An empirical approach towards the efficient and optimal production of influenza-neutralizing ovine polyclonal antibodies demonstrates that the novel adjuvant CoVaccine HT(TM) is functionally superior to Freund's adjuvant

Passive immunotherapies utilising polyclonal antibodies could have a valuable role in preventing and treating infectious diseases such as influenza, particularly in pandemic situations but also in immunocompromised populations such as the elderly, the chronically immunosuppressed, pregnant women, infants and those with chronic diseases. The aim of this study was to optimise current methods used to generate ovine polyclonal antibodies. Polyclonal antibodies to baculovirus-expressed recombinant influenza haemagglutinin from A/Puerto Rico/8/1934 H1N1 (PR8) were elicited in sheep using various immunisation regimens designed to investigate the priming immunisation route, adjuvant formulation, sheep age, and antigen dose, and to empirically ascertain which combination maximised antibody output. The novel adjuvant CoVaccine HT™ was compared to Freund’s adjuvant which is currently the adjuvant of choice for commercial production of ovine polyclonal Fab therapies. CoVaccine HT™ induced significantly higher titres of functional ovine anti-haemagglutinin IgG than Freund’s adjuvant but with fewer side effects, including reduced site reactions. Polyclonal hyperimmune sheep sera effectively neutralised influenza virus in vitro and, when given before or after influenza virus challenge, prevented the death of infected mice. Neither the age of the sheep nor the route of antigen administration appeared to influence antibody titre. Moreover, reducing the administrated dose of haemagglutinin antigen minimally affected antibody titre. Together, these results suggest a cost effective way of producing high and sustained yields of functional ovine polyclonal antibodies specifically for the prevention and treatment of globally significant diseases.Natalie E. Stevens, Cara K. Fraser, Mohammed Alsharifi, Michael P. Brown, Kerrilyn R. Diener, John D. Haybal

Targeting transcription regulation in cancer with a covalent CDK7 inhibitor

Tumour oncogenes include transcription factors that co-opt the general transcriptional machinery to sustain the oncogenic state, but direct pharmacological inhibition of transcription factors has so far proven difficult. However, the transcriptional machinery contains various enzymatic cofactors that can be targeted for the development of new therapeutic candidates, including cyclin-dependent kinases (CDKs). Here we present the discovery and characterization of a covalent CDK7 inhibitor, THZ1, which has the unprecedented ability to target a remote cysteine residue located outside of the canonical kinase domain, providing an unanticipated means of achieving selectivity for CDK7. Cancer cell-line profiling indicates that a subset of cancer cell lines, including human T-cell acute lymphoblastic leukaemia (T-ALL), have exceptional sensitivity to THZ1. Genome-wide analysis in Jurkat T-ALL cells shows that THZ1 disproportionally affects transcription of RUNX1 and suggests that sensitivity to THZ1 may be due to vulnerability conferred by the RUNX1 super-enhancer and the key role of RUNX1 in the core transcriptional regulatory circuitry of these tumour cells. Pharmacological modulation of CDK7 kinase activity may thus provide an approach to identify and treat tumour types that are dependent on transcription for maintenance of the oncogenic state.National Institutes of Health (U.S.) (Grant HG002668)National Institutes of Health (U.S.) (Grant CA109901

The Wooster Voice (Wooster, OH), 1949-12-08

Dr. T. Cuyler Young addresses the campus during the annual Wooster Day celebration. Dr. Delbert Lean will give his 40th annual reading of Charles Dickens\u27 Christmas Carol. Plans to build a darkroom for student publications are announced. Additionally, Wooster host the fall conference of the Ohio division of the National Student Association.https://openworks.wooster.edu/voice1941-1950/1204/thumbnail.jp

Wear and corrosion interactions on titanium in oral environment : literature review

