemolytic-uremic syndrome (HUS), caused by Shiga toxin (Stx)-producing Escherichia coli (STEC), remains untreatable. Production of human monoclonal antibodies against Stx, which are highly effective in preventing Stx sequelae in animal models, is languishing due to cost and logistics. We reported previously that the production and evaluation of a camelid heavy-chain-only V(H) domain (VHH)-based neutralizing agent (VNA) targeting Stx1 and Stx2 (VNA-Stx) protected mice from Stx1 and Stx2 intoxication. Here we report that a single intramuscular (i.m.) injection of a nonreplicating adenovirus (Ad) vector carrying a secretory transgene of VNA-Stx (Ad/VNA-Stx) protected mice challenged with Stx2 and protected gnotobiotic piglets infected with STEC from fatal systemic intoxication. One i.m. dose of Ad/VNA-Stx prevented fatal central nervous system (CNS) symptoms in 9 of 10 animals when it was given to piglets 24 h after bacterial challenge and in 5 of 9 animals when it was given 48 h after bacterial challenge, just prior to the onset of CNS symptoms. All 6 placebo animals died or were euthanized with severe CNS symptoms. Ad/VNA-Stx treatment had no impact on diarrhea. In conclusion, Ad/VNA-Stx treatment is effective in protecting piglets from fatal Stx2-mediated CNS complications following STEC challenge. With a low production cost and further development, this could presumably be an effective treatment for patients with HUS and/or individuals at high risk of developing HUS due to exposure to STEC

Better Together? The Cognitive Advantages of Synaesthesia for Time, Numbers and Space

Synaesthesia for time, numbers and space (TNS synaesthesia) is thought to have costs and benefits for recalling and manipulating time and number. There are two competing theories about how TNS synaesthesia affects cognition. The ‘magnitude’ account predicts TNS synaesthesia may affect cardinal magnitude judgements, whereas the ‘sequence’ account suggests it may affect ordinal sequence judgements and could rely on visuospatial working memory. We aimed to comprehensively assess the cognitive consequences of TNS synaesthesia and distinguish between these two accounts. TNS synaesthetes, grapheme-colour synaesthetes and non-synaesthetes completed a behavioural task battery. Three tasks involved cardinal and ordinal comparisons of temporal, numerical and spatial stimuli; we also examined visuospatial working memory. TNS synaesthetes were significantly more accurate than non-synaesthetes in making ordinal judgements about space. This difference was explained by significantly higher visuospatial working memory accuracy. Our findings demonstrate an advantage of TNS synaesthesia which is more in line with the sequence account

Immunoglobulin G immune response to SARS-CoV-2 vaccination in people living with multiple sclerosis within Multiple Sclerosis Partners Advancing Technology and Health Solutions

The impact of multiple sclerosis (MS) disease-modifying therapies (DMTs) on SARS-CoV-2 vaccination response is uncertain. Post-SARS-CoV-2 vaccination blood samples across multiple DMTs were tested for SARS-CoV-2 immunoglobulin G (IgG) response. Three hundred twenty-two people with MS were included; 91.9% received an mRNA vaccine. Post-vaccination reactive IgG rates (IgG index > 1) were 40% for anti-CD20 (32/80 patients); 41% for sphingosine 1-phosphate receptor modulators (S1PRM, 16/39); and 100% for all other classes, including the no DMT group. Anti-CD20 therapies and S1PRMs reduce IgG response to SARS-CoV-2 vaccination; IgG response is preserved with other DMTs

Using ePrognosis to estimate 2-year all-cause mortality in older women with breast cancer: Cancer and Leukemia Group B (CALGB) 49907 and 369901 (Alliance A151503)

Tools to estimate survival, such as ePrognosis (http://eprognosis.ucsf.edu/carey2.php), were developed for general, not cancer, populations. In older patients with breast cancer, accurate overall survival estimates would facilitate discussions about adjuvant therapies