The oral cavity is a complex environment where corrosive substances from dietary, human saliva, and oral biofilms may accumulate in retentive areas of dental implant systems and prostheses promoting corrosion at their surfaces. Additionally, during mastication, micromovements may occur between prosthetic joints causing a relative motion between contacting surfaces, leading to wear. Both processes (wear and corrosion) result in a bio-tribocorrosion system once that occurs in contact with biological tissues and fluids. This review paper is focused on the aspects related to the corrosion and wear behavior of titanium-based structures in the oral environment. Furthermore, the clinical relevance of the oral environment is focused on the harmful effect that acidic substances and biofilms, formed in human saliva, may have on titanium surfaces. In fact, a progressive degradation of titanium by wear and corrosion (tribocorrosion) mechanisms can take place affecting the performance of titanium-based implant and prostheses. Also, the formation of wear debris and metallic ions due to the tribocorrosion phenomena can become toxic for human tissues. This review gathers knowledge from areas like materials sciences, microbiology, and dentistry contributing to a better understanding of bio-tribocorrosion processes in the oral environment.(undefined

Anti-angiogenic therapy for cancer: Current progress, unresolved questions and future directions

Tumours require a vascular supply to grow and can achieve this via the expression of pro-angiogenic growth factors, including members of the vascular endothelial growth factor (VEGF) family of ligands. Since one or more of the VEGF ligand family is overexpressed in most solid cancers, there was great optimism that inhibition of the VEGF pathway would represent an effective anti-angiogenic therapy for most tumour types. Encouragingly, VEGF pathway targeted drugs such as bevacizumab, sunitinib and aflibercept have shown activity in certain settings. However, inhibition of VEGF signalling is not effective in all cancers, prompting the need to further understand how the vasculature can be effectively targeted in tumours. Here we present a succinct review of the progress with VEGF-targeted therapy and the unresolved questions that exist in the field: including its use in different disease stages (metastatic, adjuvant, neoadjuvant), interactions with chemotherapy, duration and scheduling of therapy, potential predictive biomarkers and proposed mechanisms of resistance, including paradoxical effects such as enhanced tumour aggressiveness. In terms of future directions, we discuss the need to delineate further the complexities of tumour vascularisation if we are to develop more effective and personalised anti-angiogenic therapies. © 2014 The Author(s)

From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways

The human body hosts an enormous abundance and diversity of microbes, which perform a range of essential and beneficial functions. Our appreciation of the importance of these microbial communities to many aspects of human physiology has grown dramatically in recent years. We know, for example, that animals raised in a germ-free environment exhibit substantially altered immune and metabolic function, while the disruption of commensal microbiota in humans is associated with the development of a growing number of diseases. Evidence is now emerging that, through interactions with the gut-brain axis, the bidirectional communication system between the central nervous system and the gastrointestinal tract, the gut microbiome can also influence neural development, cognition and behaviour, with recent evidence that changes in behaviour alter gut microbiota composition, while modifications of the microbiome can induce depressive-like behaviours. Although an association between enteropathy and certain psychiatric conditions has long been recognized, it now appears that gut microbes represent direct mediators of psychopathology. Here, we examine roles of gut microbiome in shaping brain development and neurological function, and the mechanisms by which it can contribute to mental illness. Further, we discuss how the insight provided by this new and exciting field of research can inform care and provide a basis for the design of novel, microbiota-targeted, therapies.GB Rogers, DJ Keating, RL Young, M-L Wong, J Licinio, and S Wesseling

MAXIMAL VO2 AT EXTREME ENDS OF THE DAY FOLLOWING GLUCOSE PROVISION

Jenna L. Carducci1, Matthew J. Garver1, Whitley J. Stone1, Meera Penumetcha1, Dustin W. Davis1, Adam R. McMillin1, Josie N. Hair1, Nicolas M. Philipp1, Jordan R. Elledge1, Emily B. Sheck1, & Katherine M. Scherry1 1University of Central Missouri, Warrensburg, Missouri Exercise programs are more favorable when individualized to particular needs and preferences. Controlling training and exercise characteristics such as time of day and glucose provision may enhance subsequent performance. PURPOSE: The purpose of this research was to investigate maximal VO2 at extreme ends of the day following a standardized glucose provision. METHODS: Thirteen participants (Females: 8, Males: 5, Age: 20.7 ± 1.4 yrs., BMI: 24.9 ± 3.0 kg/m2) volunteered to complete two maximal VO2 tests, one between 06:00-09:00 and the other between 21:00-24:00. A familiarization trial was utilized to mitigate a learning effect and determine the speed that elicited a perceived effort of 12-13 on the Borg 6-20 RPE scale when steady-stated. Considering body mass and activity level, a standardized test meal of approximately 80% carbohydrates, 3% fat, and 17% protein was provided 2 hours prior to testing. For the maximal testing, treadmill speed was maintained at the predetermined intensity, and grade was increased 2% every 2 minutes until volitional fatigue. Maximal VO2 was determined via a metabolic cart using a 15-breath moving average. RESULTS: The maximal tests lasted 10.13 ± 2.15 minutes. There was no statistical difference (p \u3c .05) found for morning vs. evening tests for maximal VO2 (47.0 ± 7.0 vs. 47.3 ± 8.0 ml/kg/min). CONCLUSION: The glucose provision prior to exercise was intended to standardize nutrient intake prior to completing the maximal VO2 tests. The results of this study align with the available literature suggesting that maximal VO2 does not significantly differ between morning and evening exercise tests. Exercising at extreme ends of the day may not result in a significant difference in maximal VO2 among a group of younger, recreationally active adults provided a high-glucose test meal. ACKNOWLEDGEMENTS: This research was funded by the Graduate Student Research Fund from the University of Central Missouri

MAXIMAL PERCEIVED EFFORT DURING MAXIMAL RUNNING AT EXTREME ENDS OF THE DAY

Nicolas M. Philipp1, Jenna L. Carducci1, Matthew J. Garver1, Whitley J. Stone1, Meera Penumetcha1, Dustin W. Davis1, Adam R. McMillin1, Josie N. Hair1, Jordan R. Elledge1, Emily B. Sheck1, & Katherine M. Scherry1 1University of Central Missouri, Warrensburg, Missouri Borg’s RPE Scale is commonly used to measure perceived exertion during exercise. Imposed exercise times, such as early morning or late evening, may impact perceived exertion. PURPOSE: Perceived exertion was recorded during maximal treadmill running to determine if there was a significant difference between extreme ends of the day. METHODS: Thirteen (Females: 8, Males: 5) recreationally trained individuals (Age: 20.7 ± 1.4 yrs.) underwent maximal testing on two occasions—a morning session (6:00-9:00) and an evening session (21:00-24:00). Prior to maximal testing, participants completed a familiarization trial purposed to limit learning effect and establish an individualized, comfortable jogging speed eliciting a steady-state RPE of 12-13 on the 6-20 Borg scale. Participants were provided a standardized meal (high CHO smoothie based on body weight and activity level) to be consumed 2h before testing. During maximal testing, participants maintained the constant jogging speed at the intensity determined during familiarization. Every 2 minutes, grade increased by 2% until volitional exhaustion. The RPE was recorded near the completion of each stage and immediately after termination of the test. RESULTS: The mean maximal test duration was 10.13 ± 2.15 minutes. A paired samples t-test indicated that maximal RPE did not differ (p = .25) between morning (18.9 ± 1.1) and evening (18.8 ± 1.5) tests. A paired samples t-test between session 1 and session 2 revealed an order effect (18.5 vs. 19.1, p = .047), with session 2 being perceived as exertionally more demanding. CONCLUSION: No difference was found in maximal RPE between the tests performed at 6:00-9:00 and 21:00-24:00. Interestingly, session 2 was perceived as more exertionally demanding when compared to session 1. These data support that there is no difference in maximal RPE when exercising at extreme ends of the day; however, recreationally trained individuals may perceive a maximal exercise test as more difficult if repeated within 36-72h. ACKNOWLEDGEMENTS: This research was funded by the Graduate Student Research Fund from the University of Central Missouri